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Biomedical subjects

S Reddy

Publications and source records attributed to S Reddy.

At least 199 records · Page 11Linked to original sources

Isolated vaginal recurrences of endometrial carcinoma.

PURPOSE: The authors undertook this study to evaluate the results of radiation therapy (RT) for vaginal recurrence in early stage endometrial carcinoma. MATERIALS AND METHODS: Between 1964 and 1987, 34 patients with isolated vaginal recurrences of endometrial carcinoma were treated with RT. The records were reviewed for outcome and prognostic factors, such as location of tumor recurrence, time to recurrence, size of tumor at recurrence, tumor differentiation, and total radiation dose delivered at RT. RESULTS: With a median follow-up of 48 months, the 5-year actuarial survival and disease-free survival rates were 68% +/- 4 and 60% +/- 3, respectively. Results were statistically significant for some prognostic factors, including time to tumor recurrence and total radiation dose delivered at RT to the recurring tumor. CONCLUSION: Long-term survival can be obtained for patients with an isolated vaginal recurrence of endometrial cancer treated with aggressive local-regional radiation therapy.

Actuarial Analysis↗

Enhanced expression of rat hepatic CYP2B1/2B2 and 2E1 by pyridine: differential induction kinetics and molecular basis of expression.

Expression of the cytochrome P450 (CYP) 2B subfamily in rat and rabbit hepatic tissues after pyridine (PY) treatment has been examined, and the molecular basis for enhanced 2B1/2B2 expression has been determined. P450 expression was monitored using metabolic activity, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblot analyses, and the identity of the proteins was confirmed through N-terminus microsequence analysis. PY caused a dose-dependent elevation of hepatic CYP2B1/B2B levels in rats, which ranged from 4- to 22-fold over the dosing regimen of 100 to 400 mg PY/kg/day, for 3 days, respectively. PY at low dose failed to induce CYP2B in rabbit hepatic tissue, suggesting a species-dependent response in 2B expression. Anti-2B1 IgG addition to PY-induced microsomes inhibited benzphetamine N-demethylase activity by only approximately 15%, in sharp contrast to the approximately 73% inhibition observed for phenobarbital-induced microsomes, suggesting the induction of other form(s) of P450 having benzphetamine N-demethylase activity. Northern blot analysis revealed that PY treatment increased 2B1 and 2B2 poly(A)+ RNA levels approximately 69- and approximately 34-fold, respectively, whereas the 2E1 poly(A)+ RNA levels failed to increase. The results of this study show that PY induces CYP2B1/2B2 and that induction is species-dependent and kinetically distinguishable from 2E1 induction. Moreover, 2B1/2B2 induction occurs as a result of elevated mRNA levels associated with either transcriptional activation or mRNA stabilization, and it differs from the mechanism of hepatic 2E1 induction by PY.

Animals↗

Fluorescence-activated sorting of totipotent embryonic stem cells expressing developmentally regulated lacZ fusion genes.

Murine embryonic stem (ES) cells were infected with a retrovirus promoter trap vector, and clones expressing lacZ fusion genes (LacZ+) were isolated by fluorescence-activated cell sorting (FACS). Of 12 fusion genes tested, 1 was repressed when ES cells were allowed to differentiate in vitro. Two of three lacZ fusion genes tested were passed into the germ line, indicating that FACS does not significantly affect stem cell totipotency. The pattern of lacZ expression observed in vivo was consistent with that seen in vitro. Both fusion genes were expressed in preimplantation blastulas. However, a fusion gene whose expression was unaffected by in vitro differentiation was ubiquitously expressed in day-10 embryos, while the other, which showed regulated expression in vitro, was restricted to cells located along the posterior neural fold, the optic chiasm, and within the fourth ventricle. These results demonstrate the utility of using promoter trap vectors in conjunction with fluorescence sorting to disrupt developmentally regulated genes in mice.

Animals↗

The systemic availability of oral glutathione.

