Occupational asthma in a grain worker due to Lepidoglyphus destructor, assessed by bronchial provocation test and induced sputum

BACKGROUND: Occupational asthma (OA) can be a debilitating disease even when removal from the workplace is achieved. Today, the "gold standard" in the assessment of OA is the bronchial provocation test (BPT). Induced sputum is a non-invasive method of exploring airway inflammation which can provide additional information about such challenges and thus could be applied in OA diagnosis and monitoring. METHODS: We report the study carried out in a grain worker sensitized to Lepidoglyphus destructor (Ld), who suffered from mild asthma at the workplace. Skin prick test and specific serum IgE were measured. Ld-BPT was performed, and the changes in eosinophil rates, and ECP and tryptase levels in induced sputum were studied 30 min and 18 h after Ld-BPT. We also determined the changes in nonspecific bronchial hyperresponsiveness (NSBH), given as PD20 values. To assess the specificity of the changes, we also carried out sputum induction and methacholine challenge after barley-BPT. RESULTS: An isolated immediate response was obtained with Ld-BPT, while barley-BPT was negative. Induced sputum showed higher tryptase levels 30 min after Ld-BPT, and higher eosinophil and epithelial cell percentages and ECP levels 18 h after Ld-BPT. There was also a decrease in methacholine PD20 values after Ld-BPT. Those changes were not observed after barley-BPT. CONCLUSIONS: The study of eosinophilic and mast-cell markers in induced sputum provides additional knowledge about the inflammatory process occurring in the airways, suggesting that the study of induced sputum should be considered in the assessment of OA.     

Anti-soluble liver antigen (SLA) antibodies in chronic HCV infection

Hepatitis C infection is associated with autoimmune disorders, such as the production of autoantibodies. Anti-LKM1 and anti-LC1, immunomarkers of type 2 autoimmune hepatitis, have been previously associated with a HCV infection. Anti-Soluble-Liver-Antigen autoantibodies (SLA) are specifically associated with type 1 and type 2 autoimmune hepatitis and more closely related to patients who relapse after steroid therapy. The recent molecular cloning of the soluble liver antigen provides the opportunity to develop more specific tests for the detection of antibodies against it. The aim of this work is to characterize anti-soluble-liver autoantibodies in sera from patients chronically infected by HCV. A recombinant cDNA from activated Jurkat cells coding for the full length tRNP(Ser)Sec/SLA antigen was obtained. ELISA, Western Blot and immunoprecipitation tests were developed and used to search for linear and conformational epitopes recognized by anti-SLA antibodies in sera from patients chronically infected by HCV. Anti-soluble liver antigen antibodies were found in sera from 10.4% of HCV-infected patients. The prevalence was significantly increased to 27% when anti-LKM1 was also present. Most anti-SLA reactivity was directed against conformational epitopes on the antigen. The means titers by ELISA were lower than those obtained in type 2 AIH. The result of autoantibody isotyping showed a subclass restriction to IgG1 and also IgG4. This study shows the presence of anti-SLA antibodies in approximately 10% of HCV infected patients. The prevalence of SLA autoantibodies in HCV infected patients increases when LKM1 autoantibodies are also present. The relationship between the prevalence of this characteristic autoimmune hepatitis autoantibody and the implication of an autoimmune phenomenon in the liver injury of patients chronically infected by HCV needs further investigation.     

Serum levels of total IgE in non-allergic children

The purpose of this study was to establish the range of total serum IgE in a healthy population lacking personal and family history of allergy, as well as the influence of genetic factors (family history of allergy), environmental factors (degree of air pollution), age, and sex on the serum IgE levels. Using a commercial enzyme immunoassay (Phadezym IgE Prist) the mean serum level of IgE was determined in 363 non-atopic children from 0 to 12 years of age. The geometric mean of serum IgE increased according to age, indicating a positive correlation between both. Higher mean values of serum IgE were found for children with a family history of allergy, than for children without (27.82 and 14.49 U/ml respectively). The percentage of variation due to age was about 94.5% in children with no family history of allergy. The mean value of serum IgE increased with the degree of air pollution in the living area (15.49 U/ml in non-polluted areas, 20.78 U/ml in very polluted areas). However, the influence of air pollution was smaller than the influence of family history on the mean values of serum IgE. The mean value of serum IgE was not modified by sex.     

