Adjunctive treatment of compartment syndrome with hyperbaric oxygen

Trauma-induced compartment syndrome and other acute traumatic peripheral ischemias have been effectively treated with hyperbaric oxygen therapy. We describe a case of compartment syndrome associated with an acute exertional injury. After surgical decompression, hyperbaric oxygen therapy reduced edema and improved tissue viability. The mechanisms of hyperbaric oxygen applicable to the pathophysiology of compartment syndrome are described. We believe that hyperbaric oxygen is a useful intervention in the management of compartment syndrome.     

Genetic and immunologic analyses of PlpE, a lipoprotein important in complement-mediated killing of Pasteurella haemolytica serotype 1

Pasteurella haemolytica serotype 1 is the bacterium most commonly associated with bovine shipping fever. The presence of antibodies against P. haemolytica outer membrane proteins (OMPs) correlates statistically with resistance to experimental P. haemolytica challenge in cattle. Until now, specific P. haemolytica OMPs which elicit antibodies that function in host defense mechanisms have not been identified. In this study, we have cloned and sequenced the gene encoding one such protein, PlpE. Analysis of the deduced amino acid sequence revealed that PlpE is a lipoprotein and that it is similar to an Actinobacillus pleuropneumoniae lipoprotein, OmlA. Affinity-purified, anti-PlpE antibodies recognize a protein in all serotypes of P. haemolytica except serotype 11. We found that intact P. haemolytica and recombinant E. coli expressing PlpE are capable of absorbing anti-PlpE antibodies from bovine immune serum, indicating that PlpE is surface exposed in P. haemolytica and assumes a similar surface-exposed conformation in E. coli. In complement-mediated killing assays, we observed a significant reduction in killing of P. haemolytica when bovine immune serum that was depleted of anti-PlpE antibodies was used as the source of antibody. Our data suggest that PlpE is surface exposed and immunogenic in cattle and that antibodies against PlpE contribute to host defense against P. haemolytica.     

A logistic dose-ranging method for phase I clinical investigations trials

This paper describes an alternative to the continual reassessment method (CRM) for phase I trials. The logistic dose ranging strategy (LDRS) uses logistic regression and a dose allocation scheme similar to the CRM. It can easily be implemented from any logistic regression program. The LDRS can be a stand alone dose allocation scheme or it can be incorporated into standard three on a dose strategies to indicate when escalation can proceed more rapidly. Finally, the effect of covariates such as age or comorbid conditions on the toxicity expected for the dose selected for a phase II trial can be examined.     

False aneurysm with median nerve palsy after iatrogenic brachial artery puncture

We report on a case in which a patient on oral anticoagulation for her aortic valve replacement, with an International Normalised Ratio of 2.13, developed a false aneurysm of the brachial artery after a routine arterial puncture, despite direct pressure to the aspiration site. The false aneurysm was complicated by the development of median nerve palsy.     

Selenium regulation of selenium-dependent glutathione peroxidases in animals and transfected CHO cells

Glutathione peroxidase (GPX1) was the first identified selenium-dependent enzyme, and this enzyme has been most useful as a biochemical indicator of selenium (Se) status and the parameter of choice for determining Se requirements. We have continued to study Se regulation of GPX1 to better understand the underlying mechanism and to gain insight into how cells themselves regulate nutrient status. In progressive Se deficiency in rats, GPX1 activity, protein and mRNA all decrease in a dramatic, coordinated and exponential fashion such that Se-deficient GPX1 mRNA levels are 6-15% of Se-adequate levels. mRNA levels for other Se-dependent proteins are far less decreased in the same animals. The mRNA levels for a second Se-dependent peroxidase, phospholipid hydroperoxide glutathione peroxidase (GPX4), are little affected by Se deficiency, demonstrating that Se regulation of GPX1 is unique. Se regulation of GPX1 activity in growing male and female rats shows that the Se requirement is 100 ng/g diet, based on liver GPX1 activity; use of GPX1 mRNA as the parameter indicates that the Se requirement is nearer to 50 ng Se/g diet in both male and female rats. This approach will readily detect an altered dietary Se requirement, as shown by the incremental increases in dietary Se requirement by 150, 100 or 50 ng Se/g diet in Se-deficient rat pups repleted with Se for 3, 7 or 14 d, respectively. Studies with CHO cells stably transfected with recombinant GPX1 also show that overexpression of GPX1 does not alter the minimum level of media Se necessary for Se-adequate levels of GPX1 activity or mRNA. We hypothesize that classical GPX1 has an integral biological role in the mechanism used by cells to regulate Se status, making GPX1 an especially useful and effective parameter for determining Se requirements in animals.     

Adenocarcinoma of the urachus and bladder expresses a unique colonic epithelial epitope: an immunohistochemical study

PURPOSE: Primary adenocarcinoma of the bladder is a rare neoplasm whose histogenesis is poorly understood. Current data support the concept that adenocarcinoma of the bladder and urachus evolves from zones of intestinal metaplasia that become dysplastic and invasive. To address this hypothesis further we determined the immunoreactivity of benign and malignant epithelial tissue from the bladder and urachus with a monoclonal antibody that is reactive with colonic epithelium to evaluate the presence of a common reactive epitope. MATERIALS AND METHODS: The monoclonal antibody 7E12H12 (IgM isotype), developed against a colonic epithelial protein, was used in an immunoperoxidase assay to survey formalin fixed, paraffin embedded archival tissue specimens. A total of 26 specimens obtained by endoscopic biopsy or extirpative surgery, including benign and malignant bladder and urachal epithelial abnormalities, was chosen for retrospective evaluation. RESULTS: All adenocarcinoma reacted positively regardless of the histological variant, differentiation, or bladder or urachal origin. In contrast, transitional cell and squamous cell carcinomas were nonreactive. Also, the pattern of reactivity in tissues that contained benign epithelial proliferations suggested a stepwise transition with no reactivity in normal urothelium or Brunn's epithelial nests, rare staining of cystitis cystica, and uniformly positive reactivity in cystitis glandularis and frank colonic intestinal metaplasia of the bladder and urachus. CONCLUSIONS: The shared, aberrant phenotypic expression of a unique colonic epitope in benign epithelial metaplasia, and adenocarcinoma of the bladder and urachus suggests a common underlying pathway toward adenocarcinoma in cystic and urachal adenocarcinoma. The implications for diagnostic pathology are discussed.