Pneumothorax associated with mechanical insufflation-exsufflation and related factors

Impaired cough that results in ineffective airway secretion clearance is an important contributor to pulmonary complications in patients with neuromuscular weakness including spinal cord injury. Mechanical insufflation-exsufflation (MI-E) is a respiratory aid used by patients with weak respiratory muscles to increase cough peak flows and improve cough effectiveness. Relative contraindications to MI-E are said to include susceptibility to pneumothorax, but the association of pneumothorax with MI-E use has never before been described. We report two cases of pneumothorax in patients with respiratory muscle weakness associated with daily use of MI-E: one was a 58-yr-old male with C4 ASIA C tetraplegia, and the other was a 26-yr-old male with Duchenne muscular dystrophy. Both patients also used positive-pressure ventilatory assistance. Although seemingly rare in this patient population, ventilator users also using MI-E who have increasing dyspnea or who require increasing positive inspiratory pressures when using noninvasive ventilation should be evaluated for pneumothorax.     

CD8+ T-cell responses identify beta-cell autoimmunity in human type 1 diabetes

Despite the understanding that type 1 diabetes pathogenesis is mediated by T-cells, detection of these rare lymphocytes remains largely elusive. Suitable T-cell assays are highly needed, since they could offer preclinical diagnoses and immune surrogate end points for clinical trials. Although CD4+ T-cell assays have met with limited success, CD8+ T-cells are increasingly recognized as key actors in the diabetes of the NOD mouse. CD8+ T-cells are likely to play a role also in humans and may provide new markers of beta-cell autoimmunity. Taking advantage of a panel of HLA-A2-restricted beta-cell epitopes derived from preproinsulin, GAD, and islet glucose-6-phosphatase catalytic subunit-related protein (IGRP), we have implemented an islet-specific CD8+ T-cell interferon-gamma enzyme-linked immunospot (ISL8Spot) assay. The ISL8Spot assay is capable of detecting and quantifying beta-cell-reactive CD8+ T-cells directly ex vivo, without any preliminary expansion, using either fresh or frozen samples. Positive ISL8Spot responses separate new-onset diabetic and healthy samples with high accuracy (86% sensitivity, 91% specificity), using as few as five immunodominant epitopes. Moreover, sensitivity reaches 100% when the ISL8Spot assay is complemented by antibody determinations. Combination of CD8+ T-cell measurements with immune intervention strategies may open new avenues toward type 1 diabetes prediction and prevention.     

Klinische Möglichkeiten zur Steuerung der Körpertemperatur

The constancy of body temperature (CBT) is a cornerstone of homeostatic, homothermic organisms and is essential for a regulated course of biochemical and biophysical reactions. Severe deviations from normothermia (36.8+/-0.4 degrees C) are life threatening and even a moderate perioperative reduction of the CBT is coupled with an increased morbidity and mortality especially in high-risk patients. The relevant factors are coagulation disturbances, increased infection rate and increased cardiac risk. Normothermia should be achieved by the consistent use of warmth-conserving measures. On the other hand, a deliberate reduction in temperature or induced hypothermia is a neuroprotective procedure, which offers a therapeutic option to minimize neuronal secondary damage after primary hypoxic-ischemic events as well as extending the neuronal tolerance to ischemia. Management includes the practice of cooling down to a defined temperature, rewarming as well as a differentiated control of various parameters. Furthermore, side-effects which increase in severity with decreasing temperature must be taken into consideration.     

Synaptic contact number and size in stratum radiatum CA1 of APP/PS1DeltaE9 transgenic mice

Synaptic changes occur early in the course of Alzheimer's disease and are key to understanding the initial events in associated neurodegenerative processes. The quantitative analysis of synaptic morphology in transgenic mouse models of Alzheimer's disease can provide important insights into these processes. To this end, the total number and the distribution of the diameters of synaptic contacts in the stratum radiatum of the CA1 region of the hippocampus of 12-month-old APP/PS1DeltaE9 transgenic mice and wild type littermates have been evaluated by applying design-based stereological methods to material prepared for electron microscopy. Although there were no differences in the size of the synaptic contacts, the total number of synaptic contacts was significantly larger in the transgenic mice, suggesting that the transgenic effect at this age is synaptotrophic and that the presence of amyloid plaques and an elevated Abeta42/40 ratio are not necessarily detrimental to populations of synapses. The potential of this type of data in evaluating synaptic changes related to Alzheimer's disease is discussed and the methodology described in detail.     

