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Biomedical subjects

G Rodriguez

Publications and source records attributed to G Rodriguez.

At least 91 records · Page 5Linked to original sources
PubMed1995

Initial phase I evaluation of the novel thymidylate synthase inhibitor, LY231514, using the modified continual reassessment method for dose escalation.

PURPOSE: To determine the toxicities, maximal-tolerated dose (MTD), pharmacokinetic profile, and potential antitumor activity of LY231514, a novel thymidylate synthase (TS) inhibitor. PATIENTS AND METHODS: Patients with advanced solid tumors were administered LY231514 intravenously over 10 minutes, weekly for 4 weeks, every 42 days. Dose escalation was based on the modified continual reassessment method (MCRM), with one patient treated at each minimally toxic dose level. Pharmacokinetic studies were performed in all patients. RESULTS: Twenty-five patients were administered 58 courses of LY231514 at doses that ranged from 10 to 40 mg/m2/wk. Reversible neutropenia was the dose-limiting toxicity. Inability to maintain the weekly treatment schedule due to neutropenia limited dose escalation on this schedule. Nonhematologic toxicities observed included mild fatigue, anorexia, and nausea. At the 40-mg/m2/wk dose level, the mean harmonic half-life, maximum plasma concentration, clearance, and apparent volume of distribution at steady-state were 2.02 hours, 11.20 micrograms/mL, 52.3 mL/min/m2, and 6.64 L/m2, respectively. No major antitumor responses were observed; however, minor responses were achieved in two patients with advanced colorectal cancer. CONCLUSION: The dose-limiting toxicity, MTD, and recommended phase II dose of LY231514 when administered weekly for 4 weeks every 42 days are neutropenia, 40 mg/m2, and 30 mg/m2, respectively.

Adult↗
PubMed1994

5-day methotrexate for women with metastatic gestational trophoblastic disease.

The objective of this study was to analyze the toxicity and the efficacy of single-agent 5-day methotrexate for women with metastatic gestational trophoblastic disease. The study is a retrospective analysis of 52 patients who received repetitive 5-day cycles of intramuscular methotrexate as primary therapy for metastatic trophoblastic disease between 1975 and 1990. The majority of patients were low-risk by both clinical and World Health Organization prognostic index score criteria. Sixty percent achieved primary remission with a median of 3 cycles of single-agent methotrexate. Therapy was changed because of toxicity and drug-resistance by hCG criteria in 11 (21%) and 10 (19%) patients, respectively. Pretherapy hCG > 10,000 mIU/ml was associated with the development of drug-resistance. Remission was achieved in all patients, with only 2 (4%) requiring multiagent therapy. The use of repetitive 5-day cycles of methotrexate is efficacious therapy of low-risk metastatic trophoblastic disease. Future studies are needed to define a cost-effective and minimally toxic therapy that retains a high primary remission rate in these patients.

Analysis of Variance↗
PubMed1994

Fludarabine phosphate. A new anticancer drug with significant activity in patients with chronic lymphocytic leukemia and in patients with lymphoma.

Fludarabine phosphate is a purine antimetabolite approved for use in the management of patients with chronic lymphocytic leukemia. Fludarabine works primarily by inhibiting DNA synthesis. The compound also possesses lymphocytotoxic activity with preferential activity toward T-lymphocytes. Initial preclinical studies demonstrated antitumor activity with fludarabine against L1210 murine leukemia. In phase I studies, myelosuppression was identified as the dose-limiting toxicity in patients with solid tumors and fatal neurotoxicity as the dose-limiting toxicity in adult patients with acute hematologic malignancies. The recommended dose and schedule was determined to be 18-25 mg/m2/d for five days, repeated every 28 days. Unlike preclinical studies, phase II trials showed a lack of significant effect when fludarabine was given to patients with solid tumors. However, phase II investigations have confirmed the efficacy of fludarabine in lymphoid malignancies, including non-Hodgkin's lymphoma, mycosis fungoides, prolymphocytic leukemia, and chronic lymphocytic leukemia. The place of fludarabine in the management of leukemias in children is under investigation. Early results indicate an unusual degree of antitumor activity when the agent is used in combination chemotherapy for patients with refractory disease. Fludarabine is an effective antitumor agent in the management of lymphoid malignancies. Studies are ongoing to more completely define the role of fludarabine in these malignancies as well as in the pediatric leukemias. Additional studies evaluating the activity of fludarabine as an immunomodulator are warranted, due to the lymphocytotoxic properties associated with this agent.

