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Biomedical subjects

H Möller

Publications and source records attributed to H Möller.

At least 37 records · Page 2Linked to original sources

Symptoms and signs reported during patch testing.

BACKGROUND: In a pilot questionnaire study, there was a high frequency of subjective complaints and distant skin reactions during patch testing as reported at the day of test reading, particularly in female patients. OBJECTIVE: To document in a controlled study possible side-effects of a generalized nature occurring during the test procedure. METHODS: A questionnaire study on symptoms and signs reported at application and at reading of standard patch tests was conducted with 401 patients, with the patients serving as their own controls. RESULTS: An eczematous flare-up during patch testing was observed in 3.7% of the patients. There were plenty of different symptoms of malaise but, with one exception (itch on the back), the number of symptoms tended to be less on the day of reading than on the day of application of the tests. This held true also for itch occurring in the patients' dermatitis. There was no statistical correlation between symptoms and signs on the one hand and positive patch tests on the other. CONCLUSION: Distant skin reactions and impairment of general health occurring during patch testing are often reported at the time of test reading. However, with the exception of itch on the back, symptoms and signs are rather less common after the application of patch tests than before.

Adult↗

Exposure to metallic gold in patients with contact allergy to gold sodium thiosulfate.

Gold allergy is common, with approximately 10% of patients patch tested because of eczematous disease being positive to gold sodium thiosulfate (GSTS). However, clinical relevance seems to be rare. The aim of this prospective double-blind study was to demonstrate the effects of exposure to metallic gold, in this case earrings, in gold-positive patients. 60 female patients with pierced earlobes test-positive to GSTS were included in the study. The patients were randomized into 2 groups, 30 patients receiving earrings with a surface layer consisting of 24-carat gold and 30 patients earrings with a surface layer of titanium nitride, virtually indistinguishable from gold. The patients wore the earrings for 8 weeks. During the study, any dermatitis on the earlobes, as well as on other body sites, was registered. The skin reactions observed were weak but, in total, 17 of the 60 patients had a skin reaction (local or remote) during the study, 12 of whom had received gold earrings and 5 titanium (p<0.05). 11 patients had a reaction on the earlobes, 7 of whom had received gold earrings and 4 titanium (NS). With these facts it is hard to exclude that exposure to gold jewelry can be clinically relevant in persons hypersensitive to gold.

Adult↗

Melanocytes in nevi and melanomas synthesize basement membrane and basement membrane-like material. An immunohistochemical and electron microscopic study including immunoelectron microscopy.

Light microscopic studies have shown that nevus cell nests and melanoma nests are surrounded by basement membrane (BM) material containing type IV collagen and laminin. This study confirms this by electron microscopy and relates it to proteins which interact with the basement membrane. Nevi except for dysplastic and Spitz nevi, malignant melanomas, and melanoma metastases were studied by immunohistopathology, routine electron microscopy (EM), and immunoelectron microscopy. The lesions were incubated with monoclonal antibody (moAb) against type IV collagen, laminin, and the integrin alpha6 and studied by light microscopy. In addition, melanomas were studied by immuno-EM after incubation with a moAb against matrix metalloproteinase-2 (MMP-2). Nevus cell nests and melanoma nests are surrounded by BM material containing type IV collagen and laminin by immuno-EM. The BM material various in thickness and is amorphous. Type IV collagen, laminin, and MMP-2 are synthesized by melanoma cells as well as adjacent fibroblasts. Destruction or loss of the BM is not mandatory for melanoma invasion or even metastasis. Possibly the BM material is a protective wall for melanoma cells. Interactions between melanocytes and the extracellular matrix of which the BM is a part, can be traced back to the migration of melanocytes from the neural crest.

Antibodies, Monoclonal↗

Increased non-major histocompatibility complex-restricted lytic activity in melanoma patients vaccinated with cytokine gene-transfected autologous tumor cells.

