Significance and specificity of antibodies to neutrophils detected by western blotting for the serological diagnosis of primary sclerosing cholangitis.

Antibodies against neutrophils have been detected in sera from patients with primary sclerosing cholangitis and inflammatory bowel diseases either by immunofluorescence or by enzyme-linked immunosorbent assay. To assess primary sclerosing cholangitis-specific antibodies, we examined sera from 30 patients with clinically and morphologically well-established primary sclerosing cholangitis by Western blotting against neutrophils and compared these results with those obtained by testing sera from patients with inflammatory bowel diseases. By Western blot using sonified neutrophils, 24 (80%) of 30 primary sclerosing cholangitis sera were positive. Five antigenic determinants at 95, 60, 55, 40 and 30 kD were visualized. Twenty-eight of the primary sclerosing cholangitis sera also showed the characteristic perinuclear fluorescence pattern by immunofluorescence on neutrophils. Thus a serological diagnosis of primary sclerosing cholangitis could be made in 80% of patients based on these two methods. In contrast, only 9% of 23 patients with ulcerative colitis and 10% of 60 patients with Crohn's disease were positive by Western blot, and these patients also showed positive perinuclear fluorescence pattern by immunofluorescence, suggesting an overlap between inflammatory bowel diseases and primary sclerosing cholangitis. Although some patients with classical primary biliary cirrhosis and autoimmune chronic active hepatitis had antibodies against primary sclerosing cholangitis epitopes, none of the patients with obstructive bile duct disorders, collagen diseases, Wegener's granulomatosis or other hepatic and nonhepatic disorders were positive by Western blot, indicating the specificity of these five primary sclerosing cholangitis-related neutrophilic epitopes.     

Using serial observations to identify predictors of progression to AIDS in the Toronto Sexual Contact Study.

The Toronto Sexual Contact Study comprises a cohort of 249 male sexual contacts of men with HIV disease which has been followed every 3 months for almost 5 years. On enrollment 143 were seropositive and 16 seroconverted during the follow-up period. By 31 December 1989, 41 of the 159 seropositive cohort members had developed AIDS. Using Cox relative risk regression models, we investigated the association of a number of laboratory and clinical variables and progression to AIDS. Fixed covariate models examined laboratory variables from the enrollment visit of cohort members, with time calculated from this date. In models assessing time dependent covariates, time was calculated from the estimated date of HIV infection. In the univariate models of either fixed or time dependent covariates, many variables were significantly associated with risk of progression to AIDS (T4 cell count, T4/T8 ratio, blastogenic responses to phytohemagglutinin, concanavalin A, and pokeweed mitogen, serum IgA, appearance of p24 antigen, and the development of oral hairy leukoplakia, thrush, or herpes zoster). Appearance of persistent generalized lymphadenopathy was not associated with increased risk of progression. In the multivariate model which evaluated fixed laboratory covariates, T4/T8 ratio, IgA level, and PHA response at enrollment were significantly associated with elevated risk.(ABSTRACT TRUNCATED AT 250 WORDS)     

Brain abscess mimicking brain tumor

We review our experience with brain abscesses presenting as primary brain tumor over a 5-year period (1983 to 1988). Four of 66 (6%) patients admitted with the diagnosis of primary brain tumor by computed tomographic scans were found at craniotomy to have brain abscesses. Periapical abscesses found after surgery were determined to be the cause of brain abscess in two of four patients. Our experience suggests that periapical abscess may be a more frequent cause of brain abscess than previously thought, and should be considered before surgery in patients with a suspected brain tumor.     

Diagnosis of susceptibility to malignant hyperthermia using the in vitro contracture test

Though a malignant hyperthermia (MH) crisis is still a critical event during general anesthesia, recent developments in prophylaxis and treatment should help in avoiding fatal episodes. The best means to avoid MH episodes would be early recognition of MH susceptibility. Today the only reliable test to identify MH susceptibility is the in vitro contracture test. Thus, to diagnose MH susceptibility we performed this test on muscle biopsies from 26 individuals who: (1) had an event during general anesthesia that may have been indicative of MH (4 patients); (2) had a family member with a medical history of MH (20 patients); or (3) had unexplained elevated CK levels (1 patient). The criteria according to which patients were submitted to the testing are shown in detail in Table 1. We used the standardized version of the contracture test that has been proposed by the European Malignant Hyperpyrexia Group. Muscle biopsies (20-30 mm long, 8 mm diameter) were dissected into 8-10 small bundles (2-3 mm diameter) and tested within 3 h post-biopsy in four independent tissue baths with various concentrations of caffeine or halothane. According to the concentration of caffeine or halothane necessary to elicit contractures exceeding a predefined force threshold (20 mN), it was possible to classify the patients as MHS (MH-susceptible), MHE (equivocal), or MHN (negative). In addition to the in vitro test, clinical, laboratory, and neurophysiological data were collected from these patients and correlated with the individual test results (Table 2). Thirteen patients were classified as MHS, five were MHE, and seven patients MHN (Fig. 3).(ABSTRACT TRUNCATED AT 250 WORDS)     