Animals↗
PubMed1994

Longitudinal study of cerebral blood flow following early or delayed surgery for ruptured intracranial aneurysms.

Out of a series of 43 cases operated on for ruptured intracranial aneurysms over a 12-month-period, 32 patients were followed up to 12 months postoperatively with repeated evaluations of cerebral blood flow, using the Xenon133 inhalation technique. No statistically significant differences in cerebral perfusion were detected between the subgroups of good-grade patients, who were submitted respectively to early, or delayed surgery. Depression of flow in the affected hemisphere of poor-grade patients was principally related to the preoperative occurrence of an intracerebral haematoma. The overall results were not consistent with the hypothesis that early surgical intervention results in long-lasting effects on the cerebral circulation.

Adult↗
PubMed1994

Chest pain self-management training for patients with coronary artery disease.

This study was designed to evaluate the efficacy of a brief, structured pain management program to improve control over chest pain episodes in patients diagnosed with coronary artery disease. Twenty-six male veterans who attended the three-session program were compared with twenty-six matched controls. Results indicated significant short-term reductions in self-report of number of chest pain episodes in treated subjects. Self-report of pretreatment daily physical activity level moderated treatment outcome, as individuals reporting lower levels of physical activity derived greater benefit than their high-activity counterparts. These results suggest the potential utility of incorporating chest pain control strategies into comprehensive cardiac rehabilitation programs.

Adult↗
PubMed1994

Phase I clinical trial of ormaplatin (tetraplatin, NSC 363812).

Ormaplatin is a platinum analog that was developed because of an altered toxicity profile and non-cross resistance to cisplatin in both in vitro and in vivo models. To determine the toxicities and maximum tolerated dose of ormaplatin on a daily times five schedule, patients with refractory solid tumors received ormaplatin on five consecutive days at nine dose levels ranging from 1.0 to 15.0 mg/m2/day. A total of 35 patients received 70 cycles of therapy. Nausea and vomiting and myelosuppression were moderate and not dose-limiting. Dose-limiting neurotoxicity, consisting of a sensory peripheral neuropathy, was seen in all five patients who received cumulative doses greater than or equal to 165 mg/m2. This neurotoxicity was symptomatic in all patients and caused significant functional impairment in four patients with inability to walk in two patients. A sensitive atomic absorption spectroscopy analysis performed for one patient at the 13.0 mg/m2/day dose level showed a Cpmax of 163 ng/ml and a t1/2 of 10.9 min for free platinum. A phase II dose could not be determined due to the onset of peripheral neuropathy at low cumulative doses and not at absolute dose levels.

Adult↗
PubMed1994

Regional cerebral blood flow in familial hypercholesterolemia.

BACKGROUND AND PURPOSE: Although epidemiologic investigations are trying to clarify the role of plasma lipid concentrations (primarily cholesterol and its subfractions) as risk factors for both ischemic and hemorrhagic stroke, little information is available regarding the effect of sustained hypercholesterolemia on cerebral perfusion. METHODS: Regional cerebral blood flow (CBF) was measured by the 133Xe inhalation method in 25 heterozygous patients (four untreated) affected with familial hypercholesterolemia. In 15 patients regional CBF was repeated 20 minutes after intravenous administration of acetazolamide (10 mg/kg body wt) to evaluate cerebrovascular reactivity. Correlations among cerebral perfusion data, present or pretreatment plasma lipid concentrations, and certain other clinical features were assessed by ANOVA. RESULTS: Both basal regional CBF and cerebrovascular reactivity were normal in the vast majority of patients compared with age- and sex-matched normal control subjects. CBF was significantly dependent on pretreatment low-density lipoprotein cholesterol (LDL-C) concentration (P = .005) and the presence of symptomatic ischemic heart disease (P = .015). CBF was only slightly dependent on age (P = .05) and was not dependent on either lipoprotein(a) or present LDL-C concentration. CBF did not differ between treated and untreated patients, and the perfusional increase induced by acetazolamide was not related to any other variable. CONCLUSIONS: Cerebral perfusion and cerebrovascular reactivity were maintained within the normal range despite long-lasting, severe hypercholesterolemia, even if a somewhat lower CBF was found in those patients with the highest LDL-C pretreatment levels. These results are in accord with the epidemiologic data that implicate hypercholesterolemia as a minor risk factor, if a risk factor at all, for intracranial atherosclerosis and ischemic stroke.

