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Biomedical subjects

H Möller

Publications and source records attributed to H Möller.

At least 19 recordsLinked to original sources
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1996

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↗
PubMed1996

Clinical reactions to systemic provocation with gold sodium thiomalate in patients with contact allergy to gold.

In a double blind experimental study, 20 patients with a contact allergy to gold sodium thiosulphate were challenged intramuscularly with the chemically similar gold sodium thiomalate and with placebo. The most spectacular clinical reaction in the 10 patients given the active agent, was an epidermal and dermal flare up of healed patch-test reactions to the gold salts, as well as a high, but transient, rise in body temperature. Previous intradermal tests were similarly reactivated. In addition, toxicoderma-like rashes were observed in several cases, but a flare up of a previous contact dermatitis site was seen in one patient only. The specificity of the positive provocations was demonstrated.

Adult↗
PubMed1995

Therapy of complex I deficiency: peripheral neuropathy during dichloroacetate therapy.

A therapeutic trial with polyvitamins and dichloroacetate (DCA) in combination with thiamine in a 13-year-old girl with complex I deficiency is reported. The polyvitamin therapy included thiamine, riboflavin, ascorbate, coenzyme Q 10 and carnitine. This therapeutic regine was used over a period of 17 months without any effect. Although DCA lowered the lactate concentration in blood and CNS--measured by magnetic resonance spectroscopy--no clinical benefit was achieved. After 20 weeks of DCA therapy a distal polyneuropathy with areflexia developed although 100 mg thiamine daily as comedication was given from the beginning of DCA therapy. Nerve conduction velocity of the peroneal nerve was not detectable, sensible evoked potentials of the tibialis posterious nerve were normal. This side-effect resolved completely within 6 months after omission of DCA. Our observation suggests a direct toxic effect of DCA only on the peripheral nervous system in our patient since several cerebral MRI and magnetic resonance spectroscopy studies showed no abnormalities. CONCLUSION. DCA lowers the lactate concentration in children with complex I deficiency of the respiratory chain in a dose of 100 mg/kg body weight without clinical benefit. Reversible peripheral polyneuropathy may develop under DCA therapy despite thiamine medication.

Adolescent↗
PubMed1995

A study on expert reading of patch test reactions: inter-individual accordance.

To diagnose allergic or irritant contact dermatitis, a clinically relevant contact allergy has to be demonstrated or ruled out, respectively. Although patch testing has been used for 100 years, it remains the method of choice for diagnosing contact allergy. A disadvantage of patch testing is that reading is subjective, based on inspection and palpation of the test area, implying that the assessment is subject to the reader's knowledge and experience. This study was carried out to investigate the accordance in reading patch test reactions between 5 dermatologists. 4 groups, each with 10 patients, participated. Within each group, all 10 were allergic to one and the same sensitizer; nickel, epoxy resin, ethylenediamine, or Kathon CG. The sensitizers were tested in serial dilutions and applied randomly to the back. The tests were read independently by the dermatologists in a blinded fashion. A protocol was used where the dermatologists had to note the presence of the morphological features erythema, infiltration, papules, vesicles, and bullae. In this way, it was possible to allocate the various readings into 4 classification systems, 3 European and one American, although the definition of the various classifications might differ slightly. Based on the readings and classifications, it was possible to calculate the degree of accordance within the 4 systems used. It was also possible to analyze the degree of accordance for the various morphological features. Total accordance for the 5 reading dermatologists for positive and negative test reactions was noted in 36% and 46%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Skin testing with gold sodium thiomalate and gold sodium thiosulfate.

Recently gold sodium thiosulfate was found to be the most common sensitizer after nickel sulfate in our routinely patch tested dermatitis patients. When patients hypertensive to gold sodium thiosulfate were tested with another monovalent gold salt, gold sodium thiomalate, at equimolar concentrations, in principle, no positive reactions were obtained. Gold sodium thiomalate is used for treatment of rheumatoid arthritis, a treatment with a high frequency of adverse skin reactions. To investigate whether the reactivity difference between the 2 gold salts was due to differences in bioavailability, some experiments were carried out. Intracutaneous tests with the 2 gold salts at equimolar concentrations yielded equivalent reactions. When the concentration of gold sodium thiomalate for epicutaneous testing was increased, all 12 gold-allergic patients reacted positively. Therefore, in our department, contact allergy to gold sodium thiomalate is probably as common as contact allergy to gold sodium thiosulfate.

Administration, Cutaneous↗
PubMed1995

The development and course of test reactions to gold sodium thiosulfate.

