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Biomedical subjects

Patrick Koch

Publications and source records attributed to Patrick Koch.

11 recordsLinked to original sources

Patch testing with components of water-based metalworking fluids: results of a multicentre study with a second series.

BACKGROUND: Although many allergens in metalworking fluids (MWF) are identified, there are still some MWF components, which are not sufficiently investigated concerning their sensitizing properties. OBJECTIVES: To investigate sensitization to 10 frequently used MWF components, which are not part of the established MWF test series, in metalworkers with suspected occupational dermatitis due to MWF. PATIENTS/METHODS: Oleyl alcohol, myristyl alcohol, dimethylolurea, 4,4'-methylenebis morpholine, imazalil, 1-amino-2-propanol (monoisopropanolamine; MIPA), 2-amino-2-ethyl-1,3-propanediol (AEPD), 2,5-bis(n-octyldithio)-1,3,4-thiadiazole, zinc alkyl dithiophosphate and dibenzyl disulfide have been patch tested in 144 patients. RESULTS: 7 patients reacted positively to the formaldehyde releaser 4,4'-methylenebis morpholine, and 6 of these patients also reacted to formaldehyde and/or other formaldehyde releasers. 4 patients reacted positively to myristyl alcohol tested at 10% petrolatum (pet.). Additionally, 20 doubtful or irritant reactions occurred. 1 patient each reacted positively to oleyl alcohol, MIPA, and AEPD. None of the other test substances mentioned above elicited any clear-cut positive reaction. Patch testing with well-known MWF allergens showed proportions of positive reactions, which were comparable to those from other studies, e.g. 11% to monoethanolamine, 8% to colophonium and 3%-5% to various preservatives. CONCLUSIONS: 4,4'-methylenebis morpholine may be an important MWF allergen, although clinical relevance could not be stated definitely in every case. Myristyl alcohol should not be patch tested at 10% pet., but at a lesser concentration, due to irritant properties.

Adult↗

Positive patch test reactions to nickel sulphate are not modified by neighbouring negative fragrance patch tests. A multicenter-study by the German contact dermatitis research group.

It is tacitly assumed that a positive patch test reaction is not affected by adjacent negative tests. However, despite its fundamental importance for the interpretation of test reactions this assumption has not been proven. To test this assumption, special TRUE-test strips were prepared containing placebo, nickel sulphate and fragrance mix as the only allergens, separated by distances of 1 cm and 7 cm and blinded to the investigators. Patients were synchronously tested with two strips. Out of 493 patients tested in 6 centres, the 93 with positive reactions to nickel sulphate only were evaluated. No relevant difference was found between positive nickel reactions in the two different distances to a negative fragrance patch test. We conclude that a positive patch test reaction is not affected by adjacent negative patch tests, which therefore can be neglected for the interpretation of positive reactions.

Allergens↗

Derivatives of tramadol for increased duration of effect.

Tramadol is a centrally acting opioid analgesic structurally related to codeine and morphine. Analogs of tramadol with deuterium-for-hydrogen replacement at metabolically active sites were prepared and evaluated in vitro and in vivo.

Analgesics, Opioid↗

Patch test results with the metalworking fluid series of the German Contact Dermatitis Research Group (DKG).

Based on the information of the interdisciplinary task force on allergy diagnostics in the metal branch, in 2001, the German Contact Dermatitis Research Group (DKG) compiled two metalworking fluid (MWF) test series with currently and previously used components, respectively. After 2 years of patch testing, we present results obtained with these series, based on data of the Information Network of Departments of Dermatology (IVDK). 251 metalworkers who were patch tested because of suspected MWF dermatitis in 2002 and 2003 were included in this retrospective data analysis. Of these, 206 were tested with the current MWF series and 155 with the historical MWF series. Among the current MWF allergens, monoethanolamine ranked 1st with 11.6% positive reactions. Diethanolamine (3.0%), triethanolamine (1.1%), and diglycolamine (1.9%) elicited positive reactions far less frequently. Allergic reactions to p-aminoazobenzene were frequently observed (6.0%), but the relevance of these reactions is still obscure. Positive reactions to biocides ranged from 4.5% for Bioban CS 1135 to 0.5% for iodopropynyl butylcarbamate and 2-phenoxyethanol. Concomitant reactions to formaldehyde, which caused positive reactions in 3.3%, and formaldehyde releasers occurred to varying extents without conclusive pattern. No positive reactions were seen to dibutyl phthalate, di-2-ethylhexyl phthalate, tricresyl phosphate, isopropyl myristate or benzotriazole. With the historical MWF test series, positive reactions to methyldibromo glutaronitrile (MDBGN) were observed most frequently. However, sensitization via allergen sources other than MWF seems likely, as MDBGN, during the study period, has been one of the most frequent preservative allergens in cosmetics and body care products. Other historical MWF allergens comprised morpholinyl mercaptobenzothiazole (3.3%), benzisothiazolinone (BIT; 2.0%) and Bioban P 1487(1.3%). BIT is currently used in MWF again, so it was shifted to the current MWF test series. As decreasing reaction frequencies to former MWF allergens that are no longer used can be expected, the historical series should be re-evaluated after some years. The test series with current MWF allergens has to be kept up-to-date based on information from industry and to be kept concise by eliminating test substances which never cause positive reactions.

