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Biomedical subjects

H Behrendt

Publications and source records attributed to H Behrendt.

At least 55 records · Page 3Linked to original sources

H1- and H2-antagonists in allergic and pseudoallergic diseases.

Although known for more than 80 years, histamine still remains a fascinating substance for allergy research. Histamine antagonists have been in clinical use since 1942. The classical H1-antagonists with sedative side-effects have been more or less replaced by newer non-sedating H1-antagonists; the role of H2-receptors in allergic diseases is still controversial. There, are however, increasing reports of beneficial effects of H2-antagonists, mostly in combination with H1-antagonists, in a variety of allergic and pseudoallergic conditions such as chronic urticaria, anaphylactoid reactions due to colloid volume substitutes, opioid analgesics and radiographic contrast media. The combined use of H1- and H2-antagonists might not only act as specific histamine antagonism but exert a mast cell stabilizing effect, as demonstrated in animal experiments and some clinical studies. Future research will show whether the combined use of H1- and H2-antagonists will become a routine therapeutic procedure in allergy therapy.

Anaphylaxis

Histamine, antihistamines and atopic eczema.

Histamine is known to be a classical inducer of pruritus. In atopic eczema, itch is a prominent feature (regarded by some even as a 'primary lesion'!). One of the most potent chemical mediators of itch is histamine. Histamine, together with other mediators may play a role in the pathophysiology of atopic eczema: the increased release of histamine from basophil leucocytes of atopic patients has been described, as well as elevated histamine levels in plasma and skin during acute exacerbations of eczematous lesions. Therefore, application of H1 antagonists seems to be a rational regime in the symptomatic treatment of atopic eczema. Nevertheless, some controversy exists regarding the clinical efficacy of orally applied H1 antagonists in this disease, especially with regard to the newer non-sedating compounds such as terfenadine, astemizole, loratadine and cetirizine. Review of the literature shows that there are studies demonstrating a clear-cut antipruritic effect of non-sedating H1 antagonists. Thus the sedative action does not seem necessarily to be connected with therapeutic efficacy in treating itch in atopic eczema. Newer studies show that cetirizine exerts an additional inhibitory effect on eosinophils. This may broaden the therapeutic spectrum of this H1 antagonist in diseases with eosinophil involvement.

Dermatitis, Atopic

Experimental evidence for amide hydrolysis of indomethacin in rabbit skin.

Amide hydrolysis of indomethacin was investigated in rabbit skin using the isolated perfused rabbit ear model. Indomethacin was applied topically on the surface area of 4 rabbit ears using a 1% alcoholic solution (Elmetacin). Indomethacin and its hydrolytic product N-deschloro-benzoyl-indomethacin (DBI) were determined in the venous efflux. The concentrations of indomethacin and DBI increased during the first 160 min and remained constant thereafter, the concentrations amounting from 0.041 +/- 0.001 to 0.497 +/- 0.018 nmol/min/cm2 (indomethacin) and from 0.84 +/- 0.03 to 3.24 +/- 0.31 pmol/min/cm2 (DBI). Thus steady state was reached with both substances, indicating a formation of DBI in the range of 0.65-2.01%. Considering the low hydrolytic turnover rate, the limited efficacy of topically applied indomethacin in the treatment of skin diseases does not seem to be due to extensive metabolic inactivation via amide hydrolysis in this target organ.

Amides

[A clinical trial of desired and unwanted effects of topically applied glucocorticosteroids in the human].

Several methods are available for testing the clinical efficacy of topical glucocorticosteroids, some of which only check single parameters relevant to the inhibition of inflammation. These methods include the vasoconstriction assay, the erythema inhibition assays, the psoriasis-plaque assay and the contact sensitization inhibition assay. The methods of testing side-effects include the Duhring chamber assay, the ammonium hydroxide blister assay and the corticoid stratum corneum assay. Provided the most appropriate of these methods are carefully selected, reliable data on the efficacy of topical glucocorticosteroids can be obtained.

Administration, Topical

[Osteomyelitis in newborn infants].

This article describes 12 patients (aged 1-28 days) suffering from neonatal osteomyelitis diagnosed between 1975 and 1987. Complications had occurred during 5 pregnancies, 9 patients had problems in the perinatal period (5 infections). In 9 cases (75%) only local symptoms existed, of which localized swelling, erythema, and loss of function were the most common. Deep soft-tissue swelling was the most common initial radiographic finding. Staphylococcus aureus (penicillin-resistant in all cases) was the most important aetiological organism (66%). Haemolytic streptococci occurred in 3 patients (group B twice, group A once). Six of 12 patients showed multifocal lesions, in 7 out of 12 patients concomitant septic arthritis existed. All patients received antibiotics (at least 2 weeks parenterally, total duration 6 weeks), while surgical intervention (exploration and drainage) took place in 8 patients. On follow-up (8 months-13 years) 4 patients showed deformity of the affected limb, leading to impaired function in 2 cases. Patients suffering from neonatal osteomyelitis require fast and properly directed therapy in order to prevent serious sequelae. Early surgical intervention is necessary if joint involvement exists.

