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Biomedical subjects

G Pauli

Publications and source records attributed to G Pauli.

At least 73 records · Page 4Linked to original sources

Quaternary ammonium compounds and occupational asthma.

OBJECTIVE: Quaternary ammonium compounds, among which benzalkonium chloride is one of the best-known, are commonly used as antiseptics, disinfectants, detergents and preservatives. They can cause occupational asthma, which however, has been rarely reported so far, despite wide use of these products. We report three such cases. Possible mechanisms causing asthma are discussed, taking into account their characteristics. METHODS AND RESULTS: Our patients, all female nurses, manifested asthma symptoms upon handling disinfectant solutions containing benzalkonium chloride. Work-related fall in PEFR was observed in all of them. The diagnosis was confirmed by challenge tests where the patients were exposed, in a closed chamber, to suspected disinfectant contained in a tray. All of the women developed early or delayed symptoms upon exposure. Similar challenge tests to placebo or other disinfectants devoid of quaternary ammonium compound were negative. CONCLUSION: These three cases, in addition to others reported in the literature, point out an as yet poorly known etiology of occupational asthma to quaternary ammonium compounds in hospital employees. The exact mechanism of the action remains unexplained.

Adult↗

Quantitative IgE inhibition experiments with purified recombinant allergens indicate pollen-derived allergens as the sensitizing agents responsible for many forms of plant food allergy.

BACKGROUND: Type I allergic symptoms in the oropharyngeal mucosa upon contact with plant-derived food in patients with pollen allergies have been termed oral allergy syndrome (OAS). IgE cross-reactivity between pollen and food allergens represents the molecular basis for this phenomenon. The sensitizing allergen source (pollen or plant food) in OAS is a controversial issue. OBJECTIVE: We sought to determine the primary sensitizing molecules in patients with OAS. METHODS: We used recombinant birch pollen (rBet v 1 and rBet v 2) and plant food allergens (apple, rMal d 1; celery, rApi g 1; and carrot, rDau c 1), as well as natural pollen (birch and timothy grass) and plant food (apple, peach, kiwi, hazelnut, celery, and carrot) allergens, to identify cross-reactive allergens by using qualitative immunoblot inhibitions. In addition, we determined the percentage of plant food-specific IgE that can be preadsorbed with recombinant and natural pollen allergens by quantitative RAST inhibitions by using sera from 71 patients with OAS. RESULTS: Preincubation of sera with recombinant and natural pollen allergens led to an almost complete inhibition of IgE binding to plant food allergens in Western blots, as well as in RAST inhibition experiments. In contrast, recombinant plant food allergens poorly inhibited IgE binding to Bet v 1. CONCLUSION: Most IgE epitopes in plant food recognized by patients with OAS are resembled by pollen allergens. Thus pollen allergens may be responsible for the elicitation and maintenance of OAS.

Adult↗

Comparative prognostic value of lactate dehydrogenase and neuron-specific enolase in small-cell lung cancer patients treated with platinum-based chemotherapy.

The influence of pretreatment serum levels of lactate dehydrogenase (LDH) and neuron-specific enolase (NSE) on survival was investigated in a series of 263 consecutive patients with small-cell lung cancer. LDH was elevated in one-half of the patients, NSE in 79%. Both were significantly higher when the disease was considered extensive than when it was limited. The markers were significantly correlated (r= 0.54, P=1.03 x 10(-20)), and both had a significant impact on survival in the univariate analysis. The multivariate survival analysis of the entire population showed that LDH, along with performance status, extent of disease, and albumin, was a more important prognostic factor than NSE. Only when LDH was removed from the model did NSE become an independent prognostic factor. In the separate multivariate survival analyses of limited and extensive disease, LDH remained an independent prognostic factor. For extensive disease, NSE did not even appear in the model when LDH was excluded; for limited stage disease, NSE did become a weak independent prognostic factor when LDH was excluded. In conclusion, LDH, which is less expensive to assay than NSE, is also a stronger independent prognostic factor for small-cell lung cancer and should be part of the initial work-up. In clinical trials, stratification for LDH levels should be considered because of its prognostic weight.

Adult↗

Hepatitis B and C among Berlin dental personnel: incidence, risk factors, and effectiveness of barrier prevention measures.

