Biomedical subjects
Publications and source records attributed to G Pauli.
The differential diagnosis between infectious complications and tumor progression is sometimes difficult in patients given cytotoxic drugs. We report a case of diffuse interstitial lung disease induced by gemcitabine, a new agent used for the treatment of advanced-stage non-small-cell lung cancer.
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We report the case of a 28-year old man suffering from rhinitis and asthma which appeared 8 years after exposure to different woods, especially abachi wood. Serial PEFR monitoring at work and away from work were consistent with occupational asthma. Spirometry showed an airway obstruction, and metacholine inhalation test was positive. Skin prick-tests performed with different woods were only positive to abachi wood extract. The search for specific IgE was positive to abachi wood (4, 98 KU/l, class 3). The diagnosis of occupational asthma caused by exposure to abachi wood was established, the mechanism underlying this asthma was IgE mediated. Despite respiratory protection measures, the patient had persisting symptoms and was laid off. The German service for social cover asked for an expert evaluation: specific nasal and inhalation provocation tests performed by exposure to fine abachi wood dust were positive. This is an observation with a double significance: first, although the mechanisms underlying wood occupational asthma remain largely unknown, an IgE mechanism for abachi wood was demonstrated; second, legislation is different in France and Germany where occupational asthma will only be acknowledged if inhalation tests are positive.
Genotypic and phenotypic resistance of viral reverse transcriptase (RT) and protease (PR) was determined for 64 therapy-naive, HIV-1-infected seroconverters of the German Seroconverter Study coordinated by the Robert Koch-Institut, Berlin. The date of seroconversion of patients and the laboratory, clinical, and therapeutic follow-up data were documented. Samples were collected between 1996 and 1999. Phenotypic resistant HIV-1 were found in 8 (13%) seroconverters; in most cases resistance was weak and mainly directed against RT inhibitors (4 nucleoside reverse transcriptase inhibitors [NRTIs], 2 nonnucleoside reverse transcriptase inhibitors [NNRTIs], 1 combination NRTI/NNRTI). Only one infection with a weak PR inhibitor resistance was identified. Transmission of multidrug-resistant HIV-1 has not yet been observed. Frequently at least one or more amino acid mutations associated with antiretroviral drug resistance were detected by genotypic analysis. The mean number of resistance-associated mutations in the RT of the transmitted virus has increased significantly since 1996. Studies have shown the improved benefit of initial antiretroviral therapy if based on genotypic resistance data. In view of the considerably high level of transmission of resistant HIV-1 in Germany, which is also seen in other studies in Europe and the United States, we suggest determining the genotypic resistance pattern before starting therapy of newly HIV-1-infected patients.
Different procedures are available to inactivate bacteria and fungi, including their spores, as well as viruses in human bone transplants. The most efficient methods are considered to be gamma irradiation and thermal inactivation as well as chemical sterilization methods like the peracetic acid-ethanol treatment (PES). Following national and international standards or draft standards, the antimicrobial effectiveness of this procedure was evaluated. Due to the standardizable size as well as the clinical relevance, defatted human spongiosa cuboids (15x15x15 mm) served as model system. After treatment with PES for 2 and 4 hours, respectively, the titre of living micro-organisms was determined in the supernatant and the cuboid. A reduction in the titre of viable micro-organisms below the detection level (reduction factor >5 log10) was already achieved after an incubation time of 2 hours (Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, Bacillus subtilis, Clostridium sporogenes, Mycobacterium terrae, Candida albicans as well as spores of Bacillus subtilis). No viable micro-organisms could be detected in any of the PES-treated test cuboids. Spores of Aspergillus niger were also completely inactivated. The PES procedure proved to be a reliable method for the sterilization of human bone transplants derived from spongiosa.
