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Biomedical subjects

R Walker

Publications and source records attributed to R Walker.

At least 37 records · Page 2Linked to original sources

Agaritine does not mediate the mutagenicity of the edible mushroom Agaricus bisporus.

Ethanolic extracts of the edible mushroom Agaricus bisporus displayed a direct-acting mutagenic response in various Salmonella typhimurium strains, TA104 being clearly the most sensitive. Incorporation of an activation system derived from the liver of mice, hamsters or Aroclor 1254-induced rats failed to increase the mutagenic response. The mutagenic response of ethanolic extracts from various types of mushroom, containing different levels of agaritine (range 0.3-6.5 g/kg fresh weight), was very similar and did not correlate with the agaritine levels. Moreover, use of gamma-glutamyl transpeptidase, the enzyme catalysing the activation of agaritine, as an activation system did not enhance the mutagenicity of the mushroom ethanolic extracts. It is concluded that agaritine is not responsible for the mutagenicity of mushroom extracts.

Animals

Extradural vein puncture--an avoidable complication.

Accidental cannulation of an extradural vein is a troublesome and potentially serious complication of extradural catheter insertion. This study was conducted to assess the influence of posture, catheter size and the injection of saline before catheter insertion, on its occurrence. Eight different techniques were studied based on combinations of these three factors. There was no difference in incidence with respect to posture. The use of 18-gauge catheters, after injection of 10 ml of 0.9% saline, resulted in a significant (p less than 0.01) reduction in the incidence of extradural vein cannulation. This technique is recommended in obstetric patients as a means of avoiding accidental intravenous injection of local analgesic.

Adolescent

The psychosocial effects of acne on adolescents.

To describe the psychosocial impact of acne on adolescents, and, in particular, to assess whether self-concept is affected by medical treatment, we evaluated 39 teenagers presenting for care to a community-based dermatologist. Prior to and following treatment, subjects completed a self-assessment questionnaire, the Piers-Harris self-concept scale, and underwent an objective assessment of acne severity. Fifty-eight percent of subjects were dissatisfied with their facial appearance and this in turn was correlated with feelings of embarrassment and social inhibition (for each, r = 0.48, P less than or equal to 0.005). Subjects' rating of acne severity, but not the dermatologist's, was correlated with dissatisfaction with facial appearance (r = 0.45, P less than or equal to 0.005). Despite these findings, the mean Piers-Harris total t-score (55.4 +/- 7.4) was within the normal range. Fourteen subjects (36%) returned for follow-up and 71% of these were judged by both the dermatologist and themselves to have improved. Following therapy, significant reductions in the adverse consequences of acne were observed with 42% of subjects reporting that their facial appearance was more acceptable to peers, 50% being less embarrassed, and 58% feeling less socially inhibited. Minimal improvement in mean Piers-Harris total t-score was observed (54.6 to 57.4, P = 0.004, paired t-test). Our data demonstrate that acne is perceived by adolescents to have important negative personal and social consequences, and that improvement in these areas may accompany medical treatment.

Acne Vulgaris

Ion exchange chromatography of purified colonic mucus glycoproteins in inflammatory bowel disease: absence of a selective subclass defect.

Previous reports of a selective mucin subclass defect in ulcerative colitis have been reassessed using high performance chromatography (Superose 6 and Mono Q) for mucin purification and fractionation coupled with analysis of the fractions obtained using a combination of enzyme linked lectin and mucin antibody assays. Mucin samples purified from snap frozen rectal biopsy specimens obtained from patients with ulcerative colitis (n = 12), Crohn's disease (n = 5), and non-inflammatory bowel disease control subjects (n = 9) were subject to ion exchange chromatography using a continuous 0-0.35 mol/l NaCl salt gradient with a final 2.5 mol/l NaCl step. In all samples the major proportion (mean (SD) 86.7 (8.9)%) of the mucin detectable by wheat germ agglutinin binding eluted between 0.15 and 0.35 mol/l NaCl with no significant difference in elution profile between ulcerative colitis and control subjects. Significant elution of glycoprotein at less than 0.15 mol/l NaCl did occur, however, when a lower molecular weight mucin containing fraction which contained concanavalin A positive (glucose or mannose containing) material was analysed similarly. Similar ion exchange profiles were obtained when (3H)N-acetylglucosamine labelled mucins were studied after tissue culture of rectal biopsy specimens. No significant alteration in the ion exchange profile of purified mucins in ulcerative colitis has been shown in these studies. It is possible that the previously reported relative depletion of mucin subclass IV (eluting with 0.20 mol/l NaCl) may simply have reflected mucin depletion.

