Adverse effects associated with use of nevirapine in HIV postexposure prophylaxis for 2 health care workers.
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Adult↗
Biomedical subjects
S Johnson
Publications and source records attributed to S Johnson.
Distribution of ecto 5'-nucleotidase on Mycoplasma species associated with arthritis.
The enzyme ecto 5'-nucleotidase (5'N) was found to be active on 8/14 strains of Mycoplasma fermentans, K(m) (+/-S.D.) 3.8+/-2.8 microM 5'-AMP, and on the type strain of Mycoplasma pulmonis, K(m) 0.63 microM 5'-AMP. The six M. fermentans strains lacking 5'N activity were related by restriction fragment length polymorphism typing. At pH 8.5, the type strains of Mycoplasma arthritidis, Mycoplasma buccale and Ureaplasma urealyticum showed a relatively non-specific phosphatase activity against 5'-AMP but no activity was shown by the type strains of Mycoplasma genitalium, Mycoplasma hominis, Mycoplasma orale, Mycoplasma penetrans, Mycoplasma pneumoniae and Mycoplasma salivarium at this pH. M. fermentans has been reported from rheumatoid joints, which show a raised 5'N activity on their synovial cells and in their fluid which may be associated directly or indirectly with the mycoplasma.
5'-Nucleotidase↗
Subcellular localization of cyclic ADP-ribosyl cyclase and cyclic ADP-ribose hydrolase activities in porcine airway smooth muscle.
Recent studies have provided evidence for a role of cyclic ADP-ribose (cADPR) in the regulation of intracellular calcium in smooth muscles of the intestine, blood vessels and airways. We investigated the presence and subcellular localization of ADP-ribosyl cyclase, the enzyme that catalyzes the conversion of beta-NAD(+) to cADPR, and cADPR hydrolase, the enzyme that degrades cADPR to ADPR, in tracheal smooth muscle (TSM). Sucrose density fractionation of TSM crude membranes provided evidence that ADP-ribosyl cyclase and cADPR hydrolase activities were associated with a fraction enriched in 5'-nucleotidase activity, a plasma membrane marker enzyme, but not in a fraction enriched in either sarcoplasmic endoplasmic reticulum calcium ATPase or ryanodine receptor channels, both sarcoplasmic reticulum markers. The ADP-ribosyl cyclase and cADPR hydrolase activities comigrated at a molecular weight of approximately 40 kDa on SDS-PAGE. This comigration was confirmed by gel filtration chromatography. Investigation of kinetics yielded K(m) values of 30.4+/-1.5 and 695. 3+/-171.2 microM and V(max) values of 330.4+/-90 and 102.8+/-17.1 nmol/mg/h for ADP-ribosyl cyclase and cADPR hydrolase, respectively. These results suggest a possible role for cADPR as an endogenous modulator of [Ca(2+)](i) in porcine TSM cells.
ADP-ribosyl Cyclase↗
The conformation of calreticulin is influenced by the endoplasmic reticulum luminal environment.
In order to understand the dynamics of the endoplasmic reticulum (ER) luminal environment, we investigated the role of Ca(2+), Zn(2+), and ATP on conformational changes of calreticulin. Purified calreticulin was digested with trypsin in the presence or absence of Ca(2+), Zn(2+), and ATP. At low Ca(2+) concentration (<100 micrometer), calreticulin is rapidly and fully degraded by trypsin, indicating that under these conditions the protein is in a highly trypsin-susceptible conformation. Increasing Ca(2+) concentration up to 500 micrometer or 1 mm resulted in protection of the full-length calreticulin and in generation of the 27-kDa fragment highly resistant to trypsin digestion. The 27-kDa protease-resistant core of the protein represented the NH(2)-terminal half of calreticulin and was identified by its reactivity with specific antibodies and by NH(2)-terminal amino acid sequence analysis. Ca(2+)-dependent changes in calreticulin's sensitivity to proteolysis indicate that agonist-induced fluctuation in the free ER luminal Ca(2+) concentration may affect the protein conformation and function. Trypsin digestion of calreticulin in the presence of Zn(2+) resulted in the formation of a 17-kDa central protease-resistant core in the protein corresponding to the central region of the protein, indicating that under these conditions the N- and C-domains of the protein are in an extended conformation. Here we also show that calreticulin is an ATP-binding protein but that it does not contain detectable ATPase activity. Digestion of the protein with trypsin in the presence of Mg(2+)-ATP protects the full-length protein. These results indicate that calreticulin may undergo frequent, ion-induced conformation changes, which may affect its function and its ability to interact with other proteins in the lumen of the ER.
