Impaired sodium excretion, decreased glomerular filtration rate and elevated blood pressure in endothelin receptor type B deficient rats

The renal endothelin (ET) system, particularly the ET type B receptor, has been implicated in the regulation of sodium excretion and glomerular filtration rate (GFR). We analyzed kidney morphology and function in a rat strain characterized by complete absence of a functional ETB receptor. Due to Hirschsprung's disease limiting lifetime in these rats, studies were performed in 23-day-old rats. Kidney size and morphology (glomerular and interstitial matrix content, glomerular size and cell density and intrarenal vascular morphology) were normal in ETB-deficient rats. There were also no evidence of altered kidney cell cycle regulation in these rats. GFR was significantly lower, by 72% (P<0.001), in homozygous ETB-deficient rats than in wild-type rats. Fractional sodium excretion was likewise markedly reduced by 84% in homozygous ETB-deficient rats (P<0.001 versus wild-type rats). Treatment with the specific epithelial sodium channel blocker amiloride led to a much higher increase in fractional sodium excretion in ETB-deficient rats (934.2+/-73% in ETB-deficient rats versus 297+/-20% in wild-type rats, expressed as percentage of corresponding placebo treated control; P<0.001). Mean arterial blood pressure was elevated by 7.9 mmHg in homozygous ETB-deficient rats (P<0.05 versus wild-type rats). Our study demonstrates that ETB-deficiency causes early onset kidney dysfunction characterized by a markedly reduced sodium excretion, decreased GFR, and slightly elevated blood pressure. The complete absence of the ETB receptor causes in the kidney--in contrast to the colon--a functional rather than a developmental, neural crest cell dependent disease, since kidney morphology was normal in ETB-deficient rats. The much higher increase in the fractional sodium excretion in ETB-deficient rats after pharmacological blockade of the epithelial sodium channel indicates that the decreased fractional sodium excretion in ETB-deficient rats is most probably due to a lack of the inhibitory property of the ETB receptor on the epithelial sodium channel activity.     

Blastic NK-cell lymphomas (agranular CD4+CD56+ hematodermic neoplasms): a review

Blastic natural killer (NK) cell lymphoma (also termed CD4+CD56+ hematodermic neoplasm) is a recently described entity, with the first case reported in 1994. It was suggested initially that the disease originates from NK cells. Since 1994, single cases and a few small series have been published. In this review, data from the literature and a series of 30 cases from the French and Dutch study groups on cutaneous lymphomas are discussed. The major clinical, histopathologic, and phenotypic aspects of the disease and diagnostic criteria and data suggesting a plasmacytoid dendritic cell origin for the tumor cells are provided.     

Differences in host susceptibility to disease progression in the human challenge model of Haemophilus ducreyi infection

With human volunteers inoculated at two sites with Haemophilus ducreyi, outcomes for a subject were not independent. In a reinfection trial, 2 of 11 previous pustule formers and 6 of 10 previous resolvers resolved all sites of infection. There was no correlation between serum bactericidal or phagocytic activity and outcome in the trial. These data indicate that different hosts are differentially susceptible to disease progression versus resolution in the model.     

Influence of wet surfaces and fall height on pediatric injury risk in feet-first freefalls as predicted using a test dummy

INTRODUCTION: Falls are a major cause of morbidity and mortality in children, but are also reported falsely in child abuse. Therefore, it is of interest to understand those factors which may lead to a higher likelihood of injury in a feet-first freefall. METHODS: We used laboratory freefall experiments and a 3-year-old Hybrid III anthropomorphic test dummy (ATD) to assess head and femur injury risk. Wet and dry linoleum impact surfaces were used from three fall heights: 22, 35 and 47 in. RESULTS: For a given fall height, dry surfaces were associated with higher head injury criteria (HIC) values than wet surfaces. Changes in fall height 22-47 in. did not significantly affect HIC values for falls onto either surface. Generally, compressive and bending femur loading increased significantly for wet as compared to dry linoleum. CONCLUSIONS: In simulated feet first freefall experiments up to 47 in. using a 3-year-old test dummy, a low risk of contact type head injury and femur fracture was found. However, both fall height and surface conditions influenced femur loading and head injury measures. Future efforts should explore the risk of head injury associated with angular acceleration in freefalls.     

Adverse effects of early dexamethasone in extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network

BACKGROUND: Early administration of high doses of dexamethasone may reduce the risk of chronic lung disease in premature infants but can cause complications. Whether moderate doses would be as effective but safer is not known. METHODS: We randomly assigned 220 infants with a birth weight of 501 to 1000 g who were treated with mechanical ventilation within 12 hours after birth to receive dexamethasone or placebo with either routine ventilatory support or permissive hypercapnia. The dexamethasone was administered within 24 hours after birth at a dose of 0.15 mg per kilogram of body weight per day for three days, followed by a tapering of the dose over a period of seven days. The primary outcome was death or chronic lung disease at 36 weeks' postmenstrual age. RESULTS: The relative risk of death or chronic lung disease in the dexamethasone-treated infants, as compared with those who received placebo, was 0.9 (95 percent confidence interval, 0.8 to 1.1). Since the effect of dexamethasone treatment did not vary according to the ventilatory approach, the two dexamethasone groups and the two placebo groups were combined. The infants in the dexamethasone group were less likely than those in the placebo group to be receiving oxygen supplementation 28 days after birth (P=0.004) or open-label dexamethasone (P=0.01), were more likely to have hypertension (P<0.001), and were more likely to be receiving insulin treatment for hyperglycemia (P=0.02). During the first 14 days, spontaneous gastrointestinal perforation occurred in a larger proportion of infants in the dexamethasone group (13 percent, vs. 4 percent in the placebo group; P=0.02). The dexamethasone-treated infants had a lower weight (P=0.02) and a smaller head circumference (P=0.04) at 36 weeks' postmenstrual age. CONCLUSIONS: In preterm infants, early administration of dexamethasone at a moderate dose has no effect on death or chronic lung disease and is associated with gastrointestinal perforation and decreased growth.     