Combined Modality Therapy

The significance of an isolated central nervous system relapse, occurring as first relapse in children with acute lymphoblastic leukemia.

In a retrospective study, which comprised the whole Dutch childhood population of approximately 3 million children, the authors assessed the influence of an isolated meningeal relapse, occurring as first relapse, together with some patient and treatment characteristics on prognosis in 142 children with acute lymphoblastic leukemia (ALL). Until their first relapse, patients were initially treated according to standard protocols, whereas the treatment for relapse was heterogeneous. Concerning the probability of achieving a second complete remission (CR) it appears that the duration of the first CR is the single most important prognostic factor. The duration of the first CR is also the most important factor with regard to the duration of the second CR, upon which also age and sex have a significant influence. Concerning the survival from the time of central nervous system (CNS) relapse, again the duration of the first CR appears to be the most important prognostic factor, followed by age and the institution of systemic reinduction treatment. Other factors, such as initial leukocyte count, attainment of first CR within 48 days, type of reinduction treatment, and the cerebral spinal fluid (CSF) blast count at the time of relapse, have a less important, but nevertheless significant influence on survival. The median survival from the time of CNS relapse is 25 months, the 5-year survival is 25%, whereas the ultimate survival will be less than 20%. From 90 patients who developed second or subsequent relapses, 75% experienced a bone marrow relapse during the follow-up period. From this study the authors conclude that CNS relapse in children with ALL carries a grave prognosis, which requires the institution of intensive retreatment programs.

Adolescent

Inhalation hazards from airborne particulates evaluated by in vitro cyto- and genotoxicity testing: a long-term study over a period of 14 years (1975-1988) from a highly industrialized area.

26 samples of airborne particulates collected between 1975 and 1988 in the highly industrialized Rhine-Ruhr region were analyzed for cytotoxic and genotoxic activity. Samples were extracted by organic solvents and quantitatively transferred to dimethyl sulfoxide for tissue culture experiments. Cytotoxicity testing of samples revealed a dose related loss of cell viability of mouse and human macrophages as well as an impairment of phagocytosis. We observed a reduction of "plating efficiency" of rodent and human lung cell lines induced by extracts. In the presence of extracts we found an inhibition of DNA synthesis, alterations of cell cycle progression and diminished cell growth of rodent, primate and human tissue culture cells. Genotoxic potency of extracts caused dose dependently an induction of "sister chromatid exchanges" in human lymphocyte cultures, Chinese hamster cell line V 79 and human type II pneumocytes of line A 549. Furthermore, we observed by extracts "chromosomal aberrations" in human lymphocyte cultures and a strong "enhancement" of malignant cell transformation of SV40-infected Syrian hamster kidney cells.

Air Pollutants, Occupational

Skin blister fluid levels of ketoconazole during repetitive administration in healthy man.

Ketoconazole administered orally is used in the treatment of superficial and deep mycoses. To evaluate its active concentrations in skin tissue, serum, suction blister fluid (SBF), and cantharides blister fluid (CBF) levels of total and non-protein bound ketoconazole were determined. In general, only the free drug is considered to be the active one. Six healthy subjects received 200 mg once daily for 5 days. Total ketoconazole concentrations were determined by HPLC. The unbound fractions of ketoconazole in SBF (2.3%) and CBF (1.2%) were calculated from plasma protein binding (99.0%). Before the ultimate dose, levels of unbound ketoconazole in SBF and CBF were 0.64 +/- 0.16 and 0.70 +/- 0.25 ng/ml and were thus in accordance with free ketoconazole serum levels (0.52 +/- 0.24 ng/ml; p greater than 0.05). Furthermore, following the ultimate dose, the areas under the blister fluid level-time curves of unbound ketoconazole did not differ from the respective areas under the serum level time curves, thus distribution equilibrium between serum and skin blister fluid was obtained. Peak concentrations of free ketoconazole were (SBF) 8.6 +/- 2.9 ng/ml and (CBF) 8.9 +/- 2.3 ng/ml. Free concentrations in SBF and CBF were far below the MIC values for dermatophytes and Candida ssp. reported in the literature, leaving the concentration-effect relationship of ketoconazole still open for discussion.