When the plasma glutathione concentration is low, such as in patients with HIV infection, alcoholics, and patients with cirrhosis, increasing the availability of circulating glutathione by oral administration might be of therapeutic benefit. To assess the feasibility of supplementing oral glutathione we have determined the systemic availability of glutathione in 7 healthy volunteers. The basal concentrations of glutathione, cysteine, and glutamate in plasma were 6.2, 8.3, and 54 mumol.l-1 respectively. During the 270 min after the administration of glutathione in a dose of 0.15 mmol.kg-1 the concentrations of glutathione, cysteine, and glutamate in plasma did not increase significantly, suggesting that the systemic availability of glutathione is negligible in man. Because of hydrolysis of glutathione by intestinal and hepatic gamma-glutamyltransferase, dietary glutathione is not a major determinant of circulating glutathione, and it is not possible to increase circulating glutathione to a clinically beneficial extent by the oral administration of a single dose of 3 g of glutathione.

Administration, Oral↗

An immunocytochemical study of endocrine cell development in the early fetal guinea pig pancreas.

The presence of insulin, glucagon, pancreatic polypeptide, and somatostatin containing cells and their ontogenic changes were investigated immunocytochemically in the early fetal pancreas of the guinea pig (Days 25-40). In the earliest tissues examined (Day 25 and Day 30) brightly staining glucagon cells were the most predominant endocrine cell population, followed by slightly fewer and weaker staining pancreatic polypeptide cells. Insulin and somatostatin immunoreactive cells were less numerous. At Day 25 all endocrine cells were located within the pancreatic tubules where some glucagon cells also coexpressed insulin. Similar dual immunoreactivity was present at Day 30. At Day 25 some of the pancreatic polypeptide cells also showed coexpression of somatostatin which persisted until Days 35-40. At these later stages insulin and somatostatin cells were increasingly frequent. Glucagon and pancreatic polypeptide cells were also conspicuous. The four endocrine cell types were found either in the pancreatic tubules or in the developing islets where they began to acquire an adult-like topographic distribution. These studies in the fetal guinea pig show that the four islet hormonal cells cytodifferentiate from an early stage. A small proportion of endocrine cells coexpress either insulin and glucagon or pancreatic polypeptide and somatostatin.

Animals↗

Lipoprotein risk factors in vegetarian women of Indian descent are unrelated to dietary intake.

Dietary intakes, anthropometric indices and plasma lipoprotein and alpha-tocopherol concentrations were measured in premenopausal vegetarian women of Indian descent (n = 22) and in white women of European descent consuming either mixed (n = 22) or vegetarian diets (n = 18). The Indian women were shorter in height than the white women and had a higher proportion of body fat. Energy intakes were lower in the Indian women, both in absolute terms and per kg body weight. The proportion of energy derived from saturated fatty acids was lower and that from polyunsaturated fatty acids was greater in both Indian and white vegetarians compared with the subjects on mixed diets. Intakes of dietary fibre and vitamins C and E were higher in the white vegetarians compared with the other groups. Plasma concentrations of total and LDL cholesterol and apolipoprotein B and the ratio of apolipoprotein B/apolipoprotein AI were lower and HDL and HDL2 cholesterol, alpha-tocopherol concentrations and the ratio of alpha-tocopherol/cholesterol were greater in the white vegetarian group than in the other groups. Total plasma cholesterol was associated with measures of truncal obesity, especially subscapular skinfold thickness and the percentage energy derived from saturated fatty acids. Plasma concentrations of apo(a) were higher and those of HDL and HDL2 cholesterol and sex hormone binding globulin (SHBG) were lower in the Indian vegetarian women compared with both groups of white women. No relationship could be found between apo(a), HDL and HDL2 cholesterol concentration and nutrient intake but HDL and HDL2 were negatively associated with the proportion of body fat and apo(a) weakly with subscapular skinfold thickness.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Composition↗

First phase insulin release in the non-obese diabetic mouse: correlation with insulitis, beta cell number and autoantibodies.