Adenosine Triphosphate↗
Strategic planning? Try strategic doing.
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Community-Institutional Relations↗
Practice parameters for the evaluation of chronic insomnia. An American Academy of Sleep Medicine report. Standards of Practice Committee of the American Academy of Sleep Medicine.
Chronic insomnia is the most common sleep complaint which health care practitioners must confront. Most insomnia patients are not, however, seen by sleep physicians but rather by a variety of primary care physicians. There is little agreement concerning methods for effective assessment and subsequent differential diagnosis of this pervasive problem. The most common basis for diagnosis and subsequent treatment has been the practitioner's clinical impression from an unstructured interview. No systematic, evidence-based guidelines for diagnosis exist for chronic insomnia. This practice parameter paper presents recommendations for the evaluation of chronic insomnia based on the evidence in the accompanying review paper. We recommend use of these parameters by the sleep community, but even more importantly, hope the large number of primary care physicians providing this care can benefit from their use. Conclusions reached in these practice parameters include the following recommendations for the evaluation of chronic insomnia. Since the complaint of insomnia is so widespread and since patients may overlook the impact of poor sleep quality on daily functioning, the health care practitioner should screen for a history of sleep difficulty. This evaluation should include a sleep history focused on common sleep disorders to identify primary and secondary insomnias. Polysomnography, and the Multiple Sleep Latency Test (MSLT) should not be routinely used to screen or diagnose patients with insomnia complaints. However, the complaint of insomnia does not preclude the appropriate use of these tests for diagnosis of specific sleep disorders such as obstructive sleep apnea, periodic limb movement disorder, and narcolepsy that may be present in patients with insomnia. There is insufficient evidence to suggest whether portable sleep studies, actigraphy, or other alternative assessment measures including static charge beds are effective in the evaluation of insomnia complaints. Instruments such as sleep logs, self-administered questionnaires, symptom checklist, or psychological screening tests may be of benefit to discriminate insomnia patients from normals, but these instruments have not been shown to differentiate subtypes of insomnia complaints.
Chronic Disease↗
Multiple lethal effects induced by a benzimidazole anthelmintic in the anterior intestine of the nematode Haemonchus contortus.
A mechanism of benzimidazole efficacy against parasitic nematodes is postulated to involve inhibition of intestinal secretory vesicle transport via depolymerization of microtubules. We show that fenbendazole (FBZ) treatment of lambs causes pathology localized to the anterior intestine in the parasitic nematode Haemonchus contortus. The pathology included gross disintegration of the anterior intestine, DNA fragmentation in anterior intestinal nuclei with characteristics of an apoptosis-like process, and inhibition of host erythrocyte digestion. These lethal effects were associated with inhibited transport of apical secretory vesicles in the anterior intestine, and then generalized dispersal of these vesicles contents throughout the intestinal cytoplasm and worm body. Cytoplasmic accumulation of secretory vesicles and undigested erythrocytes preceded DNA fragmentation and vesicle content dispersal. Both DNA fragmentation and vesicle content dispersal were detected in disintegrated intestine and intestine that had not yet undergone disintegration. These pathologic effects in the anterior intestine appear sufficient to explain the efficacy of FBZ against adult H. contortus. The results implicate mechanisms in the anterior intestine that govern dispersal of apical secretory vesicle contents, DNA fragmentation and tissue disintegration as effectors of this pathology.
Animals↗
Expression and purification of mammalian calreticulin in Pichia pastoris.
Calreticulin is a 46-kDa Ca(2+)-binding chaperone of the endoplasmic reticulum membranes. The protein binds Ca(2+) with high capacity, affects intracellular Ca(2+) homeostasis, and functions as a lectin-like chaperone. In this study, we describe expression and purification procedures for the isolation of recombinant rabbit calreticulin. The calreticulin was expressed in Pichia pastoris and purified to homogeneity by DEAE-Sepharose and Resource Q FPLC chromatography. The protein was not retained in the endoplasmic reticulum of Pichia pastoris but instead it was secreted into the external media. The purification procedures reported here for recombinant calreticulin yield homogeneous preparations of the protein by SDS-PAGE and mass spectroscopy analysis. Purified calreticulin was identified by its NH(2)-terminal amino acid sequences, by its Ca(2+) binding, and by its reactivity with anti-calreticulin antibodies. The protein contained one disulfide bond between (88)Cys and (120)Cys. CD spectral analysis and Ca(2+)-binding properties of the recombinant protein indicated that it was correctly folded.
