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J Rosenthal

Publications and source records attributed to J Rosenthal.

At least 163 records · Page 9Linked to original sources
PubMed1986

Long-term use of oral contraceptives and risk of invasive cervical cancer.

To evaluate the relationship between use of oral contraceptives and risk of invasive cervical cancer, a case-control study involving 479 patients and 789 population controls was undertaken in 5 geographic regions of the US. Initially, the relationship was obscured by confounding variables, particularly the interval since last Pap smear. Control for this variable as well as for sexual and sociodemographic factors revealed an RR of 1.5 overall, with long-term users (5 or more years) being at a 2-fold higher risk than non-users. Pill associations prevailed for both adenocarcinomas and squamous-cell tumors, and risks were highest for those using pills containing high estrogen potencies. In addition, there was some evidence that pill associations were most pronounced among women who had never used barrier methods of contraception or who had histories of genital infections, suggesting that oral contraceptives may act as co-carcinogens with transmissible agents. Our findings provide further evidence that long-term use of oral contraceptives may have a carcinogenic effect on cervical epithelium, but emphasize the need for careful evaluation of confounding influences.

Adenocarcinoma↗
PubMed1986

Diphenylhydantoin and phenobarbital suppress the dopaminergic neurotoxicity of MPTP in mice.

The combined administration of MPTP with the anticonvulsant drugs diphenylhydantoin or phenobarbital suppressed the MPTP-induced striatal DA depletions in mice. Co-treatment with diazepam, sodium valproate or carbamazepine was ineffective. The mechanism responsible for the protective effect of diphenylhydantoin and phenobarbital against DA neurotoxicity of MPTP is unknown but some previously available findings suggest that they may act, in part, via inhibition of MAO-B and/or DA reuptake in the striatum.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Systemic administration of antioxidants does not protect mice against the dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP).

We examined whether DA neurotoxicity of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) can be prevented by combined systemic administration of antioxidants. C57 black mice were injected s.c. with MPTP (30 mg/kg), once daily for two days, alone, or with ascorbic acid (1 g/kg), alpha-tocopherol (100 mg/kg), or dimethylsulfoxide (50 microliters) i.p. for two days before, two days with and two days after MPTP, and decapitated 30 days later. MPTP once (30 mg/kg), alone, or with ascorbic acid (200 mg/kg) or cysteamine (75 mg/kg), two days before, one day with and 4 days after, and decapitated 10 days post-MPTP. MPTP once (15 mg/kg), alone, or with ascorbic acid (500 mg/kg, alpha-tocopherol (100 mg/kg), cysteamine (50 mg/kg) or sodium selenite (2.5 mg/kg), 90 min before and again 90 min after MPTP, and decapitated 7 days later. In all experiments, the marked striatal DA depletions produced by MPTP alone (by 40-70% from controls) were unchanged by cotreatments with the various antioxidants. Findings do not favor intraneuronal generation of superoxides and related cytotoxic free radicals as a major factor in the DA neurotoxicity of MPTP. They suggest that if natural Parkinson's disease is caused by an MPTP-like neurotoxin, early treatment with antioxidants is unlikely to protect nigrostriatal neurons and prevent disease progression.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Evidence for a potent angiotensin I degrading enzyme different from angiotensin I converting enzyme in rat vascular tissues.

There are indications for the existence of an intrinsic renin angiotensin system in vascular walls, which is assumed to participate in blood pressure regulation and in pathogenesis of arterial hypertension. It was evaluated if and to what extent the decapeptide angiotensin (A) I, one of the natural substrates of A I converting enzyme (ACE), is degraded by other peptidases than ACE in rat vascular tissues. A I and A II degradation was studied in arterial and venous vascular wall extracts. The activities ranged between 0.068 +/- 0.025 U and 0.044 +/- 0.025 U. The enzymes involved were biochemically characterized by determination of isoelectric points (pI), pH optima, molecular weights and by investigation of their inhibition behavior in vitro. One potent A I degrading enzyme (AIDE) was identified with pI between 3.6 and 3.9, and pH optimum at 7.75. In vitro studies revealed that AIDE activity was not blocked by the specific ACE inhibitors MK 421 or MK 422 (both 11 nMol/ml). The molecular weight of AIDE ranged between 440,000 and 457,000. The results indicate that AIDE is not identical to ACE (pI 4.2-5.0; pH optimum 8.3). AIDE was also observed in aortic smooth muscle cells cultured in vitro. AIDE decreased following bilateral nephrectomy or administration of aldosterone combined with sodium chloride loading, whereas it was elevated in spontaneously hypertensive rats (Okamoto strain). Since AIDE metabolizes A I, one of the substrates of ACE, it may indirectly affect A II formation and bradykinin inactivation as well.

