pmid
stringlengths 4
8
| title
stringlengths 1
1.27k
| text
stringlengths 1
14.3k
|
|---|---|---|
7786693
|
Magnesium status and parenteral magnesium sulphate therapy in acute aluminum phosphide intoxication.
|
The results of an open randomized study on magnesium status and parenteral magnesium sulphate therapy in acute aluminium phosphide intoxication are presented. The study was conducted on 105 patients divided into two group (I & II). Patients of Group I did not receive parenteral magnesium and acted as blank. Magnesium levels were monitored every 6 h for 24 h. Patients of group II received magnesium sulphate therapy. It was administered as 1.0 g (8.1 mEq or 4.05 mmol) magnesium sulphate dissolved in 100 ml of 5 per cent dextrose intravenously as a bolus dose followed by 1.0 g every hour for three successive hours, then 1.0 g every 6 h as a maintenance dose for the next 24 h as intravenous infusion in 5 per cent dextrose. The total dose of magnesium sulphate infused was 30.0 mmol over a period of 24 h (initial dose), then 16.0 mmol (4.0 g) daily till final outcome or a maximum of five days. All the vital parameters were monitored. All the patients were followed till final outcome. The resuscitation methods used were the same in both groups. At the end of the study, mortality rates were calculated in both groups. Hypomagnesaemia was observed as the constant finding in patients of Group I. It was transient and reversed itself without MgSO4. The mortality rate was 52 per cent. On the other hand, magnesium levels rose immediately after parenteral MgSO4 administration in patients of group II and they remained persistently above normal during the observed period.(ABSTRACT TRUNCATED AT 250 WORDS)
|
7786692
|
Selenium and magnesium status in fibromyalgia.
|
Muscle pain has been associated with magnesium (Mg) and selenium (Se) deficiency: magnesium and selenium status were investigated in fibromyalgia (FM). Erythrocyte (E), leucocyte (L) and serum (S) magnesium, serum selenium and zinc, and vitamin B1, B2, A or E status were assessed in 22 patients with fibromyalgia and in 23 age-matched healthy controls. LMg is significantly increased (P < 0.05) and EMg slightly decreased in fibromyalgia. These magnesium abnormalities are associated with previously-reported impairment of thiamin metabolism. Antioxidant status (as well as plasma malondialdehyde) is unchanged in fibromyalgia and serum selenium levels, slightly but not significantly correlated with serum magnesium, is normal.
|
7786691
|
Nutritional magnesium supplementation does not change blood pressure nor serum or muscle potassium and magnesium in untreated hypertension. A double-blind crossover study.
|
The aim of this study was to evaluate if a nutritional dose of magnesium given orally changes the blood pressure in untreated hypertensive patients and if orally-given magnesium had any influence on serum and muscle magnesium and potassium. A randomized, double-blind crossover study design was followed with magnesium 15 mmol/day or placebo treatment for two months. Thirty-nine patients aged 20-59 years, were treated. Samples for magnesium and potassium in blood, muscle and urine were taken at entry time, after two months (crossover time) and after four months (end of study). Systolic and diastolic supine and standing blood pressures were measured at the same times. No significant change in blood pressure, serum or muscle concentrations of electrolytes were observed on magnesium treatment. Urine magnesium rose significantly on magnesium, and it decreased significantly on placebo. Therefore results suggest that 15 mmol magnesium/day, given to untreated mild-to-moderate hypertensives does not alter blood pressure nor the concentrations of magnesium and potassium in serum and muscle, in patients with normal magnesium turnover.
|
7786690
|
Long-term follow-up after acute myocardial infarction in patients randomized to treatment with intravenous magnesium or intravenous propranolol in the acute phase.
|
Ninety-five patients with acute myocardial infarction were followed up for 6 months to 3 years (mean 25.4 months) in a preliminary study to compare the effects of intravenous magnesium (49 patients) with that of intravenous propranolol (44 patients) given immediately after admission to the intensive care unit. There were four cardiac deaths in the propranolol group and no deaths in the magnesium group (P < 0.046) and 27 per cent of patients who received propranolol subsequently developed cardiac failure as opposed to 12 per cent of those who had received magnesium (P < 0.04). Intravenous magnesium given in the early stages of myocardial infarction reduces the subsequent cardiac death rate possibly by reducing infarct size.
|
7786689
|
A prospective randomized trial of intravenous magnesium versus intravenous propranolol in acute myocardial infarction.
|
A total of 266 patients entered into a study comparing the effect of intravenous magnesium and propranolol following acute myocardial infarction. Of these, 97 were able to receive either drug and were therefore randomized into the magnesium (n = 51) or propranolol group (n = 46). 88 patients were unable to receive propranolol and formed a third group (NR) while a further 81 patients could not receive either drug and formed a fourth group (N). The study showed that intravenous magnesium was as effective in preventing potentially lethal arrhythmias as propranolol and could be given to some 70 per cent of such patients whereas propranolol could only be given to 36 per cent.
|
7786688
|
Parenteral magnesium sulphate restores regional contractile function in the post-ischaemic canine myocardium.
|
The effects of parenteral magnesium sulphate (MS) on the regional contractile response of stunned myocardium was examined in 45 pentobarbital anaesthetized dogs. The hearts were instrumented to measure left ventricular pressure (LVP), coronary flow velocity (CFV), mean arterial blood pressure (MAP), and regional contractile function (percent segment shortening, %S; and end-diastolic segment length, EDL). Stunning was produced by a 10 min occlusion of the first descending branch of the left circumflex coronary artery. Immediately upon release of the occlusion, either magnesium sulphate or a dextrose vehicle (D5W, n = 15) was infused. Magnesium sulphate was given intravenously (IV-MS, 100 mg/kg, n = 15) or intracoronarily (IC-MS, 1.5 mg/kg, n = 15). Coronary occlusion was consistently associated with significant decreases in coronary flow velocity and %S in all groups. Following IV-MS, heart rate (HR) and mean arterial blood pressure decreased significantly from preocclusion values, whereas end-diastolic segment length tended to increase and left ventricular pressure remained constant. IC-MS did not produce any changes in heart rate, mean arterial blood pressure, end- diastolic segment length or left ventricular pressure. At the end of the magnesium sulphate infusion (IV or IC), and for the next 60 min, %S returned to or above pre-occlusion values (P < 0.05 vs. D5W). Dyskinesia and hypokinesia were abolished in the magnesium sulphate groups, but were still present in the D5W group at the end of the 60 min period (P < 0.05 vs. pre-occlusion). We conclude that parenteral magnesium sulphate significantly improves regional contractile function in the stunned myocardium. Data from the IC-MS group would suggest a direct myocardial effect, independent of changes in preload, afterload, heart rate or flow.
|
7786687
|
Potentiation of magnesium-deficiency-induced foetotoxicity by concomitant iron deficiency and its prevention by adequate supply via drinking water.
|
Magnesium (Mg) and iron (Fe) deficiency frequently develop during pregnancy. Therefore these factors were studied alone (Mg-L, resp. Fe-L) or in combination (Mg-L/Fe-L) on 16 female and 8 male adult fertile Sprague-Dawley rats. The animals were offered a basal diet containing 30 per cent and 17 per cent of the rat's requirement for magnesium and iron, respectively, starting 21 days before mating (2:1) until 49 days after mating. Offspring were also kept on this regimen during a 3-week lactation period and 7 days post weaning. Drinking water was either enriched with 101 ppm Fe2+ (ferrous gluconate): Mg-L, or 365 ppm magnesium (magnesium-L-aspartate hydrochloride trihydrate, MAH): Fe-L, or with any: Mg-L/Fe-L or with both electrolytes: Controls. Fertility remained unaffected under these conditions. Clinically, Fe-L induced iron deficiency and growth retardation of offspring. Pronounced reproductive toxicity was elicited by Mg-L and was even potentiated by Mg-L/Fe-L. In the parental generation, too, adverse effects of Mg-L were aggravated by Mg-L/Fe-L despite the fact that no iron accumulation occurred. Bioavailability of iron was not impaired by magnesium as MAH. With respect to human pregnancy magnesium supplementation has higher priority over iron supplements. To improve tolerance and compliance both minerals are suggested to be taken simultaneously.
|
7786686
|
Influence of high and low dietary magnesium levels on functional, chemical and morphological parameters of 'old' rats.
|
The effect of dietary magnesium deficiency has so far been studied preferentially in rapidly growing rodents or in adult animals. Since magnesium deficiency frequently occurs in elderly persons too, magnesium- and calcium-deficient diets were offered during 32 and 64 days to 'old' rats (34 months old, spontaneous mortality of 15 per cent). The calcium-deficient diet (2.5 per cent of the requirement) was well tolerated and no profound biochemical disturbances were noted. In contrast, dietary magnesium deficiency (12.5 per cent of the requirement) induced loss of body weight, formation of erythema, severe hypomagnesaemia and increase of tissue calcium levels. No seizures were noted and mortality did not increase, in contrast to growing magnesium-deficient rats. Histologically, age effects were present in bone tissues of old rats, however no additional dietary effects became visible. Tensile strength of femur and rib did not reveal treatment-related changes. Fourteen days preloading with high dietary magnesium increased plasma magnesium and also skeletal concentrations, although to an only small degree. Nevertheless, time until the appearance of erythema in 50 per cent of the rats subsequently fed the magnesium-deficient diet was significantly delayed.
|
7786685
|
Oestrogen but not testosterone increases bone density in orchiectomized rats more when fed moderately magnesium-deficient fructose than moderately magnesium-deficient cornstarch.
|
To investigate interactions between circulating sex hormones, dietary fructose and magnesium on bone mineral density and numbers of trabeculae, 10 weeks old orchiectomized and sham-orchiectomized rats were studied. One-third of the orchiectomized animals were injected with beta-oestradiol-3-benzoate twice per week in sesame oil; another one-third, testosterone cypionate; the remaining one-third as well as the sham-orchiectomized animals, sesame oil only. All animals were fed either fructose or cornstarch without added magnesium. After 14 weeks, a 24 h urine sample was collected for measurements of calcium, magnesium, phosphorus, and cAMP. Blood was collected for determinations of calcium, magnesium, phosphorus, 25-monohydroxy and 1,25-dihydroxycholecalciferols, oestrogen, testosterone, and parathyroid hormone. Femurs were used for measurements of bone mineral density, and tibiae, for numbers of trabeculae. Exogenous testosterone interacted with starch and magnesium deficiency to decrease serum calcium concentration significantly, which increased circulating parathyroid hormone. High circulating parathyroid hormone raised urinary cAMP and serum 1,25-dihydroxycholecalciferol. Increased parathyroid hormone, cAMP and 1,25-dihydroxycholecalciferol may be responsible for bone resorption which was noted in reductions of bone mineral density and the numbers of trabeculae in the group. In contrast, exogenous oestrogen interacted with fructose and magnesium deficiency to increase serum calcium concentration which caused a reduction of circulating parathyroid. Low parathyroid hormone, reduced 1,25-dihydroxycholecalciferol and cAMP may explain the increased bone mineral density and the numbers of trabeculae in this group.
|
7786684
|
Cholesterol oxides in plasma and lipoproteins of magnesium-deficient rabbits and effects of their lipoproteins on endothelial barrier function.
|
The cholesterol oxide (ChO) levels in the plasma and low density lipoproteins (LDL and VLDL) in four groups of rabbits fed for seven weeks either normal (NC) or high cholesterol (HC) with low or normal magnesium (Mg) diets were determined and compared with the NC group fed a standard rabbit diet. The plasma from the NC group contained low levels of different cholesterol oxides. These cholesterol oxides were significantly elevated in the plasma of rabbits fed a HC-normal magnesium or a HC-low magnesium diet. In the NC-low Mg group, 7 alpha-hydroxycholesterol, 7 beta-hydroxycholesterol and 7-ketocholesterol were elevated while the other cholesterol oxides remained within the normal range of the NC group. When the cholesterol oxides were assayed in the LDL and VLDL fractions as micrograms/mg protein, the fractions obtained from the groups fed NC-low Mg, HC-normal Mg or HC-low Mg diets showed higher levels of cholesterol oxides than the fractions obtained from the NC group. When LDL and VLDL fractions from the different groups were incubated at equal protein concentration with confluent endothelial cell monolayers, transendothelial albumin transfer was significantly increased by the lipoproteins from the experimental groups as compared to the control group. These results suggest that elevation of cholesterol oxides in magnesium deficiency or hypercholesterolaemia may be related to their atherogenic effects through decreasing the endothelial barrier function which could enhance the deposition of cholesterol rich lipoproteins into the arterial wall.
|
7786683
|
Enhanced contractile response to phenylephrine and increased density of [3H]PN200-110 binding sites in thoracic aorta isolated from dietary magnesium-deficient rats.
|
The present study was undertaken to examine whether the enhanced contractile response to phenylephrine observed in thoracic aorta isolated from dietary magnesium-deficient rats depends on an increased density of alpha 1-adrenoceptor or calcium channels. Adult male Wistar rats were fed with a magnesium-deficient diet (0.001 per cent magnesium) for 30 days with control groups (0.07 per cent magnesium). The contractile response to phenylephrine was significantly inhibited by nifedipine in both aortas without endothelium, and the degree of the inhibition was significantly greater in magnesium-deficient rats than in controls. Membranes were isolated from both thoracic aortas without endothelium, and the binding of [3H]PN200-110 or [3H]prazosin to the membranes was studied. A single binding site for [3H]PN200-110 or [3H]prazosin was evident for both membranes with high affinity. Dietary magnesium-deficiency increased significantly the maximal number (Bmax) of [3H]PN200-110 binding sites, but not Bmax of [3H]prazosin, and did not alter the binding affinity of both ligands. These results suggest that increased density of calcium channels participates in the enhanced contractile response to phenylephrine in thoracic aortas isolated from dietary magnesium-deficient rats.
|
7786682
|
Effects of extracellular magnesium and beta adrenergic stimulation on contractile force and magnesium mobilization in the isolated rat heart.
|
This study investigates the metabolism of the divalent cation, magnesium (Mg2+) in the isolated perfused Langendorff's rat heart and ventricular slices in the absence and presence of catecholamines including isoprenaline, noradrenaline and adrenaline. Perfusion of the isolated rat heart with a physiological salt solution containing elevated extracellular Mg2+ [Mg2+]o (2.4 mM-6.0 mM) resulted in a marked and progressive decrease in the amplitude of contraction compared to control [Mg2+]o (1.2 mM). In contrast, perfusion of hearts with low (0-0.6 mM) [Mg2+]o caused a small transient increase in the amplitude of contraction which was often accompanied by arrhythmic activity. Perfusion of the heart with a nominally Mg2+ free medium resulted in a time-dependent net efflux of Mg2+ reaching a steady state after approximately 40-50 min of perfusion. This release of Mg2+ was associated with a concurrent decrease in total heart Mg2+. Stimulation of the heart with the beta adrenergic agonist, isoprenaline (10(-7) M) caused large increases in net Mg2+ efflux which was associated with marked increased in both rate and the amplitude of contraction. Similar effects on Mg2+ efflux were also observed during perfusion of the heart with the adenylate cyclase activator, forskolin (10(-5) M). Superfusion of paced ventricular segments with either isoprenaline, adrenaline or noradrenaline (all 10(-6) M) also resulted in a marked transient net efflux of Mg2+. Pre-treatment of segments with the beta adrenergic antagonist, propranolol (10(-5) M) competitively blocked the Mg2+ efflux evoked by the catecholamines. Similarly, pre-treatment of segments with the calcium (Ca2+) channel blocker, verapamil (10(-5) M) caused a significant (P < 0.05) decrease in net Mg2+ efflux evoked by isoprenaline. The results of this study indicate that (1) the perturbation of [Mg2+]o has an important influence on myocardial contractility and (2) the mobilization of Mg2+ in the heart is associated with beta adrenergic stimulation possibly via an elevation in intracellular adenosine 3.5 cyclic monophosphate (cyclic AMP).
|
7786681
|
Magnesium and lithium antagonism of carbachol- and electrically-induced smooth muscle contractions in the rat gastrointestinal tract.
|
The pharmacological actions of lithium and magnesium have been investigated using isolated smooth muscle preparations from the rat gastrointestinal tract. Tissue contraction was evoked by means of carbachol or electrical field stimulation and the degree of inhibition of contraction caused by lithium was measured. Lithium effects were compared with those of the chemically similar ions, magnesium and calcium, by manipulation of the physiological buffer solutions. Lithium antagonism was enhanced when tissue contractile mechanisms were dependent on extracellular calcium concentration in the bathing fluid. This suggests that lithium is acting at the cell membrane by preventing calcium entry via ion channels. These results are consistent with evidence from clinical studies which indicate low cellular accumulation of lithium at therapeutic concentrations.
