Family planning knowledge, attitudes and practices in women with schizophrenic spectrum disorders

This study set out to test three hypotheses about family planning in women with schizophrenic spectrum disorders, as compared to demographically comparable non-mentally ill control women: that they (1) report at least as much unprotected intercourse while not desiring pregnancy; (2) have less knowledge about contraception; and (3) perceive more, and different, obstacles to obtaining or using birth control. A semistructured Family Planning Interview was administered to subjects (n = 44) with Research Diagnostic Criteria diagnoses of schizophrenia and schizoaffective disorder, and to non-mentally ill control subjects (n = 50). The participants had high rates of unprotected intercourse, as did non-mentally ill controls. They had significantly less reproductive and contraceptive knowledge than the control subjects, and were more likely to perceive birth control as difficult to obtain. The most common reason women with schizophrenic spectrum disorders gave for failing to use birth control was that they did not expect to have sex, while that given by non-mentally ill subjects related to side-effects of birth control. Important obstacles to family planning in women with schizophrenic spectrum disorders include relative lack of knowledge and difficulty planning ahead. Although many women with schizophrenia could benefit from long-acting, reversible contraception, many may be unaware of those options and/or may find them difficult to obtain. Integrating family planning with mental health care might better address the unique needs of this population.     

Cognitive ability and cerebral lateralisation in transsexuals

INTRODUCTION: The application of high-frequency current to the AV junctional area results in a temperature rise in the myocardium and may cause accelerated junctional rhythm (AJR). The aim of the study was to characterize heat-induced AJR in an in vitro animal model. METHODS AND RESULTS: Studies were performed in isolated perfused pig and rabbit hearts. Using a small heating probe, we could induce AJR from a discrete area located in the middle of the triangle of Koch, which was smaller than the area from which RF energy application could elicit AJR. Histology showed that the heat-sensitive area was located over, or close to, the compact AV node. It did not correspond with the areas where double potentials were found or with the site(s) of earliest atrial activation during VA conduction. Microelectrode recordings revealed that AJR arose in nodal-type cells. Heat increased the slope of the phase 4 depolarization and shortened the action potential duration. Two types of AJR were observed: the first one was regular and the second one showed irregularity in the intervals. Interaction of multiple foci and the presence of conduction block between the foci and the His bundle caused the irregularity of the His-His intervals during the second type of AJR. CONCLUSION: AJR observed during heat and RF application in the AV nodal area results from the effect of heat on AV nodal cells with underlying pacemaker activity. The heat-sensitive area is located over, or very close to, the compact AV node.     

Drug-induced reinstatement of heroin- and cocaine-seeking behaviour following long-term extinction is associated with expression of behavioural sensitization

The present study was designed to evaluate the relationship between reinstatement of drug-seeking behaviour following long-term extinction of intravenous (i.v.) drug self-administration (an animal model for craving) and long-term behavioural sensitization. Rats were allowed to self-administer heroin (50 microg/kg per inj., 14 daily sessions), cocaine (500 microg/kg per inj., 10 daily sessions) or saline. Following a 3-week extinction period, reinstatement tests were performed to evaluate priming effects of amphetamine, cocaine and heroin on nonreinforced drug-seeking behaviour. In addition, the occurrence of long-term behavioural sensitization in rats with a history of heroin or cocaine self-administration was determined. Heroin-seeking behaviour was reinstated by heroin (0.25 mg/kg), amphetamine (1.0 mg/kg) and cocaine (10 mg/kg). In addition, animals with a history of heroin self-administration displayed locomotor sensitization to both heroin and amphetamine. Cocaine-seeking behaviour was reinstated by cocaine and amphetamine, but not by heroin. Interestingly, locomotor sensitization to amphetamine, but not heroin, was observed in animals with a history of cocaine self-administration. In other words, the induction of drug-seeking behaviour following a prolonged drug-free period was found to be associated with the expression of long-term behavioural sensitization. These data provide experimental evidence for a role of behavioural sensitization in the incentive motivation underlying drug-seeking behaviour. If drug hyperresponsiveness would indeed be a crucial factor in drug-induced craving in human addicts, pharmacological readjustment of the neuroadaptations underlying drug sensitization may prevent relapse to drug use long after detoxification.     

S-fluoxetine in the prophylaxis of migraine: a phase II double-blind randomized placebo-controlled study

A tubular bioassay was used to measure analytically the local production and concentration of the antifungal Trichoderma secondary metabolite 6-n-pentyl-2H-pyran-2-one (6PAP) at the Trichoderma antagonist/pathogen interface. 6PAP levels significantly increased in the presence of the pathogen Botrytis cinerea, typically 300-700%, and were highest near the pathogen source. The level of response for a particular Trichoderma isolate was found to vary with the test organism used. Two products produced by biotransformation of 6PAP by B. cinerea in response to the interaction were also detected.     

