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Biomedical subjects

H U Koch

Publications and source records attributed to H U Koch.

At least 19 recordsLinked to original sources

Allergologically relevant rubber accelerators in single-use medical gloves.

To prevent contact with specific rubber accelerators, sensitized patients have to know in which glove brands these accelerators are present. Additionally, quantitative measurements of the bioavailable amounts of accelerators are needed to assist consumers in selecting gloves with the lowest possible amount of residual rubber accelerators. The aim of the study was to develop an analytical method by which residuals of rubber accelerators in single-use medical gloves could be determined qualitatively and quantitatively. 19 different glove brands were analysed for content of accelerators, and the results were compared to manufacturers' ingredient claims of the identical gloves. ZDEC, ZDBC, ZMBT and ZPC were the most frequently detected chemicals. In 9 of 15 gloves discrepancies were found, usually minor, between content of accelerators declared by manufacturers to be present and accelerators detected by analysis. Both phosphate buffer and acetone were tested as extraction media. No accelerators were detectable with the described chemical analysis in phosphate extracts, whereas acetone was demonstrated to be a technically suitable medium for extraction. However, more kinetic studies of the extraction procedure and studies of skin penetration are needed to document that the extraction procedure simulates the clinical situation.

Allergens↗

Formation of autocrine loops in human cerebral meningioma tissue by leukemia inhibitor factor, interleukin-6, and oncostatin M: inhibition of meningioma cell growth in vitro by recombinant oncostatin M.

OBJECT: It has been demonstrated that growth of cerebral meningiomas found in humans is controlled by a variety of factors, including growth factors, aminergic agents, neuropeptides, and steroids. To further our knowledge of this process, the authors investigated the presence and function of the cytokines leukemia inhibitory factor (LIF), interleukin-6 (IL-6), and oncostatin M (OSM) on meningioma cell proliferation. METHODS: Active transcription of LIF, IL-6, and OSM, their related receptors (LIF-R, IL-6-R, and gp130), and the consecutive signal-transducing molecules (STAT 1, STAT 3, and STAT 5a) were analyzed in reverse transcriptase-polymerase chain reaction experiments. The presence of endogenous LIF, IL-6, and OSM proteins was demonstrated in the supernatant of cultured meningioma cells using the enzyme-linked immunosorbent assay and Western blot experiments, thus indicating an autocrine signaling pathway for all three cytokines. The biological function of all three cytokines was evaluated by studying their effects on meningioma cell growth. Recombinant LIF and IL-6 showed no significant growth modulating effects; however, recombinant OSM decreased meningioma cell growth by 66%. The antiproliferative potency of OSM was demonstrated by cell count experiments, the [3H]thymidine incorporation assay, and cell cycle analysis. CONCLUSIONS: These in vitro data support the concept that growth of meningioma cells may be modulated by cytokines, and they also indicate that recombinant OSM may be one future candidate for use in the adjuvant treatment of inoperable and recurrent meningiomas.

Acute-Phase Proteins↗

Physical stress-induced secretion of adrenal and pituitary hormones in patients with atopic eczema compared with normal controls.

Atopic eczema is a chronic inflammatory skin disease which shares some psychological and neuroendocrine disturbances with patients suffering from depression. In view of recent findings of an attenuated response of the hypothalamic-pituitary-adrenal (HPA) system in patients with atopic eczema during a human corticotropin-releasing hormone (hCRH) challenge paradigm fourteen consecutive non-specifically trained in-patients with atopic eczema (8 men, 6 women) and an age-matched control group (8 men, 6 women) performed exhausting incremental graded bicycle exercise to evaluate cortisol, adrenocorticotropin (ACTH), beta-endorphin, epinephrine and norepinephrine releases induced by physical stress. The exercise yielded significant increases in cortisol, ACTH, beta-endorphin, epinephrine and norepinephrine concentrations in both groups. Patients with severe eczema displayed a significantly lower increase in norepinephrine levels when compared with the less affected patient group. In contrast to the challenge with exogenous hCRH no substantial difference in the net responses of ACTH and cortisol could be detected between patients with atopic eczema and controls using the physical stress paradigm. These substantial differences in the net outcome between both challenges may be related to the potential synergizing effects of various neuropeptides, e.g. CRH and vasopressin, when activating the HPA system by challenges at a suprapituitary site which may override subtle disturbances in the responsivity of the HPA system as revealed by CRH challenge alone in patients with atopic eczema.

Adrenocorticotropic Hormone↗

Type I allergies to latex and the aeroallergenic problem.