|
7786676
|
[Results of flexor tendon repair using the Tsuge technic. Apropos of a series of 95 fingers].
|
The authors review a series of 76 patients with 95 fingers involved, 66.6% of them occurring in zone II. The core stitch was performed according to the Tsuge technique (type II) combined with a peritendinous running suture. Results based on TAM were excellent or good in 60%, fair in 22%, and poor in 18%. Influencing factors were associated lesions, mainly vascular and lesions in zone II. Rupture occurred in 5% and adhesion in 22% of cases. Providing similar results to those of other techniques published in the current literature, the Tsuge techniques is preferred because it is simpler and faster to perform.
|
7786678
|
[Vasomotor disorders of the hand and carpal tunnel syndrome].
|
Clinical electrophysiological and chronothermodynamic examinations were performed on 71 patients with paresthesiae and pain of the hands. In 35 patients, the electromyographic examination confirmed the diagnosis of carpal tunnel syndrome on the basis of clear signs of chronic compression of the median nerve at the carpal tunnel. In the other 36 patients, the electro-physiological findings were normal. Twenty-nine patients with bilateral (n = 24) or unilateral (n = 5) carpal tunnel syndrome, and 29 patients without, this syndrome had chronothermodynamic abnormalities demonstrating the vascular origin of the disorders of the hands; in 18 patients, a Raynaud's syndrome was suspected on the basis of severe dysthermia. In 7 patients, the origin of pain and paresthesiae remained unknown. This study shows that (i) vascular disorders of the hand are very frequent in patients with paresthesiae and pain of the hands and may mimic a carpal tunnel syndrome, and (ii) clinical examination is insufficient to assess the diagnosis of carpal tunnel syndrome. Before deciding on any kind of therapy, this diagnosis has to be assessed on electrophysiological and chronothermodynamic examinations performed according to precise protocols.
|
7786677
|
[A comparative study of metacarpal resection and translocation after amputation of the middle finger].
|
The authors studied 43 patients having sustained an amputation of one middle finger treated either by simple ray resection or translocation. The index-middle translocation was followed by more minor postoperative complications compared to all other techniques. A global score, taking into account daily activities, cosmetic result lack of mobility, residual pain, decreased strength, time off work, and return to work gave 131 points for simple third ray resection compare to index middle translocation (-252 points). Surprisingly, reduction of hand span on X ray study was minimal but strength was not correlated and translocation gave better strength, and therefore appears to be more appropriate for manual workers. For ring amputation, the score was definitely better for Leviet translocation with intracarpal osteotomy (143 points versus -36 for simple ray resection). However, the only drawback is more frequent (but minor) residual pain.
|
7786675
|
[A psychological approach to patients undergoing ambulatory surgery].
|
200 patients undergoing outpatient hand surgery were included in a sociological and psychological study. Certain points were found to be important: structure adapted to outpatient surgery, a single team, availability of the surgeon 24 hours a day, telephone call on the day after the operation, etc. Only 0.5% of operated patients claimed to be unhappy with their outpatient experience, but 2.5% would have preferred admission to hospital (for comfort reasons). Overall, outpatient procedures make the patient and his family responsible, by stimulating his cooperation and avoiding regression and dependence, frequently encountered in conventional hospitalization. Psychoanalysis has an important place in the pre- and postoperative approach to the patient.
|
7786673
|
[Modification of the Furnas-Vilkki technic in the reconstruction of congenital or traumatic carpal hands].
|
A technique is described for reconstruction of a pincer, by a second toe transfer, in traumatic and congenital deformities, leaving only the wrist. Transfer on the anterior aspect of the radius allows to benefit from the wrist mobility to compensate for the limited range of motion of the second toe. Proximal situation of the toe gives the possibility of harvesting plenty of tendons to balance the toe. Results have been encouraging in two traumatic and 6 congenital cases of peromelic type of symbrachydactyly.
|
7786668
|
Reversal of haemochromatotic cardiomyopathy in beta thalassaemia by chelation therapy.
|
Haemochromatotic cardiomyopathy is the main cause of morbidity and mortality in patients with beta thalassaemia major. Once congestive heart failure develops most patients die in a few months. Congestive heart failure was reversed and echocardiographic findings were restored to normal in a 24 year old woman with beta thalassaemia who resumed treatment with chelation therapy (desferrioxamine).
|
7786667
|
Systemic thromboembolism leading to myocardial infarction and stroke after fenestrated total cavopulmonary connection.
|
Thromboembolic phenomena involving the caval veins, right atrium, and pulmonary artery are recognised complications after the Fontan operation and other forms of total cavopulmonary connection. A rare case of systemic thromboembolism is reported in a 3 year old girl who had repeated coronary and cerebral thromboembolic events after a fenestrated total cavopulmonary shunt operation. A survey of the 18 paediatric cardiac units in the United Kingdom and Ireland showed a wide discrepancy in anticoagulation policies after Fontan-type operations. Prevention of thrombotic complications by lifelong postoperative anticoagulation may outweigh the risk of haemorrhage.
|
7786666
|
Combined atrial and arterial switch procedure for congenital corrected transposition with ventricular septal defect.
|
A combined atrial and arterial switch procedure was performed in selected patients with congenitally corrected transposition to establish the morphological left ventricle as the systemic ventricle. Immediate and early follow up results are presented. Progressive right ventricular dysfunction and tricuspid regurgitation are common in patients with congenitally corrected transposition who undergo repair of associated lesions. A surgical procedure which re-establishes the left ventricle as the systemic ventricle should improve functional results. Four symptomatic children aged from 9 months to 3 years 1 month (mean 2 years 3 months) with congenitally corrected transposition and ventricular septal defect underwent both an atrial and arterial switch procedure and were followed up for a mean of 12 months (range 6-21 months). There were no early or late deaths. Conduction abnormalities worsened in two patients. Hospital stay ranged from 8 to 17 days (mean 13 days). The cardiothoracic ratio decreased from a mean (range) of 0.65 (0.6 to 0.71) to 0.58 (0.52 to 0.6). Currently, three patients are in functional class I and one child is in functional class II. The combination of an atrial and an arterial switch procedure in symptomatic children with congenitally corrected transposition establishes the left ventricle as the systemic ventricle. The initial experience is encouraging with excellent immediate and early follow up results.
|
7786665
|
Permanent pacemaker practice at a Scottish district general hospital between 1987 and 1993.
|
Raigmore is a district general hospital offering a permanent pacemaker service to its catchment population of 233,500. It has been argued that the British public would be better served by a less centralised pacing service. There also exists the view, however, that a lower rate of complications and best follow up practice are achieved by specialised centres. The pacemaker practice over a 79 month period (January 1987 to July 1993) was thus reviewed with these issues in mind. The pacemaker records of all new implantations for the period under observation were reviewed retrospectively. Data were acquired under the headings age, sex, symptoms, electrocardiographic (ECG) indications, and complications (early and late). Comparison was made with United Kingdom national data, a previous audit from Raigmore, and two recently published large series from specialist centres (one British and the other French). The mean age of patients who underwent implantation was 74 years and 47.5% were male. The most common presenting symptoms were syncope (46%), dizzy spells (24.5%), and heart failure (11.5%). The most common ECG indications for pacing were complete heart block (wide QRS) (28%), atrial flutter/fibrillation with bradycardia (21.6%) and complete heart block (narrow QRS) (9.6%). The implantation rate was 184/million population/year in 1993. The early and late complication rates were low (2.48%). The presence of a pacing centre in a remote part of the United Kingdom fulfils a necessary service and has low complication rates, with implantation rates and patterns that are comparable with those in other parts of the country.
|
7786664
|
ACE for whom? Implications for clinical practice of post-infarct trials.
|
To determine how many lives would be saved if patients were routinely treated with ACE inhibitors after myocardial infarction according to the criteria of four recent major clinical trials, and to estimate the costs and benefits of these approaches. Retrospective survey. The Nottingham Health District. Data from 7855 patients admitted between 1989 and 1990 were combined and the selection criteria of four major clinical trials (AIRE, SAVE, GISSI-3, and ISIS-4) were applied. Of the patients admitted in Nottingham with confirmed myocardial infarcts 39% were eligible for AIRE and 8% for SAVE. In patients with suspected myocardial infarction as defined by the major trials, 60% would have been eligible for GISSI-3 and 63% for ISIS-4. Treating appropriate patients in accordance with these trials would have saved 20 (AIRE), 3 (SAVE), 4 (GISSI-3) and 5 (ISIS-4) lives each year in Nottingham at a drug cost of 5400 pounds, 33 pounds 791, 2730 pounds, and 4116 pounds per life per year saved respectively. Short-term treatment with ACE inhibition appears to be cheaper but such an approach would save fewer lives. The AIRE study is the most applicable to current clinical practice but ACE inhibitors should be offered routinely to patients satisfying the criteria of any of the four major clinical trials.
|
7786663
|
Do radionuclide and echocardiographic techniques give a universal cut off value for left ventricular ejection fraction that can be used to select patients for treatment with ACE inhibitors after myocardial infarction?
|
To determine whether echocardiography and radionuclide angiography give comparable results when the left ventricular ejection fraction is measured early after myocardial infarction and thus whether, irrespective of the method used, a single value for the ejection fraction could be used as a guide for starting treatment with an angiotensin converting enzyme inhibitor. Prospective comparison of measurement of left ventricular ejection fraction by echocardiography and radionuclide angiography. Coronary care units of two university teaching hospitals in Glasgow. 99 patients studied within 36 hours of acute myocardial infarction. Left ventricular ejection fraction assessed by echocardiography and radionuclide angiography. 70 (77%) of the 99 patients had ejection fraction measured by both echocardiographic and radionuclide techniques, 30 in centre 1 and 40 in centre 2. In centre 1 the mean difference (SD) in ejection fraction (radionuclide angiography--echocardiography) was -8 (10%); 95% CI -12 to -4%. In centre 2 the mean difference was -14 (11%); 95% CI -17 to -11%. If patients had been treated with an ACE inhibitor on the basis of a radionuclide ejection fraction of < 40% then 93% in centre 1 (28 of 30) and 98% in centre 2 (39 of 40) would have been treated. This compares with 63% (19 of 30) and 50% (20 of 40), respectively if echocardiography had been used as a guide. Measurement of ejection fraction is highly dependent on the method used and it is therefore impossible to quote a universally applicable figure for left ventricular ejection fraction below which an ACE inhibitor should be used after myocardial infarction.
|
7786661
|
Effects of type 1 diabetes mellitus on cardiac function: a study of monozygotic twins.
|
To investigate left ventricular size and function in type 1 diabetes and their relation with diabetes duration, glycaemic control, autonomic dysfunction, and complications of diabetes. Cross sectional study using a pulsed wave Doppler echocardiogram to assess left ventricular dimensions, wall thickness, and transmitral blood flow velocity signals. 40 monozygotic twin pairs (23 male, mean age 26 years) discordant for type 1 diabetes and 40 non-diabetic singleton controls with no clinical evidence of cardiac ischaemia. For all Doppler echocardiographic measurements there were strong correlations between monozygotic twins but not between twins and control subjects. Left ventricular dimensions, wall thickness and systolic function, peak E velocity, and the velocity integrals of early left ventricular filling were similar in all three groups. Peak A velocity and the velocity integrals of late ventricular filling (mean (SD)) were greater in diabetic twins (45 (12) v 38 (8) cm/s, P = 0.002; and 32 (11) v 26 (6), P = 0.0002). Diabetic twins had lower E/A ratio (1.59 (0.39) v 1.83 (0.39), P < 0.001), greater atrial filling fraction to total diastolic filling (28 (6) v 25 (5)%, P = 0.002), and prolonged isovolumic relaxation time (72 (12) v 63 (9) ms, P < 0.001). The differences in Doppler findings between diabetic and non-diabetic twins were related to disease duration whereas the prolongation of the isovolumic relaxation time was related to cardiac autonomic dysfunction. These results show that twins with type 1 diabetes have left ventricular diastolic dysfunction related to diabetes duration and cardiac autonomic dysfunction but not to glycaemic control or microvascular complications. In addition, genetic factors contribute to left ventricular dimension and function.
|
7786662
|
High wall shear stress proximal to myocardial bridging and atherosclerosis: intracoronary ultrasound and pressure measurements.
|
Studies have shown that myocardial bridging may prevent coronary atherosclerosis and that the segment proximal to the bridge is often sclerosed. The underlying mechanism is still unknown. Intracoronary ultrasound and pressure measurements were performed in a patient with myocardial bridging in the left anterior descending coronary artery. A 3.5 F, 20 MHz probe was used to measure the change in cross sectional area of the lumen during the cardiac cycle. Intracoronary pressure was measured with a Double tip, end mounted pressure transducer system, the catheter having two pressure sensors located at the end of the catheter 3 cm apart. Intracoronary pressure was recorded as the catheter was slowly advanced and pulled back through the left anterior descending coronary artery. Systolic compression of the bridge segment was clearly visualised on ultrasonography and an eccentric plaque with calcium deposit was found in the segment proximal to the bridge. The pressure in the segment proximal to the bridge (160/26 mm Hg) was higher than that of the proximal normal segment (126/68 mm Hg). The pressure distal to the bridge was 68/30 mm Hg. A highly characteristic "sucking effect" was found in the bridge segment. The pressure in the bridge segment was 102/-40 mm Hg. The pressure in the segment proximal to the myocardial bridging was higher than aortic pressure. Disturbance of blood flow and high wall stress proximal to myocardial bridging was a main contributor to the development of atherosclerosis in the segment proximal to the bridge.
|
7786660
|
Ventilatory responses to exercise in adults after repair of tetralogy of Fallot.
|
Adult patients with total correction of tetralogy of Fallot may have poor exercise capacity associated with impaired right heart function and in particular pulmonary regurgitation. The ventilatory responses to exercise were studied in a group of such patients to assess relations between ventilation, exercise capacity, and right ventricular function. 30 patients (7 female) (aged 27.8 (6.0) years) and 30 (7 female) controls of a similar age range were studied prospectively. All underwent exercise testing with metabolic gas exchange to determine peak oxygen consumption (peak VO2), and (as indices of the ventilatory response) the slope of the relation between both respiratory rate (RR) and ventilation (VE) against carbon dioxide production (VCO2). Patients were studied with pulsed wave Doppler echocardiography to determine pulmonary arterial systolic and diastolic flow characteristics. Patients were defined as having restrictive right ventricular function where diastolic pulmonary forward flow was seen coincident with atrial systole. In the group with tetralogy of Fallot mean (SD) peak VO2 was 35.3 (7.5) ml/kg/min (93.6 (15.3) % of expected for age, weight, height and sex). The RR/VCO2 slope was steeper in the Fallot group (6.8 (2.6) v 9.6 (4.7), P < 0.02). Those with restrictive right ventricles achieved a higher peak VO2 than those without (82.5 (10.1) % v 100.9 (13.8), P < 0.001). In the Fallot group alone, there was an inverse relation between ventilatory response and peak VO2 (RR/VCO2 v peak VO2; r = -0.63, P = 0.003: VE/VCO2 v peak VO2; r = -0.62, P < 0.001). Many of these patients with repaired tetralogy of Fallot had near normal exercise capacity, but as exercise capacity decreased, the ventilatory response to exercise increased. This was not due to alterations in pulmonary function tests or to the effects of cardiac size causing decreased lung volume. It may be that the increased ventilatory rate at a given level of carbon dioxide production acts as a respiratory pump aiding right ventricular function.
|
7786658
|
Peripheral haemodynamic effects of inhibition of prostaglandin synthesis in congestive heart failure and interactions with captopril.
