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8042772 | Partial characterization of a fraction from bull seminal vesicle fluid that potentiates the bull sperm acrosome reaction in vitro. | A fraction from bovine seminal vesicle fluid that initiated acrosome reaction of bovine epididymal spermatozoa in vitro in the presence of heparin was prepared by sequential chromatographies on heparin-Sepharose, gel filtration (Superose 12) and reversed phase chromatography (ProRPC). Sequence analysis of the separated fraction showed that it contained the major protein (PDC-109) with 100% homology. This fraction contained also Ca(2+)-dependent phospholipase A2-like activity which hydrolysed phosphatidylethanolamine and phosphatidylcholine with 14C-labelled linoleic (lino-PE, lino-PC) or arachidonic acid (ara-PE, ara-PC) at sn-2 position. This protein was not detected in N-terminal sequence analysis. Lysophosphatidylcholine, lysophosphatidylethanolamine, and p-bromophenacyl bromide (p-BPB) inhibited this lipolytic activity. Sulfoglycolipid (Seminolipid) had inhibitory effect at concentrations above 0.1 mM but activated slightly the enzyme at lower concentrations. Boiling destroyed acrosome initiating activity in the separated fraction. |
8042771 | Effect of lipid peroxidation on beating frequency of human sperm tail. | The tail beat frequency (TBF) of sperm was measured with a sperm-head fixation method which was based on the tendency of sperm to attach its head to the surface of a glass slide. Ferrous sulphate, a promotor of lipid peroxidation, inhibited TBF within 5 min of mixing with sperm. This inhibition can be reversed dose-dependently by superoxide dismutase, catalase, glutathione, and albumin. It was concluded that TBF could be a new pharmacological model for studying the effect of lipid peroxidation and antioxidant on sperm motility. Both enzymatic and non-enzymatic antioxidants can be screened with this method. |
8042770 | Assessment of sperm function in fertile and infertile men. | The sperm function of fertile men (control), infertility patients (experimental), and men with varicocele were compared. The bioassays used were the follicular fluid-induced acrosome reaction, the binding to the zona pellucida, and the penetration of zona-free hamster oocytes. The percentage (mean +/- SEM) of reacted spermatozoa was 35 +/- 3 in the control, 22 +/- 1 in the experimental, and 22 +/- 3 in the varicocele. The minimum value of acrosome reaction in control men was 20%. The mean number of zona-bound spermatozoa was 250 +/- 30 in the control, 160 +/- 28 in the experimental, and 196 +/- 44 in the varicocele. The minimum number of zona bound spermatozoa in control men was 50. The mean number of hamster oocytes penetrated was 50 +/- 8 in the control, 19 +/- 3% in the experimental, and 10 +/- 3 in the varicocele. The minimum number of oocytes penetrated in control men was 6%. In the experimental group, 22 men had a normal sperm function, 58 had 1 or 2 bioassays below the minimum (relative dysfunction), and 10 had all bioassay below the minimum (abnormal sperm function). The results of these bioassays could help to reclassify the infertile men in several subgroups. |
8042769 | A new device for microsurgical sperm aspiration. | A new device for microsurgical aspiration of seminal fluid is presented. It is simple to use, flexible, and watertight, allowing maximum retrieval of seminal fluid. |
8042768 | Role of FSH in regulating testicular germ cell transformations in the rat: a study using DNA flow cytometry. | The role of FSH in regulating testicular germ cell transformations during initiation and maintenance of spermatogenesis in the pubertal and adult rat has been studied using DNA flow cytometry (FCM). The cell types were quantified on the basis of their DNA content using DNA specific fluorochrome DAPI (4,6-diamidino phenylindole). Pubertal (30-d old) and adult (100-d old) rats were deprived of endogenous FSH support for 10 d by daily injection (200 microliters d-1) of a characterized FSH antiserum; the control group received an equivalent volume of normal rat serum. FSH deprivation did not lead to any change in serum testosterone levels. The relative proportion of testicular germ cells in the FSH deprived pubertal rat showed a 90% reduction in 1C (round spermatids) and 260% and 90% increase in 2C (spermatogonia) and 4C (spermatocytes) cells respectively. While the overall conversion of 2C to 1C (1C:2C ratio) was reduced by 98%, the transformation of 2C to 4C (4C:2C ratio) and 4C to 1C (meiotic division 1C:4C ratio) was inhibited by 43% and 93% respectively. In the FSH-deprived adult rat the overall conversion of 2C to 1C was reduced by 26% (P < 0.05) only. The 2C and 4C population of cells increased by 47% and 97% respectively (P < 0.025) and the 4C:2C ratio by 47% (P < 0.05). While the meiotic division (1C:4C ratio) was reduced by 54% (P < 0.001), the post-meiotic differentiation of round spermatids to elongate-spermatids (HC:1C) was inhibited by 68% (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) |
8042767 | Three-dimensional photographic study of cancellous bone in human fourth lumbar vertebral bodies. | In an analysis of the 3D architecture of cancellous bone, two-dimensional techniques are of limited value. A simple technique employing stereophotographs of whole sections of lumbar vertebrate made possible a detailed description of the 3D structure of the normal fourth lumbar vertebral body and its changes with ageing and osteoporosis. Parallax measurements were used to calculate the real lengths of horizontal trabeculae. The bone presented a continuous spectrum of microstructure, from a honeycomb of tubes, to plates and braces and, finally, fragile rods. A distinct pattern was produced in osteoporotic samples by the removal of horizontal and selected vertical trabeculae followed by a thickening of the remaining vertical trabeculae in the peripheral regions. Very long, thin horizontal trabeculae were formed in all three zones (superior, middle and inferior) during this process. The observation of porotic architecture in intact specimens points to the inadequacy of the clinical criterion of the occurrence of a fracture in judging the osteoporotic state. |
8042766 | Morphological indications for considerable diffuse reabsorption of cerebrospinal fluid in spinal meninges particularly in the areas of meningeal funnels. An electronmicroscopical study including tracing experiments in rats. | Transmission and scanning electron microscopical observations in the rat indicate a considerable capacity of the spinal meninges to reabsorb cerebrospinal fluid. The density of blood vessels and lymphatics in the duramater is extremely high, particularly in the areas of meningeal funnels and spinal nerve root sleeves. Arterioles with closely related unmyelinated nerve fibres, many fenestrated capillaries and venules predetermine these areas as sites where absorption processes could take place. At certain sites of the meningeal angle region, the arachnoid membrane, mostly multilayered, is reduced to only three or four layers. Intercellular discontinuities and cytoplasmic fenestrations occurring in the arachnoid lining cell layer result in direct communications between the subarachnoid space and cisterns of the arachnoid "reticular layer". These cisterns are partly fluid-filled, partly occupied by a net of collagen fibre bundles. Some cisterns harbour macrophages that often project filiform processes through the lining cell layer into the subarachnoid space, contacting cerebrospinal fluid. Desmosomes and gap junctions are present in all layers of the arachnoid. However, tight junctions and the continuous electrondense intercellular gap, known to occur normally within the "arachnoid barrier layer", were not seen in many sites of the meningeal angle region. Numerous arachnoid cells display a high degree of vesiculation. Cationized ferritin, introduced in vivo into the rat subarachnoid space, passes inter- and intracellularly from the cerebrospinal fluid compartment through the arachnoid membrane, reaching dural blood vessels and lymphatics. Tracer could be visualized both in the cytoplasm of the endothelium and on the luminal surface of the cells. Tracer also passed through pial cell layers into pial vessels, through leptomeningeal sheaths into vessels crossing the subarachnoid space, into the connective tissue compartment and into vessels of spinal dorsal root ganglia. In the angle region, a particularly large number of macrophages can be found on the surface of leptomeninges, within the arachnoid reticular layers, and in close relation to dural and epidural capillaries, venules and lymphatics. Their possible role in the process of cerebrospinal fluid reabsorption is discussed. |
8042765 | Configuration of myoepithelial cells in various exocrine glands of guinea pigs. | To study the configuration of myoepithelial cells, we isolated glandular endpieces of various guinea pig glands by collagenase, and visualized the myoepithelial cells by immunohistochemistry for actin, or by Bodipy-phallacidin, under both a light microscope and laser scanning confocal microscopes. In parotid and mandibular glands, the glandular acini were small (about 20-30 microns diameter) and spherical, and each acinus had one or two myoepithelial cells attached that were stellate in shape (central cell body and four to six thin processes). Most of the basal surface of the glandular cells was not covered by myoepithelial cells, and processes often extended to the neighboring acinus. The tubular glandular endpieces of the major sublingual gland, which secretes a mucous substance, were almost fully encircled by band-like myoepithelial cells (about 3-6 microns wide). Although there were many differences between the lacrimal gland and the Harderian gland (e.g., the secretory product of the lacrimal gland was mucous, and glandular lumina were narrow; the Harderian gland secreted lipids and showed wide lumina), the outer contours of both glandular endpieces were the same (about 50-100 microns diameter, ellipsoid or spherical in shape). In both glands, 5-20 stellate myoepithelial cells were attached onto a glandular endpiece, and their arrangement had a lacy appearance. Actin filaments in myoepithelial cells aggregated and formed bundles in the broad processes and cell bodies. The bundles ran across the cell body, but there was no point where the bundles converged. In the arborization, some distal processes reversed their direction. We conclude that the configuration of myoepithelial cells depends on the outer contour of the glandular endpieces rather than on the secretory material or luminal width. The variety of myoepithelial cell configurations in the different exocrine glands we examined suggests that it is quite difficult to assign to myoepithelial cells the general role of expelling secretory products from glandular lumina. These cells seem to maintain the contour of the glandular endpieces, serving as the exoskeleton of the endpieces. |
8042764 | Light and electron microscopic study of omental milky spots in New Zealand black mice, with special reference to the extramedullary hematopoiesis. | Omental milky spots are especially large and numerous in New Zealand Black (NZB) mice, which are known to develop spontaneous autoimmune diseases. We investigated omental milky spots in NZB mice by light and electron microscopy. The milky spots were composed of abundant lymphocytes/plasma cells with macrophages, neutrophils, eosinophils, megakaryocytes, and various stromal cells. In addition, clustered neutrophils in various maturation stages with occasional mitotic figures were frequently present in the milky spots: apparent neutrophilic myelopoiesis was present. The presence of megakaryocytes was sporadic. Considering the giant size of megakaryocytes, their direct migration into the milky spots from the bone marrow or spleen seems improbable. Thus, the presence of megakaryocytes was interpreted as probable megakaryopoiesis. Erythroblasts were not contained in the milky spots. These findings seem to indicate that the milky spots in NZB mice represent a special type of lymphoid tissue with active neutrophilic myelopoiesis and probable megakaryopoiesis. Reticulum cells in the milky spots in NZB mice had well-developed dense bodies consisting of clustered parallel tubules that showed a hexagonal array. However, the biological significance of these cells remains unknown. |
8042763 | [Anesthesia and diabetes mellitus]. | There are two types of diabetes mellitus. Type I, insulin-dependent diabetes (IDDM), which becomes manifest before the age of 40, is the result of an absolute deficiency of insulin. Type II, the non-insulin-dependent diabetes (NIDDM), develops in the elderly and is caused by a relative insulin deficiency. Patients with type-I diabetes are prone to the development of ketoacidosis, while type II causes hyperglycaemic, hyperosmolar, nonketotic coma. Apart from these acute metabolic alterations, the long-term complications of diabetes are of concern to the anaesthesiologist. Hypertension, coronary artery disease, renal insufficiency and autonomic neuropathy are common and can result in myocardial ischaemia, cardiovascular instability and gastroparesis, with an increased risk of aspiration. Limited movement of the atlanto-occipital joint can cause difficult intubation. To avoid perioperative metabolic catastrophy, blood glucose concentration should be kept between 6.7 and 10 mmol.l-1 (120-180 mg.dl-1). Hypoglycaemia can result in neurological damage, whereas hyperglycaemia causes impaired wound healing and susceptibility to infections and worsens ischaemic damage to the myocardium and brain. Perioperative diabetes management depends on the severity of the surgical procedure and the type of diabetes. All type-I diabetics, whatever operation being performed, need insulin. The intravenous route is recommended as it allows better adjustment. After determination of the fasting blood glucose level, insulin is given at a dosage of 0.5-1 U.h-1 (at gluc < 11.1 mmol.l-1), 1.5-2 U.h-1 (at gluc 11.1-16.7 mmol.l-1) or 3 U.h-1 (at gluc > 16.7 mmol.l-1). In addition, 5-10 g glucose.h-1 is given. In type-II diabetes the oral antidiabetic drug is withheld. During minor surgery the blood glucose concentration is monitored frequently, and if necessary insulin (with gluc > 13.9 mmol.l-1) or glucose is given. In most cases of major surgery insulin therapy will be necessary. Administration should follow the guidelines listed for type-I diabetes. Whether the intravenous or the subcutaneous route is used for insulin, repeated glucose determinations are mandatory. If ketoacidosis develops the volume depletion is treated with normal saline. For hyperglycaemia and acidosis insulin (3-6 U.h-1) with 10-20 mmol.h-1 potassium phosphate is given. Bicarbonate is only indicated when the serum pH is lower than 7.1. It must be borne in mind that perioperative management of diabetes does not end with postanaesthesia care. |