Effects of nitric oxide on neuroendocrine function and behavior

Nitric oxide (NO) is an unusual chemical messenger. NO mediates blood vessel relaxation when produced by endothelial cells. When produced by macrophages, NO contributes to the cytotoxic function of these immune cells. NO also functions as a neurotransmitter and neuromodulator in the central and peripheral nervous systems. The effects on blood vessel tone and neuronal function form the basis for an important role of NO on neuroendocrine function and behavior. NO mediates hypothalamic portal blood flow and, thus, affects oxytocin and vasopression secretion; furthermore, NO mediates neuroendocrine function in the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal axes. NO influences several motivated behaviors including sexual, aggressive, and ingestive behaviors. Learning and memory are also influenced by NO. Taken together, NO is emerging as an important chemical mediator of neuroendocrine function and behavior.     

Structure and practice of institutional review boards in the United States

OBJECTIVE: The institutional review board (IRB) is a critical element in the protection of patients' and subjects' rights with regard to their participation in research protocols. The purpose of this study was to describe the structure and current practices of IRBs in the United States. METHODS: A self-administered questionnaire was mailed to the IRB chair of each U.S. hospital with a capacity of at least 400 beds (n = 907). The survey contained 21 questions outlining committee size and structure, review of research proposals, and policies concerning scientific misconduct. Chairs also were asked what advice they would offer a young investigator preparing a proposal for submission. RESULTS: A total of 488 surveys (54%) were returned; 447 of the responding institutions had an IRB committee. Committees had an average of 14 members, representing 27 medical specialties. Orthopedics had the least IRB representation (10% of committees), followed by emergency medicine (12%) and ophthalmology (15%). The majority of research proposals go through 5 specific steps once submitted for review. Common reasons for proposal rejection were improperly designed consent form (54%), poor study design (44%), unacceptable risk to subjects (34%), ethical or legal reasons (24%), and scientific merit (14%). When a research proposal is rejected, 86% of the responding IRBs assist the investigator in making appropriate revisions. Although a number of IRBs (17%) have dealt with scientific misconduct allegations, only 58% have a written policy regarding research integrity. CONCLUSION: Despite variations in committee structure and representation, IRBs have similar procedures for governing research. Investigators should be familiar with these procedures and are encouraged to discuss their proposal with an IRB representative prior to formal review.     

Matrilineal inheritance of complex I dysfunction in a multigenerational Parkinson's disease family

Recent data suggesting complex I dysfunction in Parkinson's disease (PD) arises from mitochondrial DNA (mtDNA) mutation does not conclusively answer whether the responsible genetic lesion is inherited (primary) or somatic (secondary). To address this question, we identified a family in which multiple members over three generations are affected with PD through exclusively maternal lines. Cytoplasmic hybrids (cybrids) were created for 15 family members over two generations by transferring each individual's mtDNA to mtDNA-depleted human neuroblastoma cells. Eight of the 15 cybrid lines contained mtDNA obtained from maternally descended family members and seven contained mtDNA from paternally descended family members. After 6 weeks of culture, cybrid cell lines were assayed for complex I activity and oxidative stress, and mitochondrial morphology was analyzed by electron microscopy. Compared with the cybrid lines containing mtDNA from paternal descendants, cybrid lines containing mtDNA from maternal descendants had lower complex I activity, increased reactive oxygen species production, increased radical scavenging enzyme activities, and more abnormal mitochondrial morphologic features. These findings were present in cybrid lines containing mtDNA from maternal descendants with PD as well as in currently asymptomatic young maternal descendants, and support a precedent for inherited mtDNA mutation in some persons with PD.     

Preovulatory overripeness of the oocyte as a cause of ovarian dysfunction in the human female

A variety of gynaecological phenomena such as menstrual disorders, infertility and premature menopause are associated with ovarian dysfunction. In this paper, a factor is considered that may play a role in the aetiology of ovarian dysfunction. Animal research has shown that preovulatory overripeness of the oocyte may cause various developmental and chromosomal anomalies. Among the developmental anomalies observed in amphibia and fish are a number of gonadal aberrations, often occurring in otherwise normal specimens. This may be the consequence of a degeneration of the 'germinal cytoplasm', cytoplasmic structures located in the vegetative pole region of the oocyte, destined to become part of future primordial germ cells. Indirect evidence suggests that preovulatory overripeness of the oocyte also plays a significant role in human reproductive failure. An increased risk of preovulatory overripeness is expected during periods of endocrine irregularities, such as the first postmenarcheal years, the last premenopausal years, the first months after a pregnancy and, possibly, during certain seasons. If the overripeness-induced gonadal maldevelopment observed in animals also occurs in humans, this may explain variations in reproductive function according to month of birth, as observed in women. It is hypothesized that females conceived during periods of maternal endocrine irregularities face an increased risk of ovarian dysfunction through overripeness-induced gonadal maldevelopment.     