Paired Epstein-Barr virus (EBV)-negative and EBV-converted Burkitt lymphoma lines: stimulatory capacity in allogeneic mixed lymphocyte cultures

Epstein-Barr virus (EBV)-negative Burkitt lymphoma lines (BLE-) and their in vitro EBV-converted sublines (BLEc), obtained by infection with the P3HRI and B95-8 strains of EBV, were compared for their capacity to induce T-lymphocyte proliferation in allogeneic mixed lymphocyte cultures (MLC). Regardless of the virus strain used for conversion, the BLEc lines induced a considerably stronger primary MLC response than their EBV-negative parentals. Only the BLEc lines were able to maintain T-lymphocyte proliferation in repeated stimulations. The low proliferative response observed in cultures stimulated with BLE- cells was not due to the generation of suppressor cells or to the release of inhibitory factors. The increased stimulatory capacity of BLEc lines was unrelated to changes in expression of MHC class-I and class-II antigen, or of B-cell activation markers, and was not due to the reactivation of EBV-specific memory T cells, since lymphocytes from EBV-seropositive and seronegative donors responded similarly. The results indicate that the capacity of BL cells to elicit cellular immune responses may be influenced by their EBV-carrying status.     

Effects of chronic fluoxetine treatment on behavioral and neuroendocrine responses to meta-chlorophenylpiperazine in obsessive-compulsive disorder

To investigate the effect of fluoxetine on serotonergic sensitivity in obsessive-compulsive disorder (OCD), the partial serotonin agonist metachlorophenylpiperazine (mCPP) was compared to placebo under double-blind conditions in six patients with OCD before and during treatment with fluoxetine. Readministration of oral mCPP (0.5 mg/kg) after at least 12 weeks of fluoxetine treatment did not increase obsessive-compulsive (OC) symptoms, in contrast to exacerbation of OC symptoms produced by mCPP before treatment. Chronic fluoxetine treatment resulted in a significant increase in prolactin and cortisol response to mCPP. This may be accounted for, however, by substantially increased plasma mCPP levels during fluoxetine treatment. Chronic fluoxetine treatment diminished the behavioral sensitivity to mCPP and did not diminish, but may have partially normalized, the neuroendocrine response to mCPP in patients with OCD. These adaptive homeostatic effects may reflect fluoxetine's antiobsessional mechanism.     

Experimental transmission of Plasmodium mexicanum by bites of infected Lutzomyia vexator (Diptera: Psychodidae)

Lutzomyia vexator is an efficient experimental vector of Plasmodium mexicanum, infecting 69.2% (9/13) of the Sceloporus undulatus lizards with as few as one bite. Sporozoites were present in the salivary glands by day 6.5 postfeed and infective by day 8 postfeed at 27 degrees C. The prepatent period was relatively long, ranging from 23 to 40 days for bite-induced infections and appears to be related to the number of sporozoites injected. The acute phase of the infection is initially exponential and rapid. All lizards (6) that were not sacrificed, died of fulminating infections from 13 to 56 days after parasites were seen in the blood films. Gametocytes from 2 experimentally infected lizards were infective to L. vexator during the course of the acute infection. The majority of P. mexicanum parasites were in erythrocytes of Sc. undulatus. Exoerythrocytic forms were observed in circulating lymphocytes and thrombocytes, lymphocytes of spleen and bone marrow, and endothelial cells of brain capillaries.     

Assessing speech recognition in noise for listeners with a signal processor hearing aid

Hearing aids with signal processors use advanced circuitry to enhance speech recognition in noise. The effectiveness of these processors has not been well established. The purpose of this study was to evaluate performance on a speech recognition in noise task for listeners wearing a Zeta signal processor aid with the processor turned on and with the processor turned off. In addition, comparisons were made to performance while unaided and aided with a conventional hearing aid. A simple adaptive procedure and a psychometric function were the procedures used. Results for normal-hearing subjects indicate performance was usually better without a hearing aid. Performance when aided was similar for the processor on and the conventional aid. Performance in both of these conditions was clearly better than with the signal processor off. Although results for the hearing-impaired subjects varied widely, there was a trend for better performance with the conventional aid and with the signal processor on than for the signal processor off condition.     

The effect of naloxone on the preoperative gastric volume and pH

The effect of 4 mg oral naloxone on preoperative gastric volume and pH of gastric aspirate was studied in a double-blind, randomized study. Twenty patients received 10 ml of naloxone (4 mg) mixed with 10 ml of orange juice, and 20 patients received 10 ml of isotonic saline mixed with 10 ml of orange juice, 2 h before surgery. Gastric content was obtained immediately after intubation of the trachea. No significant difference in gastric volume and pH of gastric aspirate was found between the two groups. It is concluded that naloxone does not affect gastric emptying and gastric acid secretion to a degree great enough to protect against aspiration of gastric contents into the lungs.