pmid
stringlengths 4
8
| title
stringlengths 1
1.27k
| text
stringlengths 1
14.3k
|
|---|---|---|
8042927 | Overview of clinical trials of hydergine in dementia. | To assess the overall effect of Hydergine (a combination drug called ergoloid mesylates) on patients with possible dementia and to investigate potential moderators of an effect. MEDLINE, EMBASE, and two proprietary databases were searched for reports of clinical trials. Included were randomized, placebo-controlled, double-blind, parallel-group trials in subjects with symptoms consistent with dementia performed with specified outcome instruments and sufficient statistical information to calculate effect sizes. Forty-seven (31%) of 151 trials reviewed met selection criteria. Potential moderating variables were extracted from each trial: sample size, inpatient-outpatient status, trial duration, age, gender, medication dose, publication year, and diagnostic grouping. Outcome measures were extracted with their associated statistics. The overall combined treatment effects ("adjusted d") for three types of outcome measures were calculated. Overall, Hydergine was more effective than placebo as assessed by comprehensive ratings (d = 0.47; 95% confidence interval [CI], 0.38 to 0.56; P = .0001), clinical global ratings (d = 0.56; 95% CI, 0.44 to 0.68; P = .0001), and combined neuropsychological measures (d = 0.27; 95% CI, 0.22 to 0.32; P = .0001). Inpatient status, daily doses of 4 mg or more, and vascular dementia were generally associated with larger effects. The effect in patients with possible Alzheimer's dementia was significant only for combined neuropsychological measures in five trials (d = 0.30; 95% CI, 0.16 to 0.44; P = .0001; and with a dose-response, P = .001). Overall, ergoloid mesylates were more effective than placebo. However, the effect in patients with possible Alzheimer's dementia was very modest at best. The dose-response relation suggests that potentially effective doses may be higher than the currently approved. The circumstances of the efficacy of Hydergine remain inadequately defined. |
8042926 | Screening for cognitive impairment in older individuals. Validation study of a computer-based test. | This study examined the validity of a computer-based cognitive test that was recently designed to screen the elderly for cognitive impairment. Criterion-related validity was examined by comparing test scores of impaired patients and normal control subjects. Construct-related validity was computed through correlations between computer-based subtests and related conventional neuropsychological subtests. University center for memory disorders. Fifty-two patients with mild cognitive impairment by strict clinical criteria and 50 unimpaired, age- and education-matched control subjects. Control subjects were rigorously screened by neurological, neuropsychological, imaging, and electrophysiological criteria to identify and exclude individuals with occult abnormalities. Using a cut-off total score of 126, this computer-based instrument had a sensitivity of 0.83 and a specificity of 0.96. Using a prevalence estimate of 10%, predictive values, positive and negative, were 0.70 and 0.96, respectively. Computer-based subtests correlated significantly with conventional neuropsychological tests measuring similar cognitive domains. Thirteen (17.8%) of 73 volunteers with normal medical histories were excluded from the control group, with unsuspected abnormalities on standard neuropsychological tests, electroencephalograms, or magnetic resonance imaging scans. Computer-based testing is a valid screening methodology for the detection of mild cognitive impairment in the elderly, although this particular test has important limitations. Broader applications of computer-based testing will require extensive population-based validation. Future studies should recognize that normal control subjects without a history of disease who are typically used in validation studies may have a high incidence of unsuspected abnormalities on neurodiagnostic studies. |
8042925 | Clinical correlates of cortical and nucleus basalis pathology in Alzheimer dementia. | We correlated severity of dementia in Alzheimer's disease with the degree of neuropathology in cortical and subcortical brain regions. In 13 patients with Alzheimer's disease who underwent neuropsychological testing before death, we assessed neurofibrillary tangles, senile plaques, and neuronal and synaptic density in the midfrontal cortex and the nucleus basalis of Meynert. In the midfrontal cortex, synapse density was the strongest correlate of dementia severity, followed by neurofibrillary tangles. In the nucleus basalis, by contrast, neurofibrillary tangles were the strongest correlate, followed by synapse density. Stepwise regression analyses showed midfrontal synapse density to be the strongest predictor of tests emphasizing higher cortical functions, but neurofibrillary tangles in the nucleus basalis were the strongest predictor on memory-oriented tests. The specificity of pathology in cortical vs subcortical locations for predicting a particular quality of neuropsychological deficit probably reflects disruption of corticocortical connections vs derangement of the basal forebrain cholinergic system. |
8042924 | Cerebellar atrophy in patients with long-term phenytoin exposure and epilepsy. | Cerebellar atrophy has been noted in patients with phenytoin exposure. This finding has been attributed by some investigators to seizures, but by others to phenytoin. Previous studies included patients with mental retardation and convulsive seizures. We undertook a study in a group of nonretarded patients with partial epilepsy to better elucidate the cause of the cerebellar atrophy. Case control study. Referral population from an epilepsy center. Thirty-six patients with partial epilepsy and long-term phenytoin exposure were selected from a consecutive sample of admissions to an epilepsy center. Patients with histories of ethanol abuse, perinatal distress, anoxia, status epilepticus, or neurodegenerative disorders were excluded. Age- and sex-matched controls were selected from a pool of healthy volunteers and patients who had undergone magnetic resonance imaging for complaints of headache and dizziness. All patients and controls underwent magnetic resonance imaging. Degree of cerebellar atrophy. The magnetic resonance imaging scans were reviewed in a blind fashion. A rating was assigned to each scan based on the degree of cerebellar atrophy. Cerebellar atrophy was significantly more pronounced in patients than in controls. No correlation was found between cerebellar atrophy and variables reflective of seizure severity or degree of phenytoin exposure. Cerebellar atrophy may be seen in phenytoin-exposed patients with epilepsy in the absence of generalized tonic-clonic seizures or preexistent brain damage. Whether it is the phenytoin or the seizures that play the primary etiologic role remains unanswered. These factors may be synergistic. |
8042923 | Clinical and pathological features of an autosomal dominant, adult-onset leukodystrophy simulating chronic progressive multiple sclerosis. | To study the clinical and pathological features of a kindred with an adult-onset autosomal dominant leukodystrophy. Five symptomatic and nine asymptomatic at-risk members of the kindred. Subjects underwent detailed histories and general and neurologic examinations. Further evaluation included electroencephalography, evoked potentials, electromyography, autonomic testing, and analysis of serum, urine, and cerebrospinal fluid. One patient underwent sural nerve biopsy and analysis. Another, previously studied patient, underwent a limited autopsy. Cerebellar and pyramidal dysfunction began in the fourth and fifth decades of life; subtle autonomic symptoms were often present years earlier. Frontal lobe dysfunction and abnormalities of the central visual pathways were mild and of late onset. Sensorineural hearing loss was common. The peripheral nervous system was spared. Autopsy results of one patient revealed severe degeneration of the white matter at all levels of the neuraxis, but most prominent in the frontoparietal and cerebellar regions, with sparing of the subcortical U fibers. Histological and ultrastructural examinations failed to show evidence of a specific pathogenetic mechanism or etiology. This disorder seems to be a distinct type of hereditary leukodystrophy, but its exact nature remains unknown. |
8042914 | Neuropsychological functioning in siblings discordant for schizophrenia and healthy volunteers. | To determine whether schizophrenics and their nonschizophrenic siblings have a similar pattern of neuropsychological deficit when compared with normal controls. Fifteen probands with schizophrenia, 16 of their nonschizophrenic siblings, and 31 unrelated, demographically balanced, normal individuals underwent evaluation with a comprehensive neuropsychological test battery. All subjects were screened for history of head injury, neurologic illness, major medical conditions, substance use, and axis I psychiatric disorders other than schizophrenia. Probands underwent evaluation twice: once at intake when half had never received neuroleptic medication and the other half had received none for a minimum of 2 weeks, and again at the 2- to 4-week follow-up, after stabilization with neuroleptic medications. Both schizophrenics and their nonschizophrenic siblings were impaired neuropsychologically compared with normal controls, with the nonschizophrenic siblings' performance intermediate between that of the schizophrenic siblings and the normal controls on all measures of functioning. The shapes of the deficit profiles of schizophrenic patients and their siblings were similar; in patients, verbal memory, abstraction, attention, and language functions were significantly more affected compared with spatial abilities, spatial memory, and sensory-motor functions, with a nonsignificant trend in the same direction in siblings. Cognitive functioning in patients was found to be stable across changes in medication status and clinical state. Four fifths of patients obtained more deviant scores than their nonschizophrenic siblings. Among the sibling group, those with probable and certain diagnoses of schizotypal personality disorder were more impaired compared with those without schizophrenia-spectrum symptoms. These results support the hypothesis that impaired information processing aggregates in the family members of schizophrenics and may serve as an indicator of genetic vulnerability to the disorder. Further work is needed to establish whether particular areas of functioning are selectively impaired in relatives and to determine whether the performance deficits are mediated by structural and/or metabolic disturbances in specific brain regions. |
8042913 | Risk factors for spontaneous dyskinesia in schizophrenia. | We describe the prevalence, clinical correlates, and prognostic significance of spontaneous dyskinesias among 100 patients with schizophrenia from the Chestnut Lodge Follow-up Study who had never received treatment with neuroleptic agents up to and including the baseline assessment. Extensive case records were screened and descriptions of abnormal movements were recorded verbatim for blind rating. Neuroleptic-naive patients with and without abnormal oral-facial movements were compared across sign and symptom, schizophrenia subtype, and illness natural history variables. Excluding three patients with motor symptoms who had a history of neurologic illness or injury and three who had received prochlorperazine maleate therapy (Compazine), 23% of patient records documented some form of movement disorder; 15% documented oral-facial dyskinesias with sufficient detail so that their presence was considered nearly certain. Compared with patients with schizophrenia without oral-facial movements, patients with oral-facial dyskinesias were more likely to demonstrate a lower IQ score, had more negative symptoms at index admission, and were more symptomatic at follow-up an average of 23 years later. Both the classic hebephrenic schizophrenia subtype and Carpenter's Criteria for the Deficit Syndrome defined high-risk groups for spontaneous oral-facial dyskinesia. In previous studies, intellectual impairment and negative symptoms have been described as risk factors for neuroleptic-induced tardive dyskinesia. The present data, however, suggest that in many cases oral-facial dyskinesias in patients with intellectual impairment and negative symptoms may actually represent spontaneous movement disorders associated with hebephrenic or deficit forms of schizophrenia. |
8042912 | Elevation of serum free triiodothyronine, total triiodothyronine, thyroxine-binding globulin, and total thyroxine levels in combat-related posttraumatic stress disorder. | This study was designed to assess both central and peripheral aspects of thyroid function in combat-related posttraumatic stress disorder (PTSD), with the particular purpose of finding a mechanistic explanation for an imbalance between serum levels of free thyroxine (T4) and total T4 previously observed in pilot work. A total of 96 male combat veterans with PTSD diagnosed by DSM-III-R (72 from the West Haven, Conn, Veterans Affairs Medical Center and 24 from the Menlo Park, Calif, Veterans Affairs Medical Center) were compared with 24 male control subjects. One or more serum samples were analyzed by radioimmunoassays for levels of total T4, free T4, total triiodothyronine (T3), free T3, T4-binding globulin, and thyrotropin. The pilot observation of moderately elevated total T4 levels with no elevation in free T4 levels in patients with PTSD was confirmed, suggesting the hypotheses that (1) there may be an increased peripheral conversion of free T4 by deiodination to T3 or (2) there may be an increased binding of T4 secondary to elevated T4-binding globulin levels. Our findings support both hypotheses. The PTSD groups all showed a marked and sustained elevation in levels of both total T3 and free T3, as well as elevated T3/T4 ratios, supporting the increased T3 conversion hypothesis. The PTSD groups also showed a marked and sustained increase in T4-binding globulin levels, supporting the increased binding hypothesis. Thyrotropin levels did not differ between PTSD and control groups. These findings demonstrate an unusual pattern of thyroid alterations, featuring substantial elevations in total T3, free T3, and T4-binding globulin levels, in combat-related PTSD that differs from established endocrinopathies, such as classic hyperthyroidism, T3 thyrotoxicosis, or chronic T4-binding globulin elevation. |
8042911 | Carbamazepine increases cerebrospinal fluid thyrotropin-releasing hormone levels in affectively ill patients. | Thyrotropin-releasing hormone is an endogenous tripeptide with endocrine-independent neurophysiologic properties that may be relevant to affective or seizure disorders. We studied the effect of carbamazepine, which has both mood-stabilizing and anticonvulsant properties, on cerebrospinal fluid thyrotropin-releasing hormone levels in affectively ill patients. Paired cerebrospinal fluid samples were collected from nine inpatients with mood disorders, both while medication free and while taking carbamazepine for an average of longer than 1 month at 950 mg/d, achieving blood levels of 8.8 mg/L. Carbamazepine treatment was consistently and significantly associated with increased cerebrospinal fluid thyrotropin-releasing hormone levels (P < .0001). As carbamazepine-induced increases in thyrotropin-releasing hormone levels could be relevant to either its psychotropic or anticonvulsant properties, further clinical and preclinical investigation of this finding appears indicated. |
8042910 | The 24-hour profiles of cortisol, prolactin, and growth hormone secretion in mania. | To characterize sleep and the 24-hour profiles of cortisol, prolactin (PRL), and growth hormone (GH) secretion in mania. Blood was sampled at 15-minute intervals, and sleep was polygraphically recorded in eight unmedicated male patients with pure mania and the results compared with those from a group of 14 healthy age-matched controls. The circadian, sleep-related, and pulsatile hormonal variations were quantitatively characterized using specifically designed computer algorithms. The manic state was associated with alterations of corticotropic activity and circadian rhythmicity partially overlapping those previously observed in acute endogenous depression, consisting of an elevation of nocturnal cortisol levels and an early timing of the nadir of the circadian variation. Sleep onset was delayed and the sleep period was reduced. A trend for short rapid eye movement latencies was apparent in the adult patients. Both the amount and the temporal organization of PRL and GH secretion were normal. The manic state seems to be characterized by similar but less severe neuroendocrine and circadian abnormalities, compared with major depression. |
8042909 | Interpersonal psychotherapy. Current status. | Interpersonal psychotherapy (IPT), a time-limited treatment for major depression, was developed, defined in a manual, and tested in randomized clinical trials by the late Gerald L. Klerman, MD, and collaborators. It has subsequently been modified for different age groups and types of mood and nonmood disorders and for use as a long-term treatment. Having begun as a research intervention, IPT has yet to be well disseminated among clinicians or in residency training programs. The publication of efficacy data, the recent appearance of two practice guidelines that include IPT among treatments for depression, and the interest in defined treatments for managed care have led to increasing requests for information and training. |
8042908 | Restriction endonucleases from Selenomonas ruminantium which recognize and cleave 5'-AT/TAAT-3'. | Two natural isolates from fallow-deer rumen identified as Selenomonas ruminantium were found to produce a restriction endonuclease which we called Sru4DI. This enzyme was isolated from cell extracts by phosphocellulose chromatography. Analysis of the Sru4DI recognition site showed that Sru4DI recognizes the hexanucleotide sequence 5'-AT/TAAT-3' generating 5'dinucleotide protruding ends upon cleavage and thus is a true isoschizomer of vspI, a restriction enzyme isolated from Vibrio sp. |
