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Biomedical subjects

R Stone

Publications and source records attributed to R Stone.

At least 235 records · Page 13Linked to original sources

Pituitary-adrenal axis rhythm disturbances in psychiatric depression.

We studied disturbances in the circadian pattern of plasma corticotropin and cortisol concentrations in 25 depressed patients (eight dexamethasone suppression test [DST] nonsuppressors and 17 suppressors) and 21 normal control subjects. Blood samples were drawn every 20 minutes for 24 hours before the administration of dexamethasone, and for a second 24 hours after the administration of 1 mg of dexamethasone. The corticotropin and cortisol level rhythms were examined using three different statistical methods. Nonsuppressors averaged greater elevations in plasma cortisol and corticotropin levels than did subjects in the other two groups, both before and after administration of the dexamethasone. The cortisol levels of the suppressors were virtually identical to those of the control subjects. However, the suppressors had significant elevations of corticotropin levels compared with normal control subjects, especially on the day before taking dexamethasone. Before taking dexamethasone, the depressed patients reached a daily nadir of cortisol concentration approximately two hours earlier than did the normal control subjects. The DST nonsuppressors also exhibited a blunting in the expected circadian rhythm of the corticotropin level.

Adrenocorticotropic Hormone↗

Genetic control of mitogen-induced B-cell hyperproliferation in SM/J mice.

Previous studies have shown that B cells from SM/J mice exhibit hyperproliferative responsiveness to several bacterial-derived B-cell mitogens. This hyperresponse trait was found to be under autosomal, polygenic control by non-H-2 genes. We have now estimated the number of genes involved by statistical analysis of the proliferative responses of splenocytes from SM/J and low-responder C57BL/6J strains, and progeny from the (B6 X SM)F1, F2 and (F1 X B6) crosses. The number of loci involved was ascertained using two different statistical approaches. An estimate of two loci was determined using chi-squared statistics. The second approach, based on an additive model in the natural log scale, also pointed to a lower bound of two genes. We conclude that the hyperresponse to B-cell mitogens in SM/J mice is determined by two autosomal genes which are not linked to the H-2 major histocompatibility complex.

Animals↗

Immunoregulation in severe generalized periodontitis.

Severe generalized periodontitis (SGP) is an inflammatory disease which leads to extensive alveolar bone loss in young adults. Peripheral blood lymphocytes from SGP patients have been previously reported to exhibit an in vitro hyperproliferative response when exposed to B cell mitogens derived from Staphylococcus aureus and Actinomyces viscosus. Therefore hyperresponsiveness to B-cell mitogens could be an important pathogenic factor in the susceptibility to and progression of SGP. We have tested whether the hyperproliferative response of lymphocytes from SGP patients was due to (i) a functional deficiency of suppressor T cells, or (ii) to numerical alterations of lymphocytes. Supernatant fluids from concanavalin A-stimulated T cells from 14 SGP patients and 14 normal subjects were compared for their ability to suppress the IgM synthesis of B-cell mitogen-stimulated mouse splenocytes. No significant differences were noted in suppressor T-cell function between control subjects and SGP patients. However, SGP patients had significantly higher lymphocyte counts than control subjects, and there was a positive correlation between high lymphocyte counts and high mitogen-stimulated proliferation. SGP patients also had higher lymphocyte:monocyte ratios than control subjects, suggesting that a defect in macrophage-mediated suppression might be involved in the hyperproliferation phenomenon. Our data do not support the hypothesis that a suppressor T-cell defect is the cause of mitogen-induced hyperproliferative responsiveness of peripheral blood lymphocytes from SGP patients. Rather, hyperproliferation may be due to an expansion of the lymphocyte pool which responds to mitogens, or/and a regulatory disturbance which arises because of altered lymphocyte:macrophage ratios.

Actinomyces↗

The effect of d-timolol on intraocular pressure in patients with ocular hypertension.

The stereoisomer form of timolol used in the treatment of glaucoma is l-timolol. Although d-timolol is a less potent beta-adrenergic receptor blocker than l-timolol, several laboratory studies have found that d-timolol has ocular hypotensive effects. Thus, d-timolol may be a useful therapeutic agent for glaucoma that has fewer systemic side effects than l-timolol. We conducted a randomized, double-masked, single-drop study of the effects of d-timolol and placebo on intraocular pressure in 34 patients with ocular hypertension. d-Timolol significantly lowered intraocular pressure for the six-hour duration of the study. No patients receiving the drug reported subjective side effects. There was no change in visual acuity, pupil size, or results of external ocular or slit-lamp examinations during the study. No changes in pulse rate or blood pressure were attributable to the drug.

