Reinforcement and reversal learning in first-episode psychosis

Background: Abnormalities in reinforcement learning and reversal learning have been reported in psychosis, possibly secondary to subcortical dopamine abnormalities. Methods: We studied simple discrimination (SD) learning and reversal learning in a sample of 119 first-episode psychosis patients from the Cambridge early psychosis service (CAMEO) and 107 control participants. We used data on reinforcement learning and reversal learning extracted from the Cambridge Neuropsychological Test Automated Battery Intradimensional-Extradimensional shift task, which measures cognitive flexibility but also involves simple reinforcement learning (SD learning) and reversal learning stages. We also gathered diagnostic information to examine whether there were any differences between patients ultimately diagnosed with schizophrenia-spectrum disorders and those diagnosed with affective psychosis. Results: Psychosis patients demonstrated deficits in simple reinforcement learning (SD learning) and in reversal learning, with no differences between affective psychosis and schizophrenia-spectrum psychosis. There was a significant modest correlation between reversal errors and negative symptoms (Spearman rho = 0.3, P = .02). Conclusions: There are reinforcement learning abnormalities in first-episode psychosis, which correlate with negative symptoms, suggesting a possible role for orbitofrontal cortex and ventral striatal pathology in the pathogenesis of motivational deficits in psychosis.     

Spinal Cord Stimulation in Pregnancy: A Literature Review

Objective: Currently, the use of spinal cord stimulation (SCS) therapy is not recommended in pregnancy because the effects of SCS on the pregnancy and developing fetus are unknown. However, many SCS recipients are women of childbearing age who may later become pregnant. The purpose of the present report is to review and summarize the existing literature on the use of SCS therapy during the prenatal period. Methods: We first present the case of a 38‐year‐old woman from our center who became pregnant after receiving an SCS implantation. We then provide a synopsis of previous reports that were identified in a literature search. We highlight the key findings from these cases as they relate to the course of pregnancy, fetal development, labor and delivery management, fertility, and technical complications. Results: In our literature review, we identified 12 cases of pregnancy in 8 women. To these we add the present case. Conclusions: Women of childbearing age who are candidates for SCS implantation should be tested for pregnancy prior to implantation surgery. They also should be informed about the limited state of our scientific knowledge regarding the impact of this technology on reproductive health. For patients already implanted with SCS, decisions about ongoing use in the event of pregnancy should be made on an individual basis after a careful consideration of potential risks and benefits.     

Immunotherapy with live BCG plus heat killed Leishmania induces a T helper 1-like response in American cutaneous leishmaniasis patients

Previous work has shown that American cutaneous leishmaniasis (ACL) patients treated with viable BCG plus heat killed promastigotes of Leishmania amazonensis show the same rate of cure as patients receiving conventional chemotherapy. The treatment is safe and economical, but the immunological correlates of cure have not been examined. In the present study, T cell responses have been analysed in 43 ACL patients, including patient groups sampled before and after therapy, and in 10 endemic controls. Lymphocyte proliferation, interferon (IFN)-gamma and interleukin (IL)-5 responses to crude antigen (L. amazonensis, MEL; Mycobacterium tuberculosis PPD; M. bovis BCG) stimulation, and serum IL-5 levels, were analysed. In endemic volunteers, proliferative responses to BCG were high and IFN-gamma responses low. In contrast, localized cutaneous (LCL) and mucocutaneous (MCL) patients showed low proliferative and high IFN-gamma responses to BCG. Treatment enhanced the IFN-gamma response and further decreased the proliferative response to BCG, especially in MCL patients. LCL and MCL patients showed an increase in proliferative and IFN-gamma responses to MEL with treatment, but the response was not exaggerated in MCL patients, either before or after treatment, compared to LCL patients. IL-5 production was low in T cell assays, and > 62% of untreated patients had very low serum IL-5 levels. There were no significant changes in serum IL-5 with treatment. Overall results show enhanced antigen-specific IFN-gamma responses to the two components of the immunotherapy, live M. bovis BCG and heat killed L. amazonensis, which is consistent with a shift in balance of T cell response towards a T helper 1 response and clinical cure mediated by IFN-gamma.     

Dehydration activates an NF-kappaB-driven, COX2-dependent survival mechanism in renal medullary interstitial cells

Renal prostaglandin (PG) synthesis is mediated by cyclooxygenase-1 and -2 (COX1 and COX2). After dehydration, the maintenance of normal renal function becomes particularly dependent upon PG synthesis. The present studies were designed to examine the potential link between medullary COX1 and COX2 expression in hypertonic stress. In response to water deprivation, COX2, but not COX1, mRNA levels increase significantly in the renal medulla, specifically in renal medullary interstitial cells (RMICs). Water deprivation also increases renal NF-kappaB-driven reporter expression in transgenic mice. NF-kappaB activity and COX2 expression could be induced in cultured RMICs with hypertonic sodium chloride and mannitol, but not urea. RMIC COX2 expression was also induced by driving NF-kappaB activation with a constitutively active IkappaB kinase alpha (IKKalpha). Conversely, introduction of a dominant-negative IkappaB mutant reduced COX2 expression after hypertonicity or IKKalpha induction. RMICs failed to survive hypertonicity when COX2 was downregulated using a COX2-selective antisense or blocked with the selective nonsteroidal anti-inflammatory drug (NSAID) SC58236, reagents that did not affect cell survival in isotonic media. In rabbits treated with SC58236, water deprivation induced apoptosis of medullary interstitial cells in the renal papilla. These results demonstrate that water deprivation and hypertonicity activate NF-kappaB. The consequent increase in COX2 expression favors RMIC survival in hypertonic conditions. Inhibition of RMIC COX2 could contribute to NSAID-induced papillary injury.     