8042907 | Comparative aspects of utilization of sulfonate and other sulfur sources by Escherichia coli K12. | Selected biochemical features of sulfonate assimilation in Escherichia coli K-12 were studied in detail. Competition between sulfonate-sulfur and sulfur sources with different oxidation states, such as cysteine, sulfite and sulfate, was examined. The ability of the enzyme sulfite reductase to attack the C-S linkage of sulfonates was directly examined. Intact cells formed sulfite from sulfonate-sulfur. In cysteine-grown cells, when cysteine was present with either cysteate or sulfate, assimilation of both of the more oxidized sulfur sources was substantially inhibited. In contrast, none of three sulfonates had a competitive effect on sulfate assimilation. In studies of competition between different sulfonates, the presence of taurine resulted in a decrease in cysteate uptake by one-half, while in the presence of isethionate, cysteate uptake was almost completely inhibited. In sulfite-grown cells, sulfonates had no competitive effect on sulfite utilization. An E. coli mutant lacking sulfite reductase and unable to utilize isethionate as the sole source of sulfur formed significant amounts of sulfite from isethionate. In cell extracts, sulfite reductase itself did not utilize sulfonate-sulfur as an electron acceptor. These findings indicate that sulfonate utilization may share some intermediates (e.g., sulfite) and regulatory features (repression by cysteine) of the assimilatory sulfate reductive pathway, but sulfonates do not exert regulatory effects on sulfate utilization. Other results suggest that unrecognized aspects of sulfonate metabolism, such as specific transport mechanisms for sulfonates and different regulatory features, may exist. |
8042906 | Evidence for the involvement of multiple pathways in the biodegradation of 1- and 2-methylnaphthalene by Pseudomonas putida CSV86. | Pseudomonas putida CSV86, a soil bacterium, grows on 1- and 2-methylnaphthalene as the sole source of carbon and energy. In order to deduce the pathways for the biodegradation of 1- and 2-methylnaphthalene, metabolites were isolated from the spent medium and purified by thin layer chromatography. Emphasis has been placed on the structural characterisation of isolated intermediates by GC-MS, demonstration of enzyme activities in the cell free extracts and measurement of oxygen uptake by whole cells in the presence of various probable metabolic intermediates. The data obtained from such a study suggest the possibility of occurrence of multiple pathways in the degradation of 1- and 2-methylnaphthalene. We propose that, in one of the pathways, the aromatic ring adjacent to the one bearing the methyl moiety is oxidized leading to the formation of methylsalicylates and methylcatechols. In another pathway the methyl side chain is hydroxylated to -CH2-OH which is further converted to -CHO and -COOH resulting in the formation of naphthoic acid as the end product. In addition to this, 2-hydroxymethylnaphthalene formed by the hydroxylation of the methyl group of 2-methylnaphthalene undergoes aromatic ring hydroxylation. The resultant dihydrodiol is further oxidised by a series of enzyme catalysed reactions to form 4-hydroxymethyl catechol as the end product of the pathway. |
8042905 | Neighboring plasmid sequences can affect Mini-Mu DNA transposition in the absence of expression of the bacteriophage Mu semi-essential early region. | Bacteriophage Mu DNA, like other transposable elements, requires DNA sequences at both extremities to transpose. It has been previously demonstrated that the transposition activity of various transposons can be influenced by sequences outside their ends. We have found that alterations in the neighboring plasmid sequences near the right extremity of a Mini-Mu, inserted in the plasmid pSC101, can exert an influence on the efficiency of Mini-Mu DNA transposition when an induced helper Mu prophage contains a polar insertion in its semi-essential early region (SEER). The SEER of Mu is known to contain several genes that can affect DNA transposition, and our results suggest that some function(s), located in the SEER of Mu, may be required for optimizing transposition (and thus, replication) of Mu genomes from restrictive locations during the lytic cycle. |
8042904 | Isolation of Serratia marcescens mutants which could overproduce and excrete Escherichia coli alkaline phosphatase and beta-lactamase. | Serratia marcescens mutants, which excrete Escherichia coli alkaline phosphatase (APase) encoded by the plasmid-bearing phoA gene, were isolated after mutagenesis by N-methyl-N'-nitro-N-nitrosoguanidine. These mutants produced two to four times as much APase as did the parent strain under a phosphate-limiting condition, and more than 70% of the enzyme was released into the culture medium. In addition, overproduction and excretion of beta-lactamase was observed in these mutants. |
8042903 | Characterization of the Rhizobium leguminosarum biovar phaseoli nifA gene, a positive regulator of nif gene expression. | We report the isolation, mutational analysis and the nucleotide sequence of the Rhizobium leguminosarum bv. phaseoli nifA gene. Comparison of the deduced amino acid sequence with other NifA sequences indicated the presence of the conserved central activator and the C-terminal DNA-binding domains. Nodules elicited by a R. leguminosarum bv. phaseoli nifA mutant were symbiotically ineffective. The expression of a nifA-gusA fusion was shown to be independent on the oxygen status of the cell. We cloned the three nifH copies of R. leguminosarum bv. phaseoli and determined the nucleotide sequence of their promoter regions. The expression of nifH-gusA fusions is induced under microaerobic conditions and is dependent on the presence of NifA. |
8042902 | Inactivation of Escherichia coli threonine synthase by DL-Z-2-amino-5-phosphono-3-pentenoic acid. | The rhizocticines and plumbemicines are two groups of di- and tripeptid antibiotics thought to interfere with threonine or threonine-related metabolism. Z-2-amino-5-phosphono-3-pentenoic acid, the common unusual amino acid constituent of the rhizocticines and plumbemicines, was found to irreversibly inhibit Escherichia coli threonine synthase in a time-dependent reaction that followed pseudo-first order and saturation kinetics. These data provide evidence that the toxicity of the rhizocticines and plumbemicines is due to the inhibition of threonine synthase by Z-2-amino-5-phosphone-3-pentenoic acid, which is liberated by peptidases after uptake into the target cell. Additionally, methods for the purification of threonine synthase from an overproducing E. coli strain and for the enzymatic synthesis of L-homoserine phosphate are described. |
8042901 | Urease from Staphylococcus saprophyticus: purification, characterization and comparison to Staphylococcus xylosus urease. | Urease from Staphylococcus saprophyticus was purified more than 800-fold by liquid chromatography reaching homogeneity, as shown by isoelectric focussing, at a maximum specific activity of 1979 U/mg. The molecular weight of the native enzyme was 420,000; it consisted of subunits with molecular weights of 72,400 (alpha), 20,400 (beta), 13,900 (gamma) in an estimated (alpha beta gamma)4 stoichiometry. In native gradient polyacrylamide gel electrophoresis urease exhibited a multiple activity band pattern with molecular weights ranging from 420,000 to 100,000. In the native enzyme, 4.09 (+/- 0.25) atoms of nickel per molecule were detected. The N-terminal amino acids of the urease subunits were identical to those from Staphylococcus xylosus, and amino acid analysis revealed high similarities in both enzymes; no cysteine was detected after acid hydrolysis of vinylpyridinylated urease. Electron micrographs of negatively stained urease specimens from both staphylococci showed identical size and structure. |
8042900 | Threonine is present instead of cysteine at the active site of urease from Staphylococcus xylosus. | DNA sequence analysis of the structural urease genes from Staphylococcus xylosus revealed that three enzyme subunits are encoded in the order of 11,000, 15,400 and 61,000 (mol. mass), which correspond to the single polypeptide chain of jack bean urease (90,800). Comparing the deduced amino acid sequence of S. xylosus urease with the amino acid sequence of jack bean urease an overall portion of 56% identical residues was found. For S. xylosus urease a subunit structure of (alpha beta gamma)4 was proposed, based on the comparison of the deduced amino acid content of the enzyme subunits with the total amino acid content of the purified enzyme. The staphylococcal enzyme contained no cysteine, as deduced from DNA sequence and confirmed by the determination of the total amino acid content in the purified enzyme. Instead of cysteine, known to be catalytically essential in the plant enzyme, and conserved among all bacterial ureases analyzed so far, threonine was found in S. xylosus. This amino acid-exchange was located within a highly conserved domain of 17 amino acids, supposed to be part of the active site. Sequence analysis of the respective region of Staphylococcus saprophyticus urease showed that it also contains threonine instead of cysteine. In contrast to jack bean urease S. xylosus urease was not affected by the SH-group inhibitor dipyridyl disulfide but was completely inhibited by the serine protease inhibitor phenylmethanesulfonyl fluoride. The presented results indicate that in these staphylococcal strains urea hydrolysis might function in a manner similar to the peptide bond cleavage by chymotrypsin. |
8042899 | A novel, "hidden" penicillin-induced death of staphylococci at high drug concentration, occurring earlier than murosome-mediated killing processes. | In log-phase cells of staphylococci, cultivated under high, "non-lytic" concentrations of penicillin G, there occurred a novel killing process hitherto hidden behind seemingly bacteriostatic effects. Two events are essential for the appearance of this "hidden death": (i) the failure of the dividing cell to deposit enough fibrillar cross-wall material to be welded together, and (ii) a premature ripping up of incomplete cross walls along their splitting system. "Hidden death" started as early as 10-15 min after drug addition, already during the first division cycle. It was the consequence of a loss of cytoplasmic constituents which erupted through peripheral slit-like openings in the incomplete cross walls. The loss resulted either in more or less empty cells or in cell shrinkage. These destructions could be prevented by raising the external osmotic pressure. In contrast, the conventional "non-hidden death" occurred only much later and exclusively during the second division cycle and mainly in those dividing cells, whose nascent cross walls of the first division plane had been welded together. These welding processes at nascent cross walls, resulting in tough connecting bridges between presumptive individual cells, were considered as a morphogenetic tool which protects the cells, so that they can resist the otherwise fatal penicillin-induced damages for at least an additional generation time ("morphogenetic resistance system"). Such welded cells, in the virtual absence of underlying cross-wall material, lost cytoplasm and were killed via ejection through pore-like wall openings or via explosions in the second division plane and after liberation of their murosomes, as it was the case in the presence of low, "lytic" concentrations of penicillin. Bacteriolysis did not cause any of the hitherto known penicillin-induced killing processes. |
8042898 | The arrangement of F-actin and microtubules during germination of Mucor rouxii sporangiospores. | The distribution of F-actin microfilaments and microtubules was analyzed in germinating sporangiospores of Mucor rouxii by labeling with rhodamine-tagged phalloidin and by immunofluorescence microscopy. The transition from isodiametrical to apical growth was accompanied by a switch from uniform distribution of F-actin patches to a polarized accumulation of F-actin material at the germ tube tips. Immunoblotting of cell-free extracts of M. rouxii with a monoclonal anti-porcine alpha-tubulin antibody (TU-01) disclosed two discrete bands of alpha-tubulin suggesting the existence of two alpha-tubulin genes in this fungus. Immunofluorescence microscopy of germinating cells stained with the same antibody revealed an elaborate network of cytoplasmic microtubules that persisted during the entire germination process and extended into the apex of the germ tube. Although their precise roles remain undetermined, the observed arrangement of cytoskeletal elements during germination is consistent with their presumed involvement in cell wall morphogenesis: the long axial microtubules serving as long-distance conveyors of wall-building vesicles to the apical region while the concentrated F-actin patches mark the participation of microfilaments in the zone of intense vesicle exocytosis at the hyphal apex. |
8042897 | Muscle spindle and periodontal trigeminal afferents modulate the hypoglossal motoneuronal activity. | Hypoglossal responses to electrical or natural activation of the afferent fibers of the masseteric nerve and to periodontal mechanoreceptors were recorded in rats. Electrical stimulation of the masseteric nerve, at an intensity adequate to excite prevalently the primary spindle afferents, induced various sequences of excitation-inhibition and inhibition-excitation in 55% of the tested hypoglossal motoneurons. Responses were characterized by excitation, inhibition or excitation-inhibition sequences occurring at short and long latencies. Different pattern of responses were evoked in both the protrusive and the retractive motoneurons of the homolateral hypoglossal nucleus. Moreover, jaw lowering and pressure on the incisor tooth induced antagonistic and synergistic effects on the electrical activity of the same hypoglossal motoneurons. The results show for the first time that afferent signals from both muscle spindles and periodontal receptors modulate the activity of the hypoglossal motoneurons aimed at controlling the tongue position in the mouth during mastication. |
8042896 | Passive avoidance response distribution by post-training substantia nigra functional tetrodotoxin inactivation in the rat. | The tetrodotoxin (TTX) functional ablation technique was employed to assess the temporal coordinates of rat's substantia nigra (SN) in memory processing. TTX (10 ng in 1 microliter saline) was stereotaxically administered to rats under general ketamine anesthesia, either bilaterally or unilaterally. TTX was injected in different groups of rats respectively 0.25, 6, 24, and 48 hours after passive avoidance acquisition testing. Rats always underwent retrieval testing 48 hours later, after full recovery from TTX effects. The results show that: i) unilateral TTX blockade significantly impairs PAR only up to 0.25 h and not 6 h after acquisition testing, and ii) bilateral TTX blockade dramatically disrupts passive avoidance responding up to 24 but not 48 hours after acquisition testing. The results indicate a much more important SN role in memory processing than was previously assessed. The experimental evidence is discussed both in relation to previous TTX functional ablation findings (amygdala, parabrachial nuclei, nucleus basalis magnocellularis) and in relation to SN anatomical and functional connections with other subcortical structures. |
8042895 | Power spectral analysis of blood pressure fluctuations during sleep in normal and decerebrate cats. | Arterial blood pressure fluctuations during sleep were investigated with power analysis technique in both normal and decerebrate cats. In the initial postoperative stage lasting about 3 to 4 days, intact cats displayed, during paradoxical sleep, phasic increases in arterial blood pressure which were superimposed on a tonic hypotension. In the later chronic stage, however, the animals showed the phasic hypertension being superimposed on the background of a tonic hypertension. Regardless of these stages, the blood pressure during paradoxical sleep exhibited a 1/f-like spectrum, expressed by the power spectral density which is inversely proportional to the Fourier frequency f. On the other hand, a power spectral profile of the blood pressure during slow wave sleep presented a white noise-like pattern within the same frequency range of 0.1-0.01 Hz. After brainstem transections at the pontomesencephalic border, the cats exhibited consistently a sustained fall in blood pressure during paradoxical sleep and the power spectral density of the blood pressure displayed a white noise-like pattern throughout the survival periods of one month or more. These observations indicate that the blood pressure fluctuations in the 1/f spectrum during paradoxical sleep originate in rostral brain structures. |
8042893 | Atheromatous embolization resulting in acute pancreatitis after cardiac catheterization and angiographic studies. | Acute pancreatitis has a spectrum from mild disease to severe organ destruction resulting in multiple system organ failure. In this study, we report data from 21,680 discharge summaries during a 10-year period of patients who had undergone transabdominal angiographic procedures in whom the diagnosis of pancreatitis was noted in the discharge coding. We detected 39 patients in whom pancreatitis was coded during the same hospitalization, but only nine patients had no other risk factors for pancreatitis other than the temporal relation with the angiographic procedure. Three of these nine patients died of complications caused by pancreatitis. All of the patients with poor outcomes in this report fulfilled more than three Ranson criteria within 48 hours of the original angiographic procedure. Abdominal imaging with ultrasound or computed tomography was abnormal in all the patients who fulfilled more than three Ranson criteria. The histology from the surgical procedures or the autopsies performed on the three patients who died showed extensive cholesterol embolization primarily to the visceral organs. Extensive pancreatic necrosis was evident in these patients. We conclude that acute pancreatitis after transabdominal angiographic procedures is a rare but a potential fatal event. The prognosis from this event is partially predicted by the Ranson criteria that are evident within the first 48 hours. |
8042892 | Onchocerciasis in New York City. The Moa-Manhattan connection. | When faced with a patient with travel-associated dermatitis, clinicians often diagnose and treat for a suspected hypersensitivity reaction or infestation with an ectoparasite. We studied a small cluster of travelers from New York, NY, to the Moa River in Sierra Leone who developed dermatitis caused by Onchocerca volvulus. Our patients had relatively long stays in an endemic area and numerous bites by blackflies. Such patients represent a subset of travelers in whom dermatitis should prompt evaluation for onchocerciasis. |