8042761 | [Combined lung and liver transplantation. Anesthesiologic management]. | A 53-year-old man with alpha-1-antitrypsin deficiency had an 8-year history of progressive dyspnoea and two episodes of bleeding oesophageal varices with liver decompensation. After the diagnosis of terminal pulmonary emphysema (Fig. 1) and liver cirrhosis with progressive liver failure was made, he was accepted for combined lung and liver transplantation. METHODS. Anaesthesia was induced with thiopentone and fentanyl and maintained with fentanyl, midazolam, and isoflurane. After relaxation with succinylcholine, the patient's trachea was intubated with a left endobronchial double-lumen tube. Haemodynamic monitoring included arterial, central-venous, pulmonary-artery, and capillary-wedge pressures and cardiac output measurement. Ventilatory monitoring consisted of pulse oximetry, side-stream spirometry, and continuous measurement of arterial and mixed-venous blood oxygen saturation with fibreoptic catheters. A left single-lung transplantation was performed under one-lung ventilation without cardiopulmonary bypass. Prostacyclin was infused to reduce pulmonary vascular resistance. The transplant was ventilated separately with 50% oxygen and positive end-expiratory pressure of 8-10 cm H2O, and then liver transplantation was carried out. The institution of veno-venous bypass during the anhepatic phase failed because of portal-vein and axillary-vein thrombi. RESULTS. Total operation time was 6 h 30 min. Clamping of the left pulmonary artery lasted 45 min and the duration of the anhepatic phase was 92 min. Ventilation and oxygenation during lung transplantation caused no problems (Table 1). Clamping of the left pulmonary artery caused a slight increase in pulmonary vascular resistance (104 to 124 dyn.s.cm-5) and mean pulmonary artery pressure (25 to 27 mm Hg) without a decrease in cardiac index (Table 2). During the anhepatic phase with exclusion of the portal vein and inferior vena cava, a marked decrease in cardiac index (-27.2%) was seen (Table 4). The operation required substitution with 10 units packed red blood cells, 12 units fresh frozen plasma, and 5 platelet concentrates. The post-operative course showed normal liver graft function (Table 5). Acute pulmonary rejection on the 7th day was treated successfully with methylprednisolone. The patient's trachea has extubated 10 days after transplantation and he was discharged from the intensive care unit 2 weeks later. CONCLUSION. The management of this combined lung and liver transplantation was performed according to the experience with isolated lung and liver transplants in our hospital. Aggressive haemodynamic and ventilatory monitoring, including systemic and pulmonary arterial fibreoptic catheters, seems of particular importance in such high-risk procedures. |
8042760 | [Postoperative analgesia with tramadol. Continuous infusion versus repetitive bolus administration]. | Postoperative pain relief can be achieved by several methods, including the use of systemic opioids and regional anaesthesia with intrathecal or epidural opioids or local anaesthetics. On-demand analgesia using a PCA (patient-controlled analgesia) system is regarded as the ideal option for systemic opioid analgesia. While PCA devices are not yet commonly used in all recovery units, the use of repetitive boluses on demand is still the most frequent form of administration in postoperative pain therapy. The objective of the present study was to show if continuous infusion of the opioid tramadol could produce better analgesia than repetitive administration of boluses. METHOD. In a study under double-blind conditions 135 ASA I and II patients were assigned at random to group I (infusion group) or group B (bolus group) when they first requested pain treatment after abdominal surgery. The patients in group I received an initial intravenous loading dose of 100 mg tramadol, followed by an infusion of 12 mg/h tramadol for 24 h; if necessary, repeated boluses of 50 mg tramadol were given. In group B the patients received a placebo infusion instead of the tramadol infusion; otherwise, the procedure was the same. Pain relief was monitored by means of a VAS (visual analogue scale) up to 6 h after surgery. We investigated the retrograde assessment of analgesia by the patients after 6 h, how often repetitive boluses were required, and the amount of analgesics administered in 6 and 24 h. RESULTS. The pain relief was assessed as excellent or good by 76.5% of group I and 65.6% of group B; 19.1% of group I and 26.9% of group B assessed the analgesic effect as satisfactory; 4.4% of group I and 7.5% of group B complained of insufficient analgesia. In group I 69.2% requested only one or no repetitive bolus, compared with 40.3% in group B, while two or more boluses were demanded by 30.8% in group I und 59.7% in group B. The average analgesic consumption after 6 h was 223.5 +/- 53.7 mg tramadol in group I and 176.6 +/- 63.1 mg tramadol in group B, respectively. After 24 h it was 449.5 +/- 66.0 mg tramadol in group I and 201.6 +/- 83.9 mg tramadol in group B. While the consumption during the first 6 h was comparable, from then on the consumption in group I increased significantly. Side effects were reported by 25% in both groups. They were clinically irrelevant and did not necessitate termination of the clinical trial in any case. During the study period pulse and blood pressure remained within the normal range and did not show any significant changes. CONCLUSION. The fact that the patients in group I requested far fewer repetitive boluses than those in group B and the assessment by the patients led to the conclusion that treatment in the infusion group is better than that in the bolus group. Concerns that a significantly higher consumption of analgesics would cause unwanted side-effects have proven unfounded. Six hours after surgery, when analgesia was evaluated by the patients, there was no significant difference between the two groups. Not until the maintenance infusion had been administered for a further 18 h, was the tramadol consumption within the infusion group significantly higher. Thus, we should consider continuing unreduced administration of the maintenance infusion 6 h after operation. |
8042759 | [What's new in cardiopulmonary resuscitation? American Heart Association]. | A strong consensus was reached for several changes in the guidelines for cardiopulmonary resuscitation (CPR) and emergency cardiac care (ECC) in the 1992 conference on CPR and ECC held by the Emergency Cardiac Care Committee of the American Heart Association. These new recommendations, together with differing recommendations of the European Resuscitation Council, are described. An unresponsive person with spontaneous respirations should be placed in the recovery position if no cervical trauma is suspected. Compared with endotracheal intubation, other airway-protecting devices such as combination esophageal-tracheal tubes are of minor acceptance. During ventilation, the time for filling the lungs is increased to 1.5-2 s to decrease the likelihood of gastric insufflation. Delivery of i.v. drugs can be enhanced by an i.v. flush of sodium chloride. In endotracheal drug administration, higher doses and drug dilution are recommended. In infants and children up to 6 years of age, the value of intraosseous drug administration is emphasized. For pulseless adult victims, the initial dosage of epinephrine of 1 mg i.v. remains unchanged. For repeat doses, high-dose epinephrine up to 0.1 mg/kg is classified as of uncertain but possible efficacy. For lidocaine, the recommended i.v. dosage is 1.5 mg/kg. Sodium bicarbonate and calcium are not routinely recommended for resuscitation. For atropine, the maximum dose is 0.04 mg/kg. If hypomagnesaemia is present in recurrent and refractory ventricular fibrillation, it should be corrected by administration of 1 to 2 g magnesium sulfate i.v. Thrombolytic agents are classified as useful and effective in acute myocardial infarction and should be administered as early as possible. Glucose-containing fluids are discouraged for resuscitative efforts. |
8042758 | [Therapy of ARDS. 1. Current therapeutic strategy including extracorporeal gas exchange]. | Recent studies and reviews continue to report a high mortality associated with the acute respiratory distress syndrome (ARDS), which involves a severe inflammatory reaction within the whole lung that is frequently associated with multiple-organ failure. Important factors contributing to the poor results in severe ARDS are the aggressive procedures required to maintain sufficient arterial oxygenation, such as mechanical ventilation with high inspiratory pressures and high inspired oxygen concentrations (FiO2) which themselves contribute to the progression of the disease. As no specific therapy that reduces or prevents the general inflammatory reaction is known, current therapy is limited to procedures that minimize peak inspiratory pressures and FiO2. Therefore, pressure- and volume-limited ventilation modes with positive end-expiratory pressure, controlled hypercapnia, differential lung ventilation when appropriate, positioning (particularly prone), and aggressive dehydration are used. Should these procedures fail to improve arterial gas exchange, the patients may be additionally treated by veno-venous extracorporeal gas exchange. To reduce the risk of severe haemorrhagic complications due to high levels of systemic heparinization, systems internally coated with covalently bound heparin, which allow a lower level of systemic anticoagulation, should be used. From April 1989 to August 1993, 89 patients were transferred to our intensive care unit for treatment of severe ARDS; 52 were treated by combining the described conventional methods without artificial gas exchange (survival rate 88%) and 37 additionally underwent artificial gas exchange (survival rate 57%). The overall survival rate was 75%. On the basis of these experiences, we conclude that this step-by-step approach may improve survival in patients with severe ARDS. |
8042757 | [Anesthesia with flunitrazepam/fentanyl and isoflurane/fentanyl. Unconscious perception and mid-latency auditory evoked potentials]. | There is a high incidence of intraoperative awareness during cardiac surgery. Mid-latency auditory evoked potentials (MLAEP) reflect the primary cortical processing of auditory stimuli. In the present study, we investigated MLAEP and explicit and implicit memory for information presented during cardiac anaesthesia. PATIENTS AND METHODS. Institutional approval and informed consent was obtained in 30 patients scheduled for elective cardiac surgery. Anaesthesia was induced in group I (n = 10) with flunitrazepam/fentanyl (0.01 mg/kg) and maintained with flunitrazepam/fentanyl (1.2 mg/h). The patients in group II (n = 10) received etomidate (0.25 mg/kg) and fentanyl (0.005 mg/kg) for induction and isoflurane (0.6-1.2 vol%)/fentanyl (1.2 mg/h) for maintenance of general anaesthesia. Group III (n = 10) served as a control and patients were anaesthetized as in I or II. After sternotomy an audiotape that included an implicit memory task was presented to the patients in groups I and II. The story of Robinson Crusoe was told, and it was suggested to the patients that they remember Robinson Crusoe when asked what they associated with the word Friday 3-5 days postoperatively. Auditory evoked potentials were recorded awake and during general anaesthesia before and after the audiotape presentation on vertex (positive) and mastoids on both sides (negative). Auditory clicks were presented binaurally at 70 dBnHL at a rate of 9.3 Hz. Using the electrodiagnostic system Pathfinder I (Nicolet), 1000 successive stimulus responses were averaged over a 100 ms poststimulus interval and analyzed off-line. Latencies of the peak V, Na, Pa were measured. V belongs to the brainstem-generated potentials, which demonstrates that auditory stimuli were correctly transduced. Na, Pa are generated in the primary auditory cortex of the temporal lobe and are the electrophysiological correlate of the primary cortical processing of the auditory stimuli. RESULTS. None of the patients had an explicit memory of intraoperative events. Five patients in group I, one patient in group II, and no patients in group III showed implicit memory of the intraoperative tape message. They remembered Robinson Crusoe spontaneously when they were asked their associations with Friday. In the awake state AEP peak latencies were in the normal range. During general anaesthesia in group I, the peaks Na, Pa did not increase in latency or decrease in amplitude before and after the audiotape presentation. The primary cortical complex Na/Pa could be identified as in the awake state. In contrast, in group II Na, Pa showed a marked increase in latency and a decrease in amplitude or were completely suppressed. CONCLUSIONS. During general anaesthesia auditory information can be processed and remembered postoperatively by an implicit memory function, when the electrophysiological conditions of primary cortical stimuli processing is preserved. Implicit memory can be observed more often when high-dose opioid analgesia is combined with receptor-binding agents like the benzodiazepines than under non-specific anaesthetics like isoflurane. Non-specific anaesthetics seem to provide a more effective suppression of auditory stimuli processing than receptor-specific agents. |
8042756 | [Muscle relaxation in patients with neuromuscular diseases]. | The classification of neuromuscular diseases with regard to the use of muscle relaxants is based on the localisation of the particular abnormality. Three types of syndromes can be differentiated: (1) denervation states; (2) disturbances of neuromuscular transmission; and (3) intracellular disease. Succinylcholine should be avoided in all types of denervation syndrome due to the possibility of life-threatening hyperkalaemia. The time frame during which succinylcholine must be avoided following a traumatic denervation or burn begins 24 h after the event. The exact period of risk is unknown, but a duration of 6 months can be considered the absolute minimum. Patients may display increased sensitivity to non-depolarising muscle relaxants following damage to the second motoneuron (e.g., amyotrophic lateral sclerosis), whereas in diseases of the first motoneuron (e.g., cerebral apoplexy), increased resistance to muscle relaxants may be observed in the affected parts of the body. In diseases of the neuromuscular junction (myasthenia gravis) there is increased sensitivity to non-depolarising muscle relaxants. No complications have been described following the use of succinylcholine in these patients, however, the use of reversal agents may lead to prolongation of the effect of succinylcholine. Patients with a primary myopathy may display increased sensitivity to non-depolarising muscle relaxants. The use of drugs with acetylcholine-like actions (succinylcholine, reversal agents) should be avoided due to the danger of triggering muscle spasms in patients with myotonic disease and the risk of rhabdomyolysis in patients with dystrophic muscle disease. Irrespective of the type of muscle disease present, titration of the dose of muscle relaxant should always be done using a nerve stimulator.(ABSTRACT TRUNCATED AT 250 WORDS) |
8042736 | Extension of epidural blockade for emergency caesarean section. Assessment of a bolus dose of bupivacaine 0.5% 10 ml following an infusion of 0.1% for analgesia in labour. | A safe and predictable method by which an epidural infusion sufficient for pain control in labour can be rapidly converted to a more intense block adequate for emergency Caesarean section continues to present a challenge. A prospective study was undertaken. The routine use of a bolus dose of 10 ml of 0.5% bupivacaine was assessed as a top-up for emergency Caesarean section following a 0.1% infusion for labour. This produced an adequate block in 11 out of 18 patients. There were no significant differences in duration of infusion, cumulative local anaesthetic dose or pre-existing block height in these patients when compared with the remaining seven patients who required an additional top-up. |
