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Right to refuse psychotropic medication: an interdisciplinary proposal.
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Low sweat electrolytes in a patient with cystic fibrosis.
A patient with the clinical syndrome of cystic fibrosis characterized by chronic pulmonary disease, infection with mucoid Pseudomonas aeruginosa, sinusitis, nasal polyposis, abnormal pancreatic bicarbonate response to secretin stimulation, but normal levels of trypsin and chymotrypsin in the duodenal drainage, and a sibling with autopsy-documented cystic fibrosis, is described. Sweat chloride ranged from 20 to 44 meq/liter and sweat sodium from 36 to 55 meq/liter. Immunoglobulin deficiency, alpha 1-antitrypsin deficiency, tuberculosis and abnormalities of ciliary ultrastructure were excluded. Review of sweat electrolytes in 213 patients with cystic fibrosis revealed that patients with normal pancreatic enzyme release have significantly lower sweat sodium and chloride concentrations (p < 0.0005) than do patients with pancreatic insufficiency. Chronic pulmonary disease, pancreatic insufficiency and elevated levels of sweat electrolytes comprise the classic diagnostic triad for cystic fibrosis. The expression of these features may be variable, but the sweat test remains the cardinal laboratory confirmation of the diagnosis. Over 98 percent of patients with cystic fibrosis have sweat chloride values greater than 60 meq/liter, 1 to 2 percent between 50 and 60 meq/liter, and only about one in 1,000, like our patient, less than 50 meq/liter. Patients with cystic fibrosis with borderline sweat chloride values frequently have chronic pulmonary disease but intact pancreatic enzyme release. In such patients, family history, ancillary clinical features and systemic exclusion of other syndromes assume special diagnostic importance.
Familial bronchiectasis.
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Bronchiectasis and oligospermia: two families.
Five patients from two families had a bronchiectasis syndrome; the men also had oligospermia with poor progressive sperm motility. None of the patients had cystic fibrosis, alpha 1 antitrypsin deficiency, immunoglobulin deficiency, structural abnormalities of the bronchi, or abnormalities of ciliary ultrastructure. Onset of pulmonary symptoms was in the neonatal period or infancy, and bronchitis and bronchiectasis were most severe in the middle and lower lobes. Two patients had sinusitis and two otitis. The two men old enough to be studied had 2-10 X 10(6) sperm/ml of ejaculate with less than 10% progressively motile. There were no other associated anomalies. These patients probably had a distinct genetic error predisposing to pulmonary infection leading to bronchiectasis and, in men, oligospermia with poor progressive motility.
Effects of alpha-tocopherol on platelet membrane function in cystic fibrosis.
Patients with cystic fibrosis and their parents were reported to have abnormal platelet aggregation responses to prostaglandin E1. To determine whether this is a property of the platelets, we studied the adenosine 3':5'-cyclic monophosphate (cAMP) response of washed platelets to prostaglandin E1. The cAMP response to prostaglandin E1 was the same in platelets from obligate heterozygotes for cystic fibrosis and from those of healthy controls. Patients with cystic fibrosis who had deficient vitamin E levels (plasma alpha-tocopherol, less than 500 micrograms/dl) had significantly (p less than 0.01) reduced platelet cAMP response to prostaglandin E1 compared with patients who had sufficient vitamin E, and supplementation with water-miscible vitamin E in these patients resulted in significant increases in plasma alpha-tocopherol levels (p less than 0.01) and in cAMP response to prostaglandin E1 (p less than 0.05). Plasma alpha-tocopherol levels correlated significantly with platelet cAMP response to prostaglandin E1 in patients with cystic fibrosis (r = 0.58, p less than 0.05). However, plasma alpha-tocopherol level was unrelated to the lymphocyte and granulocyte cAMP response to prostaglandin E1 or to the platelet cAMP response to alpha 2-adrenergic stimulation. Our data suggest that patients with cystic fibrosis have no inherited defect in platelet cAMP response to prostaglandin E1. In patients who have sufficient vitamin E, cAMP responses to prostaglandin E1 are normal in all the formed elements of the blood.