Chromatography, Ion Exchange

Determination of local myocardial electrical activation for activation sequence mapping. A statistical approach.

Electrical activation sequence mapping requires accurate identification of local activation, but because extracellular recordings do not exclusively reflect local events, complex electrograms may be difficult to interpret. In such cases, the assignment of local activation is subject to error that could affect interpretation of the resulting activation maps. The purpose of this investigation was to develop an approach that would provide quantitative indexes of error in the determination of local activation. An electrode array with 64 closely spaced unipolar electrodes was used to record from the left ventricular surface during open heart surgery. Electrograms with multiple deflections were recorded from four patients with scarred myocardium; two other patients with normal myocardial function served as controls. Each of 784 deflections was scored on the basis of three features: evidence for propagation, the configuration of the bipolar signal, and the effect of changing from the chest to an average reference. Local activation was considered probable if evidence for all three features was present and improbable if none of the three features was present. Deflections that were ambiguous with respect to this standard were excluded. Of over 30 test variables analyzed, the three with the greatest power to discriminate signals due to local activation from those due to distant activity were 1) a linear combination of the extracellular potential plus the ratio of the second derivative and the extracellular potential, 2) the second derivative, and 3) the minimum (greatest negative) first derivative. For each of these variables, the threshold value providing the greatest performance was identified by the maximum quality of efficiency, an index of agreement. This statistical approach provides an objective basis for determining local activation and provides a quantitative assessment of error that could enhance interpretation of electrical activation sequence maps.

Differential Threshold

Do obstetrical charts present a liability risk?

The practice of obstetrics is well-known as a medicolegal, high-risk profession. Poor charting is considered an area of serious deficiency for physicians and especially for obstetricians. We reviewed the charting practices of obstetricians in a level II community hospital. The traditional 1- and 5-minute Apgar scores were employed as the screening criteria. Apgar scores of 7 or lower at 5 minutes were used to identify charts considered vulnerable to litigious activity. Of 1437 deliveries, 115 charts with 5-minute Apgar scores of 7 or lower were reviewed. Traditional requirements for charting, eg, history and physical exams, admission notes and diagnoses were recorded fairly consistently. However, elements such as statements of judgment, autopsy reports, scalp pHs, and extended Apgar scores that would render a chart defensible were sorely lacking. Charting skills, not necessarily the quality of care, may render obstetricians medicolegally vulnerable.

Apgar Score

Gastric ulcer healing: a comparison of enprostil versus ranitidine.

Enprostil is a synthetic prostaglandin E2 analogue with gastric antisecretory and mucosal protective properties. We compared the effects of enprostil and ranitidine on the healing of gastric ulcers and the subsequent relapse rates over 6 months. Patients (N = 156) were recruited for a double-blind study from 12 centers in Europe; 71 were randomly assigned to oral treatment with 35 micrograms enprostil twice daily and 85 to 150 mg ranitidine twice daily for up to 8 weeks. Both groups were of similar demography; their healing rates were also similar. Cumulative intent-to-treat healing rates were at 4 weeks enprostil 48%, ranitidine 41%: at 6 weeks enprostil 65%, ranitidine 68%; and at 8 weeks enprostil 72%, ranitidine 80%. Of those patients who met all protocol criteria and completed treatment, and were endoscoped at the prescribed times, healing rates were at 4 weeks enprostil 55%, ranitidine 54%, at 6 weeks enprostil 75%, ranitidine 84%; and at 8 weeks enprostil 80%, ranitidine 90%. Relief of pain was rapid and similar in both groups. The incidence of adverse events was low and similar in the two groups. The treatment-free relapse rate at 6 months was enprostil 64%, ranitidine 49%; the median times to relapse were 169 and 203 days, respectively. Enprostil and ranitidine appear to be equally effective in healing gastric ulcers.