|
To investigate the role of prostaglandins in maintaining circulatory homoeostasis in chronic heart failure and the hypothesis that an increase in vasodilatory prostaglandin synthesis may contribute to the actions of angiotensin converting enzyme inhibitors in heart failure. Randomised, double blind, placebo controlled studies. Cardiac output and renal and limb blood flow were measured after oral indomethacin 50 mg or placebo followed by "open" intravenous infusion of prostaglandin E2 (study A). In a second study the same measurements were made after oral indomethacin 50 mg or placebo was given 30 min before "open" captopril (study B). Blood pressure was measured using a mercury sphygmomanometer. Cardiac output was determined by Doppler interrogation of blood flow in the ascending aorta and echocardiographic measurement of aortic root diameter. Renal blood flow was calculated from the effective renal plasma flow measured by p-aminohippurate clearance and the haematocrit, and glomerular filtration rate by endogenous creatinine clearance. Limb blood flow was measured by venous occlusion plethysmography using mercury in silastic strain gauges. The concentration of plasma prostaglandin E2 was measured by radioimmunoassay. University department of cardiovascular medicine. 12 patients with chronic stable heart failure before starting treatment with angiotensin converting enzyme inhibitors. Indomethacin resulted in adverse effects on cardiac output, systemic vascular resistance, renal blood flow, glomerular filtration, urinary sodium excretion, and calf vascular resistance. Changes were reversed with infusion of prostaglandin E2. Pretreatment with indomethacin resulted in the attenuation of the acute increase in cardiac output and decrease in systemic vascular resistance that occurred with captopril. Similarly, an increase in renal blood flow with captopril was attenuated by indomethacin. The acute adverse effects of indomethacin on central and peripheral haemodynamic and renal function suggest that prostaglandins have a significant role in the regulation of peripheral blood flow and renal function in patients with stable chronic heart failure. The attenuation by indomethacin of captopril induced improvements in haemodynamic function and renal blood flow is consistent with the hypothesis that captopril may act in part via an increase in prostaglandin synthesis.
|
7786659
|
Change in delay of atrioventricular conduction after radiofrequency catheter ablation for atrioventricular nodal re-entry tachycardia.
|
To monitor atrioventricular conduction after radiofrequency ablation for atrioventricular nodal re-entry tachycardia. Measurement of PR interval from 12 lead surface electrocardiograms before; at 0, 24, 48, 72, and 96 hours; and at 1 and 6 months after radiofrequency ablation. 40 consecutive patients with atrioventricular nodal re-entry tachycardia. The anterior approach was used in 23 patients, the posterior approach in 17. With the anterior approach the PR interval increased significantly and progressively until 48 hours after ablation (maximum 282 (SD 62.2) ms, before ablation 142 (29.5) ms; P < 0.0001). Up to 96 hours no further change was observed, but one month after ablation the PR interval had decreased to a value not significantly different from that 24 hours after the procedure (231 (51.2) ms). In one patient total atrioventricular block developed 24 hours after an uncomplicated procedure and a permanent pacemaker was implanted. With the posterior approach the PR interval increased slightly in the first 24 hours (156 (22.7) ms, before ablation 144 (21.2) ms P = 0.004), but it had returned to preablation values at 1 month. One patient developed second degree atrioventricular block during the first 24 hours after ablation, despite delivery of all radiofrequency pulses posterior to Koch's triangle at sites without His bundle deflection. PR intervals at 6 months did not differ significantly from the values at 1 month. After the anterior approach the progressive delay in atrioventricular conduction up to 48 hours after radiofrequency ablation for atrioventricular nodal re-entry tachycardia warrants continuous in hospital monitoring of patients for at least two days after the procedure.
|
7786657
|
Placebo controlled trial of felodipine in patients with mild to moderate heart failure. UK Study Group.
|
To compare the effects of felodipine and placebo in patients with New York Heart Association functional class II or III and stable congestive heart failure despite treatment with an angiotensin converting enzyme inhibitor, diuretic, or digoxin, or any combination of these three drugs. 252 patients were randomised in a double blind, parallel group study after a 2-4 week placebo run-in to oral treatment with either felodipine extended release formulation or placebo 2.5-10 mg twice daily given in addition to existing background medication for a further 12 weeks. Patients aged 18-75 years of either sex with chronic congestive heart failure due to ischaemic heart disease, hypertensive heart disease, or dilated cardiomyopathy with or without secondary mitral insufficiency that was stable during the preceding two months were included in the study. Treadmill exercise tests according to the modified Naughton protocol were performed at baseline, and after six, 11, and 12 weeks of treatment. Signs and symptoms of heart failure were assessed at every visit. Physical examination was performed and left ventricular ejection fraction measured at baseline and after 12 weeks. Mean (SD) baseline exercise test times increased from 434 (162) s and 480 (157) s for felodipine and placebo groups respectively to 541 (217) s and 591 (218) s at 12 weeks or the last visit. The change in exercise from baseline to last visit was 107 (141) s for patients given felodipine and 112 (128) s for those given placebo (P > 0.20). There was also no difference between treatments with respect to the other efficacy variables. There were few deaths in the study (felodipine n = 3, placebo n = 2). More patients who received felodipine were withdrawn from treatment (n = 29) than those who received placebo (n = 17). The most common adverse events of the 54 and 28 cited as reasons for withdrawal in the felodipine and placebo groups respectively were increased need for non-study heart failure treatment (n = 10; 8%)--that is, starting new medication or changes in the dosage of existing treatment for patients given felodipine, and nausea (n = 4; 3%) for those given placebo. Patients withdrawn from the study due to increased need for non-study heart failure treatment rapidly stabilised and recovered. Felodipine has not been shown to be of benefit in patients with mild to moderate heart failure.
|
7786655
|
Familial dilated cardiomyopathy in the United Kingdom.
|
To determine the frequency and mode of inheritance of familial dilated cardiomyopathy in the United Kingdom. Two recent prospective studies have suggested that familial forms of dilated cardiomyopathy are common but have been limited by selective screening methods, inadequate diagnostic criteria, and low rates of ascertainment. Prospective screening study of 236 relatives from 40 families of patients with dilated cardiomyopathy. Screening consisted of clinical examination, 12 lead electrocardiogram, and two-dimensional Doppler echocardiography. Relatives with systemic hypertension and other cardiac diseases were excluded from the study. All echocardiograms were performed by an experienced echocardiographer who was blinded to clinical information. Relatives were classified as having dilated cardiomyopathy, left ventricular enlargement (method of Henry), depressed fractional shortening, or as being normal. Relatives with abnormal investigations underwent further evaluation as appropriate. Twenty five cases of dilated cardiomyopathy were identified and came from 10 (25%) of the 40 families screened. Pedigree analysis was most consistent with autosomal dominant inheritance and variable penetrance (65-95%). Of the remaining apparently healthy relatives, 37 (18%) were found to have left ventricular enlargement and nine (4%) depressed fractional shortening; these values were significantly higher than those observed in 239 healthy controls (24 (10%), P = 0.02 and one (0.4%), P = 0.01, respectively). Patients with dilated cardiomyopathy commonly have an affected family member and a high proportion of apparently healthy relatives with minor echocardiographic abnormalities. Segregation analysis suggests that familial dilated cardiomyopathy is the result of the transmission of a rare autosomal dominant gene. Further studies are currently underway to characterise the molecular basis of familial dilated cardiomyopathy and identify early disease within these families.
|
7786656
|
Comparison of five cardiac markers in the detection of reperfusion after thrombolysis in acute myocardial infarction.
|
To investigate and compare the clinical usefulness of serial measurements of five cardiac marker proteins, namely creatine kinase (CK), CK-MB mass, myoglobin, troponin T, and myosin light chain 1, in the early detection of reperfusion after thrombolytic treatment. Serial blood samples were taken from 26 patients presenting with acute myocardial infarction. Concentrations of the five markers were assayed in each sample. Thrombolytic treatment was given to the patients who were divided into those who reperfused (n = 17, group A) and those who failed to reperfuse (n = 9, group B) on the basis of clinical signs and angiography within 24 h. The release profiles of CK, CK-MB mass, myoglobin, and troponin T for patients in group A differed from those of patients in group B. No difference was observed in the release profile of myosin light chain 1 between the two groups. The time to peak concentration of CK, CK-MB mass, myoglobin, and troponin T occurred significantly earlier in patients of group A than in those of group B, with myoglobin peaking earlier than the other markers. An index, defined as the ratio of the concentration of each marker immediately before and 2 h after the start of thrombolytic treatment, was calculated for each marker in groups A and B. The 2 h myoglobin and troponin T indices were significantly different between groups A and B. The diagnostic efficiency of the myoglobin index, however, was best at 85%. These studies suggest that myoglobin has greater potential than the other markers examined in the detection of reperfusion after thrombolytic treatment.
|
7786643
|
Cross calibration of QDR-2000 and QDR-1000 dual-energy X-ray densitometers for bone mineral and soft-tissue measurements.
|
Replacement of dual energy X-ray densitometry (DXA) equipment may be necessary in many labs with time, or new equipment may be added. In this context we compared patient scans between a Hologic QDR-1000W and a QDR-2000 (n = 29-43, depending on anatomic region) and between QDR-2000 single beam (SB) and fan beam (FB) modes (n = 40-62) as a quality control measure. A total of 83 subjects (79 females and four males) with a wide range of bone mineral densities (BMD) were studied. There was a linear relationship between results with the QDR-1000W and QDR-2000 in SB mode, and between SB and FB mode on the QDR-2000, but the magnitude of the coefficients and constants differed for the different anatomic regions. In SB mode the QDR-2000 underestimated whole body and forearm BMD by 3% relative to the QDR-1000W, even after cross calibration using a spine phantom. Femoral total BMD was slightly, but not significantly, underestimated. Thus, additional postanalysis correction had to be applied to forearm and whole-body scans. In FB with the QDR-2000, spine and whole-body BMD was underestimated by 3%, but femur total and neck BMD was overestimated by 2.2 and 2.8%, respectively, compared with SB scans on the same device. Soft-tissue composition with FB (enhanced analysis protocol) on the QDR-2000 differed greatly from that obtained using SB (standard protocol). Lean tissue mass was 4 kg lower and fat mass 4 kg higher in FB mode.(ABSTRACT TRUNCATED AT 250 WORDS)
|
7786642
|
Validation of wall thickness estimates obtained with polarized light microscopy using multiple fluorochrome labels: correlation with erosion depth estimates obtained by lamellar counting.
|
Numerous methods are currently being employed to estimate completed wall thickness and final erosion depth. Conflicting estimates of calculated bone balance have been obtained from the estimates of wall thickness and erosion depth using these various methods. To assess the utility of two specific methods to estimate wall thickness (polarized microscopy) and erosion depth (lamellar counts), we conducted a study in normal young adult beagle dogs, a model where bone balance should approximate 0. Dogs were administered multiple fluorochrome labels in vivo to label activity forming bone pockets. These labels were used to confirm the position of the cement line of the bone structural unit (BSU) in fluorescent light. Parallel measurements of wall thickness were then collected in polarized light. These estimates were compared to estimates of erosion depth obtained by lamellar counting and bone balance was calculated. Estimates of wall thickness correlated well with estimates of erosion depth with bone balance not differing significantly from 0. These data suggest that the combination of these two methods is a reasonable approach to obtaining estimates of bone balance at the level of the remodeling unit.
|
7786641
|
Cortical mineral content of the radius assessed by peripheral QCT predicts compressive strength on biomechanical testing.
|
Our aim was to evaluate the role of cortical bone in resistance to compression in the human radius. Thirty-three left cadaver forearms were scanned on an XCT 960 Stratec CT scanner. Cortical density and cortical thickness were measured at the junction of the middle and distal third of the radius. Subsequently, 2-cm-high cylindrical specimens, centrated on the level of the CT slice, were cut. After removal of the endosteal trabecular bone, the specimens were submitted to compressive testing, using an Instron machine, and load deformation curves were obtained. Maximal stress (load corrected for cross-sectional area) showed a significant relationship with the density (r = 0.78) as well as with the thickness (r = 0.74) of the cortex. The closest correlation involved the maximal load and the mineral content of the cortex specimens (r = 0.87). We conclude that the mineral content of these radius cortex specimens, measured using peripheral QCT, predicts their compressive strength on biomechanical testing.
|
7786640
|
Effects of basic fibroblast growth factor (bFGF) on bone formation in growing rats.
|
The effects of basic fibroblasts growth factor (bFGF) administered intravenously at dosages of 0.1 and 0.3 mg/kg per day for 7 days to growing rats are reported. Static and dynamic histomorphometry techniques were applied to the microradiographs and undecalcified ground sections of the proximal tibiae and tibial shafts. The bone histomorphometric analyses in the proximal tibia revealed that 0.1 mg/kg per day of bFGF increased longitudinal growth rate, cartilage cell production rate, and metaphyseal bone area. In the tibial shaft, the endocortical mineral apposition and bone formation rates, total bone area, total osteoid area, and medullary bone area were increased, but the periosteal mineral apposition and bone formation rates were depressed. Two weeks after the cessation of treatment, the increased osteoid bone on the endocortical surface and in the marrow cavity was completely calcified, and the total mineralized area in the tibial shaft was significantly increased. The rats given 0.3 mg of bFGF/kg per day showed retarded weight gain, defective calcification at the growth plate metaphyseal junction, and on the endocortical surface. The growth plate width was increased, and the longitudinal growth rate, cartilage cell production rate, endocortical labeled surface, and bone formation rate were decreased. Two weeks after the cessation of treatment, these changes were almost reversed, and the longitudinal growth rate and cartilage cell production rate were increased as rebound phenomena. These results suggest that a low dose (0.1 mg/kg per day) of bFGF stimulates endosteal and endochondral bone formation and depresses periosteal bone formation in growing rats.
|
7786638
|
Bone resorption induced by a metastatic human melanoma cell line.
|
Bone resorption resulting from the metastatic human melanoma cell line (A375) was investigated morphologically using an experimental model of bone metastases in nude mice. An injection of A375 (1 x 10(5)) in the left ventricle produced multiple osteolytic lesions. Many TRAPase-positive multinucleated cells, identified by EM as osteoclasts, were observed on the bone surface at the site of metastases. The findings suggest that bone resorption was caused by osteoclasts developed in the presence of tumor cells. Even where tumor cells were juxtaposed to bone surface, small and flat TRAPase-positive cells were shown to exist on the bone surface. Thus, bone resorption was mainly associated with the occurrence of osteoclasts. A large number of osteoclast progenitor cells were also observed adjacent to tumor cells and/or stromal cells located apart from bone, indicating possible participation of tumor cells and/or stromal cells in the differentiation of osteoclasts. Ultrastructurally, stromal cells and/or extracellular matrices were present between tumor cells and osteoclast progenitor cells. Immunohistochemical observation clarified the localization of heparan sulfate proteoglycan (HSPG) and fibronectin (FN) around osteoclast progenitor cells. These findings suggest that they play an important role in providing a microenvironment favorable for osteoclast differentiation and activation. The immunohistochemical localization of IL-6, PGE2, and TGF-alpha also indicates that they are involved in osteoclast differentiation and activation. In conclusion, bone resorption at the metastatic sites of A375 is mediated via osteoclasts and A375 cells may be involved in the differentiation and activation of osteoclasts in association with stromal cells, extracellular matrices (HSPG, FN) and osteotropic cytokines (IL-6, PGE2, TGF-alpha).
|
7786639
|
Parathyroid hormone restores bone mass and enhances osteoblast insulin-like growth factor I gene expression in ovariectomized rats.
|
In the osteopenic rat model, estrogen deficiency results in increased bone turnover with net bone loss occurring during cancellous modeling. However, estrogen-deficient rats treated with parathyroid hormone (PTH) experience a net gain of bone tissue due to the anabolic effects of PTH. To evaluate the possibility that local insulinlike growth factor I (IGF-I) production modulates the in vivo balance of bone formation and resorption in ovariectomized (OVX) estrogen-deficient rats and in OVX rats treated with PTH, we have studied the expression of IGF-I mRNA in cancellous bone osteoblasts using in situ hybridization techniques. Three-month-old virgin rats were subjected to sham surgery or OVX. Two weeks later, half the OVX rats began treatment with hPTH(1-34), 5 micrograms/100 g body weight, 5 days/week for 4 weeks. All animals were killed at the same time, providing three groups: sham surgery alone; OVX alone; and OVX + PTH. Bone histomorphometry performed in undecalcified sections of tibial metaphysis confirmed that OVX rats had significantly (p < 0.05) increased bone surface formation rates (BFR/BS, micron 3/micron 2/year) with osteopenia while OVX + PTH rats had increased BFR/BS with increased bone volumes compared to sham animals (p < 0.05). Decalcified tissue from all three groups contained immunoreactive IGF-I. Similar tissue sections were hybridized with an 35S-labeled IGF-I antisense riboprobe. Evaluation of the specific signal over cancellous osteoblasts allowed a relative estimate of IGF-I mRNA transcript abundance in the three groups by counting silver grains per osteoblast, corrected for background activity.(ABSTRACT TRUNCATED AT 250 WORDS)
|
7786636
|
Hypercalciuria in osteogenesis imperfecta: a follow-up study to assess renal effects.
