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Biomedical subjects

H Behrendt

Publications and source records attributed to H Behrendt.

At least 37 records · Page 2Linked to original sources

Cyclophosphamide-induced disturbance of gonadotropin secretion manifesting testicular damage.

UNLABELLED: Gonadal function was evaluated in 23 men (aged 14.8-28.8 years) treated in childhood with cytotoxic drugs for a solid tumour. Group 1 (N = 14) had been treated with non-alkylating drugs only, while group 2 (N = 9) received the alkylating drug cyclophosphamide in addition (range 3.8-19.5 g/m2). Median age at the start of treatment was 4.6 years (range 0.6-16.1) in group 1 and 13.9 years (range 3.7-16.9) in group 2. Data of the patients were compared with a reference group consisting of 14 normal men. Almost all patients of both groups showed normal development of puberty; 13 of the 14 men in group 1 showed normal hormonal values. In group 2, basal LH and FSH as well as the LH and FSH responses to GnRH showed higher levels compared to those of a reference group (p less than 0.001). Correlation analysis showed an evident correlation between the total dose of received cyclophosphamide and the basal FSH level (r = 0.78; p = 0.002), the FSH response to GnRH (r = 0.73; p = 0.002) and the LH response to GnRH (r = 0.67; p = 0.002). There was no correlation between the hormonal parameters and the doses of the other cytotoxic drugs. Semen analysis showed azoospermia in four boys of group 2 and in none of group 1. Two patients in group 2 had an elevated FSH response to GnRH while their semen analysis was normal. CONCLUSIONS: (1) There is a dose-response relationship between the basal FSH, the LH and FSH responses to GnRH and the dose of cyclophosphamide.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

[Multiple angiolipomas--analgesics therapy with doxepin].

Angiolipomas are rare benign tumours of the subcutaneous fat; they are sometimes solitary but their occurrence is more frequently multiple. Angiolipomas can be differentiated from lipomas clinically by their pronounced tenderness and histologically by their variable vascularization. The disease occurs mostly in young adults, the sites of predilection being the trunk and proximal extremities. Multiple angiolipomas have to be differentiated from other lipomatoses, especially from adiposis dolorosa (Dercum's disease). The case reported in this paper was characterized by typical clinical and histological findings. The systemic administration of acetylsalicylic acid, diclofenac, ketotifen, ranitidine, tramadol, tilidine combined with naloxone did not provide adequate pain relief. In contrast, the therapeutic efficiency of the antidepressant doxepin, which also displays antihistaminic effects, suggests a possible role of mediators in the development of pain in angiolipomas.

Biopsy

[Neurothekeoma. A light and electron microscopy, histochemical and immunohistochemical study].

We report a 37-year-old man with neurothekeoma that developed on the tip of the nose. Histopathological examination revealed a lobulated myxoid dermal tumour. The tumour cells were spindle-shaped or bizarre configuration. In the lower part of the dermis the lesion contained abundant cells simulating glomus tumour or melanocytic naevus. Staining with S-100 protein, epithelial membrane antigen (EMA), neuron-specific enolase (NSE) and desmin were negative. The matrix of the tumour was positive for Alcian blue and periodic acid-Schiff (PAS). Electron microscopic examination showed that the lesion was composed of dendritic cells separated by abundant glassy matrix and varying amounts of collagen fibres. Some of the cells looked like fibroblasts, and others like perineurial cells. The histogenesis of the tumour is discussed with particular attention to histochemical, immunohistochemical, light and electron microscopic findings.

Adult

Possible role of macrophages in allergic rhinitis.

Mononuclear phagocytes have been investigated in biopsies taken from the nasal mucosa and in epithelial cell samples from 22 grass-pollen-allergic subjects before season, after allergen challenge and during season by means of immunohistochemistry and electron microscopy. The cells were positive for CD68/EBM11 and HLA-DR, but failed to react with CD1 and CD23/BB10. The cells increased in number during season as well as after allergen challenge, especially in the upper part of the mucosa. Heteromorphy of macrophages, as seen by transmission electron microscopy, confirmed the presence of diverse macrophage subpopulations in the nasal mucosa of allergic subjects. Using brush sampling techniques, CD68-positive and HLA-DR-positive cells significantly increased in epithelial cell samples 4-8 h after allergen challenge, indicating a central role of these cells not only in antigen processing but also in late phase reactions of allergic rhinitis.