8042735 | Lignocaine 0.5% for spinal anaesthesia in gynaecological day surgery. | Spinal anaesthesia with 5 ml of lignocaine 0.5% was administered to 30 women presenting for day case minor gynaecological surgery. They were allocated at random to receive the anaesthetic via either a 26-gauge Atraucan (pencil point) or a 29-gauge Spinocan (cutting bevel) spinal needle. Onset, duration, spread and regression of sensory and motor blockade, haemodynamic parameters and postoperative complications were studied. An upper sensory level of T10 (93.3%) was obtained in all except two patients. No patient complained of discomfort during surgery. The mean onset time was less than 8 min and the mean duration of sensory block was 32.5 min. All patients had complete return of motor power within 1 h and were discharged the same day. Only one patient had a transient episode of hypotension which was easily treated with intravenous fluids. There were no serious side effects seen postoperatively. We conclude that spinal anaesthesia with 5 ml of lignocaine 0.5% provides a useful alternative to general anaesthesia for day case minor gynaecological surgery. |
8042734 | Pre-oxygenation: a comparison of two techniques using a Bain system. | Pre-oxygenation using a standard technique of tidal breathing for 3 min through a Bain system with a fresh gas flow of 8 l.min-1 was compared with up to six vital capacity breaths from the same system. The technique of vital capacity breaths involved initial expiration to residual volume and use of the oxygen flush throughout controlled full inspirations, ensuring that the reservoir bag remained full. No significant problems were encountered using this method. Although three vital capacity breaths produced significantly inferior pre-oxygenation compared to 3 min of normal breathing, four and five vital capacity breaths were equally effective. With six vital capacity breaths, superior pre-oxygenation was produced. The use of four or more vital capacity breaths with this technique is a reliable and rapid alternative to 3 min of tidal breathing. |
8042733 | Analgesic effect of intra-articular morphine after arthroscopic meniscectomy. | A study was performed to assess the analgesic effect of intra-articular morphine 2 mg in 33 patients undergoing elective arthroscopic meniscectomy. Patients were randomly allocated to receive either 2 mg of morphine hydrochloride in 40 ml of normal saline intra-articularly and 1 ml of normal saline intramuscularly (n = 18), or 40 ml of normal saline intra-articularly and 2 mg of morphine hydrochloride intramuscularly (n = 15). The latter group was to act as a control for any potential systemic effects of the morphine. All patients received an identical general anaesthesia consisting of propofol, alfentanil, enflurane and nitrous oxide/oxygen. No significant differences between the groups were found in pain scores at rest or during active flexion of the knee at 1-6 h postoperatively, or during walking at 6 h postoperatively (p > 0.05). Six and two patients in the intra-articular and intramuscular morphine group, respectively, requested supplemental morphine given intravenously (p > 0.05). In conclusion, no significant differences in pain scores or in requirements for supplemental morphine were observed between patients receiving intra-articular versus intramuscular morphine 2 mg after elective arthroscopic meniscectomy and consequently no specific local analgesic effect of intra-articular morphine could be demonstrated. |
8042732 | Importance of components of the curriculum vitae in determining appointment to senior registrar posts. | To evaluate the opinions of regional education advisers, academics and other consultants about features of the curriculum vitae, we undertook a small attitude survey. The response rate was 73%, which provided data from a total of 78 influential anaesthetists. The respondents' attitude to each feature of the curriculum vitae was reported using a linear visual analogue scale. The three groups had similar attitude scores to most features, but not to research time, training time, higher degrees and abstracts of papers presented to the Anaesthetic Research Society. Publications in the main anaesthesia journals, time in other major medical specialties, research and the possession of a higher degree were scored highly by all respondents. Papers in non-peer-reviewed journals, letters, unsubmitted papers, and time in training for general practice attracted lower scores. The free text comments of many respondents indicated a considerable disillusionment about the whole appointments process. |
8042731 | The renin-angiotensin system and angiotensin converting enzyme (ACE) inhibitors. | Anaesthetists will encounter increasing numbers of patients who are receiving long-term treatment with ACE inhibitors for hypertension, congestive heart failure and prophylactically following myocardial infarction. Our understanding of the physiology and pharmacology of the renin-angiotensin system has dramatically increased in the last decade, and has led to the discovery of endogenous renin-angiotensin systems which may be physiologically more important than the better understood circulating system. There are several reports of adverse interactions between anaesthesia and ACE inhibitors, manifested as hypotension and bradycardia, which may be delayed until the postoperative period. The mechanism behind them is not understood and, as yet, no published studies have attempted to address this issue. It is possible, however, that dehydration associated with the pre-operative fast may play an important role. ACE inhibitors may, in the future, prove to be useful in the subspecialties of cardiac and vascular anaesthesia, where they might be used in an attempt to preserve cardiac function following periods of ischaemia and cardiopulmonary bypass, and to avoid renal damage following aortic cross-clamping. Meanwhile, it would seem prudent to exercise caution when anaesthetising patients taking ACE inhibitors and to be fully prepared to treat the hypotension and bradycardia which may occur. |
8042730 | Air inlets for infusion bottles. | We assessed the resistance to air flow in four commonly used air inlets. The Avon A81 and Codan air inlets provide the least resistance to flow, followed by the Baxter CO413 and lastly the Braun air inlet. The presence of a valve confers an advantage when rapid infusion of fluid is attempted. The valve in the Codan air inlet performed best out of the inlets tested. |
8042728 | A novel approach to insertion of the Montgomery T-tube. | We describe a novel method of inserting a silicone tracheal Montgomery T-tube using a gum elastic bougie. The advantages of this method over previously described methods are discussed. |
8042727 | Unilateral hypoglossal nerve paralysis following the use of the laryngeal mask airway. | We report a unilateral hypoglossal nerve paralysis following the use of a laryngeal mask airway in a 62-year-old woman with rheumatoid arthritis undergoing a shoulder joint replacement. Cervical epidural anaesthesia was combined with general anaesthesia using nitrous oxide administered via a laryngeal mask airway with the patient in the right lateral decubitus position. The next morning, the patient was noted to have a right hypoglossal nerve palsy. Compression of the nerve between the laryngeal mask airway cuff, distended with nitrous oxide, and the hyoid bone, was considered to be the cause of the nerve paralysis. |
8042725 | Anaesthesia and the new generation monoamine oxidase inhibitors. | The new generation monoamine oxidase inhibitors are short acting and specific for monoamine oxidase A. Evidence to date suggests that there is little potential for significant interaction with most drugs used in anaesthesia. |
8042724 | The effect of parenteral diclofenac and morphine on duration and height of blockade of continuous epidural infusion of bupivacaine 0.5%. | Twenty-six patients undergoing abdominal hysterectomy (ASA 1-2) were entered into a double-blind randomised trial to determine: (a) whether diclofenac given intravenously could influence the effective duration of a continuous epidural infusion of bupivacaine 0.5%, and (b) whether morphine given intravenously altered the height of the regressing block. A block to T4 was established pre-operatively and a continuous infusion of 0.5% bupivacaine 8 ml.h-1 ran for 14 h. Thirteen patients received 50 mg diclofenac intramuscularly before surgery repeated at 4 and 10 h later and 13 patients received saline intramuscularly. The height of blockade and pain scores were measured hourly. Effective block duration was defined as regression to T10 or lower and/or a pain score of 2 or more. At this point 10 mg of morphine was given intravenously and the height of the block reassessed. Duration of blockade was not significantly prolonged (p > 0.05), but pain scores were significantly reduced with diclofenac (p < 0.01). Morphine did not alter blockade height. It is concluded that epidural bupivacaine and diclofenac act additively on postoperative pain. |
8042723 | Pre-emptive analgesia from intravenous administration of opioids. No effect with alfentanil. | Forty patients undergoing total abdominal hysterectomy were randomly allocated to receive either 40 micrograms.kg-1 of alfentanil on induction of anaesthesia or 40 micrograms.kg-1 of alfentanil after the skin incision. Postoperative pain relief was provided with morphine from a patient-controlled analgesia system. The amount of morphine consumed in the operating theatre, while in recovery and for the first 24 h postoperatively was recorded. Pain scores were assessed at 24 h using a visual analogue scale. There were no differences found between the two groups for morphine consumption but the 'pre-emptive' group had significantly higher pain scores at rest. We conclude that there is no clinically useful pre-emptive analgesic effect with this dose of alfentanil and that therefore systemic opioid premedication is unlikely to decrease postoperative analgesic requirements through the mechanism of pre-emptive analgesia. |
8042722 | Continuous measurement of systemic vascular resistance. | We have successfully linked a standard patient monitor system (Hewlett Packard M1166A-A66) with the Baxter Edwards Critical-Care Swan Ganz Intellicath continuous cardiac output catheter and the Vigilance continuous cardiac output monitor system to produce continuous values of systemic vascular resistance. Six cases are presented in which marked changes in indexed systemic vascular resistance were observed as a result of clinical interventions. The continuous derivation of systemic vascular resistance has much potential as a diagnostic and research tool as well as allowing rapid accurate assessment of the response of patients to therapy. |
8042721 | Effect of three different surgical prone positions on lung volumes in healthy volunteers. | Ten healthy volunteers were placed in three different surgical prone positions (knee-chest, Eschmann frame and two supports, one each for the thorax and pelvis); the normal prone position without any supports was used as a control. Lung volumes using helium dilution and spirometry were calculated for each volunteer in each position. Compared with the control position, functional residual capacity, expiratory reserve volume, residual volume and total lung capacity were significantly higher in the knee-chest position. Functional residual capacity and expiratory reserve volume were significantly higher in the frame position. No advantage was gained with the use of the two supports position. We conclude that, of these three prone positions in awake volunteers, the knee-chest position causes least respiratory restriction. |
8042720 | Pulmonary function tests before and after laparoscopic cholecystectomy. | Pulmonary function tests were performed in 22 patients undergoing laparoscopic cholecystectomy. Measurements were made before, 24 h after, and 6 weeks after operation (12 patients). At 24 h postoperatively there were significant decreases in forced expiratory volume in 1 s, vital capacity, functional residual capacity and total lung capacity to 75% (p < 0.001), 73% (p < 0.001), 92% (p = 0.002) and 83% (p < 0.001) of pre-operative values respectively. Inspiratory and expiratory mouth pressures decreased to 66% (p < 0.001) and 63% (p < 0.001) of the pre-operative pressures respectively. There was a reduction in PaO2 (p < 0.01) and an increase in alveolar-arterial gradient (p < 0.001) but no change in PaCO2 at 24 h. The pulmonary function tests measured in the patients who returned after 6 weeks had returned to pre-operative values. |
8042719 | Effects of surgical stimulation on midlatency auditory evoked potentials during general anaesthesia with propofol/fentanyl, isoflurane/fentanyl and flunitrazepam/fentanyl. | During general anaesthesia, midlatency auditory evoked potentials are suppressed in a dose dependent manner by a number of general anaesthetics. The activating effects of surgical stimuli on midlatency auditory evoked potentials have been demonstrated during light inhalational anaesthesia, and indicate that midlatency auditory evoked potentials reflect the activity of the central nervous system and not only anaesthetic concentrations. We investigated the effect of surgical stimulation (skin incision, sternotomy) on midlatency auditory evoked potentials under high dose opioid analgesia in 30 patients undergoing elective cardiac surgery. High dose opioid analgesia was maintained using fentanyl (1.2 mg.h-1) and combined with either propofol (4-8 mg.kg-1.h-1) (group I, n = 10), isoflurane (0.6-1.2 vol%) (group II, n = 10) or flunitrazepam (1.2 mg.h-1) (group III, n = 10). Midlatency auditory evoked potentials were recorded in the awake state, during general anaesthesia before skin incision, after skin incision and after sternotomy. During general anaesthesia there were marked statistically significant increases in latencies and decreases in amplitudes of midlatency auditory evoked potentials in the propofol/fentanyl and isoflurane/fentanyl groups. In contrast, in the flunitrazepam/fentanyl group there were only small changes of midlatency auditory evoked potentials. The latencies of the early cortical potentials were similar to those in the awake state. After skin incision as well as after sternotomy no significant changes of midlatency auditory evoked potentials could be observed in any of the experimental groups. These results indicate that activation of the auditory pathway by surgical stimuli may be blocked when analgesia is provided by high dose fentanyl.(ABSTRACT TRUNCATED AT 250 WORDS) |
8042718 | Sevoflurane anaesthesia for major intra-abdominal surgery. | The cardiovascular effects and recovery characteristics of sevoflurane and isoflurane anaesthesia were compared in 30 gynaecological and 20 general surgical patients undergoing elective intra-abdominal surgery. Patients were randomly allocated to receive either sevoflurane or isoflurane as the volatile agent, in a balanced anaesthetic technique including morphine and atropine premedication and thiopentone, fentanyl, vecuronium and nitrous oxide. The concentration of volatile agent was titrated according to clinical variables. Mean heart rate, systolic and diastolic arterial pressure and duration of surgery did not differ between the two groups. Time to emergence from anaesthesia in the gynaecological patients was significantly faster after sevoflurane compared with isoflurane (p < 0.005). Sevoflurane provided stable anaesthesia during major intra-abdominal surgery. |
