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Biomedical subjects

G Ramirez

Publications and source records attributed to G Ramirez.

At least 199 records · Page 11Linked to original sources

Gastric ulceration in patients receiving intrahepatic infusion of 5-fluorouracil.

Gastric ulceration developed in eight patients during intrahpeatic arterial infusion of 5-FU. Bleeding occurred in four instances and perforation in one. In all cases the catheter tip had been dislodged and was proximal to its correct position, allowing the stomach to be directly infused with 5-FU. No duodenal ulcers were noted. All patients were symptomatic for several days before the diagnosis was made. Of 20 patients with catheter dislodgement, five had documented ulcers, three had upper gastrointestinal bleeding of undetermined etiology, eight had epigastric pain or vomiting and only four were asymptomatic. Prompt determination of catheter position is necessary in patients receiving intrahepatic arterial infusion of 5-FU if symptoms consistent with gastric ulceration occur. Gastric ulcers should be vigorously treated because of the high rate of complications in patients receiving chemotherapy.

Adult↗

Stage III ovarian carcinoma: treatment and results. Comparison of multiple drugs, a single drug, and irradiation.

Multiple drugs, a single drug, and irradiation were compared in patients with Stage III ovarian carcinoma. The results were categorized as "favorable" [pelvic mass less than 8 cm and/or upper abdominal tumor nodule(s) less than 2 cm] or "unfavorable" (more massive disease). A total of 62 patients are reviewed of whom 25 had irradiation and 37 had chemotherapy. It was found that patients with slight residual disease after celiotomy did equally well with either irradiation or chemotherapy, but survival was improved using a combination of both. Use of 5 drugs did not significantly improve survival beyond that obtained with a single drug.

Drug Therapy, Combination↗

The role of iodine in the pathogenesis of thyroid enlargement in rats with chronic renal failure.

In rats with mild renal failure produced by a 2/3 nephrectomy on one side followed by a total nephrectomy on the other, ingestion of a high (10 mg/kg) iodine diet for two months resulted in thyromegaly, high serum iodine levels and a good correlation between thyroid weight and serum iodine (r = 0.75, P less than 0.01) or thyroid weight and blood urea nitrogen (r = 0.745, P less than 0.01). Iodine may potentiate the effects of unidentified gointrogens that accumulate in rats with renal failure. Since the serum iodine levels were higher in the animals with renal failure, it is also possible that iodine alone may have been responsible for the observed differences in thyroid weight.

Animals↗

Abnormalities in the regulation of prolactin in patients with chronic renal failure.

We have investigated the hypothalamic-hypophyseal regulation of prolactin secretion in patients with chronic renal failure treated with chronic hemodialysis. When compared to control subjects, baseline serum prolactin levels were elevated in the renal failure patients (range 11 to 16 mmicrogram/ml for renal failure patients, 6 to 9 mmicrogram/ml for controls, P less than 0.05). In addition, serum prolactin levels in the renal failure patients failed to suppress significantly following the administration of L-dopa, and did not increase in response to chlorpromazine or thyrotropin releasing hormone. These findings suggest an abnormal regulation of prolactin secretion and appear to be another example of the endocrine dysfunction that occurs in uremic subjects.

Adult↗

Further clinical studies with megestrol acetate in advanced breast cancer.

A previous study showed activity of megestrol acetate in advanced breast cancer; as a result the study was expanded. Of 101 patients treated with this compound, 26 (26%) met our criteria of improvement. The drug was well tolerated and produced no toxicity and, as opposed to androgens and estrogens, no endocrine effects were observed. Prior hormonal or cytotoxic compounds, including alkylating agents, did not appear to reduce the subsequent responsiveness to this potent progestational compound. We now include it, often as the initial hormonal trial in postmenopausal patients, in our sequential treatment of disseminated breast cancer because of its favorable therapeutic ratio.

Breast Neoplasms↗

Combined radiation therapy and 5-fluorouracil for advanced squamous cell carcinoma of the oral cavity and oropharynx: a randomized study.

In 1961, a randomized study was begun at the University of Wisconsin Medical Center in which the treatment of advanced squamous cell carcinoma of the head and neck with radiation therapy was compared with combined treatment with radiation therapy and 5-Fluorouracil. One hundred and thirty-six patients with primary lesions in the oral cavity, the base of the tongue, and the oropharynx were analyzed. Both local control and survival were better in the combined treatment group than in the group with radiation therapy alone. However, in only the oral cavity patient population was the difference statistically significant. Both acute and late complications were also increased in this group of patients who received combined treatment.

Carcinoma, Squamous Cell↗

Thyroid dysfunction in uremia: evidence for thyroid and hypophyseal abnormalities.

Disturbances in thyroid function and a high prevalence of goiter develop in patients on chronic hemodialysis. This study shows that in patients on dialysis, mean serum thyroxine and triiodothyronine levels are lower than normal. Patients with chronic renal failure not on dialysis, have mean serum thyroxine levels similar to normal subjects and low mean serum triiodothyronine levels. However, both serum thyroxine and triiodothyronine concentrations decrease as the renal failure worsens. In addition, both groups of patients with renal failure have a decreased serum thyroxine response to oxogenous thyrotrophin and a diminished serum thyrotrophin response to thyrotrophin-releasing hormone. These data suggest the presence of an intrathyroidal and an hypophyseal defect in uremic patients. Although serum iodide concentrations are elevated, there is no correlation between the level of serum iodide and the degree of renal failure. Therefore, we have no direct evidence that iodide excess is responsible for the abnormalities observed.

Adolescent↗

Studies on adriamycin using a weekly regimen demonstrating its clinical effectiveness and lack of cardiac toxicity.

