Genomic HLA-DQβ Polymorphism Associated with Insulin-Dependent Diabetes Mellitus

Twelve insulin-dependent diabetes mellitus (IDDM) patients and healthy controls, who all carried the serologically defined DR3 and DR4 antigens, were compared with respect to other HLA polymorphisms. No significant differences between patients and controls were found by typing for HLA-Dw determinants by homozygous cell typing, nor by studies of their genomic DR beta polymorphism using different restriction enzymes. In contrast, certain DR beta polymorphism using different restriction enzymes. In contrast, certain DR4-associated genomic DQ beta fragments had a significantly different distribution among the IDDM patients than among the controls. Furthermore, when the distribution of all DQ beta-specific fragments which demonstrated polymorphism in our material was taken into account, nine of the 12 DR3, 4 IDDM patients demonstrated a similar DQ beta polymorphism compared with only two out of the 12 DR3, 4 controls (P = 0.006; corrected P = 0.037). Cells from patients and controls who demonstrated this IDDM-associated DQ beta polymorphism stimulated each other significantly less in reciprocal MLC tests, compared with the responses seen when their cells were confronted with cells from the DR3, 4 individuals with other genomic DQ beta polymorphisms.     

Turbulent Stresses Downstream of Porcine and Pericardial Aortic Valves Implanted in Pigs

Because late valve-related complications such as hemolysis and thromboembolic events are considered related to flow disturbances caused by the inserted valve, velocity fields downstream of aortic valve prostheses were studied in pigs. Acute hemodynamic evaluation of size 25-mm porcine and pericardial aortic valve prostheses 1 diameter downstream of the valve ring was performed using dynamic three-dimensional visualization of velocity profiles and spatial distribution of turbulence. Point blood velocity signals obtained with a 1-mm hot-film anemometer needle probe were used to compute Reynolds normal stresses (RNS) by calculation of the turbulent velocity energy of the axial velocity component in the systole. The porcine valves caused a skewed velocity and turbulence profile revealing mean spatial systolic RNS at 70 nm-2 +/- 35 nm-2 (+/- SD). The spatial maximum RNS was 275 +/- 139 nm-2. Corresponding values for the pericardial valves were 20 +/- 11 nm-2 and 72 +/- 46 nm-2. The pericardial valves revealed plug-shaped velocity profiles and turbulent profiles with slightly higher RNS values at the stent posts. From a hemodynamic point of view, these acute studies indicate superiority of the pericardial valves compared to the porcine valves. The turbulent stresses found in this study are of a magnitude that may cause blood corpuscular and endothelial damage.     

Tissue-Toxic Effects of Phosphatidylcholine/Deoxycholate after Subcutaneous Injection for Fat Dissolution in Rats and a Human Volunteer

BACKGROUND The safety of the lipodissolution procedure for the cosmetic treatment of fat is unknown.
OBJECTIVES The objective was to determine the subcutaneous tissue effects of phosphatidylcholine solubilized with deoxycholate (PC/DC) in rats and a human volunteer.
METHODS Rats were treated subcutaneously three times with 50, 300, or 600 μL of PC/DC formula on the abdomen in a chronic study (30 days). A human volunteer undergoing elective liposuction was similarly treated. Cell membrane lysis, cell viability, and histologic status were determined on fresh biopsies of subcutaneous fat from the injection sites.
RESULTS PC/DC dose-dependently reduced membrane integrity and cell viability. Histologic alterations induced by PC/DC included fibroplasia, bandlike fibrosis in the region of the cutaneous muscle, and partial muscle loss. The highest dose caused widespread fat necrosis, fat cyst formation, and necrotic changes of the walls of small blood vessels. Histologic sections of subcutaneous tissue from the human volunteer showed dose-dependent panniculitis, fat cysts, and vessel necrosis. DC (2.5%), tested for comparison in the rat, exerted membrane and histologic effects similar to those of PC/DC. Solvent controls caused negligible alterations.
CONCLUSIONS Injection lipolysis with PC/DC causes tissue fibrosis and necrosis of adipose and vascular tissues in rat and man, making the long-term safety of PC/DC for nonsurgical treatment of subcutaneous fat deposits uncertain.     

Polarity Reversal Improves Defibrillation Efficacy in Patients Undergoing Transvenous Cardioverter Defibrillator Implantation with Biphasic Sbocks

The purpose of this study was to determine the influence of polarity reversal on DFT in patients undergoing implantation of nonthoracotomy defibrillators with biphasic shocks. Previous studies have shown higher defibrillation efficacy with using the distal electrode as anode in implantation of nonthoracotomy defibrillators and monophasic shocks. However, it is as yet unclear whether biphasic shock defibrillation will also be influenced by polarity reversal. Using a transvenous lead system with a proximal electrode in the superior caval vein and a distal electrode in the RV apex, 27 patients undergoing defibrillator implantation were randomized to DFT testing with "initial" (distal electrode = cathode) or "reversed" polarity (distal electrode = anode). Defibrillation energy was reduced stepwise until defibrillation failure occurred. At this point, polarity was switched and testing continued until the lowest energy requirement was determined for both polarities. With reversed polarity, DFT was 11.1 ± 5.7 J versus 13.3 ± 5.8 J with initial polarity (P = 0.033). This means a 17% reduction of the DFT. In 10 patients, the threshold was lower with reversed, whereas in 3 patients it was lower with initial polarity. In conclusion, changing electrode polarity in transvenous implantable defibrillators with biphasic shocks may significantly influence defibrillation energy requirements. Therefore, polarity reversal should always be attempted before considering patch implantation.     

Susceptibility of glycans to β-elimination in Fmoc-based O-glycopeptide synthesis

order to investigate the possible extent of β-elimination occuring in Fmoc-based continuous-flow solid-phase glycopeptide synthesis, the influence of the pK_b of the base used for N^α-deprotection has been studied. A glycosylated pentapeptide as synthesized using 50%morpholine, 10%, piperidine or 2% DBU, respectively, in DMF for deprotection. The dehydropentapeptide N^α-.Ac-Thr-Thr-δAba-Val-Thr-NH₂, which would be formed in the case of β-elimination, was prepared independently and used as a control in HPLC analysis; however, this product was not formed under any of the deprotection conditions applied. Furthermore, a 23 amino acid long glycopeptide from human intestinal mucin was prepared using 2% DBU as a base for Fmoc cleavage, and similarly no β-elimination was observed. The glycopeptide products were subjected to a prolonged treatment with sodium hydroxide in methanol/water without significant formation of byproducts, and the pure glycopeptides were isolated and characterized by ¹H-NMR spectroscopy.     

A population study of alpha-keto acid reductase

An electrophoretic survey of 509 individuals of Japanese, Mexican American, American Negro, Eskimo, Amerindian and Anglo-American origin failed to reveal genetically determined variation at the alpha-keto acid reductase locus by starch gel electrophoresis. Additional screening of 232 individuals by thin layer isoelectric focusing in polyacrylamide gels detected a single phenotype. Interspecific variation at the alpha-keto acid reductase locus is clearly resolved using either method. These results indicate that the alpha-keto acid reductase locus is monomorphic in most human population groups despite earlier results suggesting the existence of genetic polymorphism.     

Adrenal carcinoma with intravenous extension into the tricuspid valvular plane in a patient with patent foramen ovale

We report on an adrenal carcinoma growing via the inferior venacava into the right atrium and prolapsing into the right ventricle.A patent foramen ovale determined the pathophysiological andclinical appearance. Instead of an expected caval congestionthe main features were paroxysmal dyspnoea and cyanosis. The patient was investigated using echocardiography, magneticresonance tomography and angiography.