8042713 | The "new" democratic woman of modernity: Georgia O'Keeffe and Melanie Klein. | O'Keeffe put into visual language the psychic splitting that had occurred between the sexes in the United States, attempting to integrate what had formerly been separated as feminine and masculine into the female psyche. In her most important contribution, she explored presence rather than absence and opened up possibilities for thinking about openings. The concept of the female opening in particular had heretofore been assigned a negative meaning, signifying more often than not a gaping wound rather than a space and place of possibilities. Klein's complex and evocative understanding of some of the earliest mental processes of life enabled researchers to delve into the meanings made of the presence of the mother and father and baby, in the context of the baby's body-mind. Klein's female or male baby desires to know from the beginning. She discovered splitting and projective identification, the development of anxiety and guilt under the aegis of these mental processes, the multiple meanings of aggression, and, significantly, she permitted the female baby's body to have its own language. The answers provided by O'Keeffe and Klein bequeathed new possibilities for women's self-invention and remain pivot points for female identity throughout the century, to be confronted again by the second wave of feminism beginning in the late 1960s, by "postfeminist" debates, and by a challenged psychoanalysis. A more careful probing of these issues may help us to better understand our past so as to have greater resources for a more comprehensive reading of our present. |
8042710 | Narrative scripts: composing a life with ambition and desire. | The "formative and deformative narratives" and the psychodynamics of male-female relations permeate us all, and are revealed in theme and variations in our consulting rooms. Conventional narrative forms are largely androcentric, action-oriented, and point single-mindedly toward a goal (Van Buren, 1991), whereas women's stories and their identities--digressive and complex weavings--are built around the significant relationships in their lives (Gilligan, 1982; Kaplan, 1984; Bernay, 1986). As clinicians, we must be mindful of derangements of our own desire, shaped by our biological mothers and fathers, our psychoanalytic fathers, Freud, and his early followers, and sometimes our own analysts. We must attend to the voice of our own ambition and trace its flourishes and derailments, understanding female ambition from a woman's point of view in order to assist our patients in reconstructing deformative narratives into healthier and more enabling ones. We need to take responsibility for our own ambition, stilling the disabling voices of the characters in our own intrapsychic dramas, maintaining consciousness of the deformative voices in the culture at large, and attunement to voices of support for ambition integrated with nurturance and aggression. |
8042708 | Molecular evolutionary processes and conflicting gene trees: the hominoid case. | Molecular evolutionary processes modify DNA over time, creating both newly derived substitutions shared by related descendant lineages (phylogenetic signal) and "false" similarities which confound phylogenetic reconstruction (homoplasy). However, some types of DNA regions, for example those containing tandem duplicate repeats, are preferentially subject to homoplasy-inducing processes such as sporadically occurring concerted evolution and DNA insertion/deletion. This added level of homoplasic "noise" can make DNA regions with repeats less reliable in phylogenetic reconstruction than those without repeats. Most molecular datasets which distinguish among African hominoids support a human-chimpanzee clade; the most notable exception is from the involucrin gene. However, phylogenetic resolution supporting a chimpanzee-gorilla clade is based entirely on involucrin DNA repeat regions. This is problematic because (1) involucrin repeats are difficult to align, and published alignments are contradictory; (2) involucrin repeats are subject to DNA insertion/deletion; (3) gorillas are polymorphic in that some do not have repeats reported to be synapomorphies linking chimpanzees and gorillas. Gene tree/species tree conflicts can occur due to the sorting of ancestrally polymorphic alleles during speciation. Because hominoid females transfer between groups, mitochondrial and nuclear gene flow occur to the same extent, and the probability of conflict between mitochondrial and nuclear gene trees is theoretically low. When hominoid intraspecific mitochondrial variability is taken into account [based on cytochrome oxidase subunit II (COII) gene sequences], humans and chimpanzees are most closely related, showing the same relative degree of separation from gorillas as when single individuals representing species are analyzed. Conflicting molecular phylogenies can be explained in terms of molecular evolutionary processes and sorting of ancient polymorphisms. This perspective can enhance our understanding of hominoid molecular phylogenies. |
8042707 | Levels of the genealogical hierarchy and the problem of hominoid phylogeny. | Molecular data are widely used to reconstruct phylogenetic relationships among species, and these phylogenies are often used as the basis for inferences about the history of evolutionary change in other nonmolecular characters. This approach is an appropriate and powerful one in many circumstances. But when several lineages diverge over a relatively short period of time, the assumption that a molecular (gene) tree will always be a valid basis for such inferences may not hold. Empirical evidence from humans, nonhuman primates, and other mammals indicates that the relationships among molecular divergence, morphological differentiation, and the origin of reproductive isolation between diverging lineages are complex. The simple dichotomously branching trees that result from molecular systematic studies of Homo, Gorilla, and Pan may be a misleading basis for reconstructions of evolutionary change in nonmolecular characters. |
8042706 | Blood will tell (won't it?): a century of molecular discourse in anthropological systematics. | Being derived from the hereditary material, molecular genetic data are often assumed to be a source of sounder inferences about evolution than data from other kinds of investigations. This, however, tends to be taken in the absence of a clear knowledge of the evolutionary processes at work, the technical shortcomings, and the manner of deriving the specific conclusions. The history of biological anthropology shows that, from the beginning of the 20th century, grossly naive conclusions have been promoted simply on the basis that they are derived from genetics, without having been fully thought-out. A balanced consideration of the shortcomings as well as the advantages of genetic data are necessary for its proper integration into the advantages of genetic data are necessary for its proper integration into the field. When molecular and morphological data disagree, both must be re-examined carefully, for genetics has been used irresponsibly as a form of scientific validation, both in American society and in American science. Contemporary data bearing on the molecular relationships of the apes are note-worthy for their diversity in quality, and need to be evaluated in the light of molecular and microevolutionary theory. |
8042705 | Generic level relationships of the Papionini (Cercopithecoidea). | Phylogenetic hypotheses for the Old World monkey tribe Papionini based on molecular data are incongruent with those inferred from previous morphological analyses. Morphologists have often inferred a close relationship between Mandrillus and Papio based on their overall similarity. Theropithecus has been variously proposed to be either quite distantly related to these two genera, their sister taxon, or anywhere in between. Molecular and chromosomal analyses on the other hand unambiguously group Theropithecus and Papio together to the exclusion of Mandrillus. Additionally, molecular and chromosomal analyses reveal that mangabeys (Cerocebus) are paraphyletic. Morphologists have acknowledged this possibility resurrecting the genus name Lophocebus for one group of mangabeys. A review and reanalysis of the morphological characters put forth by various researchers find little to contradict the consensus phylogeny derived from analysis of chromosomal banding, nuclear RNA restriction mapping, alpha and beta hemoglobin sequences, albumin and transferrin microcomplement fixation, DNA-DNA hybridization, repetitive DNA patterns, immunodiffusion, hemoglobin and adenylate kinase isozymes, and mitochondrial cytochrome oxidase subunit II DNA sequences. |
8042704 | Molecular evidence on primate phylogeny from DNA sequences. | Evidence from DNA sequences on the phylogenetic systematics of primates is congruent with the evidence from morphology in grouping Cercopithecoidea (Old World monkeys) and Hominoidea (apes and humans) into Catarrhini, Catarrhini and Platyrrhini (ceboids or New World monkeys) into Anthropoidea, Lemuriformes and Lorisiformes into Strepsirhini, and Anthropoidea, Tarsioidea, and Strepsirhini into Primates. With regard to the problematic relationships of Tarsioidea, DNA sequences group it with Anthropoidea into Haplorhini. In addition, the DNA evidence favors retaining Cheirogaleidae within Lemuriformes in contrast to some morphological studies that favor placing Cheirogaleids in Lorisiformes. While parsimony analysis of the present DNA sequence data provides only modest support for Haplorhini as a monophyletic taxon, it provides very strong support for Hominoidea, Catarrhini, Anthropoidea, and Strepsirhini as monophyletic taxa. The parsimony DNA evidence also rejects the hypothesis that megabats are the sister group of either Primates or Dermoptera (flying lemur) or a Primate-Dermoptera clade and instead strongly supports the monophyly of Chiroptera, with megabats grouping with microbats at considerable distance from Primates. In contrast to the confused morphological picture of sister group relationships within Hominoidea, orthologous noncoding DNA sequences (spanning alignments involving as many as 20,000 base positions) now provide by the parsimony criterion highly significant evidence for the sister group relationships defined by a cladistic classification that groups the lineages to all extant hominoids into family Hominidae, divides this ape family into subfamilies Hylobatinae (gibbons) and Homininae, divides Homininae into tribes Pongini (orangutans) and Hominini, and divides Hominini into subtribes Gorillina (gorillas) and Hominina (humans and chimpanzees). A likelihood analysis of the largest body of these noncoding orthologues and counts of putative synapomorphies using the full range of sequence data from mitochondrial and nuclear genomes also find that humans and chimpanzees share the longest common ancestry. |
8042703 | Relative position of the Cheirogaleidae in strepsirhine phylogeny: a comparison of morphological and molecular methods and results. | An examination of previous morphological and molecular studies of strepsirhine systematics suggests a conflict between the two types of data. Cladistic analyses of morphological data have indicated that the Malagasy primate family Cheirogaleidae is the sister taxon of the Afro-Asian lorisiforms and that together, cheirogaleids and lorisiforms comprise a monophyletic clade that excludes the Malagasy lemuriforms. Molecular studies, on the other hand, have consistently found that cheirogaleids and lemuriforms together are monophyletic to the exclusion of lorisiforms. Both types of studies, however, have suffered from methodological weaknesses: the morphological studies looked at too few characters and the molecular studies looked at too few taxa. This study examines a large and diverse morphological data set as well as molecular data from a comprehensive sample of strepsirhine taxa. The data sets are considered independently and jointly. When they are analyzed independently, the morphological data give weak support, and the molecular data strong support, to the hypothesis of Malagasy primate monophyly. When the two data sets are combined in a single analysis, the results are decisive. The "total evidence" approach yields compelling support to the hypothesis that cheirogaleids and remaining Malagasy lemuriforms comprise a monophyletic assemblage that excludes lorisiforms. |
8042702 | Cladistic analysis of molecular and morphological data. | Considerable progress has been made recently in phylogenetic reconstruction in a number of groups of organisms. This progress coincides with two major advances in systematics: new sources have been found for potentially informative characters (i.e., molecular data) and (more importantly) new approaches have been developed for extracting historical information from old or new characters (i.e., Hennigian phylogenetic systematics or cladistics). The basic assumptions of cladistics (the existence and splitting of lineages marked by discrete, heritable, and independent characters, transformation of which occurs at a rate slower than divergence of lineages) are discussed and defended. Molecular characters are potentially greater in quantity than (and usually independent of) more traditional morphological characters, yet their great simplicity (i.e., fewer potential character states; problems with determining homology), and difficulty of sufficient sampling (particularly from fossils) can lead to special difficulties. Expectations of the phylogenetic behavior of different types of data are investigated from a theoretical standpoint, based primarily on variation in the central parameter lambda (branch length in terms of expected number of character changes per segment of a tree), which also leads to possibilities for character and character state weighting. Also considered are prospects for representing diverse yet clearly monophyletic clades in larger-scale cladistic analyses, e.g., the exemplar method vs. "compartmentalization" (a new approach involving substituting an inferred "archetype" for a large clade accepted as monophyletic based on previous analyses). It is concluded that parsimony is to be preferred for synthetic, "total evidence" analyses because it appears to be a robust method, is applicable to all types of data, and has an explicit and interpretable evolutionary basis. |
8042701 | Flies and congruence. | Competing phylogenetic hypotheses have become the rule in modern systematics. While the problem of incongruence between character sets has become extremely acute due to the generation of molecular data, it is by no means specific to molecular and morphological comparisons. The role of the modern systematist is to interpret incongruence between character sets and to come to some conclusion regarding a phylogenetic hypothesis of the organisms in question. Two aspects of congruence analysis are examined using the Drosophilidae as an example. The first includes the quantification of congruence and the types of phylogenetic inference that can be made from such analyses. The second aspect concerns an examination of character evolution in order to identify characters and taxa that might be contributing to incongruence in phylogenetic analysis. |