Adult

Absorption and ester cleavage of methyl salicylate by skin of single-pass perfused rabbit ears.

1. Rabbit ears were single-pass perfused with a cell-free medium. Arterial pressure, oxygen consumption, and lactate production increased with flow rate. 2. Methyl salicylate was hydrolysed with an apparent Vmax of 1.5 nmol/min per cm2 surface area, a rate about 25 times greater than after arterial administration. 3. Estimation of the Km was not possible, due to oedema developing at arterial concentrations greater than 100 microM methyl salicylate. 4. The model appears suitable to compare absorption, as well as metabolic rates, of xenobiotics in rabbit skin.

Animals

[Quality control in medicine. Analysis of death certificate entries with a personal computer].

Important information obtained from autopsies may be statistically evaluated by means of decentralized data processing, using the personal computer. A method for precise evaluation of death certificates against autoptic findings is described in this paper. This computer-assisted approach facilitates statistical analysis of mortality and supports the accuracy of clinical diagnoses.

Cause of Death

[Prevention of oral side effects in children receiving chemotherapy].

Especially in children the frequency of oral complications associated with cancer chemotherapy is high. The dentist plays an important role in preventing or reducing these sometimes life-threatening problems. Oral symptoms of the underlying disease, oral sequelae from chemotherapy, patient-related factors and a preventive oral care program will be discussed.

Candidiasis, Oral

[Metabolism of drugs in the skin].

The principle metabolic pathways in the skin and their practical implications are still largely unknown. Some insight has already been gained from a few in vivo methods (application of radiolabelled substances in animal and man) and several in vitro methods (skin slice models, use of skin homogenates, skin perfusion models). Most of the drugs investigated with these methods have been glucocorticosteroids: cortisol (oxidation to cortisone, reduction at C-20 and delta 4), diflucortolonvalerate, fluocortinbutylester (ester cleavage). Estradiol (oxidation to estrone) and vidarabine-5-valerate (ester cleavage) are drugs of a different type that have been examined.

Animals

[Significance of recurrence in children with acute lymphatic leukemia].

UNLABELLED: Relapse is the main obstacle on the way to cure in children with acute lymphoblastic leukemia. In a retrospective study the influence of some prognostic factors and the prognosis have been evaluated in children with an isolated bone marrow relapse and an isolated CNS relapse. The median survival in 152 children with an isolated bone marrow relapse was 13.3 months. Favourable prognostic factors were: duration of first complete remission (CR) longer than 24 months, age at diagnosis between 2 and 6 years, initial leucocyte count below 50 X 10(9)/l, re-induction treatment with four drugs and the institution of a second central nervous system (CNS) prophylaxis. The most important prognostic factor was the duration of the first CR. The median survival in 140 children with a CNS relapse was 25 months. Favourable prognostic factors were: duration of first CR more than 24 months, age at diagnosis between 2 and 10 years, initial leucocyte count below 10 X 10(9)/l and a low blast count at the time of diagnosis of CNS relapse. The estimated survival in children with bone marrow relapse as well as in children with CNS relapse is less than 20%. IN CONCLUSION: with current treatment regimens both bone marrow and CNS relapse have a very poor prognosis in children with acute lymphoblastic leukemia.

Antineoplastic Combined Chemotherapy Protocols

Treatment of Hodgkin's disease in children with or without radiotherapy.

From 1975 until 1984 37 children with newly diagnosed Hodgkin's disease were treated with six mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) courses with or without involved field radiotherapy (25 Gy) independent of the stage of their disease. Patients with small lymph node tumors (less than 4 cm) received only six MOPP-courses. Patients with large lymph node tumors (greater than 4 cm) received involved field radiotherapy, 25 Gy to the large tumor masses, between the third and fourth MOPP-course. For the 21 patients with "small" tumors, the disease-free survival (DFS) rate is 90%. In this group two patients with clinical stage (CS) III disease have relapsed but both are alive after successful salvage treatment. The median follow-up time is 69.7+ months. For the 16 patients with larger tumor masses (greater than 4 cm) the DFS rate is 87.5%. In this group one patient with CS II relapsed and died of Hodgkin's disease, and one with CS III relapsed after 37 months, but is now without evidence of disease, 61 months from diagnosis. The median follow-up time is 62+ months. Most of the children with Hodgkin's disease diagnosed before or during puberty can be cured with chemotherapy alone, and thus will not suffer from the damaging late effects of radiotherapy.

Adolescent