Is processing speed a valid cognitive endophenotype for bipolar disorder?

ObjectivesThe current study investigated whether a single brief cognitive assessment, processing speed, could be considered as a valid endophenotype for bipolar disorder (BD).MethodsProcessing speed was assessed using the Digit Symbol Test (DST) in 53 euthymic BD probands (BD-P), 50 unaffected first-degree relatives (UFDR) and 60 unrelated healthy controls (HC).ResultsEuthymic BD-P and the UFDR were significantly more impaired on DST performance even after controlling for demography and current mood symptoms (effect sizes 0.89 and 0.52). Clinically significant performance impairment was present in about 30% BD-P and 25% UFDR.LimitationsPharmacotherapy was not controlled for.ConclusionsProcessing speed, as measured with the DST, is a brief reliable measure that could be used in clinical assessments of at risk populations. Our findings support the hypothesis that processing speed may be a valid endophenotype, highly specific for differentiating both euthymic BD-P and UFDR, from HC.     

Is dopamine required for natural reward?

Reward is fundamental to the organization of behavior, and the neurotransmitter dopamine (DA) is widely recognized to be critical to the neurobiology of reward, learning and addiction. Virtually all drugs of abuse, including heroin and other opiates, alcohol, cocaine, amphetamine and nicotine activate dopaminergic systems. So called "natural" rewards such as food, positive social interactions and even humor, likewise activate DA neurons and are powerful aids to attention and learning. Sweet solutions are a well-characterized natural reward. When a source of sugar is encountered, animals will consume substantial amounts, return to it preferentially, and will work to obtain access. Dopamine systems are activated in animals drinking sugar solutions, and lesions of dopaminergic neurons or pharmacological blockade of DA receptors seem to reduce the reward value of both sweet tastes and drugs of abuse. However, we have recently demonstrated that genetically modified mice that cannot make DA (DD mice) manifest normal sucrose preference. During preference tests, mutant mice initiated licking less frequently than did normal mice, but the rate of licking by DD mice for sweets was actually higher than that of normal mice, indicating that their motor ability to lick is intact. We conclude that DA is not required for the hedonic response to sweets nor for their discrimination. This brief and slightly humorous review discusses these findings in the context of current and historical answers to the question, "What is the role of DA in reward?"     

Is rheumatoid arthritis a consequence of natural selection for enhanced tuberculosis resistance?

Although the bubonic plague or "Black Death" is notorious for the toll it took on the population of Europe in the middle ages, another epidemic, the "White Death" of tuberculosis is responsible for millions of deaths worldwide over the past 300 years. With one in four deaths due to tuberculosis in Western Europe and the United States in the 19th century, this disease undoubtedly acted as a powerful genetic selective force. The epidemiology of modern day rheumatoid arthritis (RA) is strikingly similar to the epidemiology of tuberculosis 100-200 years ago, suggesting the possibility that genetic factors that enhanced survival in tuberculosis epidemics are now influencing susceptibility to RA. Recent advances in the analysis of genetic polymorphisms associated with disease have identified several genes linked to RA susceptibility that encode proteins involved in the immune response to Mycobacterium tuberculosis infection, including TNF-alpha, NRAMP1, PARP-1, HLA-DRB1, and PADI4. These results suggest that rheumatoid arthritis, and possibly other autoimmune diseases, are modern day manifestations of the genetic selective pressure exerted by tuberculosis epidemics of the recent past.     

Should ART be offered to HIV-serodiscordant and HIV-seroconcordant couples: an ethical discussion?

Increasingly, fertility clinics are offering their services to human immunodeficiency virus (HIV)-serodiscordant couples where the woman is seropositive. In the case of HIV-seroconcordant couples, there remains a general reluctance to provide treatment. This attitude to seroconcordant couples is reminiscent of that once widely held towards serodiscordant couples when the risk of vertical transmission rates in pregnant women was greater than 1-2%. Due to recent advances in HIV clinical care and assisted reproduction technique (ART) procedures directed at reducing the risk of viral transmission during gamete transfer, where good healthcare is available, the current risk rate has fallen to 1-2%. This article deals with the ethical arguments of those who remain opposed to offering HIV-serodiscordant and HIV-seroconcordant couples access to ART. Until these arguments have been addressed, clinics providing ART to such couples cannot be assured that their practices are ethical.     

Cytotoxic natural antibodies against human tumours: an option for anti-cancer immunotherapy?