Acetazolamide↗
PubMed1994

Alternating weekly chemotherapy with etoposide-methotrexate-dactinomycin/cyclophosphamide-vincristine for high-risk gestational trophoblastic disease.

OBJECTIVE: To evaluate the response rate and toxicity of alternating weekly therapy with etoposide-methotrexate-dactinomycin/cyclophosphamide-vincristine for women with high-risk gestational trophoblastic disease. METHODS: Twenty-two women with gestational trophoblastic disease received 126 cycles of the study regimen. Response was evaluated by serial hCG monitoring. Toxicity was assessed using standard criteria. RESULTS: Six women (27%) were treated for primary therapy and 16 (73%) for secondary therapy. The median prognostic index score was 11 (range 7-19). Only 23% of the patients and 11% of the 126 treatment cycles had grade 4 neutropenia, despite the heavily pretreated patient population. Only 2% of the cycles were associated with neutropenic sepsis or required platelet transfusions. Nonhematologic toxicity was modest. Among 16 women who received chemotherapy alone, there were 11 (69%) complete and three (19%) partial responses. When adjuvant therapies are included, the overall complete and partial response rates were 77 and 14%, respectively. Six (35%) of 17 complete responders developed recurrences. Five patients with partial response or relapse were salvaged with additional therapy. Fifteen of the 22 patients (68%) have sustained remissions. CONCLUSION: The regimen of alternating weekly etoposide-methotrexate-dactinomycin/cyclophosphamide-vincristine is effective and well-tolerated chemotherapy for patients with high-risk gestational trophoblastic disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Prevention of superficial wound separation with subcutaneous retention sutures.

The objective of this prospective study was to determine the efficacy of subcutaneous retention sutures in the prevention of superficial wound separation in obese women undergoing gynecologic surgery. From 1985 to 1990, 80 women with subcutaneous tissue of 5 cm or greater undergoing laparotomy were randomly assigned to either standard wound closure (37 patients) or closure including subcutaneous retention sutures (43 patients). We examined the relationship of the following factors to the development of superficial wound dehiscence: malnutrition (total protein < 6.0 mg/dl, albumin < 3.0 mg/dl), minidose heparin (5000 U subcutaneously every 8 hr for 5 days), diabetes mellitus, prolonged operative time (> 180 min), intraoperative spillage of enteral contents, and subcutaneous retention sutures. In a univariate analysis, malnutrition (P = 0.02), the use of heparin (P = 0.03), and the absence of retention sutures (P = 0.02) were associated with an increased risk of separation. In a multivariate analysis, malnutrition (P = 0.02), low-dose heparin (P = 0.03), and the absence of retention sutures (P = 0.04) retained their independent association with superficial wound separation. This study suggests that the use of subcutaneous retention sutures reduces the incidence of superficial wound separation in obese women undergoing gynecologic surgery.

Adult↗
PubMed1993

The effects of the posterior sagittal approach on rectal function (experimental study).