8042891 | A coordinated, communitywide program in Monroe County, New York, to increase influenza immunization rates in the elderly. | Despite the efficacy of influenza vaccination in preventing complications of influenza, rates of immunization among high-risk populations remain low. The Monroe County (New York) Influenza Vaccination Demonstration was a communitywide, collaborative effort to increase the rates of influenza immunization to greater than 60% in elderly Medicare recipients. The local health department, university medical center, and practicing physicians collaborated to develop a communitywide demonstration directed to all Medicare part B enrollees 65 years of age or older, multiple coordinated approaches were used over a 4-year period (1988 to 1992). Most providers, including public agencies, private providers, hospital outpatient facilities, nursing homes, and insurance providers, were enrolled in a comprehensive program that included centralized claims processing, vaccine distribution and promotion, and extensive provider and public education efforts, including a special urban outreach program. An office-based, denominator-driven physician incentive project was also evaluated. The demonstration project resulted in a 1991 influenza immunization rate of 74.3% among 88,811 Medicare enrollees 65 years of age or older. The increase in immunization rate occurred primarily among the patients of private physicians. A communitywide, collaborative approach can succeed in achieving high rates of influenza immunization. |
8042890 | Evaluation of ondansetron prescribing in US academic medical centers. | The study objectives were to characterize the use of the antiemetic ondansetron, a serotonin subtype 3 receptor antagonist, in US academic medical centers, and to assess ondansetron prescribing with consensus-derived prescribing guidelines used as evaluation criteria. A multicenter, prospective, observational study was conducted in the inpatient and outpatient care areas of 23 US academic medical centers. A total of 670 patients received ondansetron (508 inpatients and 162 outpatients). The use of ondansetron was compared with consensus-derived prescribing guidelines on the basis of indication for use and dose administered. Only 253 (37.8%) of the 670 patients satisfied for prescribing guidelines for both indication for use and dose administered. The remainder of the patients did not satisfy the guidelines, in whole or in part. If all ondansetron use had met the prescribing guidelines in the patients studied, a reduction in ondansetron use of 31% (16 185/52 260 mg) would have been realized. At an estimated cost of $5 per milligram, this reduction represents a potential cost savings of nearly $81,000, or $121 per patient studied. Since its introduction in 1991, ondansetron has become a commonly used antiemetic in US academic medical centers. Although ondansetron is safe and effective in improving patients' tolerance of emetogenic therapies, including cancer chemotherapy, its high cost has added a significant burden to the pharmaceutical budgets of many institutions. The study data suggest that compliance with ondansetron prescribing guidelines, with elimination of indiscriminant use, could result in significant cost savings. |
8042889 | A case manager intervention to reduce readmissions. | Acute hospitalizations represent substantial financial liability to closed health care systems. Among hospitalized patients, those with repeated admissions are high-cost users. Most managed care plans employ case management to control hospital use. This technique attempts to detect and fulfill unmet medical and social needs, intensify postdischarge care, identify and mobilize effective community services, and enhance primary care access. Despite the popularity of case management to control hospital use, few trials have examined its efficacy. We conducted a randomized controlled trial of an intervention of case managers at a university-affiliated Veterans Affairs medical center. Six hundred sixty-eight patients aged 45 years or older who were discharged from the general medicine inpatient service, who had access to a telephone, and who received primary care at the hospital's clinics were randomized to the intervention (N = 333) and control (N = 335) groups. Within 24 hours of discharge, case managers mailed educational materials and access information to intervention patients, and within 5 days they called to review and resolve unmet needs, early warning signs, barriers to keeping appointments, and any readmissions. Case managers contacted intervention patients if they made no visits for 30 days. This resulted in a total of 6260 patient-case manager contacts. Control and intervention patients were followed up for 12 months. Intervention patients had more frequent visits per patient per month to the general medicine clinic (0.30 +/- 0.23 vs 0.26 +/- 0.22, P = .008), but we detected no significant differences between groups in nonelective readmissions, readmission days, or total readmissions. Frequent contacts for education, care, and accessibility by case managers using protocols were ineffective in reducing nonelective readmissions. |
8042888 | Typhoid fever in New York City, 1980 through 1990. | Although typhoid fever incidence decreased in the 1960s and 1970s in New York City and elsewhere, it did not disappear. In this article, trends associated with various modes of transmission of Salmonella typhi in New York City patients are described. Typhoid fever surveillance reports from 1980 to 1990 were reviewed for clinical, demographic, and epidemiologic characteristics. Cases of typhoid fever were classified as travel related or domestically acquired. In all, 479 typhoid cases were identified, of which 67% were travel related. The age groups most frequently affected were children and adolescents. Cases more than doubled in the decade, and the ratio of travel-related cases to domestically acquired cases increased steadily from 63% to 80%. Travelers to Southeast Asia were at three times higher risk than those visiting South America and eight times higher than those visiting the Caribbean. The case-fatality proportion was 1.5%. The trends of S typhi infection in New York City followed the trends observed in the United States since 1978, which demonstrates the importance of international travel. Although food and water precautions may be effective for short-term travelers, selective use of oral antityphoid vaccines for New York City travelers to high-risk endemic countries should be encouraged. |
8042886 | Life expectancy following dietary modification or smoking cessation. Estimating the benefits of a prudent lifestyle. | To evaluate the maximum benefits of dietary modification or smoking cessation to the life expectancy of North American adults. Using a computer model, we estimated the change in life expectancy for men and women following risk factor modification. We then estimated the total number of adults who would be targeted by national guidelines and the total person-years of life that would be saved. Men and women aged 30 to 74 years who were free of coronary heart disease. Smoking cessation or serum cholesterol-reducing diets with 8% to 10% saturated fat and 240 to 300 mg of daily cholesterol, respectively. On average, dietary modification would reduce serum cholesterol levels from 0.45 mmol/L (17.4 mg/dL) to 0.75 mmol/L (29.1 mg/dL) in men and 0.12 mmol/L (4.6 mg/dL) to 0.55 mmol/L (21.4 mg/dL) in women, thereby increasing life expectancy by 0.03 to 0.4 year and 0.01 to 0.16 year, respectively. Smoking cessation would increase life expectancy from 2.59 to 4.43 years among men and from 2.6 to 3.68 years among women. Among adult Canadians, dietary modification would save 373,000 to 683,000 person-years of life. The majority of these benefits would occur among men who start dieting at ages 30 to 59 years. Smoking cessation would add more than 4 million person-years of life to the Canadian population. The relative impact of either intervention among American adults would be similar to these Canadian estimates. Younger men, aged 30 to 59 years, might live slightly longer after dietary change, but among women and older men the average benefits would be negligible. The benefits of smoking cessation are more uniform across age and sex and are substantially greater than those predicted for dietary change. |
8042887 | Sleep apnea and sleep disruption in obese patients. | To describe the frequency and severity of sleep apnea in obese patients without a primary sleep complaint and to assess the sleep patterns of obese patients without apnea and compare them with the sleep patterns of nonobese controls. Prospective case series with historical controls in an obesity and sleep disorders clinic. Two hundred obese women and 50 obese men (mean body mass index, 45.3) consecutively referred for treatment of their obesity and 128 controls matched for age and sex. Eight-hour sleep laboratory recording, including electroencephalogram, electro-oculogram, electromyogram, and respirations. Subjectively reported sleep-related symptoms and signs were also recorded. Twenty men (40%) and six women (3%) demonstrated sleep apnea warranting therapeutic intervention. Another four men (8%) and 11 women (5.5%) showed sleep apneic activity that warranted recommendation for evaluation in the sleep laboratory. In contrast, none of the 128 controls demonstrated sleep apneic activity severe enough for therapeutic intervention. The best clinical predictors of sleep apnea in the obese population were severity of snoring, subjectively reported nocturnal breath cessation, and sleep attacks. Obese patients, both men and women, without any sleep-disordered breathing demonstrated a significant degree of sleep disturbance compared with nonobese controls. Wake time after sleep onset, number of awakenings, and percentage of stage 1 sleep were significantly higher in obese patients than in controls, while rapid eye movement sleep was significantly lower. Severely or morbidly obese men are at extremely high risk for sleep apnea and should be routinely evaluated in the sleep laboratory for this condition, while for severely or morbidly obese women the physician should include a thorough sleep history in the clinical assessment. |
8042885 | Laboratory diagnosis of factitious disorders. | Self-induced factitious disorders are defined and distinguished from conditions they may resemble. Review of the literature since 1965 indicates much more frequent reporting in recent years, but most health care providers are still not sufficiently aware of the common factitious disorder. Up to 5% of physician-patient encounters may be because of factitious disorders, but these are only suspected when the workup leads to contradictory findings. Laboratory tests are often the only definitive diagnostic method, and clinicians may not be familiar with current technologies. Some clinical clues are listed; heightened awareness and the need for early diagnosis are emphasized. Discordant laboratory results should raise the possibility of a factitious disorder. Sophisticated laboratory tests that can accurately assay very small amounts of specific hormones or foreign substances in body fluids facilitate the diagnosis. The primary physician can now confirm an initial clinical diagnosis of factitious disorder promptly and directly rather than only by exclusion. |
8042884 | Perioperative care of the renal patient. | Due to the hormonal and hemodynamic alterations inherent in the surgical experience, acute renal failure is common during the perioperative period. Acute renal failure occurs in 5% of hospital admissions, and the surgical setting is the second most common cause of inpatient acute renal failure. Because this setting has the highest mortality for acute renal failure, recognition of high-risk patients is essential for careful monitoring and prophylactic measures. Patients with chronic renal insufficiency, elderly patients, jaundiced patients, diabetics, and those undergoing cardiac or aortic surgery are at greatest risk for perioperative acute renal failure. Patients with severe chronic renal failure or end-stage renal disease are at significant risk for development of complications during the perioperative period, due both to renal and nonrenal reasons. Hyperkalemia, infections, arrhythmias, and bleeding commonly occur in these patients during the perioperative period. This population has a reasonable surgical mortality for both general and cardiac surgery, but the extremely high morbidity warrants careful perioperative monitoring and care. |
8042882 | False changes in CA 125 levels in ovarian cancer patients after infusion of OC125 fragments for diagnostic and therapeutic purpose. | The influence of human anti-OC125 antibodies formed after multiple infusions of OC125 F(ab')2 fragments on the apparent levels of CA 125 measured with four different tests were examined in two ovarian cancer patients. With the homologous Assay 1, involving only OC125 antibodies, false increases of CA 125 values were observed after infusion of OC125 fragments, which completely covered real CA 125. In contrast, with Assay 2, 3 and 4, which involve no OC125 antibodies as capture antibodies, only slight false increases occurred in the presence of very high anti-OC125 antibody concentrations. Interference was eliminated by addition of non-specific murine IgG in Assay 2 and 4, but not in Assay 1 and 3 indicating that the false increases in Assay 1 and 3 were caused by anti-idiotypic anti-OC125 antibodies. In the presence of elevated real CA 125, with Assay 2 and to a considerably lesser degree with Assay 4, an inhibitory effect of anti-OC125 antibodies became evident leading to false decreases of CA 125 values. In Assay 4 reduction of assay response was eliminated by addition of nonspecific murine IgG. The results confirm that all available CA 125 tests are influenced by interference with human anti-OC125 antibodies. Thus, CA 125 levels in patients who have been treated with OC125 fragments should be interpreted with care. |
8042881 | Late recurrence of fallopian tube carcinoma in an incisional hernia. | A 53 year old woman who had surgery for carcinoma of the Fallopian tube had an operation for an incisional hernia 15 years later. Histology of resected tissues revealed metastatic Fallopian tube carcinoma. |
8042879 | Pneumomediastinum in labor. | We describe pneumomediastinum in a primigravida with delay in the second stage of labor. The pathophysiology, clinical presentation, and management are reviewed. |
8042880 | Idiopathic dilated cardiomyopathy in pregnancy. | We report a 34-year-old woman who presented at 21 weeks with cardiac failure due to idiopathic dilated cardiomyopathy. Following refusal of pregnancy termination, she was treated conservatively with good maternal and neonatal outcome. |
8042878 | Skeletal maturation and hormonal levels after the menarche. | Skeletal maturity was studied in 82 healthy adolescent girls age between 12 and 19 who had reached the menarche from 0.5 to 5 years previously. 56 subjects (68.2%) had closed epiphyses while they were open in 26 (31.8%). The incidence of open epiphyses was 61% in the first year after the menarche and progressively decreased showing negative correlation with time elapsed since the menarche (r = 0.98, P < 0.0001). The mean +/- SE height increased from 158.7 +/- 1.3 cm in the first year after the menarche, to 162.7 +/- 1.3 cm in the fifth year after the menarche. No significant differences were seen in estradiol, estrone, testosterone, dihydrotestosterone and androstenedione levels between subjects with open or closed epiphyses while dehydroepiandrosterone and its sulfate levels were higher in the closed epiphyses group. Girls with open epiphyses at first evaluation grew about 3.5 cm in the next three years. |
8042877 | The value of Doppler ultrasound in the diagnosis and management of twin-to-twin transfusion syndrome. | To evaluate the efficiency of the Doppler examination of umbilical arterial blood flow for the antenatal diagnosis and the monitoring of fetal condition during intrauterine treatment of twin-to-twin transfusion syndrome (TTTS), we studied 33 pairs of twins including 5 TTTS cases. In all cases umbilical arterial blood flow was examined by Doppler ultrasound and pulsatility index (PI) was calculated as umbilical arterial impedance. In twins with TTTS, PI of the recipient was outside the normal range and the difference of PI was greater than +0.5. In discordant twins without TTTS and concordant twins, the PI was within the normal range and the difference of PI ranged from -0.5 to +0.5. In 2 cases these findings were found before the appearance of fetal hydrops. In 2 TTTS cases transmaternal digitalization prevented the development of hydrops in the recipient. The difference of PI decreased with improvement in the fetal condition, and vice versa. Our data suggested that, in cases with TTTS, Doppler examination of umbilical arterial blood flow was effective in predicting fetal hydrops. Doppler was also very useful for monitoring the fetal condition during intrauterine treatment. |
8042876 | A survey of non-cardiac fetal intrathoracic malformations diagnosed by ultrasound. | Between November 1986 and April 1993, 22 cases of intrathoracic abnormality were detected prenatally by ultrasound, and examined postnatally. There were 11 cases of diaphragmatic hernia, 5 cases of cystic adenomatoid malformation of lung, one case of chylothorax, two cases of lung sequestration, and three cases of bronchogenic cyst. The total number of deliveries during that period was 48,281 and the total number of major anomalies at that time was 669 (1.38%). Cases of hydrothorax of various etiology, as well as thoracic cage anomalies were excluded. Prenatal diagnosis allows planned delivery and the assembly of neonatologists and pediatric surgeons. |
8042875 | Amniocentesis in mothers who are hepatitis B virus carriers does not expose the infant to an increased risk of hepatitis B virus infection. | Sixty-seven pairs of mothers with hepatitis B virus (HBV) surface antigen (HBsAg) and their infants were divided into two study groups to determine the effect of amniocentesis on intrauterine HBV infection. In the first study group (35 pairs), the infant's HBsAg status in cord blood was studied and the results were compared with those obtained in the cord blood from 65 infants born to HBsAg-positive women who did not have an amniocentesis. In the second study group (32 pairs), the HBV status of the infants was studied at the age of three months to five years and compared with the HBV status of 3,454 infants in the National HBV Prevention Program. In the first study group, one sample (2.9%) was weakly positive for HBsAg; while in the first control group, two (3.1%) were positive. In the second study group, three (10%) infants were positive for HBsAg. The failure rates of immunoprophylaxis in the second study and control groups were similar (9.4% vs 11% for HBsAg carrier mothers; 30% vs 14% for HBe antigen-positive carrier mothers). This suggested that genetic amniocentesis did not increase the risk of intrauterine HBV infection. |
