Early participation in an HIV cohort study slows disease progression and improves survival. The Swiss HIV Cohort Study

Unprecedented mortality occurred in bald eagles (Haliaeetus leucocephalus) at DeGray Lake, Arkansas, during the winters of 1994-1995 and 1996-1997. The first eagles were found dead during November, soon after arrival from fall migration, and deaths continued into January during both episodes. In total, 29 eagles died at or near DeGray Lake in the winter of 1994-1995 and 26 died in the winter of 1996-1997; no eagle mortality was noted during the same months of the intervening winter or in the earlier history of the lake. During the mortality events, sick eagles were observed overflying perches or colliding with rock walls. Signs of incoordination and limb paresis were also observed in American coots (Fulica americana) during the episodes of eagle mortality, but mortality in coots was minimal. No consistent abnormalities were seen on gross necropsy of either species. No microscopic findings in organs other than the central nervous system (CNS) could explain the cause of death. By light microscopy, all 26 eagles examined and 62/77 (81%) coots had striking, diffuse, spongy degeneration of the white matter of the CNS. Vacuolation occurred in all myelinated CNS tissue, including the cerebellar folia and medulla oblongata, but was most prominent in the optic tectum. In the spinal cord, vacuoles were concentrated near the gray matter, and occasional swollen axons were seen. Vacuoles were uniformly present in optic nerves but were not evident in the retina or peripheral or autonomic nerves. Cellular inflammatory response to the lesion was distinctly lacking. Vacuoles were 8-50 microns in diameter and occurred individually, in clusters, or in rows. In sections stained by luxol fast blue/periodic acid-Schiff stain, the vacuoles were delimited and transected by myelin strands. Transmission electron microscopy revealed intramyelinic vacuoles formed in the myelin sheaths by splitting of one or more myelin lamellae at the intraperiodic line. This lesion is characteristic of toxicity from hexachlorophene, triethyltin, bromethalin, isonicotinic acid hydrazide, and certain exotic plant toxins; however, despite exhaustive testing, no etiology was determined for the DeGray Lake mortality events. This is the first report of vacuolar myelinopathy associated with spontaneous mortality in wild birds.     

Depression in borderline adolescents

Etiologically, adolescents considered borderline by the criteria in common use are on a continuum between primarily biological and primary psychological disorders. Depression is common, and may be masked (in many cases of ulcer, anorexia, substance abuse, school avoidance) or overt (viz., early onset endogenous depression, hysteroid dysphoria, cases with severe deprivation). Illustrative cases are provided, along with recommendations for treatment.     

Marginal ulcer after gastric bypass: a prospective 3-year study of 173 patients

BACKGROUND: Marginal ulceration (MU) after Roux-en-Y gastric bypass (RYGB) is a well-recognized complication. Its incidence varies between 1% and 16%. Factors associated with the development of MU include pouch size, pouch orientation, staple line integrity, and mucosal ischemia. Nonsteroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori may also contribute to MU, but their mechanism of action in the RYGB patient has not been studied. METHODS: In 1994 a prospective 3-year study was designed to document the incidence of MU after near-total gastric bypass (NTGB). In this procedure the transected pouch was limited to the cardia, and the gastrojejunostomy was made along the greater curvature. A total of 173 patients entered the study. All patients who experienced postoperative nausea, vomiting, or abdominal pain underwent endoscopic examination of the pouch, stoma, and proximal Roux-en-Y limb. Gastrograffin studies were used within the first 2 weeks of operation. RESULTS: One year after operation, MU was not identified in any patient. At 3 years follow-up, MU was documented in one patient (0.6%) with a dilated gastric reservoir (60 cc). CONCLUSION: This study reviews the etiology, diagnosis, and treatment of MU in the RYGB patient and offers specific recommendations to reduce its occurrence. It also confirms a preliminary impression that NTGB is an effective operation in preventing MU formation.     

Molecular analysis of bovine spongiform encephalopathy and scrapie strain variation

Five mouse scrapie strains, a mouse-passaged scrapie isolate derived from a field case in sheep in Germany, and 2 mouse-passaged bovine spongiform encephalopathy (BSE) isolates were analyzed by immunoblot in regards to banding patterns of proteinase K-digested pathologic prion proteins (PrPres). To obtain reliable results, the photo-imager technique was used for measurement of staining band intensities. Distinct and reproducible profiles were observed for the different strains or isolates. A British and a German BSE isolate were similar, suggesting the same source of infection. The German scrapie isolate resembled scrapie strain ME7, which has frequently been isolated from sheep scrapie in the past. In selected strains or isolates, no influence of the mouse lines used was observed on PrPres profiles, nor were brain region-specific differences apparent. This investigation suggests that PrPres glycotyping can be an invaluable tool for the in vitro differentiation of BSE and scrapie isolates.     

