Onchocerciasis in members of an expedition to Cameroon: role of advice before travel and long term follow up.
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Biomedical subjects
Publications and source records attributed to R Davidson.
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The pairing of the half-cysteine residues of human prostatic acid phosphatase was established by proteolytic digestion and analysis of the resulting peptide mixtures by fast atom bombardment mass spectrometry (FAB-MS). An independently derived, full length cDNA clone was used as the basis for the interpretation of the FAB-MS data. The sequence of the native protein is that predicted from the present cDNA sequence, except for the carboxyl-terminal end and some possible post-translational deamidations. Isolated human prostatic acid phosphatase was found to have multiple carboxyl-terminal ends, terminating in Thr, Glu, and Asp, corresponding to residues 349-351 of the 354-residue protein that is predicted from the cDNA sequence after removal of a leader peptide. The protein contains no free sulfhydryl groups. The identical monomer chains of the dimeric native enzyme are found to contain three disulfide bonds, specifically Cys-129 to Cys-340, Cys-183 to Cys-281, and Cys-315 to Cys-319. In view of the conserved positions of cysteines in the homologous human and rat liver lysosomal acid phosphatases, an identical disulfide bonding pattern may be predicted for those proteins. The location of a potential antigenic site was established by selective labeling of proximate tyrosine residues predicted to be on the surface. A conserved RHGXRXP sequence is present in the prostatic, lysosomal, Escherichia coli, and yeast acid phosphatases and is predicted to be of mechanistic significance. In addition, residue Arg-54 is shown to be an active site residue by reaction of the enzyme with phenylglyoxal. Interestingly, this residue is present in a sequence RXRY (R,H) that is also present in lysosomal phosphatase and in recently described protein tyrosine phosphatases.
Eosinophils (EOSs) cultured in the presence of 50% peripheral blood mononuclear cell (PBMC)-derived culture supernatants remained 67% +/- 7% (mean +/- SEM; n = 5) viable for 7 days. In the absence of PBMC supernatant, only 15% +/- 7% of cells remained viable for 7 days. PBMC supernatants from six atopic individuals, with eosinophilia, and six normal subjects, with no eosinophilia, were compared for EOS viability-enhancing activity with the same target EOSs. Optimal conditions for the production of viability-enhancing activity by mononuclear cells were established as a 24-hour culture period, with a concentration of 2 x 10(6) cells per milliliter. Comparison of monocyte-enriched and lymphocyte-enriched culture supernatants for the production of the EOS viability-enhancing activity indicated that both cell types released the factor. C-18 Sep-Pak separation of the PBMC culture supernatant yielded a major EOS viability-enhancing activity in the aqueous eluent, suggesting a hydrophilic molecule. This major activity was neutralized by a specific antibody to granulocyte/macrophage colony-stimulating factor but was unaffected by specific antibodies to interleukin-3 and interleukin-5. A second, minor viability-enhancing activity was observed in the 100% methanol fraction, indicating the presence of a more hydrophobic molecule. The supernatants from the PBMCs of the atopic individuals consistently enhanced EOS survival to a greater extent than supernatants from the PBMCs of the normal, nonatopic individuals.
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Sweat glands isolated from skin obtained from normal subjects and patients with cystic fibrosis (CF) were pre-loaded with 86Rb+ and superfused with a physiological salt solution and the rate of 86Rb+ efflux was measured as an indicator of cellular potassium permeability. Acetylcholine always evoked a permeability increase in the glands from control subjects and this response could be resolved into calcium-dependent and calcium-independent components. Sweat glands from CF patients did not show such consistent responses. In three individuals the glands were abnormally insensitive to acetylcholine but normal responsiveness was seen in a fourth case. It is proposed that CF can induce dysfunction of calcium-dependent control processes in sweat glands.