8042874 | Evaluation of adjuvant therapy after surgery for primary carcinoma of the fallopian tube. | To evaluate the impact of postoperative therapy (chemotherapy vs. irradiation) on overall survival. A nationwide retrospective analysis. Hanusch-Krankenhaus, Department of Gynaecology, 115 patients with histologically proved primary carcinoma of the Fallopian tube: 49 received six treatment cycles of a cis-platinum regimen (group I), 24 patients were treated by full irradiation using 50 Gray minimum (group II). The two groups had a similar distribution of stage I and II; in the more advanced stages chemotherapy was the predominant method of treatment. The five-year survival rate was 53% for women receiving irradiation as against 27% for those given cis-platinum. If the analysis was restricted to those patients with comparable stage I and stage II lesions, the p-value (0.07) was of borderline significance. There was no advantage in adding abdominal to pelvic irradiation (P = 0.62). Stage I and stage II carcinoma is probably better treated postoperatively by radiotherapy than chemotherapy. Chemotherapy may have more therapeutic potential in patients with more advanced lesions. |
8042873 | Glandular inclusions in lymph nodes: pattern of distribution and metaplastic transformation. | Pelvic and paraaortal lymph nodes of 499 gynecologic cancer patients were screened for the occurrence of metaplastic changes and their topographic pattern. Glandular inclusions in lymph nodes were distributed evenly across all lymphatic areas and there was no correlation to the extent and the kind of carcinoma. In most cases the benign nature of these inclusions was obvious even in the presence of metaplasias and there was no difficulty in differentiating them from metastases. |
8042872 | Falling apart: a process integral to the remodeling of male incest offenders. | This article describes the falling apart component of a theoretical framework for incest offenders, the remodeling process. Methodology included 20 audiotaped interviews, 65 direct observations during group therapy, and record analysis of a theoretical sampling of adult male incest offenders currently in, graduates of, and dropouts from a community sexual abuse treatment program. Constant comparative analysis was used to collect and analyze data concurrently. Falling apart, a dynamic multifaceted process, occurs first when offenders are discovered, can be life-threatening, and few resources are presently available. Dimensions, properties, strategies, and contexts are discussed. |
8042871 | Patterns of coping and characteristics of high-functioning incest survivors. | An exploratory study using a phenomenological approach was designed to examine methods of coping and adaptation that may facilitate a healthy adjustment after sexual abuse. In-depth interviews were conducted with a sample of 15 high-functioning adult female incest survivors. The results identify the capacity of sexually abused children to use avoidance strategies and use psychological escape mechanisms to cope with the abuse; and helped explicate the adult process of separation, self-discovery, and revisiting the past trauma. The victim's cognitive appraisals and responses emerged as important variables in managing the trauma of sexual abuse. The capacity to protect the integrity of the self appeared central to the adult developmental process of integrating the incest experience. |
8042870 | Psychiatric hospitalization as an experience of trauma. | The experience of being a client in a locked, inpatient psychiatric unit can be considered trauma-producing. This article examines that phenomenon, offers suggestions for reform, and recommends dialogue for further change. |
8042869 | An attributional study of seclusion and restraint of psychiatric patients. | This descriptive study used two attributional frameworks to examine the causes psychiatric inpatients and nurses gave for the seclusion and restraint of patients. Patients were interviewed in restraints. The reasons patients and nurses gave for the patients restraint were recorded verbatim. A nominal system using the recorded responses was developed by two attribution researchers and were also coded along the dimensions of locus, controllability, and stability. The findings supported attribution theory and research in that most patients and nurses gave causes for the patients' restraint. However, the data suggest more research is needed in this area. |
8042867 | Depression in hospitalized medically ill elders: evolution of the concept. | Recent research confirms high prevalence rates of major depression and appreciable depressive symptoms in hospitalized medically ill elders. Evidence also exists supporting that depressive symptoms, when combined with medical illness, have additive effects on patient function and well-being, in addition to raising the older person's risk of death from suicide as well as from nonsuicidal causes. Appropriate nursing identification and management of this problem is currently hindered by an unclear description of depression in these patients. The focus of this article will be a synthesis of the existing knowledge of depression in elderly patients hospitalized with medical illness. An evolving concept of depression will be described that is amenable to clinical nursing research with this population. |
8042866 | Perceptions of inner city substance abusers about their families. | This study involved 12 in-depth interviews of inner city rehabilitating substance abusers. An exploration of their perception about their families of origin and their families of today was the purpose of this study. The topic outline, coding system, and qualitative analysis was guided by concepts of the framework of systemic organization. Common family characteristics were lack of togetherness, nonexistent or peripheral role of fathers, and underused or overused controlling power with victimization of the weakest. Regenerative strengths were seen in some families. Family integration of addicts seemed more difficult than anticipated by the subjects and demanded major changes in family processes. |
8042865 | Lifelong maternal caregiving for children with schizophrenia. | Maternal caregiving for adult children with schizophrenia is described using a lifespan perspective. Principles of naturalistic inquiry and a grounded-theory design guided field work methods. Nineteen in-depth interviews with ten participants averaged 4 hours each. Data analysis involved coding and classifying themes, constant comparison, and saturating theme categories. A model depicts findings including stages of learning in the experience. The stages are as follows: (1) perceiving a problem; (2) searching for solutions; (3) enduring the situation; and (4) surviving the experience. Implications include use of the model in developing intervention and education models. |
8042864 | Potential health hazards of pornography consumption as viewed by psychiatric nurses. | Adverse effects of pornography consumption (PC) have been identified from over 150 empirical studies conducted since 1970. Yet, the practice literature of psychiatric nurses does not address the health risks of PC. This study determines the perceptions of psychiatric nurses (n = 194) with regard to PC effects. A significant majority of psychiatric nurses agreed (72%) that there are potential adverse effects to PC, that there are risks for preadult consumers of pornography (78% agreement), and that PC risks need to be addressed by their profession (68% agreement). Agreement lends support for expanding nurses' knowledge concerning PC. |
8042863 | Measurement of HBsAg to monitor hepatitis B viral replication in patients on alpha-interferon therapy. | HBsAg was measured quantitatively in serum samples collected serially before and after the HBeAg seroconversion date from 69 patients with HBeAg seroconversion and 17 patients with both HBeAg and HBsAg seroconversion. In patients with only HBeAg seroconversion the median HBsAg level decreased from 8.39 micrograms/ml (range 0.01-57.51) before HBeAg seroconversion to 3.53 micrograms/ml (range 0.002-68.66) after seroconversion (P < 0.001). No significant drop in HBsAg was found for the control group (18 HBeAg-positive patients without seroconversion). From 12 other patients on alpha-interferon therapy HBsAg was quantitatively assayed monthly during and after therapy; HBsAg levels were compared to the levels of HBV-DNA and HBeAg. We observed a good correlation between the HBsAg level and both the HBV-DNA (r = 0.76; P < 0.001) and the HBeAg (r = 0.70; P < 0.001) level, irrespective of the response to alpha-interferon. Quantified assessment of HBsAg appears promising as a simple and cheap method for monitoring viral replication in chronic hepatitis B in patients undergoing interferon therapy. |
8042862 | Solar simulator-induced herpes simplex labialis: use in evaluating treatment with acyclovir plus 348U87. | Models of UV radiation induced herpes labialis utilizing crude light sources have previously been used to examine the efficacy of antivirals. We sought to improve upon this model by using a solar simulator. Initial studies revealed that 13 of 34 (38%) subjects with a history of recurrent HSV labialis receiving three minimal erythema doses (MED's) of UV light developed herpes labialis. We next evaluated the effects of combined therapy with topical ACV and 348U87, a ribonucleotide reductase inhibitor, begun immediately after UV exposure for the prevention and treatment of herpes labialis. No significant reduction in the incidence or severity of herpes labialis was detected although the study was terminated after the interim analysis revealed no benefit, thus reducing the power to detect a difference. This lack of effect may be explained by the general poor efficacy of topical treatment for recurrent HSV infection. Further studies of ACV + 348U87 in vehicles that should increase the penetration and stability of the drugs are planned. |
8042861 | Pharmacokinetics and antiviral activity of a novel isonucleoside, BMS-181165, against simian varicella virus infection in African green monkeys. | A novel nucleoside analog BMS-181165 with potent activity against varicella-zoster virus was tested for efficacy in a simian varicella virus infection in African green monkeys. BMS-181165 was effective in preventing the development of a rash, decreasing the development of viremia and preventing death in infected monkeys when administered orally at 4, 16 or 64 mg/kg/day. The compound is well orally absorbed in monkeys, between 44 to 50% oral bioavailability, and may prove of value in therapy of varicella-zoster infections in humans. |
8042860 | Cyclocreatine (1-carboxymethyl-2-iminoimidazolidine) inhibits the replication of human herpes viruses. | The creatine kinase/creatine phosphate (CK/CrP) system plays an important role in cellular energy homeostasis. CK isoenzymes, which reversibly generate ATP from CrP, are compartmentalized at cellular sites where energy is produced or utilized. It has been noted that the expression of CK is induced in cells infected by several DNA viruses, implicating a role for cellular energy modulation as an important step for efficient viral replication. A CK substrate analog, 1-carboxymethyl-2-iminoimidazolidine (cyclocreatine; CCr), was tested in vitro for antiviral activity against a variety of herpes viruses and RNA viruses. Several members of the human herpes virus family were found to be sensitive to CCr, including herpes simplex types 1 and 2 (HSV-1 and HSV-2). varicella-zoster virus, and cytomegalovirus. When administered to mice infected vaginally with HSV-2, CCr significantly reduced mortality, reduced vaginal lesion scores, and lowered the titers of recoverable virus. This treatment combined with acyclovir appeared to enhance the antiviral effects of acyclovir. In a second model, mice infected intraperitoneally with HSV-2 and treated with CCr showed a significant increase in survival compared to placebo. We conclude that CCr is the first example of a new class of antiviral compounds that target the CK/CrP system. |
8042859 | Cytokine regulation of lactate dehydrogenase-elevating virus: inhibition of viral replication by interferon-gamma. | The mechanisms which regulate the replication of lactate dehydrogenase-elevating virus (LDV), a persistent murine model virus which infects macrophages, are unclear. For this study, the effects of murine recombinant interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) on LDV replication were examined. LDV permissiveness was reduced in macrophages obtained from uninfected mice treated with IFN-gamma prior to cell harvest and in vitro LDV infection. Virus inhibition by IFN-gamma was also observed when neonatal LDV-infected mice were injected with this cytokine prior to macrophage harvest and analysis of LDV replication-positive cells. Persistently LDV-infected mice demonstrated an increase in viremia levels following treatment with TNF-alpha. Neither IFN-gamma nor TNF-alpha had any direct in vitro effect on LDV replication in cultured macrophages, suggesting that the actions of these cytokines required secondary or accessory in vivo events. These results provide evidence for cytokine-mediated regulation of LDV infection and support a role for the immune system in the LDV-host relationship. |
8042850 | Pharmacological implications of the flow-dependence of vascular smooth muscle tone. | The recognition that the wall tone of most arteries and veins can change in response to shear stress has several implications for our understanding of the effects of drugs on the circulation. By a primary action on the heart and vasculature, drugs can cause changes in cardiac output and blood pressure that lead to changes in blood flow. These changes in blood flow can secondarily change vascular diameter, thus complicating the basic response. Furthermore, drugs can modify the local flow-sensitive mechanism directly. The flow-initiated effect seems to depend, both qualitatively and quantitatively, on the level of wall tone and is not entirely endothelium-dependent. If the primary action of a drug is to alter the tone level of vascular smooth muscle directly or if tone changes as a result of a change in blood pressure (and thus in local myogenic control), then it follows that these changes in turn influence the flow response, both quantitatively and qualitatively. The vascular response to flow is complex both in its site of origin and the functional changes initiated. It is not synonymous with the endothelial-dependent action of acetylcholine. |
8042849 | Complement activation and inhibition in myocardial ischemia and reperfusion injury. | The myocardial inflammatory response that occurs as a result of ischemia and reperfusion is similar to that which occurs in other tissues. Activation of the complement system is an integral part of the initiation and maintenance of any inflammatory response. It and other immune system mediators participate in the promotion of neutrophil adherence to endothelium by modulating expression of various adhesion molecules. The complement system also serves an integral role in mediating neutrophil activation, the results of which have been documented in the setting of myocardial ischemia and reperfusion. Another aspect of the complement cascade, which has received little attention with respect to the heart, is the direct effects of complement activation such as endothelial and myocardial cell cytotoxicity mediated by the membrane attack complex. It is likely that this form of tissue injury contributes significantly to myocardial reperfusion injury. Given the numerous contributions of the complement system to the generation of the inflammatory response, and to directly-mediated tissue injury, selective inhibitors of the complement system have great potential to limit reperfusion injury. This has already been demonstrated for the complement inhibitor sCR1. In the future, it is likely that any therapeutic treatment of reperfusion injury will include modulation of the effects of complement activation. |
8042848 | Mechanisms of aflatoxin carcinogenesis. | Much progress has been made in elucidating the biochemical and molecular mechanisms that underlie aflatoxin carcinogenesis. In humans, biotransformation of AFB1 to the putative carcinogenic intermediate. AFB-8,9-exo-epoxide, occurs predominantly by cytochromes P450 1A2 and 3A4, with the relative importance of each dependent upon the relative magnitude of expression of the respective enzymes in liver. Genetic variability in the expression of these and other cytochromes P450 may result in substantial interindividual differences in susceptibility to the carcinogenic effects of aflatoxins. Detoxification of AFB-8,9-epoxide by a specific alpha class glutathione S-transferase is an important protective mechanism in mice, and it accounts for the resistance of this species to the carcinogenic effects of AFB. This particular form of GST is expressed constitutively only at low levels in rats, but it is inducible by antioxidants such as ethoxyquin, and it accounts for much of the chemoprotective effects of a variety of substances, including natural dietary components that putatively act via an "antioxidant response element" (ARE). In humans, the constitutively expressed GSTs have very little activity toward AFB1-8,9-exo-epoxide, suggesting that--on a biochemical basis--humans should be quite sensitive to the genotoxic effects of aflatoxins. If a gene encoding a high aflatoxin-active form of GST is present in the human genome, but is not constitutively expressed, and is inducible by dietary antioxidants (as occurs in rats), then chemo- and/or dietary intervention measures aimed at inducing this enzyme could be highly effective. However, as it is possible that human CYP 1A2 may also be inducible by these same chemicals (because of the possible presence of an ARE in this gene), the ultimate consequence of dietary treatment with chemicals that induce biotransformation enzymes via an ARE is uncertain. The balance of the rate of activation (exo-epoxide production) to inactivation (GST conjugation plus other P450-mediated non-epoxide oxidations) may be a strong indicator of individual and species susceptibility to aflatoxin carcinogenesis, if the experimental conditions are reflective of true dietary exposures. There is strong evidence that AFB-8,9-exo-epoxide binds to G:C rich regions of DNA, forming an adduct at the N7-position of guanine. Substantial evidence demonstrates that AFB1-8,9-epoxide can induce activating mutations in the ras oncogene in experimental animals, primarily at codon 12.(ABSTRACT TRUNCATED AT 400 WORDS) |