Genetically modified antitumoral vaccines focus on eliciting or increasing the T-cell-mediated antitumoral response. Little is known about non-major histocompatibility complex-restricted responses. In two phase I studies, we have immunized advanced melanoma patients with either interleukin-7 (IL-7) gene-transfected or IL-12 gene-transfected, autologous, irradiated melanoma cells. To monitor the immune response, peripheral blood mononuclear cells were collected before the first vaccination and 2 weeks after the third vaccination. Spontaneous lytic activity and lymphokine-activated killer (LAK) activity after a 5-day culture in the presence of 1000 U/mL IL-2 against autologous and against allogeneic melanoma cells were measured. In parallel, a precursor cytotoxic T-cell frequency analysis was performed using a 25-day limiting dilution analysis assay. A total of 10 of 14 immunologically evaluable patients demonstrated a marked increase in LAK activity, and 7 of 14 showed increased spontaneous lytic activities against autologous melanoma cells after three vaccinations. Remarkably, two patients with a good clinical performance status (Karnofsky index of >70; Multitest Merieux of >13.4 mm/3) and -the highest cytotoxic T-lymphocyte (CTL)-response after vaccination showed the only clear decrease in LAK and spontaneous lytic activity. Otherwise, three patients with no detectable CTL response after vaccination demonstrated an increase in LAK activity and the strongest increase in the autologous spontaneous lytic activity. This group of patients was associated with a poor clinical performance status (Karnofsky index of <70; Multitest Merieux of <4 mm/1) and with no clinical response. In conclusion, in accordance with other studies, a good clinical and immunological performance status appears to be the prerequisite for a successful CTL response. However, even strong non-major histocompatibility complex-restricted responses could be generated in patients with reduced clinical performance in vaccination therapies with gene-transfected autologous tumor cells.

Adult↗

Platelet monoamine oxidase activity in alcoholics with and without a family history of alcoholism.

A number of studies point at platelet monoamine oxidase (MAO) activity being reduced in alcoholics with a family history of drinking, this being a possible vulnerability marker for alcoholism. To test this hypothesis, we examined a group of recently detoxified alcoholics with high (n = 25) and low genetic loading for alcoholism (n = 28) and a group of healthy controls (n = 21). Clinical assessments were made using the SCID II interview for psychiatric disorders, the Family History Assessment Module and the Semi-Structural Assessment of Genetics in Alcoholism, a questionnaire especially designed for genetic studies. Platelet MAO activity with and without ethanol stimulation and the percentage of MAO activity with ethanol did not differ between groups. The only significant difference was a lower inhibition of MAO activity with ethanol in alcoholics both with and without a family history compared to controls. In patients with antisocial personality traits, platelet MAO activity was also not found to be different from other alcoholics. Our findings question the hypothesis of reduced platelet MAO activity to be a possible vulnerability marker for alcoholism.

Adult↗

Late auditory evoked potentials (P300) do not discriminate between subgroups of alcohol-dependent patients defined by family history and antisocial personality traits.

Alcohol dependent patients with a family history of alcoholism and with antisocial personality traits were supposed to have frontal brain dysfunction. Late evoked potentials may be useful to discriminate these patients from patients without family history or antisocial behavior. We investigated 56 abstinent patients hypothesizing that four subgroups of abstinent alcoholics with regard to family history (FHP: family history positive, FHN: family history negative) and antisocial behavior (ASP: antisocial traits present, ASN: antisocial traits not present) would exhibit differences in P300, particularly when recorded by frontal electrodes. FHP/ASP patients were expected to show the lowest P300 amplitudes in frontal electrode sites. Beside single electrode recordings, a new method in analyzing P300 scalp data by dipole source analysis (BESA: Brain electric signal analysis) was used. No difference in the P300 values was observed between the FHP/FHN and ASP/ASN groups. Similar results were found by analyzing ASP/ASN and FHP/FHN groups separately. The findings of single electrode recordings were consistent with BESA-dipole results. In conclusion, auditory P300 had a low discriminative power with regards to subgroups of inpatient alcoholics defined by family history and antisocial personality traits. Reasons for the negative findings in this study are discussed.

Adult↗

[Postoperative delirium: risk factors, prophylaxis and treatment].

After surgical operations delirium can occur as a serious and possible lethal complication in about 5-15% of patients. Additionally, risk factors such as old age, polymedication, organic and psychiatric diseases raise the incidence. After open-heart and orthopedic surgery more than half of the patients are affected. Delirium has negative effects on postoperative mobilization and reconvalescence and prolongs treatment on the ward. It is discussed in the literature that delirium may induce dementia in older patients. The correction of metabolic and electrolyte imbalances, as well as the therapy of neurologic and psychiatric diseases, belongs to prophylactic treatment. Environmental conditions which facilitate reorientation of the patient after operation have beneficial effects. Some success has been achieved by using the nootropic substance piracetam as a prophylactic. In acute treatment, the butyrophenon-neuroleptic haloperidol is the drug of choice. In delirium caused by intoxication with anticholinergic agents, physostigmin is indicated. Benzodiazepines, clonidine and clomethiazole are used in particular for the treatment of withdrawal delirium.

Aged↗

The flare-up reactions after systemic provocation in contact allergy to nickel and gold.