8042700 | A critique of homology as a morphological concept. | Two sequences of nucleotides are homologous if they are descended through a chain of replication from a common precursor molecule. Since organs are not copies or transcriptions of organs, the concept of morphological homology has no such simple and unambiguous definition. The theoretical vagueness of morphological homology is reflected in its many and inconsistent criteria of identification. Structures may be conventionally deemed homologous even though they are radically dissimilar in form, relationships, or function, or develop via dissimilar ontogenetic processes, or originate from nonhomologous embryological precursors. Hypothesis of homology are conventionally rejected when they are contradicted by known patterns of phylogenetic relationships, even if the structures in question are minutely similar in their form, function, and development. The dependence of interspecific homology on phylogeny is often expressed by saying that two structures are homologous if they are inherited from corresponding structures in a common ancestor. However, this is a circular definition (what counts as a "corresponding" structure is itself a question of homology), and it falsely assumes that structures can be inherited. At bottom, homology is an essentialist concept; two things are homologous only if they are in some essential sense the "same" thing and properly called by the same word. The concept can be made intelligible in an evolutionary context only by giving it a cladistic interpretation that makes homology judgments dependent on the outcome of a phylogenetic analysis. It follows that such judgments cannot play a role in evaluating conflicting phylogenetic hypotheses. |
8042697 | Heterochrony and sexual dimorphism in the pigtailed macaque (Macaca nemestrina). | Somatic growth is not a simple linear process with a constant rate of growth. The most successful attempts to quantify growth as a function of age or size have employed nonlinear techniques. Sexual dimorphism of primate growth, weight vs. age, was examined using nonlinear models with Sirianni and Swindler's ([1985] Growth and Development of the Pigtailed Macaque, Boca Raton, FL: CRC Press) growth data on the pigtailed macaque (Macaca nemestrina). The best fit of several exponential growth models was the Gompertz curve: Weight = a*e-b*e-K*age Different multiple phase models were also fit, where each phase represents a distinct exponential component. The two-phase models proved to be the best (R2 = .0.84 for females, 0.91 for males), suggesting that there are two growth spurts, one in infancy and one at puberty. The timing of the beginning and end of the first spurt is the same in males and females, but the rate, and value of the asymptote for this phase, is greater in males. The timing of the second spurt is earlier, and the rate of growth for this spurt is smaller in females than males. The sexual dimorphism in these species is not a simple rate change, but a complex interaction of timing and rate over the entire period of growth. It would be impossible to separate these entities with a linear, polynomial, or single-phase model of the data. While these data and results complement much of the existing work on adult dimorphism, they also emphasize the vital role that ontogenetic data have in elucidating the underlying evolutionary mechanisms that generate sexual dimorphism. |
8042696 | Terrestrial adaptations in the postcranial skeletons of guenons. | Arboreal and semiterrestrial guenons show similar osteological features of the limbs across a wide range of species, environments, and geography, while the more terrestrially committed guenons exhibit greater morphological divergence. An ecomorphological comparison of two sympatric guenons living in Kibale Forest, Uganda, reveals an array of anatomical adaptations for terrestriality in the limbs of Cercopithecus lhoesti similar to those found in Erythrocebus patas. In contrast, Cercopithecus aethiops, although also frequent users of the terrestrial environment, generally exhibit fewer morphological adaptations characteristic of a terrestrial lifestyle. It appears that significant morphological modification for terrestriality has occurred twice within the diverse radiation of living guenons with C. aethiops perhaps representing a third group in the making. |
8042695 | New early eocene anaptomorphine primate (Omomyidae) from the Washakie Basin, Wyoming, with comments on the phylogeny and paleobiology of anaptomorphines. | Recent paleontological collecting in the Washakie Basin, southcentral Wyoming, has resulted in the recovery of over 100 specimens of omomyid primates from the lower Eocene Wasatch Formation. Much of what is known about anaptomorphine omomyids is based upon work in the Bighorn and Wind River Basins of Wyoming. This new sample documents greater taxonomic diversity of omomyids during the early Eocene and contributes to our understanding of the phylogeny and adaptations of some of these earliest North American primates. A new middle Wasatchian (Lysitean) anaptomorphine, Anemorhysis savagei, n. sp., is structurally intermediate between Teilhardina americana and other species of Anemorhysis and may be a sister group of other Anemorhysis and Trogolemur. Body size estimates for Anemorhysis, Tetonoides, Trogolemur, and Teilhardina americana indicate that these animals were extremely small, probably less than 50 grams. Analysis of relative shearing potential of lower molars of these taxa indicates that some were primarily insectivorous, some primarily frugivorous, and some may have been more mixed feeders. Anaptomorphines did not develop the extremes of molar specialization for frugivory or insectivory seen in extant prosimians. Incisor enlargement does not appear to be associated with specialization in either fruits or insects but may have been an adaptation for specialized grooming or food manipulation. |
8042694 | Longitudinal analysis of adolescent growth in height, fatness, and fat patterning in rural South African black children. | Adolescent growth in height, fatness, and fat patterning was investigated in a sample of 79 rural South African black children studied longitudinally from 6-18 years. Data were analyzed relative to peak height velocity (PHV) to identify the phenomenon of "compensatory" growth in height during adolescence and to describe changes in fatness and fat patterning. Compensatory growth following PHV was clearly observed relative to NHANES data for African-Americans in that Z-scores for height at the start of the adolescent growth spurt were greater than those at the end of the spurt. Statistically significant differences in fatness and centralization between males and females did not occur until about 2 years after PHV was attained. Centralization of fat occurred in both sexes but more so in males. The lack of centralization in females was due to relatively greater triceps skinfold velocities. The rapid gain in post-PHV fatness in females may represent a physiological adaptation to an energetically sub-optimal environment, buffering the energetic costs of reproduction. |
8042693 | Enamel hypoplasia and age at weaning in 19th-century Florence, Italy. | A sample representing a population of the Florence district of middle 19th century was studied to determine the age of occurrence of enamel hypoplasias. The age interval most affected was that between 1.5 and 3.5 years. Historical sources on weaning habits of 19th-century Italian populations indicate a weaning period between 12 and 18 months. This is in agreement with the data on enamel defects, showing that children of post-weaning age are more subject to stress. Wide "grooves", with prolonged duration, are concentrated between 2 and 2.5 years, whereas "lines" occur primarily between 2.5 and 3 years. We suggest that this distribution could reflect the gradual introduction of dietary supplements until weaning is complete. |
8042692 | Developmental, diachronic, and demographic analysis of cribra orbitalia in the medieval Christian populations of Kulubnarti. | Previous analysis of cribra orbitalia in the medieval populations of Kulubnarti focused only on the presence or absence of the lesion relative to age, sex, and cultural period. Demographic consideration of the lesion was limited to a gross comparison of lesion frequencies and probabilities of dying by age group. The scope of the earlier work has been expanded in the present research to include the consideration of cribra orbitalia from a developmental, demographic, and diachronic perspective. The sample consisted of the same 334 crania analyzed by Van Gerven et al. ([1981] J. Hum. Evol. 10:395-408). All skulls showing the lesion were dichotomized as active or healing, and separate life tables were constructed for those with lesions and those without. The results demonstrate that active lesions are confined entirely to infancy and childhood with formation beginning as early as six months and ending by the twelfth year. This childhood pattern is consistent with the iron deficiency anemia hypothesis proposed by Carlson et al. ([1974] J. Hum. Evol. 3:405-410). Among young adults (16-40), healing lesions occur more frequently in males than females. In the older age categories, however, females exhibit a higher frequency of partially healed lesions than males. A life table comparison of those with and those without cribra orbitalia reveals a dramatic reduction in mean life expectancy for those with the lesion across the formative childhood years (birth-16). This reduction peaks at age 5 where 78% of the children exhibit lesions and where they, as a group, have a mean life expectancy 15.5 years below those without the lesion. |
8042689 | Enhancing occupational performance through an understanding of perceived self-efficacy. | The construct of perceived self-efficacy, proposed to explain the discrepancy between skill and actual performance, has received widespread attention in the psychological and medical literature. This paper describes the construct in detail, including the difference between self-esteem and perceived self-efficacy, and proposes a goodness of fit with occupational therapy practice. It is postulated that attention to the assessment and monitoring of perceived self-efficacy, along with the use of activities that closely approximate the actual activities to be performed in the community, will result in improved occupational performance and thus, better occupational therapy outcomes. Occupational therapists are challenged to identify and incorporate this construct into their day-to-day clinical programs to enhance treatment outcomes. |
8042688 | COMPETE: a model for vocational evaluation, training, employment, and community for integration for persons with cognitive impairments. | This paper describes a job skills training program for young adults with cognitive impairments called COMPETE, an acronym for Computer Preparation: Evaluation, Training, and Employment. Participants in COMPETE trained in use of information-age machines, (e.g., computers, fax machines). The 3-year demonstration project resulted in successful placement of 17 of 27 persons who were unemployed before entering the program. |
8042687 | Interdisciplinary team approach in the rehabilitation of hip and knee arthroplasties. | Use of an interdisciplinary case management team approach in the treatment of patients with hip or knee arthroplasty has resulted in a decrease in length of stay and achievement of functional outcomes at the authors' center. Case management was used to standardize patient care and to measure each patient's progress toward independence against established criteria of treatment outcomes. Outcomes established for physical therapy were ambulation distance, performance of a home exercise program, stair climbing, amount of active knee flexion (for knee arthroplasties), and incorporation of hip precautions. Outcomes for occupational therapy were bed mobility, chair transfers, toilet transfers, and activities of daily living with emphasis on lower extremity dressing. The case management team consists of an occupational therapist, an occupational therapy assistant, a physical therapist, and two nurses. The specific role of the occupational therapy personnel in this team approach is to maximize, by discharge, a patient's functional level of independence in activities of daily living. Data from a 6-month period indicated that occupational therapy goals were achieved for 79% of the 33 knee arthroplasty patients and 73% of the 37 hip arthroplasty patients. |
8042686 | A meal preparation treatment protocol for adults with brain injury. | Adults with acquired brain injury often demonstrate dysfunction in meal preparation due to deficits in component cognitive-perceptual skills. Although occupational therapy for these clients routinely includes meal preparation training, there are no protocols in the occupational therapy literature to help structure that activity to address clients' cognitive-perceptual deficits. This paper describes a meal preparation treatment protocol based on cognitive-perceptual information processing theory that has been pilot tested in a treatment outcome study with adult men with traumatic or anoxic acquired brain injury. In that study, the group of 23 subjects treated with this meal preparation protocol showed significant improvement in their meal preparation skill, as measured by the Rabideau Kitchen Evaluation-Revised (RKE-R), a test of meal preparation skill, and in their cognitive-perceptual skill, as measured by the WAIS-R Block Design Test. The treatment protocol includes descriptions of the structure, grading, and cuing methods for light meal preparation activities. |
8042685 | The neurobiology of learning: implications for treatment of adults with brain injury. | The effectiveness of occupational therapy interventions for adults with brain injury is largely dependent on how well clients are able to learn the new strategies, techniques, and information therapists are trying to teach them. Neuroscience research in the past two decades has provided some intriguing hints about the neurological processes that may underlie that learning. Understanding this research might stimulate new occupational therapy ideas about more effective ways to facilitate recovery and learning in adults with brain injury. This review presents an overview of the physical, biochemical, and electrical changes in nerve cells that have been found to accompany learning in adults with and without brain injury. Recommendations for treatment derived from the review include teaching to clients' levels of learning and information-processing strengths. |
8042684 | Occupational cumulative trauma disorders of the upper extremity. | The umbrella term cumulative trauma disorders (CTDs) (also known as repetitive strain injuries, overuse syndromes, and repetitive motion disorders) covers a number of similar conditions arising from overuse of the joints or soft tissues of the upper extremity. Occupational CTDs have become a common problem in the workplace. These disorders are costly to the employer, the worker, and society in terms of time lost from work and resulting disability. Within the past decade, occupational therapists and physical therapists specializing in rehabilitation of work-related musculoskeletal injuries have seen an increase in the incidence of CTDs of the upper extremity in the workplace. Therapists are called upon not just to treat these injured workers, but also to help them regain a functional level for work reentry and to educate them to prevent reinjury. This article reviews the literature on the epidemiology, etiology, pathophysiology, and management of upper-extremity occupational CTDs. Because the ultimate goal of the workplace is to maintain the health and safety of the employee, an educational approach to hand, wrist, elbow, and shoulder use is essential to prevent, decrease, or eliminate the risk of occupational CTDs of the upper extremity. |
