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Biomedical subjects

A Munoz

Publications and source records attributed to A Munoz.

At least 19 recordsLinked to original sources

A phase II trial of didemnin B (NSC No. 325319) in advanced and recurrent cervical carcinoma: a Gynecologic Oncology Group study.

Didemnin B was administered to 24 women with recurrent squamous cell cervical carcinoma. The initial dose was 4.2 mg/m2, intravenously, repeated every 28 days. Twenty-three patients were evaluable for toxicity and twenty-one for response. Toxicity was mild, consisting mainly of nausea and vomiting. There were no objective responses; 43% had stable disease for at least 3 months. Didemnin B, when given in this dosage schedule, appears to have minimal effect against this tumor.

Adult

[Primary prevention trial. Methodological problems].

Primary prevention trials are the best method of demonstrating the true value of medical intervention to correct abnormalities of lipid metabolism. A large number of patients must be followed up for a long period and this explains the complexity of the logistic problems which are encountered. However, these trials must conform to the classical guide lines of all clinical trials: an accurate definition of the study population, a principal criterion of adjustment which satisfies the golden rule "One question, one study".

Clinical Trials as Topic

[Salazosulfapyridine in rheumatoid arthritis. A study of 49 patients].

The results of an open retrospective study of 49 patients treated with salazosulfapyridine (SASP) (sulphasalazine) for rheumatoid arthritis (RA) are reported. The patients, 7 men and 42 women, had a mean age of 53 years, and their mean duration of evolution of RA was 13.3 years. Sixty percent of them had undergone more than 3 previous disease-modifying drugs. The mean length of SASP treatment was 15.3 months. The initial response was favorable in 34 patients (69%). Treatment was ineffective and stopped in 12 cases (24.5%); the inefficacy was primary in 6 and tachyphylactic in the other 6. Twenty patients (41%) experienced at least one side effect. SASP was stopped in 11 patients (20.4%) due to undesirable side effects; 9 of the 11 times were during the first 2 months of treatment. Digestive system intolerance was the most common but led to drug withdrawal in less than half the patients. In all cases, mucocutaneous, neurosensory, hematological and hepatic side effects regressed during the month following SASP withdrawal. The therapeutic maintenance level was 67% at 1 year, 60% at 18 months, 52% at 2 years and 45% at 3 years. SASP has a role in the treatment of relatively slightly evolved forms of RA, before prescribing methotrexate. The possibility of delayed intolerance reactions, notably hematological and hepatic, justify prolonged biological monitoring of these patients.

Adult

Influence of thyroid hormone on brain gene expression.

Brain development in mammals is dependent on thyroid hormone. In the rat, the T3 receptor is present as early as the 14th day of fetal life and increases during the periods of neuroblast proliferation and oligodendrocyte differentiation. The mRNAs encoding the receptor isoforms can also be demonstrated by in situ hybridization, with different distribution of the alpha or beta forms. Expression of several genes was studied in hypothyroid animals during the neonatal period. The lack of thyroid hormone affects the expression of most oligodendrocyte genes in a time- and region-dependent fashion. The major role of thyroid hormone on myelin genes is on their timing of expression. Among the neuronal genes studied, thyroid hormone influences the expression of RC3, a brain specific gene encoding a protein kinase C substrate. Thyroid hormone is not require for the timing of expression of this gene, but is needed for its full expression both during the neonatal period and in adult animals.

Animals

[Amiodarone and secondary prevention. The EMIAT study].

The EMIAT is a randomized, double-blind trial versus placebo, designed to evaluate the efficacy of amiodarone in the prevention of total mortality in patients with left ventricular ejection fraction of under 40% after myocardial infarction. This multicenter European trial initiated by SANOFI Research in association with the Arrhythmia Working Group of the European Society of Cardiology, is part of a larger program of evaluation (3,400 patients) of the benefit-risk ratio of the use of amiodarone for secondary prevention in high risk patients.

Amiodarone

Phase II study of N-methylformamide (N-MF) (NSC 3051) in patients with advanced epithelial ovarian cancer. A Gynecologic Oncology Group study.

Forty-four patients with advanced, measurable, epithelial carcinoma of the ovary were treated with 97 courses of N-methylformamide (N-MF) at doses ranging from 600-800 mg/m2, intravenously, daily for 5 days every 28 days. Forty-one patients had prior surgery and had received one prior chemotherapy regimen. Only seven patients had received any prior radiation therapy. All patients were Gynecologic Oncology Group (GOG) performance status 0, 1, or 2. Three partial responses were seen. Hematologic adverse effects were extremely rare as predicted by early clinical trials. One major toxicity was a syndrome consisting of some combination of myalgias, arthralgias, pleuritic pain, abdominal pain, peripheral neuropathy, anorexia, lethargy, and declining performance status (pain-lethargy syndrome) that was reversible with discontinuation of the drug. This adverse effect was as common a reason as hepatic toxicity for discontinuation of N-MF. As reported in previous studies with this drug, hepatic toxicity was also common, usually reversible, and also a cause for discontinuation of the drug. The low level of clinical activity and the unpleasant adverse effects in this population of patients with previously treated ovarian cancer makes it unlikely that this drug will play any significant role in treatment of epithelial ovarian cancer.