Adolescent↗

Patch testing with components of water-based metalworking fluids.

Water-based metalworking fluids (MWFs) may cause both irritant and allergic contact dermatitis. Several well-known MWF allergens are available for patch testing, but considering the wide variety of possible components used in MWF, our diagnostic arsenal covers only a small part of potential allergens. We therefore selected 13 frequently used MWF components that might be sensitizers and had not yet been tested routinely. In 5 centres, 233 dermatitis patients with present or past occupational exposure to MWF were patch tested with this and other panels. Only 7 patients showed positive reactions to the study panel. Allergic reactions to the emulsifier diglycolamine [syn. 2-(2-aminoethoxy) ethanol] were seen in 5 patients, and 1 patient each reacted positively to 2-amino-2-ethyl-1,3-propanediol (AEPD) and methyldiethanolamine (MDEA). Clinical relevance of the reactions to diglycolamine was unequivocally proven by its presence in the MWF from the patients' workplace in 3 cases. Diglycolamine seems to be an important MWF allergen, independently from monoethanolamine and diethanolamine. A test concentration of 1% petrolatum (pet.) appears to be appropriate. The importance of AEPD and MDEA as MWF allergens still remains to be established. The lack of positive test reactions to the other MWF components tested may be due to their low-sensitizing potential or too low a patch test concentration being used.

Adult↗

Delayed-type hypersensitivity skin reactions due to heparins and heparinoids. Tolerance of recombinant hirudins and of the new synthetic anticoagulant fondaparinux.

Eczema-like, infiltrated plaques at subcutaneous heparin-injection sites are well-documented side effects of these anticoagulants. They are due to delayed-type hypersensitivity. In 4 patients, patch, intradermal and subcutaneous tests were performed with a panel of unfractionated heparins (UFHs), low-molecular-weight heparins (LMWHs), heparinoids, recombinant hirudins and a new synthetic pentasaccharide anticoagulant fondaparinux sodium, to find safe alternatives. 3 patients were sensitized to all the UFHs and LMWHs. The LMWH tinzaparin sodium and the heparinoid pentosan polysulfate were found to be a possible substitute in patient no. 1 and 2, respectively. The recombinant hirudins and fondaparinux sodium were tolerated without any side effects in all patients tested. Fondaparinux is a synthetic copy of a pentasaccharide sequence in the heparin molecule. It is the first in a new class of antithrombotic agents. Our study suggests that it is a new safe alternative in patients with eczema-like, infiltrated plaques at subcutaneous heparin-injection sites.

Aged↗

Effects of prototypical microsomal enzyme inducers on cytochrome P450 expression in cultured human hepatocytes.

Cultured human hepatocytes are a valuable in vitro system for evaluating new molecular entities as inducers of cytochrome P450 (P450) enzymes. The present study summarizes data obtained from 62 preparations of cultured human hepatocytes that were treated with vehicles (saline or dimethylsulfoxide, 0.1%), beta-naphthoflavone (33 microM), phenobarbital (100 or 250 microM), isoniazid (100 microM) and/or rifampin (20 or 50 microM), and examined for the expression of P450 enzymes based on microsomal activity toward marker substrates, or in the case of CYP2C8, the level of immunoreactive protein. The results show that CYP1A2 activity was markedly induced by beta-naphthoflavone (on average 13-fold, n = 28 preparations), and weakly induced by phenobarbital (1.9-fold, n = 25) and rifampin (2.3-fold, n = 22); CYP2A6 activity tended to be increased with phenobarbital (n = 7) and rifampin (n = 3) treatments, but the effects were not statistically significant; CYP2B6 was induced by phenobarbital (6.5-fold, n = 13) and rifampin (13-fold, n = 14); CYP2C8 was induced by phenobarbital (4.0-fold, n = 4) and rifampin (5.2-fold, n = 4); CYP2C9 was induced by phenobarbital (1.8-fold, n = 14) and rifampin (3.5-fold, n = 10); CYP2C19 was markedly induced by rifampin (37-fold, n = 10), but relatively modestly by phenobarbital (7-fold, n = 9); CYP2D6 was not significantly induced by phenobarbital (n = 5) or rifampin (n = 5); CYP2E1 was induced by phenobarbital (1.7-fold, n = 5), rifampin (2.2-fold, n = 5), and isoniazid (2.3-fold, n = 5); and, CYP3A4 was induced by phenobarbital (3.3-fold, n = 42) and rifampin (10-fold, n = 61), but not by beta-naphthoflavone. Based on these observations, we generalize that beta-naphthoflavone induces CYP1A2 and isoniazid induces CYP2E1, whereas rifampin and, to a lesser extent phenobarbital, tend to significantly and consistently induce enzymes of the CYP2A, CYP2B, CYP2C, CYP2E, and CYP3A subfamilies but not the 2D subfamily.