Healthy individuals may contain in their peripheral blood antibodies which are able to destroy human tumour cells mediated either by complement-dependent cytotoxicity or by apoptosis. The largest proportion of these antibodies is of IgM isotype and directed against distinct tumour associated carbohydrate epitopes. Although the origin of these antibodies is not clear they seem to belong to the class of natural antibodies because they are not affinity matured and are encoded by distinct germ-line restricted gene families. It is most likely that this class of natural antibodies has in vivo an anti-tumour protective effect which may contribute to so-called tumour surveillance. On the other hand malignant tumour cells exert mechanisms to counteract such an antibody attack. These comprise soluble factors as well as cell surface expressed membrane complement regulatory proteins (mCRP). Further studies are needed to elucidate molecular mechanisms leading to either tumour destruction induced by natural antibodies or to overcome the protective strategies of the tumour against antibody attack.     

Is ADHD a valid disorder in children with intellectual delays?

To assess the validity of ADHD in children with mental retardation, we applied Robins and Guze's [Robins, E., and Guze, S.B. (1970). Establishment of diagnostic validity in psychiatric illness: Its application to schizophrenia. American Journal of Psychiatry, 126, 983-987.] criteria for determining the validity of a psychiatric disorder. We review the literature describing clinical correlates, family history, treatment response, laboratory studies, course, and outcome of children with ADHD and mental retardation. Although clearly an area in need of further research, there is preliminary evidence to suggest that ADHD is a valid psychiatric condition in children with mental retardation. Nevertheless, without knowing the base rates of ADHD symptoms in the mental retardation population, the positive predictive power and negative predictive power of ADHD symptoms in this population remain an open question. In addition to assessment of base rate symptoms, future research should consider what diagnostic algorithm may best be applied to the diagnosis of ADHD in mental retardation.     

Is there a role for hemoperfusion/hemodialysis as a treatment option in severe tricyclic antidepressant intoxication?

OBJECTIVE: Suicidal self-poisoning with tricyclic antidepressants like doxepin is a major therapeutic problem in emergency medicine with a high fatality rate. Deaths are mainly caused by cardiotoxicity with arrhythmias, intraventricular conduction disturbances and myocardial depression. For treatment, alkalinization and hypertonic saline are recommended. The role of extracorporeal, treatment procedures is not clear. The possible benefit of hemoperfusion/hemodialysis is discussed in a case report with respect to the published literature. CASE REPORT: After ingestion of an amount of at least 5000 mg doxepin a 37-year-old man with endogenous depression developed cardiac arrest. After preclinical resuscitation with prolonged external cardiac massage, he was admitted to the intensive care unit with persistently severe hypotension and wide QRS complexes (230-260 ms). Despite fluid load, alkalinization, hypertonic saline and high-dose vasoactive substances the patient's condition did not improve. Hemoperfusion over hemoresin combined with hemodialysis led to an impressive clinical improvement with shortening of QRS duration (from 230 to 120 ms) and hemodynamic stabilization. The patient fully recovered without neurologic deficits. CONCLUSION: We report a successful treatment with hemoperfusion over hemoresin and hemodialysis in a patient with life-threatening doxepin poisoning intractable with the generally recommended treatment. In such acute TCA intoxication with severe cardiotoxicity, hemoperfusion/hemodialysis should be considered a potential treatment option, as the "toxicokinetics" of drugs may totally differ from their usual pharmacokinetic behaviour. Experimental and clinical studies are needed to clarify the toxicokinetics of TCA in order to improve the therapeutic approach.     

Is it time for a meta-analysis?

Sir, Recent issue of the Hum Reprod Update included a meta-analysisby Gelbaya et al. (2007) that systematically evaluated the currentstate of evidence regarding the effects of aspirin in IVF. Theauthors found non-significant point estimates for pregnancy,miscarriage and cancellation rates with confidence intervalsoverlapping the null hypothesis. Based on these results,     

Pros and cons: Is faecal microbiota transplantation a safe and efficient treatment option for gut dysbiosis?

Faecal Microbiota Transplantation (FMT) is well established as an effective treatment for Clostridioides difficile infection (CDI), restoring gut microbiome diversity and function. The utility of FMT is currently being explored in relation to other immune-mediated pathologies, such as allergic disease, inflammatory bowel diseases and autoimmune diseases. Clinical trials in these areas are ongoing, and the altered gut microbiota (dysbiosis) that is often observed in these pathologies provides a rationale for the application of FMT to restore the microbiome. However, there is controversy on the risk-benefit ratio as it relates to the use of FMTs in pathologies other than CDI. In this Pro and Con article, we present the arguments for and against the use of FMT in immune-mediated pathologies, such as allergic disease. We further identify research gaps and recommend how these may be addressed in future studies.     

Is there a future for spermatid injections?