Radioisotopic renal scanning after angiotensin converting enzyme inhibition (ACEI) has proven to be an exciting area for research. The biologic activity of markers such as DTPA and hippuran, when combined with the physiological effects of ACEI, may provide noninvasive methods of diagnosing both renal artery stenosis and renovascular hypertension. Recent investigators have demonstrated that the sensitivities and specificities of these tests may vary widely; these differences are probably due to variations in study design, patient population, diagnostic criteria, and outcome measurements. We have reviewed these studies and discuss these possible sources of variation and their impact on the clinical usefulness of these diagnostic tests, especially in relation to the prevalence of disease in the population. Current results suggest that the post-ACEI DTPA scan is relatively accurate in the diagnosis of renal artery stenosis, with sensitivity generally greater than 90% and specificity around 95%. However, the best results in predicting the response to angioplasty or surgery in patients with renal artery stenosis have been with the use of post-ACEI hippuran in combination with furosemide (sensitivity, 96%; specificity, 95%). With confirmation of these findings and continued investigation, it is expected that accurate noninvasive tests will be available for widespread clinical use in the near future.
Acquired torticollis in children is a symptom that may be due to a number of underlying causes, some of which are severe and life threatening. Musculoskeletal, ophthalmologic, infectious, neurologic, and neoplastic conditions may present early with only torticollis. Because torticollis is a symptom, the broad spectrum of possible diagnoses requires a thorough and methodical workup. A wide variety of tests may be necessary, as well as specialty consultation. No matter how common or rare the disorder, it must be considered when evaluating a child with acquired torticollis. The first step in evaluation is always a careful and complete physical examination. An outline of the disorders associated with torticollis is presented, as are illustrative case histories.
Peripheral blood lymphocytes from healthy, Epstein-Barr virus (EB-virus)-seropositive donors and from patients with acute Plasmodium falciparum malaria were tested for their cytotoxicity towards autologous EB-virus-infected B-cells using an in vitro regression assay. Of the 18 cultures from control donors, 88.8% showed the normal pattern of regression. Of the 20 malaria patients in the study, 40% failed to exhibit the normal pattern observed in the control group. Analysis of the lymphocyte subsets showed a high incidence of inverted CD4:CD8 ratios in the patient group due to an absolute rise in the CD8 population. This data suggests that the immunosuppressive effects of acute malaria extend to defective control over EB-virus. The relevance of the observations to the aetiology of EB-virus-associated, endemic Burkitt's lymphoma (eBL) is discussed.
Pantothenate-derived coenzymes are extensively involved in intermediary metabolism, particularly in the metabolism of lipids. Using a rat model of diet-induced pantothenate deficiency, we hoped in this study to relate pantothenate status, as indicated by serum pantothenate and hepatic coenzyme A, to levels of circulating triglycerides and free fatty acids. Although commercial "vitamin-free" casein contained approximately 3 mg total pantothenate per kilogram, marked changes in serum pantothenate and hepatic CoA still occurred during weeks when rats were fed purified diets supplemented with 0 to 1600 mg pantothenate per kilogram of diet. Conditions in different experiments included ad libitum or pair-feeding of 3- or 6-wk-old rats and blood sampling from 3 to 24 h after feeding. Under most conditions of mild pantothenate deficiency in which weight differences between groups were not statistically significant, serum triglyceride and free fatty acid levels were significantly elevated in pantothenate-deficient groups. Mild pantothenate deficiency appears to have observable in vivo effects on triglyceride metabolism before severe deficiency causes significant weight loss.
In this short study the relationship between recency discrimination ability and a measure of alcohol intake was examined using a series of regression analyses. Semi-partial correlations were extracted in order to evaluate which variables (level of alcohol consumption, age and IQ) best predicted recency discrimination performance on both verbal and non-verbal tasks. Results showed that while IQ best predicted performance on the verbal task both IQ and alcohol intake were significant predictors on the non-verbal task. The results are discussed in relation to current findings and the continuity hypothesis.
A recent survey of antibiotic prophylaxis found that local practice often differed from that recommended by authoritative bodies such as the British Society for Antimicrobial Chemotherapy (BSAC) and the American Heart Association (AHA). Practitioners found the subject confusing and requested guidance. For these reasons we present current recommendations. Unfortunately all recommendations are based on animal studies and an understanding of the pathogenesis of bacterial endocarditis in humans. There are no controlled trials in humans on which to base guidelines, so rigidity is inappropriate. It is also important to realise that optimal prophylaxis will not eliminate bacterial endocarditis. In developed countries it has been estimated that only 10% of cases of endocarditis are theoretically preventable.