8042847 | Alpha 1-adrenergic receptor subtypes. | Investigators have not yet reached a consensus on the number and signaling mechanisms of alpha 1-adrenergic receptor (AR) subtypes. Two native subtypes (alpha 1A and alpha 1B) can be distinguished pharmacologically, and three subtypes (alpha 1B, alpha 1C, and alpha 1D) have been cloned. One of the cloned subtypes (alpha 1D) was originally thought to encode the pharmacologically defined alpha 1A subtype. However, recent data suggest otherwise, and many investigators now agree that the alpha 1A subtype has probably not yet been cloned. The relationship between the cloned receptors and the native subtypes must be understood, and any additional cDNA clones obtained, before the drug specificities and second messenger pathways of alpha 1-AR subtypes can be clearly defined. Little is yet known about the cellular and tissue distribution of these subtypes, their developmental profiles, or their functional importance. Molecular cloning of complementary DNA sequences for the remaining subtypes will help to clarify the number and properties of these subtypes. Identification of drugs that can selectively target particular subtypes is an important goal that may result in therapeutic advances in numerous disease states, including benign prostatic hyperplasia. The newly recognized complexity of the adrenergic receptors presents us with both important challenges and new therapeutic targets. The potential impact of this field on medical therapeutics remains to be clearly defined. |
8042827 | Joseph Goldberger: an unsung hero of American clinical epidemiology. | Pellagra, a disease rarely seen in developed countries today, was common during the first half of this century in the United States. The disease was initially believed to be infectious, and severe "pellagraphobia" left many victims and their families ostracized. This paper calls attention to Joseph Goldberger, an American physician whose remarkable research helped correct the erroneous belief in an infectious cause for pellagra and led to the elimination of pellagra epidemics in the United States. |
8042826 | The cardiomyopathy of overload: an unnatural growth response in the hypertrophied heart. | Heart failure is a progressive condition with a 5-year survival of less than 50%. This poor prognosis, which can be reproduced by overloading the hearts of experimental animals, may reflect molecular abnormalities caused when overload stimulates adult cardiac myocytes to undergo hypertrophy. Because these terminally differentiated cells have little or no capacity to divide, hypertrophy represents an unnatural growth response; however, the mechanism by which overload shortens survival remains speculative. Modification of this unnatural growth response by converting enzyme inhibitors and nitrates, which have growth inhibitory as well as vasodilator effects, may contribute to the ability of these drugs to improve prognosis in patients with heart failure. |
8042825 | Limitations of angiography for analyzing coronary atherosclerosis progression or regression. | To analyze the utility and limitations of serial coronary angiography for determining atherosclerosis progression and regression. A MEDLINE search of the English-language literature (1966 to January 1994) using the keywords atherosclerosis regression, atherosclerosis progression, lipid reduction therapy, and coronary angiography. Selected articles on the effects of cholesterol reduction and lifestyle modification on angiographic coronary artery disease, on the animal models of atherosclerosis progression and regression, and on the limitations of coronary angiography. Independent extraction by two authors. Although several studies have reported that the rate of atherosclerosis progression, defined by serial coronary angiography, can be reduced and that luminal diameter can be improved somewhat by aggressive lipid modification, the reported changes are small (0.3 mm or 10% change) and have required a prolonged study duration (range, 1 to 10 years). More importantly, angiography simply does not measure atherosclerosis and cannot assess lesion composition. Angiography also underestimates the extent of atherosclerosis, especially in angiographically normal segments. In addition, difficulties with data acquisition, such as substantial variabilities in serial measurements of percent diameter stenosis and minimal luminal diameters, require large sample sizes to show statistically significant regression, even with computerized quantification. Given its current limitations, serial coronary angiography is not a satisfactory means of detecting atherosclerosis progression or regression. |
8042823 | An outbreak of fatal fluoride intoxication in a long-term hemodialysis unit. | To determine the cause of an outbreak of acute illness and death in a long-term hemodialysis unit. A retrospective cohort and case-control study of patients receiving hemodialysis and a laboratory study of a model deionization system to purify water for hemodialysis. An outpatient hemodialysis unit of a university hospital. 12 patients who became severely ill after hemodialysis treatment and 20 patients who did not become ill after receiving hemodialysis treatment in the same unit. Medical and dialysis unit records were reviewed to identify and characterize cases. Fluids for dialysis were tested for toxic substances, and fluoride was measured in patients' serum. Resistivity and fluoride were measured in effluent from a model deionization system operated in the same way as the system associated with illness. During five consecutive hemodialysis shifts, 12 of 15 patients receiving dialysis treatment in one room became acutely ill, with severe pruritus, multiple nonspecific symptoms, and/or fatal ventricular fibrillation (3 patients). None of 17 patients treated in the adjacent room became ill (P < 0.0001). Death was associated with longer hemodialysis time and increased age compared with other patients who became ill. Serum concentrations of fluoride in the sick patients were markedly increased to as high as 716 mumol/L, and the source of fluoride was the temporary deionization system used to purify water for hemodialysis only in the affected room. Operation of a model deionization system showed how fluoride was adsorbed and then displaced in a massive efflux. Because deionization systems are used widely in hemodialysis and can cause fatal fluoride intoxication, careful design and monitoring are essential. |
8042821 | Preserving renal function in patients with membranous nephropathy: daily oral chlorambucil compared with intermittent monthly pulses of cyclophosphamide. | To compare oral chlorambucil and intravenous cyclophosphamide-based drug regimens in the treatment of patients with membranous nephropathy and deteriorating renal function. Randomized study. University hospital and teaching hospitals. 18 patients with membranous nephropathy, a nephrotic syndrome, and deteriorating renal function. Chlorambucil (0.15 mg/kg body weight per day orally in months 2, 4, and 6) and prednisone (three intravenous pulses of 1 g of methylprednisolone followed by oral prednisone at 0.5 mg/kg per day in months 1, 3, and 5) or intravenous cyclophosphamide (750 mg/m2 body surface area once every month for 6 months) and methylprednisolone (three intravenous 1-g pulses in months 1, 3, and 5). Serum creatinine, serum cholesterol, serum albumin, and urinary protein levels. Before treatment, no statistical differences were found between the treatment groups. Six months after treatment was started, serum creatinine levels had decreased in the group treated with chlorambucil, methylprednisolone, and prednisone from a mean of 260 +/- 112 mumol/L to 186 +/- 74 mumol/L (P = 0.003) and had increased in the group treated with intravenous cyclophosphamide and methylprednisolone from 218 +/- 85 mumol/L to 297 +/- 143 mumol/L (P = 0.02; difference between both groups, P < 0.001). Serum albumin levels increased in both groups by 9 and 6 g/L, respectively, and the urinary protein/creatinine ratio decreased by 2.6 and 3.1 g/10 mmol, respectively. At the end of follow-up (median, 15 months; range, 6 to 36 months), one patient in the chlorambucil group and four patients in the cyclophosphamide group had reached end-stage renal failure after 36, 12, 12, 18, and 18 months of therapy, respectively. One patient in the intravenous cyclophosphamide group died after 6 months of therapy. Thus far, both oral chlorambucil and oral cyclophosphamide have been shown to be effective in the treatment of patients with membranous nephropathy and deteriorating renal function. Our study shows that intermittent monthly pulses of low-dose cyclophosphamide are ineffective in preserving renal function in such patients. |
8042822 | Herpes simplex virus infection as a cause of benign recurrent lymphocytic meningitis. | To identify the role of herpes simplex virus (HSV) in causing benign recurrent lymphocytic meningitis. Prospective cohort study. Tertiary referral center. 20 consecutive patients with a provisional diagnosis of benign recurrent lymphocytic meningitis had cerebrospinal fluid specimens submitted between 1990 and 1993 to the diagnostic virology laboratory. Thirteen patients met our criteria for benign recurrent lymphocytic meningitis. Herpes simplex virus DNA was detected in cerebrospinal fluid specimens using the polymerase chain reaction, followed by hybridization with a HSV-specific DNA probe. Herpes simplex virus type 1 and type 2 DNA products were distinguished by digestion with restriction enzymes and analysis by gel electrophoresis. Anti-HSV antibodies in cerebrospinal fluid were detected by immunoblot. The patients had 3 to 9 attacks (mean, 4.6 attacks) of benign recurrent lymphocytic meningitis during periods ranging from 2 to 21 years (mean, 8.4 years). Three of 13 patients had known recurrent genital herpes. Cerebrospinal fluid analysis showed 48 to 1600 cells/microL, glucose levels of more than 2.22 mmol/L (40 mg/dL), and protein levels of 41 to 240 mg/dL (0.41 to 2.4 g/L). Herpes simplex virus DNA and anti-HSV antibodies were detected in cerebrospinal fluid samples in 11 of 13 patients (84.6%; 95% CI, 55% to 98%). Ten of these 11 patients had HSV type 2 DNA and HSV type 2 antibodies. One patient had HSV type 1 DNA and HSV type 1 antibodies in the cerebrospinal fluid. The remaining two patients had only anti-HSV type 2 antibodies. Herpes simplex virus, predominantly HSV type 2, was the major agent causing benign recurrent lymphocytic meningitis that met our specified diagnostic criteria. |
8042820 | The metyrapone and dexamethasone suppression tests for the differential diagnosis of the adrenocorticotropin-dependent Cushing syndrome: a comparison. | To develop criteria for interpreting results of the metyrapone test for the differential diagnosis of the adrenocorticotropin (ACTH)-dependent Cushing syndrome and to compare its diagnostic accuracy with that of the high-dose dexamethasone suppression test. Retrospective cohort study. Inpatient research ward. 186 patients believed to have the ACTH-dependent Cushing syndrome who had the metyrapone test, the dexamethasone test, and a surgical procedure to remove the source of excessive ACTH. The sensitivity, specificity, and diagnostic accuracy were determined for the metyrapone test using urine excretion of hydroxysteroid and plasma levels of 11-deoxycortisol. For the dexamethasone suppression test, urine excretions of 17-hydroxysteroid (17-OHS) and free cortisol were used. 156 patients had pituitary disease, 15 had ectopic ACTH secretion, and 15 had no diagnosis after pituitary surgery. Of those 15 patients, 14 were ultimately classified as having pituitary disease on the basis of follow-up, and 1 was found to have ACTH-independent Cushing syndrome. After administration of metyrapone, stimulation of 17-OHS excretion greater than 70% or of a plasma 11-deoxycortisol level greater than 400-fold did not result in the misclassification of any of the patients with surgically confirmed cases of ectopic ACTH secretion. When these criteria were combined, the percentage of correct predictions (122 of 186 [71%; 95% CI, 62% to 79%]) was higher than that for either steroid alone (116 of 186 [62%; CI, 52% to 71%]) for excretion of 17-OHS and that for plasma 11-deoxycortisol (82 of 186 [44%; CI, 34% to 54%]). When the criteria for both the metyrapone test and the dexamethasone test were combined, the percentage of correct predictions (153 of 186 [82%; CI, 75% to 87%]) was higher than that obtained when the criteria for either test alone were used (P = 0.001). Similar results were found when the 15 patients with indeterminate surgery were assigned to the appropriate group on the basis of follow-up. When the criteria for both the metyrapone and dexamethasone tests were combined to identify patients with the pituitary Cushing syndrome, the sensitivity and diagnostic accuracy improved to 88% and 89%, respectively. The metyrapone test, which can be done in 48 hours, has a sensitivity and specificity for the diagnosis of the Cushing syndrome identical to that of the standard 6-day high-dose dexamethasone suppression test. Combining both tests results in greater accuracy than that obtained with either test alone. |
8042819 | Risks for major bleeding from thrombolytic therapy in patients with acute pulmonary embolism. Consideration of noninvasive management. | To assess the relative risks for bleeding with thrombolytic therapy in patients who are managed using pulmonary angiograms compared with those managed using noninvasive tests, primarily the ventilation-perfusion lung scan. A decision analysis based on data from other studies. The risk for major bleeding in patients with pulmonary embolism who receive thrombolytic therapy after a noninvasive diagnosis was assessed from complications of thrombolytic therapy in patients with myocardial infarction, assuming that the same risk ratio for major bleeding when comparing an invasive with a noninvasive approach applied to patients with pulmonary embolism. The risk ratio was 3.3 (95% CI, 1.5 to 9.8) for major bleeding in patients with myocardial infarction. One or more major complications of pulmonary angiography occurred in 1.3% of patients (CI, 0.6% to 1.9%). The average reported risk was 14% (18 of 129 patients) (CI, 7.9% to 20.1%) for major bleeding in patients who had pulmonary angiography before receiving tissue plasminogen activator (tPA). The estimated risk was 4.2% (estimated CI, 1.4% to 9.3%) for major bleeding with tPA after a noninvasive diagnosis of pulmonary embolism. Assuming a risk of 1.3% for major complications from pulmonary angiography, a risk for major hemorrhage of 14.0% for an invasive diagnosis, and a risk of 4.2% for a noninvasive diagnosis, fewer complications would occur with noninvasive management if the prevalence of pulmonary embolism exceeded 21%. Among patients with suspected pulmonary embolism who are candidates for thrombolytic therapy, it is safer to use noninvasive diagnostic tests in many patients. |
8042818 | What we know about leadership. Effectiveness and personality. | Although psychologists know a great deal about leadership, persons who make decisions about real leaders seem largely to ignore their accumulated wisdom. In an effort to make past research more accessible, interpretable, and relevant to decision makers, this article defines leadership and then answers nine questions that routinely come up when practical decisions are made about leadership (e.g., whom to appoint, how to evaluate them, when to terminate them. |
8042816 | Jaw relaxation after a halothane/succinylcholine sequence in children. | Lack of complete jaw relaxation after a halothane-succinylcholine sequence has been described in the literature. To date, however, most existing studies are retrospective, and lack agreement on the magnitude and incidence of this phenomenon. This prospective study examined the incidence and degree of incomplete jaw relaxation in 500 children who were given intravenous succinylcholine during halothane anesthesia. Five hundred consecutive unmedicated children received a minimum dose of 2 mg/kg intravenous succinylcholine after induction of anesthesia with halothane. The degree of jaw relaxation was assessed 45-60 s later by the same observer using a standardized clinical scale. The degree of relaxation was correlated with the type of surgical procedure, and the presence and intensity of fasciculations. Complete relaxation (mouth opened easily and fully) occurred in 95.4% of study patients. Incomplete relaxation (firm manual separation required to open the mouth fully) was seen in 4.4% of the patients. One child (0.2%) had masseter muscle rigidity (mouth could not be fully opened but intubation possible). There were no incidents of trismus (teeth clamped shut and intubation via direct visualization impossible). The incidence of incomplete relaxation and masseter muscle rigidity did not correlate with the presence or degree of fasciculations or the type of surgical procedure. There were no clinical signs of a hypermetabolic state or myoglobinuria in any patient. Incomplete jaw relaxation after a halothane-succinylcholine sequence is not uncommon in children, and is considered a normal response. |
8042815 | Rapid 1% increases of end-tidal desflurane concentration to greater than 5% transiently increase heart rate and blood pressure in humans. | Large (0.5-1.0 MAC), rapid increases of desflurane to concentrations greater than 5% can transiently increase heart rate, mean arterial blood pressure (MAP), sympathetic nerve activity, and plasma epinephrine concentration. We tested the hypothesis that small (1% = 0.14 MAC), rapid increases of desflurane concentration to greater than 5% do not increase heart rate, blood pressure, and plasma catecholamine concentrations. Anesthesia was induced with intravenous propofol, 2 mg/kg, in 13 healthy male volunteers, 19-33 yr of age, and ventilation was controlled to maintain normocapnia. We gave 4% end-tidal desflurane in oxygen for 32 min and then imposed successive 1% increases in end-tidal desflurane concentration, each new concentration maintained for 4 min, to a final concentration of 12%. We measured heart rate, MAP and plasma catecholamine concentrations in the awake state, after 4 min at each 1% step, and at times of peak increase of MAP (> or = 10% change). Increases in heart rate and blood pressure of more than 10% occurred with 1% step-increases in only 1 volunteer at 5% desflurane but in 7-10 (MAP) and 8-12 (heart rate) of the 13 volunteers at higher desflurane concentrations. The 1% increases in desflurane concentration to greater than 5% also transiently increased plasma epinephrine concentrations but not vasopressin concentration or plasma renin activity in those volunteers in whom MAP increased. Small (1%) increases in desflurane concentration to and greater than 6% can transiently increase heart rate, mean arterial pressure, and plasma epinephrine concentration. These data and those from a previous study indicate that these increases occur with a lesser frequency and magnitude than those associated with a single, rapid step from 4% to 12% end-tidal desflurane. |