Adult

[A simplified surgical approach in choledochal lithiasis reducing the complexity and severity of this surgery. Study of a series of 153 cases].

The surgical treatment of stones of the common bile duct by transcystic extraction of stones without biliary and peritoneal drainage greatly simplifies biliary surgery. Postoperative course and average hospital stay are similar to those encountered after conventional cholecystectomy. This surgical option was successfully achieved in almost 60% of the 153 patients with stones of the common bile duct of our series, operated between 1981 and 1987. Other patients were treated more conventionally because of failure or impossibility of complete transcystic extraction of stones. A choledochoduodenostomy was performed in 28 patients. In a limited number of patients (n = 12) endoscopic sphincterotomy was associated pre or postoperatively with the surgical treatment. Although 25% of the patients were older than 75 years, there was no operative mortality, which demonstrates that biliary surgery can be performed safely without any vital risk. Successful transcystic extraction of stones simplifies the course of stones of the common bile duct and should be attempt more often.

Adult

A micro ELISA for the diagnosis of cerebral cisticercosis.

A micro ELISA for cysticercosis in the central nervous system was evaluated in 24 patients and compared with indirect hemagglutination. CSF ELISA results were positive in 17 of 20 patients (sensitivity 85%), whereas CSF indirect hemagglutination was positive in only 14 patients (sensitivity 70%).

Brain Diseases

Local control and survival of Ewing's sarcoma in children with radiotherapy and chemotherapy without radical surgery.

The present study was undertaken in 27 children with localized Ewing's sarcoma treated at our hospital. In 9 cases the lesion was central and in 18 peripheral. Treatment consisted of: 1) Chemotherapy with 6 drugs (vincristine, cyclophosphamide, methotrexate, bleomycin, dactinomycin and doxorubicin) for one year in all patients; 2) Radiotherapy in 24 patients at a dose of 30-40 Gy in the entire bone with a booster dose of 10-15 Gy in the lesion. In 7 patients debulking surgery was performed followed by irradiation. Two cases with tumor in expendable bones and one with extensive destructive lesion in the tibia underwent radical surgery. One patient suffered local recurrence (femur) and 6 developed distant metastases. The remaining 20 (74%) patients were alive and tumor-free after follow-up periods of 17-80 months. Among the 12 patients with extremity lesions who were alive, 7 (58%) had minimal or mild treatment sequelae, 2 moderate, and 3 severe sequelae but no amputation has been required. Our study shows that local control can be achieved in almost all patients without radical surgery and with acceptable extremity function in the majority.

Adolescent

Acetazolamide: maternal toxicity, pattern of malformations, and litter effect.

Thirty litters of C57BL 6J mice were administered intraperitoneally one of four doses (0, 500, 750, and 1,000 mg/kg maternal weight) of acetazolamide on day 9 of gestation. The fetuses were removed on day 18 and fixed, stained, cleared, and examined for the pattern of malformations. The forelimb postaxial limb deficiency was the most common abnormality, but forelimb postaxial polydactyly and a postaxial deficiency in the hindlimb were also observed. Males were significantly more likely to be malformed than females at all doses, in contrast to the predominance of females observed in rat fetuses exposed to acetazolamide (Scott et al.: Teratology 6:239-240, '73). The occurrence of limb malformations did not correlate with maternal weight loss, the birth weight of the fetus, or the position of the fetus in the uterus. A "litter effect" was demonstrated in that there was a nonuniform distribution of litters with different proportions of malformed fetuses.

Abnormalities, Drug-Induced

Safe and cost-effective cleaning of pressure-monitoring transducers.

The CDC category I recommendation for high-level disinfection of pressure-monitoring transducers between uses imposes substantial costs. This practice has not been shown to be useful when disposable transducer domes are used. A prospective, randomized, double-blind study assessed the consequences of wiping transducers with alcohol between uses rather than sterilizing with ethylene oxide. We studied 5,197 transducer courses with disposable domes involving 2,202 patients in intensive care units during 15 months. There was no significant difference between the two treatment regimens in the risk of positive cultures of fluids from monitored lines, of cultures of cannula tips or of a positive blood culture. We conclude that under normal conditions, ie, in the absence of a cluster of transducer-related bacteremias, wiping transducers with alcohol between uses is sufficient when disposable domes are used.

Catheterization

Immunogenicity and safety of measles vaccine in ill African children.

A concurrent prospective study was conducted in Rwanda to compare the immunogenicity and safety of live, attenuated measles vaccine in ill and well children. Five hundred and eighteen children aged 8 to 19 months were selected from children attending the acute care and immunization services of two clinics. Two hundred and sixty-seven ill children and 251 well children were enrolled and examined. Serological tests were performed on blood samples obtained before and 40 days after measles immunization. Among the 208 ill children and 215 well children who were seronegative at baseline and had unequivocal follow-up serological results, seroconversion rates were 81% and 80%, respectively. Side effects were modest and were equally frequent in the two study groups (15.4% among ill children versus 15.1% among well children). These results support a change in measles immunization policy in developing countries with respect to immunization of children with acute illnesses. Such a change would make a great contribution to decreasing the enormous burden of measles in the developing world through increased immunization coverage.