The ileoanal J pouch: radiographic evaluation

Endorectal ileoanal pull-through offers an attractive alternative to proctocolectomy and ileostomy for patients with ulcerative colitis, Gardner syndrome, and familial polyposis. To our knowledge, a careful radiographic analysis of the ileum, ileal pouch, and ileoanal anastomosis after ileoanal pull-through has not been reported. Thirty-two patients with ulcerative colitis, Gardner syndrome, and familial polyposis underwent colectomy, mucosal proctectomy, and endorectal ileoanal pull-through of a 15-cm ileal "J" pouch and loop ileostomy. Twenty-five (78%) of 32 of all the pouches radiographically demonstrated spiral folds extending from the middle of the pouch to the pectinate line. Other radiographic features included a mesenteric mass effect, pseudopolyps, and a central lucency that indicated intrapouch sutures. Radiographs provide useful information in the postoperative management of the ileal pull-through.     

Radioimmunoscintigraphy and radioimmunotherapy of renal cell carcinoma xenografts

From a panel of monoclonal antibodies (MAb) reactive with human renal cell carcinoma generated by this laboratory, three (designated A6H, C5H, and D5D) were selected for in vivo studies with a nude mouse xenograft model. These studies included 131I- and 111In-labeled MAb radioimmunoscintigraphy and 131I-labeled MAb radioimmunotherapy. In the imaging studies, these radiolabeled MAb allowed visualization of subcutaneous xenografts larger than 40 mg and subrenal capsule xenografts smaller than 20 mg. Comparisons of tumor to non-tumor tissue radiolabel distribution yielded unusually high ratios and depended on the MAb-xenograft combination. The 111In-radiolabeled A6H showed increased accumulation in the liver compared with 131I-A6H, but this still did not necessitate background subtraction for good visualization of small, subrenal capsule renal cell carcinoma xenografts. Radioimmunotherapy studies with 131I-A6H in BALB/c nu/nu mice bearing established renal cell carcinoma xenografts showed a prolonged (greater than 90 days) regression in tumor burden and possible "cures," whereas three sets of control mice showed progressive and rapid increases in tumor size. These studies indicated that MAb, which show good tissue biodistribution and high imaging sensitivity, could also be capable of delivering effective radiotherapy to the tumor when "human equivalent" radiolabeled-MAb doses are used.     

Isolation and partial characterization of neurofibrillary tangles and amyloid plaque core in Alzheimer's disease: immunohistological studies

Fractions enriched in neurofibrillary tangles (NFT) and amyloid fibrils were isolated from the cerebral cortex of three cases of senile dementia of the Alzheimer type. Distilled water suspensions of these fractions were excluded from all pore size gels and resisted digestion with various proteolytic enzymes. Formic acid/chloroform treatment of each fraction resulted in the appearance of 4,000-6,000, 15,000-17,000 and 24,000 molecular weight proteins, with concomitant diminution in the amount of excluded material at the top of each gel. The 4,000-6,000 dalton band was best seen in fractions containing randomly arranged amyloid fibrils, and its amino acid composition resembled that of the recently reported "beta" protein. A polyclonal antiserum to purified NFT reacted with tangles in neurons and in dystrophic neurites around plaques by immunoperoxidase staining. No reaction was obtained with cerebrovascular or plaque core amyloid immunohistologically, or with the 4-6 kD protein on immunoblots. Cross-reactivity with the neurofibrillary lesions occurring in Pick's disease, progressive supranuclear palsy, postencephalitic Parkinsonism and dementia pugilistica was also seen. Specific binding of this antiserum to the double filamentous structure was confirmed by immunoelectron microscopy. Although the presence of "beta" protein in both NFT and amyloid-containing fractions suggests that it may be an important constituent of both, cross-contamination cannot be excluded.     

Complicaciones durante la intubación traqueal repetida en la unidad de cuidados intensivos. Estudio prospectivo,observacional comparando primera intubación y reintubación

Background of the studyThe goal of the study was to compare the incidence of complications, technical difficulty of intubation and physiologic pre-intubation status between the first intubation and reintubation performed on the same patient in an ICU.Materials and methodsThe study was approved by the ethics committee of Galicia (Santiago-Lugo, code No. 2015-012). Due to the observational, noninterventional, and noninvasive design of this study, the need for written consent was waived by the ethics committee of Galicia. Patients requiring tracheal intubation and reintubation in the ICU were included in this prospective observational study. Main endpoint was to compare the incidence of complications, physiologic pre-intubation status, and the rate of technical difficulty of intubation between the first intubation and reintubation performed on the same patient in an ICU.Results and discussion504 patients were intubated in our ICU during the study period, and 82 (16%) required reintubation. There was no difference between the first intubation and reintubation regarding number of total complication (35% vs 33%; P = .86), hypotension (24% vs 24%; P = 1), hypoxia (26% vs 26%; P = 1), esophageal intubation (1% vs 1%; P = 1), and bronchoaspiration (2% vs 1%; P = .86). Physiologic pre-intubation status and technical difficulty of intubation did not differ between the first intubation and reintubation.ConclusionsIn our ICU patients requiring tracheal reintubation, incidence of complications, physiologic pre-intubation status, and technical difficulty of intubation did not differ between the first intubation and reintubation.     

