Interaction between the serotonergic system and HPA and HPT axes in patients with major depression: implications for pathogenesis of suicidal behavior

Disturbances in the serotonin (5-hydroxytryptamine, 5-HT) system constitute the neurobiological abnormality most consistently associated with suicide. This abnormality could be a marker of vulnerability predisposing individuals to auto-aggressive and impulsive behavior. However, other abnormalities, such as hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, have also been described in suicide victims. While inhibitory effects of adrenocorticosteroids on 5-HT(1A) receptor function have been shown in animals, HPA axis hyperactivity does not seem to be responsible for the reduced 5-HT activity found in depressed patients with a history of suicidal behavior. On the other hand, hypothalamic-pituitarythyroid (HPT) axis dysfunction, frequently observed in depression, may represent a compensatory response to reduced central 5-HT neurotransmission. Moreover, in depressed patients with a history of suicidal behavior, the absence of a functional link between HPT and dopamine activity at the hypothalamic level may be implicated in the pathophysiology of suicidal behavior. Future research is needed to determine why compensatory mechanisms are not efficient in patients with suicidal behavior.     

Neuropsychological deficit in early subcortical vascular dementia: comparison to Alzheimer's disease

To further clarify the cognitive syndrome in subcortical vascular dementia (VaD), we investigated 20 patients with early-stage VaD as compared with 30 patients with Alzheimer's disease (AD) and 22 normal controls using episodic memory, attention/executive function and language tests. The patient groups were closely matched in terms of age, education and severity of dementia. The VaD patients had a significantly better free recall, cued recall and recognition memory than AD patients, the recognition being within normal limits in VaD. In addition, VaD patients had a greater number of perseverative errors during the Modified Card Sorting test, while AD patients exhibited more perseverations of semantic fluency. The results of retrieval deficit syndrome and increased number of perseverations during tasks sensitive to frontal lobe function are in agreement with the studies emphasizing the importance of frontal dysfunction in subcortical VaD. These findings are relevant for the early diagnosis of VaD and might be useful in the differential diagnosis with AD.     

The role of sexually transmitted infections in male circumcision effectiveness against HIV – insights from clinical trial simulation

Background  

A landmark randomised trial of male circumcision (MC) in Orange Farm, South Africa recently showed a large and significant reduction in risk of HIV infection, reporting MC effectiveness of 61% (95% CI: 34%–77%). Additionally, two further randomised trials of MC in Kisumu, Kenya and Rakai, Uganda were recently stopped early to report 53% and 48% effectiveness, respectively. Since MC may protect against both HIV and certain sexually transmitted infections (STI), which are themselves cofactors of HIV infection, an important question is the extent to which this estimated effectiveness against HIV is mediated by the protective effect of circumcision against STI. The answer lies in the trial data if the appropriate statistical analyses can be identified to estimate the separate efficacies against HIV and STI, which combine to determine overall effectiveness.     

Fatal neonatal respiratory distress in Niemann-Pick C2 and prenatal diagnosis with mutations in gene HE1/NPC2]

We report the fifth case of neonatal form of type C2 (NP-C2) Niemann-Pick disease with early and fatal respiratory distress. Eleven families presenting such cases are known to date in the world. Since December 2000, isolation of the underlying gene HE1/NPC2 and its mutations has allowed major advances in diagnosis. CASE REPORT: Elisa was born in May 2000. NP-C2 disease was associated with severe respiratory distress leading to death at the age of four months. On the next pregnancy in September 2000, prenatal diagnosis was performed by means of biological tests that required four weeks response time. In December 2000, isolation of the HE1/NPC2 gene located to 14q24.3 and of some of its mutations allowed to characterize the patient as being homozygote for the nonsense mutation E20X. On the the two next pregnancies, prenatal diagnosis was performed at 12 SA, in 48 hours, by the means of mutation analysis. The last fetus was heterozygote for the mutation E20X, allowing the birth at term of a healthy male newborn baby. CONCLUSION: Niemann-Pick type C disease is a rare lysosomal lipid storage disease with severe prognosis. It is characterized by abnormalities of intracellular transport of endocytosed cholesterol. Diagnosis relies on biological tests that require cultured cells. Genetic heterogeneity defines two different genetic complementation groups C1 and C2. Severe and early respiratory distress is more likely to be associated with the rare type C2. Since December 2000, after identification of the disease-causing mutations in the proband, mutation analysis of gene HE1/NPC2 on direct chorionic villus samples allows early and fast (48 hours) prenatal diagnosis.     

