The effectiveness of early endoscopy for upper gastrointestinal hemorrhage: a community-based analysis

OBJECTIVES: The effectiveness of upper endoscopy in unselected patients with upper gastrointestinal hemorrhage has not been well studied. This study was undertaken to identify factors associated with the performance of early endoscopy (ie, within 1 day of hospitalization) and, after adjusting for these factors, to determine associations between early endoscopy and in-hospital mortality, length of stay, and performance of surgery. METHODS: Subjects in this observational cohort study were 3,801 consecutive admissions with upper gastrointestinal hemorrhage to 30 hospitals in a large metropolitan region. Demographic and clinical data were abstracted from hospital records. A multivariable model based on factors that potentially could relate to the decision to perform endoscopy was developed to determine the propensity (0 to 100%) for early endoscopy in each patient. RESULTS: Early endoscopy was performed in 2,240 patients (59%), and although it was not associated with mortality after adjusting for severity of illness among all patients, it was associated with a higher risk of death for patients in the lowest propensity group. Early endoscopy was associated with a lower likelihood of upper gastrointestinal surgery in all patients and in the two highest propensity groups and with a shorter length of stay in the entire cohort and in all subgroups. CONCLUSIONS: In the absence of specific contraindications, early endoscopy should be considered because of associated reductions in length of stay and surgical intervention. Further studies are needed to identify subgroups in whom the procedure may be associated with adverse effects on survival.     

HLA-DRB1 genes and disease severity in rheumatoid arthritis. The MIRA Trial Group. Minocycline in Rheumatoid Arthritis

OBJECTIVE: To examine the effect of alleles encoding the "shared"/"rheumatoid" epitope on rheumatoid arthritis (RA) disease severity in patients who participated in the minocycline in RA (MIRA) trial. METHODS: Of 205 patients with a week-48 visit, blood was available for typing of HLA-DRB1 and HLA-DQB1 in 174 (85%) and successfully completed in 169 (82%). Baseline erosions were used to assess disease severity and new erosions at the last visit served as a proxy for progression. RESULTS: At baseline, there was no association between the presence of erosive disease or rheumatoid factor status and the dose of rheumatoid epitope (homozygous, heterozygous, none) or the specific alleles identified. At the final visit, a gradient was observed for the 3 allelic subgroups (and their gene doses) in the occurrence of new erosions among the Caucasian placebo-treated, but not the minocycline-treated, patients. A treatment group/HLA-DR4 epitope interaction was demonstrated in multivariate analyses. Approximately two-thirds of African-American patients did not have the rheumatoid epitope. CONCLUSION: HLA-DRB1 oligotyping may be useful in predicting the progression of disease in some Caucasian patients. Our study corroborates the infrequency of the epitope among African-American patients with RA.     

Clinical evaluation of 0.5% ferric hyaluronate adhesion prevention gel for the reduction of adhesions following peritoneal cavity surgery: open-label pilot study

The objective of this study was to assess the safety and to make a preliminary assessment of the efficacy of 0.5% ferric hyaluronate adhesion prevention gel in reducing adhesions in patients undergoing peritoneal cavity surgery by laparotomy, with a planned 'second-look' laparoscopy. The study was a randomized, open-label, placebo-controlled, parallel-group design in patients desirous of fertility at the Women's and Children's Hospital, Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles, California. Female patients aged 24 to 41 years received 300 ml 0.5% ferric hyaluronate adhesion prevention gel or lactated Ringer's solution as an intraperitoneal instillate at the completion of the laparotomy procedure. At second-look laparoscopy 4-12 weeks after the laparotomy, the presence of adhesions was evaluated. Haematology and serum chemistry were determined throughout the study interval. All patients tolerated the procedures well and did not manifest any serious adverse events. At second-look laparoscopy, patients treated with 0.5% ferric hyaluronate adhesion prevention gel had significantly fewer adhesions than control patients. When adhesions did form, they were significantly less extensive and less severe in patients who received 0.5% ferric hyaluronate adhesion prevention gel. In conclusion, 0.5% ferric hyaluronate adhesion prevention gel was safe and highly efficacious in the reduction of the number, severity and extent of adhesions throughout the entire abdomen following peritoneal cavity surgery.     