Hepatic giant cell carcinoma. An ultrastructural and immunohistochemical study

Hepatocellular carcinoma with osteoclast-like giant cells (hepatic giant cell carcinoma [HGCC]) is a rare entity, with only three cases reported. The tumor is histologically similar to giant cell tumor (GCT) of bone, and the origin of the multinucleated giant cells and mononuclear stromal cells has not been determined. The purpose of this report is to present a case of this rare tumor and compare its ultrastructural and immunohistochemical features with those of a conventional GCT of bone. Histologically, the HGCC consists of sheets of osteoclast-like giant cells with a background of mononuclear cells. The giant cells lack the pleomorphism seen in hepatocellular carcinomas with anaplastic giant cells. At the light microscopic level, most of this tumor was nearly identical to a GCT of bone, but several microscopic fields (less than 5% of the tumor) had the histologic appearance of a "usual" hepatocellular carcinoma. The hepatic tumor was negative for HAM 56, epithelial cytokeratins, muramidase, and alpha-1-antitrypsin, with only focal positivity for chymotrypsin in mononuclear and giant cells. The GCT was strongly positive for alpha-1-antitrypsin and chymotrypsin in both the mononuclear and giant cells and showed focal, weak staining for AE1 and AE3 in the mononuclear stromal cells. Ultrastructurally, both mononuclear and giant cells of the HGCC showed features typical of hepatocellular carcinoma. Although the patient presented in this report died, the pattern of growth was different from most hepatocellular carcinomas. The overall histologic features of this tumor are distinctive and appear to justify separating this variant from other types of hepatocellular carcinoma.     

Pneumonien bei akuten Leukämien

Summary Acute leukaemia was complicated by pneumonia in 38 (34.8%) of 109 patients treated between 1979 and 1983; in 39.5% of the patients pneumonia occurred more than once. In 23 patients (60.5%) pneumonia occurred during cytostatic therapy, and 25 patients (65.8%) had less than 1000 mm² granulocytes. Antibiotic therapy had no or only little effect in 70%. A total of 21 patients (55.3%) died of pneumonia. In 15 patients a direct relationship could be seen between pneumonia and the bacterial spectrum in the sputum. A prevalence of gram-negative bacteria was found (24 of 40 bacteria isolated, especially Enterobacteriaceae (19). Fungi were cultivated in 10 cases. Each of the typical pneumonia bacteria was only seen once respectively. It is most important that therapy begin immediately, even before the bacteria have been identified. Only then is there hope that the survival time of patients with acute leukaemia can be influenced.

     

Competence of mentally ill patients: a comparative empirical study

BACKGROUND: This study investigates the competence of patients with dementia, depression and schizophrenia to make treatment decisions. The outcome of an objective test instrument is presented and compared with clinical assessment of competence by the attending physician. METHOD: The MacArthur Competence Assessment Tool-Treatment (MacCAT-T), a test instrument to assess abilities in different standards of competence, was administered to patients with diagnoses of dementia (N = 31), depression (N = 35) and schizophrenia (N = 43). Statistical significance of group differences in the MacCAT-T results were tested with the chi-square test. The concordance of the test and clinical assessment of competence by the attending physician were evaluated by Cohen's kappa coefficient. RESULTS: Patients with dementia, as a group, showed significantly more often impaired performance than those with schizophrenia who were still more impaired than depressed patients. Patients were classified as impaired or not depending on the standards used. By combination of all standards substantially more patients were classified as impaired than by clinical assessment (67.7 v. 48.4% of patients with dementia, 20.0 v. 2.9% of patients with depression, 53.5 v. 18.4% of patients with schizophrenia). CONCLUSIONS: Using different standards of competence the study showed substantial differences among patients with dementia, depression and schizophrenia. The high proportion of patients identified as incompetent raises several ethical questions, in particular, those referring to the selection of standards or the definition of cut-offs for incompetence. The discrepancy between clinical and formal evaluations points out the influence of the used procedure on competence judgements.     

Sensitivity of respiratory virus culture when screening with R-mix fresh cells

Use of R-Mix Fresh Cells has been shown to be a rapid and sensitive method for the detection and identification of respiratory viruses. We prospectively evaluated the impact of incorporation of R-Mix shell vials on the sensitivity and time to detection of seven respiratory viruses recovered in a comprehensive culture during the course of an entire respiratory season in a high-volume clinical laboratory. In this study, R-Mix shell vials were used as part of the culture of 3803 respiratory specimens. A total of 428 respiratory viruses were recovered. Staining of R-Mix vials after overnight incubation allowed initial detection of 274 of 279 influenza viruses, 33 of 38 parainfluenza viruses, 35 of 51 adenoviruses, and 52 of 60 respiratory syncytial viruses (RSVs). The time to reporting of all positive cultures after in-lab specimen receipt was 2.9 days on average and those initially detected in R-Mix cells were reported in 2.3 days on average. A combination of direct fluorescent-antibody (DFA) staining and virus culture was performed on a subset of 711 respiratory specimens. Of 152 viruses identified, 57 were observed only with DFA testing (55 RSV and 2 influenza A viruses) and 31 were recovered only in cell culture. After overnight incubation, R-Mix cells detected 87.1% of respiratory viruses not observed by DFA testing and 96.9% of viruses positive by both methods. The sensitivities of DFA testing and R-Mix cells for identification of influenza viruses were 70.5% and 96.7%, respectively. The R-Mix method detected influenza virus in 18 samples that were negative by DFA testing.