Selective effects of CPAP on sleep apnoea-associated manifestations

Background   Visceral adiposity and obstructive sleep apnoea (OSA) may be independently associated with daytime sleepiness/low performance, insulin resistance, hypercytokinaemia, and/or hypertension. The objectives of this study are to simultaneously test these associations at baseline and after 3 months of continuous positive airway pressure (CPAP) therapy.
Materials and methods   Sixteen obese men with OSA; 13 non-apnoeic, obese controls, and 15 non-obese controls were monitored in the sleep laboratory for four consecutive nights. Objective measures of daytime sleepiness and performance, serial 24 h plasma measures of interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), TNF receptor 1 (TNF-r1) and adiponectin, fasting blood glucose and insulin, visceral adiposity and blood pressure were obtained. Sleep apnoeics were re-assessed using the same protocol after 3 months of CPAP.
Results   At baseline, IL-6, TNF-r1, and insulin resistance were highest in OSA patients, intermediate in obese controls, and lowest in non-obese controls ( P  < 0·05). Visceral fat was significantly greater in sleep apnoeics than obese controls and predicted insulin resistance and IL-6 levels, whereas OSA predicted TNF-r1 levels ( P  < 0·05). CPAP decreased daytime sleepiness and blood pressure ( P  < 0·05), but did not affect fasting glucose or insulin or around the clock adiponectin, IL-6, TNF-α, or TNF-r1 levels.
Conclusions   In obese sleep apnoeics, visceral fat is strongly associated with insulin resistance and inflammation. CPAP decreases sleepiness and moderates hypertension but does not affect visceral adiposity, insulin resistance, hypoadiponectinaemia or hypercytokinaemia, all of which are independent risk factors for cardiovascular disease and diabetes.     

Dépistage tardif de l’infection à VIH à la clinique des maladies infectieuses de Fann,Dakar : circonstances de diagnostic,itinéraire thérapeutique des patients et facteurs déterminants

Background and methodology

The delay in the diagnosis of HIV infection is a major obstacle to optimal care for this disease. To deal with this problem, we conducted this study among newly diagnosed HIV patients hospitalized in the Fann University Hospital Infectious Diseases Clinic in Dakar. The epidemiological, clinical, biological and outcome aspects are described and patient history reviewed. A qualitative socio-anthropological study was made to understand and describe the logic of the decision processes in the patient's search for treatment.

Results

One hundred patients were included, with a mean age of 39.5 ± 11.1 years and a sex-ratio: 1.08. The transmission was mainly heterosexual (90%), and chronic diarrhea (64%) and/or chronic cough (66%) were the principal symptoms leading to diagnosis. The mean delay before diagnosis was 5 ± 4.27 months. The major opportunistic diseases were tuberculosis (44 cases) and infectious diarrhea (23 cases). Most patients were diagnosed at the AIDS stage (97%) and the death rate was 30% among hospitalized patients after admission. Sixty-eight percent of patients had consulted at least three times, generally a “traditional practitioner”, at first and 43% had been hospitalized at least once. The qualitative investigation revealed that the “representation” or the “feeling of severity” of the disease were the principal justifications for consulting the “traditional practitioner” or the physician, respectively.

Conclusion

Better information for health workers and global population is necessary for an earlier diagnosis of HIV infection in Dakar.     

Differential oncogenic potential of activated RAS isoforms in melanocytes

RAS genes are mutated in approximately 30% of all human cancers. Interestingly, there exists a strong bias in favor of mutation of only one of the three major RAS genes in tumors of different cellular origins. NRAS mutations occur in approximately 20% of human melanomas, whereas HRAS and KRAS mutations are rare in this disease. To define the mechanism(s) responsible for this preference in melanocytes, we compared the transformation efficiencies of mutant NRAS and KRAS in immortal, non-transformed Ink4a/Arf-deficient melanocytes. NRAS mutation leads to increased cellular proliferation and is potently tumorigenic. In contrast, KRAS mutation does not enhance melanocyte proliferation and is only weakly tumorigenic on its own. Although both NRAS and KRAS activate mitogen-activated protein kinase signaling, only NRAS enhances MYC activity in these cells. Our data suggest that the activity of specific RAS isoforms is context-dependent and provide a possible explanation for the prevalence of NRAS mutations in melanoma. In addition, understanding this mechanism will have important implications for cancer therapies targeting RAS pathways.     

