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Biomedical subjects

G Halpern

Publications and source records attributed to G Halpern.

15 recordsLinked to original sources

Amyloidosis in familial mediterranean fever is associated with a specific ancestral haplotype in the MEFV locus.

Familial Mediterranean fever (FMF) is a recessive disease characterized by recurrent attacks of inflammation of serosal membranes, and the gene responsible, MEFV, has been recently identified. Amyloidosis is considered to be the most severe complication. Since colchicine is effective in preventing FMF amyloidosis and since this process can develop even prior to the FMF symptoms, lifelong colchicine treatment is recommended for all FMF patients. Identification of the factor which determines amyloidosis will allow treatment to be directed only to those at risk. In order to investigate the association between amyloidosis and MEFV haplotypes, we studied 56 families from three ethnic groups. We compared the haplotypes of FMF patients with and without amyloidosis in each ethnic group separately and identified 14 different MEFV core haplotypes. A significant association (P < 0.004) was found between amyloidosis and a specific core haplotype, 153bp:104bp at markers D16S3370 and D16S2617, respectively. Amyloidosis was present in 20 out of 70 homozygotes for this haplotype and in 6 out of 35 compound heterozygotes for this and other core haplotypes. None of the patients who did not carry this allele had amyloidosis. There was no association between the various haplotypes and severity of the FMF symptoms, age of onset, or age at commencement of colchicine. Further investigation of the MEFV haplotypes in additional patients is recommended as such an association may save many mildly affected or asymptomatic patients with non-amyloidotic genotypes from receiving unnecessary lifelong colchicine treatment.

Adolescent↗

Detection of antifood IgE by in vitro tests and diagnosis of food allergy.

The diagnosis of IgE-dependent food allergy relies on the demonstration of specific IgE by prick tests or biological tests. A radioimmunoassay (RAST Phadebas) is completed by several immuno-enzymatic methods: RAST Phadezym, FAST, MAST-CLA, AlaSTAT, etc. The allergen is bound to solid or liquid phases, by different binding agents. Various enzyme-substrate systems, and several systems for expression are used (RIA, fluorescence, chemoluminescence, colorimetry, etc.). Another aspect of modern technics is the trend towards high automated processes. A second group of tests aims to detect the release of mediators from sensitized basophils: leucocyte histamine release test, human basophil degranulation test and a leucocyte leukotriene release test. The specificity of tests for detection of anti-food IgE is lessened by numerous cross reactivities between pollens, fruit, and vegetable. The study of the sensitivity of such tests needs strictly standardized food challenge tests in order to firmly establish the diagnosis of food allergy. Multiscreen tests have to be assessed, in order to validate their efficacy for detecting frequency allergens. Whatever the test to be used, its positivity means only sensitization, and food challenge tests are mandatory to recognize true food allergy, as latent sensitization to food is a current phenomenon in atopic children. The possibility of reliable diagnosis of food allergy by using challenge tests makes now possible and advisable to set up quality controls for all biological tests applied to the detection of antifood IgE, thanks to the possibility to dispose of reference sera.

Adult↗

Localization, molecular weight and immunoglobulin subclass response to Aspergillus fumigatus allergens in acute bronchopulmonary aspergillosis.

A specimen of Aspergillus fumigatus was isolated from a patient with acute bronchopulmonary aspergillosis (ABPA). Cultures were allowed to propagate and were separated into spores and mycelium to greater than 95% homogeneity. Extracts of both the spores and mycelium were prepared and used for study by both dot blot analysis and immunoblotting to study the major allergens. By dot blot analysis, 22 of 22 patients with ABPA and none of 10 healthy controls reacted with mycelium when probed for both IgG and IgE anti-Aspergillus reactivity. Similar results were obtained when these extracts were separated on polyacrylamide gel electrophoresis and then probed; this included both IgG and IgE reactivity. Further, the reactivity to preparations of whole extract was absorbed with mycelium but not spores. Several distinct protein bands were detected with IgG, ranging from 30 to 110 kilodaltons (kD). In contrast, the majority of patients with ABPA, when studied for IgE reactivity, reacted only with a 70-kD protein, although 1 out of 22 patients reacted with a 30-kD protein. Subclass analysis of IgG reactivity demonstrated that 90% of reactive sera contained IgG2 and 73% IgG4 reactivity. IgG1 and IgG3 reactivity were present but less frequently detected. The use of immunoblotting will enable the identification of relevant allergens. Further, the demonstration that the allergenicity is located primarily in mycelium will allow more definitive studies of allergen isolation for studies of reactivity and, ultimately, cloning of the 70-kD protein and, finally, epitope mapping.

Acute Disease↗

Grass pollen immunotherapy: a single year double-blind, placebo-controlled study in patients with grass pollen-induced asthma and rhinitis.