BACKGROUND: Cetirizine and fexofenadine, the active metabolite of terfenadine, are powerful and well-tolerated H1 receptor antagonists effective in the treatment of skin and nose atopic diseases. OBJECTIVE: We have compared the pharmacodynamic activity of the two antihistamines at therapeutic dosages, cetirizine at 10 mg and fexofenadine at 120 mg and 180 mg, on histamine-induced skin reactivity during a 24-hour period after single intake. METHODS: Twenty-six healthy volunteers participated in a randomized, double-blind, crossover, placebo-controlled study. The areas of wheal and flare induced by histamine (100 mg/mL) administered by prick test were measured at 0, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose. Statistical analysis of the areas under the time-response curves was performed by a Friedman's ANOVA followed by a Wilcoxon test and Bonferroni's correction. RESULTS: The three active treatments clearly inhibited the wheal and flare areas throughout the 24-hour period compared with placebo. Maximal inhibition occurred at 4 hours postdose. Between 4 and 24 hours postdose, the time course of inhibition by cetirizine differed significantly (P < 0.001) from that by fexofenadine at either dose, which did not differ from each other. At 24 hours, fexofenadine inhibited <40% of the skin reaction, whereas cetirizine reduced 60% of the wheal. The duration of effect, considered as the time for wheal to be inhibited by at least 70%, also significantly favored cetirizine (19 hours) compared with fexofenadine (9.3 and 8.5 hours for 180 and 120 mg, respectively; P < 0.001). Consistency of activity was evaluated by the frequency of total inhibition of the wheal (> or =95%). Consistency was observed in 26 of 26 participants for cetirizine, 21 of 26 for fexofenadine, 180 mg, and 10 of 26 for fexofenadine, 120 mg (P < 0.001), suggesting better consistency for cetirizine. There was no serious adverse event. CONCLUSIONS: Our study clearly shows better duration of action and consistency of the antihistaminic activity of cetirizine compared with fexofenadine (120 and 180 mg) in the histamine-induced skin reaction during a 24-hour period.
Several procedures for inactivating viruses are used presently in the context of bone tissue transplants. Common methods used are gamma irradiation (25 kGy), treatment with moist heat (82.5 degrees C/15 min., lobator-sd2-system) as well as chemical sterilisation using peracetic acid-ethanol treatment (PES, 2% peracetic acid, 96% ethanol, Aqua [2:1:1], 200 mbar, agitation, 4 hours). Based on national and international guidelines, we tested the antivirucidal effectiveness of these methods in human bone transplants. Three enveloped viruses: human immunodeficiency virus type 2 (HIV-2), pseudorabies virus (PRV), bovine virus diarrhoea virus (BVDV), and three non-enveloped viruses were used: hepatitis A virus (HAV), poliovirus (PV-1), porcine/bovine parvovirus (PPV, BPV). Defatted spongiosa cuboids served as model in chemical treatment experiments, while cortical diaphyses were used in gamma irradiation experiments, and the effects of thermal treatment were tested in prepared femoral heads. The log(10) reduction was measured by cytopathogenic effects after virus titration (TCID(50)/mL). A dose of at least 33.9 kGy (bone model) at -30 +/- 5 degrees C was necessary to achieve a sufficient reduction (4 log(10) steps) of BPV, the most resistant one of all viruses investigated. Thermal treatment as well as PES treatment led to a reduction of virus titres by more than 4 log(10). Only HAV showed a reduction below 4 log(10) (2.87) with PES. After validation of the defatting step included for HAV-infected cells, a HAV-reduction of over 7 log(10) was found. All three sterilisation methods tested are recommended for bone transplant sterilisation, but only provided that additional safety measures (anamnestic informations, infectious serology, PCR in case of multiorgan donors) are taken.