Between 1989 and 1995, a 12-fold increase in latex allergy was documented amongst our patients. Similar findings have been noted elsewhere. Increase in type I allergies to latex has become an international problem. The issues associated with latex allergy are described, including those posed by the ubiquitous nature of latex in medical equipment, and in commonplace domestic objects. The potential for allergic patients to cross react to a variety of fruits or plants is an added problem for sensitized patients. This paper concludes that the universal introduction of powder-free surgical gloves with low protein content would be a very important measure in the prevention of acquired latex allergy.

Air Pollutants, Occupational↗

[Update on the latex allergy topic].

Type I allergies to latex have become an increasing problem in occupational dermatology during the past few years, especially since at least 10% of health care workers are affected. In the Department of Dermatology, University Erlangen-Nuremberg, a 12-fold increase in latex-allergic patients has been documented between 1989 and 1995 with a clear trend to more severe systemic manifestations (from 10.7% in 1989/ 1990 to 44% in 1994/1995). Among the water soluble proteins (molecular weights 2 to 200 kD) which may induce latex allergy, at least 5 are considered as main proteins with known primary structure. In addition some "marker' proteins seem to induce specific IgE antibodies in special risk groups (e.g. 46 kD-protein in medical professions, 14.6 kD- and 27 kD-proteins in children with spina bifida). Cross reactions between latex and several fruits (especially avocado, kiwi, banana and chestnut) in 60 to 70% of latex-allergic patients have to be taken into account when evaluating and counselling affected patients. Most important in prophylaxis is the complete change to powder-free latex gloves in medical institutions, since these gloves usually have a low protein content. Our listing of surgical and examination gloves according to their protein content (as measured by the modified Lowry- and High Pressure Liquid Chromatography method) should be a useful guideline for the choice of suitable gloves.

Adult↗

[Incidence and increase in type I allergies to rubber gloves in dental medicine students].

The prevalence of type I allergy against latex was investigated in dental students by questionnaire, prick tests and the determination of specific IgE antibodies. Positive prick tests against different latex fluids were found in 18 (8.7%) of 206 students, with clinical relevance in 11 cases. When the total number of students in each semester was taken into account an increase in the minimal prevalence of clinically relevant latex allergy from 2% in the second semester to 10.4% in the tenth semester was seen. A history of glove intolerance presenting as a wheal-and-flare reaction was associated with a type I allergy against latex in only 50% of the affected subjects. Atopic diseases and hand eczema of different causes proved to be risk factors in 16 and 5 of 18 students with latex allergy, respectively. A high-ammonia accelerator-free latex fluid proved to be a very reliable test medium compared to the less sensitive determination of specific IgE antibodies to latex.

Adult↗

Cortisol, corticotropin, and beta-endorphin responses to corticotropin-releasing hormone in patients with atopic eczema.

Alterations in the hypothalamic-pituitary-adrenal (HPA) system are well documented in affective disorders. In depression these include increased secretion of cortisol, an insufficient suppressibility of cortisol by dexamethasone, a blunted corticotropin (ACTH) response to corticotropin-releasing hormone (CRH) and a dysfunction of the glucocorticoid receptor. Patients with atopic eczema, a common chronic skin disease, show seasonal variations in disease activity, symptoms of minor depression and immunological disturbances similar to those seen in patients with depression. To explore the integrity of the HPA system integrity in individuals with atopic eczema we studied the 24-h cortisol secretion and the cortisol, ACTH and beta-endorphin responses to CRH in such individuals and in healthy controls matched for sex and age. The 24-h secretion of cortisol did not differ between the patients with atopic eczema and the controls. The net response to CRH administered as a 100 micrograms i.v. bolus was significantly attenuated for both cortisol (24,235 +/- 12,443 vs. 47,019 +/- 34,515 nmol.min/dl; p < .03) and for ACTH (546 +/- 205 vs. 727 +/- 310 pmol.min/l; p < .05) in the patient group, whereas the beta-endorphin response did not differ between the groups (1072 +/- 448 vs. 1603 +/- 421 nmol.min/l). The blunted response of cortisol and ACTH cannot be explained by hypercortisolism as it is the case in major depression. Rather, it may be related to a prolonged underexposure to hypothalamic CRH or to an increased sensitivity of glucocorticoid feedback inhibition.

Adolescent↗

Effects of interferon-alpha-2b on the clinical course, inflammatory skin infiltrates and peripheral blood lymphocytes in patients with severe atopic eczema.