|
In 1991, we reported that hypercalciuria is a common finding in our pediatric patient population with osteogenesis imperfecta (OI) (17 of 47 = 36%). Here, we prospectively screened 12 of these hypercalciuric children, on average 4 years subsequent to the discovery of elevated urine calcium levels, for adverse effects on renal function. Despite an ad libitum decrease since initial investigation of about 30% in their previously normal dietary calcium intake (adjusted for body weight), 8 of the 12 patients remained hypercalciuric (urine calcium/creatinine > 0.62 mmol/mmol). We found, once again, that urinary calcium levels significantly correlated with the severity of the skeletal disease as assessed by z-score for height (r = -0.75, p = 0.005). Evaluation of kidney function, however, revealed: (i) normal routine urinalysis in all but 1 subject who had transient microscopic hematuria; (ii) unremarkable concentrating ability determined by fasting urine osmolality; (iii) normal creatinine clearance, and (iv) unremarkable ultrasonography to measure renal size and to screen for nephrocalcinosis or nephrolithiasis. Although no significant renal compromise was detected with these studies in our hypercalciuric pediatric OI patients, investigation of affected adults, especially those severely affected, will be important to assess whether this is a long-term problem and if adverse effects on the kidneys do develop.
|
7786637
|
Evidence for the synthesis of parathyroid hormone-related protein (PTHrP) by nontransformed clonal rat osteoblastic cells in vitro.
|
Parathyroid hormone-related protein (PTHrP) is synthesized by a variety of tumors and is thought to be the main cause of the clinical syndrome of humoral hypercalcemia of malignancy (HHM). In addition to its parathyroid hormone (PTH)-like actions, novel actions of PTHrP on placental calcium transport and inhibition of in vitro osteoclast activity have been demonstrated. The fact that osteoblasts act as mediators of osteoclastic bone resorption prompted us to investigate whether nontranformed, osteoblastlike cells produce PTHrP. PTHrP has been detected in developing human fetal bones and in rat long bones in culture. For this study, osteogenic cells, CRP 5/4 and CRP 10/30, were employed. Both cell types represent clonal bone cell populations established from 1-day-old rats. While CRP 10/30 cells express the osteoblastic phenotype, CRP 5/4 cells resemble cells with preosteoblastic properties. With a radioimmunoassay (RIA), utilizing antiserum directed against the amino-terminal PTHrP(1-40), it was found that both cell types synthesize PTHrP constitutively. CRP 10/30 cells produce about twice as much as CRP 5/4 cells. Transforming growth factor-beta (TGF-beta 1) was shown to increase the synthesis of PTHrP in CRP 5/4 cells by about 2.5-fold, while in CRP 10/30 cells it caused an approximate 50% reduction of PTHrP. Employing the reverse transcriptase polymerase chain reaction (RT-PCR) technique it was found that both bone cell types express mRNA for PTHrP and that the modulation of the PTHrP mRNA levels by TGF-beta 1 in CRP 5/4, and to a lesser degree in CRP 10/30 cells, was reflected in a change in the level of PTHrP protein in the culture medium.(ABSTRACT TRUNCATED AT 250 WORDS)
|
7786635
|
Predicting vertebral deformity using bone densitometry at various skeletal sites and calcaneus ultrasound.
|
We investigated the usefulness of bone density measurements from multiple skeletal sites and calcaneus ultrasound for evaluating the probability of vertebral deformation. Bone mineral density (BMD) was measured at the second metacarpal and middle phalanges using radiographic absorptiometry of hand radiographs, and at the lumbar spine using dual-energy x-ray absorptiometry. Distal radius and proximal radius were measured using single-energy x-ray absorptiometry (SXA), expressed as bone mineral content (BMC, grams per centimeter), and as BMD (grams per square centimeter). The calcaneus was measured using both SXA (BMD) and broadband ultrasound attenuation (BUA). Among the women in this study (mean age 74, SD = 5), 84 women developed new vertebral deformations (57 cases with one and 27 cases with two or more deformations), which were identified on serial radiographs during an average of 9 years prior to the measurements of bone density. Logistic regression analysis was used to calculate odds ratios for risk of deformation corresponding to a 1-SD difference in density or ultrasound, adjusted for age. All bone measurements were significantly associated with vertebral deformation, with odds ratios (95% confidence intervals) ranging from 1.40 (1.10, 1.78) for proximal radius BMD to 1.88 (1.45, 2.44) for calcaneus BMD measurements. Measurements of calcaneal BUA, calcaneal BMD, and hand BMD generally remained significant when included simultaneously with another measurement in the same model, suggesting that spine or radius BMD may not provide much additional information about risk of deformation. It appears that all of the measurements of bone density and ultrasound provide useful information regarding the probability of deformation. These findings await confirmation in a prospective study.
|
7786634
|
Stimulation of bone formation by dynamic mechanical loading of rat caudal vertebrae is not suppressed by 3-amino-1-hydroxypropylidene-1-bisphosphonate (AHPrBP).
|
We have recently developed an experimental system whereby pins inserted into the seventh and ninth caudal vertebrae of rat tails are used to load the eighth caudal vertebrae (C-8) in compression. In this model, a single 5-min period of dynamic loading, sufficient to induce strains within the range to which bones are exposed under physiological circumstances, stimulates lamellar bone formation in the cancellous bone of the vertebrae. The rapidity with which the increase in bone formation was induced raised the possibility that this bone formation might have occurred without prior resorption. To test the role of bone resorption in the response of the bone to mechanical stimulation, we compared the anabolic response to a single period of loading, of rats treated with 3-amino-1-hydroxypropylidene-1-bisphosphonate (AHPrBP) or vehicle. We found that mechanical loading caused a significant increase in dynamic and static indices of bone formation. The same indices were unaffected by AHPrBP, while the bone formation rate in the tibiae was reduced by AHPrBP. These results suggest that the increased bone formation induced by mechanical stimulation in the cancellous bone of rat vertebrae is not dependent on bone resorption.
|
7786633
|
Intervertebral variation in trabecular microarchitecture throughout the normal spine in relation to age.
|
The vertebral bodies of the complete spine (C-3-L-5) were removed in 26 autopsy cases without evidence for primary or secondary bone disease (13 males aged 19-79 years and 13 females aged 17-90 years). A sagittal segment through the center of all vertebral bodies was embedded undecalcified in hydroxyethylmethacrylate and processed to so-called surface stained block grindings. Histomorphometric analysis of the complete segment was performed using a computer-assisted image analysis system (IBAS 2000). The structural parameters investigated were bone volume (BV/TV) and trabecular interconnection quantificated by trabecular bone pattern factor (TBPf). A close correlation of BV/TV and TBPf was found in all vertebral bodies irrespective of vertebral region (r = 0.8, p < 0.001). This indicates that the age-related decrease of trabecular bone mass is primarily the consequence of the transformation from plates to rods and the loss of whole trabecular structures. This basic principle is valid throughout the complete spine. However, the systematic analysis of vertebral trabecular bone from C-3 to L-5 revealed a significant intervertebral variation of trabecular microarchitecture. The density of trabecular structure of cervical vertebrae is much higher than that of thoracic and lumbar vertebrae (p < 0.001). The extent of age-related loss of trabecular bone mass and structure showed a decrease within the spine from the caudal to the cranial region (p < 0.05). The loss of bone volume in individuals between the ages of 30 and 80 years in the lumbar spine was 53%, whereas in the thoracic spine the decrease was 41%, and in the cervical spine only 24%.(ABSTRACT TRUNCATED AT 250 WORDS)
|
7786632
|
Do ultrasound measurements on the os calcis reflect more the bone microarchitecture than the bone mass?: a two-dimensional histomorphometric study.
|
Few studies have analyzed the relationship between ultrasound measurements (US) and corresponding histomorphometric parameters of the calcaneus. To address this question we have compared US and histomorphometric parameters in 17 whole human os calcis from amputation or necropsy. Speed of sound (SOS), broadband ultrasound attenuation (BUA), and bone mineral density (BMD) were measured on the whole foot at the calcaneal site using an Achilles device and a DPX-L densitometer (Lunar). The os calcis was dissected and a 1-cm-wide transcortical parallelepiped extracted with a biopsy needle, focused on the center of the measured area. Histomorphometry was performed on undecalcified biopsies. Structural and connectivity parameters were measured on 7-microns-thick sections with both automatic (Biocom) and semiautomatic analyzers (Ibas 1, Kontron). We found that all ultrasonic and densitometric parameters reflected the true amount of bone and were correlated with only some of the parameters reflecting bone microarchitecture. From stepwise regression analysis, we found that 68%, 67%, 72%, and 74% of the variance of SOS, BUA stiffness, and BMD, respectively, were explained significantly by trabeculae thickness only. Ultrasonic measurements appear to reflect bone quantity rather than bone microarchitecture. The current conclusion is fairly negative with respect to the ability of ultrasound to assess structural parameters, but our limited sample size did not give enough power to our study to reach statistically significant correlations. In addition, the calcaneus is anisotropic and the ultrasound interaction in bone is a three-dimensional phenomenon. So, a three-dimensional study rather than a two-dimensional one should be performed.
|
7786631
|
Osteoblasts and osteoclasts in adult human osteophyte tissue express the mRNAs for insulin-like growth factors I and II and the type 1 IGF receptor.
|
Insulin-like growth factors (IGFs) are among the most abundant growth factors present in bone. In vitro, bone-derived cells both produce and respond to IGFs I and II, suggesting that these growth factors play an autocrine role in the regulation of bone turnover. In vivo, however, particularly in adult bone, their sites of expression have not been well documented. We have used, therefore, the technique of in situ hybridization to study the expression of the mRNAs for IGFs I and II and the type 1 IGF receptor in adult human osteophyte tissue. Throughout the developing osteophyte there was a strong association between osteogenesis and the expression of all three mRNA transcripts. The highest levels of expression were observed in active osteoblasts. Hybridization signals were weak or absent in flat cells lining quiescent surfaces and in cells of the bone marrow, including those that expressed alkaline phosphatase activity. Osteocytes and cells of the periosteum were negative. At sites of endochondral bone formation newly differentiated and hypertrophic chondrocytes expressed the mRNAs for IGFs and IGF receptor whereas cells of the perichondrium were negative. A striking finding of this investigation was that osteoclasts at sites of bone and calcified cartilage resorption expressed high levels of all three mRNA transcripts. These results support the hypothesis that locally produced IGFs are important regulators of bone formation. The differential expression of all three transcripts among cells of the osteoblast lineage suggests that IGFs may be involved in the maintenance of the mature osteoblast phenotype rather than in inducing the differentiation of marrow precursors or controlling the osteoblast-osteocyte transition.(ABSTRACT TRUNCATED AT 250 WORDS)
|
7786629
|
[A 21-year-old man with distal dominant progressive muscle atrophy].
|
We report a 21-year-old man with distal dominant progressive muscle atrophy. The patient was apparently well until 17 years of age when he noted a decrease in exercise tolerance. One year later, he noted difficulty in arising his heels when the walked. He was admitted to our service for the work up in June 10, 1992. On admission, the patient was rather slender in the body build up; otherwise general physical examination was unremarkable. Upon neurologic examination, mental status and higher cerebral functions were normal. In the cranial nerves, the sternocleidomastoid muscles were atrophic bilaterally; other cranial nerves appeared intact. His gait was unstable and he showed steppage gait; walking on toes and heels were impossible. Distal dominant muscle atrophy was noted in both upper and lower extremities. Muscle strength in the deltoid, biceps brachii and triceps brachii was normal. In the lower extremities, both tibialis anterior and triceps surae muscles were weak (3/5). The iliopsoas and quadriceps femoris muscles were normal, however, the adductor muscles of the thigh showed marked weakness (2/5). Myotonia was absent. Deep reflexes were decreased; sensation was intact. Routine blood tests were unremarkable; CK was 96 IU/l, lactate 6.9 mg/dl, and pyruvate 0.61 mg/dl. After an ischemic forearm exercise test, blood lactate level rose to 22.5mg/dl (base line 11.2), and blood ammonia to 88.3 micrograms/dl (base line 71.2). EMG showed myogenic changes and myotonic discharges. A diagnostic biopsy was performed. The patient was discussed in a neurologic CPC, and the chief discussant arrived at the conclusion that the patient had type III glycogen storage disease. The differential diagnosis included rimmed vacuole type myopathy, Miyoshi type distal muscular dystrophy, Welander type muscular dystrophy, adult type acid-maltase deficiency, and lysosomal glycogen storage disease with normal acid maltase. However, characteristic clinical presentation of initial weakness in the triceps surae muscle associated with atrophy of the sternocleidomastoid muscle confirmed best of the clinical characteristics of type III glycogen storage disease; the only finding which did not fit with its diagnosis was elevation of the blood lactate level after the ischemic exercise test. The muscle biopsy specimen showed marked vacuole formation; approximately 20 to 30% of the vacuoles were rimmed vacuoles, however, the majority was not rimmed. PAS staining on an epon-embedded specimen revealed marked accumulation of PAS-positive materials in those vacuoles as well as in the interfascular space. The non-rimmed vacuoles were not positively stained in the acid-phosphatase staining, which exclude the diagnosis of acid maltase deficiency. No mitochondrial abnormalities were found.(ABSTRACT TRUNCATED AT 400 WORDS)
|
7786628
|
[A case of deep sylvian meningioma presenting temporal lobe epilepsy].
|
A rare case of deep sylvian meningioma is presented. A 62-year-old woman was admitted to our hospital because of one year history of temporal lobe epilepsy. She had no neurological deficit except for EEG abnormality. CT scans showed a small calcified mass in the left temporal lobe adjacent to the sylvian fissure with no enhancement by contrast medium. The mass was low-intense in both T1- and T2-weighted MR images. The T1-weighted image after the infusion of gadolinium revealed enhancement of the middle cerebral artery adjacent to the mass, similar to dural tail sign. Left external carotid angiography did not show any tumor stain nor the dilatation of the middle meningeal artery. Left internal carotid angiography disclosed enlarged middle cerebral artery without tumor stain. A left frontotemporal craniotomy was performed and the mass was totally removed. The tumor was located deep in sylvian fissure without any connection to the dura or ventricular system, which was firmly adherent to the middle cerebral artery. The histological examination of the surgical specimen revealed a psammomatous meningioma. Meningiomas are believed to originate from the arachnoid cap cells and can arise from various intracranial locations where arachnoid cap cells exist. The majority of them are attached to the dura, choroid plexus, or the tela choroidea. Only eleven cases of deep sylvian meningiomas have been presented in the literature. We have reviewed the clinical and radiological findings in such meningiomas. MR findings in deep sylvian meningioma have not been described.(ABSTRACT TRUNCATED AT 250 WORDS)
|
7786627
|
[HTLV-I-associated neuropathy].
|
A 70-year-old man was admitted to our hospital because of a 15-year history of walking difficulty, disturbance of sensation in the palm for 2 years and hand tremor for 6 months. On admission, the scapulohumeral muscles showed fasciculation and atrophy. There was action tremor in the upper limb, and the proximal lower limb showed atrophy and weakness. Standing and walking were impossible. Deep tendon reflexes were decreased in lower limbs. Pathologic reflexes were not found. There was distal dominant sensory disturbance, and urination was difficult. Needle EMG showed a neurogenic pattern in 4 all limbs. MCV and F-latency were delayed. SCV in the median nerve and the amplitude in the sural nerve were decreased. Biopsy of the sural nerve revealed both axonal change and demyelination. Biopsy of the quadriceps femoris muscle showed neurogenic change with helper T-cell infiltration. Anti-HTLV-I antibody and ATL-like cells in both blood and CSF were positive. There were HTLV-I provirus DNA with a polyclonal pattern and the type of HLA as HAM. The HTLV-I infection was of the HAM type. As the present patient showed mainly neuropathy without pyramidal signs, was not considered to have HAM.
|
7786625
|
[The effects of mild hypothermia on expression of stress protein (HSP72) after experimental brain injury].