A study of 215 Berlin dentists and 108 dental assistants recruited at the 1997 Berlin Dental Society meeting assessed their occupational risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. HBV vaccine coverage, and barrier prevention methods used. Among dentists, 7% (95% CI 4-11) and 0.5% (95% CI 0-3) had serological evidence of previous HBV and HCV infection, respectively. Similar figures for dental assistants were 1% (95% CI 0-5) and 0% (95% CI 0-4). Only 74% of dentists and 63% of dental assistants reported HBV vaccination. Approximately half always used gloves, eye glasses, or face masks. HBV unvaccinated dentists whose patients had HBV risk factors had a greater risk of HBV infection; those who always wore face masks were at lower risk (OR 0.2, 95% CI 0.02-0.98). These data indicate that among Berlin dentists, the HCV risk was lower than that of HBV and that face masks may have lowered the risk of HBV. The use of eye glasses or gloves did not appear to lower the risk of HBV acquisition in this population.

Adult↗

Comparison of genetically engineered hypoallergenic rBet v 1 derivatives with rBet v 1 wild-type by skin prick and intradermal testing: results obtained in a French population.

BACKGROUND: Bet v 1, the major allergen in birch pollen, is recognized by more than 90% of patients allergic to birch in northern and central Europe. Immunotherapy is commonly performed with birch pollen extracts. Recently, hypoallergenic derivatives of Bet v 1 (rBet v 1 fragments, rBet v 1 dimer and trimer) were constructed and purified. OBJECTIVE: Our aim was to compare the allergenic activity of wild-type rBet v 1 with recombinant Bet v 1 derivatives (rBet v 1 fragments, dimer and trimer) with potentially reduced anaphylactic activity by skin testing in a French population. METHODS: Among the 36 birch pollen allergic patients included in the study, 29 were tested by skin prick testing and 30 by intradermal injections with purified monosubstances: rBet v 1 fragments (F1: aa1-74 and F2: aa75-160), Bet v 1 dimer and trimer. Intradermal tests were performed by the end-point intradermal titration method. Eight of the intradermally-tested patients were previously hyposensitized. Tests were performed over a period of 6 months (before, during and after birch pollen season); Bet v 1-specific IgE and IgG4 subclass responses were measured by immunoblotting and ELISA. RESULTS: All patients showed lower reactivity with the modified rBet v 1 allergens, both in skin prick and intradermal tests. In 25 and 23 out of 29 patients the lowest concentration of fragment 1 and 2, respectively, resulting in a positive prick test was 100-fold higher than the lowest concentration of monomer resulting in a positive prick test. For dimer it was 100-fold or more in 25 out of 29 patients, and for trimer it was 100-fold or superior in 26 out of 29 patients. By intradermal testing, the end-point concentration was 160-fold higher for trimer than for monomer in 24 patients and 40-fold higher in five patients. For the two fragments the end-point concentration was 160-fold higher in 20 out of 22 patients. CONCLUSION: Genetically modified hypoallergenic derivatives of the major birch pollen allergen, Bet v 1 showed reduced capacity to induce immediate type skin reactions. They may represent candidate molecules for immunotherapy of birch pollen allergy with reduced risk of anaphylactic side-effects.

Adolescent↗

Anaphylactic shock during endodontic treatment due to allergy to formaldehyde in a root canal sealant.

A 41-yr-old patient experienced an anaphylactic shock reaction caused by formaldehyde in a root canal sealant during endodontic treatment. The clinical events, positive skin tests, and a high level of immunoglobin E to formalin RAST (class 4) suggest the involvement of immunoglobin E-dependent mechanisms toward formaldehyde. This very infrequent observation in endodontic therapy focuses attention on the different pathological manifestations related to formalin, their mechanisms, and the prevention possibilities in dentistry.

Adult↗

Mechanisms of epithelial barrier impairment in HIV infection.