Fifteen grass pollen--sensitive asthmatic patients were selected from 200 patients with grass pollenosis on the basis of positive SPTs and RASTs that were restricted to grass pollens (except Bermuda grass), no previous IT, and residence and occupation in an area monitored by serial pollen counts. They underwent a double-blind trial of specific IT with a mixture of three grass pollen--aqueous extracts (velvet, sweet vernal, and timothy) or placebo. After 10 mo, the mean maintenance dose of pollen extract (assayed by RAST inhibition) in eight actively treated patients was 6000 RAST units (range 3000 to 8000) and the mean total dose was 18,700 RAST units (range 10,200 to 30,000). Results were assessment done by the following clinical and immunological data: (1) during the pollen season, daily symptom scores; (2) PD 20% FEV1, IgE antibody to timothy by RAST in serum and in nasal secretions, serum IgG antibody to purified timothy allergen D by solid-phase radioimmunoassay, and the four IgG subclass antibodies by enzyme immunoassay were all measured before treatment and before and after the pollen season. Symptom scores of both treated patients and controls correlated with pollen counts (R = 0.88, p less than 0.05 and R = 0.71, p less than 0.05, respectively). There was a significant difference between the mean symptom score values of treated patients versus controls (Kruskal-Wallis test, p less than 0.001). No significant differences or changes either in the PD 20% FEV1 or IgE antibody to timothy in serum and nasal secretions were found in the two groups before or after IT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Treatment of malignant biliary obstruction by endoscopic implantation of iridium 192 using a new double lumen endoprosthesis.

Iridium 192 seeds contained in a ribbon were preloaded into a new double lumen 11 Fr endoprosthesis which was then inserted into malignant strictures of the bile duct and ampulla and left in place for 48 hours until 5000 rads were delivered to the tumor. The procedure was carried out in 14 patients (7 women, 7 men; mean age, 63.2 years; range, 46 to 86 years). Six patients were treated for cholangiocarcinomas, four with pancreatic carcinomas, and four with ampullary carcinomas. No complications occurred. The mean survival of the group was 7 months (range, 3 days to 27 months). This new technique provides both intraluminal brachytherapy and biliary drainage and is inserted intraduodenally across the papilla of Vater avoiding puncture of the liver and external hardware required by the percutaneous technique and hardware necessitated with a nasobiliary tube. Following removal of the iridium prosthesis, a large caliber endoprosthesis is inserted for continued decompression. Because of proven efficacy of endoprostheses, this new technique should be considered when intraluminal irradiation is indicated.

Adenoma, Bile Duct↗

The evaluation of immediate hypersensitivity reactions: current concepts and future directions.

In the past, and for the majority of clinicians, methods of evaluating allergic reactions have centered on attempts to associate specific allergen contact with induction of symptoms. In this regard, it has always been emphasized that a careful history obtained by a knowledgeable physician is the single most important aspect of an allergic evaluation. Attention to the nature of the reaction and its proximity to possible allergic contact, and variations based on seasonal, regional and climatic changes, as well as avoidance and modification by medication can do more to establish a probable cause and effect relationship than any isolated test. However, there are now a multitude of in vivo and in vitro tests which may be employed to confirm or deny a clinical suspicion of a specific allergen-induced reaction. The majority of these procedures have less variability but suffer from the traditional problems of the imprecision of allergens. Additionally, in the case of skin testing, inhalation challenges and histamine release, these tests may be used to quantitate the degree of reactivity by titration of the response with varying doses of antigen. The improvement in allergy testing has occurred because of the better quantitation of some in vitro testing and will improve with standardization of extracts. The latter may some day include the use of recombinant allergens.

Drug Hypersensitivity↗

Modification of human LDL by in vitro incubation with cigarette smoke or copper ions: implications for allergies, asthma and atherosclerosis.

Cigarette smoking has been linked to a higher risk of not only atherosclerosis and related diseases, but asthma and allergies as well. The mechanisms linking smoking to these diseases may be due in part to increased low density lipoprotein (LDL) modification. In the current study, we compared the modification in vitro of LDL isolated from healthy volunteers that had been exposed to either the gas phase of cigarette smoke or copper ion mediated oxidation. The study used as measures of modification/damage the levels of protein carbonyl groups, changes in electrophoretic mobility on agarose gel electrophoresis and levels of thiobarbituric-reacting substances. Other measures used to assess other aspects of LDL modification included SDS PAGE and immunoblotting. Both copper ion or exposure to the gas phase of cigarette smoke increased electrophoretic mobility of LDL but the increase was greater in the gas phase smoke group. In contrast, thiobarbituric reacting substance levels were increased primarily in copper oxidized LDL. Protein carbonyl levels were increased to a similar extent in both copper ion and smoke exposed samples. Addition of EDTA prevented the modifications found upon copper mediated oxidation of LDL, but EDTA did not prevent the modification of the gas phase cigarette smoke exposed LDL. In summary, the results indicate that protein carbonyl formation can be used as a measure of the modification of LDL particles and, using several different assessment techniques, there are distinct differences in the modified LDL produced by in vitro incubation with gas phase cigarette smoke relative to that found upon incubation of LDL with copper ion. The in vitro smoking-produced LDL modifications may potentially be relevant to the process of lipoprotein modification in vivo and to the subsequent biological effects of these modified lipoproteins on processes affected by the immune system involvement, such as atherosclerosis and allergy/asthma.

Aerosols↗