Dissolved organic carbon of coal slurry transport water

The qualitative and quantitative occurrence and fate of dissolved organic carbon (DOC) leaching into coal slurry transport water was examined in laboratory-generated coal slurries and wastewaters from the Black Mesa coal slurry pipeline. Laboratory slurries were formulated for both western coals (Wyodak, Montana Rosebud and Black Mesa) and eastern coals (Illinois No. 6 and Pittsburgh No. 8). Sephadex G-25 elution profiles and ultrafiltration studies indicate that the majority of the organic compounds in western coal slurry wastewaters were lower (less than 1000) molecular weight species (62% for Wyodak and 74% for Montana Rosebud). Biochemical Oxygen Demand (BOD) for these particular wastewaters ranged from 50 to 150 mg l⁻¹ as determined through the use of an electrolytic respirometer. Also, there was a concomitant 51–74% reduction in the DOC levels in the wastewaters. This removal was primarily due to the removal of the lower (< 1000) molecular weight compounds by the seed inoculum. There was no evidence for the presence of mutagenic organics in the raw wastewater.     

Synthesis and intestinal metabolism of ursodeoxycholic acid conjugate with an antiinflammatory agent, 5-aminosalicylic acid

5-Aminosalicylic acid conjugate of ursodeoxycholic acid was synthesized in above 90% yield by adding a basic solution of 5-aminosalicylic acid into the mixed anhydride formed with ursodeoxycholic acid and ethyl chloroformate. The 5-aminosalicylic acid conjugate of ursodeoxycholic acid was poorly secreted into the bile and was deconjugated with cholylglycine hydrolase and Clostridium perfringens, that deconjugate naturally occurring glycine and taurine conjugates of bile acids. However, ursodeoxycholic acid 5-aminosalicylic acid conjugate was not absorbed from the duodenum but was concentrated in the colon where it was partially hydrolyzed by the intestinal bacteria to ursodeoxycholic acid and 5-aminosalicylic acid. We believe that this unique conjugation of ursodeoxycholic acid with 5-aminosalicylic acid may facilitate the transport of both 5-aminosalicylic acid and ursodeoxycholic acid to the colon and may be useful for the treatment of colonic inflammatory bowel diseases, ulcerative colitis and Crohn's disease.     

Global brain ischemia and reperfusion: modifications in eukaryotic initiation factors associated with inhibition of translation initiation

We used in vitro translation and antibodies against phosphoserine and the eukaryotic initiation factors elF-4E, elF-4G, and elF-2 alpha to examine the effects of global brain ischemia and reperfusion on translation initiation and its regulation in a rat model of 10 min of cardiac arrest followed by resuscitation and 90 min of reperfusion. Translation reactions were performed on postmitochondrial supernatants from brain homogenates with and without aurintricarboxylic acid to separate incorporation due to run-off from incorporation due to peptide synthesis initiated in vitro. The rate of leucine incorporation due to in vitro-initiated protein synthesis in normal forebrain homogenates was approximately 0.4 fmol of leucine/min/microgram of protein and was unaffected by 10 min of cardiac arrest, but 90 min of reperfusion reduced this rate 83%. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blots of these homogenates showed that neither 10 min of global brain ischemia nor 90 min of reperfusion induced significant alterations in the quantity or serine phosphorylation of elF-4E. However, we observed in all 90-min-reperfused samples elF-4G fragments that also bound elF-4E. The amount of elF-2 alpha was not altered by ischemia or reperfusion, and immunoblotting after isoelectric focusing did not detect serine-phosphorylated elF-2 alpha in normal samples or in those obtained after ischemia without reperfusion. However, serine-phosphorylated elF-2 alpha was uniformly present after 90 min of reperfusion and represented 24 +/- 3% of the elF-2 alpha in these samples. The serine phosphorylation of elF-2 alpha and partial fragmentation of elF-4G observed after 90 min of reperfusion offer an explanation for the inhibition of protein synthesis.     

