Niemann-Pick C disease (NP-C) is a neurovisceral atypical lysosomal lipid storage disorder with an estimated minimal incidence of 1/120 000 live births. The broad clinical spectrum ranges from a neonatal rapidly fatal disorder to an adult-onset chronic neurodegenerative disease. The neurological involvement defines the disease severity in most patients but is typically preceded by systemic signs (cholestatic jaundice in the neonatal period or isolated spleno- or hepatosplenomegaly in infancy or childhood). The first neurological symptoms vary with age of onset: delay in developmental motor milestones (early infantile period), gait problems, falls, clumsiness, cataplexy, school problems (late infantile and juvenile period), and ataxia not unfrequently following initial psychiatric disturbances (adult form). The most characteristic sign is vertical supranuclear gaze palsy. The neurological disorder consists mainly of cerebellar ataxia, dysarthria, dysphagia, and progressive dementia. Cataplexy, seizures and dystonia are other common features. NP-C is transmitted in an autosomal recessive manner and is caused by mutations of either the NPC1 (95% of families) or the NPC2 genes. The exact functions of the NPC1 and NPC2 proteins are still unclear. NP-C is currently described as a cellular cholesterol trafficking defect but in the brain, the prominently stored lipids are gangliosides. Clinical examination should include comprehensive neurological and ophthalmological evaluations. The primary laboratory diagnosis requires living skin fibroblasts to demonstrate accumulation of unesterified cholesterol in perinuclear vesicles (lysosomes) after staining with filipin. Pronounced abnormalities are observed in about 80% of the cases, mild to moderate alterations in the remainder ("variant" biochemical phenotype). Genotyping of patients is useful to confirm the diagnosis in the latter patients and essential for future prenatal diagnosis. The differential diagnosis may include other lipidoses; idiopathic neonatal hepatitis and other causes of cholestatic icterus should be considered in neonates, and conditions with cerebellar ataxia, dystonia, cataplexy and supranuclear gaze palsy in older children and adults. Symptomatic management of patients is crucial. A first product, miglustat, has been granted marketing authorization in Europe and several other countries for specific treatment of the neurological manifestations. The prognosis largely correlates with the age at onset of the neurological manifestations.
Yankelovich2 points out that despite better methods of measuring public opinion, little is known about how to improve its quality. Although information has become widely available, it plays only a limited role in shaping public opinion. Opinion polls can be misleading because they do not distinguish between people's immediate reactions and their thoughtful, considered judgments. Patient satisfaction surveys often fail to even measure, let alone correct for, the nature, severity and intractability of the conditions for which care is received.
Chronic hepatitis B virus (HBV) infection is estimated to affect > 350 million people worldwide and represents a significant cause of morbidity and mortality related to cirrhosis and hepatocellular carcinoma. Mother-to-child transmission (MTCT) of HBV remains an important source of incident cases of HBV. Current barriers to eradication of incident HBV infections via MTCT include underutilization of immunoprophylaxis with hepatitis B vaccination and hepatitis B immune globulin in certain endemic regions as well as failure of immunoprophylaxis.
Introduction. Chronic pelvic pain (CPP) affects about 10-40% of women presenting to a physician, and is characterised by pain within the minor pelvis persisting for over 6 months. Materials and method. The Medline database was searched using the key words 'chronic pelvic pain' and 'pelvic congestion syndrome', published in English during the past 15 years. The condition markedly deteriorates the quality of life of the affected. Its aetiology has not been fully described and elucidated, although organic, functional and psychosomatic factors are implicated. Pain associated with parametrial varices was defined as pelvis congestion syndrome (PCS). Since the aetiology of CPP is complex, multi-directional diagnostic procedures are required. Results. The main diagnostic methods employed are imaging examinations (ultrasound, computer tomography, magnetic resonance). Advances in interventional radiology considerably contributed to the CPP treatment. Currently, embolization of parametrial vessels is one of the most effective methods to relieve pain associated with pelvic congestion syndrome. Conclusions. Due to the complex aetiology of chronic pelvic pain, the most beneficial effects are obtained when the therapy is based on cooperation of the gynaecologist, physiotherapist, psychologist and interventional radiologist.
J. Neurochem. (2010) 114, 728–738. Hypoglycemia is common during development and is associated with the risk of neurodevelopmental deficits in human infants. The effects of hypoglycemia on the developing hippocampus are poorly understood. The sequential changes in energy substrates, amino acids and phosphocreatine were measured from the hippocampus during 180 min of insulin‐induced hypoglycemia (blood glucose < 2.5 mmol/L) in 14‐day‐old rats using in vivo1H NMR spectroscopy. Hypoglycemia resulted in neuroglycopenia (brain glucose < 0.5 μmol/g). However, the phosphocreatine/creatine (PCr/Cr) ratio was maintained in the physiological range until approximately 150 min of hypoglycemia, indicating that energy supply was sufficient to meet the energy demands. Lactate concentration decreased soon after the onset of neuroglycopenia. Beyond 60 min, glutamine and glutamate became the major energy substrates. A precipitous decrease in the PCr/Cr ratio, indicative of impending energy failure occurred only after significant depletion of these amino acids. Once glutamate and glutamine were significantly exhausted, aspartate became the final energy source. N‐acetylaspartate concentration remained unaltered, suggesting preservation of neuronal/mitochondrial integrity during hypoglycemia. Correction of hypoglycemia normalized the PCr/Cr ratio and partially restored the amino acids to pre‐hypoglycemia levels. Compensatory neurochemical changes maintain energy homeostasis during prolonged hypoglycemia in the developing hippocampus.
The Paris Prospective Study is a long-term investigation of the incidence of coronary heart disease in a large population of working men. The first follow-up examination involved 7,038 men, aged 43–54 years. Subjects with impaired glucose tolerance or diabetes (n=943) were selected from the total population for a separate analysis of coronary heart disease mortality risk factors. During a mean follow-up of 11 years, 26 of these 943 subjects with abnormal glucose tolerance died from coronary heart disease. Univariate analysis showed that plasma triglyceride level (p<0.006), plasma cholesterol level (p<0.02), and plasma insulin level both fasting and 2-h post-glucose load (p<0.02), were significantly higher in subjects who died from coronary heart disease compared to those who did not. In multivariate regression analysis using the Cox model, plasma triglyceride level was the only factor positively and significantly associated with coronary death. The distribution of plasma triglyceride levels was clearly higher for the subjects who died from coronary heart disease compared to those who did not die from this cause or were alive at the end of the follow-up. This new epidemiological evidence that hypertriglyceridaemia is an important predictor of coronary heart disease mortality in subjects with impaired glucose tolerance or diabetes suggests a possible role of dyslipidaemia in the excessive occurrence of atherosclerotic vascular disease in this category of subjects.