1. Supersensitivity or up-regulation of presynaptic alpha 2-adrenoceptors may be involved in the pathogenesis of depression. 2. The authors used a thermoregulation paradigm to test the hypothesis that chronic treatment with a tricyclic antidepressant amitriptyline (AMI) produces subsensitivity to the hypothermic effects of the alpha 2 agonist clonidine. 3. Treatment with amitriptyline produced blunting of the hypothermic response to clonidine. 4. Subsensitivity persisted for at least 21 days--that point after the discontinuation of the tricyclic at which the animals were last challenged with clonidine. 5. These findings are consistent with previous reports that tricyclic antidepressants produce subsensitivity of alpha 2 adrenoceptors.
The Severity of Alcohol Dependence Data (SADD) questionnaire was administered under different conditions to three groups of patients in Leeds, Derry and Omagh. The results were then factor analysed using both exploratory and confirmatory procedures. There was a consistent and strong first factor which suggests that with some small modifications the SADD is a unidimensional scale. The results are interpreted as providing further evidence for the homogeneity of the alcohol dependence syndrome.
Two regimens of lithium prophylaxis with different pharmacokinetic characteristics were compared under double-blind conditions in 25 bipolar patients in remission already stabilized on lithium, to determine the relative effects of each regimen on renal function. Once-daily lithium carbonate (Priadal), which gives a peak lithium plasma level 2-3 h post-administration with a low level 24 h later, was compared with twice-daily lithium citrate (Litarex), which maintains a steadier 24 h plasma level. Patients were allocated randomly to one of the 2 regimens. They were seen monthly for clinical ratings over the course of 12 months. A comprehensive battery of renal function tests was undertaken at the start of the trial, between 6-9 months after the start and again after 1 year. No significant differences were observed in clinical outcome, side effects or renal function between the 2 regimens.
Incubation of eosinophils (EOS) with alveolar macrophage (AM) supernatants isolated from asthmatic subjects followed by stimulation with the calcium ionophore A23187 resulted in enhancement of the capacity of EOS to elaborate leukotriene C4 (LTC4) (mean enhancement 169 +/- 37%, n = 31). Pretreatment of EOS with AM supernatants derived from normal individuals did not enhance LTC4 generation as compared with control medium. Enhancement was maximal when EOS were preincubated with a 1:6 dilution of AM supernatants for 5 min at 37 degrees C and were then stimulated with 5 microM A23187 for 15 min. Separation of AM supernatants by size-exclusion HPLC using a TSK G3000 SW column resulted in a peak of enhancing activity with an estimated molecular mass of approximately 30,000 D. Further purification by anion exchange HPLC using a TSK DEAE 5PW column (pH 7.4) resolved the activity into a minor peak at 0.17 M NaCl and a major peak at 0.2 M NaCl. The activities were distinct from interleukin-1 and tumor necrosis factor. Resolution of the major peak of activity by reverse-phase HPLC using a C18 spherisorb ODS column and a slope gradient of 0 to 100% acetonitrile/0.1% trifluoroacetic acid demonstrated a single peak of activity that eluted at 41% acetonitrile. The enhancing activity was sensitive to trypsin and heat and was neutralized by a specific antibody to granulocyte-macrophage colony-stimulating factor (GM-CSF). Pretreatment of EOS with recombinant GM-CSF primed the cells for enhanced LTC4 generation following subsequent stimulation with A23187. GM-CSF may play a role in the amplification of the eosinophilic inflammation in asthmatic airways.
A newborn infant with marked hydrocephalus had a large papilloma of the choroid plexus originating in the fourth ventricle and infiltrating the brain stem. The computed tomographic (CT) scan appearance was distinctive, showing vascularity and marked enhancement with contrast medium. Histological confirmation was made from several surgical sites. Total removal of the tumor was not possible. Review of congenital choroid plexus brain tumors reveals the location of this child's tumor in the fourth ventricle to be uncommon.