BACKGROUND: Repeated inhalation of allergen at low-dose induces an increase in bronchial hyper-responsiveness, without any associated symptom. The concomitant events in the bronchus have not been described. OBJECTIVE: We have studied the dynamic number of mast cells in the airways of patients with mild asthma before and after repeated inhalation of allergen at low-dose and the expression of nerve growth factor (NGF), which is reported to promote growth and survival of mast cells. METHODS: Twelve patients with mild asthma to cat allergen were enrolled at random in a blind placebo-controlled study, and submitted to repeated low-dose allergen exposure (1/5 of the provocative dose). Mast cells were immunolocalized using an antibody against mast cell tryptase. NGF and its high affinity receptor, TrkA, were immunolocalized using anti-NGF and anti-TrkA antibodies, respectively. NGF mRNA was quantified by competitive polymerase chain reaction (PCR) after reverse transcription of total RNA extracted from bronchial biopsy. NGF protein levels were measured by ELISA in bronchoalveolar lavage (BAL) fluid. RESULTS: Bronchial mast cell number was increased significantly after allergen exposure as compared with before. NGF expression in the bronchus was immunolocalized mainly to epithelial cells, but also to fibroblasts, blood vessels, and a few infiltrated cells. NGF mRNA levels in bronchial biopsies were increased significantly after allergen exposure. The high affinity receptor for NGF, TrkA, was immunolocalized to the infiltrated mast cell membrane. CONCLUSION: Our study shows that the increase in the number of mast cells and in the expression of NGF induced by allergen exposure in the bronchus of asthmatic patients is occurring before the onset of symptoms. In addition, our finding of the presence of the TrkA receptor on the membrane of the infiltrated mast cell in situ brings evidence of the mast cell as a target cell for the growth factor activity of NGF in the airways in asthma.
UNLABELLED: Endotoxins found in occupational settings constitute a risk factor in the severity of respiratory allergic symptoms. OBJECTIVES: To assess the airborne concentrations of major rat allergen (Rat n 1) and endotoxin under various circumstances. METHODS: We took 483 airborne samples from 12 sites: 114 individual samples for endotoxin measurements and 113 for Rat n 1, from 38 workers (nine animal technicians, nine laboratory technicians, nine scientists and 11 students); and 256 static samples in rat rooms and experimental rooms, with or without disturbance, for simultaneous endotoxin and Rat n 1 measurements. Rat n 1 was measured with a two-site monoclonal ELISA and endotoxins with the Limulus method. RESULTS: Airborne Rat n 1 and endotoxin were significantly higher in rat rooms than in experimental rooms. Animal technicians had the greatest exposure to both Rat n 1 and endotoxin. Cage cleaning and rat feeding induced the highest exposure to Rat n 1 and endotoxin. Furthermore, we observed no significant difference in endotoxin exposure between researchers with or without rat contact during the sample period. There was no correlation between the number of rats present and airborne endotoxin concentrations. CONCLUSIONS: Exposure to airborne Rat n 1 and endotoxin is higher during cleaning and feeding tasks than during any other task, we feel that a major source of both is contaminated bedding that becomes airborne during disturbance.
BACKGROUND: We report the case of a road worker with a food allergy to banana, who developed urticaria and rhinitis when cutting shrubs of Ficus benjamina and breadfruit. He did not develop an allergy to latex of Hevea brasiliensis. RESULTS: Sensitization to latex of F. benjamina, H. brasiliensis, breadfruit and banana was demonstrated using skin tests and specific IgE measurements. RAST inhibitions procedures showed that specific IgE to breadfruit latex cross-reacted more strongly with latex of H. brasiliensis and banana than with latex of F. benjamina with the same extract. CONCLUSION: Given the wide distribution of Moracea trees in tropical regions, sensitization to latex of H. brasiliensis and banana could be a consequence of sensitization to Moracea members; F. benjamina does not seem to be the only Moracea responsible for cross-allergy with latex and fruit. Consequently, it seems interesting to test other members of the Moracea family in patients sensitized to latex of H. brasiliensis and banana. Sensitization to breadfruit could be a risk factor for sensitization to latex of H. brasiliensis.