Lymphocytic insulitis in a juvenile dog with diabetes mellitus

Autoimmune diabetes has never been described in a juvenile dog, whereas serologica evidence has established its development in adult dogs. Diabetes mellitus was diagnosea in a 3-mo-old Donge de Bordeaux dog suffering from persistent hyperglycemia and concurrent insulinopenia. Histological analysis of the pancreas revealed in flammatory lesions in 40% of the islets of Lagerhans, with infiltration predominantly by T lymphocytes (more than 90%), either at the edge (peri-insulitis: 10%) or in the islets (insulitis: 30%). The remaining 60% of the islets showed a marked atrophy due to massive beta cell loss with no loss of alpha cells. This pattern is quite similar to that observed in humans in which a characteristic insulitis containing high numbers of T lymphocytes is found in 20% of the islets at diabetes diagnosis. By contrast, in rodent models, nearly 70% of the islets of langerhans show inflamation at diagnosis and macrophages and dendritic cells predominate in the inflamatory lesions. This is the first report of lymphocytic insulitis in a juvenile dog exhibiting diabetes mellitus. Our observations suggest an autoimmune origin for the disease in this dog that is similar to human type 1 diabetes mellitus, for which there is no accurate spontaneous large animal model. These authors contributed equally to this work     

Association of estrogen receptor alpha gene polymorphisms and lifestyle factors with calcaneal quantitative ultrasound and osteoporosis in postmenopausal Vietnamese women

Abtract Genetic and lifestyle factors are important in the pathogenesis of osteoporosis. We investigated the relationships of PvuII and XbaI polymorphisms of the estrogen receptor alpha (ER-α) gene, lifestyle factors with speed of sound at the calcaneus (calcaneal SOS) and osteoporosis in a population-based study of 140 healthy postmenopausal women. By an analysis of covariates, women with higher copies of P or X alleles had higher calcaneal SOS compared with others (P=0.012, PP vs. pp; P=0.045, Xx vs. xx). Women with lower copies of px or higher copies of PX haplotypes had higher calcaneal SOS compared with others (P=0.021, 0 px vs. 2 px; P=0.011, 1 PX vs. 0 PX). The px and PX haplotypes, age and years since menopause were found to be independent predictors of calcaneal SOS in multiple linear regression models. Using logistic regression, we found an increased osteoporosis risk with evidence for a px haplotype dose effect (OR=2.82, 95% CI=1.50–5.31, P=0.001) and for a PX haplotype dose effect (OR=0.42, 95% CI=0.19−0.93, P=0.033). An increased educational level was associated with a reduced risk of osteoporosis (P=0.035 in the model with px, P=0.044 in the model with PX). In conclusion, the present study suggests that PvuII and XbaI polymorphims of the ER-α gene, age, years since menopause and educational level are associated with bone density, as assessed by calcaneal SOS, and osteoporosis in postmenopausal Vietnamese women.     

Expression of Galectin-3 in Pancreatic Ductal Adenocarcinoma

Galectin-3 influences neoangiogenesis, tumor cell adhesion, and tumor-immune-escape mechanisms. Hence, the expression of galectin-3 in pancreatic ductal adenocarcinoma (PDAC) was evaluated. Galectin-3 expression in PDAC cell lines was proven by the presence of intracellular protein and by release into the supernatant. Furthermore, galectin-3 was found in the majority of human tissue samples. Serum concentrations of galectin-3 in PDAC patients did not differ significantly from healthy donors and did not correlate with established tumor markers. In conclusion, galectin-3 is expressed in PDAC tissues suggesting a role in tumor development; however, no relationship between expression and clinical findings could be established.