|
Recent studies have demonstrated that mild hypothermia protects brain from ischemic insults. In the present study, we investigated the effects of mild hypothermia on stress responses of the neurons and glia after experimental brain injury. We evaluated the immunocytochemical expression of 72kDa molecular weight heat shock protein (HSP72) as a marker of cellular injury. Adult male Sprague-Dawley rats were subjected to a lateral fluid percussive injury. After injury the animals were divided into two groups (normothermic and hypothermic groups). Body temperature of the normothermic groups was maintained at 37.0-37.5 degrees C throughout the experiment. In the latter groups, the rats were exposed to hypothermia of 30.0-31.5 degrees C by surface cooling for 150 minutes beginning at 15 minutes after injury. Animals in each groups were sacrificed at 24, 48, and 72 hours after injury. Vibratomed brain sections were provided for immunocytochemical staining of HSP72 and hematoxyline-eosin staining. The induction of HSP72 was evaluated under the light microscopic level. Results 1) The rats that produced HSP72 in the hypothermic group were significantly less than those in the normothermic group. 2) HSP72 was expressed in the neurons and glia in the various brain regions including the impact site, parasagittal cortex, deep cortical layer, hippocampus, caudate-putamen and midbrain in both groups. However HSP72 positive cells in each brain region of the hypothermic group were significantly less than those in the corresponding regions of the normothermic group.(ABSTRACT TRUNCATED AT 250 WORDS)
|
7786626
|
[Prognostic evaluation of patients with severe head injury by motor evoked potentials induced by transcranial magnetic stimulation--combined analysis with brainstem auditory evoked potentials].
|
Prognostic evaluation of severe head injury was performed on the basis of transcranial magnetic motor evoked potentials (MEPs) and brainstem auditory evoked potentials (BAEPs). The subjects were 43 severe head injury patients with Glasgow Coma Scale Scores (GCS) of 9 or less. MEPs were recorded within 3 days after the injury. Patient outcome at 1, 6 and 12 months after the injury was correlated with the MEPs and BAEPs. Differences between MEP and BAEP findings in focal lesions and diffuse lesions also were analyzed. MEP wave latencies and inter-peak latencies between BAEP waves IV and V and between waves I and V were evaluated. There was a closer relationship between MEP latency and GOS, especially between the good recovery group and other outcome groups. At 1 month after the injury, there was a closer correlation between MEP latency and BAEP latency in those who died than in those who survived, and this tendency was more evident with regard to focal lesions. However, there was no significant correlation between MEP and patient outcome when the lesions were diffuse. There was no correlation between BAEP latencies and patient outcome, but there was a good, close correlation between prolonged MEP latency and unfavorable outcome at 1, 6, 12 months after injury. In conclusion, the combined use of BAEPs and MEPs induced by transcranial magnetic stimulation is useful in prognostic evaluation of acute head injury patients, especially when the brain lesions are focal.
|
7786624
|
[Jacksonian seizure model induced by a kainic acid microinjection into unilateral sensori-motor cortex].
|
Kainic acid microinjection into unilateral sensori-motor cortex induced focal seizure status and secondarily generalized seizure status for about 4 hours. After these seizure status, focal myoclonic jerkings were induced for about 2 days. EEG demonstrated generalized synchronous periodic spikes with these myoclonic jerkings. This phenomenon was very similar to those symptoms of epilepsia partialis continua in man. During focal seizure status, autoradiographic study with 14C-deoxyglucose demonstrated increased local cerebral glucose utilizations in the injected site of the sensori-motor cortex, ipsilateral caudate nucleus, globus pallidus, substantia nigra and thalamic nuclei. The result suggested that subcortical pathways played an important roles in the seizure propagation from the cortical epileptogenic focus.
|
7786623
|
[Subset analysis of tumor infiltrating lymphocytes and peripheral blood lymphocytes in malignant glioma patients].
|
It has already been reported that T cell infiltration is observed in brain tumor tissue but that general cellular immunity is suppressed in malignant brain tumor patients. In this report, the subsets of tumor infiltrating lymphocytes (TILs) and peripheral blood lymphocytes (PBLs) were analyzed in 8 patients with malignant glioma in order to investigate the relationship between the local and systemic immunological response in malignant brain tumor patients. TIL subsets in surgical specimens were analyzed immunohistochemically using the ABC method and monoclonal antibodies of the Leu series (anti-Leu 2a, 3a + b, 4 + 5b, 7, 12 and M5), and identified more precisely by double immunofluorescence staining (DIFS) using paired fluorescein isothiocyanate (FITC)-Leu 3a + b and phycoerythrin (PE)-Leu8 or FITC-Leu 2a and PE-Leu 15. PBL subsets were determined preoperatively by two-color analysis with a fluorescence-activated cell sorter (FACS) using fluorescence-labeled monoclonal antibodies (paired FITC-Leu 4 and PE-Leu 12, FITC-Leu 3a and PE-Leu 8, or FITC-Leu 2a and PE-Leu 15). Most TILs proved to be T lymphocytes containing Leu 3a + b+ (T helper/inducer) cells and Leu 2a+ (T suppressor/cytotoxic) cells in almost equal numbers, but there were too few TILs to kill the tumor cells. Detailed examination by DIFS revealed that 93% of the Leu 3a + b+ cells were helper T cells (Leu3a + b+.Leu8- cells) and that 88% of the Leu 2a+ cells were cytotoxic T cells (Leu 2a+.Leu15- cells). Analysis of PBLs showed statistically significant decreases in T cells as a whole and in helper T cells (Leu 3a+.Leu 8- cells).(ABSTRACT TRUNCATED AT 250 WORDS)
|
7786622
|
[Study on the anti-dementia therapies for rats with a unilateral basal forebrain lesion--serial changes of the cholinergic markers' activities and event-related potentials after the administration of bifemelane hydrochloride or autotransplantation of the vagal nodosal ganglion].
|
Using rats with a unilateral lesion in the nucleus basalis magnocellularis (NBM), we examined electrophysiologically the therapeutic effects of bifemelane (BIF) and autotransplantation of the vagal nodosal ganglion (X) on the event-related potential (P300) serially for 4 weeks, and also neurochemically their effects on cholinergic markers--the specific binding of 3H-QNB (quinuclidinyl benzilate) on muscarinic acetyl-choline receptor (mAChR) and the activities of acetylcholinesterase (AChE) and choline acetyltransferase (CAT). The latency of P300 was continuously delayed and its amplitude remained low voltage until 4 weeks in the NBM-lesioned rats (No-Tx group). Whereas the latency and amplitude returned to normal after 2-3 weeks in the rats given daily intraperitoneal injection of 15 mg/kg BIF (BIF group) and autotransplanted ones (X group). The cortical CAT and AChE levels on the lesion side did not recover until 4 weeks in No-Tx group, but the CAT levels recovered after 3 weeks in both BIF and X group; the AChE levels, after 1 week in BIF group and after 3 weeks in X group. The cortical mAChR on the lesion side was within or more than normal range in all rats. These results might indicate as follows: 1) Compensatory postsynaptic process such as cortical mAChR increase and AChE decrease occurred after acute cholinergic depletion. 2) Administration of BIF and X autotransplantation recovered cortical CAT and AChE levels and normalized cholinergic neuronal activity of P300.
|
7786610
|
Steroid receptor distribution in 47,892 breast cancers. A collaborative study of 7 European laboratories. The EORTC Receptor Study Group.
|
Seven laboratories of the EORTC Receptor Study Group reported the distribution of oestrogen (ER) and progesterone receptors (PR) routinely assayed in breast cancer cytosols. A low interlaboratory variability was demonstrated for the median values, and for the frequency of positive tumours as measured by enzyme immunoassay (EIA). Larger variations were found for the frequency of positive tumours, as measured by radioligand binding assay (RLA). They are probably due to differences in the cut-off levels and in the sensitivity of the assay. Analysis of the variability over time clearly demonstrated that the ER-EIA values initially increased compared with RLA. A possible source of variations could be the calibration drift in the ER-EIA kit. In conclusion, quality assessment of steroid receptors should be monitored by comparison of both common standards and distributions routinely obtained in each laboratory. In-house analysis over time is also essential for reagent survey.
|
7786608
|
Clonal diversity, measured by heterogeneity of Ig and TCR gene rearrangements, in some acute leukaemias of childhood is associated with a more aggressive disease.
|
The pattern of immune system gene rearrangements in acute leukaemias of childhood is heterogeneous. The biological significance of this heterogeneity in childhood acute leukaemia is still poorly understood. In this study, we analysed 49 children with acute leukaemia (29 B-precursor acute lymphoblastic leukaemia (ALL), 5 relapsed cALL, 6 T-ALL, 7 acute non-lymphocytic (ANLL) and 2 mixed lineage leukaemias), for the presence of different immune system gene rearrangements (Ig JH, C kappa, C lambda, TCR J gamma, C beta, J delta and J alpha) by Southern blot hybridisation. The most prominent heterogeneity of immune system gene rearrangements was observed in the group of B-precursor ALL. The results from our study suggest that the heterogeneity of immune system gene rearrangement reflects clonal diversity in approximately one-third of patients with B-precursor ALL at presentation and in most patients in relapse. The observed association of clonal diversity with high white blood cell count, pre-B immunophenotype and age under 1 year in B-precursor ALL may have clinical significance. There was a significantly shorter disease-free survival in the group of B-precursor ALL patients with clonal diversity compared with those without clonal diversity. Clonal diversity may, therefore, be a mechanism of disease progression common to different types of aggressive B-precursor ALL.
|
7786607
|
Failure of liposomal encapsulation of doxorubicin to circumvent multidrug resistance in an in vitro model of rat glioblastoma cells.
|
We studied the capacity of doxorubicin encapsulation in liposomes of various lipid compositions to circumvent multidrug resistance in several variants of the C6 rat glioblastoma cell line in culture, and to inhibit azidopine binding to membranes isolated from these cells. Three formulations of liposomes were prepared: (a) phosphatidylcholine (PC)/phosphatidylserine (PS)/cholesterol (cho) at a 9/24 ratio; (b) PC/cardiolipin (CL)/cho at 10/1/4 ratio; (c) dipalmitoylphosphatidylcholine (DPPC)/cho at 11/4 ratio. Unloaded liposomes presented no cytotoxicity against sensitive or resistant cells. Doxorubicin encapsulated in PC/PS/cho and PC/CL/cho liposomes had a cytotoxic activity close to that of free doxorubicin, whereas doxorubicin encapsulated in DPPC/cho liposomes was significantly less active than free doxorubicin in sensitive as well as in two of the three multidrug resistant cell lines, and as active as free doxorubicin in the third one. Free doxorubicin was able to decrease 50% of [3H]azidopine photolabelling to P-glycoprotein at a concentration of 40 microM; doxorubicin encapsulated in PC/CL/cho or PC/PS/cho liposomes was able to inhibit [3H]azidopine binding similarly as free drug, whereas doxorubicin encapsulated in DPPC/cho liposomes had no significant effect on this parameter. Unloaded liposomes of either lipid composition had no effect on [3H]azidopine binding. Together with physical studies performed in parallel on doxorubicin trapping in liposomes (J Liposome Res 1993, 3, 753-766), these results suggest that doxorubicin leaked out of fluid liposomes (PC/PS/cho or PC/CL/cho), whereas rigid liposomes (DPPC/cho) were able to sequester the drug more efficiently. In that case, however, no availability of the drug to the cells was possible and only a weak cytotoxicity was exhibited, especially without any favourable effect on multidrug resistance. In conclusion, no reversal of doxorubicin resistance was found to occur through liposomal encapsulation of the drug.
|
7786606
|
KT-5720 reverses multidrug resistance in variant S49 mouse lymphoma cells transduced with the human MDR1 cDNA and in human multidrug-resistant carcinoma cells.
|
T-25-Adh cells, cell variants derived from S49 mouse lymphoma, were transduced with a retrovirus containing the human MDR1 cDNA. The resultant cells (HU-1) are cross-resistant to colchicine, doxorubicin, vinblastine and actinomycin D, and their resistance to colchicine is reversed by verapamil. HU-1 cells were used to screen several protein kinase modulators for their ability to reverse multidrug resistance. Among the tested indole carbazole (K-252a) family of protein kinase inhibitors, only the antibiotic alkaloid KT-5720 (9-n-hexyl derivative of K-252a) could overcome the multidrug resistance of HU-1 cells and KB-V1 human carcinoma cells. Since other protein kinase A, C and G modulators did not reverse multidrug resistance in the tested multidrug-resistant cells, the chemosensitising activity of KT-5720 on these cells is apparently independent of its kinase inhibitory effects. Since KT-5720 fully reversed multidrug resistance at non-toxic concentrations, it might be a candidate for clinical chemosensitisation in combination chemotherapy.
|
7786605
|
Opposite effect of miltefosine on the antineoplastic activity and haematological toxicity of cyclophosphamide.
|
The effect of pretreatment with miltefosine (MIL) on the antineoplastic activity of cyclophosphamide (CPA) was evaluated in subcutaneous benzo(a)pyrene-induced sarcomas (BPS) of the rat. MIL alone had no antineoplastic effect on this autochthonous tumour, but enhanced the chemotherapeutic effect of CPA. Conversely, MIL counteracted the myelotoxicity of CPA in normal adult rats. Although the nadir of the leucocyte count remained unchanged, the recovery phase was considerably shortened, an effect which resembled the pharmacological action of GM-CSF.
|
7786604
|
Prophylaxis and therapy of mouse mammary carcinomas with doxorubicin and vincristine encapsulated in sterically stabilised liposomes.
|
This study tested the prophylactic efficacies of doxorubicin hydrochloride and vincristine sulphate, encapsulated in sterically stabilised long circulating liposomes, against the spontaneous development of mammary carcinomas in C3H/He mice. Monthly prophylactic intravenous (i.v.) injections of 6 mg/kg doses of liposome-encapsulated doxorubicin (DOX-SL) or 1 mg/kg doses of liposome-encapsulated vincristine (VIN-SL) were begun when retired breeding mice were 26 weeks old. Mice that developed a mammary carcinoma while on the monthly prophylactic protocols were then given weekly i.v. injections of 6 mg/kg DOX-SL or 1 mg/kg VIN-SL to test the therapeutic efficacies of the drugs, and to determine whether the tumours were susceptible or resistant to therapy. The monthly prophylactic injections reduced the incidence of first mammary carcinomas from 87/88 (99%) in untreated mice to 24/42 (57%) in DOX-SL-treated mice and to 26/32 (81%) in VIN-SL-treated mice. Of the mice that developed a mammary tumour while on the prophylactic protocols, 12 of 30 mice were cured by the weekly therapeutic use of DOX-SL, and the growth of 18 tumours was inhibited. The weekly therapeutic use of VIN-SL cured 3 of 8 mice, and inhibited the growth of five tumours. Weekly DOX-SL therapy cured 7 of 22 previously untreated mice. The mean survival of tumour-bearing mice was extended from 24 days in untreated mice to 87 days in DOX-SL-treated mice, which had not received prophylactic treatment. Metastases were found in 29 of 54 untreated mice, and in 3 of 72 mice treated with DOX-SL and VIN-SL. Toxic side effects were limited to a transient weight loss during the weekly treatments. Drug resistance as a result of treatments was not observed.
|
7786603
|
Growth factor requirement, oncogene expression and TP53 mutations of a tumorigenic and a non-tumorigenic subline of the human breast carcinoma cell line, HMT-3909.
|
From a human breast carcinoma cell line, HMT-3909, a tumorigenic and a non-tumorigenic subline have previously been described. Cells of both sublines have been characterised as carcinoma cells. In the present work we examined whether differences in growth factor requirements or oncogene expression may explain the difference in tumorigenicity. We found that exogenous growth factor dependence discriminated between the two sublines. No alterations in oncogenes or tumour suppressor genes were demonstrated that could explain the differences in tumorigenicity. The lower growth factor requirement and the higher growth rate of the tumorigenic subline indicates that, in these cells, growth potential may determine the outcome of the tumorigenicity assay.
|
7786602
|
Cycloplatam: a novel platinum compound exhibiting a different spectrum of anti-tumour activity to cisplatin.
