High-density lipoprotein subclasses and esterification rate of cholesterol in children: effect of gender and age

Since the development of coronary heart disease (CAD) is affected by a specific pattern of plasma high density lipoprotein (HDL) effects it may be useful to know whether this occurs already in childhood. In this study we evaluated particle size distribution of HDL by gradient gel electrophoresis and the determination of cholesterol esterification rate (FER_HDL) in plasma depleted of apo B lipoproteins in 221 children (108 boys and 113 girls) aged 4 months to 20 years. Total plasma- (TC), low-density lipoprotein- (LDL-C) and HDL- (HDL-C) cholesterol, HDL unesterified cholesterol (HDL-UC) and plasma triglycerides (TG) were also measured. There were no significant gender and age differences with respect to the plasma TC, LDL-TC and TG but concentration of HDL-TC increased with age. Post-pubertal girls had significantly higher relative concentrations of HDL_2b compared to boys (30.4% vs 17.2%), while HDL_3b,c was lower in post-pubertal girls (8.7% vs. 16.5 %). FER_HDL correlated inversely with HDL_2b and positively with HDL_3b,c particles and was significantly higher in boys of the post-pubertal group compared to girls (16.9%/h vs 12.5%/h). While in girls there was a positive correlation between age and HDL-C, HDL-UC and the relative concentration of HDL_2b no significant correlation were observed in boys. In girls the increase in TC showed a significant correlation with a simultaneous increase in HDL-C, HDL-UC and HDL_2b. In boys TC correlated significantly with changes in TG only. When HDL_2b and HDL_3b,c cholesterol levels are calculated from HDL-C concentration and per cent distribution the differences between males and females are further emphasized. These data indicate that HDL particle size distribution is age- and gender-dependent.     

Hypoglycémie hyperinsulinémique persistante du nouveau-né et du nourrisson

Persistent hyperinsulinemic hypoglycaemia of infancy (PHHI) is the most frequent cause of hypoglycaemia in infancy. Clinical presentation is heterogeneous, with variable onset of hypoglycaemia and response to diazoxide, and presence of sporadic or familial forms. Underlying histopathological lesions can be focal or diffuse. Focal lesions are characterised by focal hyperplasia of pancreatic islet-like cells, whereas diffuse lesions implicate the whole pancreas. The distinction between the two forms is important because surgical treatment and genetic counselling are radically different. Focal lesions correspond to somatic defects which are totally cured by limited pancreatic resection, whereas diffuse lesions require a subtotal pancreatectomy exposing to high risk of diabetes mellitus. Diffuse lesions are due to functional abnormalities involving several genes and different transmission forms. Recessively inherited PHHI have been attributed to homozygote mutations for the beta-cell sulfonylurea receptor (SUR1) or the inward-rectifying potassium-channel (Kir6.2) genes. Dominantly inherited PHHI can implicate the glucokinase gene, particularly when PHHI is associated with diabetes, the glutamate dehydrogenase gene when hyperammonaemia is associated, or another locus.     

Differential expression of glutamate receptor subtypes in human brainstem sites involved in perinatal hypoxia-ischemia

This study delineates the development of N-methyl-D-aspartate (NMDA) and non-NMDA receptor binding in the human brainstem, particularly as it relates to issues of the trophic effects of glutamate, the glutamate-mediated ventilatory response to hypoxia, and regional excitotoxic vulnerability to perinatal hypoxia-ischemia. We used tissue autoradiography to map the development of binding to NMDA, alpha-amino-3-hydroxy-5-methyl-4-isoxazole-proprionate (AMPA), and kainate receptors in brainstem sites involved in the glutamate ventilatory response to hypoxia, as well as recognized sites vulnerable to perinatal hypoxia-ischemia. NMDA receptor/channel binding was virtually undetectable in all regions of the human fetal brainstem at midgestation, an unexpected finding given the trophic role for NMDA receptors in early central nervous system maturation in experimental animals. In contrast, non-NMDA (AMPA and kainate) receptor binding was markedly elevated in multiple nuclei at midgestation. Although NMDA binding increased between midgestation and early infancy to moderately high adult levels, AMPA binding dramatically fell over the same time period to low adult levels. High levels of kainate binding did not change significantly between midgestation and infancy, except for an elevation in the infant compared with fetal inferior olive; after infancy, kainate binding decreased to negligible adult levels. Our data further suggest a differential development of components of the NMDA receptor/channel complex. This baseline information is critical in considering glutaminergic mechanisms in human brainstem development, physiology, and pathology.     

The L-DOPA story revisited. Further surprises to be expected?

