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Biomedical subjects

G Pauli

Publications and source records attributed to G Pauli.

At least 145 records · Page 8Linked to original sources

[Radiation- and chemically-induced respiratory manifestations].

There are frequently respiratory complications with cancer particularly in primary lung carcinoma. Among these are bronchopulmonary infections with or without endobronchial obstruction, carcinomatous lymphangitis, thromboembolic disease and haemorrhagic disease as well. Radiotherapy and chemotherapy may induce various respiratory complications which diagnosis can be of varying shades of difficulty. The classical post radiation pneumonitis occurring exclusively in the field of radiation hardly poses any problem unless it could be masking a recurrence. Certain clinical manifestations address very difficult problems of differential diagnosis by their lack of specificity and by their often unforeseeable character (except for bleomycin fibrosis which is perfectly dose dependent). Moreover patients often have multiple treatments and the identification of the single responsible agent becomes very difficult. We will not discuss here the infectious or secondary haemorrhagic complications of radiotherapy or chemotherapy but rather the anaphylactic manifestations, diffuse interstitial pneumonia with lymphocytic alveolitis or fibrosis, eosinophilic pneumonia, non-cardiogenic pulmonary oedema, bronchiolitis obliterans with organising pneumonia and the rare pulmonary vascular disorders such as pulmonary veno-occlusive disease.

Alveolitis, Extrinsic Allergic↗

[Pollen environment and its evaluation].

We review the methods available for determining airborne pollen. In addition to the classical gravimetric and volumetric methods, new immunochemical techniques are also used for detecting allergenic pollen and measuring of the size of allergen-carrying particles. Pollen counts are available in France for 39 urban sites. In the last decade changes in the pollen environment have basically concerned higher counts from resinous trees in southern France and birch tree counts in northern France as well as a lesser role for ash trees. Among the recent acquisitions, it has been demonstrated that allergens are present in twigs and leaves, or even the bark of certain trees. Interactions with atmospheric pollution is better understood and could be a contributing factor to the increasing number of people allergic to pollen. Pollen allergens can be carried on particles of various sizes and immunochemical studies have demonstrated that gramineous pollen allergens can be carried on starch particles less than 3 mu in diameter. These recent studies would explain the apparent disagreement between pollen counts and the number of clinical manifestations.

Air Pollutants↗

Selective endocytosis of fluorothymidine and azidothymidine coupled to LDL into HIV infected mononuclear cells.

Drug targeting via lipoproteins may be of benefit for use of cytotoxic drugs like fluorothymidine (FLT) or azidothymidine (AZT). Both drugs are potent inhibitors of the human immunodeficiency virus (HIV) reverse transcriptase and are used in the therapy of HIV infection. With regard to this project, the selective endocytosis in HIV infected human macrophages was studied after covalent coupling of AZT and LDL to low density lipoproteins (LDL). Cultured human macrophages and the lymphocytic Molt 4/8 cell line were infected with HIV-1 in vitro and subsequently treated with FLT-LDL or AZT-LDL. Viral replication was followed by determination of cell-released capsid antigen p24. Internalisation into HIV-1 infected human macrophages by the scavenger receptor pathway leads to a dose dependent inhibition of HIV replication. Otherwise, in HIV infected, but scavenger receptor missing lymphocytes (Molt 4/8 cells), neither endocytosis nor inhibition of HIV replication results. Thus, covalent coupling of drugs to LDL leads to a macrophage specific transport. This strategy could possibly avoid toxic side effects in the therapeutic use of antiretroviral drugs and thus may open a way for an earlier chemotherapy in HIV infection.

Cells, Cultured↗

Transmission of HIV-1 from productively infected mature Langerhans cells to primary CD4+ T lymphocytes results in altered T cell responses with enhanced production of IFN-gamma and IL-10.

Mature Langerhans cells (mLC), the ex vivo correlates of interdigitating dendritic cells (IDC), are susceptible to infection with HIV-1. As IDC are important activators of T helper (Th) cells in vivo, we examined the interaction of HIV-1-infected mLC with CD4+ T lymphocytes. HIV-1-infected mLC readily formed clusters with the T cells and efficiently transmitted HIV-1 to the CD4+ Th cells. Formation of syncytia between mLC and T cells was initiated by HIV-1-infected mLC. In the clusters of HIV-1-infected mLC and activated T cells a massive HIV-1 production was observed leading to the subsequent elimination of the activated and infected T helper cells. Examination of the cytokine pattern produced during interaction of infected mLC with CD4+ T cells revealed an enhanced production of IFN-gamma and IL-10 in the cocultures. These results suggest that during antigen presentation-driven T cell activation by IDC in the lymphoid tissues, HIV-1-infected IDC might efficiently transmit the virus to Th cells, leading to altered Th cell responses.

