Anterior rhinomanometry in nasal allergen challenges

Even simple and relatively safe provocation procedures like nasal allergen challenges, should aim to allow detection of positivity with the less possible discomfort to the patient. The objective of this work was to evaluate if the use of rhinomanometric measurements during nasal provocation procedures could allow a decrease in the total administered allergen dose, causing less symptoms to the patients but without increasing the number of false-negatives, comparatively to clinical scores or nasal peak-flow measurements. Our results showed that performing rhinomanometric measurements during nasal HDM challenge procedures can lead in many patients to a reduction in the total dose of allergen administered during the challenge, without loss of sensitivity or specificity. This allergen dose reduction translates in less time consumed during the provocation and less patients' discomfort.     

Disposition of 14C-eptifibatide after intravenous administration to healthy men

Eptifibatide, a synthetic peptide inhibitor of the platelet glycoprotein IIb/IIIa receptor, has been studied as an antithrombotic agent in a variety of acute ischemic coronary syndromes. The purpose of the present study was to characterize the disposition of 14C-eptifibatide in man after a single intravenous (i.v.) bolus dose. 14C-Eptifibatide (approximately 50 microCi) was administered to eight healthy men as a single 135-microgram/kg i.v. bolus. Blood, breath carbon dioxide, urine, and fecal samples were collected for up to 72 hours postdose and analyzed for radioactivity by liquid scintillation spectrometry. Plasma and urine samples were also assayed by liquid chromatography with mass spectrometry for eptifibatide and deamidated eptifibatide (DE). Mean (+/- SD) peak plasma eptifibatide concentrations of 879 +/- 251 ng/mL were achieved at the first sampling time (5 minutes), and concentrations then generally declined biexponentially, with a mean distribution half-life of 5 +/- 2.5 minutes and a mean terminal elimination half-life of 1.13 +/- 0.17 hours. Plasma eptifibatide concentrations and radioactivity declined in parallel, with most of the radioactivity (82.4%) attributed to eptifibatide. A total of approximately 73% of administered radioactivity was recovered in the 72-hour period following 14C-eptifibatide dosing. The primary route of elimination was urinary (98% of the total recovered radioactivity), whereas fecal (1.5%) and breath (0.8%) excretion was small. Eptifibatide is cleared by both renal and nonrenal mechanisms, with renal clearance accounting for approximately 40% of total body clearance. Within the first 24 hours, the drug is primarily excreted in the urine as unmodified eptifibatide (34%), DE (19%), and more polar metabolites (13%).     

Blood and plasma selenium levels and GSH-Px activities in patients with arterial hypertension and chronic heart disease

Among the 57 monoclonal antibodies analyzed within the T-cell group of the Second International Swine CD Workshop, one mAb fell within cluster T14a that included the CD6 standard a38b2 (No. 175). The new mAb MIL8 (No. 082) and a38b2 both precipitated from activated T-cells a 150 kDa monomeric protein. Staining patterns on the various cell types were similar. There was no inhibition of binding of either mAb to peripheral blood T-cells with the opposite mAb. The new mAb, MIL8, reacts with a separate epitope on porcine wCD6.     

Necrotizing fasciitis

Necrotizing fasciitis is a rare soft tissue infection with a high rate of mortality. Decreased capacity of the immune response is the overall disposing factor. Necrotizing fasciitis can develop very rapidly, and a rapid diagnosis and aggressive surgery provides the best prognosis.     

The use of oral contraceptives by adolescents for contraception, menstrual cycle problems or acne

BACKGROUND: Oral contraceptives are prescribed as contraception but also as therapy for menstrual cycle disturbances and acne. We studied the prevalence of oral contraceptive (OC) use and the indications to start OC use among adolescents. METHODS: A cohort consisting of ninth grade secondary school girls (mean age 15.3+/-0.6 (s.d.) years) answered a questionnaire on their menstrual cycle. OC users were asked about duration and reasons for OC-use and the name of the preparation they used. The influence of calendar age, gynecological age and level of education on the prevalence of OC was studied by multiple logistic regression analysis. RESULTS: The response on the questionnaire was 92%. Of 2248 responders 248 (11%) used oral contraceptives: 74% used low dose 'sub 50' preparations, 3% pills with 50 microg estrogen, 3% tri-phase preparations and 17% pills with antiandrogens. Of girls aged 14, 15 and 16 years 4%, 12% and 28% respectively, used OC. Of the 15-year-olds 31% mentioned contraception as most important reason for OC use, 18% menstrual cycle irregularity, 26% dysmenorrhea, 10% acne and 5% other reasons. Calendar age, gynecological age and level of education were independent variables for OC use in general and for OC use for contraception or dysmenorrhea, but less so for OC use for menstrual cycle irregularity or acne. CONCLUSIONS: During adolescence low dose OC's were frequently used. In The Netherlands OC use among girls aged 15 and 16 years doubled in comparison with 1982. One third of the adolescent OC-users mentioned contraception as most important reason to start OC. Gynecological age (a determinant of biological maturation), calendar age (a determinant of biological maturation and lifestyle in peer groups), and level of education (a determinant of lifestyle in peer groups) were associated with OC use.     