We report 13 cases of nasosinusal sarcoidosis. Sarcoidosis is a chronic, non caseating granulomatous disease. Nasosinusal involment is rare or exceptional and may be isolated (1 case in our series) or associated (12 cases in our series) with other lesions of the chest, skin, liver, spleen, bone, eyes, salivary glands, peripheral lymph nodes or with neurosarcoidosis. The clinical and CT features are various and often non specific. Nasal biopsy guided by physical examination is easy and constitute the main diagnostic criterion. The course of nasosinusal sarcoidosis is variable and no standard treatment has been established. Response to local or systemic corticosteroid therapy is also variable. The recurrence is frequent after tapering off or interrupting corticosteroids that also have important side effects.
Mite allergens are the main allergens in indoor environment. Using different means of assessing exposure to house dust mites (Acarex-test, major allergen (Der p 1 + Der f 1, Der p 2 + Der f 2), content measured by ELISA) has allowed better identification of mite reservoirs and allergens in patients' homes. House dust mite control measures are based on the knowledge of factors contributing to mite development, especially indoor relative humidity. Mite allergen avoidance strategies include 3 different methods: avoidance of mite producing allergens, elimination of mite reservoirs, especially textile reservoirs, dwellings designed so as to inhibit mite proliferation. Only controlled trials can estimate patients' compliance with proposed avoidance measures. Avoidance protocols should be adjusted to each individual by medical indoor environment counselors in order to optimize mite allergen reduction.
We report the case of a 38 year-old man admitted for the treatment of a neuroendocrine carcinoma of the lung with multiple bone metastases. At the diagnosis, the serum biochemistry revealed an evidence of malignant hypercalcemia with acute renal impairment. At this point, a Tc 99-m MDP bone scan was performed and showed intense uptake throughout the gastric walls. The patient underwent a repeat bone scan after normalization of biochemistry; no more abnormal uptake was noted in the stomach. Hypercalcemia is an abnormality of the calcium metabolism frequently associated with malignant condition. Metastatic calcification results from increased accumulation of the calcium-phosphate salts in different tissues related to a local physiological alcalinity. Usually reversible, metastatic calcifications appear as various extraskeletal uptake at Tc 99-m MDP bone scan.
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A real-time quantitative polymerase chain reaction assay was devised to determine the load of human herpesvirus (HHV)-6A and -6B DNA in paired samples of plasma and peripheral blood leukocytes (PBL) of 25 bone marrow transplant patients. The assay detects HHV-6 DNA variants A and B in a linear range of 10(7)-10(1) genome equivalents per assay. Viral DNA was measured in 336 paired DNA PBL samples and in corresponding plasma samples. HHV-6A and/or -6B DNA was detected in PBL of 23 of 25 patients and in plasma of 24 of 25 patients. HHV-6B was the predominant variant found in PBL and also was detected in the corresponding plasma. Surprisingly, only 1 of 25 patients had detectable HHV-6A DNA in PBL, although 23 of 25 patients were positive for HHV-6A DNA in plasma. HHV-6 DNA load in plasma was significantly higher for HHV-6A than for HHV-6B (P=.0066).
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Chimeric bcr/abl fusion proteins are thought to be the molecular 'pathogen' of chronic myelogenous leukaemia (CML). Expression levels of the respective fusion RNAs reflect disease progression as well as remission upon therapeutic intervention in CML patients. However, there is no quick and reliable method that would allow the quantitative routine monitoring of bcr/abl hybrid transcripts. A fluorescent probe-based PCR assay (TaqMan) has been described to quantitfy the exact amount of target sequences. We have established TaqMan real-time RT-PCRs for M-bcr/abl (b2a2, b2a3, b3a2, b3a3) and m-bcr/abl (e1a2) fusion transcripts as well as for beta-actin. All PCRs quantified as little as 10 copies/100 ng total cDNA. In order to investigate whether this procedure is appropriate for routine diagnostic monitoring, we performed retrospective measurements on 9 documented CML disease courses. Our data show that ongoing or relapsing CML is paralleled by increasing peripheral levels of bcr/abl fusion RNAs. Furthermore, sucessful anti-leukemic treatment is reflected by decreasing absolute bcr/abl transcript numbers. In contrast with conventional bcr/abl PCR techniques we could distinguish single positive values and gradually increasing copy numbers.