Reversal of antidepressant activity of fluoxetine by cyproheptadine in three patients

Three male patients are described in whom anorgasmia developed during treatment with fluoxetine for depression. During attempts to treat the anorgasmia with cyproheptadine, all three patients suffered a relapse of depressive symptoms. The possible mechanism of this effect is discussed in relation to serotonergic systems.     

Pediatric EMS transport: are we treating children in a system designed for adults only?

Unlike adults, small children and infants do not require stretchers or ambulances for transport from a prehospital scene to the emergency department (ED). This study was designed to determine the importance of this difference in patient transport needs. A Macintosh Classic computer was programmed to compare the time to intubation (TTI) of a child with impending respiratory arrest treated in a standard paramedic/ambulance transport system versus that of a child treated in a system in which a patrolling police car transports the child directly to an ED. The dependent variable TTI was determined, with travel times from the scene to the ED and paramedic intubation success rates as the independent variables. Utilizing this model, police transports demonstrate shorter TTIs for brief scene-to-ED travel times or limited paramedic success rates, while paramedic intubations produced shorter TTIs for long scene-to-ED transports. These results suggest that nonambulance transport of pediatric patients be considered in the development of urban or suburban pediatric Emergency Medical Services.     

Possible role of alpha-2-noradrenergic receptors in modulation of sexual behavior in female guinea pigs

These studies examine whether alpha 1-noradrenergic receptor stimulation alone is sufficient to facilitate lordosis behavior in ovariectomized, estrogen-primed female guinea pigs and to what extent alpha 2-noradrenergic receptors are involved in this steroid-dependent behavior. Neither of the alpha 1-agonists, phenylephrine or methoxamine, significantly facilitated lordosis in ovariectomized females primed with 10 micrograms of estradiol benzoate for 1 or 3 days. Animals exhibiting estrogen plus clonidine-facilitated lordosis showed a decrease in the behavior when given one of two alpha 2-antagonists (yohimbine or idazoxan). Idazoxan also attenuated lordosis in animals given estrogen plus progesterone. These findings, in combination with previous findings (that specific alpha 1-antagonists block lordosis), suggest that alpha 2-receptors, in addition to alpha 1-receptors play a role in modulation of lordosis behavior.     

Can patients with severe left ventricular dysfunction be treated by coronary artery bypass surgery?]

Forty three men and 3 women, with an average age of 59 years (13 to 78 years) underwent aorto-coronary bypass surgery despite severe left ventricular dysfunction (ejection fraction < 35%); 96% of the patients had previous infarction; 60% (N = 28) had unstable angina, 52% (N = 24) had had pulmonary oedema or an episode of congestive cardiac failure. The average ejection fraction was 29 +/- 4%, range 17 to 35%. Thirteen patients had ventricular aneurysms, 4 had grade 3 or 4 mitral regurgitation. The coronary lesions were usually multivessel left main coronary (6), triple vessel disease (27), double vessel disease (12), single vessel disease (1). The average number of bypass grafts per patient was 2.3. The average aorting clamping time was 63 minutes (range 26 to 133 minutes). There were 4 mitral valve replacements, 4 resections of ventricular aneurysms and 1 double procedure (aneurysmectomy and valve replacement). The operative mortality was 2.1% (1 death). During an average follow-up period of 27 months (range 3 to 90 months), there were: 2 recurrent infarctions, 13 episodes of cardiac failure and 8 cardiac deaths (cardiac failure: 5, sudden death: 2, recurrent infarction: 1). Two patients underwent cardiac transplantation. The regression of angina (90% of operated patients were asymptomatic) and the low operative risk, justify aortocoronary bypass surgery despite left ventricular dysfunction in patients with severe symptoms (unstable angina, chronic, invalidating angina). The medium-term results indicate a high risk of cardiac failure which is partially responsible for the secondary mortality rate of 17% at 2 years.     

A controlled trial of acyclovir for chickenpox in normal children

BACKGROUND. Chickenpox, the primary infection caused by the varicella-zoster virus, affects more than 3 million children a year in the United States. Although usually self-limited, chickenpox can cause prolonged discomfort and is associated with infrequent but serious complications. METHODS. To evaluate the effectiveness of acyclovir for the treatment of chickenpox, we conducted a multicenter, double-blind, placebo-controlled study involving 815 healthy children 2 to 12 years old who contracted chickenpox. Treatment with acyclovir was begun within the first 24 hours of rash and was administered by the oral route in a dose of 20 mg per kilogram of body weight four times daily for five days. RESULTS. The children treated with acyclovir had fewer varicella lesions than those given placebo (mean number, 294 vs 347; P less than 0.001), and a smaller proportion of them had more than 500 lesions (21 percent, as compared with 38 percent with placebo; P less than 0.001). In over 95 percent of the recipients of acyclovir no new lesions formed after day 3, whereas new lesions were forming in 20 percent of the placebo recipients on day 6 or later. The recipients of acyclovir also had accelerated progression to the crusted and healed stages, less itching, and fewer residual lesions after 28 days. In the children treated with acyclovir the duration of fever and constitutional symptoms was limited to three to four days, whereas in 20 percent of the children given placebo illness lasted more than four days. There was no significant difference between groups in the distribution of 11 disease complications (10 bacterial skin infections and 1 case of transient cerebellar ataxia). Acyclovir was well tolerated, and there was no significant difference between groups in the titers of antibodies against varicella-zoster virus. CONCLUSIONS. Acyclovir is a safe treatment that reduces the duration and severity of chickenpox in normal children when therapy is initiated during the first 24 hours of rash. Whether treatment with acyclovir can reduce the rare, serious complications of chickenpox remains uncertain.     

What evidence is there for the existence of individual genes with antagonistic pleiotropic effects?

Classical evolutionary theory predicts the existence of genes with antagonistic effects on longevity and various components of early-life fitness. Quantitative genetic studies have provided convincing evidence that such genes exist. However, antagonistic pleiotropic effects have rarely been attributed to individual loci. We examine several classes of longevity-assurance genes: those involved in regulation of the gonad; the insulin-like growth factor pathway; free-radical scavenging; heat shock proteins and apoptosis. We find initial evidence that antagonistic pleiotropic effects are pervasive in each of these classes of genes and in various model systems--although most studies lack explicit studies of fitness components. This is particularly true of human studies. Very little is known about the early-life fitness effects of longevity loci. Given the possible medical importance of such effects we urge their future study.     

In vitro biosynthesis and core glycosylation of the histidine-rich protein of Plasmodium lophurae

We have characterized the early biosynthetic forms of the histidine-rich protein (HisRP), a major, granule-bound protein (Mr 58 000) of the avian malarial parasite Plasmodium lophurae. We have translated poly(A)-containing, size-selected parasite mRNA in the wheat germ cell-free system in the presence of [3H]histidine. HisRP was synthesized as a larger precursor (Mr 63 000). When dog pancreas microsomal membranes were present in the cell-free system during translation, a still larger form of HisRP (Mr 66 000) was detected. This larger form was segregated into the dog pancreas microsomal vesicles and was core glycosylated. Presumably, it corresponds to an intermediate form located in the parasite rough endoplasmic reticulum (RER). The difference in the Mr of approx. 8 000 between this RER associated 'pro' form and the granule-bound, mature form of HisRP suggests that proteolytic processing occurs upon transport from the RER to the granule. Segregation and core glycosylation were strictly coupled to translation and were not observed upon posttranslational addition of microsomal membranes. Thus, the early events in the biosynthesis of HisRP are similar to those established for secretory and lysosomal proteins.