Technology transfer in digital mammography. Report of the Joint National Cancer Institute-National Aeronautics and Space Administration workshop of May 19-20, 1993

Digital mammography is one of the most promising novel technologies for further improvement of early detection of breast cancer, offering important potential advantages: 1) improved image quality; 2) digital image processing for improved lesion contrast; 3) computer-aided diagnosis for enhanced radiologic interpretation; and 4) teleradiology for facilitated radiologic consultation. The Diagnostic Imaging Research Branch of the National Cancer Institute (NCI) recently funded an international, multidisciplinary, multi-institutional Digital Mammography Development Group for collaborations between NCI, the academic community, and industry to facilitate the integrated development and implementation of digital mammographic systems. Currently, however, digital mammography faces a number of fundamental technological roadblocks: 1) cost-effective digital detectors and displays for imaging systems; 2) the need for novel algorithms for image processing and computer-aided diagnosis; and 3) high performance, low cost digital networks to provide an "information superhighway" for teleradiology. To solve some of these technological problems, the Diagnostic Imaging Research Branch of NCI joined efforts with the Technology Transfer Division of the National Aeronautics and Space Administration to pursue a federal technology transfer program in digital mammography. The authors discuss the findings and recommendations of the workshop entitled "Technology Transfer in Digital Mammography," which was organized and held jointly by the NCI and the National Aeronautics and Space Administration in May, 1993. Numerous innovative technologies of varying degree of promise for digital mammography were presented at the conference. In this article, specific technologies presented at the workshop by the federal and federally-supported laboratories are described, and critiques of these technologies by the leaders of the medical imaging community are presented.     

Interleukin-1 mediates a rapid inflammatory response after injection of adenoviral vectors into the brain

Adenovirus-mediated gene transfer into the brain is associated with significant inflammation and activation of anti-vector and anti-transgene immune responses that curtail the gene delivery of adenoviruses and therapeutic efficacy. Elucidating the molecular mediators of inflammatory and immune responses to adenoviruses injected into the brain should allow us to inhibit their inflammatory actions, thereby reducing vector clearance and enhance adenoviral-mediated gene transfer into the CNS. Cytokines are primary mediators of the immune response and are released during inflammation. Here we report for the first time that injection of replication-deficient adenovirus vectors into the cerebral ventricles of rats causes a rapid increase in body temperature. This fever response precedes any vector-encoded transgene expression and occurs with vectors encoding no transgene, as well as with vectors encoding a therapeutic transgene i.e., HSV1-thymidine kinase. No fever is detected after infection of the striatum, an important brain target in studies on neurodegeneration. After infection of the brain ventricles, CSF levels of immunoreactive tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta increase significantly (up to 300-fold). In the hypothalamus, the locus of thermoregulation in the brain, only IL-1beta and IL-6 are significantly elevated. A neutralizing TNF-alpha antibody has no effect on adenovirus-induced fever. However, pretreatment with either the IL-1 receptor antagonist or the cyclooxygenase inhibitor flurbiprofen completely abolishes adenovirus-induced fever, suggesting that IL-1 and prostaglandins are direct mediators of this response. These results are the first to demonstrate that IL-1, but not TNF-alpha, is the main mediator of a very early inflammatory response to adenovirus in the brain.     

Wegener's granulomatosis presenting with a renal mass

Wegener's granulomatosis (WG) is a systemic disease characterized by necrotizing granulomatous vasculitis that involves primarily the upper and lower respiratory tracts and, in most cases, the kidneys. Kidney involvement in WG presenting as a mass is recognized, but is very rare. We describe a case of WG presenting with upper and lower respiratory symptoms and a renal mass due to both WG and renal cell carcinoma.