|
Cycloplatam is a novel platinum compound which has shown anti-tumour activity in murine tumour models. In this study, cycloplatam was found to have anti-tumour activity in vitro and in vivo in human tumour models. In 15 cell lines (mainly ovarian), cycloplatam showed similar cytotoxicity as cisplatin, using the sulphorhodamine B assay. Determination of the resistance factor (IC50 of cisplatin-resistant divided by IC50 of parental cell line) clearly showed lower values for cycloplatam than for cisplatin. In the parental ovarian cell line CH1 and the cisplatin-resistant CH1 cisR model, we observed no cross-resistance of cycloplatam and cisplatin. The in vitro anti-tumour activity was confirmed in human tumour xenografts using the clonogenic assay. Mean IC70 values of cycloplatam were 0.54 microgram/ml (1.25 microM) and of cisplatin 0.42 microgram/ml (1.4 microM), respectively. In the murine subcutaneously implanted ADJ/PC6 plasmacytoma in vivo cycloplatam showed less activity than cisplatin, with a 2-fold smaller therapeutic index than cisplatin. In ovarian cancer xenografts cycloplatam was less active than cisplatin. However, anti-tumour activity of cycloplatam in lung cancer xenografts was quite different from cisplatin. In LXFS 538, a model moderately sensitive to cisplatin, a partial remission was observed, but in LXFL 529, a cisplatin-sensitive model, cycloplatam was inactive, cycloplatam thus demonstrating a different spectrum of anti-tumour activity. Based on these results, further preclinical investigations with other tumours, such as cisplatin-sensitive and -resistant gastric cancer models, are warranted with cycloplatam.
|
7786599
|
Rapidly alternating combination of cisplatin-based chemotherapy and hyperfractionated accelerated radiotherapy in split course for stage IIIA and stage IIIB non-small cell lung cancer: results of a phase I-II study by the GOTHA group. Group d'Oncologie Thoracique des Régions Alpines.
|
The prognosis of stage III non-small cell lung cancer (NSCLC) can be improved by a combination of radiotherapy (RT) and chemotherapy (CT). In this study, the GOTHA group evaluated the feasibility, tolerance, tumour response, pattern of failure and effect on survival of a combination alternating accelerated hyperfractionated (AH) RT and CT in patients with tumour stage III NSCLC. 65 patients received 3 cycles of cisplatin 60 mg/m2 and mitomycin C 8 mg/m2 on day 1, and vindesin 3 mg/m2 on days 1 and 8 in weeks 1-2, 5-6 and 9-10, alternating with AHRT, 2 daily 1.5 Gy fractions, 5 days/week, in weeks 2-3 (30 Gy) and weeks 6-7 (33 Gy). The dose actually delivered was > 98% for RT, and 85-100% for CT. Mean duration before last CT cycle was 9.5 weeks. Toxic effects were leucopenia, nausea and vomiting, mucositis, diarrhoea, alopecia and peripheral neuropathy. 1 patient died of bronchial haemorrhage at the end of RT. 1 of 5 patients, who underwent secondary pulmonary resections, died of acute respiratory distress syndrome. Evaluation of tumour response was hampered by lung condensations in radiation fields. Some long-term survivors had an initial tumour response assessed as partial response or no change. First failures were more frequent outside (34) than within (21) radiation fields. The median survival was 15.7 months and the 5 year survival rate was 15% (95% CI = 6-26%). 1 patient died of bladder cancer and another of myocardial infarction. Alternating CT and AHRT, as used in this study, were well tolerated and allowed full dose delivery within less than 12 weeks. Initial response was not predictive of survival. The survival curve is encouraging and the 5 year survival is superior to the 5% generally observed with conventionally fractionated radiotherapy.
|
7786601
|
Trends in cervical cancer incidence in the district of Florence.
|
The trend in cervical cancer incidence in the District of Florence from 1975 to 1989 was investigated. Tuscany Cancer Registry data were available since 1985. Incidence data from 1975 to 1985 were obtained through a retrospective survey of all the Departments of Pathology and Gynaecology in the district. Cytological screening for cervical cancer has been available in the district since 1973, and since 1980 active invitation of residents aged 25 to 59 years has been in use. A significant trend in decreasing incidence was evident for the overall population (P = 0.003) and for 40-49 (P = 0.028), 50-59 (P < 0.001) and 60-69 (P = 0.002) year age groups, whereas no significant trend was observed for the age group 30-39 years. An association between attendance to screening and reduced incidence was evident, in that a greater reduction was evident for those cohorts (ages 50-59 and 60-69) who had a higher compliance to screening 10-15 years before. If the decrease in cervical cancer incidence was spontaneous, a parallel decrease of CIN3, which is commonly assumed to be the precursor of invasive carcinoma, would be expected. On the contrary, the detection rate of CIN3 at first Pap test showed a significant increase in the study period. All these findings suggest that the observed reduction in cervical cancer incidence was mostly due to the effect of screening, and stress the need for optimising the coverage of the invited population.
|
7786600
|
A model-based prediction of the impact on reduction in mortality by a breast cancer screening programme in the city of Florence, Italy.
|
The efficacy of breast cancer screening for women older than 50 years has been shown in several studies. Service screening is now ongoing or planned in several countries in Europe. MISCAN, a computer simulation programme, has been used to analyse data from the Florence District Programme (FDP) breast cancer experience. First, the model was fitted to the screening results for the period 1975-1986. A good correspondence between the model outcomes and the FDP results was achieved. It was then used to predict the impact on mortality of the new starting programme of the city of Florence (63,000 women, 50-69 years old). Assuming a 70% attendance rate, then for the city of Florence, 2563 screen-detected breast cancers are predicted for the period 1991-2020 out of the total number of 9095 breast cancers for all ages (28%). A total of 3720 deaths for breast cancer are expected without screening. An absolute reduction of 472 deaths (13%) is predicted for the whole population. The estimated number of years of life gained by screening until 2020 is 4354. Simulation by MISCAN has previously been a useful support tool for decision-making about screening. The present paper is the first based on a southern European experience. The possibility of applying MISCAN to predict the impact of a national programme in Italy is discussed.
|
7786598
|
Parathyroid hormone-related protein (PTHrP) in breast cancer and benign breast tissue.
|
Parathyroid hormone-related protein (PTHrP) 1-86 was quantified by immunoassay in extracts of 132 breast cancers, 27 samples of normal breast tissue and four fibroadenomas. PTHrP 1-86, was detected in 68% of primary tumours (range 40-302,000 fmol/g), 33% of normal breast tissues (range 100-1800 fmol/g), and all four fibroadenomas (range 110-11,600 fmol/g). PTHrP displayed molecular heterogeneity on gel filtration chromatography, and 1-86, 1-34 and 37-67 immunoreactivity eluted as 25-27 kDa together with a peak of 19-21 kDA containing only 37-67 activity. Tumour PTHrP 1-86 levels correlated inversely with age (P < 0.05) and were higher in premenopausal women (P = 0.05). The proportion of tumours containing PTHrP was higher in axillary node positive premenopausal women (P < 0.05). These data suggest that oestrogen may regulate expression of PTHrP in breast cancer and that production of PTHrP may be linked to development of axillary node metastases.
|
7786597
|
Expression of retinoblastoma gene protein (Rb) in breast cancer as related to established prognostic factors and survival.
|
The expression of retinoblastoma gene product (Rb protein) was studied by immunohistochemical analysis of 205 cases of breast cancer. Rb protein was invariably expressed in non-neoblastic breast epithelium, in dysplastic and hyperblastic lesions adjacent to tumours, and none of the breast tumours was totally negative for Rb protein. According to the scoring system used, the expression of Rb protein was abnormal in 36.6% of cases. Abnormal expression of Rb protein was significantly related to grade (P < 0.00004), type (P = 0.0183), margin formation (P = 0.0116), DNA ploidy (P < 0.0002) and nuclear pleomorphism (P < 0.0001). Abnormal expression of Rb protein was related to high S phase fraction (P = 0.004), high mitotic index (P < 0.001) and high morphometric nuclear factor values (P < 0.01). The expression of Rb protein had no prognostic value in univariate or multivariate analysis. The results show that the tumour suppressor gene Rb participates in the growth regulation of breast cancer cells in vivo, but immunohistochemical assessment of the expression of Rb protein has no prognostic significance in clinical breast cancer over already established prognostic factors.
|
7786596
|
Timing of surgery during the menstrual cycle for breast cancer: possible role of growth factors.
|
Premenopausal patients undergoing surgery for breast cancer were prospectively studied. Data regarding menstrual history, pathological parameters and hormone receptor status were collected. Serum oestradiol, prolactin and progesterone levels, tumour epidermal growth factor receptor (EGFR) levels, tumour epidermal growth factor (EGF) levels and flow cytometry were measured. Patients were allocated to the follicular or luteal phase of their cycle both by history and progesterone level. No significant differences were seen in hormone receptor levels, pathological parameters or EGF levels between the two groups. EGFR levels were significantly higher in women undergoing surgery during the follicular phase of their cycle, when classified by menstrual history. Patients operated on during this phase have previously been found to have a poorer prognosis, and these results may provide a basis for this finding. This may have implications for prognosis and timing of surgery, and further investigation is warranted.
|
7786594
|
Different dose regimens of 5-fluorouracil and interferon-alpha in patients with metastatic colorectal carcinoma.
|
Three different 5-fluorouracil (5-FU)-interferon-alpha-2b (IFN)-containing regimens were designed for treatment of patients with advanced colorectal cancer. 87 patients with a Karnofsky index > or = 70 were included in three sequential non-randomised phase II trials. Regimen A consisted of 5-FU (750 mg/m2/day) given as a continuous infusion on days 1-5 followed by weekly 1-h intravenous infusions until week 8. IFN (5 MU) was given subcutaneously on days 1, 3 and 5 followed by injections (9 MU) every second day until week 8. The cycle was then repeated. Regimen B consisted of 5-FU (750 mg/m2/day) given as a continuous infusion on days 1-5 followed by 5-min intravenous injections on days 12 and 19. IFN (3 MU) was given subcutaneously on days 1-5 followed by injections (5 MU) on days 11-13 and 18-20. The cycle was repeated every fourth week. Regimen C consisted of 5-FU (750 mg/m2/day) given as a continuous infusion on days 1-5. IFN (3 MU) was given subcutaneously on days 1-5. The cycle was repeated every third week. The objective response rates (complete response (CR) and partial response (PR)) after approximately 4 months of therapy or longer were as follows: regimen A (n = 27) 22% (2 CR, 4 PR), regimen B (n = 33) 42% (4 CR, 10 PR) and regimen C (n = 27) 22% (1 CR, 5 PR). The corresponding response figures for previously untreated patients were regimen A 50%, regimen B 64% and regimen C 38%. Response durations varied from a few weeks up to 142 + weeks. Toxicities were generally mild and reversible, and the treatments were convenient for the patients and cost effective since the 5-day infusions could be given by a portable pump without hospitalisation. Our results are in agreement with those of others showing that 5-FU/IFN combinations can be highly effective in advanced colorectal cancer, and that a number of factors such as doses, dose intensities, infusion rates and timing of the two drugs may be crucial for the anti-tumour activity of this drug combination.
|
7786595
|
Prognostic parameters in localised melanoma: gender versus anatomical location.
|
Extremity location and female gender are both considered favourable prognostic parameters in primary melanoma, but since they cluster in the same group of patients, the question remains as to whether they are both independent variables. Multivariate analysis of 695 patients with primary, localised melanoma was used. The effects of gender and anatomical location were compared directly by sequentially controlling one factor while the other remained free. Following multivariate analysis, significant prognostic factors related to survival were the thickness of the primary lesion (P < 0.0001), the age of the patient at diagnosis (P < 0.0001), the gender of the patient (P = 0.0008) and the anatomical location of the primary lesion (P = 0.005). Thicker lesions, patients older than 50 years, males, and trunk, head and neck locations had poorer prognoses. There was a significant difference in survival according to gender within each location, extremity (P = 0.002) or trunk, head and neck (P = 0.0004); however, there was no significant difference in survival according to anatomical location within each gender, male (P = 0.11) or female (P = 0.29). The thickness of the primary lesion, the age of the patient at diagnosis, the gender and the anatomical location of the melanoma are all significant prognostic parameters in localised melanoma. Gender appears to have a more pronounced effect on survival than anatomical location.
|
7786593
|
Is neuro-ectodermal differentiation of Ewing's sarcoma of bone associated with an unfavourable prognosis?
|
Among Ewing's sarcoma (ES) of bone and related entities are tumours with neuro-ectodermal features that could represent a biologically distinct type. In order to assess the prognostic significance of the various forms of ES, a retrospective joint study involving three cancer centres in Europe and the U.S.A. was initiated. The material from 315 primary ES was reviewed by a panel of five pathologists and classified as typical ES (220 cases), atypical ES (48 cases) or ES with neuro-ectodermal features (47 cases). Prognostic factor analysis on treatment failure-free survival was performed using the Cox model. It included histopathological classification, initial patient characteristics, clinical presentation and treatment type. After multivariate analysis, in addition to treatment type (P < 0.001), metastases (P = 0.003) and proximal tumour location (P = 0.006), two histopathological parameters correlated with poor treatment failure-free survival, the presence of filigree pattern (P = 0.044) and dark cells (P = 0.043). We conclude that ES with neuro-ectodermal features does not appear to have a different outcome to the other subtypes.
|
7786592
|
Long-term prognosis following macroscopic complete response at second-look laparotomy in advanced ovarian cancer patients treated with platinum-based chemotherapy. The Gruppo Oncologico Nord Ovest.
|
Survival (S) and progression-free survival (PFS) were evaluated in 129 advanced ovarian cancer patients, who achieved a macroscopic complete response (112 pathological complete response and 17 microscopic disease) at second-look after platinum-based combination chemotherapy with or without doxorubicin (DX). The impact on S and PFS of age, performance status (PS), stage, histology, grade (G), residual disease after first surgery (RD), chemotherapy regimen, disease status at second-look and consolidation therapy were evaluated by univariate and multivariate analysis. In the 118 months observation period, median S and PFS were 81 and 34 months, respectively. Stage, G, RD, PS and disease status at second-look had significant impact on both S and PFS in univariate analysis, whereas consolidation therapy did not influence outcome. Cox's regression analysis showed that G, RD and PS had an independent impact on PFS. Test for interaction demonstrated no statistically significant relationship between RD, chemotherapy regimen and outcome. In conclusion, advanced ovarian cancer patients with macroscopically complete remission at second-look have a substantial risk of relapse after aggressive treatment. The risk of recurrence was estimated to be maximal in the first 3 years after restaging, and was correlated with poor PS, RD > 2 cm after first surgery and undifferentiated tumour.
|
7786587
|
Differential Tax expression in HTLV type I-infected asymptomatic carriers.
|
tax gene expression in a family cluster of three HTLV-I-infected asymptomatic individuals was investigated. Two carriers had normal tax mRNA, Tax-specific humoral antibody, and cell-mediated immune (CMI) response. In one carrier who had only weak Tax-specific humoral and no Tax-specific CMI response, an abnormal Tax-related mRNA product was detected. This product was sequenced and found to consist of two exons derived from the LTR gag and pX regions. The abnormal mRNA has an ORF predicting a 17-kDa protein, the translation of which is initiated in the first exon. The presence of this protein, of antibody to it, and of its function remain to be elucidated.
|
7786585
|
Polyclonal rabbit antisera that detect the Vpr protein of SIVSM and SIVMAC on immunoblots of purified virions.
|
Antisera suitable for detection of SIVSM or SIVMAC Vpr proteins on Western blots of purified virions are currently not available. We have expressed the Vpr protein of SIVSMPBj1.9 in a gst-based prokaryotic expression system and used it to raise polyclonal antisera in rabbits. Two immune sera were obtained that specifically recognized both cell- and virion-associated Vpr protein on immunoblots of three different SIV isolates (SIVSMPBj1.9, SIVMACBK28, and SIVMAC239). Because Vpr is believed to play an important role in HIV/SIV replication and pathogenesis, these reagents will allow the extension of functional analyses of this protein to a broader spectrum of viruses. Both antisera and the gst-Vpr expression plasmid have been submitted to the NIAID AIDS Research and Reagent Program and are available to interested investigators.
|
7786586
|
Evaluation of HIV type 1 western blot-indeterminate blood donors for the presence of human or bovine retroviruses.