The ontogenic variation of beta cell function and its relationship with the degree of islet damage and levels of autoantibodies have been studied in the non-obese diabetic (NOD) mouse model. We conducted in vivo first phase insulin release (FPIR) in response to intravenous glucose and studied its correlation with the degree of insulitis, islet cell antibody (ICA) and insulin autoantibody (IAA) levels in female NOD mice cross-sectionally at days 40 (n = 19), 90 (n = 21), 150-160 (n = 21) and day 250 (n = 20). The mean +/- SEM FPIR values showed an age-related decline from day 40 (46.2 +/- 5.3 microU/ml) to day 150-160 (17.8 +/- 2.5 microU/ml) and then doubled at day 250 (34.5 +/- 5 microU/ml), while the mean +/- SEM insulitis scores increased progressively until day 150-160 (61.7 +/- 6.1%) and then declined slightly at day 250 to 50.2 +/- 6.2%. In female NOD mice with spontaneous diabetes (n = 4) and streptozotocin-induced diabetic Swiss mice (n = 5) FPIR was either absent or greatly attenuated. A statistically significant inverse correlation between FPIR and insulitis was found among NOD mice at days 90 (P = 0.02; r = -0.52) and 150-160 (P = 0.03; r = -0.48). However, no statistically significant correlation was observed at days 40 and 250. Morphometric techniques applied to day 150-160 pancreatic sections showed a statistically significant negative correlation between insulitis and beta cell number per unit area of islet tissue (P = 0.0001; r = - 0.75). At this age some islet beta cells showed different intensities of staining by immunofluorescence.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Combined modality therapy for stage III non-small cell lung carcinoma: results of treatment and patterns of failure.

Patients with Stage III non-small cell lung carcinoma continue to pose a therapeutic problem with dismal cure rates. In an effort to improve on these results, 129 patients with biopsy-proven clinical Stage III non-small cell lung carcinoma from November 1982 through November 1987, were entered into two consecutive Phase II studies at Rush-Presbyterian-St. Luke's Medical Center. Treatment in the first study consisted of Cisplatin and 5-Fluorouracil infusion with concomitant split course radiation; in the second Etoposide was added. Radiation and chemotherapy were given simultaneously on days one through five of each cycle in a preoperative fashion for four cycles in patients considered eligible for surgery and in a definitive fashion for six cycles in patients considered ineligible for surgery. Radiation was given in 2 Gy fractions for a planned preoperative dose of 40 Gy and a definitive dose of 60 Gy. Surgical resection was attempted four to five weeks later in patients treated preoperatively. Thus, 83 patients were treated preoperatively and 46 definitively. Eighty-three patients (64%) had IIIA disease and IIIB disease was found in the remainder of the patients. Sixty-two patients (75%) in the eligible for surgery group had a thoracotomy after the combined treatment with a resectability rate of 97% and an operative mortality rate of 5%. There were 17 patients (27%) with no evidence of residual cancer in the resected specimen. Three-year survival for the eligible for surgery group at 40% was significantly better than 19% observed in the ineligible for surgery group (p = 0.003). Seventy-six percent of the patients with no residual cancer in the resected specimen are recurrence-free at three years compared to 34% of the patients with gross residual. A total of 81 patients have failed after their treatment; 49 (59%) in the eligible for surgery group and 32 (70%) in the ineligible for surgery group. Of all the patients who failed, local failure alone and as a component occurred in 21 (26%) and 36 (44%) patients, respectively. Failure in distant sites alone was noted in 56% of the overall failures. Severe toxicity was unusual. There were three treatment related deaths (2%). Radiation esophagitis and pneumonitis were only mild to moderate seen in less than 10% of the patients. Survival rates and patterns of failure according to the stage of the disease, histology, treatment group and pathologic response will be presented in detail.

Antineoplastic Combined Chemotherapy Protocols↗

The influence of a vegetarian diet on the fatty acid composition of human milk and the essential fatty acid status of the infant.