Adriamycin has been given to 442 patients using the weekly regimen as initially described by Bonadonna et al. Hematologic toxicity and clinical effectiveness have been similar to those described with regimens in which the drug is given every 3 weeks. Stomatitis is more frequent with the weekly regimen than with the usual triweekly regimen. The incidence of electrocardiographic changes and arrhythmias was similar to that reported in other studies. Nine patients received between 500 and 550 mg/m2, nine between 550 and 600 mg/m2, 28 between 600 and 1000 mg/m2, and 22 between 1000 and 2500 mg/m2. None of the patients developed definite evidence of cardiomyopathy although six showed some disturbance of myocardial function. In each of the six patients, factors other than adriamycin cardiotoxicity were believed to play a major role in the myocardial abnormality. The difference between the incidence of cardiomyopathy seen in this series and that previously reported is statistically significant. The reasons for the difference are not clear but are probably related to the schedule that was used.

Adult↗

Interaction of ethidium bromide with the transport system for monovalent cations in yeast.

Ethidium was found to be taken up by yeast cells in a process that, at certain concentrations has the main following characteristics: a) a substrate is required; b) it presents cooperative kinetics, with n, according to the Hill equation approximately 3; c) ethidium can be concentrated more than 100-fold; d) the uptake is inhibited by Ca2+; e) the uptake of the dye is inhibited by monovalent cations with a selectivity pattern similar to that observed in their transport by yeast; f) ethidium inhibits the uptake of K+, and, at concentrations up to about 250 muM produces a competitive inhibition on the uptake of Rb+; and g) ethidium produces the same effects as K+ on respiration and the extrusion of H+. It is concluded that ethidium is taken up by yeast cells in a selective way by the same transport system normally employed for monovalent cation uptake.

Binding, Competitive↗

Clinical and theoretical aspects of the treatment of surgically unresectable retroperitoneal malignancy with combined intra-arterial actinomycin-D and radiotherapy.

A small pilot series (eight patients) of surgically unresectable retroperitoneal tumors treated with radiotherapy and a selective, prolonged, continuous intra-arterial infusion of actinomycin-D is discussed, in addition to the possible theoretical advantages for this therapy. For such tumors, there is a very low probability of obtaining local control with conventional radiotherapy alone. However, on the basis of recent knowledge from radiobiology and molecular biology, the technique is a rational attempt to improve the local control probability. Geographic miss with radiotherapy portals is another major cause for local failure with such tumors. We also emphasize the importance of detailed tumor localization procedures. The local responses, some of the local controls, the palliation achieved, and the lack of significant morbidity with this technique have been encouraging. We therefore consider it worthy of further clinical investigation.

Adolescent↗

Further clinical studies with intrahepatic arterial infusion with 5-fluorouracil.

A total of 419 patients with progressive liver disease, in nearly all cases metastatic from gastrointestinal primaries, were treated by intrahepatic arterial infusion with 5-FU. Three-fourths of these patients had had prior trials with intravenous 5-FU for 1 or 2 months to several years and had been switched to the infusion upon the development of progression. Catheters were placed percutaneously and the patients infused with 5-FU at a dose of 20 to 30 mg/kg/day X 4, then 15 mg/kg/day X 17, at which point the catheter was removed and the patient sent home on weekly i.v. doses at 15 mg/kg. Toxicity, morbidity, and mortality were minimal with the intrahepatic arterial infusion treatment and the rigid criteria of improvement were met by 55% of the study cases. The survival rate of those patients who responded to the treatment was greater than the survival rate of those who failed to respond.

Fluorouracil↗

Combined intra-arterial actinomycin D and radiation therapy for surgically unresectable hypernephroma.

One primary goal of preoperative radiotherapy for hypernephroma is to reduce the volume of tumor and, therefore, improve the possibility of resection. It is important that this goal be accomplished promptly so that 4 to 6 weeks after radiation therapy nephrectomy can be attempted. A longer waiting period may allow fibrosis of the normal surrounding tissues and make surgery more difficult. In addition, longer waiting periods could theoretically increase the probability of metastasis. Therefore, we plan to continue clinical investigation on the use of combined intra-arterial actinomycin D and radiotherapy as a possible useful means of improving the possibility of prompt surgical resection, since theoretically this regimen may be a method of increasing the effective radiation dose to the hypernephroma without increasing the effective radiation dose to surrounding normal tissue, such as bowel. The method may also have merit as an improved means of palliating selected patients with metastases who are symptomatic from a bulky primary hypernephroma.

Adenocarcinoma↗

Combination chemotherapy in breast cancer: a randomized study of 4 versus 5 drugs.

A randomized clinical trial, involving approximately 100 patients, that compared two combination therapy regimens (5 FU, methotrexate, vincristine, cyclophosphamide with and without prednisone) in advanced breast cancer showed a significantly higher rate of response for the 5-drug therapy group (62.5 versus 44.2%). However, no significant difference in survival has been observed to date. Some differences in toxicity were observed, e.g. a significantly greater number of cases with mild diarrhea for the 5-drug regimen, and a few more cases of sensory loss (not significant) and significantly more severe leukopenia (p value 0.06) for the 4-drug regimen.

Breast Neoplasms↗

Phase I study of L-asparaginase (NSC 109229).

22 patients received intravenously infused L-asparaginase (Escherichia coli) on a protocol for 5 weekly doses. 13 patients received 100 U/kg, 1 patient 500 U/kg, and 8 patients 1,500 U/kg. Only 3 of the 9 patients receiving 500 U/kg or more were able to complete the 5-week protocol. 11 of the 13 patients receiving 100 U/kg were able to complete the 5-week protocol. Significant tumor responses were not seen. CNS toxicity and allergic reactions were observed at high- and low-dose levels. There was no difference as to the degree of protein changes, BUN elevation, or liver function abnormalities at the different dose levels.

Asparaginase↗