New incidence, prevalence, and survival of Aicardi syndrome from 408 cases

We sought to determine the incidence, prevalence, and life expectancy of Aicardi syndrome from 408 cases compiled from multiple international sources. Last known age ranged from less than 1 month to 42 years. The incidence rates per live births for the United States and The Netherlands were 1 per 105 000 and 1 per 93 000, respectively. The prevalence in the United States is greater than 853 cases, and the worldwide estimate is several thousand. Forty-five cases were deceased (age range, 1 month to 33 years), and the risk of death peaked at age 16. The probability of survival at 27 years of age was 0.62 (95% CI, 0.47-0.77). The risk of death by age follows other congenital neurological disorders with a wide range in severity of functional disability. The longer life expectancy found in our study hints at a higher functioning capacity in Aicardi syndrome and may inform counseling to families.     

Pediatric functional magnetic resonance imaging (fMRI): issues and applications

Functional magnetic resonance imaging (fMRI) represents a useful tool for studying brain functions and the neural basis of cognition in healthy children and in those in disease states. Functional magnetic resonance imaging is a relatively new use of existing magnetic resonance imaging technology that allows scientists and practitioners to observe the brain at work. It is based on the observation that local increases in blood flow are related to neural activity. This review considers principles of functional magnetic resonance imaging, issues relevant to imaging children, and research using functional magnetic resonance imaging to examine cognitive processing in pediatric populations. The focus is specifically on language studies to review strengths, limitations, and practical applications of this technology with children. Future directions for functional magnetic resonance imaging are presented.     

Hopes for future practice of junior orthopedic surgeons in France: a sociological study

Medical demographics have become a major public health issue in France since the publication of the Berlan report in 2002 which announced an upcoming shortage in the next 20 years. But demographic projections cannot be limited to an accounting of training and retirement figures. Other factors such as demographic distribution, changing societal aspirations (free time), modes and sites of occupational activities, the influence of feminization, and initial training and its effects on professional practice must be taken into consideration. The purpose of this work was to study these parameters in orthopedic and traumatology surgery. This was a sociological study designed to ascertain the aspirations of junior orthopedic surgeons. Forty-seven interns in orthopedic surgery in the Paris area were invited to complete a questionnaire in March 2003. Forty-two responded. The choice of orthopedics was an intellectual choice. The attractiveness of the specialty was particularly important during the final years of medical school. Fewer junior surgeons would rather practice in a university hospital setting, more preferring a mixed setting with a private (fees) and a public (salary) component. The desire for "free time" was particularly important. Fewer juniors wanted to practice in general hospitals. For orthopedic surgeons, private practice and payment by fees are the cornerstones of medical practice.     

Angiotensin II type 1 receptor blockade improves hyperglycemia-induced endothelial dysfunction and reduces proinflammatory cytokine release from leukocytes

Angiotensin II and glucose share components of their intracellular redox signaling pathways in endothelial and inflammatory cells. We hypothesized that valsartan, an angiotensin II blocker, attenuates hyperglycemia-induced endothelial dysfunction and downregulates release of proinflammatory cytokines from leukocytes. A sustained hyperglycemic clamp (12 mmol/L) to induce endothelial dysfunction was performed in healthy volunteers before and after 4 weeks of treatment with 160 mg of valsartan. Brachial artery flow-mediated vasodilation (FMD), lipopolysaccharide-induced release of interleukin-6 and TNF-alpha from peripheral blood leukocytes ex vivo, and circulating proinflammatory cytokines were determined before and during the clamp. The hyperglycemic clamp induced a decrease in FMD from 9.2 +/- 0.8 (t = 0 hr) to 4.4+/- 0.5 (t = 2 hr), 3.8 +/- 0.5 (t = 4 hr), and 4.8 +/- 0.5% (t = 22 hr) during the clamp. Valsartan attenuated endothelial dysfunction [FMD 7.0 +/- 0.7 (t = 2 hr), 6.1 +/- 0.7 (t = 4 hr), 6.2 +/- 0.6% (t = 22 hr); P < 0.005] and decreased the release of interleukin-6 and TNF-alpha from leukocytes both before and during the clamp (P < 0.05). Valsartan improves hyperglycemia-induced endothelial dysfunction and reduces the cytokine response to an inflammatory stimulus. A pathophysiological link between the effects of hyperglycemia and the renin-angiotensin system on endothelium and peripheral blood leukocytes may underlie the beneficial effects of inhibitors of the renin-angiotensin system on cardiovascular outcome in patients with diabetes mellitus.     