Diarrhea and malabsorption due to intestinal dysfunction are common symptoms in HIV infection. The pathophysiologic mechanisms of these alterations are often not known, and the role of HIV per se is still controversially discussed. We measured the epithelial transport and barrier function by means of a miniaturized Ussing chamber system in the duodenum of HIV-infected patients in different disease stages, determined by the CD4 cell count in the serum as well as symptoms in patients with and without diarrhea. We could show that diarrhea induced by HIV per se is caused by a leak flux mechanism due to impaired epithelial barrier function. Antisecretory therapy does not seem to be useful in these patients, because we did not find increased active ion secretion. Along the course of the HIV infection, the epithelial transport and barrier function varies with HIV disease stage (expressed by CD4 cell status). In addition, an in vitro model was studied to characterize the effect of HIV-infected human immune cells on the epithelial barrier function using the human colonic epithelial cell line HT-29/B6. HIV infection of human immune cells induced an increase in cytokine release--for example, TNF-alpha, IL-1 beta, IFN-alpha, and IFN-gamma--downregulating the epithelial barrier function of the human colonic epithelial cell line HT-29/B6. Taken together we postulate a specific stage-dependent cytokine pattern released from HIV-infected immune cells in the mucosa, which, corresponding to the HIV disease stage, is responsible for the variation in epithelial function.

Biopsy↗

Application of a fluorogenic PCR assay for typing and subtyping of influenza viruses in respiratory samples.

A fluorogenic PCR-based method (TaqMan-PCR) was developed for typing and subtyping of influenza virus genomes in clinical specimens. The TaqMan-PCR employs a probe technology that exploits the endogenous 5'-3' nuclease activity of the Taq DNA polymerase to allow direct detection of the amplicon by release of a fluorescent reporter during the PCR. Therefore, post-PCR analysis is avoided since hybridization with the fluorogenic probe and quantification of the amplified product is performed simultaneously during PCR cycling. The specificity of the method was evaluated on 86 influenza A (25 H1N1 and 61 H3N2) and 49 influenza B virus reference strains and isolates. The sensitivity of the technique was found to be at the level of 0.1 50% tissue culture infective dose. This TaqMan-PCR was applied prospectively to surveillance work by community-based sampling in Germany during the last two influenza seasons. Seven hundred five throat swabs were analyzed during the winter of 1997-1998. A total of 195 of 705 samples (28%) were positive by PCR. Influenza viruses could be isolated from 125 specimens (18%). During the 1998-1999 season, 1,840 respiratory samples were received. Influenza viruses were isolated from 281 specimens (15%) out of 525 throat swabs (29%) which were positive for influenza A or B virus by TaqMan-PCR. Further differentiation of influenza A virus-positive swabs revealed an intensive circulation of the subtype H3N2 during both seasons, 1997-1998 and 1998-1999. The TaqMan-PCR was much more sensitive than culture and revealed an excellent correlation for typing and subtyping of influenza viruses when samples were positive by both methods.

DNA Primers↗

Detection of human cytomegalovirus DNA by real-time quantitative PCR.

A real-time PCR assay was developed to quantify human cytomegalovirus (CMV) DNA. This assay was used to demonstrate a higher CMV DNA load in plasma of bone marrow transplant patients than in that of blood donors. The CMV load was higher in CMV antigen-positive patients than in antigen-negative patients.

Blood Donors↗

Evolution in the understanding of cross-reactivities of respiratory allergens: the role of recombinant allergens.

The aim of this review is to show the impact of the use of purified and recombinant allergens to discriminate between co- and cross-sensitization to respiratory allergens. The author describes the evolution of diagnostic tests over the last decades; the tests initially allowed the detection of simultaneously positive cutaneous tests and/or simultaneous positivity of specific IgE to different allergen extracts, but they did not differentiate cross-sensitization from co-sensitization. RAST inhibition studies with crude extracts then established cross-reactivity, but did not identify the cross-reactive allergens involved. Later, immunoblot and CRIE inhibition were able to detect multiple cross-reactive allergens and to assess their physicochemical properties. But it is only since purified and recombinant allergens have been used in the different investigations that identification of cross-reactive allergens has been made possible at a molecular level. This historical approach is illustrated by examples selected from some of the main respiratory allergen sources: tree pollen, grass pollen, weed pollen, acarids, cockroaches and mammalians. For each of these allergen sources, the author gives an updated presentation of major and minor cross-reactive allergen molecules and refers to the last decade's major publications concerning immunochemical investigations carried out in the field of cross-reactive respiratory allergens. Emphasis is placed on the clinical applications for allergic patients: improvement in the accuracy of the diagnosis of sensitization, new concepts of immunotherapy based on genetically engineered hypoallergenic variants of cross-reactive allergens used alone or in combination, evaluation of allergen load with environmental tests using monoclonal antibodies against cross-reactive allergens.

