Occupational exposure to organic solvents.
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Alkanes↗
Biomedical subjects
G Ramirez
Publications and source records attributed to G Ramirez.
Phase I trial of hepatic artery infusion of 5-iodo-2'-deoxyuridine and 5-fluorouracil in patients with advanced hepatic malignancy: biochemically based combination chemotherapy.
Eighteen patients with hepatic metastases primarily from colorectal carcinoma were treated on a phase I protocol employing hepatic artery infusion (HAI) of 5-fluorouracil (FUra) and 5-iodo-2'-deoxyuridine (IdUrd) via implantable infusion pump. Patients received a 14-day continuous HAI of 300 mg/day FUra. During days 8-14 of therapy, patients received IdUrd as a separate 3-h HAI daily x 7. Treatment cycles were repeated every 28 days. IdUrd was escalated from 0.1 to 2.86 mg/kg/day x 7. Myelosuppression and stomatitis were mild and not dose limiting. Hepatotoxicity was dose limiting and similar to that reported for 5-fluoro-2'deoxyuridine alone administered as a 14-day infusion every month. One patient developed a clinical picture consistent with sclerosing cholangitis and another had biopsy-proven cholestasis and triaditis. Catheter complications occurred in 7 of 18 patients. Plasma concentrations of FUra during the 7-day continuous HAI of FUra alone were consistently either undetectable or very low (less than or equal to 0.1 microM). At level 3 (1.0 mg/kg/day IdUrd) and beyond, measurable plasma concentrations of FUra, iodouracil, and IdUrd were found at the end of the daily 3-h infusion of IdUrd. The maximum tolerated dose of IdUrd as administered in this trial is 2.2 mg/kg/day x 7 and the recommended starting dose for further clinical investigation is 1.7 mg/kg/day x 7.
Animals↗
Combined hepatic artery 5-fluorouracil and irradiation of liver metastases. A randomized study.
The effect of hepatic irradiation (RT) after intraarterial 5-fluorouracil (5-FU) was evaluated in 37 randomized patients with colorectal adenocarcinoma hepatic metastases. Patients underwent percutaneous transbrachial artery catheterization of the hepatic artery followed by 21-day continuous 5-FU infusion (CT). Hepatic irradiation of 25.5 Gy was delivered to 19 patients 14 days after completion of infusion (CT + RT). All patients received subsequent weekly maintenance 5-FU. A 37% (seven of 19) response rate was observed in CT + RT, and a 50% response rate (nine of 18) in CT: median survival was 6 months for CT + RT, and 8 months for CT, (P = 0.106). Improved survival was observed in two subsets of patients. Tumor vascularity was graded angiographically from 0 to 4+; those patients with highest vascularity (4+) had a 20-month median survival (P = 0.0009). Patients with Grade 1, well-differentiated, histologic type had a median survival of 20 months (P = 0.0001). Four patients with both 4+ vascularity and Grade 1 histologic type had 27.5 months' median survival (P = 0.0019). Age, performance status, elevated liver function tests, previous systemic therapy, and time interval between diagnosis and entry on this study did not impact on survival (P greater than 0.05), nor did these variables eliminate the significance of vascularity and grade (P less than 0.05). Survival after intraarterial 5-FU infusion was not improved by this regimen of sequential external irradiation. Regional therapy may benefit those patients with 4+ vascular tumors and/or well-differentiated tumor grade. Future trials are needed to explore the interaction of halogenated pyrimidines with irradiation and determine whether these prognostic factors can aid in patient selection for regional therapy of hepatic metastases.
Adenocarcinoma↗
Effects of dilevalol on rest and supine exercise hemodynamics in mild to moderate systemic hypertension.
Eight mildly to moderately hypertensive subjects free of any antihypertensive medications and on a normal salt diet performed maximal supine arm exercise. Before starting the exercise, a right-sided cardiac catheterization was performed to measure hemodynamic parameters before and during exercise. All patients had normal increases in cardiac output for the level of exercise performed and the peripheral vascular resistance diminished appropriately. An increase in the right atrial and pulmonary artery wedge pressures during exercise could be explained by increased venous return. After the baseline testing, rest and exercise hemodynamics were repeated 2 hours after the administration of 400 mg of dilevalol, a new beta blocker. For the next 2 weeks the patients received 400 mg of the study drug twice a day, with repeat studies obtained thereafter. As with other beta blockers, dilevalol decreases the heart rate and cardiac output on exercise, but, in addition, it induces a decrease in the resting systemic vascular resistance. This action is similar to its isomer, labetalol.
Adrenergic beta-Antagonists↗
Granulomatous myocarditis with unusual histologic features.