Prospective study comparing hepatic steatosis assessment by magnetic resonance imaging and four ultrasound methods in 105 successive patients

BACKGROUND Non-alcoholic fatty liver disease(NAFLD) is becoming a major health problem, resulting in hepatic, metabolic and cardio-vascular morbidity.AIM To evaluate new ultrasonographic tools to detect and measure hepatic steatosis.METHODS We prospectively included 105 patients referred to our liver unit for NAFLD suspicion or follow-up. They underwent ultrasonographic measurement of liver sound speed estimation(SSE) and attenuation coefficient(AC) using Aixplorer MACH 30(Supersonic Imagine, Fr...     

Human hair greying is linked to a specific depletion of hair follicle melanocytes affecting both the bulb and the outer root sheath

BACKGROUND: Although hair greying is a very common phenomenon characterized by loss of pigment in the hair shaft, the events that cause and control natural hair whitening with age in humans are still unclear. OBJECTIVES: To decipher the origin of natural hair whitening. METHODS: Human hair melanocytes were immunohistochemically characterized at different stages of whitening. RESULTS: Loss of hair shaft melanin was found to be associated with a decrease in both bulb melanin content and bulb melanocyte population. Although few melanocytes were present in the bulbs of grey hair, they still expressed tyrosinase and tyrosinase-related protein-1, synthesized and transferred melanins to cortical keratinocytes as seen by the presence of melanin granules. In white hair bulbs, no melanocytes could be detected either with pMel-17 or vimentin labelling. Pigmented hair follicles are known to contain inactive melanocytes in the outer root sheath (ORS), and grey and white hairs were also found to contain some of these quiescent melanocytes. However, their population was decreased compared with pigmented hair follicles, ranging from small to nil. This depletion of melanocytes in the different areas of white hairs was detected throughout the hair cycle, namely at telogen and early anagen stages. In contrast, the infundibulum and sebaceous gland of both pigmented and white hairs showed a similar distribution of melanocytes. Furthermore, other distinct cell populations located in the ORS, namely putative stem cells, Merkel cells and Langerhans cells were equivalently identified in pigmented and white hairs. CONCLUSIONS: Thus, hair greying appears to be a consequence of an overall and specific depletion of bulb and ORS melanocytes of human hair.     

Percutaneous absorption of griseofulvin and proquazone in the rat and in isolated human skin

Summary Ointments containing griseofulvin and proquazone, respectively, were made up of monoglycerides of medium chain length and an aprotic solvent, glycerinformal. The ointments were applied topically on the back of bile cannulated rats. The total amount absorbed percutaneously and the permeability constants of both drugs were considerably higher for the ointments than for simple solutions of the drugs without monoglycerides. Distribution of the labeled drugs in rat skin has been demonstrated by microautoradiography. Concentrations of the drugs in the different layers of human skin together with the medium flow rates have been determined 16h after administration of the ointments onto isolated human skin. Monoglycerides of medium chain length enhance significantly the permeability of the stratum corneum for solutes.     

Using bone marrow matrix to analyze meprobamate for forensic toxicological purposes

Bone marrow (BM) analysis is of forensic interest for postmortem toxicological investigations where blood samples are unavailable or unusable. Due to the lack of studies, it remains difficult to interpret concentrations of xenobiotics measured in this matrix. Based on a statistical approach published previously to interpret meprobamate concentrations in bile and vitreous humor, we propose here a diagnostic test for interpretation of BM meprobamate concentrations from analysis of 99 sets of autopsy data. The mean age was 48 years (range 18–80 years, one unknown) for males and 50 years (range 19–80 years, one unknown) for females, with a male/female ratio at 0.768. A BM concentration threshold of 11.3 μg/g was found to be statistically equivalent to that of a blood meprobamate concentration threshold of 50 μg/ml in distinguishing overdose from therapeutic use. The intrinsic qualities of this diagnostic test were good with sensitivity of 0.82 and specificity of 0.92. Compared to previous tests published with the same objective on vitreous humor and bile, this study shows that BM is a useful alternative matrix to reveal meprobamate overdose when blood, vitreous humor, and bile are not available or unusable.     

Pathology of small cerebral arteries demonstrated by MRI: a marker of aging?

Brain magnetic resonance imaging frequently identifies signal abnormalities in the white matter and cerebral cortex in the elderly. They are related to a degenerative disease of the small vessels that may be of ischemic (leukoaraiosis, lacunae and infarct) or hemorrhagic (microbleeds and hematomas) origin. These lesions are part of the aging process, and compounded by vascular risk factors. They increase the occurrence frequency and severity of ischemic or hemorrhagic stroke. Their importance is also associated with the presence of cognitive and/or affective symptoms, and their impact on the occurrence and evolution of dementia remains to be evaluated. The visible consequences of this microangiopathy on MRI probably represent the focal mark of a widespread cerebrovascular disease in the brain parenchyma.