8042683 | Effects of continuous passive motion on the edematous hands of two persons with flaccid hemiplegia. | This study evaluated the effect of the use of a continuous passive motion device for the edematous hands of two persons with flaccid hemiplegia. The subjects were both 1 month post-cerebrovascular accident with left-sided hemiplegia. Each subject's routine therapy program was maintained throughout this ABA design study. During the first week, baseline data were gathered, during the second week the intervention was provided (2 hr of continuous passive motion device use), and during the third week data were gathered with treatment withdrawn. Edema was measured with a hand volumeter and finger circumference. The continuous passive motion device had an effect in reducing edema in the hands of the two subjects. The continuous passive motion device is a readily available tool that could enhance the treatment of edematous hands of persons with flaccid hemiplegia by offering a contribution to already established treatment protocols. Further research is needed, however, to establish guidelines for use. |
8042682 | Ethnographic analysis: a study of classroom environments. | Occupational therapists assess and adapt an environment to enhance clients' abilities to function. Therapists working in schools may assess several classroom environments in a week. Identifying relevant information in an efficient manner is essential yet presents a challenge for school therapists. In this study, ethnographic research methodology was used to analyze the plethora of data gained from observations in eight classrooms. Three major categories were identified to structure observations: activities, people, and communication. These categories were used to compile a Classroom Observation Guide that gives therapists relevant questions to ask in each category. Using the Classroom Observation Guide, occupational therapists can recommend classroom activities that suit a particular teacher's style. For example, working with a teacher who prefers structural activities with clear time and space boundaries for one specific purpose, a therapist might suggest organized sensorimotor games with a distinct purpose to be carried out for a given time period. |
8042681 | Prediction of preschool sensory and motor performance by 18-month neurologic scores among children born prematurely. | Premature birth places a child at risk for a number of academic and behavioral deficits. The challenge currently facing interventionists is to identify at an early age those preterm children who will develop such deficits. Identified children can then be targeted for intervention to forestall deficits at school age. This study examined the use of a neurologic assessment, administered at 18 months of age, to identify children who will have difficulties at preschool age. Premature children identified as neurologically normal or neurologically suspicious at the age of 18 months were tested with the Miller Assessment for Preschoolers. Although there was some variability in performance, as a group the children classified as neurologically suspicious at 18 months continued to fall into a risk category at 4 years of age. Because such categorization may predict inadequate performance during the school-age years, monitoring of the child's development is warranted. |
8042676 | Protelomeric sequences are deleted in cases of short arm inverted duplication of chromosome 8. | We present a patient with a de novo inverted duplication of the short arm of chromosome 8. Molecular analysis confirmed the cytogenetic suspicion of a simultaneous deletion of the tip of the short arm and indicated the maternal origin of the abnormality. This deletion made no detectable contribution to the phenotype of the patient which was comparable to that of previous cases of 8p duplication. Similar investigations of inverted duplications involving other chromosomes may reveal unexpected deletions with significant phenotypic consequences. |
8042675 | New variant of chromosome 11. | An additional C-positive band in the centromeric region (p11) was observed in a man. By GTG- and RBA-techniques it was positively stained but by QFQ-technique the staining intensity was negative. Although he was identified through fetal loss in his wife, it apparently represents a familial variant whose clinical significance is unknown. |
8042674 | Child with Sotos phenotype and a 5:15 translocation. | We report on a 4-year-old girl with Sotos phenotype and a de novo balanced translocation between the long arms of chromosome 5 and chromosome 15 [46,XX,t(5,15)(q35;q22)]. We suggest a relationship between genetic material at 5q35 or 15q22 and the expression of an autosomal dominant gene. |
8042673 | Nevoid basal cell carcinoma syndrome: review of 118 affected individuals. | One hundred eighteen cases of nevoid basal cell carcinoma syndrome (NBCCS, Gorlin's syndrome or basal cell nevus syndrome) are presented in this study. In aiming to ascertain all the affected families in Australia, we have examined the largest series to date. Relative frequencies of associated complications are presented and compared with those of the recent English survey by Evans et al. [J Med Genet 30:460-464, 1993]. The frequencies of most manifestations are similar. However, one major difference is that the multiple basal cell carcinomas are manifest from an earlier age in the Australian population, which probably reflects greater exposure to ultraviolet radiation. Of the 64 families ascertained, 37 represented simplex cases, and, accordingly, the apparent new mutation rate is surprisingly high (14-81%) given the lack of impact of NBCCS on reproductive capabilities. There is some evidence to suggest that this may be attributable to anticipation. |
8042672 | Clinical findings in two African-American families with the nevoid basal cell carcinoma syndrome (NBCC). | The nevoid basal cell carcinoma syndrome (NBCC) is an autosomal dominant multisystem disorder with variable expressivity. We present the clinical findings on 11 African-American NBCC cases from 2 families and a review of the literature of NBCC in African-Americans. The 2 new families, as well as those previously reported, suggest minimal expression of the basal cell carcinomas and full expression of the other components of the syndrome. The 3 most common findings in the 11 cases were jaw cysts, palmar and/or plantar pits, and calcification of the falx cerebri. Only 44% (4/11) of these cases had one or more confirmed basal cell carcinomas. This frequency is substantially less than that observed in whites (90% with basal cell carcinomas). The relative lack of these skin tumors in African-Americans partly reflects ultraviolet radiation protection resulting from increased skin pigmentation. Future research should help identify the specific mutation(s) in blacks as well as other modifying genes and environmental exposures that may contribute to the varied manifestations of the syndrome. |
8042671 | Leigh syndrome and hypertrophic cardiomyopathy in an infant with a mitochondrial DNA point mutation (T8993G). | Mutation of mitochondrial (mt) DNA at nucleotide (nt) 8993 has been reported to cause neurogenic weakness, ataxia, retinitis pigmentosa (NARP), or Leigh syndrome (LS). We report a family in whom the mutation was expressed clinically as LS and hypertrophic cardiomyopathy (CMP) in a boy who presented with a history of developmental delay and hypotonia, and who had recurrent lactic acidosis. The mother's first pregnancy resulted in the birth of a stillborn female; an apparently healthy older brother had died suddenly (SIDS) at age 2 months. MtDNA analysis identified the presence of the T8993G point mutation, which was found to be heteroplasmic in the patient's skeletal muscle (90%) and fibroblasts (90%). The identical mutation was present in leukocytes (38%) isolated from the mother, but not from the father or maternal grandmother. Our findings expand the clinical phenotype of the nt 8993 mtDNA mutation to include hypertrophic cardiomyopathy and confirm its cause of LS. |
8042670 | Barth syndrome: clinical observations and genetic linkage studies. | Barth syndrome is an X-linked recessive condition characterized by skeletal myopathy, cardiomyopathy, proportionate short stature, and recurrent neutropenia, but with normal cognitive function. Some, but not all patients, exhibit carnitine deficiency and/or the presence of 3-methylglutaconic and ethylhydracylic acids in urine. Recently the mutation causing Barth syndrome was localised to the Xq28 region by linkage analysis. We report 6 cases of Barth syndrome from 4 families and highlight the fact that neuromuscular and cardiovascular symptoms and the severity of infections tend to improve with age, while short stature persists. Also previously unreported was myopathic facies and nasal quality to speech in our cases. The urinary organic acid abnormalities and plasma carnitine deficiency were inconsistent findings. We propose that they may be epiphenomena rather than indicators of the primary metabolic defect, and that the primary defect or defects in this disorder may lie in the mitochondrial electron transport chain. |
8042669 | Novel karyotype in the Ullrich-Turner syndrome--45,X/46,X,r(X)/46,X, dic(X)--investigated with fluorescence in situ hybridization. | A 10-year-old girl with Ullrich-Turner syndrome was found to have the novel karyotype 45,X/46,X,r(X)(p11q11)/46,X,dic(X)(p11). Fluorescence in situ hybridization (FISH) with the alpha satellite X centromere probe established the origin of the small ring chromosome. Scanning a large number of cells by interphase FISH showed that the dicentric (X) was the least prevalent cell line. The common breakpoint of Xp11 suggests a sequence of errors as the mechanism whereby these 3 distinct cell lines have arisen. |
8042668 | Scalp-ear-nipple syndrome: additional manifestations. | Scalp-ear-nipple (SEN) syndrome is a rare, autosomal dominant condition that causes aplasia cutis congenita of the scalp, alteration of the shape of the external ear, and hypoplasia of the nipple. Women in a new family, the fifth to be described, had virtually complete aplasia of the breast and a small skin dimple without any pigmentation instead of a normal nipple, although other affected women had normal breast and nipple development. Dental changes included widely spaced or missing secondary teeth; the ears were cupped or folded and stood out from the head, axillary apocrine secretion and axillary hair growth were reduced; and finger nails were brittle. There was no generalized abnormality of sweating. Some patients had partial syndactyly of the 3rd and 4th fingers, and complete cutaneous syndactyly of the 2nd and 3rd toes. and 3rd toes. |
8042667 | Informed consent and Huntington disease: a model for communication. | American and Canadian professional accreditation standards for medical genetics, and genetic counseling require certain abilities with regard to "communication." What remains unclear is how such standards are to be interpreted in terms of appropriate clinical protocols, objectives, and values. These issues have significant medical and legal implications, particularly with regard to medical malpractice. From the perspective of genetic testing for Huntington disease, this paper identifies those clinical objectives and practices which may be described as constituting the appropriate standard of care for "communication," and informed consent. |
8042666 | Psychological aspects of genetic counseling: a legal perspective. | Carrier and presymptomatic genetic testing information can have profound psychological consequences for a patient and the family. American and Canadian professional accreditation standards for clinical genetics state that the health care provider must be prepared to provide psychological support. Through a survey of human/medical genetics journals and texts, this article identifies those protocols that constitute an appropriate standard of care, and examines the legal implications, particularly with regard to the law of medical malpractice. |
8042665 | Emery-Dreifuss syndrome: genetic and clinical varieties. | Two familial and 2 sporadic cases of Emery-Dreifuss syndrome are reported. One family presented a rare autosomal dominant variant of Emery-Dreifuss muscular dystrophy, another with X-linked recessive inheritance showed unusual intrafamilial variability. One of sporadic cases closely resembled rigid spine syndrome, the other was clinically intermediate between Emery-Dreifuss muscular dystrophy and rigid spine syndrome, showing that they are not distinct disorders. |
8042664 | Oculocutaneous albinism, immunodeficiency, hematological disorders, and minor anomalies: a new autosomal recessive syndrome? | We report on 2 related children, a boy and a girl, from a large Turkish clan. Their parents are both first cousins and have several common ancestors. Both children have tyrosinase-positive oculocutaneous albinism, recurrent bacterial infections, granulocytopenia, intermittent thrombopenia, and microcephaly, a protruding midface, rough and projecting hair, and mild mental retardation. Chromosomes are normal. Metabolic disorders were excluded. None of 14 well-known types of albinism, including Hermansky-Pudlak syndrome and Chediak-Higashi syndrome, nor any other genetic syndrome, characterizes our patients sufficiently. Thus, this combination of symptoms is considered a new autosomal recessive syndrome. |
8042663 | Familial crossed polysyndactyly. | We have observed a distinct form of "crossed" polysyndactyly in 6 generations of a family with 5 affected persons, all males. The polydactyly is postaxial in the hands and preaxial in the feet. Syndactyly in the hands is observed in some relatives, while syndactyly in the feet is present bilaterally in all affected relatives. This seems to be an autosomal dominant trait with male to male transmission over 3 generations by examination and an additional 3 generations by history. This form of polysyndactyly could not be readily categorized by the existing classification by Temtamy and McKusick [1978: BD OAS XIV 6:363-392]. We review and expand the present classification of polydactyly and syndactyly syndromes. |
8042662 | Blastocystis hominis infection and intestinal injury. | Blastocystis hominis is an enteric protozoan associated with clinical illness. To determine the prevalence of intestinal injury in patients with B. hominis infection, the authors prospectively evaluated 18 patients with B. hominis infection by endoscopy and a test of intestinal permeability. Seventeen patients had gastrointestinal symptoms. Colonic mucosa appeared normal by lower endoscopy in 12 of 13 patients, and was friable slightly in 1. Duodenal mucosa was normal by upper endoscopy in nine patients. Pathologic examination of mucosal biopsy specimens did not demonstrate evidence of mucosal invasion. 51Cr-edetic acid (51Cr-EDTA) was given to the 18 patients with stools positive for B. hominis and to 32 healthy control subjects. Approximately 100 uCi of 51Cr-EDTA was given orally after an overnight fast, and urine was collected for the following 24 hours. Mean 24-hour urinary excretion of 51Cr-EDTA, calculated as a percent of the administered dose, was 1.31% (0.34-2.76%) in patients with B. hominis infection and 1.99% (0.59-3.48%) in the control subjects. The intestinal permeability to 51Cr-EDTA in blastocystis-infected individuals was not increased, but was decreased significantly compared with healthy subjects (p < 0.005). Therefore, in a group of symptomatic patients with B. hominis infection, endoscopy typically did not show evidence of significant intestinal inflammation, and results of intestinal permeability testing with 51Cr-EDTA did not suggest impaired barrier function of the intestinal mucosa. The clinical literature on B. hominis infection and intestinal injury is reviewed. |