A 61-year-old white man was found to have granulomatous myocarditis associated with a carcinoid tumor in the ileum with local lymphatic metastasis, a mixed papillary and follicular carcinoma of the thyroid with regional lymph node metastasis, benign tubular cell adenomas of the kidneys, and chronic pancreatitis.
Adenocarcinoma↗
Aldosterone response to insulin-induced hypoglycemia in hemodialysis patients.
To investigate possible abnormalities of the hypothalamic-pituitary axis in patients with chronic renal failure on dialysis, we have examined the effects of insulin-induced hypoglycemia on the adrenal steroid responses. In normal subjects, plasma aldosterone and cortisol concentrations increase significantly in response to hypoglycemia, with good correlation. In the patients with end-stage renal disease (ESRD) however, insulin-induced hypoglycemia fails to elicit significant increases in the plasma cortisol and aldosterone levels. To test the adrenal responsiveness to adrenocorticotropin (ACTH), we administered ACTH to both groups. Plasma cortisol and aldosterone responses are similar in both groups suggesting that the adrenal responsiveness to ACTH is not impaired. We also investigated the responsiveness of the renin-angiotensin-aldosterone system in response to volume contraction by hemofiltration in patients with ESRD. Neither plasma renin activity nor plasma aldosterone concentration change significantly following such contrived volume contraction. These results reveal several endocrinologic abnormalities in the patients with ESRD on chronic hemodialysis.
Adrenocorticotropic Hormone↗
Occupational exposure to organic solvents causing chronic tubulointerstitial nephritis.
We describe a patient with a history of ulcerative colitis and long-standing occupational exposure to organic solvents. Over a follow-up period of almost four years he had progression of tubulointerstitial damage documented by two kidney biopsies. We propose that long-term exposure to organic solvents can lead to the development of chronic tubulointerstitial nephritis. We describe experimental evidence that supports our conclusion.
Adult↗
Relative efficacy of vasodilator therapy in chronic congestive heart failure. Implications of randomized trials.
We examined existing evidence concerning the relative efficacy of various vasodilator agents in chronic congestive heart failure. Only randomized placebo-controlled trials with clinical end points and treatment durations of four weeks or more were selected from an exhaustive search of the English-language medical literature. Twenty-eight trials involving 1976 patients were found. Treatment durations of the trials varied from one month to two years. Patients with symptomatic heart failure despite digitalis and diuretic therapy were studied; most were middle-aged men and approximately half had coronary artery disease. Results of the trials were appraised by three independent observers, and mortality and functional status outcomes were pooled in a meta-analysis. All vasodilator agents except hydralazine hydrochloride were associated with improvements in functional status. Angiotensin converting-enzyme inhibitors were the only agents associated with both decreased mortality (odds ratio, 0.51; 95% confidence interval, 0.34 to 0.75) and improved functional status (odds ratio, 4.53; 95% confidence interval, 3.46 to 5.92). The optimal timing for initiation of these agents was not established.
Angiotensin-Converting Enzyme Inhibitors↗
In vitro infection of human epidermal Langerhans cells with HIV.
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Antibodies, Monoclonal↗
Evaluation of the hypothalamic-hypophysial, thyroid, and gonadal axes before and after disulfiram administration in patients with chronic alcoholism.
We studied 14 alcoholic men without evidence of liver damage. After two weeks of alcohol abstinence, the patients were divided into two groups of seven patients each. Hypothalamic-hypophysial, thyroid, and gonadal axis tests were done on group 1 patients before disulfiram administration, and the tests were later repeated while the patients were taking disulfiram. Group 2 patients had initial testing done while taking disulfiram and repeat testing after the drug was stopped. The following abnormalities were found and were not affected by disulfiram: lack of suppression of both growth hormone and glucagon with oral glucose intake, and lack of response of follicle-stimulating hormone after administration of synthetic gonadotropin-releasing hormone. After disulfiram administration, we noticed a blunted response of thyrotropin to thyrotropin-releasing hormone.
Adult↗
Red cell alloimmunization in chronic renal failure patients undergoing hemodialysis.
Posttransfusion alloimmunization to red cell antigens was studied in a group of 98 chronic renal disease patients treated solely with hemodialysis. Clinically significant red cell antibodies were formed in only 6.1% of transfused patients, and only 1 patient formed more than one antibody. We do not recommend extended red cell phenotyping, beyond ABO and Rh(D), in patients with end-stage renal disease who may require transfusion.
Adult↗
Counterregulatory hormonal response to insulin-induced hypoglycemia in patients on chronic hemodialysis.