CD4-Positive T-Lymphocytes↗

Comparison of recombinant timothy grass pollen allergens with natural extract for diagnosis of grass pollen allergy in different populations.

BACKGROUND: Complementary DNAs coding for the major timothy grass pollen (Phleum pratense) allergens Phl p 1, Phl p 2, and Phl p 5 and birch profilin were isolated, expressed as recombinant nonfusion proteins in Escherichia coli, and purified. OBJECTIVE: In this study the in vitro IgE-binding capacity of recombinant Phl p 1, Phl p 2, Phl p 5, and birch profilin and their IgE recognition frequencies were investigated by using sera from different populations. METHODS: One hundred eighty-three sera from patients allergic to grass pollen were obtained from different populations in Europe, Japan, and Canada. The sera were selected according to clinical criteria, skin testing, and RAST (CAP system; Pharmacia, Uppsala, Sweden) and then tested for IgE reactivity with natural and purified recombinant timothy grass pollen allergens by ELISA and Western blot. RESULTS: Most (94.5%) of the patients allergic to grass pollen could be diagnosed with a combination of recombinant Phl p 1, Phl p 2, Phl p 5, and profilin by means of ELISA. Sera that did not react with the recombinant allergens contained low levels of timothy grass pollen-specific IgE. Although considerable variability in IgE recognition frequency of the recombinant allergens was observed in certain populations, a good correlation was found between natural timothy CAP results and the combination of recombinant allergens in all 183 tested sera (r = 0.87). CONCLUSIONS: Despite considerable variability in the IgE recognition frequency, purified recombinant timothy grass pollen allergens (Phl p 1, Phl p 2, Phl p 5) and profilin permitted successful in vitro diagnosis of grass pollen allergy in 94.5% of allergic individuals from different populations. The addition of other recombinant allergens (e.g., recombinant Phl p 4) would only slightly improve the in vitro test sensitivity.

Allergens↗

Skin testing with recombinant allergens rBet v 1 and birch profilin, rBet v 2: diagnostic value for birch pollen and associated allergies.

OBJECTIVE: This study assesses the value of two recombinant birch allergens for diagnosis of patients sensitized to birch pollen with or without associated food allergy. METHODS: Fifty-one patients with positive skin test responses to Betulaceae and seven nonallergic control subjects were investigated; specific IgE antibodies were evaluated by specific immunoassay and blot immunodetection. RESULTS: Among 51 patients, 47 reacted to rBet v 1 and 10 to rBet v 2. Seven patients reacted to both recombinant allergens. In skin prick tests we found a correlation between the wheal produced by the commercial birch extract and the wheal produced by rBet v 1. Among 47 patients with positive test responses to rBet v 1, 83% had IgE binding to the Bet v 1 protein as determined by immunoblotting. Among 10 patients sensitized to rBet v 2, six had IgE binding to Bet v 2. Eleven patients with negative results, as determined by immunoblotting, had low levels of birch IgE in the sera (less than 10 kU/L) and low concentrations of IgE to rBet v 1 or rBet v 2 in ELISA. The nonallergic control subjects (n = 7) did not react to rBet v 1 or rBet v 2 in skin prick tests, nor did they have detectable amounts of specific IgE to rBet v 1 or rBet v 2. Histamine release tests confirmed sensitization to Bet v 1 in two patients with discordant results; for Bet v 2, one patient had positive results only at a high concentration, and one had results that remained negative. Thirty-four patients had birch pollinosis, and all reacted to rBet v 1. Patients who were monosensitized to birch never reacted to rBet v 2. Sensitization to rBet v 2 was only found in patients who reacted to other pollens (mainly grass). Twenty-nine patients demonstrated allergy to apples, cherries, or hazelnuts; and all reacted to rBet v 1. Among 11 patients with allergy to Umbelliferae, only three reacted to rBet v 2. CONCLUSIONS: Use of the two recombinant allergens (rBet v 1 and rBet v 2) always permits the diagnosis of birch sensitization. Sensitization to rBet v 1 is specific for birch and Rosaceae allergies, whereas sensitization to birch profilin, Bet v 2, is encountered in multisensitized subjects and is not always related to Umbelliferae allergy.

Adult↗

Small cell carcinoma of the pleura. A case report.