8042661 | Ultraviolet B light-induced suppression of contact sensitivity is not abolished by cyclophosphamide. | Dose responses for ultraviolet B light (UVB)-induced suppression of contact sensitivity were studied in mice, with and without cyclophosphamide (Cy) pretreatment, to investigate the role of Cy-sensitive suppression. Mice were irradiated on the back, sensitized on the abdomen, and challenged on the ears. Half of the mice were injected intraperitoneally with 200 mg/kg of Cy 3 days before being sensitized. Ultraviolet B light radiation reduced the ear swelling reactions in a linear relation to the log10 of the dose. Fifty percent suppression was shown by the computer-generated regression line at approximately 4.8 kJ/m2 of UVB radiation, with complete suppression at approximately 65 kJ/m2. In mice pretreated with Cy, ear swelling was increased, showing inhibition of a Cy-sensitive suppressive component of the contact sensitivity reaction. This Cy-sensitive component also was seen in mice treated with UVB, but with higher doses of UVB, there still was a UVB-dose-dependent decline in ear swelling in Cy pretreated mice, and there was complete suppression of reactions with the highest doses of UVB in the Cy-treated mice. Therefore, there is a second mechanism, not sensitive to Cy, that causes UVB-induced immune suppression. |
8042660 | Child injury control: surveillance and research questions. | Injury is the leading cause of death for every year but the first of a child's life and, additionally, generates enormous costs in health care, disability, pain, and suffering. Research and programmatic efforts for injury control continue to have low priority relative to their modest costs and potential to reduce health-care and other costs to society. Modest improvements in data systems would lead to more effective targeting of injury control efforts that are useful in preventing injuries. Analytic studies of changeable risk factors and effectiveness of interventions would widen the range of available interventions and their cost-effectiveness. |
8042659 | Passive protection of mice against lethal Francisella tularensis (live tularemia vaccine strain) infection by the sera of human recipients of the live tularemia vaccine. | The relative role that humoral immunity plays in protection against infection with the intracellular bacterium, Francisella tularensis, remains controversial. Cellular immunity is thought to play the major and perhaps only role. The authors, in this article, investigate the immunologic and protective properties of immune serum collected from human recipients of the live tularemia vaccine (LVS). Sera of recipients of the vaccine demonstrated reactivity with the vaccine strain by enzyme-linked immunosorbent assay and Western blot analysis. This reactivity appeared to be directed primarily against the lipopolysaccharide of LVS and demonstrated complete cross-reactivity with fully virulent F. tularensis (Schu4). Pooled immune sera protected mice fully against a 10,000 LD50 challenge with the LVS strain relative to non-immune sera. The protection was abrogated by dilution or preadsorption with the LVS strain but not by preadsorption with Escherichia coli, which suggests specificity of protection. The authors conclude that antibodies to the LVS strain of F. tularensis are generated by live vaccination in humans and play a significant role in protection of mice against lethal challenge with the same organism. These antibodies crossreact completely with fully virulent F. tularensis, but whether they play a role in protection against fully virulent human tularemia strains requires further experimentation. |
8042658 | Reading deficiencies in older patients. | To participate effectively in their health care, older patients often are expected to read a wide variety of materials, including written instructions, brochures, and consent forms. This study quantitates the reading ability of older patients and compares it to that of younger patients. Two hundred seventy-two patients 30 and older were selected from five outpatient clinics at a public teaching hospital and tested for objective reading ability using the Peabody Individual Achievement Test--Revised. The 76 patients 60 and older read significantly worse (grade level 2.9) than the 196 patients younger than 60 (grade level 5.8) (P < 0.0001). Older patients also completed significantly fewer years of school than younger patients (7.3 years versus 10.6 years). Analysis of variance for age categories 30-44, 45-59, 60-74, and 75 and older confirmed declining reading ability and educational status with advancing age. Multiple regression analysis helped show that an equation could be derived to predict reading ability from age, educational status, race, and sex, but the coefficient of determination was so low (r2 = 0.39) that it cannot be considered clinically useful for individual patients. In this study, older patients read significantly worse than younger patients, and a formula that combines age, race, sex, and educational status cannot reliably predict reading ability for individual patients. Most older patients read on a level so low that they cannot be expected to read most commonly used written materials. Routine testing of reading ability may allow more appropriate design and use of written materials. |
8042656 | Opioid peptides, adrenocorticotrophic hormone, and idiopathic (orthostatic) edema. | The effect of dextroamphetamine sulfate (Dexedrine) on plasma opioid peptides, hormones, and other metabolites was studied in eight female subjects with idiopathic (orthostatic) edema and five healthy females. All subjects were given 20 mg of dextroamphetamine sulfate, a drug widely used in the treatment of this disorder, and blood samples were collected before and 30, 60, and 90 minutes after treatment. Patients with idiopathic (orthostatic) edema had significantly lower plasma sodium levels but higher blood urea nitrogen, aldosterone, and renin levels. D-amphetamine decreased aldosterone and renin levels in both groups. Plasma adrenocorticotropin levels were lower whereas met-enkephalin levels were higher in idiopathic (orthostatic) edema subjects compared to control subjects. D-amphetamine had no significant effect on plasma beta-endorphin, adrenocorticotrophic hormone, or enkephalins. Our data indicate that opioid peptides, especially enkephalins, and adrenocorticotrophic hormone may be involved in the pathogenesis of idiopathic (orthostatic) edema syndrome, but they seem uninvolved in the aldosterone- and renin-lowering action of amphetamine. It is possible that amphetamine is acting further down the chain, either directly on the adrenal and kidney or the microvasculature, rather than at hypothalamus-pituitary axis. |
8042657 | Regional metabolic dependency in obstructive sleep apnea. | Abnormalities of oxygen use occur in obstructive sleep apnea, as do impaired cerebral perfusion and alterations of cerebral function. In this case study, the authors quantitated the local cerebral glucose metabolic rate in two patients with obstructive sleep apnea (one with and one without oxygen supply dependency) and assessed cerebral glucose use by increasing oxygen delivery through passive leg elevation. Obstructive sleep apnea was confirmed by visual analysis of nocturnal pulse oximetry traces in two patients and its severity assessed from the respiratory disturbance index and minimum oxygen saturation. Awake local cerebral glucose metabolic rate (microM/min/100 g) was determined by positron-emission tomography using [18F]-2-Fluoro-2-Deoxy-D-Glucose at baseline and on the following day during passive leg elevation. Conditions otherwise were unchanged. The patient with global oxygen supply dependency exhibited a significant increase in the local cerebral glucose metabolic rate. In contrast, the patient without global supply dependency had no change in the local cerebral glucose metabolic rate. These case studies demonstrate the first evidence of improvement in regional metabolic consumption in response to increased oxygen delivery and in the presence of global oxygen supply dependency. |
8042655 | The sympathetic nervous system and the physiologic consequences of spaceflight: a hypothesis. | Many of the physiologic consequences of weightlessness and the cardiovascular abnormalities on return from space could be due, at least in part, to alterations in the regulation of the autonomic nervous system. In this article, the authors review the rationale and evidence for an autonomic mediation of diverse changes that occur with spaceflight, including the anemia and hypovolemia of weightlessness and the tachycardia and orthostatic intolerance on return from space. This hypothesis is supported by studies of two groups of persons known to have low catecholamine levels: persons subjected to prolonged bedrest and persons with syndromes characterized by low circulating catecholamines (Bradbury-Eggleston syndrome and dopamine beta-hydroxylase deficiency). Both groups exhibit the symptoms mentioned. The increasing evidence that autonomic mechanisms underlie many of the physiologic consequences of weightlessness suggests that new pharmacologic approaches (such as administration of beta-blockers and/or sympathomimetic amines) based on these findings may attenuate these unwanted effects. |
8042654 | Case report: bilateral adrenal pheochromocytoma. | Pheochromocytoma remains a clinical challenge to diagnose and manage. In addition, the association of multiple endocrine neoplasia syndromes with pheochromocytoma require the clinician's awareness to evaluate patients with pheochromocytoma (especially when bilateral) for abnormalities in thyroidal C-cell function with serum calcitonin determinations. The authors present a case of a 42-year-old woman initially diagnosed with, and treated for, cranial artery vasculitis because she had a stroke and a history of rheumatoid arthritis and asthma. Subsequent evaluation of episodic blood pressure increases, headache, and tachycardia revealed biochemical evidence of catecholamine overproduction. Bilateral adrenal masses were found on computed tomography scanning, and the functional nature of the adrenal masses was confirmed by a meta-Iodobenzylguanidine scan. Upon further evaluation, an elevated serum calcitonin concentration was demonstrated, which increased greatly with pentagastrin stimulation. C-cell hyperplasia was demonstrated by subsequent thyroidectomy, confirming the diagnosis of multiple endocrine neoplasia 2A. The difficulty in arriving at a correct diagnosis, the subsequent management, including bilateral adrenalectomy and thyroidectomy, and newer insight into the genetic abnormalities of multiple endocrine neoplasia 2A are discussed. |
8042653 | Case report: acute renal vein thrombosis in patients with spinal cord injury and secondary amyloidosis. | Chronic spinal cord injury, when complicated by chronic suppurative infections, has replaced chronic tuberculosis as a leading cause of secondary amyloidosis. Renal involvement with secondary amyloidosis is characterized by the presence of nephrotic range proteinuria and an increased incidence of renal vein thrombosis. Two cases of acute renal vein thrombosis associated with secondary amyloidosis in patients with spinal cord injury are presented. In both cases, a past history of extensive decubitus ulcerations and urinary tract infections preceded the development of nephrotic range proteinuria. In case 1, nonoliguric acute renal failure occurred after the development of acute bilateral renal vein thrombosis. The patient declined dialytic therapy and expired with uremia. In case 2, worsening renal function and increased proteinuria resulted after the development of acute unilateral renal vein thrombosis. These cases include the clinical and anatomic findings of acute renal vein thrombosis that occur as a complication of secondary amyloidosis. Acute renal vein thrombosis should be considered whenever an acute change in renal function or increase in proteinuria is noted in this setting. |
8042652 | Case report: hypercalcemia with inappropriate 1,25-dihydroxyvitamin D in Wegener's granulomatosis. | Hypercalcemia associated with the extrarenal production of 1,25-dihydroxyvitamin D (1,25(OH)2D) has been reported in several disorders, most notably granulomatous diseases such as sarcoidosis. The authors describe a woman with hypercalcemia, renal insufficiency, microscopic hematuria, and anemia. The circulating 1,25(OH)2D level was higher than appropriate for the ambient conditions (renal insufficiency, suppressed intact parathyroid hormone, and hypercalcemia). A kidney biopsy was consistent with Wegener's granulomatosis, and treatment with prednisone and cyclophosphamide was associated with normalization of serum calcium levels, improved renal function, a marked decrease in serum 1,25(OH)2D levels, and increased serum intact parathyroid hormone levels. These findings are consistent with the unregulated production of 1,25(OH)2D by inflammatory cells associated with Wegener's granulomatosis. |
8042651 | Case report: Hashimoto's thyroiditis associated with Wegener's granulomatosis. | Wegener's granulomatosis is a well-defined systemic vasculitic syndrome that primarily affects the upper and lower respiratory tracts and the kidney. Hashimoto's thyroiditis is another autoimmune syndrome with the thyroid as its primary target organ. The relation between Hashimoto's thyroiditis and Wegener's granulomatosis is not reported in the English literature. In this article, the authors describe a patient with Hashimoto's thyroiditis in whom fulminant Wegener's granulomatosis subsequently developed. The immunologic similarities between these two diseases leads to the consideration that Wegener's granulomatosis possibly may be another immunologic disorder associated with Hashimoto's thyroiditis. |
8042650 | Case report: toxic shock syndrome arising from cellulitis. | Toxic shock syndrome is a febrile, multiorgan illness related to toxins elaborated by staphylococcal or streptococcal infections. In the 1980s, most cases were associated with menstruation. More recently, many cases now are unrelated to menses. In this article, the authors describe a case of a nonmenstruating woman with toxic shock syndrome, associated with cellulitis of her arm. Cultures of the arm grew Staphylococcal aureus, which produced enterotoxin B. |
8042649 | Case report: treatment of an intracranial arteriovenous malformation in a patient with complicated hemophilia. | The authors describe a young man with hemophilia complicated by chronic hepatic dysfunction, hypodysfibrinogenemia, and immune thrombocytopenia that resulted in a complex coagulopathy. The patient had a ruptured occipital arteriovenous malformation. The malformation was managed by temporary correction of the coagulopathy using cryoprecipitate, platelet transfusions, and plasmapheresis with fresh frozen plasma replacement. The patient underwent staged preoperative embolization followed by surgical excision of the lesion. Hemostasis was acceptable during the neurointerventional and subsequent surgical management, and no complications of coagulopathy occurred. Plasmapheresis may provide effective preparation for patients with hemophilia and complex coagulation abnormalities who require neurosurgical intervention. |
8042648 | Anti-neutrophil antibodies of the immunoglobulin M class in autoimmune neutropenia. | Anti-neutrophil antibodies of the immunoglobulin G (IgG) class have been implicated in the pathogenesis of autoimmune neutropenia, but few reports have described immunoglobulin M (IgM) anti-neutrophil antibodies. To investigate the prevalence of IgM anti-neutrophil antibodies, sera from 130 patients with possible autoimmune neutropenia were studied for IgG and IgM anti-neutrophil antibodies using an immunofluorescence flow cytometric assay. Twenty-five patients (19%) had IgG anti-neutrophil antibodies exclusively, 21 patients (16%) had both IgG and IgM anti-neutrophil antibodies, and 11 patients (8%) had IgM anti-neutrophil antibodies exclusively. Immunoglobulin M anti-neutrophil antibodies were found in adults and children with isolated chronic neutropenia and in patients with Felty's syndrome, systemic lupus erythematosus, immune thrombocytopenic purpura, and human immunodeficiency virus. Patients with neutropenia with only IgM anti-neutrophil antibodies comprised almost 20% of antibody-positive patients in this study. |