8042814 | Plasma and cerebrospinal fluid concentrations of morphine and morphine glucuronides after oral morphine. The influence of renal failure. | In patients with renal failure, morphine may cause prolonged narcosis and respiratory depression. Accumulation of the pharmacologically active metabolite morphine-6-glucuronide (M-6G) may explain this effect of morphine in patients with renal failure. After a single oral dose, morphine and its conjugates were measured in the plasma and the cerebrospinal fluid (CSF) in patients with renal failure. Eight patients with normal renal function and six patients with renal failure requiring dialysis were studied after operation under spinal anesthesia. Plasma and CSF concentrations of morphine, morphine-3-glucuronide (M-3G), and M-6G were measured by high-pressure liquid chromatography every 4 h for 24 h after an oral dose of 30 mg morphine. The area under morphine plasma concentration-time curve from 0 to 24 h increased from 38 +/- 4 ng.ml-1 x h in patients with normal renal function to 110 ng.ml-1 x h in those with renal failure (P < 0.01). In patients with renal failure, plasma concentrations of M-3G and M-6G were higher at 4 h and remained at an increased level until the end of the study. The peak CSF concentration of morphine at 8 h was similar in those with renal failure or normal renal function, 1.8 +/- 0.4 and 2.0 +/- 0.6 ng.ml-1 respectively. M-3G and M-6G in CSF reached a maximum at 12 h in patients with normal renal function, whereas in those with renal failure the concentrations gradually increased so that the highest concentrations were observed at 24 h. At 24 h, CSF M-6G concentration was 15 times greater in patients with renal failure than in those with normal renal function. We conclude that M-3G and M-6G readily cross the blood-brain barrier in patients with normal renal function or with renal failure. In patients with renal failure, the retention of plasma M-6G induces a progressive accumulation of this active metabolite in CSF; this accumulation may explain the increased susceptibility to morphine in patients with renal failure. |
8042813 | Bedside assessment of intravascular volume status in patients undergoing coronary bypass surgery. | Management of intravascular volume is crucial in patients after cardiopulmonary bypass as myocardial dysfunction is common. The purpose of this study was to validate a novel bedside technique for real-time assessment of intravascular volumes. Eleven patients undergoing cardiopulmonary bypass were studied. In addition to standard monitors, a fiberoptic thermistor catheter was placed in the descending aorta and central venous injections of 10 ml ice-cold indocyanine green dye were performed. Total blood volume was measured by a standard in vitro technique. Circulating and central blood volume were calculated by using cardiac output, mean transit times, and a newly developed recursive convolution algorithm that models recirculation. Measurements were performed after induction of anesthesia and at 1, 6, and 24 h after surgery. A two-compartment model of the circulation was required for adequate fit of the data. We found a significant correlation between total and circulating blood volumes (r = 0.87). One hour after surgery, central blood volume was decreased by 10% (P < 0.05). At 6 and 24 h after surgery, circulating blood volumes were significantly increased by 29% and 20%, respectively (P < 0.01), although central blood volume was similar to control values. Before surgery stroke volume index correlated with circulating blood volume (r = 0.87) but not with pulmonary capillary wedge and central venous pressures. This study shows that bedside determinations of intravascular blood volumes are feasible and that these measurements are more indicative of intravascular volume status than are either pulmonary capillary wedge or central venous pressures in the post-cardiopulmonary bypass period. Our data also demonstrate that despite a normal central blood volume both circulating and total blood volume are significantly increased in the immediate post-cardiopulmonary bypass period. |
8042812 | What is the best way to determine oropharyngeal classification and mandibular space length to predict difficult laryngoscopy? | Previous studies have suggested that the degree of visibility of oropharyngeal structures (OP class) and mandibular space (MS) length can predict difficult laryngoscopy. However, those studies were either inconsistent or omit description of how to perform these tests with regard to body, head and tongue position, and the use of phonation, hyoid versus thyroid cartilage and inside versus outside of the mentum. The purpose of this investigation was to determine which method of testing best predicts difficult laryngoscopy. In each of 213 consenting adults the OP class was determined in 24 method combinations: two body positions (sitting and supine), three head positions (neutral, sniff, and full extension), two tongue positions (in and out), and with and without phonation. In each patient MS length was measured in 24 method combinations: two body positions (sitting and supine), three head positions (neutral, sniff, and full extension), two distal end points (hyoid and thyroid cartilage), and two proximal end points (inside and outside of the mentum). In each patient the laryngoscopic grade was determined at the time of induction of anesthesia. We defined laryngoscopic grades III (n = 24) and 4 (n = 0) as difficult. The area under the receiver operating characteristic curve (ROC area) for each combination was used to compare the combinations and determine significant differences: ROC area = 0.5 implied a totally uninformative combination and ROC area = 1.0 a combination that predicted perfectly. Logistic regression analysis was used to calculate a predictor of difficult intubation that combined both OP class and MS length (the performance index). The performance index could then be used to calculate sensitivity, specificity, positive and negative predictive value, and probability of difficult intubation. The ROC areas for the different combinations used to assess OP class ranged from 0.78 to 0.94. The best combination was with the patient sitting, head in extension, tongue out, and with or without phonation. For MS length, the ROC areas ranged from 0.58 to 0.77; the best combination was the patient sitting, with the head in extension, with distance measured from the inside of the mentum to the thyroid cartilage. Combining the OP class and MS length (performance index = 2.5 X OP class - MS length in centimeters) significantly increased predictability of difficult intubation. At performance index = 0 and = 2, the probability of difficult intubation was 3.5% and 24%, respectively. With clinically relevant cutpoints for the performance index it was found that most difficult intubations could be predicted, but approximately half of those predicted to be difficult would in fact be easy. Based on the above ROC areas and ease of performing the test for the patient, we recommend that these tests be performed with patients in the sitting position, with the head in full extension, the tongue out, and with phonation, and with distance measured from the thyroid cartilage to inside of the mentum. Nevertheless, it is clear that these two tests, either used alone or in combination, will fail to predict a few difficult laryngoscopies and that they will predict difficult laryngoscopy in a significant number of patients in whom the trachea is easy to intubate. |
8042811 | Lower-extremity motor neuropathy associated with surgery performed on patients in a lithotomy position. | Motor neuropathy of a lower extremity is well-recognized as a potential complication of procedures performed on patients in a lithotomy position. Most of this awareness is based on anecdotal reports, however, and the incidence and risk factors for this complication have not been reported. We retrospectively reviewed the perioperative courses of 198,461 consecutive patients who underwent 1 of 56 surgical procedures historically performed on patients in a lithotomy position at the Mayo Clinic, Rochester, Minnesota, from 1957 to 1991 inclusive. The medical diagnoses of patients who had procedures in a lithotomy position were scanned for 26 diagnoses associated with neuropathy. Persistent neuropathy of the lower extremity was defined as a motor deficit of at least 3 months' duration. Risk factors anecdotally associated with persistent neuropathy were analyzed by comparing identified cases of neuropathy to controls in a 1:3 case-control study. Persistent neuropathies after procedures performed on patients in a lithotomy position were identified in 55 cases for a rate of 1 per 3,608. Multivariate risk factors for development of a persistent neuropathy of a lower extremity included duration in lithotomy of 4 h or longer, a body mass index (kilograms per squared meter) of 20 or less, and a history of smoking within 30 days of the procedure. Regional anesthetic techniques were not found to be associated with an increased risk of neuropathy. Of the 53 patients who lived at least 1 yr after their procedure, 24 (45%) required either prosthetic or ambulatory support for persistent foot drop or leg weakness. These data suggest that prolonged duration in lithotomy and patient risk factors, including very thin body habitus and smoking in the preoperative period, are associated with the development of a lower-extremity neuropathy after procedures performed on patients in a lithotomy position. A reduction of time in the lithotomy position may be particularly worthwhile for patients with these risk factors. |
8042810 | Influence of phenylephrine bolus administration on left ventricular filling dynamics in patients with coronary artery disease and patients with valvular aortic stenosis. | Left ventricular diastolic function is known to be impaired in patients with coronary artery disease and patients with valvular aortic stenosis. Phenylephrine is frequently administered as an intravenous bolus in these patients perioperatively to increase coronary perfusion pressure. Although this is common practice, there is no information about the effect of phenylephrine bolus administration on left ventricular filling dynamics. Twenty patients with coronary artery disease (group 1), 15 patients with valvular aortic stenosis (group 2), and 10 subjects without cardiovascular disease (group 3, control) entered the study. Left ventricular filling was evaluated using transesophageal pulsed Doppler echocardiography before and after phenylephrine injection given to patients whose mean blood pressure has decreased by more than 20% (and was not higher than 90 mmHg). We recorded the transmitral blood flow velocity curve and measured peak early and peak atrial flow velocity, acceleration and deceleration time of the early flow velocity peak, and mitral valve diameter. We calculated the ratio of peak early to peak atrial flow velocity (PE/PA), acceleration and deceleration rate of the early flow peak, and peak filling rate. Phenylephrine effectively restored arterial pressure in all three groups. However, in group 1, phenylephrine administration resulted in a reduction of PE/PA, acceleration rate of the early flow peak, and peak filling rate from 1.25 (mean) to 0.75 (P < 0.001), 411 to 276 cm/s2 (P < 0.001), and 439 to 305 ml/s (P < 0.001), respectively. In contrast, in group 2, intravenous phenylephrine increased PE/PA, acceleration rate of the early flow peak, and peak filling rate from 0.76 to 0.97 (P < 0.001), 365 to 503 cm/s2 (P < 0.05), and 321 to 388 ml/s (P < 0.01), respectively. In the control subjects, phenylephrine caused a transient reduction of PE/PA and peak filling rate from 1.71 to 1.39 (P < 0.001) and 618 to 524 ml.s-1 (P < 0.001), respectively. Phenylephrine bolus administration causes an alteration of left ventricular filling in coronary artery disease patients that seems to be more marked than that seen in normal subjects. In patients with aortic stenosis no deleterious effects were observed in response to phenylephrine. |
8042809 | Effect of prophylactic bronchodilator treatment on lung resistance after tracheal intubation. | After induction of anesthesia, lung resistance increases. We hypothesized that prophylactic bronchodilator treatment before tracheal intubation would result in a lower lung resistance after placement of the endotracheal tube. Forty-two adult patients were randomized to receive one of three inhaled medications 1 h before surgery. All patients first underwent pulmonary function tests. Patients then received either inhaled albuterol (360 micrograms) (n = 12), inhaled ipratropium bromide (72 micrograms) (n = 15) or a placebo inhalation (n = 15). Two, 5, and 15 min after tracheal intubation, lung resistance was measured using the method of von Neergard and Wirtz. Patients who received either bronchodilator had significantly lower lung resistance after intubation than those receiving placebo. At 2 min, lung resistances were 12.7 +/- 1.4 cmH2O.l-1.s-1 (mean +/- SEM) for the placebo group, 6.4 +/- 3.1 cmH2O.l-1.s-1 for the ipratropium-treated group (P < 0.05 vs. placebo), and 7.2 +/- 0.8 cmH2O.l-1.s-1 for the albuterol-treated group (P < 0.05 vs. placebo). The differences in lung resistance persisted through the final measurement at 15 min. Three of fifteen placebo-treated patients developed audible wheezing whereas no patients developed wheezing in either bronchodilator-treated group (P < 0.05 by Fisher's exact test). Although smokers and nonsmokers in the placebo group developed similar resistances after intubation, bronchodilator treatment resulted in lower resistance in nonsmokers than in smokers (P < 0.05). Prophylactic treatment with either an inhaled beta 2-adrenergic agonist or an inhaled cholinergic antagonist produced lower lung resistance after intubation when compared with an inhaled placebo medication. The effect was more pronounced in nonsmokers than in smokers. |
8042808 | Onset of action of mivacurium chloride. A comparison of neuromuscular blockade monitoring at the adductor pollicis and the orbicularis oculi. | The optimal site for monitoring neuromuscular blockade for intubations facilitated with mivacurium chloride has not been established. The primary purpose of this evaluation was to determine the difference in onset of neuromuscular blockade between the orbicularis oculi and adductor pollicis in patients administered mivacurium chloride. We also evaluated intubating conditions when intubation was timed to maximal neuromuscular blockade at either the orbicularis oculi or the adductor pollicis. The results for patients administered mivacurium chloride were compared with those for a control group administered succinylcholine. In a double-blind randomized design, the time to loss of the compound muscle action potential at the orbicularis oculi and adductor pollicis was monitored in 20 patients administered mivacurium chloride and ten patients administered succinylcholine. After administration of mivacurium chloride (0.15 mg.kg-1), ten patients underwent tracheal intubation at maximal depression of the orbicularis oculi (group 2) and ten patients at maximal depression of the adductor pollicis (group 3). In an additional ten patients the trachea was intubated 60 s after administration of succinylcholine (1 mg.kg-1) (group 1, control). Intubation and evaluation of conditions was performed by one investigator blinded to patient treatments. Loss of compound muscle action potential at the orbicularis oculi and adductor pollicis was more rapid in group 1, and intubation was completed at 86 +/- 26 s. In the patients administered mivacurium chloride, the orbicularis oculi compound muscle action potential was lost 3 min earlier than the adductor pollicis compound muscle action potential. Subsequently, intubation was completed at 134 +/- 50 s in the orbicularis oculi group, whereas the time to intubation was 321 +/- 57 s in the adductor pollicis group. There was no significant differences in intubation conditions between the mivacurium chloride groups. When monitoring 95% twitch height depression of the orbicularis oculi muscle, intubation can be accomplished in approximately 2 min after administration of mivacurium chloride (0.15 mg.kg-1). Because intubating conditions were comparable to the patients administered succinylcholine or intubated during monitoring of the twitch height depression of the adductor pollicis, we believe that optimal site for monitoring during intubation using mivacurium chloride is the orbicularis oculi muscle. |
8042807 | Factors associated with back pain after childbirth. | Back pain after childbirth is a frequent complaint. The purpose of this study was to determine the incidence of back pain 1-2 months post partum and to identify the factors, including epidural anesthesia for labor and delivery, that may predispose to it. Women delivering a viable singleton infant were interviewed 12-48 h after delivery for a history of back pain that occurred before, during, or both before and during the recent pregnancy and for details of their delivery experience. Two months later, the women interviewed were sent a follow-up questionnaire regarding the occurrence of back pain 1-2 months post partum. Follow-up data were available for 1,042 (88%) of the 1,185 women originally interviewed. The incidence of post partum back pain in women who received epidural anesthesia was equivalent to those who did not (44% vs. 45%). Through stepwise multiple logistic regression, post partum back pain was found to be associated with a history of back pain, younger age, and greater weight. However, new-onset post partum back pain was found to be associated with greater weight and shorter stature. No statistically significant association was found between post partum back pain and epidural anesthesia, number of attempts at epidural placement, duration of second stage of labor, mode of delivery, or birth weight. The overall incidence of back pain 1-2 months post partum in this population was 44%. Predisposing factors were a history of back pain, younger age, and greater weight. Predisposing factors for new-onset post partum back pain were greater weight and shorter stature. Epidural anesthesia for labor and delivery did not appear to be associated with back pain 1-2 months post partum. |