Aldosterone↗
PubMed1986

Effect of postnatal light deprivation on the ontogenesis of dopamine neurons in rat retina.

In rats raised from birth under a regular dark-light cycle, retinal dopamine (DA) levels were low at 12 days, increased progressively and steeply at 16, 20, 30 and 60 days and peaked at about 75 days postnatally. Dark-rearing from birth suppressed the magnitude of the normal developmental pattern of DA concentrations in retina and at 20, 30 and 60 days of age they were markedly smaller compared with those in age-matched controls grown under regular cyclic illumination. In adult rats reared up to the age of 60 days in regular cyclic lighting and then transferred to complete darkness for additional periods of 7-60 days, there were marked reductions in retinal DA levels. In rats reared in total darkness for 16, 20 or 30 days after birth and then transferred to regular dark-light conditions for additional periods of up to 30 or 60 days, retinal DA levels were always higher than those in animals with continuous light deprivation. They were similar to or even higher than those in rats grown under regular dark-light cycle. Findings suggest that light stimulation is essential for the postnatal ontogenetic increases of synthesis and storage of DA within retinal DAergic neurons. Suppressed DA accumulation in retina induced by dark-rearing from birth is not irreversible and can be completely corrected by re-exposure to regular lighting conditions regardless of the durations of postnatal light deprivation.

Animals↗
PubMed1986

Response of colo-rectal hepatic metastases to concomitant radiotherapy and intravenous infusion 5 fluorouracil.

Twenty-three patients with colo-rectal hepatic metastases were retrospectively reviewed after completing treatment with split course liver irradiation and continually infused concomitant intravenous 5-fluorouracil. Although no patient attained a complete response, an objective partial response was documented in 15 (Responders). The Responders had a median survival of 45 weeks whereas Non-responders had a median survival of 17 weeks. Patients with metastatic disease solely in the liver or those with a Karnofsky performance score (k.p.s) of over sixty, had a median survival of 49 weeks. Patients with multiple organ metastatic involvement had a median survival of 25 weeks and those with a Karnofsky with less than 60 had a median survival of 27 weeks. (p values of 0.006 and 0.03, respectively.) The overall survival of the group completing treatment was 30 weeks, and 19 patients (83%) achieved subjective palliation. The patients tolerated therapy well. There was minimal hematological toxicity; 3 patients developed a leucocyte count of less than 2000 and 1 developed a platelet count of 30,000. The palliation and prolongation of survival attained with minimal complications suggest that adjuvant liver irradiation with concomitant infusion 5-fluorouracil radiosensitization may be an option to offer patients identified to be at high risk of developing subclinical liver disease.

Adult↗
PubMed1986

Community phase of cardiac rehabilitation.

Although their effects cannot be shown to statistically alter coronary heart disease mortality or morbidity, voluntary health organizations throughout the world clearly play an important role in bringing about favorable changes in the natural history of this disease and in the community phase of its management. In particular, voluntary organizations are able to conduct research surveys and field trials and by so doing favorably influence state health administration. They are able to correct temporary deficiencies in health services, particularly in the form of psychosocial support and cardiac health education. Observers note that the major change in community phase management has occurred with the wider use of coronary bypass surgery since 1975. More objective data, especially relating to psychosocial factors, can be expected when further research (especially the MONICA Study) is completed. Throughout the world, however, existing voluntary health organizations could be more active in the community phase of cardiac rehabilitation. It would seem an area where such organizations could well do more. A challenging question that should be constantly reviewed is 'Can we do more to reduce the effects of invalidism in cardiac patients?'

Australia↗
PubMed1986

An innovative approach to public health research: the case of a new center in Mexico.

This paper presents the conceptual and organizational elements that have guided the development of the Center for Public Health Research (CPHR) in Mexico. The CPHR was established in August 1984, in the midst of the most profound health care reform in Mexico in the last 40 years. The reform has included, among other measures, a Constitutional amendment recognizing the social right to health care, an energetic effort to decentralize the system so that each state will run its own services, an ambitious drive to extend primary health care coverage to all the population, and a strong promotion of research as the basis for strategic planning and for the development of standards of care. The creation of the CPHR is a response to the need for a firm base of epidemiologic and health systems research in Mexico. This need arises from the increasing complexity of the country's organizational arrangements for health care. In addition, the patterns of morbidity and mortality are also becoming more intricate, as Mexico is experiencing an epidemiologic transition whereby chronic diseases, mental ailments, and accidents are on the rise even as the incidence of infectious diseases and malnutrition continues to be high. As a unit of the Ministry of Health, the CPHR must strike a balance between relevance to decision making and excellence in the strict adherence to the norms of scientific research. To do so, it has developed a conceptual framework based on a tridimensional matrix. The dimensions of the matrix include substantive areas (i.e., the phenomena to be researched), knowledge areas (i.e., the disciplines pertinent to public health), and methodological areas (i.e., the methods to be applied in each project). The intersection of these dimensions produces different configurations of "research modules" that can be adapted to changing priorities. Current priorities of the CPHR include epidemiologic studies of the emerging conditions in the transition, migration and health, child survival, social organization and primary health care, health systems management, quality of care, and the development of information systems and quantitative models for public health research. Research projects are undertaken in a matrix type of organization in which academic departments are structured according to problems rather than disciplines. The analysis of Mexico's Center for Public Health Research may contribute to similar endeavors in other countries and also to the wider development of comparative studies on research organizations.