In a controlled double-blind experimental study, patients with contact allergy to nickel or gold were exposed systemically to their contact allergen. Nickel sulfate was given orally, gold sodium thiomalate intramuscularly, and placebo by both routes. Clinical reactions including body temperature were followed and 7 plasma cytokines and acute phase reactants were assayed before and 24 h after provocation. Clinical flare-up, with reactivation of healing patch tests and/or toxicoderma-like reactions, was observed in patients receiving their specific allergen. A transient fever was noted in patients allergic to gold when exposed to gold, not in others. There was a significant increase in plasma tumour necrosis factor-alpha, soluble tumour necrosis factor receptor 1, interleukin-1 receptor antagonist, and neutrophil gelatinase associated lipocalin in patients allergic to gold when exposed to gold allergen. Furthermore, in patients allergic to nickel exposed to nickel allergen there was a highly significant increase in plasma soluble tumour necrosis factor receptor 1. Interferon-gamma, interleukin-4, and C-reactive protein did not increase in any of the patient groups. Clinical reactions during flare-up in contact allergy are accompanied by release in the blood of several cytokines. This release is not a consequence of a toxic effect or bound to a particular allergen. Instead, the cytokine release should be considered a general phenomenon characteristic of the flare-up in contact allergy.

Acute-Phase Proteins↗

Laser Doppler perfusion imaging for the documentation of flare-up in contact allergy to gold.

A healed or healing allergic contact dermatitis is easily reactivated to a flare-up if the patient is provoked systemically with his particular allergen. 5 patients with contact allergy to gold were patch tested with a serial dilution of gold sodium thiosulfate. 1 to 2 months later, when positive test reactions were healed, the patients were given 1 intramuscular injection of gold sodium thiomalate. This resulted in a flare-up of patch tests as well as a transient fever and toxicoderma-like reactions. The flaring tests were registered by digital photographs and laser Doppler imaging (LDI). An increased cutaneous blood flow in the formerly positive patch tests was discernible within 1 h after provocation, increased to a vigorous maximum after 4-6 h, and subsided during the following few days. The earliest increase and the highest peak of blood flow were observed in the test areas of the strongest original test concentration. LDI provides a most suitable technique for studying the dynamics of this rapidly developing inflammation of a mainly dermal character.

Adult↗

Biopharmaceutical characterization of oral immediate release drug products. In vitro/in vivo comparison of phenoxymethylpenicillin potassium, glimepiride and levofloxacin.

The development of in vitro dissolution tests using the paddle and basket apparatus is described with respect to the qualification/validation of the testing procedure. Three examples of immediate release products containing phenoxymethylpenicillin potassium, glimepiride, and levofloxacin providing different solubility characteristics are evaluated. The solubility was high in the case of phenoxymethylpenicillin potassium and levofloxacin and low for glimepiride according to the biopharmaceutics classification system. The permeability is studied using the human colorectal carcinoma cell line CaCo-2. The permeability (10(-6) cm/s) of phenoxymethylpenicillin potassium, glimepiride, and levofloxacin was high. The determined permeability data are confirmed by absorption data obtained by means of numerical deconvolution of plasma concentrations. Recommendations are given for the biopharmaceutical characterization of the three immediate release drug products, taking into account in vitro and in vivo comparison as well as the biopharmaceutics drug classification system. The evaluated acceptance criteria are the following: phenoxymethylpenicillin potassium (80% in 30 min), glimepiride (80% in 15 min) and levofloxacin (80% in 30 min). Typically, for immediate release formulations, one limit is specified for the dissolution to ensure the release of the active ingredient within the present time period. Since phenoxymethylpenicillin potassium and levofloxacin belong to Case 1, no in vitro/in vivo correlation is expected, absorption may be gastric emptying dependent. Glimepiride is categorized to Case 2. Nevertheless, a correlation with the in vivo dissolution profile does not exist, because of the pH-dependent low solubility of the drug. Finally, recommendations are made for the batch control of drug products in accordance with the four Cases.

Absorption↗

Biopharmaceutical characterization of oral controlled/modified-release drug products. In vitro/in vivo correlation of roxatidine.