Acari↗

Pulmonary migratory infiltrates and pachypleuritis in a patient with Crohn's disease.

Crohn's disease can be associated with several respiratory manifestations. We report here a case of pulmonary migratory infiltrates associated with bilateral pleural thickening and peripheral eosinophilia. The histopathological findings show an association of necrotizing nodules, eosinophilic infiltration in the non-abscessed lung tissue, areas of non-caseating epithelioid granulomas, and an extensive pleural fibrosis. The different histopathological findings are detailed and the responsibility of either Crohn's disease or treatment by mesalazine is discussed.

Adult↗

[Elimination of airborne allergens from the household environment].

Exposure to allergens could be either a risk factor of sensitization and nonspecific hyperresponsiveness in genetically predisposed patients or a risk of onset of asthma attack in certain allergic asthma. During the past 20 years, in western countries the houses have become higher and the number of furred pets have increased and have been more kept inside the house which makes probable that exposure to indoor aeroallergen has increased. The development of new methods of allergen measurements allows a more precise identification of allergen source and reservoirs, an assessment of allergen exposure and a monitoring of allergen eviction methods. Concerning mite allergens, controlled studies which showed a clinical efficacy are those with a global mite eviction and at least a 6 months follow-up for cat and dog allergens, high efficiency-filters air cleaners or vacuum-cleaners are able to reduce airborne cat or dog allergen levels. According to the increasing number of papers about allergen eviction, it seems logical to propose allergen eviction as "first line treatment" of allergic asthma. In the future, it would be interesting to develop biological markers to identify more accurately patients who have a clinical improvement after allergen eviction.

Adolescent↗

[Respiratory allergies and household allergenic environment].

Based on immunoassay techniques used to identify and quantify major indoor allergens, epidemiological studies have demonstrated that level of exposure depends on the geographical situation (climate, urbanization) and that there is a relationship between exposure and sensitization of predisposed patients. Most of the major mite allergens are proteases. For mammals and cockroaches, the major allergens belong to the retinal protein binding group. Determination of the airborne characteristics of the major indoor allergens is helpful in better understanding the pathophysiology of asthma. In the future, more precise diagnosis and more efficient immunotherapy will be possible through the development of recombinant allergens. The efficacy of allergen avoidance in allergic asthma has been demonstrated in several studies. Thus the respective role of different household allergens should lead to improved diagnosis and treatment of allergic diseases.

Acari↗

[Recombinant allergens: diagnostic use and therapeutic perspectives].

Techniques of genetic engineering applied to allergens have enabled the production of recombinant allergens. The validation of recombinant allergens implies that their immunological activity and their identity with natural allergens might be confirmed by in vitro and in vivo techniques carried out on a sufficiently large number of allergic subjects. Currently available results for the principal pneumoallergens are reported. Thus the work of validating recombinant allergen BeTv1 has been confirmed by in vitro tests and also by skin tests and nasal and bronchial provocation tests. The association of four recombinant allergens of phleole has enabled the detection in vitro of sensitisation to germinated pollens in 94.5% of patients. For mites the validity of group 2 recombinant allergens has been confirmed. A system enabling the expression of glycosylation of recombinant proteins was necessary to validate recombinant proteins in group 1 allergens. The recombinant allergen Blot5 is recognised as being effective in the detection of sensitization to Blomia tropicalis, a domestic allergen in sub tropical countries. The recombinant allergens Bla g 4 and Bla g 5 have been tested in vitro and in vivo and reactions were positive in nearly 50% of subjects sensitive to cockroaches. The recombinant Asp f 1 has been tested in subjects suffering from allergic bronchopulmonary aspergillosis and is positive in 60-85% of cases. Some studies are available for recombinant allergens of certain animal antigens (Equ c 1, Bos d 2). The consequences of clarifying recombinant allergens are then analysed: obtaining better standardised allergens for diagnostic tests, studying the spectrum of specificities of IgE induced by an allergen, the quantification of specific IgE, a better approach to mixed allergies with the help of recombinant allergens of the principal mixed allergens. Some recent progress has led to the production of modified recombinant allergens: the synthesis of recombinant polypeptides corresponding to T epitopes, the production of isoform recombinant allergens with reduced allergenic activity, the production of recombinant allergens of modified allergenic molecules by directed mutations and the production of recombinant fragments of allergenic molecules. The use of modified recombinant allergens is a way of permitting research which would, in the future, lead to new modalities of specific immunotherapy.