Isolated growth hormone deficiency and cystic fibrosis: a report of two cases.
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Possible hazard of timed-release aspirin in a patient with pancreatic insufficiency.
An episode of severe small intestinal hemorrhage occurred in a cystic fibrosis patient having pancreatic insufficiency and receiving timed-release aspirin therapy for disabling hypertrophic pulmonary osteoarthropathy. The increased acidity of small intestinal contents due to decreased bicarbonate secretion observed in patients with pancreatic insufficiency may alter the luminal environment and result in mucosal erosions and/or ulcerations in association with the presence of aspirin. Thus, physicians should be aware of the possibility that timed-release aspirin causes small intestinal hemorrhage in such patients.
Veterans Administration cooperative study on aphasia: a comparison of individual and group treatment.
Five Veterans Administration Medical Centers participated in an investigation designed to compare individual with group treatment for aphasic patients who had suffered a left hemisphere cerebral vascular accident. Patients who met selection criteria were assigned randomly to either traditional, individual, stimulus-response type treatment of specific language deficits or group therapy designed to improve communication through group interaction and discussion with no direct treatment of specific language deficits. All patients received eight hours of therapy each week beginning at four weeks postonset and continuing until 48 weeks postonset or until they dropped out of the study. A battery of language measures and a clinical neurologic evaluation were administered at intake and every 11 weeks a patient was in the study. Results show both individually and group-treated patients made significant improvement in language abilities. Individual treatment resulted in significantly better overall performance on the Porch Index of Communicative Ability; however, no significant differences were observed between groups on the other language measures. If the traditional belief is correct that significant spontaneous recovery is complete by three to six months postonset, significant improvement in both groups beyond 26 weeks postonset indicates both individual and group treatment are efficacious methods for managing aphasic patients.
Clinician versus reading center assessment of cytomegalovirus retinitis lesion size.
PURPOSE: To compare clinician and fundus photograph reading center assessments of the cytomegalovirus (CMV) retinitis area and change in the CMV retinitis area over time, and to investigate how these assessments correlate with the visual field (VF) of eyes with CMV retinitis. DESIGN: Analysis of pooled data from 2 multicenter randomized clinical trials and 1 prospective multicenter epidemiologic study. PARTICIPANTS: Ninety-five eyes of 79 patients. At baseline, each eye had CMV retinitis restricted to zone 1 and/or zone 2 (approximately the photographable postequatorial retina), as assessed by the evaluating clinician. METHODS: Comparison of CMV retinitis area, change in area over time as assessed by clinicians and a fundus photograph reading center, and correlation of these assessments with VF measurement. MAIN OUTCOME MEASURES: Cytomegalovirus retinitis area, change in CMV retinitis area over time, and VF score. RESULTS: Baseline assessments of the mean retinitis area were, by clinicians, 12.8% of the total retinal area and, by the reading center, 6.3% of the total retinal area (P<0.001). There was a positive correlation between clinician and reading center assessments of retinitis area at baseline (rho = 0.77 and P<0.0001 by Pearson correlation and rho = 0.54 and P<0.001 by concordance). Both clinician and reading center size measures correlated negatively with VF (Spearman correlation rhos = -0.38 and -0.52, respectively; P<0.001 each). Mean changes in area over a 3-month interval were, by clinicians, +1.2% and, by the reading center, +1.1% (P = 0.68). Regression analysis showed a positive concordance (rho = 0.42, P<0.001). Change in VF over a 3-month interval did not correlate with change in retinitis area as assessed by clinicians or the reading center. CONCLUSIONS: Awareness of the similarities and differences between clinician and reading center assessments of CMV retinitis area should permit clinicians to apply research data to clinical practice more effectively. Clinician assessment of retinitis area correlates negatively with VF, a clinically meaningful visual outcome in patients with CMV retinitis.
Cytomegalovirus resistance to ganciclovir and clinical outcomes of patients with cytomegalovirus retinitis.