Increased serum IgE and enhanced susceptibility to viral infections, decreased levels of interferons, lymphocytic skin infiltrates and IgE-bearing epidermal Langerhans cells are striking features in patients with atopic eczema (AE). Since the hyper-IgE syndrome is known to improve under alpha-interferon (alpha-IFN) therapy, we treated 7 patients with severe AE and high serum IgE exclusively with 3 x 10(6) units IFN alpha 2b thrice weekly for 3 months. Before treatment the skin infiltrates mainly consisted of CD3+/CD4+/TcR alpha/beta + lymphocytes, whereas the CD3+/CD8+ phenotype was limited to about 10% of cells. After 6 weeks of therapy, epidermal inflammation with CD4+ and CD8+ cells was reduced but dense infiltrates remained in papillary perivascular areas. Expression of TcR gamma/delta, HLA-DR and CD25 showed no significant changes. Initially high serum IgE and soluble CD23 as well as cell-bound IgE dropped under therapy, whereas a short-term elevation in serum IL-2 receptor was observed. On peripheral blood lymphocytes slightly reduced expression of HLA-DR, LFA-1, CD23 and ICAM-1 was seen after 100 days. LFA-3 expression became reduced in 4 patients, the CD4/CD8 ratio decreased in all cases. After an initial therapeutic response of all patients, significant longer-lasting improvement of the skin lesions could only be observed in 2 of 7 patients. The data of our long-term study suggest that systemic IFN alpha 2b treatment leads to a remarkable reduction in epidermal inflammation but does not significantly influence cutaneous cell subsets. Immunomodulatory effects became obvious by reduced peripheral cell subsets expressing TcR alpha/beta, MHC class II and adhesion molecules.

Adult↗

[The coincidence of rapidly progressing dilated cardiomyopathy and primary hyperparathyroidism. The course before and after the removal of a parathyroid adenoma].

Severe cardiac arrhythmias (Lown class IVa), rapid loss of physical capacity and dyspnoea on the slightest exertion occurred in a 55-year-old man with idiopathic dilated cardiomyopathy. In the preceding year he had recurrent diarrhoea and lost 23 kg in weight. He was found to have hypercalcaemia (3-3.2 mmol/l). The heart failure significantly improved under treatment with twice daily 12.5 mg captopril, 100 mg spironolactone daily, furosemide 40 mg twice daily, and digitoxin 0.07 mg daily. The arrhythmia responded to verapamil 80 mg and quinidine 160 mg, both drugs three times daily. Primary hyperparathyroidism was found to be the cause of the hypercalcaemia (parathormone 84 pmol/l). After the parathyroid adenoma had been removed the patient's condition again improved markedly. There were only rare monotopic extrasystoles, cardiac size regressed, and diuretics were no longer necessary. His medication at present is verapamil (80 mg three times daily), captopril (12.5 mg three times daily) and digitoxin (0.07 mg daily). It is concluded that the hypercalcaemia influenced the severity of the cardiomyopathy. It would seem that both intra- and extracellular calcium homoeostasis is of great importance in dilated cardiomyopathy.

Adenoma↗

In vivo and in vitro effects of glucocorticoids on lectin-induced blastogenesis in atopic dermatitis.

The effects of glucocorticoids administered in vivo and in vitro on lectin-induced proliferation of lymphocytes sampled from venous blood were investigated in patients with atopic dermatitis (AD) and in normal controls. Stimulation by concanavalin A (Con A), phytohaemagglutinin A (PHA) and pokeweed mitogen (PWM) in patients and controls did not differ significantly under baseline conditions. After in vivo administration of methylprednisolone the decline of Con A-induced blastogenesis of leucocytes was similar in both groups, whereas PHA stimulation caused a significant reduction in the controls only. In vitro addition of different dexamethasone concentrations had a pronounced suppressive effect on Con A- and PHA-induced blastogenesis in both groups, whereas PWM stimulation was unaffected. Pretreatment in vivo with methylprednisolone further decreased the suppression of the Con A and PHA lymphocyte proliferation rate by dexamethasone added in vitro in controls but not in patients. With regard to B-cell proliferation generated by PWM, no consistent glucocorticoid effect could be observed. The impaired effect on lymphocyte blastogenesis of glucocorticoids administered in vivo, in contrast to a normal in vitro reaction to dexamethasone, together with recent findings of an altered glucocorticoid receptor pharmacology in AD, points to a decreased biological in vivo efficiency of methylprednisolone in atopic dermatitis.

Adult↗

Allergic and irritant reactions to rubber gloves in medical health services. Spectrum, diagnostic approach, and therapy.

Delayed-type allergies account for most reactions to gloves. These have been found in 32 of 39 patients (82%) attending our department with occupationally induced contact dermatitis to gloves. Accelerators, mainly of the thiuram group, antioxidants, vulcanizers, organic pigments, and, presumably, glove powder ingredients are known responsible allergens. In contrast, immediate-type allergies to rubber gloves were less frequent (13 of 39 patients [33%] with occupationally induced glove allergies). They usually present as contact urticaria. Responsible allergens are latex, glove powder, and accelerators. On the basis of the numerous glove-related allergens, a comprehensive schedule of diagnostic tests is proposed. In addition, we introduce a new classification of hypoallergenic gloves according to their basic materials and ingredients and thus provide a guideline for individual therapy.