From the marketed drug product Roxane(R) 75 mg C/MR capsules (roxatidine controlled/modified-release capsules), an in vitro/in vivo comparison was performed to demonstrate a 1:1 correlation between in vitro and in vivo dissolution, and, furthermore, to ensure bioequivalence of the roxatidine controlled/modified-release (C/MR) capsules exhibiting dissolution profiles within the defined acceptance criteria. This 1:1 in vitro/in vivo comparison was calculated using a model independent numerical deconvolution method. The high degree of correlation is extremely rare, nevertheless it allows to omit the testing of clinical side batches for the setting of acceptance criteria for the in vitro dissolution of roxatidine controlled/modified-release (C/MR) capsules. The 1:1 in vitro/in vivo correlation can be explained by the biopharmaceutical characteristics of the drug substance as well as the drug product, that is, pH-independent high solubility of the drug substance as well as dissolution which is independent of pH and agitation. These facts lead to a controlled/modified-release formulation. Therefore, it is important to keep in mind that in most cases in which a pH-dependent solubility/dissolution as well as permeability characteristics can be found, a 1:1 in vitro/in vivo correlation could not be expected.

Administration, Oral↗

Cytokines and acute phase reactants during flare-up of contact allergy to gold.

BACKGROUND AND OBJECTIVE: Patients with contact allergy experience cutaneous, as well as general reactions, when exposed systemically to their contact allergen. This study focused on the release in blood of pertinent cytokines and acute phase reactants as a consequence of parenteral allergen exposure. DESIGN: Ten patients with contact allergy to gold were given one intramuscular injection of gold sodium thiomalate; plasma levels of some cytokines and acute phase reactants were followed for 24 hours. RESULTS: There was a flare-up of 1-week-old patch tests in all 10 patients; a maculopapular rash in 5 of 10; and a transient fever in 4 of 10. Biochemical analyses showed some increase of plasma levels of several cytokines in most patients, interleukin 1 receptor antagonist (IL-ra) and tumor necrosis factor (TNF) in particular, and of C-reactive protein (CRP) and leukocyte proteins. A marked increase of IL-1ra, TNF-alpha, soluble tumor necrosis factor receptor 1 (sTNF RI), neutrophil gelatinase associated lipocalin (NGAL), human (leukocyte) elastase antitrypsin (HEAT), and CRP was observed mainly in the four patients with fever and general skin reactions. CONCLUSION: Systemic exposure to the allergen in contact allergy elicits cutaneous and general reactions; at least in the case of gold allergy, it is accompanied by an emergence of cytokines and acute phase reactants.

Acute-Phase Proteins↗

Contact allergy to gold and gold therapy in patients with rheumatoid arthritis.

Patients with rheumatoid arthritis were investigated for contact allergy to gold in connection with treatment with gold preparations. There were 57 patients with rheumatoid arthritis previously treated with gold, with or without cutaneous side-effects, as well as 20 patients intended for such treatment; all were exposed to patch and intradermal tests with gold sodium thiosulfate, gold sodium thiomalate and auranofin. Contact allergy to gold was demonstrated in 8 out of 77 patients (10.4%). In the retrospective material, gold allergy was found in 1.8%, in the prospective material in 35.0%. Contact allergy to gold is very frequent among patients with rheumatoid arthritis before gold therapy. In order to avoid early hypersensitivity reactions skin tests should be carried out before gold therapy is instituted.

Adolescent↗

Morphology of endogenous flare-up reactions in contact allergy to gold.

In a double-blind study, 20 patients with contact allergy to gold were given an intramuscular injection of gold sodium thiomalate or placebo, inducing a clinical and histological flare-up of healed patch test sites in the gold-injected but not in the placebo group. The test area of the placebo group showed some perivascular lymphocytic foci (UCHL-1+) and vascular endothelial ELAM-1 staining. The gold group, with flare-up, showed larger and more extensive lymphocytic foci with ELAM-1+ endothelium as well as lymphocytic epidermotropism. CD1a+ LC cells were downgraded, tryptase+ mast cells accumulated and CD68+ monocytes/macrophages markedly increased. Probably, a significant part of the tissue priming as a result of patch testing comprises memory T-cells and endothelial ELAM-1 upgrading, but blood-borne CD68+ monocytes may also be instrumental in the flare-up.

Antigens, CD↗

Flare-up at contact allergy sites in a gold-treated rheumatic patient.

Contact allergy to gold sodium thiosulfate and gold sodium thiomalate was established by skin testing in a rheumatic patient intended for gold therapy. An intramuscular test dose of gold sodium thiomalate (Myocrisin) induced a flare-up of previously positive epicutaneous and intradermal test reactions, with a histological and immunohistochemical picture compatible with an allergic contact dermatitis. Since gold allergy is frequent, the cutaneous side-effects of gold therapy ("gold dermatitis") may be explained by such an immunopathological reaction.

Antirheumatic Agents↗