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Biomedical subjects

R Walker

Publications and source records attributed to R Walker.

At least 271 records · Page 15Linked to original sources

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↗

Mechanism of the in vitro antimutagenic action of retinol.

The antimutagenic action of retinoids against three amino-imidazoazaarene pre-carcinogens, i.e. 2-amino-3-methylimidazo(4,5-f)quinoline (IQ), 2-amino-3,4-dimethylimidazo(4,5-f)quinoline (MeIQ) and 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline (MeIQx), was investigated using the Ames test and hepatic activation systems derived from rats pretreated with Aroclor 1254. Both retinol and retinal, when incorporated into the S9 activation system, gave rise to a concentration-dependent decrease in the mutagenicity of all three mutagens, retinol being generally the more effective. Retinol suppressed the mutagenic activity of IQ even when isolated microsomes were used as activation systems. Moreover, retinol gave rise to a concentration-dependent inhibition of the microsomal dealkylations of pentoxy- and benzyloxy- and, especially, ethoxy-resorufin, but had no effect on the NADPH-dependent reduction of cytochrome c. Exposure of the bacteria to retinol with subsequent removal of the vitamin did not influence the mutagenicity of IQ. It is concluded that retinoids suppress the mutagenicity of aminoimidazoazaarenes and this is achieved through inhibition of their cytochrome P450-dependent metabolic activation. Retinol is a non-selective in vitro inhibitor of the hepatic cytochrome P450-dependent mixed function oxidase system as predicted by a computer graphic analysis of its molecular shape.

Animals↗

Conduction velocity depression and drug-induced ventricular tachyarrhythmias. Effects of lidocaine in the intact canine heart.

Depression of myocardial conduction velocity can be an important mechanism of action of antiarrhythmic drugs but it can also facilitate arrhythmogenesis. We used lidocaine in an anesthetized canine preparation to address the hypothesis that drug-induced rate-dependent conduction velocity depression causes ventricular tachyarrhythmias. A closely spaced square array of 64 electrodes was used to determine conduction velocity longitudinal and transverse to epicardial ventricular fiber direction. Lidocaine caused rate-dependent decreases in conduction velocity that were proportionately greater in the longitudinal direction at the shortest pacing cycle lengths. Conduction velocity depression developed rapidly in the presence of lidocaine with a new steady state present by the second beat of the rapid train. Recovery from rate-dependent depression of conduction velocity was exponential with a time constant of 122 +/- 20 msec (mean +/- SD) in the longitudinal direction and 114 +/- 30 msec in the transverse direction; this difference was not significant. The relation between conduction velocity depression and ventricular arrhythmias was assessed by pacing for 3 minutes at cycle lengths of 1,000, 500, 300, and 250 msec, and for 1 minute at a cycle length of 200 msec. Arrhythmias did not occur in the baseline period in the dogs that received lidocaine, nor in 12 control dogs that were subjected to the same stimulation protocol except that saline was administered in place of lidocaine. Sustained polymorphic ventricular tachycardia (VT) occurred in six of 16 dogs given lidocaine. VT occurred in the presence of relatively high plasma lidocaine concentrations (8.4 +/- 2.3 micrograms/ml) and only at pacing cycle lengths of 300 msec or shorter. The dogs that developed VT demonstrated greater rate-dependent depression of conduction velocity than the other dogs, and activation patterns obtained just before the onset of VT showed marked conduction disturbances. Furthermore, QRS prolongation, loss of one-to-one capture, and increasingly distorted activation patterns preceded the onset of VT during fixed-rate pacing, suggesting progressive sodium channel block. In summary, rate-dependent conduction velocity depression and nonuniform activation were associated with VT in this model and can be responsible for some arrhythmias induced by antiarrhythmic drugs.

Animals↗

Effect of cyclosporin on pancreatic events and development of diabetes in BB/Edinburgh rats.

The effect of cyclosporin administered from 30 to 100 days of age on pancreatic events and the development of insulin-dependent diabetes has been studied by serial pancreatic biopsy of individual diabetes-prone BB/Edinburgh rats. Cyclosporin completely prevented the development of diabetes up to 150 days of age and reduced the incidence to 50% of controls at 452 days of age. Islet cell surface antibodies paralleled the development of diabetes. Insulin autoantibodies were unrelated to diabetes and not affected by cyclosporin. Immunohistochemical analysis of pancreatic biopsies from untreated control diabetes-prone rats with monoclonal antibodies specific for rat MHC molecules and T- and B-lymphocyte and macrophage subsets showed that the first abnormality seen in rats that subsequently developed diabetes was hyperexpression of MHC class I molecules on vascular endothelium and islet cells. This was followed by accumulation of ED1+ macrophages at perivascular and periductal sites adjacent to noninfiltrated islets. Increased expression of MHC class II molecules on vascular endothelial cells was also noted. Most cells infiltrating the islets initially were also ED1+ macrophages, followed by increasing numbers of other activated effector cells including helper and cytotoxic-suppressor T lymphocytes and natural killer cells. Obliteration of insulin-containing cells was associated with regression of the infiltrate. Treatment with cyclosporin had no effect on pancreatic hyperexpression of MHC class I molecules but markedly inhibited accumulation of ED1+ cells at extraislet sites, the subsequent recruitment of immune effector cells, and islet infiltration. This resulted in a delay of the onset of diabetes in some rats and prevention of diabetes in others.

Animals↗

Lamina-selective A68 immunoreactivity in primary visual cortex of Alzheimer's disease patients.

Sections of area 17 from 9 Alzheimer's disease (AD) and 13 control cases were stained using the monoclonal antibody, Alz-50, which identifies pathologically-involved neuronal systems in AD patients. Strong positive staining was seen only in AD cases. The pattern of staining was highly lamina-selective; laminae I-IVa and V were intensely stained and lamina VI staining was moderately intense, while laminae IVb and IVc were relatively unstained. The results support the growing consensus that cortical pathology in AD is not generalized, but affects specific neuronal populations. The specific anatomical distribution of degenerative change suggests that there may be a specific set of visual deficits in AD patients.

Adolescent↗