Insulin stimulates pp120 endocytosis in cells co-expressing insulin receptors

pp120, a substrate of the insulin receptor tyrosine kinase, is a plasma membrane glycoprotein that is expressed in the hepatocyte as two spliced isoforms differing by the presence (full-length) or absence (truncated) of most of the intracellular domain including all phosphorylation sites. Co-expression of full-length pp120, but not its phosphorylation-defective isoforms, increased receptor-mediated insulin endocytosis and degradation in NIH 3T3 fibroblasts. We, herein, examined whether internalization of pp120 is required to mediate its effect on insulin endocytosis. The amount of full-length pp120 expressed at the cell surface membrane, as measured by biotin labeling, markedly decreased in response to insulin only when insulin receptors were co-expressed. In contrast, when phosphorylation-defective pp120 mutants were co-expressed, the amount of pp120 expressed at the cell surface did not decrease in response to insulin. Indirect immunofluorescence analysis revealed that upon insulin treatment of cells co-expressing insulin receptors, full-length, but not truncated, pp120 co-localized with alpha-adaptin in the adaptor protein complex that anchors endocytosed proteins to clathrin-coated pits. This suggests that full-length pp120 is part of a complex of proteins required for receptor-mediated insulin endocytosis and that formation of this complex is regulated by insulin-induced pp120 phosphorylation by the receptor tyrosine kinase. In vitro GST binding assays and co-immunoprecipitation experiments in intact cells further revealed that pp120 did not bind directly to the insulin receptor and that its association with the receptor may be mediated by other cellular proteins.     

The transferrin binding protein B of Moraxella catarrhalis elicits bactericidal antibodies and is a potential vaccine antigen

The transferrin binding protein genes (tbpA and tbpB) from two strains of Moraxella catarrhalis have been cloned and sequenced. The genomic organization of the M. catarrhalis transferrin binding protein genes is unique among known bacteria in that tbpA precedes tbpB and there is a third gene located between them. The deduced sequences of the M. catarrhalis TbpA proteins from two strains were 98% identical, while those of the TbpB proteins from the same strains were 63% identical and 70% similar. The third gene, tentatively called orf3, encodes a protein of approximately 58 kDa that is 98% identical between the two strains. The tbpB genes from four additional strains of M. catarrhalis were cloned and sequenced, and two potential families of TbpB proteins were identified based on sequence similarities. Recombinant TbpA (rTbpA), rTbpB, and rORF3 proteins were expressed in Escherichia coli and purified. rTbpB was shown to retain its ability to bind human transferrin after transfer to a membrane, but neither rTbpA nor rORF3 did. Monospecific anti-rTbpA and anti-rTbpB antibodies were generated and used for immunoblot analysis, which demonstrated that epitopes of M. catarrhalis TbpA and TbpB were antigenically conserved and that there was constitutive expression of the tbp genes. In the absence of an appropriate animal model, anti-rTbpA and anti-rTbpB antibodies were tested for their bactericidal activities. The anti-rTbpA antiserum was not bactericidal, but anti-rTbpB antisera were found to kill heterologous strains within the same family. Thus, if bactericidal ability is clinically relevant, a vaccine comprising multiple rTbpB antigens may protect against M. catarrhalis disease.     

Oral anticoagulation in dental surgery

STUDY OBJECTIVES: To evaluate whether pediatric or emergency medicine residents exhibit a bias when they select patients from triage based on the chief complaint, ie, medical versus surgical in the pediatric emergency department (PED). DESIGN: A retrospective chart review of a convenience sample of consecutive patients, excluding those seen during times when both pediatric and emergency medicine residents were not simultaneously present. SETTING: Urban Municipal PED with 25,000 visits annually. TYPE OF PARTICIPANTS: Pediatric residents, emergency medicine residents, and medical students rotating through the PED and their supervising attending physicians. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Five hundred and ninety-nine charts were included in the study. On the basis of the triage complaint the initial diagnosis was classified as either surgical or medical. Surgical diagnoses were assigned to those patients who required a surgical procedure, involved a surgical subspecialty or were victims of trauma and represented 151 (25.2%) of the patients seen. Medical diagnoses were assigned to the nonsurgical patients and represented 448 (74.8%) of the patients seen. There are roughly three pediatric residents to each emergency resident working in our PED. Of the 367 patients seen by the pediatric residents, 73 (19.9%) had surgical diagnoses, and 294 (80.1%) had medical diagnoses. Of the 158 patients seen by the emergency residents, 59 (37.3%) had surgical diagnoses and 99 (62.7%) had medical diagnoses. chi2 analysis was used to compare categorical variables. The P value was considered significant at <0.05. DISCUSSION: Residents, both pediatric and emergency medicine, were instructed to see patients based upon the severity of the patient illness as judged by the triage nurse unless the patients' illnesses were of equal severity, in which case they were to be seen in the order in which they presented. The null hypothesis was that in the absence of physician bias, both pediatric and emergency medicine residents would see the same proportion of surgical and medical patients. The results showed that a bias exists. Emergency medicine residents saw a greater proportion of surgical patients, and pediatric residents saw a greater proportion of general medical patients. A limitation of this study may be the that the supervising attending physician selected residents to see certain patients to expedite PED flow. CONCLUSIONS: Recognizing that bias in the selection of patients seen exists is important in ensuring a balanced education experience.