Carnosine modulates zinc and copper effects on amino acid receptors and synaptic transmission

Carnosine is a dipeptide which is highly concentrated in mammalian olfactory sensory neurons along with zinc and/or copper, and glutamate. Although carnosine has been proposed as a neurotransmitter or neuromodulator, no specific function for carnosine has been identified. We used whole-cell current- and voltage-clamp recording to examine the direct effects and neuromodulatory actions of carnosine on rat olfactory bulb neurons in primary culture. Carnosine did not evoke a membrane current or affect currents evoked by glutamate, GABA or glycine. Copper and zinc inhibited NMDA and GABA receptor-mediated currents and inhibited synaptic transmission. Carnosine prevented the actions of copper and reduced the effects of zinc. These results suggest that carnosine may indirectly influence neuronal excitability by modulating the effects of zinc and copper.     

Conclusive evidence for distinct transporters for 5-hydroxytryptamine and noradrenaline in pulmonary endothelial cells of the rat

The aims of this study were to obtain conclusive evidence about the roles of a 5-hydroxytryptamine [5-HT] transporter and uptake1 in the dissipation of 5-HT in the lungs of the rat and to compare the properties of the 5-HT transporter in rat lungs with that in other tissues, including brain and platelets. In the first part of the study, the IC50 values of a range of selective inhibitors and substrates of the 5-HT transporter or uptake1 were determined for inhibition of uptake of 5-HT or noradrenaline in intact perfused lungs of rats. Monoamine oxidase was inhibited and, in experiments with noradrenaline, catechol-O-methyltransferase was also inhibited. Initial rates of uptake of 5-HT or noradrenaline were measured in lungs perfused with 2 nmol/l 3H-5-HT or 3H-noradrenaline for 2 min, in the absence or presence of at least three concentrations of paroxetine, citalopram, fluoxetine, 7-methyltryptamine, tryptamine, nisoxetine, imipramine, 5-HT, desipramine, (+)-oxaprotiline, cocaine or tyramine. The results showed that pharmacologically distinct transporters are involved in the uptake of 5-HT and noradrenaline in rat lungs, since there was no significant correlation between the IC50 values for inhibition of 5-HT and noradrenaline uptake in the lungs. However, there were significant correlations between the IC50 values for (a) inhibition of 5-HT uptake in rat lungs and of uptake by the 5-HT transporter in rat brain and (b) inhibition of noradrenaline uptake in rat lungs and of uptake1 in rat phaeochromocytoma PC-12 cells. The results support the conclusion that 5-HT uptake in rat lungs occurs, at least predominantly, by a 5-HT transporter which is very similar to or the same as that in other tissues, such as the brain, and provide further evidence for transport of noradrenaline by uptake1. Further experiments were carried out to determine whether there is any transport of 5-HT by uptake1 or of noradrenaline by the 5-HT transporter in rat lungs. Lungs were perfused with 2 nmol/l 3H-5-HT or 3H-noradrenaline for 2 min in the absence or presence of 1 mumol/l citalopram, desipramine, or citalopram and desipramine. The results showed that there was no evidence of any transport of 5-HT in the lungs by uptake1 or of noradrenaline by the 5-HT transporter, in that desipramine had no effect on 5-HT uptake (in the absence or presence of citalopram) and citalopram had no effect on noradrenaline uptake (in the absence or presence of desipramine). The final series of experiments was carried out to determine whether, at high concentrations of the amine, there is any interaction of 5-HT with uptake1 or of noradrenaline with the 5-HT transporter. Noradrenaline, at a concentration of 10 mumol/l, did not affect 5-HT uptake in lungs perfused with 2 nmol/l 3H-5-HT for 2 min (uptake1 inhibited), but 50 mumol/l 5-HT inhibited noradrenaline uptake by 56% in lungs perfused with 2 nmol/l 3H-noradrenaline for 2 min (5-HT transporter inhibited). These and the above results show that the 5-HT transporter appears to be exclusively responsible for 5-HT uptake in rat lungs, despite the possible interaction of 5-HT at high concentrations with the uptake1 transporter in the cells. On the other hand, noradrenaline is transported exclusively by uptake1 in the lungs, and there is no evidence that it interacts with the 5-HT transporter, even at high concentrations.