Outcome of treated pregnancies in women with antiphospholipid syndrome: an update of the Utah experience.

OBJECTIVE: To determine the outcome of treated pregnancies in women with well-characterized antiphospholipid syndrome. METHODS: We reviewed 82 consecutive pregnancies in 54 women with antiphospholipid syndrome who were treated during pregnancy with the following: 1) prednisone and low-dose aspirin; 2) heparin and low-dose aspirin; 3) prednisone, heparin, and low-dose aspirin; or 4) other combinations of these medications or immunoglobulin. RESULTS: The overall neonatal survival rate was 73%, excluding spontaneous abortions, but treatment failures (fetal and neonatal deaths) occurred in all treatment groups. Patients with successful treated pregnancies had fewer previous fetal deaths than those with unsuccessful treated pregnancies. There were no significant differences in outcome among the four treatment groups. Preeclampsia and fetal distress occurred in half of all pregnancies, and fetal growth impairment occurred in nearly one-third. Preterm delivery due to maternal or fetal indications was required in 37% of the pregnancies. Four pregnancies were also complicated by postpartum thrombosis during treatment. CONCLUSIONS: Pregnancy in women with antiphospholipid syndrome appears to be improved by treatment, but fetal loss may occur despite treatment. Preeclampsia, fetal distress, fetal growth impairment, and premature delivery are common. Because of the clinically significant risk of thrombotic episodes, thrombosis prophylaxis should be considered in these patients.     

Carriage of Haemophilus influenzae and Streptococcus pneumoniae in healthy Chinese and Vietnamese children in Hong Kong

Nasopharyngeal carriage of Haemophilus influenzae and Streptococcus pneumoniae was studied in 621 healthy Chinese children and 300 healthy Vietnamese children aged from 2 months to 5 years in Hong Kong. The carriage rate of H, influenzae type b in Vietnamese children was 1.3% (CI 0.04-2.63%); it was zero in Chinese. The carriage rate of non-typable H. influenzae was 5.8% (CI 1.4-7.6%) in Chinese and 65.4% (CI 58.9-69.8%) in Vietnamese. The carriage rates of S. pneumoniae were 10.8% (CI 8.3-13.2%) and 55.7% (CI 50.1-61.3%) in Chinese and Vietnamese children, respectively. Univariate and multivariate logistic regression analyses were performed to search for factors associated with differences in carriage rates of both H. influenzae and S. pneumoniae between Chinese and Vietnamese children. Although older age, smaller living area and parental smoking were associated with higher carriage rates, these could not explain the remarkably low carriage rates of both bacteria in Chinese children.     

In vitro and in vivo evaluation of latex condoms using a two-phase nonoxynol 9 system

In vitro studies were carried out that indicated that a lubricant system consisting of 0.45 +/- 0.1 ml of silicon fluid containing 6.6% +/- 0.5% by volume of nonoxynol 9 and a spermicidal cream consisting of 0.45 +/- 0.1 ml made up of 63.4% polyethylene glycol 400 and 30.0% polyethylene glycol 3350 containing 6.6% +/- 0.5% nonoxynol 9 was effective in reducing sperm motility and viability. This system was tested in vivo with the use of simulated rupture techniques and was found to be equally as effective. Double-blind preference studies were carried out in vivo which showed that the condom system is convenient and comfortable to use, nonirritating to the vagina or urethral mucosa, and esthetically pleasing to the young, reproductive-age population.     

Genetic Engineering and Medical Ethics

In the introduction I express the need of introducing the point of view of Ethics when we are dealing with problems of science, technology, and especially medicine. In the first part of my presentation I deal with the problem of the value of human life, coming to the conclusion that human life might not be completely absolute, but is extremely important and “ceteris paribus” should be respected, and the problem of when it starts. Some of the main arguments are discussed. In this connection the question of abortion is briefly discussed. In the second part I deal with some problems related to human reproduction. Most people will be willing to support programmes for treating individuals with genetic disease; but at the same time the dangers of increasing depersonalization of the reproductive process are pointed out. In the third part I take up the problem of In Vitro Fertilisation. IVF has certainly brought benefits to some couples suffering from infertility, but at the same time it has raised quite a few human and moral problems. Is it permissible to fertilise an egg with a donor sperm, replacing the embryo in the womb? What about fertilising a donor egg with the husband's sperm? Is it acceptable to store or freeze embryos for future use? Is it moral to implant such an embryo in a woman who has no genetic relationship with the embryo? Is it moral to use surrogate mothers? Is it moral for ‘spare’ embryos to be killed or used as tissue for research? At the end I stress the need of dialogue between life sciences and ethics.