Small cell carcinoma of the lung (SCLC) represents about 25% of all lung cancers. Extrapulmonary small cell carcinoma is a very uncommon feature, mostly described in the oesophagus. We report here a case of small cell carcinoma of the pleura with histopathological findings, clinical course and response to therapy typical of SCLC.

Antineoplastic Combined Chemotherapy Protocols↗

Performance of HTLV-1 screening assays in Brazil.

In recent years a variety of studies have been carried out to compare the accuracy (generally expressed in terms of sensitivity and specificity) of commercially available anti-HTLV tests. None of these studies were performed in Brazil or in any other South American country. During the characterization of our Brazilian reference panel we evaluated the sensitivities and specificities of the Abbott HTLV EIA (100%; 89.7%) and the Biochrom HTLV-1/-2 ELISA (100%; 42.4%). Our conclusion was that both assays may be problematic in terms of correctly identifying HTLV-negative sera. We therefore adjusted the cut-off values using receiver operating characteristics (ROC). ROC analysis, which involves calculating sensitivity and specificity for several cut-off values, can be used to ascertain the co-variation in the specificity and sensitivity of any assay giving quantitative results. The optimum cut-off value for the assay in a given study population is the point that gives highest possible sensitivity in conjunction with a small false-positive fraction. Using the HTLV-1/-2 Western blot as the "gold standard", we were able to improve the specificity of the Biochrom HTLV-1/-2 assay to 95% without affecting its sensitivity of 100%. However, it seems that when using the Biochrom HTLV-1/-2 ELISA, there may be problems in separating positive and negative sera. In the case of the Abbott HTLV EIA, our ROC analysis revealed that the cut-off value suggested by the manufacturer was nearly identical to the optimum cut-off value. Adjustment will affect neither sensitivity nor specificity. However, a slight adjustment of the cut-off value result in a clearer separation of the positive and negative populations. Furthermore, we assume that this adjustment will help to avoid false-positive results when larger serum panels are investigated. Further investigations will show whether or not this problem is linked to the geographical regions where the test is performed (e.g. polyclonal stimulation due to parasitic infections in tropical countries).

Blood Donors↗

[New aero-allergens].

As the number of proteins recognized as causing allergic respiratory diseases increases, new aero allergens have appeared in the animal and vegetable realms, both in home and professional environments. Lepidoglyphus destructor and Blomia tropicalis, two mites found in storage areas, are particularly important in agricultural areas and in homes. Over the last ten years, the frequency of reactions to cockroaches has also increased in several countries. The allergenicity of non-biting insects is a frequent cause of allergy in certain countries including Japan. Chironomides cause respiratory diseases in professional and outdoor environments. The important role of Alternaria, a mold, in producing severe asthma has also been demonstrated. The pathophysiology of pollen-induced asthma has been shown to result from pollen allergens carried by particles less than 5 microns in diameter. Cyprus and ash tree pollen also cause an increasing number of pollinoses and flowers can cause rhinitis and asthma. Respiratory allergy to Ficus benjamina inaugurated a new type of allergies caused airborne allergens from non-pollinating plants. Allergy to latex raises a particular problem for health care workers. The immunochemical structures of the major and minor airborne allergens are now better known and the homologous structures of different allergens largely explains certain cross-reactions. In the future, recombinant allergens will probably be used to better understand the role of allergens in inducing and maintaining the allergic reaction and should help in our approach to diagnosis and therapy.

Acari↗

[Is the bronchial provocation test justified in occupational respiratory disease?].

Specific bronchial provocation tests can confirm the diagnosis of occupational respiratory disease and also identify the causal agent of occupational asthma. The changes in French regulations established in 1993 which allow other agents to be recognized as causal in compensation for occupational diseases has increased interest in these tests. The different diagnostic methods used for occupational asthma are discussed here with special emphasis on limitations in each case: history taking, immunological investigations, respiratory function tests, measurement of peak flow during occupational activity and holidays, sequential measurements of non-specific bronchial hyperreactivity. The difficulty in standardizing specific provocation tests used for occupational asthma is related to the wide variety of causal agents which can be inhaled as gas, aerosols or powders. Because of the required precautions, these tests must be performed by specialized personnel in hospital units. There are also limitations to specific provocation tests. False positives require placebo tests and false negatives may result from insufficient identification of the causal agent. Exposure time may be too short or concentrations too low, and may depend on how long the causal agent has been evicted. Specific provocation tests may be avoided when the clinical history reveals a typical situation due to an agent known to cause occupational asthma and repeated peak flow measurements at the working site and/or immunological sensitisation tests provide objective evidence. But in a certain number of cases, specific investigations are required to obtain the precise etiological diagnosis required to evict the allergen rapidly and avoid chronic asthma.