Allergens↗

[IgE allergy due to formaldehyde paste during endodontic treatment. Apropos of 4 cases: 2 with anaphylactic shock and 2 with generalized urticaria].

We report 4 cases of allergic reaction to formaldehyde-containing root canal sealant after endodontic care: 2 anaphylactic shocks and 2 local reactions with generalized urticaria. Allergic IgE mediated mechanisms were suggested by the clinical presentation, skin tests and high levels of anti-formaldehyde IgE. These infrequent but potentially severe reactions after canal treatment led us to examine the involved mechanisms, the diagnostic procedure and the possibility of prevention in odontostomatology.

Adult↗

[Acute pleuro-pneumonitis resulting from leptospirosis].

We report a case of acute pneumonitis with pleural effusion and respiratory distress syndrome that was the inaugural sign of leptospirosis in a 37-year-old patient exposed to rat dejections at home. The patient was given penicillin and oxygen therapy with evacuation of the pleural effusion. Lung manifestations in leptospirosis usually occur as non-specific cough and hemoptysis. Pleural effusion is uncommon. Adult respiratory distress syndrome and profuse hemoptysis can also occur, requiring special care.

Adult↗

Risk and clearance of GB virus C/hepatitis G virus infection in homosexual men: A longitudinal study.

The risk and clearance of GB virus type C (GBV-C)/hepatitis G virus (HGV) infection was investigated in a cohort of homosexual men (n=180; median follow-up time, 7 years). The interaction between GBV-C/HGV RNA and antibodies against the E2 region of the virus, and the clinical impact of chronic GBV-C/HGV infection were studied. GBV-C/HGV RNA was detected by RT-PCR, and E2 antibodies were assessed by an immunoassay. At baseline, 63% of the participants had evidence of previous or current GBV-C/HGV infection. The GBV-C/HGV incidence rate was 2 per 100 person-years (95% confidence interval 0. 9-3.8) and was similar to the HIV incidence. The incidence of GBV-C/HGV infection was significantly higher in those reporting unprotected anal intercourse (3.6 per 100 person-years compared to 0 in the group without such sexual contacts). The occurrence of E2 antibodies was strongly associated with GBV-C/HGV RNA clearance. A loss of E2 antibodies was observed at a rate of 1.5 per 100 person-years. It was higher among HIV-infected individuals. Chronic GBV-C/HGV infection was not associated with clinical or biochemical evidence of liver disease.

Adult↗

Virus safety of avital bone tissue transplants: evaluation of sterilization steps of spongiosa cuboids using a peracetic acid-methanol mixture.

The aim of this study was to validate the virus-inactivating/eliminating capacity of the manufacturing process of spongiosa cuboids. Both the sterilization step with peracetic acid (PAA)/ethanol and the defatting step of bones with chloroform/methanol (2:1, v/v) were investigated. Relevant enveloped, non-enveloped, and model viruses belonging to different virus families were included in the investigation: human immunodeficiency virus type 2 (HIV-2), hepatitis A virus (HAV), poliovirus (PV-1), pseudorabies virus (PRV), porcine parvovirus (PPV), and bovine virus diarrhoea virus (BVDV). Treatment of virus-spiked spongiosa cuboids for 4 hours at room temperature (RT) with 1% PAA/24% ethanol (PES) efficiently inactivated most viruses. Titres were reduced by more than 4 log(10)with the exception of HAV. The defatting step with chloroform/methanol reduced HAV titres by a factor of >/=7.0 log(10). From these results it can be concluded that the treatment of spongiosa cuboids with (i) chloroform/methanol and (ii) 1% PAA/24% ethanol solution leads to a virus-safe medicinal product.

Bone Transplantation↗