|
From 1985 through 1990, 1100 of 500,000 human blood donations in Syracuse, New York were repeatedly reactive by ELISA for antibodies to the human immunodeficiency virus type 1 (HIV-1). Nine hundred of the ELISA-reactive samples were confirmed as negative by Western blot (WB), 40 were confirmed as positive, and the remaining 160 sera were indeterminate, reacting mainly with HIV-1 gag gene products. Twenty donors with the most reactive indeterminate WB were selected for follow-up studies. Four of these 20 donors admitted to retroviral risk factors and, interestingly, 12 (60%) had exposure to dairy cattle and drank unpasteurized milk. These 20 donors were analyzed over a 3-year period for the presence of the pathogenic human retroviruses HIV-1, HIV-2, human T cell lymphoma/leukemia virus types I and II (HTLV-I and HTLV-II), as well as bovine immunodeficiency virus (BIV) and leukemia virus (BLV). Retroviral analyses included serology, plasma antigen capture, virus culture, and the polymerase chain reaction. Only one donor seroconverted and was clearly infected with HIV-1. None of the other 19 donor serological reactivities to HIV-1 changed, nor were they positive for any of the above-mentioned retroviruses. Although we cannot ascertain whether these latter 19 HIV-1 WB-indeterminate donors were exposed to human or bovine retroviral proteins, it is unlikely that their HIV-1 seroreactivity was caused by infection with HIV-1, HIV-2, HTLV-I, HTLV-II, BLV, or BIV.
|
7786584
|
Analysis of envelope glycoprotein-specific antibodies from SIV-infected and gp110-immunized monkeys in ACC and ADCC assays.
|
Sera collected from SIV-infected or recombinant glycoprotein-immunized monkeys were characterized for antibodies participating in antibody-complement-mediated cytolysis (ACC) and antibody-dependent cellular cytolysis (ADCC) in terms of their IgG subclass and epitope specificity. In a competitive inhibition ELISA, gp110-specific antibody reactivity with nondenatured rgp110 was blocked completely by soluble homologous rgp110 and partially inhibited by heterologous rgp110, suggesting cross-reactivity between viral strains. However, only partial inhibition was observed with denatured recombinant gp140 (rgp140) in selected monkeys, indicating that the majority of gp110-specific antibodies recognized conformational epitopes. ACC activity against recombinant vaccinia-infected, envelope-expressing targets was found in sera from both infected and immunized monkeys, whereas ADCC activity was observed only in sera from infected monkeys. ACC was blocked with denatured rgp140 as well as nondenatured rgp110, indicating that ACC-mediating antibodies recognized mainly linear epitopes. In contrast, rgp140 did not compete as effectively as rgp110 in the ADCC assay, indicating that the majority of ADCC antibodies recognized conformational epitopes. Competitive inhibition using three peptide fragments of gp110 indicated that epitopes recognized by ACC antibodies lie within amino acid residues 214-471, a region that spans V3, whereas ADCC-reactive epitopes lie between amino acid residues 52 and 214 at the N-terminal end of gp110. Column chromatography of rhesus IgG resulted in three subclass-enriched fractions, designated IgG-I, IgG-II, and IgG-III. IgG-I, but not IgG-II or IgG-III, from both infected and immunized monkeys mediated ACC, whereas IgG-I and IgG-II from infected monkeys mediated ADCC.(ABSTRACT TRUNCATED AT 250 WORDS)
|
7786583
|
Humoral and cellular immune responses in rhesus macaques infected with human immunodeficiency virus type 2.
|
Eighteen rhesus macaques were inoculated with either an infectious molecularly cloned human immunodeficiency virus type 2 (HIV-2)SBL/ISY, or with one of eight mutants defective in one or more accessory genes. The immune responses generated by the macaques were monitored for up to 2 years postinfection. All the macaques except those that received mutants lacking the vpr or vif genes demonstrated low to moderate antibody titers. Macaques inoculated with vpx- mutants exhibited a persistent serological response, suggesting continuous virus expression even in the absence of detectable virus in the peripheral blood mononuclear cells (PBMCs). Neutralizing antibodies developed in only four macaques. In general, low-level cytotoxic T lymphocyte (CTL) activity, not clearly HIV-2 specific, was detected in PBMCs. However, one virus-negative macaque exhibited significant HIV-2-specific CTL activity in an enriched CD8+ cell population from PBMCs, suggesting clearance of the viral infection. In addition, CTL activity against the Env and Gag/Pol epitopes of HIV-2 by CD8+ lymphocytes from the spleens and lymph nodes of two infected macaques, in one case requiring CD8+ T cell enrichment and in the other clearly evident in unfractionated tissue lymphocytes, was demonstrated for the first time. This sequestration of tissue CTLs occurred in the absence of significant levels of circulating CTLs in the blood. Our results suggest that routine monitoring of PBMCs may sometimes be inadequate for detecting cell-mediated immune responses. Elucidation of immune correlates of vaccine protection may therefore require sampling of lymphoid tissues and assessment of enriched CD8+ populations.
|
7786582
|
Coamplification of HIV type 1 and beta-globin gene DNA sequences in a nonisotopic polymerase chain reaction assay to control for amplification efficiency.
|
The polymerase chain reaction (PCR) fails to detect HIV-1 sequences in 5% of infected individuals. To screen for false-negative PCR tests, we developed a nonisotopic PCR assay in which sequences from the beta-globin gene and from the HIV-1 vpu-env region were coamplified with biotinylated and fluorescein-labeled primers, respectively. Coamplified products were reacted with specific internal digoxigenin-labeled RNA probes. Hybrids were detected in a microtiter plate coated with streptavidin or anti-fluorescein antibody, with enzyme-labeled anti-digoxigenin antibody. After the optimization of the coamplification conditions, the assay could detect 5 proviral DNA copies in a lysate from 100,000 peripheral blood mononuclear cells. Fifty-seven samples from 55 HIV-1-seropositive patients and 25 samples from 25 seronegative individuals were evaluated. Fifty-two samples from HIV-infected individuals were positive for HIV-1 vpu-env sequences. Three of the 5 PBMC lysates falsely negative for HIV-1 sequences had reactivities for beta-globin (3-23 fu) below that of 100,000 cells (304 fu). Nonisotopic coamplification allowed for the evaluation of the quality of specimens for PCR concurrently with the detection of the presence of viral template sequences.
|
7786581
|
Clinical evaluation of branched DNA signal amplification for quantifying HIV type 1 in human plasma.
|
Quantification of HIV-1 RNA in human plasma has provided unique insight into AIDS pathogenesis and promises to hasten progress in antiretroviral therapy and vaccine research. However, no generally available HIV-1 RNA assay has yet been subjected to rigorous clinical testing or to comparative evaluation with research-based RNA assays using large numbers of well-characterized clinical specimens. In this study, the Chiron Quantiplex branched DNA (bDNA) signal amplification assay was used to measure viral RNA in the plasma of 152 HIV-1-positive individuals at all stages of infection and in 12 patients before and after initiating zidovudine therapy. Eighty-six percent of patients had bDNA assay results above the 10,000-RNA Eq/ml sensitivity cutoff. Branched DNA values were significantly correlated with plasma viral RNA levels determined by quantitative competitive polymerase chain reaction (QC-PCR) assay (Spearman rank correlation, r = 0.89), infectious plasma virus titers (r = 0.72), p24 antigen levels (r = 0.51), immune complex dissociated p24 antigen levels (r = 0.56), and CD4+ lymphocyte counts (r = -0.72; p < 0.0001 for all comparisons). Plasma viral RNA determinations by bDNA and QC-PCR assays were quantitatively similar in the range of 10(4) to 10(7) RNA molecules/ml [log bDNA = 0.93 + 0.80 (log QC-PCR); R2 = 0.81, p < 0.0001] and declined identically following the institution of zidovudine therapy (68-73% decrease from baseline). The close quantitative correlation between bDNA and QC-PCR results, and their significant association with other viral markers and CD4+ counts, support the use of plasma viral RNA measurement in HIV-1 clinical trials.
|
7786580
|
Increase in sensitivity to soluble CD4 by primary HIV type 1 isolates after passage through C8166 cells: association with sequence differences in the first constant (C1) region of glycoprotein 120.
|
Primary isolates of human immunodeficiency virus type 1 (HIV-1) were obtained by coculture of peripheral blood lymphocytes (PBLs) from HIV-1-infected people with PBLs from uninfected donors. These viral stocks tend to be resistant to neutralization/inactivation by soluble CD4 (sCD4). When these stocks were passed through the T cell line C8166, virus stocks emerged that were sensitive to sCD4. Pre- and post-C8166 stocks maintained their sCD4-resistant and -sensitive phenotypes, respectively, with further passage in PBLs. Pre- and post-C8166 stocks were biologically cloned by two cycles of limiting dilution. The majority (14 of 17) of pre-C8166 clones were sCD4 resistant, and, conversely, the majority of post-C8166 clones (11 of 12) were sensitive to sCD4. Nucleotide and predicted amino acid sequence analysis in the env (gp120) region revealed a limited number of differences between the clones. The only differences that sorted with biological phenotype were in the first constant (C1) region of gp120. Adaptation to growth in C8166 cells and conversion from the sCD4-resistant to the sCD4-sensitive phenotype represent the emergence to prominence of viral species in the pre-C8166 stock that have a replication advantage in C8166 coincident with increased sensitivity to sCD4.
|
7786579
|
Human immunodeficiency virus type 1-neutralizing antibodies raised to a glycoprotein 41 peptide expressed on the surface of a plant virus.
|
An oligonucleotide encoding the amino acids 731-752 of the gp41 envelope protein of the human immunodeficiency virus type 1 strain IIIB, which is known to induce cross-reactive neutralizing antibodies in humans, was inserted into a full-length clone of the RNA encoding the coat proteins of cowpea mosaic virus (RNA 2 of CPMV). When transfected together with RNA 1 of CPMV, transcribed RNA 2 was able to replicate in plants and form infectious virions (CPMV-HIV). Purified virions were injected subcutaneously with alum adjuvant into adult C57/BL6 mice to determine their ability to stimulate ELISA and neutralizing antibody specific for HIV-1. Antisera to CPMV-HIV obtained after only two injections gave a strong ELISA response (mean of 1:25,800) using the free gp41 peptide as antigen, showing that the gp41 peptide incorporated into the chimera was immunogenic. The same antisera gave 97% neutralization of HIV-1 IIIB at 1:100 dilution, with a highly uniform response in all (six of six) animals tested. A third injection barely increased the neutralization titer. Normal mouse serum had no neutralizing activity. Antisera also strongly neutralized the HIV-1 strains RF and SF2. ELISA and neutralizing activity to HIV-1 IIIB declined after the second injection and were undetectable after 7 weeks, but were restimulated to the same level after the third injection. Neutralization was marginally more stable after the third injection. Antibody specific for CPMV epitopes was equally short lived. A bonus of this system was unexpected neutralizing activity specifically stimulated by unmodified CPMV virions, although this amounted to no more than 10% of the neutralizing activity stimulated by the CPMV-HIV chimera.(ABSTRACT TRUNCATED AT 250 WORDS)
|
7786577
|
The autumn peak in campylobacter gastro-enteritis. Are the risk factors the same for travel- and UK-acquired campylobacter infections?
|
In the autumn of 1992 there was an excess of campylobacter cases in Nottingham compared with the national average. No relative increase was seen for salmonella infections. A case-control study with a postal questionnaire was carried out to determine exposure to possible risk factors. The patients were 282 laboratory confirmed cases of campylobacter and 318 culture negative controls who had submitted a faeces specimen. All patients were aged 18 or older. The main outcome measures were relative risks for campylobacter infection compared with controls with a negative faeces culture. Twenty-five per cent of cases were associated with foreign travel. Eating chicken and handling raw poultry were the main risk factors for UK-acquired infections. The number of cases with a history of contact with puppies or drinking milk that was either unpasteurized or from bottles with bird-damaged tops was small. Eating chicken and handling raw poultry are the main risk factors for campylobacter infections. Contact with puppies or drinking potentially infected milk can explain only a small percentage of campylobacter infections. Risk factors for infection acquired abroad follow a different pattern compared with UK-acquired cases.
|
7786575
|
Is a policy of cervical screening for all women attending a genito-urinary medicine clinic justified?
|
The study took place at the Genito-Urinary Medicine Department at the University Hospital of South Manchester and the Cytology Department at Christie NHS Trust Hospital. There were two main objectives, as follows: (1) to determine if patients attending a Genito-Urinary Medicine (GUM) Clinic are less likely to have had a cervical smear in the preceding five years than a control group drawn from the general population; (2) to compare the prevalence of cytological abnormalitity in cases and controls. Cases comprised all women attending the Withington GUM Clinic, between 1991 and 1993, who had had a cervical smear taken at this clinic. Controls were selected from residents of the North West Regional Health Authority who had a cervical smear taken either by a general practitioner (GP) or in an NHS Community Clinic during the same period. The design was a matched case-control study. The main outcome measures considered the proportion of women who had had a cervical smear taken by a GP or in an NHS Community Clinic during the five years preceding the index smear, and the prevalence of abnormal smears in cases and controls. There was no significant difference in the screening history of cases and controls; 363 (50.2 per cent) cases had had a cervical smear taken in the preceding five years as compared with 380 (52.6 per cent) controls [chi 2 (1df) = 0.95; p > 0.05; 95 per cent confidence interval (CI) on difference in proportions, -7.1 per cent to 2.4 per cent]. There was a small case-control difference of borderline significance in the prevalence of all grades of cytological abnormality: 22.7 per cent of cases had abnormal cytology as compared with 18.5 per cent of controls [chi 2 (1df) = 3.98; 0.01 < p < 0.05; 95 per cent CI on difference in proportions, 1 per cent to 8.2 per cent). This excess was largely attributable to differences in the prevalence of minor cytological abnormality. There was no significant difference in the prevalence of cytological abnormality in those case-control pairs who had had a smear in the preceding five years. A policy of cervical screening of all GUM patients can no longer be sustained. We would recommend cervical cytology only for those women who have not been screened in the previous three to five years.
|
7786576
|
Health services research in the United Kingdom 1990-1992.
|
Shortly before the National Health Service (NHS) research and development (R&D) strategy was launched in April 1991, the Department of Health commissioned a study to collect information on current health services research and related work in the United Kingdom. The term 'health services research' was interpreted as research that could usefully inform the contracting arrangements in the reformed NHS. The information was collected from funding agencies, in particular the UK health departments, the Medical Research Council and medical research charities; academic departments and research units and centres; NHS authorities; and research registers and directories. A total of 6185 projects that were either in progress or completed between January 1990 and mid-1992 were identified. Forty-three per cent of projects were disease related; 33 per cent assessed health technologies. Patterns were evident in the database. Sixty-three per cent of the projects on diseases were covered by five categories: cancer, the largest category with a quarter of the disease projects; perinatal medicine; cardiovascular disease and stroke; HIV and AIDS; and mental illness. Conditions that cause severe discomfort but are not life threatening were poorly represented. Clinical trials formed 25 per cent of the health technology projects, but only 6 per cent of the trials assessed surgical procedures. Less than 10 per cent of all health technology projects contained a costing component. In England, 34 per cent of projects with identified funding sources were supported by medical charities and other independent bodies, 31 per cent by NHS authorities, 20 per cent by the Department of Health and 15 per cent by the research councils. This collection of information represents a 'snapshot' of the scope of health services research against which it will be possible to measure the changes promoted by the NHS R&D programme.
|
7786574
|
Understanding variations in lengths of stay between hospitals for fractured neck of femur patients and the potential consequences of reduced stay targets.
|
Economic incentives exist to scrutinize length of stay variations between hospitals. However, the reasons for variations can be complex, and without knowing these the feasibility of shorter stay targets, and their implications for patient outcome, are unclear. This research compared care received by patients admitted for fractured neck of femur at an inner-city university teaching hospital, an inner-city associated teaching hospital and an associated teaching hospital in an urban setting. Multiple regression and descriptive analysis were used to examine how in-patient acute stay was affected by the severity of cases on admission and the supply of beds beyond the acute setting. Data on patient outcome were mortality up to three months post fracture and functional ability at in-patient discharge and three months post fracture. A total of 492 patients were recruited. Patient outcomes at three months were similar at the hospitals. Multiple regression revealed significant differences between the patient stay of the inner-city teaching hospital and the urban associated teaching hospital. A difference in stay of around 14 days was demonstrated, with the urban hospital having the shorter stay. These differences were linked it to having a greater supply of non-acute beds. Significant differences in patient stay between hospitals can be due to factors beyond the direct control of the acute unit. Economic incentives may mean that purchasers and providers ignore a full analysis of these factors and set length of stay targets which are not feasible in the short term. This could reduce the quality and impair the outcome of patient care.
|
7786573
|
Press coverage of the Cleveland child sexual abuse enquiry: a source of public enlightenment?
