Segregation of structural collagen genes in adolescent idiopathic scoliosis.

The etiology of idiopathic scoliosis remains unknown. The condition results in a characteristic deformity of the spine and surrounding tissues. Both Types I and II collagen are important constituents of the affected tissues, and thus defective collagens are reasonable candidates for the primary abnormality in adolescent idiopathic scoliosis (AIS). Direct analyses of the amount and solubility of collagen have revealed differences between normal individuals and those with AIS. However, these changes may be secondary to the mechanical effects of the spinal deformity. Segregation analysis was done of genetic markers linked to the structural genes encoding Types I and II collagen to test these candidate loci in four pedigrees with dominantly inherited AIS. In one pedigree, markers linked to both of the Type I collagen loci (COL1A1 and COL1A2) were found to be inherited independently of the abnormal phenotype. Two pedigrees were discordant at one of the Type I loci. The condition also segregated independently of the locus for Type II collagen (COL2A1) in three pedigrees. This is evidence against idiopathic scoliosis generally being caused by mutations in the Types I and II collagen genes.     

Contrast agents in functional MR imaging

Contrast agents have greatly expanded the role of MR imaging (MRI) to allow assessment of physiologic, or “functional,” parameters. Although activation mapping generally does not require contrast agents, other forms of functional MRI, including mapping of cerebral hemodynamics (eg, perfusion imaging), are best done with the use of contrast agents. Serial echo planar images are obtained after bolus injection of lanthanide chelates. Application of susceptibility contrast physics and standard tracer kinetic principles permits generation of relative cerebral blood volume maps. Deconvolution of cerebral blood flow and mean transit time parameters is also possible within technical limitations. By using diffusion and perfusion pulse sequences, an imaging correlate to the ischemic penumbra can be identified. Functional MRI perfusion imaging of intraaxial tumors is analogous to positron emission tomography for delineation of metabolic activity, yet may be even more sensitive to neovascularity and possesses improved image quality. Clinical applications include biopsy site selection and postirradiation follow-up. Further improvements in data analysis and map generation techniques may improve diagnostic accuracy and utility.     

Effects of Ethanol on the Contractile Function of the Heart: A Review

Chronic ethanol consumption leads to a number of alterations in the contractile function of the heart and is a leading cause of cardiomyopathy. Ethanol also has an acute negative inotropic effect mediated by direct interaction with cardiac muscle cells, although this action is often masked by indirect actions resulting from enhanced release of catecholamines in vivo. This article reviews the effects of ethanol on the contractile function of the heart. The specific targets affected by ethanol in cardiac muscle cells are discussed in terms of potential mechanisms underlying the depressions of contractility resulting from both acute and chronic actions of ethanol.     

The rhomboid flap for pilonidal disease

Introduction There have been many surgical techniques described for the treatment of pilonidal sinuses. Recurrent disease causes significant morbidity particularly with time from work. Aim To assess the rhomboid flap's role in promoting one‐stage primary healing in pilonidal disease and to evaluate the morbidity and recurrence. Methods Fifty‐three patients were prospectively recruited of which 27 had previous multiple abscess formation requiring surgical drainage from their pilonidal disease, although none had acute disease at the time of surgery. By using the transposition flap, we were able to obliterate the natal cleft and therefore the rolling action of the buttocks between the cleft in these patients and thereby remove one of the factors involved in pilonidal disease. Hospital stay, healing time, wound infection, wound breakdown and recurrence were noted. Results There were 47 males and 6 females with a median age of 28 years (range 16–64 years). Median follow‐up was 24 months (range 3–36 months). Post‐operative morbidity involved superficial wound infection in 7 (13%) which settled with out‐patient dressings. There were four recurrences (7%), two occurred between the flap and the anal canal, and the other two in the flap margin needing intervention. All the patients healed their wounds and the median healing time was 14 days. Conclusion As this condition affects a predominantly young population causing significant time off from work, we feel that the Rhomboid Flap is useful for difficult cases in that it allows early return to full activity and does not necessitate prolonged postoperative care.     

5-HT3 Receptor-independent Inhibition of the Depolarization-induced 86Rb Efflux from Human Neuroblastoma Cells,TE671, by Ondansetron

The 5-HT₃-receptor antagonist, ondansetron, has been shown to have positive effects in selected in-vivo models of memory impairment and anxiety. The exact mechanisms underlying such bioactivities are unknown. In the present work, an ⁸⁶Rb efflux bioassay was used to show that ondansetron has a unique ability to block voltage-gated potassium channels in TE671 human neuroblastoma cells. This intrinsic potassium-channel-blocking (KCB) property is relatively weak (IC50 20 (M), but is not shared by other 5-HT₃-receptor ligands including zatosetron, MDL 72222, LY 278, 584, zacopride, 1-phenylbiguanide, and ICS 205–930 (tropisetron). Pre-incubation of the target neuroblastoma cells with several 5-HT-receptor ligands including 5-hydroxytryptamine, 8-OH-DPAT, ketanserin, 2-methyl-5-HT, as well as a number of potent 5-HT₃ agonists and antagonists and two selective neurotoxins, failed to abolish the KCB action of ondansetron. A preliminary structure-activity relationship analysis indicates that the KCB activity of ondansetron is almost entirely attributable to its structural nucleus, 2,3-dihyro-9-methyl-4(lH)-carbazolone. It is hypothesized that the KCB action of ondansetron is mediated through receptors other than 5-HT₃ receptors. The KCB activity of ondansetron may be a significant factor in the in-vivo cognition-enhancing activities of this compound, conceivably due to depolarization of the hippocampal synaptic membranes and a consequent augmentation of neurotransmission.     

Low-density lipoprotein subfraction profiles in dialysis patients

Summary: Uraemic dyslipidaemia is a major risk factor for cardiovascular disease in end-stage renal failure patients. In patients without renal failure, high levels and qualitative abnormalities of low-density lipoprotein (LDL) are known to be atherogenic. Recently, LDL subfraction analysis has associated premature coronary artery disease with a high prevalence of small, dense LDL particles characterizing the LDL subclass phenotype B. We therefore examined the lipid profiles, LDL subfraction distribution and phenotypes in our population of haemodialysis (HD; n = 30) and peritoneal dialysis patients (PD; n = 17), and compared them to 40 asymptomatic, non-uraemic volunteers. Dialysis patients had significantly higher triglyceride and VLDL cholesterol concentrations and lower HDL cholesterol and smaller LDL peak particle diameters. PD patients had significantly higher total cholesterol, glycated haemoglobin and fasting blood glucose levels with smaller LDL peak particle diameters (24.4 [0.1] vs 24.8 [0.1 nm] than HD. Both groups showed significant negative correlations between plasma triglyceride and LDL peak particle diameter, and positive correlations between HDL cholesterol and LDL peak particle diameter. All the PD patients expressed the B phenotype (LDL peak diameter ± 25.5 nm) compared to 73% of HD patients. This study demonstrates that HD and especially PD patients have atherogenic lipid profiles which are associated with a predominance of small dense LDL particles and the highly atherogenic LDL subclass phenotype B.