The posterior sagittal transsphincteric approach has been used for the treatment of anorectal malformations in children and for other acquired conditions mainly in adults. Although the reports on clinical results indicate that the division of the sphincteric mechanism does not harm the function of the voluntary muscles, there are no experimental objective evaluations of the rectal function and fecal continence after a posterior sagittal transsphincteric approach. Sixteen dogs were studied forming four groups of four animals each. Group I was subjected to a posterior sagittal approach only without opening of the rectum. Group II underwent a posterior sagittal approach plus posterior and anterior rectotomy. Group III underwent a posterior sagittal approach plus a perirectal dissection, and group IV underwent only a perirectal dissection without posterior sagittal incision. All animals were evaluated clinically and manometrically preoperatively and postoperatively and were followed up to 12 weeks. Results indicated that the perirectal dissection with and without posterior sagittal incision provoked the most severe changes in bowel control and manometric parameters. Posterior sagittal approach with or without rectotomy provoked minimal or no changes in bowel function and rectal manometry. This experimental study supports the clinical experiences and indicates that the posterior approach does not interfere with the function of the sphincteric mechanism.

Anal Canal↗
PubMed1993

A phase I trial of trimetrexate (NSC352122) on a daily x 5 schedule in patients with refractory adult leukemia.

Seven adult patients with refractory acute leukemia were administered trimetrexate (TMTX), a non-classical folate antagonist, in a phase I trial. TMTX was administered as an intravenous bolus for five consecutive days at doses of 9-12 mg/m2 based on marrow response. The maximum tolerated dose was 12 mg/m2. Hepatotoxicity was the dose-limiting toxicity. Initial dosage reductions in patients with liver disease and/or low protein concentrations may be necessary since TMTX is significantly protein bound and cleared primarily by hepatic metabolism. The recommended phase II dose on this dosing schedule is 9 mg/m2.

Adult↗
PubMed1993

Regional cerebral blood flow in chronic stroke patients.

BACKGROUND AND PURPOSE: The aim of this study was to investigate regional cerebral blood flow parameters during the postacute phase of unilateral ischemic stroke and to correlate them with clinical data. METHODS: Regional cerebral blood flow was measured in 187 patients in the stabilized phase of stroke by the xenon-133 inhalation method with 32 extracranial detectors. Thirty-eight patients were reexamined after a mean +/- SD time of 32 +/- 21.4 months. RESULTS: The overall detection of hypoperfusion was 92.0%, with asymmetries as the most sensitive index, especially for patients with a lesser degree of neurological disability. Neurological disability score was strongly associated with regional cerebral blood flow in the affected hemisphere (p < 0.0001) and with asymmetries (p < 0.0001). The presence of carotid obstruction further decreased the regional cerebral blood flow in the affected hemisphere and significantly increased asymmetry (p < 0.0001). Subjects who had no hypoperfusion at absolute values analysis were more frequently free of carotid disease and had less severe disability than those who had bilateral or unilateral regional absolute cerebral blood flow reduction. In 38 patients without new cerebrovascular events, a significant (p = 0.005) reduction of hemispheric regional cerebral blood flow asymmetries was found on a follow-up examination. CONCLUSIONS: These data confirm the value of regional cerebral blood flow asymmetries in stroke detection and point out that important clinical information is also contained in absolute values analysis.

Adolescent↗
PubMed1993

Regional cerebral blood flow in chronic hypertension. A correlative study.

BACKGROUND AND PURPOSE: Cerebral hypoperfusion has occasionally been reported during essential hypertension. We explored regional cerebral blood flow in a large series of neurologically asymptomatic hypertensive patients to determine relations among cerebral blood flow, concomitant main vascular risk factors, and the most common signs of end-organ damage. METHODS: Regional cerebral blood flow was measured by the 133Xe inhalation method in 101 hypertensive patients without clinically apparent central nervous system involvement, including 39 mild to moderate untreated and 62 mild to severe treated patients. RESULTS: Compared with age- and sex-matched normal control subjects, cerebral blood flow was significantly reduced in untreated hypertensive patients (P < .01) and to a lesser extent in treated patients (P = .047). Both regional and global cerebral blood flow reductions were observed in approximately one third of patients in both groups. Analysis of variance failed to show significant correlations between cerebral blood flow and total cholesterol concentration, mean arterial blood pressure, duration of disease, or the presence of retinopathy or left ventricular hypertrophy. In the treated group, the quality of control of hypertension significantly influenced both global cerebral blood flow (P = .007) and cerebrovascular resistance (P < .0001). CONCLUSIONS: Focal or diffuse cerebral hypoperfusion is present even in neurologically asymptomatic hypertensive patients, especially when untreated; good control of blood pressure may preserve cerebral perfusion and reduce cerebrovascular resistance. Regional cerebral blood flow examination represents a relatively simple and low-cost technique to explore the perfusional condition of the brain, one of the main target organs of hypertensive disease.