Mexico↗
PubMed1986

Moderate essential hypertension control: a double-blind crossover study between a serotonin antagonist and a post-synaptic alpha-blocker.

The purpose of this study was to compare the effects of the serotonin antagonist ketanserin and the post-synaptic alpha-blocker prazosin on blood pressure in patients with essential hypertension. Both drugs lower blood pressure by a reduction in total peripheral vascular resistance and by reducing the pre- and afterload, apparently achieving these haemodynamic effects through different mechanisms. Ketanserin appears to have a greater effect on afterload. Six men and four women (mean age 47.2 years) with diastolic blood pressure greater than or equal to 100 mmHg were treated for 4 weeks with placebo and then randomized and treated for 8 weeks double-blind with either ketanserin or prazosin. A 4-week wash-out phase with placebo was then instituted followed by another 8 weeks of treatment in a crossover fashion with either ketanserin or prazosin. Blood pressure was measured on each occasion in the supine, sitting and standing positions. The results showed that both medications significantly lowered blood pressure (computed sitting values for all patients: ketanserin from 177/104 +/- 5/7 to 158/89 +/- 8/5 mmHg; prazosin from 176/103 +/- 11/8 to 156/88 +/- 6/4 mmHg). The data in this study show that ketanserin as an antihypertensive agent is as effective as prazosin, but in contrast requires no titration of dosage and better compliance can be expected with twice daily rather than three times daily dosing.

Adrenergic beta-Antagonists↗
PubMed1985

In vivo effect of MPTP on monoamine oxidase activity in mouse striatum.

Striatal monoamine oxidase (MAO)-B, but not MAO-A, activity decreased in mice at 2 and 10 days and was back to control values at 20 and 30 days after systemic administration of N-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP). Striatal dopaminergic (DA) depletions were maximal at 2 days and were only partially reversed at 30 days post-treatment. In rats, unilateral kainic acid lesions increased MAO-B but not MAO-A activity probably due to reactive gliosis, but MPTP did not affect DA levels in control and kainic acid-lesioned striata. Findings support the importance of MAO-B in the toxicity of MPTP and suggest that resistance of rat DA neurons to the neurotoxin is probably not due to species differences in MAO-B activity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1985

Dopamine but not norepinephrine or serotonin uptake inhibitors protect mice against neurotoxicity of MPTP.

Combined administration of nomifensine, a DA reuptake inhibitor, and MPTP completely prevented the long-term (30 days post-treatment) striatal DA depletions induced by MPTP in mice. Cotreatment with desipramine and clomipramine or fluoxetine, inhibitors of NE and 5-HT, respectively had no effect on DA neurotoxicity of MPTP. The findings indicate that MPTP (or MPP+) is a substrate for the specific DA reuptake system and may explain, in part, its selective toxic effects on DA neurons.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1985

Suppression of MPTP-induced dopaminergic neurotoxicity in mice by nomifensine and L-DOPA.

To examine effects of various pharmacological manipulations of dopamine (DA) metabolism on DA neurotoxicity of N-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP), C57 black mice were injected with MPTP (30 mg/kg s.c., once daily for two days) alone or in combination with apomorphine, bromocriptine, haloperidol, L-DOPA or nomifensine. MPTP markedly decreased neostriatal DA concentrations at 2, 10, 20 and 30 days post-treatment indicating persistent degeneration of nigrostriatal DA neurons. Suppression or acceleration of DA turnover rates by the DA agonists apomorphine and bromocriptine or by the DA antagonist haloperidol, respectively, did not affect MPTP toxicity. MPTP-induced neostriatal DA depletions were markedly suppressed by nomifensine, a DA reuptake inhibitor, and attenuated by exogenous L-DOPA. MPTP may be a substrate for the DA reuptake system and its specific transport into nigrostriatal terminals may be an important factor for its selective neurotoxicity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