Allergens↗

Frequency, spectrum and occupational relevance of type IV allergies to rubber chemicals.

3851 consecutive patients patch tested between January 1985 and March 1990 have been analysed for rubber allergies. The incidence of rubber allergy was 3.8% (n = 145). In 80/145 patients (55%), the source of rubber sensitization was occupational, 67 of whom (84%) had acquired allergy from wearing rubber gloves at work. Most of them (36%) were employed in the health services. The most commonly positive rubber-mix in this group was thiuram-mix (72%) followed by carba-mix (25%). 13/80 patients (16%) had occupational rubber allergy from industrial rubber products other than gloves. Patch tests revealed thiuram-mix (62%) as the most commonly positive rubber-mix but, in contrast to the group with glove-induced rubber allergy, black-rubber-mix came second (38%). In 47/145 patients (32%), the source of rubber sensitization was non-occupational; in 18/145 (13%) the origin remained unknown.

Adolescent↗

Elevated glucocorticoid receptor concentrations before and after glucocorticoid therapy in peripheral mononuclear leukocytes of patients with atopic dermatitis.

The number and affinity of glucocorticoid binding sites in peripheral mononuclear leukocytes of patients with atopic dermatitis (AD) and healthy controls were determined under baseline conditions and after a defined oral glucocorticoid treatment. Patients with AD (n = 15) exhibited significantly more glucocorticoid receptors (GR) per cell than the control group (n = 22), while the GR affinity did not differ. Methylprednisolone treatment resulted in a significant reduction of the GR sites per cell in the steroid-treated control group (n = 10) in contrast to the patients. The dissociation constant was not affected by methylprednisolone treatment in either group. In view of the therapeutic efficiency of glucocorticoids in AD and findings of abnormal cAMP and cAMP-phosphodiesterase activity, the elevated GR concentrations in AD lend support to the hypothesis of a compensatory GR upregulation due to an insufficient action of endogenous cortisol or to altered cAMP-induced GR expression.

3',5'-Cyclic-AMP Phosphodiesterases↗

Multihormonal response to dexamethasone. A study in atopic dermatitis and normal controls.

Although minor disturbances of the circadian serum cortisol rhythm and diminished excretion of steroid metabolites have been reported in patients with atopic dermatitis, test assays regarding subtle neuroendocrine alterations have not been employed so far. We therefore studied the serum concentrations of cortisol, prolactin and adrenocorticotropin under baseline conditions, after 1 mg dexamethasone and after a defined methylprednisolone treatment in 15 patients with atopic dermatitis, in comparison with 10 healthy controls. The assessment of the hormones revealed no remarkable differences between either group at any of the blood sampling time points. However, in 3 patients and 2 control subjects, though exhibiting no concomitant disease, we could find no suppression of endogenous cortisol to below 5 micrograms/dl after oral intake of 1 mg dexamethasone. These cortisol non-suppressors showed lower dexamethasone serum concentrations in the morning after its administration, as compared with the suppressors. Acute (1 mg dexamethasone) or prolonged (40 mg methylprednisolone over 6 days) intake of glucocorticoids suppressed prolactin levels in both groups, demonstrating that the effect of glucocorticoids on the hormone system is not restricted to the hypothalamic-pituitary-adrenal axis. Our results indicate an intact feedback response of this hormonal axis to 1 mg dexamethasone and the ability of long-term as well as acute glucocorticoid administration to influence the prolactin secretion in patients with atopic dermatitis.

Adolescent↗

Ultraviolet light hardening in polymorphous light eruption--a controlled study comparing different emission spectra.

Polymorphous light eruption (PLE) is a common disorder characterized by a delayed, abnormal response to ultraviolet (UV) radiation, with a varied morphology of itching efflorescences on sun-exposed areas of the skin. Thirty-one PLE subjects were treated with either UVA (340-400 nm) or UVA and UVB (300-400 nm) phototherapy during spring 1987 (10 exposures to UV light). They were randomly allocated to these 2 groups. For subjects of the UVA group, the applied dose corresponded to their individual minimal tanning dose; for subjects of the UVA and UVB group it corresponded to approximately 3/4 of their individual minimal erythema dose. The sun protection effect was studied by a high dose of UVA (80-160 J/cm2; 340-440 nm) after the treatment period, by analysing the histidine content of the stratum corneum and the urocanic acid photoisomerization, and by evaluating the subjects' diaries. The patients were asked to expose their skin to sunlight at least 3 times after UV hardening in the following 2-10 weeks. The results of both the UVA provocation and of the natural sun exposure confirmed the success of UV hardening without the occurrence of severe side effects. The content of histidine and of its metabolite urocanic acid in stratum corneum was significantly increased during the treatment. These data are interpreted to be biochemical markers for improved sun protection.

Female↗