In our department, gold sodium thiosulfate has become the 2nd most common allergen in routinely patch tested dermatitis patients, with a rate around 10%. Test reactions to this compound often appear late, sometimes so late that active sensitization may be suspected. This study was performed to study the time course of the allergic reaction to gold sodium thiosulfate and to elucidate whether late test reactions mean active sensitization. 10 patients with contact allergy to gold sodium thiosulfate (0.5% pet.) were retested epicutaneously (e.c.) and intracutaneously (i.c.) with dilution series. The clinical course was followed for 2 months with initially short intervals, later more extended. During the entire study, 26 positive e.c. reactions were diagnosed. Within the 1st week, 17 (65%) were recorded. 12 reactions (46% of 26) were noted at the ordinary reading, 3 days after test application. After 10 days, another 9 reactions (35%) appeared. The patients with the latter reactions also had positive test reactions within the 1st week. After 2 months, 9 reactions remained. Out of 30 i.c. tests applied, 25 became positive within 1 week. 19 (76%) of these reactions changed in morphology from thin infiltrates to deep nodules. Another 4 nodules appeared in patients with previous negative i.c. tests. All 23 nodules remained after 2 months. E.c. and i.c. test reactions to gold sodium thiosulfate are long-lasting. Positive patch test reactions emerging after 10 days do not automatically imply active sensitization. To diagnose contact allergy to gold sodium thiosulfate, the ordinary reading at day 3 is insufficient; even reading at 1 week is insufficient and must be supplemented by a reading at 3 weeks. All the i.c. test reactions, however, appeared within 1 week and, in several, a dermal nodule was formed.

Allergens↗
PubMed1995

Can ultraviolet erythema be used to identify the basal cell carcinoma phenotype?

Since a prolonged duration of a strong UVB erythema has been suggested as a marker for propensity to develop skin cancer, we objectively followed the duration and intensity of erythemas induced by UVB and UVA radiation for 28 days in 18 patients with basal cell carcinoma (BCC), and in 15 healthy controls using reflectance spectrophotometry. The erythema index, defined as the difference in redness between UV-exposed skin and normal, adjacent skin on the lower abdomen, did not differ significantly between the two groups at 24 h, when the reaction was maximal, following a dose of 6 MED of UVB. Erythema values after 7 and 14 days were slightly higher in the BCC group, but this difference did not reach statistical significance. At day 7 some patients in the BCC group showed very strong erythemas. At days 21 and 28 the two groups had almost identical erythemal reactions. Following a standard dose of UVA of 100 J/cm2, patients with BCC and healthy controls both showed weak erythemal reactions, which declined somewhat over the study period. No significant differences in pigmentary response were noted between the BCC and the control group, neither following UVB nor UVA. Although individual patients with BCC deviate from the normal erythemal curve for UVB, the UVB response is not a suitable predictive instrument in screening patients with the basal cell carcinoma phenotype.

Basal Cell Carcinoma↗
PubMed1994

Clinical relevance of contact allergy to gold sodium thiosulfate.

BACKGROUND: In our routinely patch tested patients with dermatitis gold was shown to be the second most common sensitizer. In most patients it was difficult to explain the source of sensitization to gold and to see any clinical relevance. OBJECTIVE: Our purpose was to elucidate the clinical relevance of contact allergy to gold sodium thiosulfate. METHODS: A questionnaire on gold exposure and gold sensitivity was answered by 156 consecutive patients with dermatitis. In another group of 1056 routinely tested patients data were collected and analyzed regarding factors such as profession, atopy, localization of the dermatitis, and presence of contact allergies. RESULTS: Gold allergy was overrepresented in those having dental gold. In persons with contact allergy to gold a dermatitis on the ears, fingers, or eye area was most frequent. CONCLUSION: Exposure to gold jewelry and to dental gold may be important in the sensitization and elicitation of dermatitis.

Allergens↗
PubMed1994

High frequency of contact allergy to gold sodium thiosulfate. An indication of gold allergy?

When gold sodium thiosulfate was added to the patch test standard series, positive reactions were obtained in 8.6% of 823 consecutive patients with suspect contact allergy. The test reactions were clinically of an allergic type and, in several cases, long-lasting. There was no correlation with other allergens in the standard series. In a special study on 38 patients with contact allergy to gold sodium thiosulfate, the following principal findings were obtained: positive patch tests to the compound itself in dilute concentration; positive patch tests to potassium dicyanoaurate; negative patch tests to gold sodium thiomalate, sodium thiosulfate, and metallic gold; positive intradermal tests to gold sodium thiosulfate. Our findings make gold sodium thiosulfate the 2nd most common contact allergen after nickel sulfate. It is suggested that a positive skin test to gold sodium thiosulfate represents gold allergy.

Adult↗
PubMed1994

All these positive tests to thimerosal.

By and large, positive patch tests with thimerosal lack clinical relevance and should cause concern neither to the dermatologist nor to the patient. The substance should be retained in standard test series for scientific purposes, but on clinical grounds its inclusion does not seem to be indicated. Nevertheless, the phenomenon is intriguing in its own right.

Cross Reactions↗