Vegan and vegetarian diets supply higher amounts of linoleic acid than those of omnivores. Intakes of alpha-linolenic acid (18:3n-3) are variable, depending on the oils used, but are generally high in vegans. Docosahexaenoic acid (22:6n-3) (DHA) is absent from vegan and many vegetarian diets. Cord plasma and cord artery phospholipid levels of Hindu vegetarians contained less DHA and more docosapentaenoic acid (22:5n-6) compared with those of omnivore control subjects. These differences in fatty acid composition were not statistically related to differences in birth weight, head circumference, or length. In human milk from vegans, vegetarians, and omnivores, the mean percentage in total fatty acids of 18:2n-6 was 23.8%, 19.7%, and 10.9%, respectively; that of 18:3n-3 was 1.36%, 1.25%, and 0.49%, respectively; and that of 22:6n-3 was 0.14%, 0.30%, and 0.37%, respectively. The proportion of DHA in erythrocyte total lipids of infants breast-fed by vegans was 1.9% compared with 3.7% in infants fed a milk formula containing butterfat as the sole source of fat and 6.2% in infants breast-fed by omnivores at 14 weeks postpartum. The ratio of linoleic/alpha-linolenic acid in the diet was predictive of the proportion of eicosapentaenoic acid but not that of DHA in infant red blood cell lipids. It is concluded that the intakes of linoleic acid and DHA are the major determinants of the proportion of DHA in plasma and red blood cell lipids.

Breast Feeding↗

Total skin electron beam radiation therapy for mycosis fungoides.

Forty-nine patients with biopsy-proven mycosis fungoides, Stages I-IV were treated using total skin electron beam irradiation (TSEBI). Total dose ranged from 600 cGy to 3,200 cGy. To evaluate the dose response relationship, patients were retrospectively divided into two groups. In Group I, 18 patients received a dose of 2,000 cGy or less, and in Group II, 31 patients received more than 2,000 cGy. The overall response rate was 87.7% with a 75.7% complete response and 12.2% partial response. Complete response was higher among patients with early stage disease: (Stage IA 1/1, Stage IB 23/35 (92%), Stage IIA 3/4 (75%), Stage IIB 4/8 (50%), Stage III 3/6 (50%), Stage IVA 1/1, Stage IVB 0/1, and unstaged group 2/3 (66.6%)). Patients treated with a higher total dose had a higher overall 5-year survival rate (Group I 38%, Group II 68%), longer median duration of complete response (Group I, 27 months; Group II, 35.3 months), slightly better complete response rate (72.2% for Group I, 77.4% for Group II), and lower recurrence rate (Group I, 94%; Group II, 83.9%) compared to patients with lower total dose. Complications from TSEBI were minimal. Total skin electron beam irradiation is effective in controlling early stage mycosis fungoides; however, a prospective study to evaluate optimum total dose is needed.

Adult↗

Comparison of radiation therapy of classic and epidemic Kaposi's sarcoma.

Between 1963 and 1990, 92 lesions in twenty patients with Kaposi's sarcoma (KS) were treated using radiation therapy (RT). Fifty-nine classic Kaposi's sarcoma (CKS) lesions in 12 patients were treated with 990 cGy in 3 fractions-5,000 cGy in 25 fractions; 39 lesions (66%) showed a complete response (CR), 15 (25%) showed a partial response (PR) with complete symptomatic relief, and 5 lesions (8%) showed no response (NR). Only 6 of 59 lesions (10%) recurred in field with a median recurrence-free duration of 8 months. Thirty-three epidemic Kaposi's sarcoma (EKS) lesions in 8 patients were treated from 1,000 cGy in 5 fractions-3,000 cGy in 10 fractions. Thirty-one EKS lesions (94%) showed CR, and two lesions (6%) showed PR. An extensive review of the literature is also presented in the study here reported.

Acquired Immunodeficiency Syndrome↗

Selective disruption of genes expressed in totipotent embryonal stem cells.