Granuloma formation and parasite disintegration in porcine cysticercosis: comparison with human neurocysticercosis

Taenia solium cysticerci infect human beings and pigs, causing cysticercosis. In this study the pig was used as a model to characterize the immune response against cysticerci, given the difficulties in analysing the developing immune response in infected human brains. Metacestodes in different stages of viability or degeneration were isolated from the brain, heart and skeletal muscle of naturally infected swine, and the adjacent tissue was examined histologically. The immune response elicited by the cysticerci was classified into four separate stages. In stage I the parasites were surrounded by a thin layer of collagen type I, and by stage II there was a sparse inflammatory infiltrate. In stage III, granuloma formation was evident, and by stage IV the parasite was surrounded by an eosinophil-rich infiltrate and its vesicular membrane had begun to degenerate. The final stage, IV, was detected mainly in the heart but not in the brain. The granulomatous reaction in swine resembled that described previously in human patients, but differed in the abundance of eosinophils, the relative paucity of plasma cells, and the discrete deposition of collagen. These differences were probably due to the fact that in pigs the immune response can be examined earlier than in human patients, in whom sampling is inevitably made at a more chronic stage.     

β-Cyclodextrin tetradecasulfate/tetrahydrocortisol±minocycline as modulators of cancer therapies in vitro and in vivo against primary and metastatic lewis lung carcinoma

Tetrahydrocortisol, -cyclodextrin tetradecasulfate, and minocycline used alone or in combination are not very cytotoxic toward EMT-6 mouse mammary tumor cells growing in monolayer. Tetrahydrocortisol (100 M, 24 h) and -cyclodextrin tetradecasulfate (100 M, 24 h) protected EMT-6 cells from the cytotoxicity of CDDP, melphalan, 4-hydroperoxycyclophosphamide, BCNU, and X-rays under various conditions of oxygenation and pH. Minocycline (100 M, 24 h) either had no effect upon or was additive with the antitumor alkylating agents or X-rays in cytotoxic activity toward the EMT-6 cells in culture. The combination of the three modulators either had no effect upon or was to a small degree protective against the cytotoxicity of the antitumor alkylating agents or X-rays. The Lewis lung carcinoma was chosen for primary tumor growth-delay studies and tumor lung-metastases studies. Tetrahydrocortisol and -cyclodextrin tetradecasulfate were given in a 1:1 molar ratio by continuous infusion over 14 days, and minocycline was given i.p. over 14 days, from day 4 to day 18 post tumor implantation. The combination of tetrahydrocortisol/-cyclodextrin tetradecasulfate diminished the tumor growth delay induced by CDDP and melphalan and produced modest increases in the tumor growth delay produced by cyclophosphamide and radiation. Minocycline co-treatment increased the tumor growth delay produced by CDDP, melphalan, radiation, bleomycin, and, especially cyclophosphamide, where 4 of 12 animals receiving minocycline (14×5mg/kg, days 4–18) and cyclophosphamide (3×150 mg/kg, days, 7, 9, 11) were long-term survivors. The 3 modulators given in combination produced further increases in tumor growth delay with all of the cytotoxic therapies, and 5 of 12 of the animals treated with the 3-modulator combination and cyclophosphamide were long-term survivors. Although neither tetrahydrocortisol/-cyclodextrin tetradecasulfate, minocycline, nor the three modulator combination impacted the number of lung metastases, there was a decrease in the number of large lung metastases. Treatment with the cytotoxic therapies alone reduced the number of lung metastases. Addition of the modulators to treatment with the cytotoxic therapies resulted in a further reduction in the number of lung metastases. These results indicate that agents that inhibit the breakdown of the extracellular matrix can be useful additions to the treatment of solid tumors.Abbreviations 14(SO₄)ßCD -cyclodextrin tetradecasulfate - THC tetrahydrocortisol - CDDP cis-diamminedichloroplatinum(II) - 4-HC 4-hydroperoxycyclophosphamide - BCNU N,N-bis(2-chloroethyl)-N-nitrosourea - CAM chick embryo chorioallantoic membrane; IC₅₀, concentration of a drug required to kill 50% of the cells This work was supported by NIH grant P01-CA38493 and a grant from Bristol-Myers-Squibb, Inc., Wallingford, Connecticut