Correlation among subcortical white matter lesions, intelligence and CTG repeat expansion in classic myotonic dystrophy type 1

Objectives –  To analyze the correlation among intelligence, brain magnetic resonance images (MRI) and genotype in classic myotonic dystrophy type 1 (DM1) patients.
Materials and methods –  Seventeen patients with classic DM1 were administered intelligence and neuropsychological tests and brain MRI focusing on a semi-quantitative rating scale of subcortical white matter lesions (WMLs). Statistical analysis was measured to evaluate the correlation among clinical manifestations, intelligence, brain MRI abnormalities, and CTG repeat expansion.
Results –  There were statistically significant correlations between intelligence test and insular WMLs for all DM1 patients and between intelligence quotient and temporal WMLs for those patients with less than 400 of the CTG repeat size. We also documented that temporal WMLs were related to the disease course, and frontal WMLs were correlated with aging in all DM1 patients. However, a poor correlation was found among CTG repeat size and clinical pictures, neuropsychological impairments, and brain MRI abnormalities in all DM1 patients.
Conclusion –  These results suggest that subcortical WMLs are correlated with focal dementia in classic DM1 patients. Temporal and insular WMLs may be responsible for the global intellectual dysfunction of adult DM1 patients.     

Epilepsy in a cohort of Senegalese children

Epilepsy is a significant health public problem in Senegal with an estimated prevalence of 8 to 14%. The aim of this study was to determine the clinical and electroencephalographic features of epilepsy in a cohort of Senegalese infants, search for etiological factors and determine the impact of disease on school life. This retrospective study concerned 459 children who attended the neurological outpatients clinic at the Fann hospital, Dakar, Senegal, between July 2003 and December 2006. All were aged under 19 years. Among the 135 children with idiopathic epilepsy, 23.7% had parental consanguinity and 37.77 % familial epilepsy. Rolandic epilepsy and epilepsy with absences were more frequent but several infants with idiopathic epilepsy were not classified. Non-idiopathic epilepsy was noted in 312 children. In this group, estimates of parental consanguinity and familial epilepsy were of 21.79 and 17.94%, respectively. Etiological factors were predominantly pregnancy and birth abnormalities (28.84%) and central nervous system infection (20.19%). Twelve children had febrile seizures. Of patients with idiopathic epilepsy, 65.18% were attending school versus only 9.29 with non-idiopathic epilepsy.     

Demands on surgeons of the Infectious Disease Control Act]

The German Infectious Disease Control Act of 2001 includes a modified regulation for reporting infectious diseases and infectious pathogens and new clauses for surveillance and infection control in medical institutions. For the first time, all health care facilities are obliged to conduct surveillance of nosocomial infections and multiresistant pathogens. This legal regulation including mandatory monitoring by local health departments aims at reducing the rates of nosocomial infection and frequency and dissemination of highly resistant pathogens. This article describes the effect of the Disease Control Act on surgical departments. Surveillance of postsurgical wound infection should lead to better understanding of the cause and effect of nosocomial infection and greater acceptance of high-quality hospital hygiene management.     

High-throughput methylation profiling by MCA coupled to CpG island microarray

An abnormal pattern of DNA methylation occurs at specific genes in almost all neoplasms. The lack of high-throughput methods with high specificity and sensitivity to detect changes in DNA methylation has limited its application for clinical profiling. Here we overcome this limitation and present an improved method to identify methylated genes genome-wide by hybridizing a CpG island microarray with amplicons obtained by the methylated CpG island amplification technique (MCAM). We validated this method in three cancer cell lines and 15 primary colorectal tumors, resulting in the discovery of hundreds of new methylated genes in cancer. The sensitivity and specificity of the method to detect hypermethylated loci were 88% and 96%, respectively, according to validation by bisulfite-PCR. Unsupervised hierarchical clustering segregated the tumors into the expected subgroups based on CpG island methylator phenotype classification. In summary, MCAM is a suitable technique to discover methylated genes and to profile methylation changes in clinical samples in a high-throughput fashion.