L-DOPA therapy for Parkinson's disease is one of the major achievements of twentieth century neurology; Parkinson's disease was the first in which specific neurochemical deficits in defined brain regions were identified, and thus for which a rational, chemical therapy could be developed, ushering in the era of clinical neurochemistry. The contributions of Birkmayer and Hornykiewicz (Vienna), Barbeau and Sourkes (Montreal) and of Cotzias (New York) to this story are well-known. Almost completely forgotten, on the other hand, is a paper presented by the Japanese neurologist Isamu Sano in 1960 which reported what is probably the first attempt to treat Parkinson's disease patients with DOPA. This is all the more remarkable as the author was also responsible for one of the key papers which led to the use of DOPA in Parkinson's disease by other workers. Despite the negative outcome of his experience with L-DOPA, Sano deserves to be remembered as one of the pioneers in catecholamine research, having been the first to map dopamine levels in the human brain, and identified the reduction of dopamine levels in the substantia nigra and striatum in Parkinson's disease.     

Interpreting the improved outcome of patients with central nervous system metastases managed in clinical trials compared with standard hospital practice*

The aims were to determine the median survival and prognostic factors of patients with central nervous system (CNS) metastases managed with whole‐brain radiation therapy (WBRT), and to explore selection criteria in recently published clinical trials using aggressive interventions in CNS metastases. A retrospective audit was performed on patients managed with WBRT for CNS metastases. Potential prognostic factors were recorded and analysed for their association with survival duration. The proportion of patients with these factors was also compared with those of patients managed under three recently reported studies investigating aggressive interventions, such as radiosurgery and chemotherapy for CNS metastases. Seventy‐three patients were treated with WBRT for cerebral metastases over a 12‐month period. The median survival of the population was 3.4 months (95% confidence interval: 2.7–4.1), with 6‐ and 12‐month survival rates of 30 and 18%, respectively. Significant prognostic factors for prolonged median survival were Eastern Cooperative Oncology Group status 0–2 (P = 0.015), Medical Research Council neurological functional status 0–1 (P = 0.006), and Recursive Partitioning Analysis Class 2 versus Class 3 (P = 0.020). On multivariate analysis, younger patient age (P = 0.02) and better performance status (P < 0.01) were associated with improved outcome. When comparing these characteristics with selected published studies, our study cohort demonstrated a higher proportion of patients with poor performance status, a greater number of metastases per patient and a higher incidence of extracranial disease. This reflects the selected nature of patients in these published studies. Central nervous system metastases confer a poor prognosis and, for the majority of patients, aggressive interventions are unlikely to improve survival. The use of potentially toxic and expensive treatments should be reserved for those few in whom these studies have shown a potential benefit.     

Group cognitive behavioural therapy for first episode psychosis: who's referred,who attends and who completes it?

Aim: Most national guidelines recommend psychological therapy for people with first‐episode psychosis (FEP) but interventions proven effective in randomized control trials (RCTs) conducted in research settings do not always translate effectively to real‐world clinical environments. In a limited health system, it is important to understand the system and patient barriers to participation in effective treatment. We sought to determine what patient characteristics influenced clinicians' decision to refer or not to refer to group cognitive behavioural therapy for FEP and what characteristics were associated with those referred attending/not attending and adhering/not adhering to the programme. Methods: Between 2006 and 2008, all cases of confirmed FEP from a defined geographical region were examined using the Structured Clinical Interview for DSM‐IV‐TR Axis I Disorders for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM‐IV) diagnoses, the Scale for Assessment of Positive Symptoms, Scale for Assessment of Negative Symptoms, Calgary Depression Scale for Schizophrenia and Birchwood Insight Scale. Duration of untreated psychosis was established using the Beiser Scale. Results: Of the 124 (77 males, 47 females) people in the final sample, 88 (72%) were referred for cognitive behavioural therapy (CBT), 52 (59%) attended and 12 (23%) did not complete CBT. Those with higher levels of insight into the need for treatment (U = 740.00, z = −2.63, P = 0.008) and higher levels of positive symptoms (t (120) = −3.064, P = 0.003) were more likely to be referred to CBT. Those with higher educational attainment (χ² = 9.48, P = 0.03) and fewer negative symptoms, particularly in relation to global attention (t (85) = 2.32, P = 0.03), were more likely to attend and complete CBT. Conclusion: Within an early intervention service for FEP, it appears that individuals with less education, more negative symptoms and less insight experienced significant barriers to successfully completing group CBT. More information for referring clinicians about the benefits of CBT for FEP could help increase referral rates. Assertive outreach for people at risk of disengaging or non‐adherence should also be considered.