Insulin induced hypoglycemia was produced in 5 chronic hemodialysis patients and 5 normal controls. Normally, several counterregulatory hormones (cortisol, growth hormone, glucagon and epinephrine) are secreted. Although we did not measure glucagon in our study, the other hormones were found to respond normally to the hypoglycemia in the control subjects. In the dialysis patients plasma epinephrine response was normal, but no responses of plasma ACTH, cortisol and growth hormone were found. Failure of the other counterregulatory hormones to respond to hypoglycemia indicates that dialysis patients probably maintain their euglycemic state by increasing plasma glucagon and epinephrine concentrations. We were unable to confirm the expected decrease of catecholamines that has been reported during hemodialysis.
Adrenocorticotropic Hormone↗
Acute effect of captopril on aldosterone secretory responses to endogenous or exogenous adrenocorticotropin.
The aldosterone secretory response to Captopril (12.5 mg, orally) was studied in five normal men. Endogenous ACTH and epinephrine secretion was stimulated by the induction of hypoglycemia. Normally this stimulus increases plasma cortisol, GH, aldosterone, and PRA. Administration of captopril resulted in a blunted plasma aldosterone response to hypoglycemia, but no concomitant blunting of the plasma cortisol response. The responses of other hormones, with the exception of PRA, were not affected. When exogenous ACTH was administered to the same men with and without captopril, the plasma aldosterone response was again blunted by captopril, while the plasma cortisol response was unaffected. We conclude that angiotensin II may be required for ACTH to stimulate aldosterone secretion. Alternatively, the possibility that captopril may selectively inhibit aldosterone secretion at the adrenal cellular level cannot be excluded.
Adrenocorticotropic Hormone↗
Regulation of aldosterone secretion during hypoxemia at sea level and moderately high altitude.
The aldosterone and cortisol responses to small doses of ACTH (0.125, 0.25, 0.5, and 1.25 micrograms) after dexamethasone administration were measured in normal subjects at sea level while breathing room air (mean O2 saturation, 97 +/- 0.9%) and again while breathing hypoxic gas to lower the O2 saturation to 90%. A population of subjects matched for age and sex adapted to 3000 meters above sea level living in Colombia, South America, was also studied (mean O2 saturation, 94 +/- 0.7%). Hypoxemia, either induced at sea level or as a consequence of high altitude living, resulted in significant inhibition of aldosterone secretion after progressive administration of increasing doses of ACTH, but did not affect the cortisol response to ACTH. In addition, it was associated with higher plasma atrial natriuretic hormone levels. PRA declined only during acute hypoxemia induced at sea level and did not change during sea level normoxemia or high altitude living. Plasma sodium and potassium concentrations were no different in the three experimental conditions. We conclude that hypoxemia inhibits ACTH-stimulated aldosterone secretion and speculate that atrial natriuretic hormone may have mediated this effect.
Adrenocorticotropic Hormone↗
Treatment of probable subclinical liver metastases and gross pancreatic carcinoma with hepatic artery 5-fluorouracil infusion and radiation therapy.
Since subclinical hepatic metastases are frequently present at time of diagnosis of pancreatic carcinoma, any meaningful effort to improve survival must include 'prophylactic' liver therapy in addition to treatment of the pancreatic primary. We report the results of a prospective, unrandomized clinical trial of a 2-week liver and pancreas infusion (by hepatic artery) of 5-fluorouracil (5-FU) and pancreatic irradiation to 50-60 Gy, combined with prophylactic irradiation of the liver with approximately 20 Gy. Of 21 evaluable patients, 17 completed therapy without excessive toxicity and had a median survival of 50 weeks. Contrary to historical controls, the liver in our series was rarely the first site of failure (6%), suggesting that the combination of hepatic artery 5-fluorouracil and 20 Gy liver radiation may suppress subclinical (microscopic) liver metastases without significant hepato-toxicity. When radiation doses to the pancreas were increased above 50 Gy there was improvement in primary tumor control, although failure in the pancreatic bed remained the most common site of failure. Future clinical investigation of this form of combined therapy for eradication of micro-metastasis in the liver, combined with more aggressive local pancreatic therapy, would seem appropriate.
Adenocarcinoma↗
Mononuclear cell phenotyping in a hemodialysis population.
A study of peripheral blood mononuclear cell phenotyping and HIV testing was performed in 39 chronic hemodialysis patients. The following abnormalities were found in comparison to a control population: 1) a lower percentage of lymphocytes in the white blood cell differential count, 2) a lower percentage of total T cells, 3) a lower percentage and absolute number of suppressor T cells and 4) a lower percentage and absolute number of B cells. Both increasing age and blood transfusions were associated with reduced helper cells.
AIDS Serodiagnosis↗
Fluid balance in acute and chronic lung disease.
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Acidosis, Respiratory↗
[Anterior open bite and respiratory function].
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Child↗