Antacids

Recruiting must adapt to MD payment changes.

In summary, the adverse effects of reimbursement reform on physician recruiting can be overcome by proper planning--starting now. Hospital administrators who respond appropriately to this challenge can preserve income levels for both physicians and hospitals in the years ahead.

Employment

Interferon-alpha in patients with asymptomatic human immunodeficiency virus (HIV) infection. A randomized, placebo-controlled trial.

STUDY OBJECTIVE: To evaluate the toxicity and clinical efficacy of interferon-alpha 2b (IFN-alpha) in patients with asymptomatic human immunodeficiency virus (HIV) infection. DESIGN: Randomized, placebo-controlled, and double-blind study. SETTING: Outpatient clinic of a government referral-based research hospital. PATIENTS: Volunteer sample of 34 patients with asymptomatic HIV infection who had CD4 counts of 400 cells/mm3 or more, positive peripheral blood mononuclear cell cultures for HIV, or p24 antigenemia. INTERVENTIONS: Patients were randomly assigned to receive either IFN-alpha or placebo, 35 x 10(6) units per day subcutaneously. Doses of IFN-alpha or placebo were modified according to predefined laboratory and clinical criteria. Therapy lasted at least 12 weeks. MEASUREMENTS AND MAIN RESULTS: Seventeen patients were randomly assigned to each group. The two groups had similar mean CD4 counts at study entry. Thirty-five percent of patients assigned to receive IFN-alpha withdrew from the study because of toxicity. The average daily dose of IFN-alpha was 17.5 x 10(6) units. All patients receiving IFN-alpha reported flu-like symptoms; other toxicities included granulocytopenia (55%) and elevated liver enzyme levels (45%). While receiving IFN-alpha, 7 patients (41%) became HIV culture negative (three or more consecutive negative peripheral blood mononuclear cell cultures taken at least 2 weeks apart). In contrast, 2 patients in the placebo group (13%) became culture negative while on study (P = 0.05). During the treatment period, CD4 lymphocyte percentages were sustained at or above the baseline level in patients receiving IFN-alpha and declined slightly in patients receiving placebo. Of the 32 study patients followed after study (range, 5 to 33 months), no patients in the IFN-alpha group developed an acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection, compared with 5 patients in the placebo group (P = 0.02). CONCLUSIONS: Treatment of early-stage HIV infection with IFN-alpha can result in a decrease in frequency of viral isolation. Although its use may be accompanied by dose-dependent toxicities, IFN-alpha may have a role in slowing progression of HIV disease.

Adolescent

Enhancement of sickle erythrocyte adherence to endothelium by autologous platelets.

The increased adhesiveness of sickle erythrocytes (SS RBC) to endothelial cells has been confirmed in a static system utilizing fresh umbilical vein endothelium. Adherence of SS RBC to the endothelium was as great in the presence of calcium-containing buffer as when incubated in plasma. SS RBC suspended in autologous platelet-rich plasma adhered to a greater extent than when suspended in autologous platelet poor plasma. Prostacyclin, thromboxane B2, and an inhibitor of collagen- and epinephrine-induced platelet aggregation (B13.177) did not affect SS RBC adherence to endothelium. Aspirin in a concentration of 5 micrograms/ml slightly decreased SS RBC adherence to endothelium in the presence of platelets. Platelets may play a significant role in the increased adhesiveness of SS RBC to endothelium. To the extent that increased SS RBC adhesiveness contributes to the genesis of painful crises and to the extent platelets augment this adhesiveness, agents affecting platelet function may prove useful in preventing painful crises.

