Identification of novel susceptibility loci for inflammatory bowel disease on chromosomes 1p, 3q, and 4q: evidence for epistasis between 1p and IBD1

The idiopathic inflammatory bowel diseases, Crohn's disease (CD) and ulcerative colitis (UC), are chronic, frequently disabling diseases of the intestines. Segregation analyses, twin concordance, and ethnic differences in familial risks have established that CD and UC are complex, non-Mendelian, related genetic disorders. We performed a genome-wide screen using 377 autosomal markers, on 297 CD, UC, or mixed relative pairs from 174 families, 37% Ashkenazim. We observed evidence for linkage at 3q for all families (multipoint logarithm of the odds score (MLod) = 2.29, P = 5.7 x 10(-4)), with greatest significance for non-Ashkenazim Caucasians (MLod = 3.39, P = 3.92 x 10(-5)), and at chromosome 1p (MLod = 2.65, P = 2.4 x 10(-4)) for all families. In a limited subset of mixed families (containing one member with CD and another with UC), evidence for linkage was observed on chromosome 4q (MLod = 2.76, P = 1.9 x 10(-4)), especially among Ashkenazim. There was confirmatory evidence for a CD locus, overlapping IBD1, in the pericentromeric region of chromosome 16 (MLod = 1.69, P = 2.6 x 10(-3)), particularly among Ashkenazim (MLod = 1.51, P = 7.8 x 10(-3)); however, positive MLod scores were observed over a very broad region of chromosome 16. Furthermore, evidence for epistasis between IBD1 and chromosome 1p was observed. Thirteen additional loci demonstrated nominal (MLod > 1.0, P < 0.016) evidence for linkage. This screen provides strong evidence that there are several major susceptibility loci contributing to the genetic risk for CD and UC.     

FDTD electromagnetic and thermal analysis of interstitial hyperthermic applicators. Finite-difference time-domain

In this paper, the electromagnetic and thermal behavior of interstitial applicators was analyzed by using the Finite-Difference Time-Domain method. Two configurations were considered: a simple insulated dipole antenna radiating in a layered tissue, and an air cooled applicator radiating in a tissue-equivalent phantom. The proposed approach allows a detailed modeling of the complete structure of the applicator. Furthermore, Specific Absorption Rate and temperature distributions can be determined considering real clinical or experimental conditions. The temperature distribution for the air cooled applicator has been compared with experimental results.     

Inducible nitric-oxide synthase generates superoxide from the reductase domain

In the absence of L-arginine, the heme center of the oxygenase domain of neuronal nitric-oxide synthase reduces molecular oxygen to superoxide (O-2). Our recent work has provided evidence that inducible NOS (iNOS) may also catalyze O-2 formation in macrophages. However, there has been a lack of direct evidence of superoxide generation from the purified iNOS, and it was previously hypothesized that significant O-2 production does not occur. Moreover, the mechanism and enzyme site responsible for O-2 generation is unknown. To determine whether iNOS produces O-2 and to identify the mechanism of this process, we performed electron paramagnetic resonance measurements on purified iNOS using the spin trap 5,5-dimethyl-1-pyrroline N-oxide. In the presence of NADPH, prominent O-2 adduct signals were detected from iNOS. These signals were totally abolished by superoxide dismutase but not affected by catalase. High concentrations of L-arginine decreased this O-2 formation, whereas its enantiomer D-arginine did not. Pre-incubation of iNOS with the flavoprotein inhibitor diphenyleneiodonium totally blocked these O-2 signals. Conversely, pretreatment of the enzyme with the heme blocker cyanide had no effect on O-2 generation. Furthermore, strong O-2 generation was directly detected from the isolated iNOS reductase domain. Together, these data demonstrate that iNOS does generate O-2, and this mainly occurs at the flavin-binding sites of the reductase domain.     

Immunosuppressive therapy with microemulsion cyclosporine A shortens the hospitalization of pediatric liver transplant recipients

Lipopolysaccharide (LPS) from S. typhimurium on exposure to gamma-radiation resulted in decrease in toxicity and was less mitogenic, Silver stained profiles of irradiated LPS on polyacrylamide gels revealed complete loss of its heteropolysaccharides which was confirmed further by analysing lipid A and LPS from Salmonella minnesota Re mutants on SDS-PAGE. Glucosamine and 2-keto 3-deoxy-octonate(Kdo) contents were significantly decreased on treatment. Lipid A obtained by removal of heteropolysaccharides from LPS was less toxic on exposure to gamma radiations.     