PURPOSE: To evaluate whether cytomegalovirus resistant to ganciclovir, detected in either the blood or urine, correlates with adverse ocular outcomes. DESIGN: Prospective cohort study. METHODS: Patients with cytomegalovirus and AIDS were enrolled in a study of the occurrence and clinical correlates of resistant cytomegalovirus. Blood and urine cultures for cytomegalovirus were performed at the time of diagnosis of retinitis, 1 and 3 months after the initiation of therapy, and every 3 months thereafter. Patients were seen monthly, at which time fundus photographs were obtained and forwarded to the Fundus Photograph Reading Center for evaluation of retinitis progression (movement of a border of a cytomegalovirus lesion > or = 750 microm, or the occurrence of a new lesion > or = 0.25 disk area in size) and the amount of retinal area affected by cytomegalovirus retinitis. Visual acuity was measured using logarithmic visual acuity charts. Phenotypic resistance to ganciclovir was defined as an IC50 > 6.0 micromol/l, and genotypic resistance to ganciclovir was defined as the occurrence of a cytomegalovirus UL97 gene mutation known to confer ganciclovir resistance. Time-dependent analyses were performed and included viral resistance, highly active antiretroviral therapy, and treatment variables as predictors of clinical outcomes. RESULTS: One hundred ninety-seven patients received ganciclovir therapy. Nineteen patients developed phenotypic resistance to ganciclovir, and 18 developed genotypic resistance. The detection of cytomegalovirus resistant to ganciclovir was associated with a 4.17- to 5.61-fold increase in the odds of retinitis progression (P values all < or = .0002), depending upon the definition of resistance and the culture sources analyzed. Resistance was associated with a greater increase in retinal area involved by cytomegalovirus by 3-month interval (1.10% vs 0.05% to 0.10%), which was significant for phenotypic resistance and for genotypic resistance in the blood or urine (P =.012 to.021). There was a suggestion that resistance was associated with a greater loss of visual acuity (P =.009 to.096). Highly active antiretroviral therapy was associated with an approximate 50% reduction in the odds of retinitis progression, and the ganciclovir implant was associated with an approximate 60% reduction. CONCLUSIONS: The detection of cytomegalovirus resistant to ganciclovir in either the blood or urine of a patient with cytomegalovirus retinitis is associated with an increased risk of adverse ocular outcomes.
Transcriptome analysis for the chicken based on 19,626 finished cDNA sequences and 485,337 expressed sequence tags.
We present an analysis of the chicken (Gallus gallus) transcriptome based on the full insert sequences for 19,626 cDNAs, combined with 485,337 EST sequences. The cDNA data set has been functionally annotated and describes a minimum of 11,929 chicken coding genes, including the sequence for 2260 full-length cDNAs together with a collection of noncoding (nc) cDNAs that have been stringently filtered to remove untranslated regions of coding mRNAs. The combined collection of cDNAs and ESTs describe 62,546 clustered transcripts and provide transcriptional evidence for a total of 18,989 chicken genes, including 88% of the annotated Ensembl gene set. Analysis of the ncRNAs reveals a set that is highly conserved in chickens and mammals, including sequences for 14 pri-miRNAs encoding 23 different miRNAs. The data sets described here provide a transcriptome toolkit linked to physical clones for bioinformaticians and experimental biologists who wish to use chicken systems as a low-cost, accessible alternative to mammals for the analysis of vertebrate development, immunology, and cell biology.
Structure and function of endoglucanase V.
Cellulose is the major polysaccharide component of plant cell walls and is the most abundant organic compound on the planet. A number of bacterial and fungal organisms can use cellulose as a food source, possessing cellulases (cellobiohydrolases and endoglucanases) that can catalyse the hydrolysis of the beta-(1,4) glycosidic bonds. They can be classified into seven distinct families. The three-dimensional structures of members of two of these families are known. Here we report the structure of a third cellulase, endoglucanase V, whose sequence is not represented in any of the above families. The enzyme is structurally distinct from the previously determined cellulases but is similar to a recently characterized plant defence protein. The active site region resembles that of lysozyme, despite the lack of structural similarity between these two enzymes.