Ovarian cancer usually remains clinically silent until it is far advanced, and is associated with significant morbidity and mortality. In view of the modest impact of adjuvant treatments on survival, much effort is devoted to early detection programs and prevention strategies. However, the usefulness of early detection programs remains to be established, with only one randomized study indicating improved median survival in screened individuals. At present, oral contraceptives and prophylactic oophorectomy are the only options for prevention of ovarian cancer. Indications for prophylactic oophorectomy either as a primary procedure, or secondary to abdominal surgery, will vary according to the estimated risk, and to the individual's perception of that risk. Genetic screening allows better identification of pre-symptomatic individuals who would benefit the most from prophylactic oophorectomy. Data concerning the benefit of prophylactic surgery, and the safety of established or innovative hormone replacement therapies in individuals at risk, are encouraging.

Age Factors↗

PubMedDate not supplied

Maternal phenylketonuria: an international study.

Maternal phenylketonuria (PKU) syndrome results in multiple congenital anomalies in the offspring, usually consisting of microcephaly, intrauterine growth retardation, dysmorphology, and congenital heart disease. Pregnancies treated preconceptionally with a phenylalanine-restricted diet and control of maternal blood phenylalanine levels within the recommended range result in normal offspring. However, in this 15-year study, several significant factors resulted in microcephaly in 27% of the offspring, and 7% exhibited serious congenital heart disease. These results occurred chiefly in women with mean IQ scores of 83 associated with low socioeconomic status and decreased educational achievement. Another important factor associated with suboptimal control of blood phenylalanine levels during pregnancy was the fact that most pregnancies were not carefully planned and occurred in women off dietary treatment with phenylalanine-restricted products. These results indicate that greater effort must be developed to assist women with PKU in remaining on diet during their reproductive years. It appears that continued adherence to the diet, resulting in normal maternal intelligence, is an important contribution to improved fetal development.

Female↗

PubMedDate not supplied

Hypertrophic cardiomyopathy: failure to demonstrate mutations in exon 13 of the cardiac beta myosin heavy-chain gene.

Familial hypertrophic cardiomyopathy (FHCM) has been linked to the cardiac beta-myosin heavy-chain (MHC) genes on chromosome 14 (14q1), and a missense mutation within exon 13 of the beta MHC gene has been implicated in the pathogenesis of the disease. To test whether this constitutional mutation occurs somatically in the myocardium of the sporadic form of the disease, we studied seven patients with familial (n = 3) or sporadic (n = 4) hypertrophic cardiomyopathy (HCM). Amplification of exon 13 of the beta MHC from paraffin-embedded myocardium using the polymerase chain reaction (PCR) was performed and analysis of the amplified product for migration abnormalities using denaturing gradient gel electrophoresis (DGGE) and direct sequencing of the PCR product were used. Neither patients with HCM nor subjects with dilated cardiomyopathy (DCM) (n = 2) exhibited an aberration within exon 13 of the myocardial beta MHC. It is concluded that a specific beta MHC gene mutation is displayed only in a subset of patients with familial disease, thus further emphasizing the notion of genetic heterogeneity. In addition, in the sporadic form of the disease, somatically occurring mutations in this particular exon could not be demonstrated.

Base Sequence↗

PubMedDate not supplied

Blood serotonin in psychotic and brain damaged children.

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Age Factors↗

PubMedDate not supplied

Anorexigenic effects of d-amphetamine and l-DOPA in the rat.

The effect of amphetamine and l-dopa was compared in 22-hr food- and water-deprived rats. Amphetamine produced marked anorexia, and l-dopa significantly reduced food intake at 200 mg/kg. Following pretreatment with RO 4-4602, a decarboxylase inhibitor, 100 mg/kg of l-dopa, a dose that did not significantly affect eating, produced marked anorexia. The anorectic effect of both amphetamine and l-dopa was antagonized by propranolol, a beta adrenergic antagonist. Phentolamine, an alpha-adrenergic antagonist, potentiated the anorectic effect of amphetamine and l-dopa. Haloperidol (0.1 mg/kg), a dopamine antagonist, failed to prevent the anorexia due to amphetamine but accentuated that due to l-dopa. Methysergide, a serotonin antagonist, also failed to prevent the anorexigenic effect of amphetamine. Finally, the administration of l-dopa with or without peripheral decarboxylase inhibition resulted in more than twice the increase in hypothalamic dopamine levels without significant changes in 5-HT or norepinephrine levels. The data show that the anorexigenic effect of amphetamine and l-dopa are similar and indicate a functional role for both norepinephrine and dopamine neurons in feeding behaviour in the rat.