Asthma↗

[Occupational asthma: medical and social prognosis].

The medical and social prognosis of occupational asthma has only been assessed with retrospective studies. The main findings are analyzed here. The wide range of methods used to obtain a positive diagnosis of occupational asthma and more or less complete eviction of the causal agent hinder interpretation of the results. Nevertheless, the findings reported in 15 studies focusing on the medical prognosis have shown that in 70% of the cases, occupational asthma remains symptomatic after eviction. The number of years the asthma existed at diagnosis is higher in subjects who remain symptomatic after eviction. In most patients with occupational asthma, the absence of eviction leads to accentuation of the obstructive syndrome and non-specific bronchial hyperreactivity. When the occupational disease has been recognized, the social-professional consequences unfortunately often include loss of employment and lower revenue.

Asthma↗

[Occupational asthma in an agricultural setting].

The prevalence of asthma in a farming environment is significant (from 3-7.7% according to various studies). The clinical picture has not been specified. The responsible agents are multiple and polysensitization frequent. Numerous substances of vegetable origin may be a cause, pollens, moulds, cereals, oil and protein producing plants, fibrous textiles, diverse plants and wood, etc. Amongst substances of animal origin the most frequent allergens incriminated are: allergens from mammals (horses, cattle, pigs), allergens from chickens and birds, arthropod allergens, insect allergens. Amongst chemical products those which are at risk to the respiratory system include insecticides, herbicides, fungicides, antibiotics and antiparasites. The diagnosis of the occupational character of asthma is sometimes difficult because of other causes of lung diseases in farm workers. The aetiological diagnosis is achieved by the clinical history, cutaneous tests, a level of specific serum IgE, and bronchial provocation tests which contrary to asthma in the industrial environment are not fundamental to the diagnosis except where chemical products are suspected. The mechanisms are sometimes intricate (IgE dependant mechanisms, non-specific liberation of histamine, activation of complement, intervention of endotoxins and pharmacological mechanisms...). Prevention may be carried out on behalf of the victim (for example wearing filtration masks in dusty work) and also carry out various methods to reduce the level of exposure to the allergen.

Agriculture↗

[Asthma, rhinitis and urticaria following occupational exposure to cyanoacrylate glues].

Cyanoacrylate glues are more and widely used in the industry because of easy handling and great sticking power. These very volatile and chemically reactive glues may not only cause contact eczema, but also rhinitis and asthma. Nineteen cases of asthma have been reported to date. We report two new cases of occupational asthma as well as one case of urticaria, a clinical symptom not yet described, to our knowledge. In the three cases, diagnosis was made based on a compatible medical history and positive realistic exposure tests. The mechanism is still unknown, due to the physical properties of cyanoacrylate glues; in fact, it is not possible to perform prick tests or specific IgE measurements. Besides the usual preventive measures, maintaining a relative humidity greater than 55% seems to induce polymerization of free monomers of alkyl cyanoacrylate, thereby reducing their volatility. Rhinitis and asthma due to cyanoacrylate glue may receive compensation as occupational diseases in France.

Adhesives↗

[Study by questionnaire of the influence of weather conditions, particularly fog, on the symptomatology of asthmatic subjects].

The role of fog in the symptomatology in asthmatic subjects has been assessed by a questionnaire concerning respiratory complaints linked to meteorological conditions and to non-specific irritant factors. In a population of 121 asthmatics (59 men and 62 women) 74.4% complained that fog was a factor aggravating their symptoms while only 3% of a group of 30 non-asthmatic subjects expressed discomfort during episodes of fog. The chemical analysis of fog during 32 episodes of local fog (pH, chloride, nitrate, sulphate, sodium, ammonia, potassium, magnesium, calcium) has shown a greater concentration of pollutants and greater acidity in the smaller particles (2-6 microns) which are able to penetrate the bronchial tree. This acidity could explain the role of fog in respiratory physiology. Certain authors have suggested that the aggravation of respiratory symptoms observed during peaks of pollution could be induced by aerosols containing sulphuric acid while others have described effects on respiratory function at the time of exposure to acid aerosols in asthmatic subjects but the results of the different studies have not all been concordant. Putting aside the role of the susceptible individual, other factors may intervene at the time inhalation of pollutants, notably the ambient humidity, the neutralising effect of endogenous ammonia and the synergystic effect between acid aerosols and atmospheric pollutants.

Adolescent↗