Aryl Hydrocarbon Hydroxylases↗

Aerosolized beta(2)-adrenergic agonists achieve therapeutic levels in the pulmonary edema fluid of ventilated patients with acute respiratory failure.

OBJECTIVE: Experimental studies demonstrate that beta-adrenergic agonists markedly stimulate alveolar fluid clearance if concentrations of 10(-6) M are achieved in alveolar fluid. However, no studies have determined whether aerosolized beta-adrenergic agonists are delivered to the distal air spaces of the lung in therapeutic concentrations in patients with pulmonary edema. DESIGN AND SETTING: This retrospective study measured albuterol levels in the pulmonary edema fluid and plasma from mechanically ventilated patients with pulmonary edema from a hydrostatic mechanism ( n=10) or from acute lung injury ( n=12). MEASUREMENTS AND RESULTS: After a total aerosolized albuterol dose of 4.2+/-3.2 mg in the prior 6 h the median pulmonary edema fluid albuterol level was 1,250 ng/ml (10(-6) M) in patients with hydrostatic pulmonary edema; after 3.5+/-2.6 mg the figure was 1,240 ng/ml (10(-6) M) in patients with pulmonary edema from acute lung injury. Plasma albuterol levels were much lower, with a median of 5.2 ng/ml (0.01 x 10(-6) M) in patients with hydrostatic pulmonary edema and 3.1 ng/ml (0.01 x 10(-6) M) in patients with pulmonary edema from acute lung injury. CONCLUSIONS: These results provide the first evidence that levels of beta-adrenergic agonists that are physiologically efficacious in experimental models can be achieved with conventional delivery systems in ventilated, critically ill patients with acute respiratory failure from pulmonary edema.

APACHE↗

An attempt to improve diagnostics of contact allergy due to epoxy resin systems. First results of the multicentre study EPOX 2002.

Epoxy resin systems (ERSs) are a frequent cause of occupational allergic contact dermatitis. Sensitization occurs not only to the resins, but also to hardeners and reactive diluents. However, only a fraction of the ERS components currently in use are available for patch testing. With the multicentre study EPOX 2002, we attempted to improve diagnostics in this field by patch testing with components currently used in ERSs. During the first study period (October 2002 to July 2003), in addition to commercially available ERS patch test substances, 16 study substances (1 resin, 9 hardeners and 6 reactive diluents) were patch tested in 70 patients with suspected contact allergy due to ERSs and 22 patients with a prior positive patch test reaction to epoxy resin (ER) in the standard series. Most frequently, allergic reactions to ER based on diglycidyl ether of bisphenol A and F were observed (55.2% and 43.7%, respectively). Agreement between positive reactions to both resins, which can be explained by immunological cross-sensitization and/or coexposure, was substantial [Cohen's kappa 0.65 (95% CI: 0.49-0.80)]. Among the reactive diluents, 1,6-hexanediol diglycidyl ether (1,6-HDDGE) and 1,4-butanediol diglycidyl ether (1,4-BDDGE) were the most frequent allergens, with 19.5% and 18.4% positive reactions, respectively. Although agreement between positive reactions to 1,6-HDDGE and 1,4-BDDGE was even better than with the 2 resins, the sample size is considered too small to decide reliably whether 1,6-HDDGE alone could serve as a marker allergen for both. Allergic reactions to p-tert-butylphenyl glycidyl ether and to phenyl glycidyl ether (PGE) occurred in 11.5% of the patients tested, with only moderate agreement. All patients positive to cresyl glycidyl ether (6.8%) also reacted to PGE. Of the hardeners tested, m-xylylene diamine was the most frequent allergen (13.8%), followed by isophorone diamine (5.7%). No reactions were observed to several substances, the test concentration of which may have been too low and will be increased in the future.

Adolescent↗