Microinjection of spermatids into oocytes has proven to be a successful assisted reproduction procedure in the animal model. In the human, low fertilization and cleavage to the 4-cell stage were reported after intracytoplasmic sperm injection (ICSI) with round spermatids. In comparison with a conventional ICSI-testicular sperm extraction (TESE) programme, the implantation rate after round spermatid injection is dramatically low. Different problems have been encountered during the development of the spermatid injection technique and they could be partially responsible for the lower outcome when using round spermatids. Compared with the round spermatid cells, spermatids in the elongation phase are easy to isolate and identify from other round cells present in a wet preparation. The morphological identification does not reveal anything about the viability or the genetic normality of the round spermatids. Severe testicular dysfunction may have consequences on the quality of the few spermatogenic cells present. Others factors, such as the pathology of the patient, play an important role in the successful treatment. Even if the results are extremely low, spermatid injection seems more favourable for men who have already proven their capacity to produce some spermatozoa. A spermatogenic block at the round spermatid level has led to early abortions, increasing the suspicion of the role of a genetic factor. In order for this technique to be safe for use in clinics, more intensive work is needed to improve the selection and handling of cells and to ascertain the genomic imprinting and gene expression necessary for embryonic development. Hence, when using immature cells for conception, the screening of the patient and the follow-up of the pregnancies and babies should be mandatory.     

Is There a Future for Neural Transplantation?

Traditionally neural transplantation has had as its central tenet the replacement of missing neurons that have been lost because of neurodegenerative processes, as exemplified by diseases such as Parkinson disease (PD). However, the effectiveness and widespread application of this approach clinically has been limited, primarily because of the poor donor supply of human fetal neural tissue and the incomplete neurobiological understanding of the circuit reconstruction required to normalize function in these diseases. So, in PD the progress from promising neural transplantation in animal models to proof-of-principle, open-labeled clinical transplants, to randomized, placebo-controlled studies of neural transplantation has not been straightforward. The emergence of previously undescribed adverse effects and lack of significant functional advantage in recent clinical studies has been disappointing and has served to cast a new, and perhaps more realistic, perspective on this treatment approach. In fact, there have been calls by some involved in neural transplantation to return to the drawing board before pressing on with further clinical trials, and the return to basic experimentation. This therefore precipitates the question — is there a future for neural transplantation? It is important to remember that there are a number of possible explanations for the disappointing results from the recent clinical trials in PD, ranging from the mode of transplantation to patient selection. Nevertheless, almost irrespective of these reasons for the current trial results, there have always been significant practical and ethical problems with using human fetal tissue, and so a number of alternative cell sources have been investigated. These alternative sources include stem cells, which are attractive for cell-based therapies because of their potential ease of isolation, propagation and manipulation, and their ability in some cases to migrate to areas of pathology and differentiate into specific and appropriate cell types. Furthermore, the availability of stem cells derived from non-embryonic sources (e.g. adult stem cells derived from the sub-ventricular zone) has removed some of the ethical limitations associated with the use of embryonic human tissue. These potentially beneficial aspects of stem cells means that there is a future for neural transplantation as a means of treating patients with a range of neurological disorders, although whether this will ever translate into a truly effective, widely available therapy remains unknown.     

Intradialytic hypotension: Is intradialytic acupuncture a complementary option? A case report

BackgroundIntradialytic hypotension (IDH) is a common complication during hemodialysis (HD) and is positively associated with either poor quality of life or mortality. The present case report described the effect of intradialytic acupuncture (IA) in decreasing the occurrence of IDH.MethodsA 70-year-old female with diabetic nephropathy had been receiving regular dialysis twice weekly since end-stage renal disease was diagnosed. She had several episodes of intradialytic systolic blood pressure (iSBP) drop accompanied with severe complications within one month. In the 10 dialysis sessions prior to IA intervention, the case patient experienced two episodes of nadir iSBP < 90 mmHg, seven episodes of iSBP drop ≥ 20 mmHg, among which two episodes occurred with symptoms; and three episodes of iSBP drop required nursing intervention.InterventionsDialysis sessions proceeded as usual with the patient receiving five sessions of 30-min IA as an add-on therapy starting from the second hour of dialysis.ResultsIn the 10 sessions with IA administered alternately, she experienced one episode of nadir iSBP < 90 mmHg and three episodes of iSBP drop ≥ 20 mmHg, among which two episodes occurred with symptoms. Occurrence of IDH reduced and no IDH necessitating nursing intervention occurred during IA-HD sessions.ConclusionsThe administration of IA showed potential effect in decreasing the occurrence of IDH.