Amino Acid Sequence↗
Sleep apnea and health-related quality of life in African-American elderly.
The relationship between health-related quality of life (HRQOL) and sleep apnea was examined in a sample of elderly African-Americans screened for snoring and daytime sleepiness. Seventy African-Americans over the age of 65 years completed a comprehensive sleep questionnaire, the Quality of Well-Being Scale (QWB), and the Medical Outcomes Study (MOS) Core Measures of HRQOL (116-item Long Version) and had sleep recorded. Those with moderate-severe sleep apnea had significantly lower Physical Component summary scores than those with no sleep apnea (p < 0.05). After controlling for medical conditions, sleep apnea was significantly related to both general physical functioning and general mental health functioning in those with mild apnea (apnea-hypopnea index [AHI] < 15), but not in those with moderate to severe apnea. There was an initial decrease in HRQOL up to an AHI level of 15, at which point HRQOL remained at a lowered level. The QWB scores of our sleep apnea sample were similar to the QWB scores found in patients with depression and chronic obstructive pulmonary disease (COPD), suggesting that sleep disturbances may impact daily living and health as much as other medical conditions.
Black or African American↗
Continuity of care and clinical outcome: a prospective cohort study.
BACKGROUND: Continuity of care is a central objective of community psychiatric services, but there is no consensus about its measurement. AIMS: We developed measures of continuity of care suitable for routine use, and measured continuity and individual patient outcome over a period in which community services were developing. METHOD: One hundred patients with severe mental illness receiving continuing care from two sectorised services were sampled and interviewed. Data were collected concerning their care over 20 months prior to interview. After 20 months prospective follow-up, they were re-interviewed. Continuity was defined as: perceived accessibility of services and knowledge about them, the number of keyworkers in a defined period of time, and the proportion of time out of contact with services. RESULTS: Continuity of care improved significantly on all measures over the period of the study. Individual patient outcome also improved, but in multiple regression models including clinical and demographic variables, measures of continuity were not significant predictors of outcome. Continuity was similar for white and non-white patients. CONCLUSION: Simple measures of continuity are useful in evaluating changes in the process of care, but they are not straightforwardly related to individual outcome.
Adult↗
The social context of insight in schizophrenia.
BACKGROUND: Psychiatrists place great weight on impaired insight in schizophrenia, generally attributing it to pathological mental processes. However, denial of illness may be based on attitudes common in patients' social and cultural groups. Moreover, even where denial of illness has a pathological element, it may be affected by the social context. In this paper, we predicted that denial of illness would be associated with social distance between clinician and patient, and reduced by access to 'normalizing' social interaction. METHOD: One hundred and fifty patients with schizophrenia in the London arm of the European Schizophrenia cohort were assessed using the 'Awareness of Illness' (AI) subscale of David's Assessment of Insight. Clinical and social attributes were related to AI. RESULTS: There was little evidence for our social distance hypotheses: there was little variation in AI by social class, ethnicity, membership of a drug taking culture or the presence of strongly held religious beliefs. However, there were strong relations between AI and the size of primary group, consistent with our normalizing hypothesis. CONCLUSIONS: The normalizing function of social support is in line with modern psychological models of delusion formation. Longitudinal data will eventually be available from the current study that will assist in establishing the causal direction of this association.
Adult↗
Minimal incision parathyroidectomy: cure, cosmesis, and cost.
The goals of operative treatment of primary hyperparathyroidism are (1) cure; (2) minimal invasion; and (3) cost-effectiveness. The optimal strategy is controversial. Retrospective review of was undertaken 66 previously unoperated patients having minimal-incision, full-neck exploration by one surgeon over 29 months. A group of 51 women and 15 men had open full neck exploration under general anesthesia through a small (25-40 mm) incision using specifically selected instruments; patients remained hospitalized overnight. Preoperative sestamibi scans were obtained before referral for 17 patients: 11 had localized disease, and 6 did not (65% sensitivity). Four parathyroid glands were identified in 98% of patients; intraoperative frozen section was used selectively on a median of one gland per patient. About 76% of patients had single-gland disease, 6% had two-gland disease, and 18% had four-gland hyperplasia. One patient had four normal cervical parathyroid glands and an aortopulmonary window parathyroid adenoma resected at thoracotomy 1 week later; preoperative sestamibi scans failed to localize his disease. There were no nerve injuries and a 98% cure rate after initial cervical exploration. Excluding the cost of the sestamibi scans, there was no difference between those who had preoperative localization and those who did not; 60% of hospital costs were operating room time-related. Minimal-incision parathyroidectomy is effective for curing hyperparathyroidism and has excellent cosmetic results with negligible scar. Preoperative sestamibi scanning had no impact on cure or treatment costs. Strategies to improve cost-effectiveness must address the substantial costs of anesthesia and operating room services.