8042642 | Pharmacy manpower: implications for pharmaceutical care and health care reform. | Our understanding of the pharmacy work force has improved substantially over the past five years. Research efforts have described the existing work force and projected for the next decade the effect that changes in educational programs, increasing numbers of female pharmacists, and increasing numbers of employee pharmacists will have on the effective work force size. Projections about the effect of pharmacy technicians and automation are less certain. Continued research is needed to document the changing nature of the pharmacy work force, to provide work force data that are essential to representing pharmacy in health care policy decisions, and to help confirm the value of pharmacy services. |
8042639 | Career expectations of pharmacists with postgraduate training in drug information. | The career expectations of pharmacists who have completed postgraduate training in drug information were studied. A questionnaire was mailed to all pharmacists who completed fellowships or residencies in drug information from 1989 to 1993 and the current preceptors of such programs. Recipients were asked to provide information about past and present positions, residency or fellowship training goals, characteristics of an ideal practice setting, satisfaction with current positions, professional activities, and future career goals. Seventy-five pharmacists (26 preceptors and 49 former trainees) returned questionnaires with usable information, for an 86% response rate. Preceptors and former trainees gave similar responses regarding the desired characteristics of an ideal practice setting, overall satisfaction with one's current position, expectations after postgraduate training in drug information, and long-term career goals. However, many former trainees did not list drug information-related positions as the desired first job after training, suggesting that the career opportunities in drug information may need to be stressed more heavily in training programs. Former drug information residents and fellows had career expectations similar to those held by current program preceptors. |
8042638 | Medication cart-filling time, accuracy, and cost with an automated dispensing system. | Medication cart filling with an automated dispensing system was compared with manual cart filling with respect to personnel time, costs, and accuracy. At a 650-bed tertiary-care medical center, technician cart filling and pharmacist cart checking were timed for the existing manual system and for the Baxter ATC-212 automated dispensing system. Subsequently, carts filled with each system were checked for accuracy of dispensing. On the basis of drugs used in the automated system over three months, drug acquisition and dispensing costs were calculated for automated and manual cart filling; the costs of personnel time were also compared. Daily cart filling time for technicians was significantly less with the automated system. The savings of pharmacist time was not significant; pharmacists had to cut the strip-packaged drugs into individual doses as they checked patients' medications. For both systems, errors were found in fewer than 1% of the doses (0.84% for the manual system and 0.65% for the automated system). Drug costs were higher with the automated system; acquisition prices for the bulk drugs purchased for use in the dispensing machine were higher than the prices of the same products in unit dose packaging. Personnel time saved amounted to less than 0.5 full-time equivalent. With the automated system, overall time savings was not great enough to substantially affect pharmacy operations, and drug costs were higher. |
8042637 | Emerging indications for octreotide therapy, Part 1. | Possible new indications for the use of octreotide are discussed. In October 1988, octreotide received FDA-approved labeling for use in the management of carcinoid syndrome and vipomas. Since that time, research results and clinical experience have accumulated that suggest a potentially much broader therapeutic role for octreotide. Reports continue to be published on the use of octreotide for treating pituitary tumors, gastroenteropancreatic tumors, diabetes mellitus, AIDS-associated diarrhea, autonomic neuropathy, pancreatitis, pancreatic pseudocysts and ascites, complications of pancreatic surgery and transplantation, ileostomy-associated diarrhea, enterocutaneous fistulas, pancreatic fistulas, dumping syndrome, short bowel syndrome, and gastrointestinal bleeding. Other emerging indications for the use of octreotide include psoriasis, hypercalcemia, cancer-related pain, polycystic ovary syndrome, and certain cancers. In children, octreotide has been studied for use in treating hyperinsulinemic hypoglycemia of infancy. Along with the common adverse effects of octreotide, such as pain at the injection site and nausea, less frequent effects, such as cholelithiasis, gallbladder hypercontractility, and gastritis have now been described. Much of what has been learned is based on small uncontrolled studies and case reports, since the rarity of many of the conditions for which octreotide has shown promise has tended to preclude larger studies. As clinical experience with octreotide accumulates and better-designed trials are completed where possible, a broader therapeutic role for octreotide is likely to be recognized. |
8042636 | Preventing stroke in patients with nonrheumatic atrial fibrillation. | Published and ongoing studies of drug therapy for preventing stroke in patients with nonrheumatic atrial fibrillation (AF) are discussed, and updated recommendations are provided. Stroke is the most common complication of nonrheumatic AF; there are more than 75,000 such strokes each year in North America. Nonrheumatic AF increases the risk of stroke almost sixfold. Emboli from clots that form in the left atrium because of ineffective atrial contraction and turbulent blood flow may cause most of these strokes. The results of six randomized trials of antithrombotic therapy in patients with nonrheumatic AF are now available. In almost all of these trials, warfarin therapy significantly reduced the risk of stroke. One trial showed that aspirin significantly reduced the risk of stroke, but another trial did not support that finding. Ongoing trials are addressing the efficacy and risks of aspirin plus low-dose warfarin and very low intensity anticoagulation. Overall, the data suggest that patients who are younger than 75 years of age and who lack risk factors can be adequately protected against stroke with aspirin. Patients younger than 75 years who have risk factors but no contraindications to warfarin should receive warfarin. Patients older than 75 years appear to benefit from anticoagulation therapy, but this benefit is offset by the higher risk of bleeding complications. Lone AF is best managed with aspirin. Warfarin is superior to aspirin as a secondary intervention in patients with a recent thromboembolic event. Strategies for preventing stroke in patients with nonrheumatic atrial fibrillation continue to be refined. |
8042618 | Inhibition by aurintricarboxylic acid of von Willebrand factor binding to platelet GPIb, platelet retention, and thrombus formation in vivo. | Commercial aurintricarboxylic acid (ATA) was separated into molecular-weight (MW) fractions of < 210 to > 25,000, using gel permeation chromatography. Fractions with MW > 1,300 effectively inhibited both botrocetin-induced vWF and bovine vWF binding to fixed human platelets. These activities decreased with a MW > 17,000. Platelet retention for a human in vitro was reduced by ATA at 150 microM, as was that for rats ex vivo at 3 mg/kg. ATA prolonged tail transection bleeding time in rats but had only a weak effect on buccal mucosal bleeding time in dogs. ATA had no effect on platelet count but markedly prolonged PTT. ATA at 10 mg/kg exhibited antithrombotic activity and caused a marked improvement in patency status following successful thrombolysis by t-PA in electrically and copper coil-induced thrombosis models. These results suggest that specific inhibitors of the vWF-GPIb interaction such as ATA may prove useful as antithrombotic agents. |
8042617 | Anti-annexin V antibody in systemic lupus erythematosus patients with lupus anticoagulant and/or anticardiolipin antibody. | We investigated anti-annexin V antibody (aANX) in patients with systemic lupus erythematosus (SLE), and correlated to positivity with lupus anticoagulant (LA)/anticardiolipin antibody (aCL). aANX was positive in 12/47 SLE patients (26%), including 7 with beta 2-glycoprotein 1 (GPI)-dependent aANX. The positivity of aANX was higher in patients with aCL (19%) and LA/aCL (50%) than in those without LA/aCL (10%). From these results, it is concluded that aANX is an autoantibody closely related to LA/aCL, and can be a possible new risk marker for thrombosis. |
8042616 | Bone marrow necrosis in two patients with acute promyelocytic leukemia during treatment with all-trans retinoic acid. | All-trans retinoic acid has been used for the treatment of acute promyelocytic leukemia (APL) with encouraging results. However, it has recently been associated with a number of potentially serious complications including the retinoic acid syndrome. We describe two patients with APL who were begun on all-trans retinoic acid therapy (45 mg/m2), but who developed leukocytosis which was treated with hydroxyurea. Both patients demonstrated clinical and laboratory findings of disseminated intravascular coagulation, massive cell lysis manifested by marked increases in serum lactic dehydrogenase, and rapid clinical deterioration. Both patients developed bone marrow necrosis within viable, noninfarcted bone trabeculae. We postulate that the development of bone marrow necrosis in these two patients was not a chance occurrence. Rather, the specific combination of cytotoxic and differentiating agents used in these patients (hydroxyurea with all-trans retinoic acid) caused massive cell lysis and death. The absence of bone marrow necrosis in the setting of induction therapy for APL both with and without all-trans retinoic acid therapy suggests that the addition of hydroxyurea was critical to the development of marrow necrosis. We, therefore, recommend caution in the use of hydroxyurea and all-trans retinoic acid in the treatment of APL. |
8042615 | Polyethylene glycolated interleukin-2 as maintenance therapy for acute myelogenous leukemia in second remission. | Seven patients in second complete remission of acute myeloid leukemia (AML) aged 19-65 years were treated with polyethylene glycolated interleukin-2 (PEG IL-2), 1 x 10(6) U/M2 IV weekly as the sole postremission therapy. Second remission duration was in the range of 4-49+ months, and three patients had a second remission duration substantially longer than their first (6, 21+, and 42+ months). The results suggest that PEG IL-2 may prolong second remission duration in AML and that a prospective randomized study designed to test that idea is warranted. |
8042614 | Recombinant activated factor VII (rFVIIa) therapy for intracranial hemorrhage in hemophilia A patients with inhibitors. | We report the use of recombinant VIIa (rFVIIa) in the treatment of five ICHs in two factor VIII-deficient patients with inhibitors. In four of five ICHs, rFVIIa was the only factor replacement used at doses of 60-135 micrograms/kg every 2-4 hr for 12-14 days. Hemostasis at the primary site of bleeding was achieved in all cases, and all patients survived with no permanent neurologic deficits. However, the patient who received the highest dose of rFVIIa during the first 4 days of therapy developed clinical symptoms consistent with a cerebral vascular accident of the brainstem characterized by acute onset of truncal ataxia and upward-gaze nystagmus on day 8 of rFVIIa therapy. While receiving rFVIIa therapy for treatment of these five ICHs, four treatment courses were complicated by bleeding at sites other than the primary site, including two episodes of localized oozing at central line insertion sites, two episodes of hemarthrosis, and two episodes of epistaxis. Antifibrinolytic therapy with tranexamic acid was effective in two of these episodes. Laboratory evaluation revealed shortening of the PT, variable shortening without normalization of the APTT, peak factor VII activity levels 7-30-fold higher than normal baseline values, and normal antithrombin III (ATIII) and alpha 2-antiplasmin levels. In four of five ICHs, there was a 20-40% decrease in fibrinogen levels from baseline. The decrease in fibrinogen was accompanied by an increase in fibrin degradation products in 3/5 episodes and a 15-35% decrease in plasminogen activity levels in 2/5 episodes. Tissue factor pathway inhibitor (TFPI) levels remained stable and in the normal range. Although rFVIIa is an effective new therapy for the treatment of ICH in hemophilia patients with inhibitors, its optimal use with respect to safety and efficacy requires further clinical study. |
8042613 | DNA diagnosis of Hb S and Hb Caribbean (alpha 2 beta 2 91 Leu-->Arg) in a Jamaican family. | We describe a Canadian infant of Jamaican descent who presented with mild anemia. Hb electrophoresis revealed Hb S and an unknown Hb variant that migrated slightly faster than Hb S on cellulose acetate. Molecular studies of the family indicated that the proband is a compound heterozygote for Hb S and Hb Caribbean. Hb Caribbean has previously been characterized as a mildly unstable hemoglobin with low oxygen affinity, due to a Leu-->Arg substitution at amino acid residue 91. The present study establishes the molecular basis for Hb Caribbean (beta 91, CTG-->CGG) and confirms that Hb S/Hb Caribbean syndrome is not associated with serious clinical manifestations. |
8042612 | Concurrent RhGM-CSF does not offset myelosuppression from intensive chemotherapy: randomized placebo-controlled study in childhood acute lymphoblastic leukemia. | To determine whether recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) can offset the myelosuppressive effects of intensive chemotherapy, we carried out a double-blind placebo-controlled trial in which 40 patients with acute lymphoblastic leukemia (ALL) were randomized into two groups of 20 each. One group received rhGM-CSF (5.5 micrograms/kg SC) coadministered with chemotherapy and the other, placebo coadministered with chemotherapy from day 5 to day 11 and from day 19 to day 25 of the 28-day intensification phase of our institutional high-risk protocol for childhood ALL. The results indicate that, at the dose and schedule used, rhGM-CSF did not prevent neutropenia or shorten the number of days required to complete this phase of therapy. In addition, the treated and placebo groups showed no significant difference in absolute neutrophil counts, number of days with neutropenia, number of days with fever, number of days spent in hospital, or number of days on antibiotics during the 28-day study period. There was also no difference between the two groups in the number, type, or severity of infectious episodes. Two of 20 patients in the treatment group have relapsed, whereas none of the patients in the placebo group has yet relapsed (follow-up: 3-37 months), but these events were not statistically significant. We conclude that treatment with rhGM-CSF at the dose and schedule employed is not clinically beneficial. |
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