A prospective 12-year study of subsyndromal and syndromal depressive symptoms in unipolar major depressive disorders

BACKGROUND: Investigations of unipolar major depressive disorder (MDD) have focused primarily on major depressive episode remission/recovery and relapse/recurrence. This is the first prospective, naturalistic, long-term study of the weekly symptomatic course of MDD. METHODS: The weekly depressive symptoms of 431 patients with MDD seeking treatment at 5 academic centers were divided into 4 levels of severity: (1) depressive symptoms at the threshold for MDD; (2) depressive symptoms at the threshold for minor depressive or dysthymic disorder (MinD); (3) subsyndromal or subthreshold depressive symptoms (SSDs), below the thresholds for MinD and MDD; and (4) no depressive symptoms. The percentage of weeks at each level, number of changes in symptom level, and medication status were analyzed overall and for 3 subgroups defined by mood disorder history. RESULTS: Patients were symptomatically ill in 59% of weeks. Symptom levels changed frequently (1.8/y), and 9 of 10 patients spent weeks at 3 or 4 different levels during follow-up. The MinD (27%) and SSD (17%) symptom levels were more common than the MDD (15%) symptom level. Patients with double depression and recurrent depression had more chronic symptoms than patients with their first lifetime major depressive episode (72% and 65%, respectively, vs 46% of follow-up weeks). CONCLUSION: The long-term weekly course of unipolar MDD is dominated by prolonged symptomatic chronicity. Combined MinD and SSD level symptoms were about 3 times more common (43%) than MDD level symptoms (15%). The symptomatic course is dynamic and changeable, and MDD, MinD, and SSD symptom levels commonly alternate over time in the same patients as a symptomatic continuum of illness activity of a single clinical disease.     

IL-5 is required for eosinophil recruitment, crystal deposition, and mononuclear cell recruitment during a pulmonary Cryptococcus neoformans infection in genetically susceptible mice (C57BL/6)

CBA/J (highly resistant), BALB/c (moderately resistant), and C57BL/6 (susceptible) mice displayed three resistance patterns following intratracheal inoculation of Cryptococcus neoformans 52. The inability to clear the infection correlated with the duration of the eosinophil infiltrate in the lungs. The role of IL-5 in promoting the pulmonary eosinophilia and subsequent inflammatory damage in susceptible C57BL/6 mice was investigated. C57BL/6 mice developed a chronic alveolar, peribronchiolar, and perivascular eosinophilia following C. neoformans infection. This resulted in the accumulation of intracellular Charcot-Leyden-like crystals in alveolar macrophages by wk 4 and the extracellular deposition of these crystals in the bronchioles with associated destruction of airway epithelium by wk 6. IL-5 mRNA was expressed in the lungs, and injections of anti-IL-5 mAb prevented eosinophil recruitment and crystal deposition but did not alter cryptococcal clearance. Depletion of CD4+ T cells (but not CD8+) ablated IL-5 production by lung leukocytes in vitro and eosinophil recruitment in vivo. Neutralization of IL-5 also inhibited the recruitment of macrophages, CD8+ T lymphocytes, and B lymphocytes by 47 to 57%. Anti-IL-5 mAb inhibited CD4+ T lymphocyte recruitment by 30% but did not affect neutrophil recruitment. Thus, the development of a chronic eosinophil infiltrate in the lungs of C. neoformans-infected C57BL/6 mice is a nonprotective immune response that causes significant lung pathology. Furthermore, IL-5 promotes the recruitment and activation of eosinophils, resulting in the recruitment of additional macrophages and lymphocytes into the lungs.     

Pigmented uveal tumours in a transgenic mouse model

Lectins are sensitive probes which bind carbohydrate structures specifically. In this study, we modified the lectin staining procedure for sensitive detection of carbohydrate structures in formalin-fixed, paraffin-embedded sections of normal and heterologous serum-induced fibrotic livers. The liver sections were heated in hot distilled water at 100 degrees C for 10 min (thermo-treatment: TT), and then stained with 24 different lectins. In comparison with the results from sections without TT (nonTT), enhanced and/or alternated staining patterns of 19 lectins were demonstrated in sections with TT, and enhanced staining of Vicia villosa agglutinin seen in Kupffer cells was noted. Interestingly, no positive staining was seen with Dolichos biflorus agglutinin, peanut agglutinin or soybean agglutinin (SBA), which recognize O-linked carbohydrate chains, in Kupffer cells of non-TT sections, but strong positive staining was demonstrated in those of TT sections. SBA-positive staining in the cytoplasm of some scattered hepatocytes located in the periportal and perifibrous zones and central zone of pseudolobules was demonstrated only in the fibrotic liver sections with TT. Such findings indicate the heterogeneity of hepatocytes in the liver with fibrosis. Formalin fixation causes masking of lectin binding sites, especially O-linked carbohydrate chains, and TT may recover such masking reactions. TT improved the staining reactions for many lectins in formalin-fixed, paraffin-embedded liver sections, and new staining patterns appear after TT. Modified TT staining procedures may be useful for the diagnosis and prognosis of liver fibrosis.     

Direct endoscopic percutaneous jejunostomy (EPJ). Clinical results

Direct puncture of the small bowel under endoscopic guidance (direct EPJ) is possible in patients whose stomach has been removed or whose small bowel cannot be punctured by other methods. From January 1990 to June 1992 a total of 39 patients underwent successful direct EPJ at our institution. The indications were malnutrition after partial or total gastrectomy (n = 19), insufficient anastomosis or a stenosis after esophageal resection and esophagojejunostomy (n = 13), esophageal perforation (n = 3), fistulas (n = 2), or severe trauma (n = 2). The tubes were inserted at the bedside under local anesthesia using the string pull-through technique. The procedure was attempted in five other patients but it was technically impossible to insert the tubes in these patients. Postoperative enteral feeding was possible in all 39 patients whose direct EPJ was successful. Complications included tube dysfunction due to plugging and fracture in five patients, pressure-induced enteric ulcers in two, and local infections in three patients. The ulcers and infections were managed conservatively. We conclude that direct EPJ is a safe, effective alternative to surgical catheter-jejunostomy.