Adult↗
Refined localization of a gene for pediatric gastroesophageal reflux makes HTR2A an unlikely candidate gene.
Our objective in this study was to determine whether mutations in the gene for the 5-hydroxytryptamine receptor 2A (HTR2A) cause the autosomal dominant form of severe pediatric gastroesophageal reflux (GER), which we had previously mapped to a 21-cM region at chromosome 13q14. Direct sequencing of the HTR2A gene was carried out on DNA from affected and unaffected members of families with severe pediatric GER displaying genetic linkage to the HTR2A locus. In addition, we performed high-resolution linkage mapping within the GER gene region using additional polymorphic markers closely linked to HTR2A. Several previously reported polymorphisms in the HTR2A gene were identified in three families affected with GER. In addition, we identified a novel polymorphism at nucleotide -1273 in the HTR2A promoter. No mutant allele cosegregated exclusively with the GER phenotype in any family. Linkage analysis using additional polymorphic markers narrowed the region of the GER gene to a 9 cM interval between markers D13S263 and CAGR1, formally excluding HTR2A as a candidate gene. In conclusion, sequence analysis of HTR2A and linkage analysis argue against mutations in HTR2A being a cause of severe pediatric GER.
Child↗
Family-style foodservice can meet US Dietary Guidelines for elementary school children.
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Carbohydrates↗
In vitro chemo-sensitivity of B-chronic lymphocytic leukaemia to ara-G.
In vitro sensitivity to ara-G of peripheral blood B-CLL lymphocytes from 23 patients was assessed using the flow cytometric TdT assay. All patients had typical B-CLL, according to immunophenotype and morphology, and none had received treatment within 1 year of testing. A wide range of spontaneous apoptosis was recorded. Exposure of the cells to a concentration of ara-G, comparable to plasma levels achieved in a phase I trial, produced significant increases in the rate of apoptosis in 21 out of 23 patients. Prior treatment, stage or lymphocyte doubling time did not influence the effect of ara-G. Ten patients' samples tested, in parallel, for sensitivity to fludarabine demonstrated a good correlation of response to both drugs. This in vitro evidence of activity against B-CLL suggests that the spectrum of clinically useful action may be broader than previously demonstrated.
Antineoplastic Agents↗
Investigation and control of aspergillosis and other filamentous fungal infections in solid organ transplant recipients.
Filamentous fungal infections are associated with high morbidity and mortality in solid organ transplant patients, and prevention is warranted whenever possible. An increase in invasive aspergillosis was detected among solid organ transplant recipients in our institution during 1991-92. Rates of Aspergillus infection (18.2%) and infection or colonization (42%) were particularly high among lung transplant recipients. Epidemiologic investigation revealed cases to be both nosocomial and community-acquired, and preventative efforts were directed at both sources. Environmental controls were implemented in the hospital, and itraconazole prophylaxis was given in the early period after lung transplantation. The rate of Aspergillus infection in solid organ transplant recipients decreased from 9.4% to 1.5%, and mortality associated with this disease decreased from 8.2% to 1.8%. The rate of Aspergillus infection or colonization among lung transplant recipients decreased from 42% to 22.5%; nosocomial Aspergillus infection decreased from 9% to 3.2%. Cases of aspergillosis in lung transplant recipients were more likely to be early infections in the pre-intervention period. Early mortality in lung transplant recipients decreased from 15% to 3.2%. Two cases of dematiaceous fungal infection were detected, and no further cases occurred after environmental controls. The use of environmental measures that resulted in a decrease in airborne fungal spores, as well as antifungal prophylaxis, was associated with a decrease in aspergillosis and associated mortality in these patients. Ongoing surveillance and continuing intervention is needed for prevention of infection in high-risk solid organ transplant patients.
Aspergillosis↗