|
The objective of this study was to assess national and local newspaper reporting of events considered by a Public Enquiry which investigated a major crisis involving child protection services. The Judicial Enquiry, held in Cleveland, North East England, examined the actions of statutory bodies and the professionals working within them following the diagnosis of suspected sexual abuse in 121 children. This is a descriptive study using analysis of legal transcripts and newspaper reports. The data involved a total of 216,360 lines of transcript evidence given by 111 witnesses and lawyers representing them at the Judicial Enquiry which lasted 74 days; together with 344,899 words in reports covering 17 newspapers (seven local and ten national). The main outcome measures were based on the volume and type of newspaper coverage including that for each witness' and lawyer's evidence. A coverage index related the amount of newspaper reporting to the extent of evidence given. The highest coverage of any single day of the Enquiry in both local and national newspapers occurred when Dr Marietta Higgs (one of the two principal paediatricians involved) made her first appearance. However, the highest interest (coverage index) was shown in evidence given by lawyers for the parents and the least in evidence given by public bodies. The evidence of witnesses was used very selectively by the press in emotive headlines to imply blame or support for the main protagonists or their actions. This sustained several lines of reporting: criticism of the doctors and social workers, inter-professional conflicts, damage and wrong-doing to the families and the search for someone to blame. The Cleveland crisis occupied newspaper headlines in the United Kingdom for more than a year. Much of the newspaper coverage took an adversarial approach which sought to apportion blame and take sides. The press appeared to report negative issues which were newsworthy and did not give a balanced view. Broader policy issues, which formed an important part of the Enquiry report's influence on subsequent child protection legislation, were largely ignored.
|
7786572
|
An investigation into the default rate at the Fife colposcopy clinic: implications for target setting.
|
High default rates have been reported from the Fife colposcopy clinic in recent years. However, it was felt that this rate was misleading, as many patients who defaulted initially attended subsequent appointments. It was therefore decided to determine the default rate of a cohort of new patients given appointments at the clinic. The objective of the study was to determine the attendance rates for these new patients, between the dates they were first invited to their various appointments and the dates that their notes were subsequently examined as part of this study in September 1992. A retrospective cohort study of new patients invited to the Fife colposcopy clinic was undertaken. The notes of 200 new patients who had been invited during the eight-month period January-August 1991 were selected by systematic sampling. The dates that they had attended for their new patient assessment/treatment, first follow-up and second follow-up appointments were recorded. Attendance rates were then calculated using an incomplete life-table method. Patients were censored if they failed to attend their assessment/treatment or review appointments by 1 October 1992. The study demonstrated that 96 per cent of patients attended their first treatment appointment within six months of their appointment date, 91 per cent of first review patients attended within six months, and 88 per cent of second review patients attended within four months. These findings suggest that there are two distinct groups of defaulters: those who default initially but subsequently re-attend, and those who default completely. We have named these type A and type B defaulters, respectively. This means that attendance within a certain period of time should also be used to monitor clinic attendance in addition to simple mean attendance rates. As patients who default completely may be more likely to have a severe histological lesion, further work is required to identify factors associated with this type of patient.
|
7786571
|
Access to elective surgery at electoral ward level: the impact of the private sector.
|
Purchasers of health care receive no routine information on the use of the private health sector by their residents, and are consequently unaware of any resulting differentials in access to health services. This information would assist in assessing need for services on a locality basis. For the period 1990-1992 surgical activity data from the single private hospital in Preston were examined by electoral ward of residence and compared with corresponding NHS data. For the procedures examined, the private sector contributed only 8 per cent to overall surgical activity within Preston. People from the more affluent wards were far more likely to use the private sector than those from deprived wards. The private sector did not introduce any inequity of access to surgery within Preston at electoral ward level. However, in districts with higher levels of private sector activity significant differentials in access may exist.
|
7786570
|
The state of primary medical care in Bulgaria.
|
This paper describes the state of primary medical care in Bulgaria and related issues. This component of the state health system is based on the so-called principle of the 'district physician'. It is built on the idea of establishing long-lasting contact between the physician and the patients. Primary care is provided by a district therapist (for populations of up to 3000 inhabitants), a paediatrician (for 800-1200 children aged up to 14 years) and an obstetrician-gynaecologist (for 16,000-18,000 female inhabitants), as well as by numerous freely accessible narrow-profile specialists. The main disadvantages of the existing system of primary medical care are the lack of opportunity for personal choice of physician, division of responsibilities among numerous physicians and other medical staff, expensive medical care owing to abundant polyclinical specialists, reduced physician's motivation and hampered users' influence on the quality of medical care. Questions about the future status of polyclinics and both children's and female health centres, as well as about the optimal ratio between family physicians and specialists, remain unresolved.
|
7786569
|
The detection and management of hypertension in the elderly of Northamptonshire.
|
The aim of this study was to apply recommendations from randomized controlled trials and guidelines on the detection and control of hypertension in the elderly to a district health authority population. A cross-sectional audit of Northamptonshire general practitioners' (GPs') records from February to June 1993 was carried out. A total of 2428 notes of men and women aged 65 or over registered with their GP was audited. A large proportion of patients, 86 per cent (95 per cent CI 84.6-87.4 per cent), had a blood pressure record taken in the last 10 years. Of those with raised blood pressure (BP > or = 160/90 mmHg) 49 per cent (95 per cent CI 46.2-51.8 per cent) were untreated, and 58 per cent (95 per cent CI 54-61.9 per cent) of those labelled as hypertensive were not adequately controlled. The prevalence of labelled hypertension was 25 per cent (95 per cent CI 23.3-26.7 per cent). From these results it is estimated that between 11 and 29 fatal and non-fatal strokes could be prevented in the 65-74-year-old age population of Northamptonshire each year if current guidelines were followed. Improved detection and management of elderly hypertensive patients in primary care could contribute significantly towards the target for stroke reduction set in the Health of the nation strategy.
|
7786568
|
The changing pattern of in-patient care.
|
A nationally representative longitudinal study presented the opportunity to describe National Health Service (NHS) and private in-patient care used over seven years by a population of young adults in relation to known risk factors for admission and for future health. Information on each hospital admission between ages 36 and 43 years, comprising length of admission and whether under NHS or private care, was collected from 1625 men and 1623 women, the population of the 1946 birth cohort study. Obstetric care was excluded from most analyses. From this population, 22 per cent of men and 39 per cent of women were admitted to hospital at least once during the seven-year period, for a total of 11,276 days, a mean of 3.5 days (SD 13.1) for each person in the study, and 11.6 (SD 21.9) days for those admitted. The proportion of admissions not under NHS care rose from 14 per cent of all admissions in 1982 to 23 per cent in 1989. Employers contributed to health insurance for 25 per cent of employed men and 7 per cent of employed women. Risk of admission was greater, and admissions were longer, in those least educated and from poorest circumstances; men with largest waist-hip ratios were admitted for longer than others. Private admissions were proportionately greater in nonmanual classes and among those from favourable social and educational backgrounds, that is, those known to be at least risk of serious and chronic illness. Heaviest users of in-patient care were those most likely to be at greatest health risk, who were least likely to have private health insurance. The rising mid-life uptake of private health insurance through employers (25 per cent of employed men by age 43 years) may foreshadow a future problem in a return to NHS care on retirement in this population, which represents the beginning of the future population bulge in the elderly.
|
7786566
|
Does routine child health surveillance reach children most at risk of accidental injury?
|
There is currently an increasing emphasis on accident prevention as part of routine child health surveillance, which unlike opportunistic accident prevention has the potential to reach the whole population. However, non-attenders at routine child health surveillance may also be children at higher risk of accidental injury, as there is some evidence that non-attenders may be more likely to live in socio-economic disadvantage, which is a risk factor for accidental injury. A case control study was carried out in one general practice in Nottingham with 253 cases and 243 controls, aged four years and under, obtained from the practice age-sex register. Cases were defined as children who had attended the accident and emergency department, the general practitioner or the practice nurse after an accidental injury at any time during their life. Controls were children who had not had a medically attended accidental injury. Attendance at routine child health surveillance, before the date of the case's accidental injury, was assessed by attendance at the eight-month hearing test, immunization status, child health clinic visits and home visits by the health visitor. There was no significant difference between cases and controls in attendance for the hearing test, or immunization status. Cases received significantly more home visits after adjusting for confounding variables (odds ratio 2.44, 95 per cent confidence intervals 1.28-4.66). These findings suggest that non-attenders at routine child health surveillance activities are not at an increased risk of medically attended accidental injury. They also suggest that health visitors can identify those children most at risk of accidental injury using criteria for classifying priorities in caseloads.
|
7786567
|
Measuring health status with the SF-36: the need for regional norms.
|
Normative data on SF-36 scores in populations from Oxford and Aberdeen have recently been published. It has been suggested that such data provide suitable normative values for the UK population. However, other indices of health vary considerably across regions, and tend to be worse in areas such as South Wales. The objective of this study was to determine whether population SF-36 scores in West Glamorgan differ from scores from other parts of the United Kingdom. The SF-36 health status questionnaire was administered to two random samples of adults aged 20-89 years, drawn from the West Glamorgan Family Health Services Authority register. One sample (n = 919) received postal questionnaires and those in the other sample (n = 1201) were interviewed in their own homes. Normative data from this study were compared with published data from other areas of the United Kingdom. SF-36 population scores were significantly lower in the two West Glamorgan samples; this was not due to differences in age, sex, social class, or response rates. Health status in West Glamorgan, as measured by the SF-36, is lower than in Oxford or Aberdeen. A national study would be required to provide appropriate normative data for the UK population.
|
7786565
|
Increasing response rates in telephone surveys: a randomized trial.
|
Sampling frames and mode of contact and administration of questionnaires are important factors contributing to response rates and selection bias in population-based research. The purpose of this paper is to evaluate whether contact by mail before contact by telephone increases response rate, and to assess the concurrent validity of telephone surveys for collecting health research and service data. Two thousand households were randomly selected from electronic white pages. Half were randomly allocated to receive or not to receive an explanatory letter before telephone contact. Interviewers were blinded to whether a household received a letter. Respondents aged 18 years or over were randomly selected from within each household using a Kish grid and interviewed by telephone. The overall response rate was 68 per cent [confidence interval (CI) 66-70]. The response rate of those who received the letter was 76 per cent (CI 73-79), and of those who did not receive the letter was 60 per cent (CI 56-63). Use of the Kish grid to select randomly a respondent decreased the response rate by less than 10 per cent. The internal validity of the data was as follows: in a 10 per cent sub-sample, the Kish grid had been correctly applied in 93 per cent of households, and in 99 per cent of households the exclusion criteria had been correctly adhered to. The external validity was as follows: comparisons with data obtained from the same reference population using similar instruments administered face-to-face revealed no meaningful or significant differences in population estimates. Mail-out before telephone contact greatly increases response rates at low cost. Telephone surveys can yield valid, useful data for health research and service evaluation.
|
7786563
|
Differences in hospital casemix, and the relationship between casemix and hospital costs.
|
The aim of the study was to examine the relationship between hospital costs and casemix, and after adjustment for casemix differences, between cost and institutional size, number of specialties, occupancy and teaching status. A retrospective analysis of all admissions to nine acute-care NHS hospitals in the Oxford region during the 1991-1992 financial year was undertaken. All episodes were assigned to a diagnosis-related group (DRG) and a cost weight assigned accordingly. Costs per finished consultant episode, before and after adjustment for casemix differences, were analysed at the hospital and specialty level. Casemix differences were significant, and accounted for approximately 77 per cent of the difference in costs between providers. Costs per casemix-adjusted episode were not significantly associated with differences in hospital size, scope, occupancy levels or teaching status, but sample size was insufficient to investigate these relationships adequately. Specialty costs were poorly correlated with specialty casemix. This was probably due to poor apportionment of specialty costs in hospital accounting returns. Casemix differences need to be taken into account when comparing providers for the purposes of contracting, as unadjusted unit costs may be misleading. Although the methods used may currently be applied to most NHS hospitals, widespread use would be greatly facilitated by the development of indigenous cost weights and better routine hospital data coding and collection.
|
7786562
|
Safety and place of birth in Scotland.
|
The recent publication of policies suggesting women should have choice about where they give birth prompted a comparison of stillbirth and neonatal mortality rates for three types of maternity unit in relation to changes in booking and place of delivery. Scottish Maternity Discharge records and data from stillbirth and neonatal death reports for Scotland were used to analyse stillbirth and neonatal mortality rates according to the level of care, birthweight and cause of death for the years 1986-1990. For those categories of stillbirths and neonatal deaths which are amenable to prevention by perinatal care, intrapartum stillbirth rates were higher in general practitioner (GP) units than in consultant units, but these accounted for only 11 stillbirths and the difference is compatible with chance variation. Neonatal mortality among babies weighting 2500 g or more was independent of type of hospital. Among babies weighing under 1500 g or 1500-2499 g, neonatal mortality was significantly higher in non-teaching hospitals than in teaching hospitals. Although the differences are compatible with chance variation, there is some suggestion that small GP hospitals might have higher rates of intrapartum stillbirths and such rates should be monitored. Provided that there are no barriers to transfer to hospitals with consultant units when appropriate, there is no evidence that these small GP hospitals are unsafe. The high neonatal mortality rates, especially among babies weighing 1500-2499 g in non-teaching consultant units, compared with teaching units, should be investigated further.
|
7786555
|
An estimate of the prevalence of drug misuse in Liverpool and a spatial analysis of known addiction.
|
The objective of this study was to determine the prevalence and distribution of opiate and cocaine misuse in the City of Liverpool in 1991. The databases included residents of the city using opiates or cocaine, who were known to the Drug Dependency Units or the Infectious Diseases Unit, or who were arrested for possession of drugs in 1991. A three-sample log-linear capture-recapture method was applied to databases containing details of drug users with City of Liverpool postcodes, to determine the prevalence of drug misuse in 1991. Linear regression analysis was performed to correlate the prevalence of known drug misuse with indices of material deprivation in each electoral ward. Data on 1427 individuals were analysed, producing an estimate of the drug-using population of 2344 [95 per cent confidence interval (CI) = 1972-2716] and a period prevalence of 5.2 per 1000 [95 per cent CI = (4.5-6.0) per 1000]. In the 15-29 year age group, the prevalence of drug abuse was 16.9 per 1000 [95 per cent CI = (13.9-19.9) per 1000]. There was a negative interdependence between the police and Drug Dependency Unit databases with attenders at the Unit being 7.2 (95 per cent CI = 4.6-11.4) times less likely to be arrested for possession than non-attenders. There was a strong correlation between the distribution of known drug use and material deprivation, as measured by the Townsend index (r = 0.75; p < 0.001). The capture-recapture method allows the prevalence of drug misuse to be estimated and provides more meaningful information than is available from the notification system. The study suggests that people in contact with drug services are less likely to commit crimes of possession of class A drugs than those not in contact with drug services. There is a strong association between drug abuse and deprivation, and therefore the purchasing of services for drug misusers should be focused on areas of deprivation.
|
7786547
|
[Peripheral neuropathy in progressive systemic sclerosis].
|
We report a patient that developed a sensorimotor polyneuropathy more than a year before the appearance of the typical clinical signs of progressive systemic sclerosis. A sural nerve biopsy showed epineural vasculitis with involvement of the basal membrane of the endoneural vessels, without proliferation of the connective tissue.
|
7786546
|
[Spontaneous syncope as the only sign of Arnold-Chiari type I malformations].
|
We present a patient suffering from spontaneous recurrent syncopes as the sole symptom of Arnold-Chiari type I malformation. The syncopes were attributed to transient compression of neural and/or vascular structures at the cranio-cervical junction by the descended cerebellar tonsils, triggered by an increase in intracranial pressure. The disappearance of symptoms after posterior fossa decompression confirmed our hypothesis.
|
7786545
|
[Palilalia due to thalamic infarctions].
|
A 45-years-old woman developed palilalia without other neurologic symptoms or signs. Cranial MR and CT scan showed only bilateral thalamic infarcts; the SPECT showed bilateral frontoparietal hypoactivity. We conclude that involvement of the supplementary motor area by diaschisis after bilateral thalamic lesions may produce palilalia.
|
7786544
|
[Multiple entrapments neuropathy in adult polyglucosan body disease].
|
Adult polyglucosan body disease (APBD) is a rare condition characterized by neuropathy, dementia, upper motor neuron dysfunction and neurogenic bladder. For diagnosis, the presence of polyglucosan bodies (PB), or PAS (+) glucose polymers, must be demonstrated. In this description of a woman with APBD and multiple entrapment neuropathy, we discuss a possible role for morphological changes induced by PB in increasing susceptibility to pressure palsies.
|
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.