Adult↗
PubMed1993

Phase I clinical trial of taxotere administered as either a 2-hour or 6-hour intravenous infusion.

PURPOSE: To determine the potential efficacy and dose-limiting toxicity of taxotere, a hemisynthetic inhibitor of tubulin depolymerization. PATIENTS AND METHODS: Fifty-eight patients were administered taxotere in this phase I clinical trial as a 6-hour or a 2-hour infusion repeated every 21 days. Forty patients received 181 courses on the 6-hour infusion schedule, and 18 patients received 105 courses on the 2-hour infusion schedule. RESULTS: Neutropenia was the dose-limiting toxicity on both schedules. The maximally tolerated dose was 100 mg/m2 on the 6-hour infusion schedule and 115 mg/m2 on the 2-hour infusion schedule. The most prominent nonhematologic toxicities included mucositis (more prominent on the 6-hour infusion schedule), transient rash (more common on the 2-hour infusion schedule), and alopecia. Hypersensitivity reactions were seen in five patients. There was no evidence of neurotoxicity or cardiotoxicity. One partial response was noted on the 6-hour infusion schedule (one in refractory breast cancer) and four additional partial responses were noted on the 2-hour infusion schedule (two in adenocarcinoma of the lung, one in refractory breast cancer, one in cholangio-carcinoma). In addition, 10 patients had minor responses. Pharmacokinetic studies showed plasma concentrations of taxotere declined in a triexponential manner, with a terminal half-life of 11.8 hours. CONCLUSION: The recommended starting dose for phase II taxotere trials is 100 mg/m2 administered as a 2-hour infusion, repeated every 21 days. Taxotere is a promising antineoplastic agent worthy of extensive phase II testing in patients with a variety of malignancies.

Adult↗
PubMed1993

Regional cerebral blood flow and cerebrovascular reactivity in IDDM.

OBJECTIVE: To investigate both rCBF and cerebrovascular reactivity, evaluated as pre- and post-ACZ rCBF differences in a group of IDDM patients with differences in duration of disease and severity of complications. RESEARCH DESIGN AND METHODS: rCBF was measured by the 133Xenon inhalation method in 20 IDDM patients and in 15 healthy control subjects before and after an intravenous injection of ACZ, a carbonic anhydrase inhibitor commonly used to assess cerebrovascular reactivity. RESULTS: Basal global CBF (the mean of 32 regional values) was within the normal range in all patients but 1, who showed slight hyperperfusion; moreover, in 3 patients with long-lasting disease, some hypoperfused regions were found. ANOVA showed an inverse correlation between basal global CBF (P < 0.01) and duration of diabetes, but no correlation with Hb, MABP, serum glucose concentration, or GHb. Compared with control subjects, the percentage of global CBF increment after ACZ administration was significantly impaired in 4 patients and gave a borderline response in 2 patients; 4 of these poor ACZ responders had retinopathy, and 1 had suffered from a TIA. Duration of diabetes, Hb, MABP, serum glucose concentration, and GHb did not correlate with the percentage of post-ACZ global CBF changes, and did not differ among the 6 poor ACZ responders and the other diabetic patients or control subjects. CONCLUSIONS: These results confirm that global CBF is within the normal range in most IDDM patients, although it is significantly influenced by the duration of diabetes; pathophysiological correlates of the altered cerebrovascular reactivity need to be further investigated. rCBF measurements, before and after ACZ administration, seem to represent a safe and reliable tool for assessing cerebrovascular function in IDDM.

Acetazolamide↗