Anemia, Sickle Cell

Plasma exchange in progressive IgA nephropathy.

A therapeutic trial of plasma exchange was performed in 13 patients with documented progressive IgA nephropathy. Comparison of the rate of deterioration in renal function before, during, and after plasma exchange demonstrated significant improvement during plasma exchange. Seven patients had a slowed rate of deterioration by plasma exchange, but achieved a decrease in serum creatinine level. Favourable response was correlated with rapidity of deterioration preplasma exchange (P less than 0.01) and was apparent within 4 weeks of commencing therapy in those patients who responded. There was no overall difference between the deterioration rates pre- and postplasma exchange. In patients in whom creatinine decreased on plasma exchange, the initiation of subsequent dialysis was delayed.

Adolescent

In situ distribution of transforming growth factor alpha in normal human tissues and in malignant tumours of the ovary.

The distribution of transforming growth factor alpha (TGF-alpha) in human normal tissues from the uterus, Fallopian tube, ovary, small and large intestine, lung, spleen, kidney, and skin was studied by immunohistochemistry. TGF-alpha was found in epidermis, bronchial epithelium, intestinal mucosa, renal tubules, endo- as well as in exocervical and endometrial epithelium, and in the serous epithelium of the Fallopian tube. No TGF-alpha was detected in the stromal components of any of the tissues nor in any of the pre- and post-menopausal ovaries studied. Twenty-nine ovarian tumours including 23 ovarian carcinomas, one malignant mixed Mullerian tumour, two ovarian metastases of gastrointestinal carcinomas, one dysgerminoma, one sarcoma, and one fibroma were studied for TGF-alpha by the same immunohistochemical method. In 25 cases, specific cytoplasmic staining for TGF-alpha of epithelial tumour cells could be demonstrated. The pattern and intensity of the TGF-alpha immunostain varied among the TGF-alpha-positive tumours. No TGF-alpha was found by immunohistochemistry in the remaining four cases nor in the stromal tumour components of any of the lesions studied. Northern blot analysis for TGF-alpha mRNA was performed on 12 of the tumours. While the immunohistochemistry and blotting results correlated well in ten cases, discordant results were obtained in two lesions.

Blotting, Northern

Hepatic peroxisomal and microsomal enzyme induction by citral and linalool in rats.

The short-term effects of oral administration of citral and linalool to rats have been compared. Male Wistar rats were given, by gastric intubation, 1.5 g citral or linalool/kg body weight/day for 5 days. Citral caused peroxisome proliferation as indicated by induction of cyanide-insensitive palmitoyl-CoA oxidation and bifunctional enzyme; levels of microsomal cytochrome P-450 IVA1 were also raised. Linalool caused induction of the peroxisomal enzymes but not of cytochrome P-450 IVA1, indicating that it possesses activity somewhat different from that of citral. These results suggest that the mechanisms of peroxisome proliferation may be independent of induction of cytochrome P-450 IVA1.

Acyclic Monoterpenes

The induction of P450 I proteins by aromatic amines may be related to their carcinogenic potential.

The hypothesis has been put forward that genotoxic aromatic amines which induce the P450 I family of haemoproteins, the major enzyme involved in their bioactivation, are more likely to be carcinogenic when compared to those chemicals that fail to do so. Induction of the hepatic P450 I family of proteins by carcinogenic aromatic amines and their non-carcinogenic isomers and analogues was investigated in the rat and correlated to their carcinogenic potential. The activity of the P450 I A1 protein was monitored by the O-deethylation of ethoxyresorufin and of the P450 I A2 by the activation of the premutagen Glu-P-1 to mutagenic intermediates in the Ames test. Results were always confirmed immunologically in Western blots employing antibodies to rat P450 I A1 which recognize both proteins of the P450 I family. With all groups of chemicals used in the present study, the members displaying carcinogenicity were always the more potent inducers, while the non-carcinogenic isomers or analogues displayed little or no induction. It appears that a relationship exists between the carcinogenicity of aromatic amines and their ability to induce hepatic P450 I activity.

Amines