Animals↗

PubMedDate not supplied

The usefulness of DST in predicting response to antidepressants: a placebo-controlled study.

Seventy-two out-patients, 55 years or older, suffering from major depression were treated with either nortriptyline or phenelzine for seven weeks under placebo-controlled double-blind conditions. The dexamethasone suppression test (DST) was administered at baseline and at weeks 3 and 7 of treatment, and its usefulness in predicting and/or paralleling clinical response was examined. No correlation was found between baseline DST results and treatment response with antidepressants. Of 13 patients whose abnormal baseline DSTs normalized during treatment, six were responders and seven were nonresponders (P = 0.24). However, all (seven) patients whose DSTs persisted to be abnormal throughout the seven weeks did not respond. The authors conclude that the DST has not been shown to have practical value as an indicator of impending recovery from major depression in the elderly, but its failure to normalize may have ominous prognostic significance.

Aged↗

PubMedDate not supplied

Size/shape analysis of aerodigestive foreign bodies in children: a multi-institutional study.

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Child, Preschool↗

PubMedDate not supplied

Aging-induced decrease in dopaminergic-stimulated phosphoinositide metabolism in rat brain.

Accumulation of [3H]inositol phosphate and [3H]inositol labeling of phosphoinositides were evaluated in brain slices of 3-, 6-, 12-, and 24-month-old Fischer-344 rats. The dopamine agonist, SKF38393, stimulated significantly lower accumulations of inositol trisphosphate, inositol bisphosphate, and inositol monophosphate in the striatum, hippocampus, and frontal cortex of 24-month-old rats compared with the 6-month-old animals. No differences, however, were observed between the 3, 6, and 12-month-old groups. Furthermore there were marked decrements of 41% to 58% in the labeling of phosphoinositides in the different brain regions of the aged animals. Dose-response studies in forebrain slices of the 6-month-old and 24-month-old animals showed aging-related decrements of 53% (p less than 0.001) and 48% (p less than 0.001) in the maximal SKF38393-stimulated labeling of phosphoinositides and accumulation of inositol phosphates, respectively. These data suggest that aging of the rat brain is associated with alterations in the basal turnover of the inositol cycle and in the sensitivity of the transduction pathway to dopamine receptor stimulation.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMedDate not supplied

Attenuated protein kinase C activity and translocation in Alzheimer's disease brain.

Protein kinase C (PKC) activity and its redistribution were determined in postmortem Alzheimer's disease (AD) and age-matched control brains. Cytosolic and membrane-associated PKC activities were lower in frontal and temporal cortices and hippocampi of AD brains. Increased concentrations of phosphatidyl-L-serine, Ca2+ or phorbol 12-myristate, 13-acetate only weakly increased enzyme activity in AD tissues. Redistribution of cytosolic PKC to the membranous fraction was elicited in control brain slices by 162 nM PMA in the presence of K+ (65 mM). This redistribution of the enzyme was markedly reduced in AD brain slices. In contrast, the immunoreactivity of the alpha- and gamma-PKC isozymes were elevated in cortical tissue from AD subjects. No changes were noted in beta-PKC immunoreactivity. These results suggest that the reduced PKC activity and the attenuated translocation of the enzyme in AD brain tissue may be attributed to down regulation of PKC or to alteration in PKC protein. The increase in PKC immunoreactivity may be a reflection of an altered susceptibility to proteolysis or a compensatory response secondary to the loss in enzyme activity.

Aged↗