CT assessment of right-left asymmetries in the human cerebral cortex

Referring to bicommissural coordinates, 10 human brains fixed within their own skull were examined for right-left differences of the posterior Sylvian cortex, a region known to bear the most striking gross anatomical asymmetries. In the first part of the study a millimetric assessment of right-left differences in this region was carried out using life-size lateral photographs of each hemisphere. The second part is more specifically devoted to CT recognition of these cortical areas: Each hemisphere was cut into horizontal, frontal, or sagittal slices in which some cortical landmarks were analyzed to allow accurate CT identification of gyri and sulci showing the most asymmetrical features. This work provides an anatomical framework for correlative studies dealing with cerebral dominance.     

Public and private pharmaceutical spending as determinants of health outcomes in Canada

Canadian per capita drug expenditures increased markedly in recent years and have become center stage in the debate on health care cost containment. To inform public policy, these costs must be compared with the benefits provided by these drugs. This paper measures the statistical relationship between drug spending in Canadian provinces and overall health outcomes. The analysis relies on more homogenous data and includes a more complete set of controls for confounding factors than previous studies. Results show a strong statistical relationship between drug spending and health outcomes, especially for infant mortality and life expectancy at 65. This relationship is almost always stronger for private drug spending than for public drug spending. The analysis further indicates that substantially better health outcomes are observed in provinces where higher drug spending occurs. Simulations show that if all provinces increased per capita drug spending to the levels observed in the two provinces with the highest spending level, an average of 584 fewer infant deaths per year and over 6 months of increased life expectancy at birth would result.     

Season of birth in valvular heart disease

This study demonstrates seasonal variations of birth dates in children with congenital valvular heart disease and in adults dying from valvular heart disease. The findings are based on the 1989-98 Swiss EUROCAT data, and on 1969-94 Swiss mortality records. Seasonality was tested with aggregated monthly data using Edwards' procedure. Both data sets showed excesses between December and March, consistent in different forms of valvular disease and in both sexes. Despite the decline of rheumatic heart disease, risk factors causing season of birth effects remain relevant for congenital anomalies.     

Subannular ventilation tubes: retrospective study

OBJECTIVE: To evaluate the efficiency of a subannular tube insertion technique in a group of pediatric patients with adhesive otitis or severe atelectasis of the tympanic membrane. DESIGN: Retrospective nonrandomized case series. Setting: Tertiary referral centre. MAIN OUTCOME MEASURES: The main outcomes of this study are tube duration according to the type of tube used, the complication rate, and the audiometric gain associated with this procedure. RESULTS: The study group consisted of 190 patients (316 tubes) aged between 3 and 19 years (average 9 years old) and operated on between 1993 and 1999 by four pediatric otolaryngologists. The average follow-up was 53 months. The tubes remained in place for an average of 21.8 months, with fluoroplastic tubes lasting 17.8 months and Goode T tubes lasting 23.8 months. When used in children between 5 and 9 years of age and in cases of adhesive otitis, Goode T tubes showed statistically significantly better results than fluoroplastic tubes. The complications of this technique were otorrhea (17.7%), perforation (7.9%), a plugged tube (7.0%), and cholesteatoma (1.6%). The 5- to 9-year-old group and the reintervention group of patients showed statistically higher complication rates compared with all other groups. Sixty-four patients (128 tubes) were eligible for audiogram analysis, which showed a gain of 13.4 dB (speech reception threshold). CONCLUSIONS: The technique of subannular tube insertion is a safe and effective method for long-term middle ear ventilation in cases of adhesive otitis or severely atelectatic tympanic membrane or for patients with pathology related to dysfunction of the eustachian tube. It offers an alternative to repeated short-term tube insertions for otitis media with effusion or recurrent acute otitis media.