Antigen-Presenting Cells

High survival rate in advanced-stage B-cell lymphomas and leukemias without CNS involvement with a short intensive polychemotherapy: results from the French Pediatric Oncology Society of a randomized trial of 216 children.

From April 1984 to December 1987, the French Pediatric Oncology Society (SFOP) organized a randomized trial for advanced-stage B-cell lymphoma without CNS involvement to study the possibility of reducing the length of treatment to 4 months. After receiving the same three intensive six-drug induction courses based on high-dose fractionated cyclophosphamide, high-dose methotrexate (HD MTX), and cytarabine in continuous infusion, patients were evaluated for remission. Those who achieved complete remission (CR) were randomized between a long arm (five additional courses with two additional drugs; 16 weeks of treatment) and a short arm (two additional courses; 5 weeks). For patients in partial remission (PR), intensification of treatment was indicated. Two hundred sixteen patients were registered: 15 stage II nasopharyngeal and extensive facial tumors, 167 stage III, and 34 stage IV, 20 of the latter having more than 25% blast cells in bone marrow. The primary sites of involvement were abdomen in 172, head and neck in 30, thorax in two, and other sites in 12. One hundred sixty-seven patients are alive in first CR with a minimum follow-up of 18 months; four are lost to follow-up. Eight patients died from initial treatment failure, 14 died from toxicity or deaths unrelated to tumor or treatment, and 27 relapsed. The event-free survival (EFS), with a median follow-up of 38 months, is 78% (SE 3) for all the patients, 73% (SE 11) for the stage II patients, 80% (SE 3) for the stage III patients, and 68% (SE 8) for the stage IV and acute lymphoblastic leukemia (ALL) patients. One hundred sixty-six patients were randomized: 82 in the short arm and 84 in the long arm. EFS is, respectively, 89% and 87%. Statistical analysis confirms equivalence of both treatment arms with regard to EFS. Moreover, morbidity was lower in the short arm. This study confirms the high survival rate obtained in the previous LMB 0281 study without radiotherapy or debulking surgery and demonstrates the effectiveness of short treatment.

Adolescent

Bone marrow relapse occurring as first relapse in children with acute lymphoblastic leukemia.

In a retrospective review which covered the whole Dutch childhood population of approximately 3 million children we studied the prognosis in 164 children with acute lymphoblastic leukemia (ALL) who were initially treated between 1973 and 1983, and who had an isolated bone marrow relapse occurring as first relapse. Until their first relapse, the patients were initially treated according to standard protocols, while treatment for relapse was heterogeneous, and not intensive. Second complete remission (CR) was attained by 78% of the patients. The median duration of second CR was 9 months, the median survival 13 months. Multivariate analysis showed that the duration of the first CR was the most significant variable with regard to prognosis. None of the patients who developed their bone marrow relapse during initial treatment, i.e., within 24 months from diagnosis, survived. Among the 73 patients who relapsed after cessation of the initial treatment there were 19 long-term disease-free survivors, 14 of whom had not developed subsequent relapses after 48(+)-125 + months. From this study we conclude that treatment in children with first bone marrow relapse has to be intensified.

Adolescent

Levels of itraconazole in skin blister fluid after a single oral dose and during repetitive administration.

Oral itraconazole is effective in the treatment of mycoses. To measure its concentrations in the tissue, levels of total and non-protein-bound itraconazole were determined in serum, suction-induced blister fluid, and cantharides-induced blister fluid. Six healthy subjects received 200 mg as a single dose, followed by 100 mg/day for 10 days. Itraconazole binding in suction-induced blister fluid (99.54%) and cantharides-induced blister fluid (99.77%) was calculated from plasma protein binding (99.8%). The single-dose study showed the drug levels in blister fluid to increase more slowly than those in serum. The terminal half-life of itraconazole in serum was 22.5 +/- 3.2 hours. Suction- and cantharides-induced blister fluid levels declined in parallel. After the final dose, itraconazole penetration into cantharides-induced blister fluid was only 70%. Moreover, trough levels of unbound itraconazole in suction- and cantharides-induced blister fluid were 0.239 +/- 0.115 and 0.334 +/- 0.101 ng/ml and thus were significantly lower than free itraconazole levels in serum (0.422 +/- 0.125 ng/ml). Thus a distribution equilibrium between serum and blister fluids was not obtained. Free drug concentrations in suction- and cantharides-induced blister fluid were far lower than the minimal inhibitory concentration values for Candida ssp. and dermatophytes.

Administration, Oral

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