Administration, Topical↗

Mitogen-induced hyperproliferation response of peripheral blood mononuclear cells from patients with severe generalized periodontitis: lack of correlation with proportions of T cells and T-cell subsets.

Severe generalized periodontitis (SGP) is a localized inflammatory disease which differs clinically from common periodontitis in that it leads to remarkable extensive alveolar bone loss in relatively young adults. There is evidence that B-cell responses to bacterial substances may play a major role in the pathogenesis of this disease. In the present report, we show that a B-cell mitogen from Actinomyces viscosus (AVIS) bacteria provokes a hyperproliferation response of peripheral blood mononuclear cells (PBMNC) from these patients. In addition, AVIS-stimulated PBMNC from SGP patients proliferate for longer periods in culture than do PBMNC from control subjects. There were, however, no differences between patients and controls in the numbers of immunoglobulin-secreting cells in these cultures as determined by an indirect plaque-forming cell assay. The possibility that differences in numerical proportions of regulatory T-cell subsets may play a role in the mitogen-induced hyperproliferation phenomenon is examined. PBMNC were stained with fluorescein isothiocyanate-conjugated monoclonal antibodies OKT3, OKT4, and OKT8 in order to identify, respectively, total T cells, helper/inducer, and suppressor/cytotoxic subsets. Flow cytometric analysis of such specifically stained cell preparations from 14 control subjects and 14 SGP patients did not reveal any significant differences between the proportions of total T cells or T-cell subsets of the two groups. Furthermore, there were no statistically significant correlations between the magnitude of proliferation responses and the proportions of total T cells or either of the T-cell subsets.

Adult↗

Antitumor imidazotetrazines. 1. Synthesis and chemistry of 8-carbamoyl-3-(2-chloroethyl)imidazo[5,1-d]-1,2,3,5-tetrazin-4(3 H)-one , a novel broad-spectrum antitumor agent.

Interaction of 5-diazoimidazole-4-carboxamide and alkyl and aryl isocyanates in the dark affords 8-carbamoyl-3-substituted-imidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-on es. In cold methanol or ethanol, the 3-(2-chloroethyl) derivative 7a decomposes to afford 2-azahypoxanthine (14) and methyl and ethyl N-(2-chloroethyl)carbamates, respectively. Compound 7a has curative activity against L-1210 and P388 leukemia and may act as a prodrug modification of the acyclic triazene 5-[3-(2-chloroethyl)triazen-1-yl]imidazole-4-carboxamide (MCTIC), since it ring opens to form the triazene in aqueous sodium carbonate.

Animals↗

A case-control study of the association of sickle cell trait and chronic open-angle glaucoma.

Chronic open-angle glaucoma is reported to be more common in blacks than in whites. The reasons for a higher prevalence of this disease in blacks are unclear. Two recent small case series from clinical practice have been published in which secondary open-angle glaucoma was diagnosed in blacks with sickle cell trait who had experienced either traumatic or nontraumatic hyphema. The association of sickle cell trait and chronic open-angle glaucoma has been tested only in a small case-control study of uncontrolled chronic open-angle glaucoma patients undergoing surgery. No significant association was found. However, the higher prevalence of sickle cell trait in blacks compared with whites raises the question of whether the presence of sickle hemoglobin is a risk factor for chronic open-angle glaucoma in the black population. To test for a possible association between this disease and sickle cell trait, we conducted a case-control study in black ophthalmic patients at the University of Pennsylvania and affiliated hospitals between December 1981 and July 1982. Sickle cell trait, as measured by the sickle cell preparation test, was no more prevalent in patients with chronic open-angle glaucoma than in age- and sex-matched ophthalmic clinic controls. It is unlikely that hemoglobin SA is a risk factor for chronic open-angle glaucoma.

Adult↗

The effect of stirring of the luminal solution on the protection of the rat intestinal mucosa during ischemic injury.