Antibodies, Viral

A randomized hemodynamic comparison of intravenous amiodarone with and without Tween 80.

In 20 patients undergoing coronary arteriography, the hemodynamic effects of an experimental preparation of i.v. amiodarone 5 mg kg-1 without Tween 80 (N) (10 patients) were compared with those of the commercial form with Tween 80 (A) (10 patients). Analysis of variance demonstrated differences during the 3 min of injection and for 3 min afterwards: left ventricular systolic pressure decreased from 110 + 11 to 86 +/- 11 mmHg (P = 0.001) after A and from 114 +/- 22 to 106 +/- 19 (P = 0.05) after N (comparison P = 0.01) while related tachycardia was also more pronounced after A (comparison P = 0.001). Left ventricular end diastolic pressure transiently decreased after A while continuously increasing after N (P = 0.05). During the following 30 min both A and N caused similar bradycardia, increase in ventricular filling pressure, vascular resistance and decrease in cardiac and contractility indexes. Amiodarone blood levels were similar after A or N. These data document a significant initial short duration vasoplegia, mainly related to Tween 80, after A, when amiodarone itself after producing a similar very slight effect causes bradycardia, and a moderate and progressive negative inotropic effect. It was concluded that while the experimental form would be of interest, the risk of severe hypotension after i.v. Cordarone can be largely avoided by using a slower rate of infusion, especially in patients with hypovolemic status.

Adult

Transmission of HIV-1 within a statewide prison system.

To assess the incidence of infection with HIV-1 in the Maryland state prison system, inmates with excess sera stored from specified intake periods between April and June 1985 and 1986 were approached in May 1987 to volunteer for venipuncture. Of the 2286 inmates for whom intake specimens were stored, 1038 (45.4%) no longer incarcerated as of April 1987 were excluded from the study; another 319 missed the survey. Of the 929 eligible inmates approached for the study, 446 (48%) consented and 422 (94.6%) provided a specimen. Twenty-nine (6.6%) were confirmed seropositive at time of entry into prison, indicating that infection had occurred prior to incarceration. Baseline seropositives were more likely (P less than 0.05) to be non-violent offenders, committed in Baltimore City, and black. The 393 participants seronegative at baseline provided a total of 482 prison-years of potential exposure to infection. Two inmates seroconverted with baseline specimens seronegative on Western blot and follow-up sera confirmed positive; their duration of pre-incarceration detention was 69 and 146 days, respectively. No interruption of incarceration was recorded for these two inmates. The rate of infection in this prison sample, which does not include an average of 2 months of pre-incarceration detention for the study sample, was 0.41% per prison-year.

Acquired Immunodeficiency Syndrome

Hemodynamic effects of penticainide (CM 7857), a novel class I antiarrhythmic drug--comparison with disopyramide.

Penticainide (CM 7857) is a new class I antiarrhythmic agent, which has been shown to suppress ventricular arrhythmias by a specific effect on repolarization, shortening the action potential duration. To assess acute hemodynamic effects of penticainide and to compare them to those of disopyramide, 20 patients with normal left ventricular function were studied by simultaneous left and right heart catheterization before as well as 5 and 30 min after intravenous drug administration (1.5 mg/kg for both compounds) in a randomized fashion. After penticainide, a maximal negative inotropic effect was noted at the end of the 5 min infusion, as reflected by reductions in stroke index and parameters of contractility despite increases in vascular resistances. These changes returned to baseline after 30 min except for ejection fraction, which was still lower than at baseline. After disopyramide, similar hemodynamic drug effects were observed that were greater than after penticainide, leading to a moderate tachycardia immediately after drug infusion. In addition, all parameters of contractility as well as stroke index were still significantly reduced 30 min after disopyramide, but not after penticainide. Thus, the hemodynamic profiles of both drugs tested were similar, but the negative inotropic effect of penticainide was less marked and of shorter duration than that of disopyramide in an equipotent antiarrhythmic dose. Penticainide may therefore be used in treatment of acute ventricular arrhythmias, but it should be administered with caution in patients with depressed left ventricular function.

Adult

The relationship of blood lead to systolic blood pressure in a longitudinal study of policemen.

We examined the relationship of blood lead level to systolic and diastolic blood pressure in a longitudinal study of 89 Boston, MA, policemen. At the second examination blood lead level and blood pressure were measured in triplicate. Blood pressure measurements were taken in a similar fashion in years 3, 4, and 5. Multivariate analysis using a first-order autoregressive model revealed that after adjusting for previous systolic blood pressure, body mass index, age, and cigarette smoking, an elevated blood lead level was a significant predictor of subsequent systolic blood pressure. Bootstrap simulations of these models provided supporting evidence for the observed association. These data suggest that blood lead level can influence systolic blood pressure even within the normal range.

Adult