3H]-SR 27897B: a selective probe for autoradiographic labelling of CCK-A receptors in the brain

The binding and distribution of radiolabelled SR27897B, a potent CCK-A antagonist, was characterized using in vitro receptor autoradiography. Rapid imaging and quantitative analysis of [3H]SR27897B binding was obtained in a very short period of time (5 days) with a highly sensitive radioimager ensuring very short exposure times for isotopes such as tritium. Tritiated SR27897B binding sites are localized almost exclusively in the area postrema and the medical part of the nucleus tractus solitarius and in this nucleus the rostral-caudal distribution of CCK-A sites differed from that of sulphated CCK8 receptors. Receptor binding properties analyzed on 15 microns serial coronal sections showed on site receptor occupancy in these two regions with high affinity and selectivity characteristic of the CCK-A receptor. These results precisely locate the SR27897B binding sites and provide further support for the absence of heterogeneity of the CCK-A receptors in the rat brain.     

Changes in blood enzyme activity and tumor necrosis factor level in the treatment of experimental pancreatitis with pentoxifylline

It was established in an acute experiment on rats of Wistar line while an acute pancreatitis simulation using the pancreatic tissue freezing that the level of a tumor necrosis factor (TNF) in a blood serum was maximal in 4 hours from the cold action onset, the activity of amylase and trypsin was heightened and trypsin activity inhibitor (TAI) had lowered. Intraperitoneal application of pentoxifylline in 100 mg/kg dose twice daily have promoted the significant lowering of TNF contents, the amylase and trypsin activity as well, and the TAI concentration increase.     

Microvascular soft-tissue coverage and distraction osteosynthesis for lower-extremity salvage

In our attempts to salvage massive lower-extremity injuries, even in the presence of severe peripheral vascular pathology, adequate soft-tissue coverage is no longer a limiting factor due to recent advances in microvascular composite tissue transfer. Restoration of tibial continuity without shortening has emerged as the last obstacle in the formidable task of salvaging lower extremities with grade III B and III C defects. Proposed solutions to this problem include conventional free cancellous bone-grafting applicable to small defects only, vascularized bone grafts, or shortening of the leg with subsequent elongation using the Ilizarov technique. We present our experience with 3 consecutive cases of lower-limb salvage, utilizing a new approach in which microsurgical soft-tissue reconstruction has been combined with bony reconstruction by distraction osteosynthesis. Bone transport by distraction osteosynthesis under a free flap performed while preserving the initial limb length throughout the treatment period proved to be superior to other methods in selected cases and is presented as a new technique for the management of problematic lower-limb injuries.     

Chronic gastrointestinal problems and bowel dysfunction in patients with spinal cord injury

In the treatment of diabetes, the importance of kinesitherapy increases steadily. In fact, a prospective study (1996) which was done on 897 Finnish middle-aged males over a period of 4 years, showed that the risk of diabetes can be reduced to 50% by moderate physical exercise of 40 minutes per week compared with less active persons of the same age. The amount of kinesitherapeutic measures depends on the physiological resilience of the diabetes patient and on the extent of existing diabetes-induced lesions. An endurance kinesitherapy activates the carbohydrate metabolism and affects the glucosensitive receptors situated in peripheral and central organs. A muscle activity of ten minutes can already multiply by fifteen the increase of glucose absorption from the blood. Another positive result by physical effort is to be seen in the preventine and therapeutic effect of an increased insuline action. The individually adapted kinesitherapeutic endurance stimulation should last from five to ten minutes each day and reach at least 50% of maximum capacity but not more than 70%. This maximum capacity can among other things be gauged from the heart rate as well as from the breathing rate.     

Carbon dioxide laser skin resurfacing

Numerous modalities have been used to achieve facial rejuvenation. The carbon dioxide laser is an instrument long familiar to the soft tissue surgeon that has recently been adapted for use in facial rejuvenation. The laser achieves this goal by ablating the epidermis and superficial dermis, while producing a limited amount of thermal damage in the underlying dermis. Actinic damage and certain forms of dyspigmentation and scarring may be improved or eliminated, and skin tone is improved. Although portions of the face may be treated in certain situations, the best aesthetic results are generally achieved with full-face treatment. Clinical results are excellent, but both patient and physician must anticipate a 12 to 16 week period of erythema in the treated region. Early complications including infection, hyperpigmentation, and scarring have been recognized for several years, but late complications such as significant hypopigmentation have been recognized more recently.