Segments of rat ileum made ischemic for 15 min by occlusion of their mesenteric vessels were intraluminally perfused at slow and rapid rates with Krebs buffer containing O2, O2 + glucose or nitrogen. Mucosal leucine influx was measured at the end of the ischemic period. O2 and O2 with glucose provided protection against the ischemic injury, particularly when the stirring of the luminal solution was increased. Rapid perfusion in the absence of oxygen or glucose also protected the intestine probably by rinsing the ischemic gut of noxious agents.

Animals↗

Modern management of anastomotic leak after esophagogastrectomy.

From 1970 to 1981, 167 patients, aged 35 to 84 years (mean 61), underwent resection of 94 adenocarcinomas and 73 squamous cell cancers. The operative mortality was 8.9 percent. Anastomotic leaks occurred in 19 patients (11.3 percent), including 18 of 72 (25 percent) after operations for palliation and 1 of 95 (1 percent) after procedures with curative potential (p less than 0.01). The leakage rate after esophagogastrostomy was 8.5 percent, compared with 43 percent after interposition operations. No leak is attributed to cancer in anastomotic margins. In contrast to previous reports of greater than 50 percent mortality from leaks, only 21 percent of our patients died in the past decade. Four of 19 contained leaks (sinus tract or upper gastrointestinal) were treated nonoperatively; esophagostomy was used only once. Factors responsible for improving results include early diagnosis with routine contrast studies on the fifth to seventh postoperative days, mandatory use of total parenteral nutrition, nonoperative management of contained leaks, accurate, aggressive use of adjuvant chest tubes, and selective esophagostomy for anastomotic disruption.

Adenocarcinoma↗

Bladder outflow obstruction treated with phenoxybenzamine.

Sixty-one male patients with urodynamically proven outflow obstruction took part in a study of phenoxybenzamine (PBZ), the initial phase of which was double-blind (41 patients). The double-blind phase of the trial showed an overall symptomatic improvement in the PBZ patients. The symptoms of slow stream and hesitancy were significantly improved. The urethral pressure profile features of prostatic plateau height and prostatic plateau area were significantly decreased in the PBZ group. Dizziness was the commonest side effect of PBZ but was well tolerated by most patients. This study shows that PBZ has an effect on bladder outflow obstruction by reducing pressure in the proximal urethra and that the drug has a place in the management of patients with symptoms attributable to such obstruction, especially where operative treatment has to be delayed.

Aged↗

Crohn's disease in children.

Forty-one children with Crohn's disease were seen over a 10 year period. Fifty percent of these patients were diagnosed at ages 13 to 16 years. The colon and small bowel were involved in half of the patients. Twenty-six patients required surgery for resection of bowel or diversionary procedures. Sixty percent of the patients with small bowel disease alone responded to medical therapy. We have been unable to document that growth failure can be predictably reversed by surgery. There were no deaths in this series and no patient was lost to follow-up. At present, only one patient is unable to perform the full-time activities of daily living. The longest period of follow-up is 10 years.

Adolescent↗

Bladder outflow obstruction treated with phenoxybenzamine.

Sixty-one male patients took part in a study of phenoxybenzamine (PBZ), the initial phase of which was double-blind (41 patients). All patients had urodynamically proven outflow obstruction. The double-blind phase of the trial showed an overall symptomatic improvement in the PBZ patients. The symptoms of slow stream and hesitancy were significantly improved. The urethral pressure profile features of prostatic plateau height and prostatic plateau area were significantly decreased in the PBZ group. Dizziness was the most common side effect of PBZ but was well tolerated by most patients. This study shows that PBZ has an effect on bladder outflow obstruction by reducing pressure in the proximal urethra and that the drug is suitable for the treatment of patients with symptoms attributable to obstruction.

Aged↗

Esophagogastrectomy using the auto suture EEA surgical stapling instrument.

A stapling instrument, which creates end-to-end inverting anastomoses, is described for esophagogastrostomy. The inverted anastomosis is held together by a double staggered row of stainless-steel wire staples. Experience with 7 consecutive patients who underwent esophagogastrectomy for carcinoma of the distal esophagus or proximal stomach using this device is reported. Postoperative complications included atelectasis in 1 patient, cardiac failure in 1, and pneumonia in 1. A fibrotic stricture developed at the anastomotic site 5 months postoperatively in 1 patient. There were no anastomotic leaks. The stapled anastomosis takes 2 to 3 minutes to perform and seems to be at least comparable to handsewn anastomoses.

Adenocarcinoma↗