8042792 | A laboratory comparison of three pulmonary artery oximetry catheters. | Measurement of mixed venous hemoglobin oxygen saturation via catheters employing reflectance spectrophotometry has been available for more than 10 yr. Despite numerous clinical reports that have presented data showing the poor accuracy of these devices when used clinically, they are still widely used in clinical care. The reason for lack of agreement with measurements made using bench spectrophotometry is unclear. The purpose of this study is to define the performance limitations of three hemoglobin oxygen saturation catheters (Oximetrix 3, SAT-2, and HEMOPRO2) in a controlled laboratory environment using a blood flow loop primed with fresh whole human blood as a model. Our hypothesis is that the performance limitations of these devices represent inherent limitations in the technology, not error introduced by patient anatomy and physiology. Blood was equilibrated in a flow loop to four analytic gas mixtures designed to achieve oxygen saturation of approximately 50%, 60%, 70%, and 80%, respectively, with carbon dioxide tension, pH, and temperature held constant. Saturation readings from the catheters were collected on-line by microcomputer. Periodic blood samples were withdrawn from the flow loop for analysis on a bench spectrophotometer and subsequent comparison with catheter-derived values. By all measures, performances of the Oximetrix 3 and SAT-2 systems were comparable (all data are presented as percent saturation unless otherwise noted); bias +/- precision was 3.20 +/- 2.47 and -1.25 +/- 3.36, respectively, versus -9.97 +/- 7.05 for the HEMOPRO2. The 95% confidence limits based on intracatheter variability were +/- 3.49, +/- 2.90, and +/- 9.13 for the Oximetrix 3, SAT-2, and HEMOPRO2, respectively. The 95% confidence limits based on total variability, although similar for Oximetrix 3 (+/- 4.83) and SAT-2 (+/- 6.59), were larger for the HEMOPRO2 (+/- 13.82). The 95% confidence intervals for agreement between catheter brands were -2.14, 11.04 (Oximetrix 3 - SAT-2); -0.18, 26.52 (Oximetrix 3 - HEMOPRO2) and -5.24, 22.68 (SAT-2 - HEMOPRO2). While the Oximetrix 3 and SAT-2 may be acceptable as continuous monitors used to detect changes or trends, none of the three systems is equivalent to conventional bench oximetry for the measurement of hemoglobin oxygen saturation. |
8042791 | Inhibition of volatile sevoflurane degradation product formation in an anesthesia circuit by a reduction in soda lime temperature. | Sevoflurane reacts with carbon dioxide absorbents, such as soda lime, to release the volatile products compounds A and B. These two products, which have been detected in anesthesia circuits, are among five formed when sevoflurane is degraded by soda lime at increased temperature; the others, compounds C, D, and E, have been detected only in heated sealed systems. The current study attempted to determine the influence of soda lime temperature on compounds A and B generation in an anesthesia circuit and whether a decrease in soda lime temperature could eliminate product formation in the circulating gases. Sevoflurane (1.5% in oxygen) was circulated (6 l/min) in a partially closed, low-flow (215 ml/min fresh gas) anesthesia circuit that included a canister containing 1.2 kg fresh soda lime. Carbon dioxide was introduced into the circuit at 200 ml/min, and gas samples for analysis of sevoflurane, compounds A, B, C, and D, and carbon dioxide were taken at the opening of an attached artificial lung. The circuit was operated for 8 h under conditions whereby the soda lime temperature could increase freely or the soda lime was chilled with ice. A maximum core soda lime temperature of about 46 degrees C was measured when the experiment was run under conditions whereby the soda lime temperature was allowed to increase. Compounds A and B increased with time to a maximum of 23 and 9 ppm, respectively. At 4.5 h of circuit operation, compound C/D was found. Chilling of the soda lime canister, which produced a maximum core soda lime temperature of 25 degrees C, resulted in neither compound B nor C/D being detected during the 8-h period. Compound A was present in the circuit at all times at approximately 10 ppm; however, its concentration did not increase as occurred when the experiment was conducted under nonchilled conditions. Carbon dioxide levels at the opening of the lung remained at a constant 5% for 8 h with or without soda lime chilling. This study demonstrates that the release of volatile sevoflurane degradation products in an anesthesia circuit is highly dependent on soda lime temperatures. A reduction of the temperature of soda lime may be a feasible method of preventing the release of significant levels of sevoflurane degradation products without interfering with carbon dioxide absorption or altering the sevoflurane concentration. |
8042790 | Effects of subanesthetic concentrations of isoflurane and their interactions with epinephrine on acquisition and retention of the rabbit nictitating membrane response. | Evidence concerning the concentrations of volatile anesthetics that prevent learning and recall is limited. Epinephrine is believed to enable learning during anesthesia. We investigated the effects of isoflurane and its interaction with epinephrine on learning and subsequent retention of the rabbit's classically conditioned nictitating membrane response. In experiment 1, a tone (conditioned stimulus, CS) preceded paraorbital shock (unconditioned stimulus, US) during 60-min daily sessions of 60 presentations of these paired stimuli for 6 days of acquisition training under 0, 0.4%, or 0.8% isoflurane (n = 8, 13, and 9, respectively). Responses were recorded as conditioned responses (CRs) if they occurred during the CS and before the onset of the US. After 1 day of rest, the animals were given 3 days of extinction consisting of 60 presentations of CS-alone and without isoflurane to assess the retention of CRs from acquisition training. In experiment 2, epinephrine in a dose of 0, 0.01, or 0.1 mg/kg was injected subcutaneously in rabbits receiving 0.4% isoflurane. Two types of epinephrine were used, a sustained release form and epinephrine hydrochloride. Acquisition and retention were tested in the same way as in experiment 1. No isoflurane or epinephrine was used during retention testing. Learning was significantly suppressed during 0.4% isoflurane (approximately equal to 0.2 MAC) treatment and eliminated during 0.8% (approximately equal to 0.4 MAC). Information learned during administration of 0.4% isoflurane was not retained (P < 0.05). Although the low doses of epinephrine improved learning during the last day of the acquisition phase (P < 0.05), there were no differences between the treatment groups on any of the remaining acquisition or extinction days. There was no learning during treatment with 0.8% concentration. Even a 0.4% concentration, which allowed some learning, abolished CRs in extinction, perhaps because of state-dependent retrieval. Epinephrine did not alter substantially the rates of CR acquisition or resistance to extinction. |
8042789 | Halothane modifies ischemia-associated injury to the voltage-sensitive calcium channels in canine heart sarcolemma. | Recent experimental data suggest that functional and metabolic changes in the myocardium caused during ischemia and subsequent reperfusion may be attenuated by the volatile anesthetics through the prevention of intracellular calcium accumulation. The main purpose of the current research is to identify a mechanism responsible for the alterations of ischemia-associated injury to the voltage-sensitive Ca2+ channels (VSCC) in the sarcolemma during halothane anesthesia. The effect of 10 min myocardial ischemia in canine heart and 20 min reperfusion on the function of the VSCC in the sarcolemma was examined in the presence or absence of 1.6 vol% halothane administered in vivo. The membranes were isolated through differential centrifugation/filtration from the ischemic (left anterior descending territory) and normally perfused myocardium. Comparison of binding characteristics in the ischemic and nonischemic zones was made using equilibrium-binding studies of a dihydropyridine calcium channel blocker, [3H]isradipine (0.05-1.0 nM), to the VSCC in the sarcolemma. Control studies were performed on membranes prepared from the same perfusion zones, but from hearts who were not exposed to ischemia. The control studies (n = 5) showed no difference in binding kinetics between the different zones in the heart. After 10 min of ischemia, a 50 to 95% increase in specific [3H]isradipine binding to the sarcolemmal membranes was observed as compared to control membranes (P < 0.001). The maximal binding capacity (Bmax) increased by 85%, whereas the dissociation constant (Kd) remained unchanged. In the reperfusion experiments, a moderately increased binding (of 32%) was observed with a 40% increase in Bmax (P = NS). In the presence of 1.6% inhaled halothane, the effect of ischemia was attenuated. A decrease of 32.1% to 41.8% in equilibrium binding was observed (31% decrease in Bmax; P < 0.03 and 0.02, respectively). Even a brief period of myocardial ischemia produces a marked increase in the available high-affinity binding sites in the VSCC, a finding that is well correlated with previous experimental observation of increased calcium ion influx to the myocardial cell. On reperfusion, some recovery of the ischemic changes in the VSCC was evident. The binding kinetics which characterize this early phase of cell injury were reversed by halothane anesthesia, indicating a possible reduction in calcium entry, which may represent one of the beneficial effects of the anesthetic in the ischemic heart. |
8042788 | Nitric oxide does not mediate coronary vasodilation by isoflurane. | Isoflurane causes vasodilation in the coronary circulation. The current study employed a canine model permitting selective intracoronary administrations of isoflurane (1) to test the hypothesis that coronary vasodilation by isoflurane is mediated by nitric oxide and (2) to evaluate the persistence of coronary vasodilation during an extended exposure to isoflurane. Open-chest dogs anesthetized with fentanyl and midazolam were studied. The left anterior descending coronary artery (LAD) was perfused via extracorporeal system with normal arterial blood or with arterial blood equilibrated with 1.4% (1 MAC) isoflurane. In the LAD bed, coronary blood flow (CBF) was measured with an electromagnetic flowmeter and used to calculate myocardial oxygen consumption (MVO2). In series 1, performed at constant coronary perfusion pressure (CPP), the LAD was exposed to 3 h of isoflurane in two groups of eight dogs: control group, normal coronary endothelium; and experimental group, intracoronary infusion of the nitric oxide synthase inhibitor L-NAME (0.15 mg/min for 30 min). Series 2 was performed with CBF constant; thus, CPP varied directly with coronary vascular resistance. In this series, initial steady-state changes in CPP by isoflurane were evaluated in the same four dogs before and after L-NAME. In the control group of series 1, isoflurane caused a maximal, initial increase in CBF of 444%; however, CBF decreased progressively reaching a value not significantly different from baseline after 3 h of isoflurane. Isoflurane caused a significant (approximately 35%) decrease in MVO2, which persisted during the 3-h administration. Findings after L-NAME (experimental group) were not significantly different from those in control group. In series 2, isoflurane caused significant decreases in CPP that were not affected by L-NAME. The lack of effect of L-NAME on isoflurane-induced coronary vasodilation suggests that nitric oxide does not mediate this response. The increase in CBF during prolonged isoflurane waned over time, perhaps because of tachyphylaxis or emergence of a competitive vasoconstrictor mechanism, e.g., metabolic factors secondary to reduced oxygen demands. |
8042787 | Methionine prevents nitrous oxide-induced teratogenicity in rat embryos grown in culture. | Nitrous oxide (N2O)-induced teratogenicity in rats is commonly believed to be due to decreased tetrahydrofolate, which results in decreased DNA synthesis. The role of decreased methionine has been largely ignored as have the sympathomimetic effects of N2O. A rat whole-embryo culture system was used to determine whether N2O-induced teratogenicity can be prevented with supplemental methionine or folinic acid and whether N2O-induced situs inversus is mediated by alpha 1-adrenergic stimulation. Embryos were explanted on day 9 of gestation, and those at stage 10b (late primitive streak stage) were cultured with or without N2O and the various chemicals, methionine (25 micrograms.ml-1), folinic acid (5 micrograms.ml-1), phenylephrine (range 0.5-50 microM) and prazosin (10 microM). Embryos in the N2O groups were exposed to a concentration of 75% for the first 24 h of culture. After 50 h of culture, embryos were examined for abnormalities including situs inversus. Treatment with N2O alone resulted in increased incidences of malformations and growth retardation. Methionine, but not folinic acid or prazosin, almost completely prevented N2O-induced malformations and growth retardation. N2O itself did not cause situs inversus but increased the incidence of phenylephrine-induced situs inversus. This additive effect was blocked by prazosin. Our results indicate that decreased methionine rather than decreased tetrahydrofolate plays the major role in N2O-induced teratogenicity in rats. They also indicate that N2O stimulates the alpha 1-adrenergic pathway in the embryo and thereby increases the incidence of phenylephrine-induced situs inversus. |
8042786 | Thermogenesis in brown adipocytes is inhibited by volatile anesthetic agents. A factor contributing to hypothermia in infants? | In infants, nonshivering thermogenesis from brown adipose tissue provides an important source of heat for thermoregulation. Infants are known to have a high susceptibility to hypothermia during anesthesia. To investigate whether this could be due to an inhibition of nonshivering thermogenesis by anesthetics, the effect of preincubation with volatile anesthetics on the norepinephrine-induced heat production of brown adipocytes was investigated. Brown adipocytes from hamsters were isolated with a collagenase digestion method and preincubated with volatile anesthetics. The cells were stimulated with norepinephrine, and heat production, measured as oxygen consumption, was monitored polarographically. Norepinephrine addition led to a 20-fold increase in the rate of oxygen consumption (thermogenesis). However, preincubation of cells with 3% halothane reduced the response to norepinephrine by more than 70%. The potency of norepinephrine (the median effective concentration) was not affected by halothane. Full effect of halothane was reached quickly, and after halothane withdrawal, the thermogenic response recovered, although rather slowly. Halothane, isoflurane, and enflurane were approximately equipotent inhibitors of thermogenesis, with concentrations of approximately 0.7% resulting in 50% inhibition. The inhibitory effect of 1% halothane was unaffected by the presence of 74% nitrous oxide, but nitrous oxide alone also reduced thermogenesis. Volatile anesthetics severely attenuated the thermogenic response to norepinephrine of isolated brown-fat cells. It is inferred that brown-adipose-tissue heat production is reduced during (and probably also some time after) anesthesia. Because infants are dependent on brown-fat-derived nonshivering thermogenesis for thermal balance, the inhibition by volatile anesthetic agents of brown-adipocyte heat production may at least partly explain the susceptibility of infants to hypothermia during and after anesthesia. |
8042785 | Direct negative inotropic and lusitropic effects of sevoflurane. | Volatile anesthetics depress left ventricular mechanical performance during multiple phases of the cardiac cycle. The effects of sevoflurane on systolic and diastolic function have yet to be fully evaluated. This investigation characterized the systemic and coronary hemodynamic, inotropic, and lusitropic actions of sevoflurane in chronically instrumented dogs in the presence and absence of autonomic nervous system (ANS) reflexes. Because ANS activity may influence the actions of volatile anesthetics in vivo, experiments were conducted in both ANS-intact and ANS-blocked animals. Eighteen experiments were performed in nine dogs chronically instrumented for measurement of aortic and left ventricular pressure, rate of change of left ventricular pressure, subendocardial segment length, diastolic coronary blood flow velocity, and cardiac output. The preload recruitable stroke work slope was used to assess myocardial contractility. Diastolic function was evaluated by a time constant of isovolumic relaxation, maximum segment lengthening velocity during rapid ventricular filling, and a regional chamber stiffness constant. Dogs were assigned to receive sevoflurane with or without pharmacologic blockade of the ANS in a random fashion. On separate experimental days, systemic and coronary hemodynamics and left ventricular pressure--segment length diagrams and waveforms were recorded in the conscious state and during sevoflurane anesthesia (1.0, 1.25, 1.5, and 1.75 MAC). In dogs with intact ANS reflexes, sevoflurane caused significant (P < 0.05) increases in heart rate and dose-related decreases in mean arterial pressure, left ventricular systolic pressure, cardiac output, and diastolic coronary vascular resistance. Sevoflurane also decreased myocardial contractility (preload recruitable stroke work slope 96 +/- 4 in the conscious state to 42 +/- 3 mmHg at 1.75 MAC). Sevoflurane prolonged isovolumic relaxation (time constant of isovolumic relaxation 35 +/- 1 in the conscious state to 51 +/- 3 ms at 1.75 MAC) and decreased rapid ventricular filling (maximum segment lengthening velocity 40.2 +/- 6.0 in the conscious state to 21.8 +/- 3.8 mm.s-1 at 1.75 MAC) without affecting regional chamber stiffness. Sevoflurane caused similar alterations in functional indices of left ventricular systolic and diastolic performance in autonomically blocked dogs. Sevoflurane caused direct negative inotropic and lusitropic effects in chronically instrumented dogs with and without ANS blockade. |