Two retrovirus promoter trap vectors (U3His and U3Neo) have been used to disrupt genes expressed in totipotent murine embryonal stem (ES) cells. Selection in L-histidinol or G418 produced clones in which the coding sequences for histidinol-dehydrogenase or neomycin-phosphotransferase were fused to sequences in or near the 5' exons of expressed genes, including one in the developmentally regulated REX-1 gene. Five of seven histidinol-resistant clones and three of three G418-resistant clones generated germ-line chimeras. A total of four disrupted genes have been passed to the germ line, of which two resulted in embryonic lethalities when bred to homozygosity. The ability to screen large numbers of recombinant ES cell clones for significant mutations, both in vitro and in vivo, circumvents genetic limitations imposed by the size and long generation time of mice and will facilitate a functional analysis of the mouse genome.

Alcohol Oxidoreductases↗

The influence of rice bran on plasma lipids and lipoproteins in human volunteers.

Eighteen healthy male normocholesterolaemic men consumed diets supplemented with 15 g wheat bran, 15 g and 30 g rice bran for 3-week treatment periods. Plasma lipoprotein concentrations were determined on the last 3 days of each treatment period. Nutrient intakes estimated by analysis of duplicate diets were similar during all treatments. Plasma triglyceride concentrations were statistically significantly (P less than 0.05) lowered by 15 g/day rice bran compared with 15 g/day wheat bran. Plasma total cholesterol, low density lipoprotein and high density lipoprotein cholesterol, apoprotein AI and B concentrations and body weight were unaffected by the supplements. It is concluded that the consumption of realistic amounts of rice bran does not contribute to a reduction in plasma cholesterol concentrations in man.

Adult↗

Syphilitic gastritis in an HIV-infected individual.

We report the first known case of syphilitic gastritis in an HIV-infected person. The presentation of nonspecific abdominal pain and weight loss in a 48-yr-old former intravenous drug user previously treated for asymptomatic syphilis led to a barium swallow which demonstrated linitis plastica. Upper endoscopy reinforced a suspicion of carcinoma, but biopsy made the diagnosis of syphilis by silver staining. Further testing revealed a positive serology for syphilis as well as HIV infection with a depressed CD-4 lymphocyte count. Treatment with parenteral penicillin led to a rapid resolution of symptoms. This case represents a rare complication of late syphilis, and is another example of the unusual manifestations of syphilis seen in the HIV-infected population.

Gastritis↗

Fingerstick glucose determination in shock.

OBJECTIVE: To evaluate the accuracy of fingerstick glucose measurements in severely hypotensive patients. DESIGN: Prospective, nonrandomized comparison study. SETTING: Emergency department in a university hospital. PATIENTS: Twenty-five severely hypotensive patients (systolic blood pressure less than or equal to 80 mm Hg) and 39 normotensive patients. MEASUREMENTS: Simultaneous fingerstick reagent strip glucose, venous reagent strip glucose, and laboratory glucose values were compared. Data were analyzed using error-grid analysis. RESULTS: In hypotensive patients, the mean fingerstick glucose values were significantly lower than the values obtained either by venous reagent strip or laboratory glucose measurements. Fingerstick glucose values in the hypotensive group were 67.5% of laboratory glucose values, and were significantly lower than the values obtained in the normotensive group (91.8%, P less than 0.001). Only 36% of the hypotensive patients had fingerstick glucose values within the acceptable range of 20% of the laboratory glucose value. Thirty-two percent of hypotensive patients were incorrectly diagnosed as hypoglycemic (glucose less than 3.89 mmol/L [70 mg/dL]); 2 of these patients were actually hyperglycemic (glucose greater than 11.10 mmol/L [200 mg/dL]). Venous reagent strip measurements accurately reflected laboratory glucose values in both hypotensive and normotensive patients. CONCLUSIONS: Fingerstick glucose testing does not accurately represent venous glucose levels in severely hypotensive patients. If fingerstick glucose testing is relied on for these patients, errors in clinical management may be made. Venous reagent strip glucose testing correlates well with laboratory glucose measurements and should be the preferred method for rapid assessment of glucose level in critically ill patients with severe hypotension.

Blood Glucose↗