8042784 | Effects of halothane and propofol on purified brain protein kinase C activation. | Protein kinase C (PKC) has been implicated as a target for general anesthetic action in the central nervous system. Previous reports have described either stimulation or inhibition of PKC activity by general anesthetics. This study examines the effects of halothane and propofol on the activity of purified rat brain PKC under various assay conditions. PKC was assayed in vitro using three previously characterized artificial substrates and three different lipid preparations in the absence or presence of halothane or propofol. Both halothane (50% effective concentration = 2.2 vol%) and propofol (50% effective concentration = 240 microM) markedly stimulated histone H1 phosphorylation by PKC in the presence of a lipid vesicle preparation consisting of phosphatidylcholine, phosphatidylserine, and diacylglycerol. Less marked or no stimulation of PKC by both anesthetics was observed in the presence of a phosphatidylserine/diacylglycerol dispersion or using protamine or poly(lysine, serine) as substrate. Neither anesthetic significantly stimulated PKC activity in the presence of phosphatidylserine/diacylglycerol/Triton X-100 mixed micelles using histone H1, protamine or poly(lysine, serine) as substrate. Slight inhibition of PKC activity by halothane was observed under specific assay conditions with protamine as substrate. The activity of the catalytic fragment of PKC or of two lipid-independent second messenger-regulated protein kinases with conserved catalytic domains was not significantly affected by halothane. Both halothane and propofol stimulated purified brain PKC activity in vitro assayed with physiologically relevant lipid bilayers in the absence or presence of Ca2+. This effect appears to be mediated through the lipid-binding regulatory domain of PKC. The potencies of halothane and propofol in stimulating PKC in vitro are consistent with submaximal activation of PKC at clinically effective anesthetic concentrations, the pharmacologic significance of this effect requires confirmation in an intact cellular system. |
8042783 | L-arginine attenuates ketamine-induced increase in renal sympathetic nerve activity. | It has been reported that ketamine produces sympathoexcitation by directly stimulating the central nervous system. It also has been shown that nitric oxide (NO) may play a role in signal transduction of the nervous system. Therefore, we hypothesized that the sympathoexcitation of ketamine may be linked to central NO formation. To test this hypothesis, we examined the effects of L-arginine, a substrate of NO formation, on renal sympathetic nerve activity (RSNA) during ketamine anesthesia. Using 45 rabbits given basal anesthesia with alpha-chloralose, we measured changes in heart rate, mean arterial pressure, and RSNA in response to intravenous ketamine (1 mg/kg) and investigated the effect of intravenous L-arginine and D-arginine (bolus 30 mg/kg followed by continuous 30 mg.kg-1.min-1). The animals were divided into intact, sinoaortic- and vagal-deafferented, and spinal cord-transected groups. Ketamine caused significant increases in RSNA (172 +/- 16%), heart rate (12 +/- 2 beats/min), and mean arterial pressure (8 +/- 1 mmHg) in the intact rabbits. Ketamine also increased RSNA in sinoaortic- and vagal-deafferented rabbits, but not in spinal cord-transected rabbits. L-Arginine attenuated the ketamine-induced increase in RSNA in intact and deafferented rabbits, whereas D-arginine had no effect on RSNA. In addition, NG-nitro-L-arginine methyl ester, a NO synthase inhibitor, increased RSNA and the increase was attenuated by L-arginine. Ketamine may act centrally to increase sympathetic outflow, and the sympathoexcitation may be attenuated by increasing NO formation with L-arginine in the central nervous system. |
8042782 | Hearing acuity of anesthesiologists and alarm detection. | With rapid technological advances in anesthesiology, we are acquiring an ever increasing number of auditory alarm systems in the operating room the value of which depend on the hearing acuity of the anesthesiologist monitoring the patient. Presbycusis, the effect of aging on the auditory system, characteristically results in a bilaterally symmetric neurosensory high-frequency hearing loss ( > 2,000 Hz). In this study we attempt to assess the impact of this common hearing disorder on alarm detection. We measured air conduction hearing acuities of 188 anesthesiologists who volunteered to participate. Subjects were divided into six age groups (25-34, 35-44, 45-54, 55-64, and > 75 yr of age). Abnormal audiograms were compared to the intensity and frequency of alarms in our operating room to determine which alarms were out of hearing range. Subjects with a history of chronic or excessive noise exposure were excluded from the study. The median hearing threshold for each age group of study subjects was compared to the median hearing threshold of similar age groups in the general population. Overall, 66% of the subjects had an abnormal audiogram, and 7% had one or more alarm intensities less than their detectability threshold (14% unilateral, 86% bilateral). Median hearing threshold was worse than the general population for men and women less than 55 yr of age. Hearing acuity worse than the general population occurred at the lower frequencies while acuity at the higher frequencies was equal or slightly better. However, inability to hear alarms occurred only with those alarms that have frequencies of 4,000 Hz or greater. Although high-frequency hearing acuity of individuals in our study was better than that of the general population, hearing deficits at high frequencies were of the magnitude to interfere with alarm detection. Also background noise levels vary greatly in different operating rooms. These two problems create a hindrance to alarm detection for certain anesthesiologists. From our data we conclude that the aging human ear may not be capable of accurately detecting some auditory alarms in the operating room. Alarm design should consider hearing acuity because high-frequency alarms may go undetected. |
8042781 | Lack of stereospecific effects of isoflurane and desflurane isomers in isolated guinea pig hearts. | Volatile anesthetics alter membrane channel proteins. It is controversial whether they act by nonspecifically perturbing lipid membranes or by directly binding to amphiphilic and usually stereoselective regions on channel macromolecules. Biologically relevant receptors are usually stereoselective. The stereochemical effect of isoflurane and desflurane can be used as a pharmacologic tool to investigate whether these drugs bind to specific target sites. The specific optical isomers of isoflurane and desflurane were used to examine whether they produce any differential effects on electrical, mechanical, and metabolic function in isolated hearts. Isolated guinea-pig hearts were perfused with Krebs-Ringer's solution containing, in random order, both isomers of either isoflurane (n = 11) or desflurane (n = 6) for 10 min with a 15-min washout period. Either anesthetic was injected into a preoxygenated, sealed bottle of perfusate, which gave concentrations of 0.28 and 0.57 mM for isoflurane and 0.48 and 0.88 mM for desflurane, which are equivalent to 1 and 2 MAC multiples. Both isomers of isoflurane and desflurane decreased left ventricular pressure, heart rate, and percent oxygen extraction and increased atrioventricular conduction time, coronary flow, and oxygen delivery. Each change was significantly different from control at each concentration, and these effects were greater with the high compared to the low concentration of each anesthetic. There was no significant difference between the (+)- and the (-)-isomers for either anesthetic for any measured or calculated variable. Also, the effects of the stereoisomers were similar to those of the racemic mixture. These data indicate that the optical isomers of isoflurane and desflurane are equipotent, as assessed by their effects on cardiac function in isolated guinea-pig hearts. Although both agents may ultimately influence hydrophilic domains of the protein channels, their major cardiac effect appears to result either from global perturbation of the membrane lipids and/or an interaction at nonstereoselective sites on channels modulating cardiac anesthetic effects. |
8042779 | Insensitivity of P-type calcium channels to inhalational and intravenous general anesthetics. | Voltage-gated Ca2+ channels long have been considered plausible targets for general anesthetics. Previous anesthetic studies have focused on L-, T-, or N-type channels, but there have been no studies on channels identified as P-type. Since P-type channels may be the most important voltage-gated Ca2+ channels involved in synaptic transmission in mammalian brain, it is important to establish their sensitivity to clinically relevant concentrations of general anesthetics. Acutely dissociated cerebellar Purkinje neurons were obtained from 7-14-day-old Sprague-Dawley rats. P-type currents were measured using the whole-cell version of the patch-clamp technique, with Ba2+ as the current carrier. General anesthetics were applied to the neurons in aqueous solution at room temperature (20-23 degrees C). P-type Ca2+ channels were found to be very insensitive to a variety of general anesthetics and ethanol. Inhibitions of less than 10% were produced by 0.35 mM halothane, 0.35 mM isoflurane, 32 microM thiopental, 50 microM pentobarbital, 2 microM propofol, and 200 mM ethanol. Substantial anesthetic inhibition was found only at free aqueous concentrations much greater than those that are clinically relevant. For halothane, the dose-response curve showed an IC50 concentration of 1.17 +/- 0.02 mM and a Hill coefficient of 2.02 +/- 0.04 (mean +/- SEM). The relatively small inhibitions of P-type Ca2+ channels produced by volatile and intravenous anesthetics at their free aqueous EC50 concentrations for general anesthesia in mammals suggest that these channels do not play a major role in the induction of general anesthesia. |
8042780 | Inhibition of [3H]isradipine binding to L-type calcium channels by the optical isomers of isoflurane. Lack of stereospecificity. | The dose-dependent myocardial depression of volatile general anesthetics such as isoflurane has been linked to blockade of L-type Ca2+ channels. The effects of (+)- and (-)-isoflurane on the inhibition of [3H]isradipine binding to L-type Ca2+ channels in membranes prepared from mouse heart were examined. In addition, because there is a stereo-specific effect of these isomers on sleep time in mice, the potential contribution of L-type Ca2+ channels to isoflurane-induced sleep was assessed by determining whether a similar stereoselectivity would be manifested at these sites in cerebral cortical membranes. The effects of isoflurane stereoisomers on the binding of an L-type Ca2+ channel ligand ([3H]isradipine) were studied in cardiac and brain cortical membranes. Their potencies and effects on the Kd and Bmax of [3H]isradipine were measured. Pharmacologically relevant concentrations of (+)- and (-)-isoflurane inhibited [3H]isradipine binding. The IC50 values for (+)-isoflurane were 0.48 +/- 0.02% and 0.40 +/- 0.01% in heart and brain membranes, respectively. The values for (-)-isoflurane were not significantly different from the respective values for the (+)-isomer. Saturation analysis demonstrated (+)- and (-)-isoflurane inhibited [3H]isradipine binding by significantly reducing Bmax and increasing Kd, but there were no significant differences between these isomers in either tissue. The stereoisomers of isoflurane are equipotent as inhibitors of [3H]isradipine binding to L-type Ca2+ channels. This lack of stereoselectivity between (+)- and (-)-isoflurane indicates that the [3H]isradipine site on L-type Ca2+ channels in brain does not contribute to the differences in isoflurane-induced sleep time reported for these stereoisomers. Taken with a lack of stereoselectivity at L-type Ca2+ channels in heart, an optically resolved isomer of isoflurane may have clinical advantages compared to the current racemic mixture. |
8042778 | Isoflurane inhibits multiple voltage-gated calcium currents in hippocampal pyramidal neurons. | The mechanisms by which volatile anesthetics produce general anesthesia are unknown. Voltage-gated calcium currents in central neurons are potential target sites for general anesthetics because they are involved in the regulation of excitability and are essential for synaptic transmission. Freshly isolated rat hippocampal pyramidal neurons were studied using the whole-cell patch clamp method. Calcium currents were isolated from other voltage-activated currents by blocking sodium and potassium channels. Calcium current subtypes were studied using the specific blockers nitrendipine and omega-conotoxin GVIA. Isoflurane inhibited multiple voltage-gated calcium currents in hippocampal neurons. Isoflurane inhibited both the high- and low-voltage-activated calcium current in a clinically relevant concentration range, giving half-maximal inhibition of the peak high-voltage-activated current (measured at current maximum) at about 2% gas phase concentration, and the sustained current (measured at the end of an 800-ms depolarization) at about 1%. Isoflurane also accelerated both components of the two-component exponential decay of the high-voltage-activated current. Studies using specific channel blockers showed that the calcium current contained contributions from T, L, N, and other channels, including probably P channels. Isoflurane inhibited all of these in clinically relevant concentrations, although detailed analysis of the effects on the individual channel types was not attempted. Given the importance of calcium currents in the regulation of excitability in central neurons and the involvement of P and N channels in neurotransmitter release, this effect may represent an important action of volatile anesthetics in producing general anesthesia. |
8042776 | Rapid screening of the Y chromosome in idiopathic sterile men, diagnostic for deletions in AZF, a genetic Y factor expressed during spermatogenesis. | A rapid molecular screening programme has been established for the long arm of the human Y chromosome in Yq11 in order to quickly detect small interstitial deletions in this chromosome region. They have been observed in idiopathic sterile males with azoospermia and a severe oligozoospermia and are therefore indicative for deletion of AZF gene sequences. AZF (i.e. azoospermia factor) is a genetic factor located in Yq11 which controls human spermatogenesis. The screening programme is based mainly on a multiplex PCR approach using a series of Y-specific primers amplifying single DNA loci in Yq11. The order of all Y-DNA loci can be unequivocally arranged along the whole long Y arm. Therefore, any detected deletion can be quickly mapped in relation to the proposed position of AZF. Benefits and pitfalls of this new diagnostic Y screening method will be discussed. |
8042774 | Study of nuclear decondensation of the rat spermatozoa by reducing agents during epididymal transit. | Chromatin packing, mostly due to disulfide bond formation, is one important step in epididymal sperm maturation. In this study the in vitro effect of a reducing agent such as thioglycolate (Tg) was tested. Thioglycolate was assayed on rat sperm obtained from caput, corpus and cauda epididymides. Changes were verified via light microscopy (and area measurements) and both transmission and scanning electron microscopy using standard techniques. Due to the low molecular weight of Tg, it does not require detergent to enter sperm. The nuclear decondensation elicited by Tg and its effect on sperm surface, differ from caput to cauda, although the final nuclear area is not significantly different. The pattern of sperm nuclear decondensation suggests that it starts at the caudal segment of the head, perhaps due to the abundance of nuclear pores in this region. Under the experimental conditions described below the perforatorium was not affected. Thus, the nature and role in the rat sperm of the perforatorium deserves more detailed analysis. |
8042775 | Percoll density gradient centrifugation and consecutive flow cytometry do not identify leukocytes and leukocyte subtypes in ejaculate specimens. | This paper describes an attempt to establish a new combined method of leukocyte analysis in human ejaculate by Percoll density gradient centrifugation and consecutive flow cytometry. As a first step, leukocyte separation was performed by Percoll density gradient centrifugation with consecutive enrichment of leukocytes, especially granulocytes, in the 40%/60% and 60%/80% Percoll interfaces. Then these fractions were stained with specific monoclonal antibodies and analysed in a Facscan flow cytometer. Flow cytometric analysis did not demonstrate identifiable leukocyte populations, indicating a questionable cross-reaction with spermatozoal elements. Therefore, the combined technique of Percoll density gradient centrifugation and flow cytometric analysis were considered unsuitable for clinical leukocyte determination. |
8042773 | Superoxide dismutase activity along rat seminiferous epithelial wave: effects of ethane dimethanesulphonate and 3.0 Gy of X-irradiation. | Changes in generation of reactive oxygen species and antioxidant enzyme activities are associated with differentiation processes. The authors have studied the activity of superoxide dismutase (SOD) in sequentially cut stage-defined segments of rat seminiferous tubules. Great variation was observed in SOD activity along the seminiferous epithelial wave. At its highest, four-fold increases were observed in individual tubules. However, these changes showed no clear correlation to the stages of the cycle. To determine the effect of testosterone withdrawal, rats treated with ethane dimethanesulphonate (EDS) were studied. This treatment had no effect on the pattern of SOD activity along the seminiferous epithelial wave. Testes of other rats were exposed to local 3.0 Gy X-irradiation to cause selective loss of germ-cell populations. SOD activity in the seminiferous epithelium was not affected at 30 min or 7 d after X-irradiation. On day 31 post-irradiation, SOD activity increased at stages XIV-VI, peaking at stage III (P < 0.01 for comparison of stages XIV-VI with the other stages). The data presented here suggest that the activity of SOD in seminiferous epithelium is regulated over a wide range during spermatogenesis. Testosterone plays no major role in the control of seminiferous tubule SOD activity. The loss of spermatocytes and early spermatids by day 31 after X-irradiation revealed a stage-specific increase in SOD activity, which may be associated with the differentiation of elongated spermatids. |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.