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Biomedical subjects

J Behr

Publications and source records attributed to J Behr.

At least 109 records · Page 6Linked to original sources
PubMed1994

Phase I evaluation of a water-soluble etoposide prodrug, etoposide phosphate, given as a 5-minute infusion on days 1, 3, and 5 in patients with solid tumors.

PURPOSE: To determine the toxicities, maximum-tolerated dose (MTD), and pharmacology of etoposide phosphate, a water-soluble etoposide derivative, administered as a 5-minute intravenous infusion on a schedule of days 1, 3, and 5 repeated every 21 days. PATIENTS AND METHODS: Thirty-six solid tumor patients with a mean age of 63 years, performance status of 0 to 1, WBC count > or = 4,000/microL, and platelet count > or = 100,000/microL, with normal hepatic and renal function were studied. Doses evaluated in etoposide equivalents were 50, 75, 100, 125, 150, 175, and 200 mg/m2/d. Etoposide in plasma and urine and etoposide phosphate in plasma were measured by high-performance liquid chromatography (HPLC). Eleven of 36 patients were treated with concentrated etoposide phosphate at 150 mg/m2/d. RESULTS: Grade I/II nausea, vomiting, alopecia, and fatigue were common. Leukopenia (mainly neutropenia) occurred at doses greater than 75 mg/m2, with the nadir occurring between days 15 and 19 posttreatment. All effects were reversible. Hypotension, bronchospasm, and allergic reactions were not observed in the first 25 patients. The MTD due to leukopenia was determined to be between 175 and 200 mg/m2/d. In 11 patients treated with concentrated etoposide phosphate, no local phlebitis was noted, but two patients did develop allergic phenomena. The conversion of etoposide phosphate to etoposide was not saturated in the dosages studied. Etoposide phosphate had peak plasma concentrations at 5 minutes, with a terminal half-life (t1/2) of 7 minutes. Etoposide reached peak concentrations at 7 to 8 minutes, with a t1/2 of 6 to 9 hours. Both etoposide phosphate and etoposide demonstrated dose-related linear increases in maximum plasma concentration (Cmax) and area under the curve (AUC). CONCLUSION: Etoposide phosphate displays excellent patient tolerance in conventional dosages when administered as a 5-minute intravenous bolus. The suggested phase II dose is 150 mg/m2 on days 1, 3, and 5. The ability to administer etoposide phosphate as a concentrated, rapid infusion may prove of value both in the outpatient clinic and in high-dose regimens.

Adult↗
PubMed1993

Fibroblast chemotactic response elicited by native bronchoalveolar lavage fluid from patients with fibrosing alveolitis.

BACKGROUND: In fibrosing alveolitis activation of lung fibroblasts is the decisive event in the pathogenetic sequence leading to pulmonary fibrosis. Fibroblast stimulating activity was measured in bronchoalveolar lavage (BAL) fluid to assess its relationship to the activity of fibrosing alveolitis. METHODS: Nine control subjects and 40 patients with fibrosing alveolitis caused by idiopathic pulmonary fibrosis (n = 22) or pulmonary involvement in systemic sclerosis (n = 18) were studied. All patients were followed up by lung function testing for a minimum of six months (mean (SE) 13.3 (1.4) months). Twenty five patients received immunosuppressive therapy and 15 refused. At the beginning of follow up BAL was performed and, as a possible indicator of fibroblast stimulating mediators within the lungs, chemotactic migration of cultured human fibroblasts elicited by native BAL fluid was measured in Boyden-type chambers and expressed as a percentage of the chemoattractant effect of 25 ng/ml platelet derived growth factor. The procollagen III peptide level in BAL fluid served as a marker for collagen synthesis. RESULTS: Chemoattractant activity was elevated in the patients with idiopathic pulmonary fibrosis and systemic sclerosis compared with the control group, (mean (SE) 56.4% (8.5%)) and 72.3% (16.3%) v 12.6% (4.0%). Chemoattractant activity was inversely correlated with total lung capacity (TLC) (r = -0.45) and with vital capacity (VC) (r = -0.33). Procollagen III peptide concentrations in BAL fluid and chemoattractant activity were not significantly correlated. For further evaluation chemoattractant activity of 36% (mean value of controls +2 SD) was used to separate normal (< 36%) from elevated (> or = 36%) activity. At the end of follow up, untreated patients with high chemoattractant activity (> or = 36%) showed a significant reduction of VC, TLC, and exercise arterial oxygen tension (PaO2) and a small decrease in carbon monoxide transfer factor (TLCO), whereas a significant improvement in VC, TLC, and TLCO and a small increase of exercise PaO2 occurred in treated patients with high chemoattractant activity. Patients with low chemoattractant activity (< 36%) showed no consistent change in lung function measurements, irrespective of treatment. In contrast, lung function results and differential cell counts in BAL fluid failed to identify progressive disease. CONCLUSIONS: In patients with fibrosing alveolitis the chemoattractant activity of BAL fluid seems to be an independent indicator of lung fibroblast stimulating activity providing relevant information about disease activity, and may help to improve the clinical management of these patients.

Adult↗
PubMed1992

Immunophenotyping of lymphocyte subsets in bronchoalveolar lavage fluid. Comparison of flow cytometric and immunocytochemical techniques.

In order to compare flow cytometry with the conventional peroxidase anti-peroxidase method for the immunophenotyping of bronchoalveolar lavage fluid (BALF) lymphocytes, we studied BALF samples from 27 patients with various interstitial lung diseases. The results achieved with both methods were consistent concerning CD3+ pan T cells, CD4+ T helper/inducer, CD8+ T suppressor/cytotoxic and CD57+ natural killer cells. In contrast, a statistically significant lower anti-HLA-DR positive subset was obtained with flow cytometry than with the immunoperoxidase method (p less than 0.005). Since regression analyses and reliability counts showed further agreement between the methods, we conclude that flow cytometric immunophenotyping of BALF lymphocytes leads to similar, if not better, subset analyses than the immunoperoxidase method.

Bronchoalveolar Lavage Fluid↗
PubMed1992

Treatment of systemic sclerosis with gamma-interferon.

Numerous drugs have been recommended for the treatment of systemic sclerosis, but without any significant effect on the fibrotic stage of this disorder. Because recombinant gamma-interferon (gamma-IFN) is a potent and selective inhibitor of fibroblast proliferation and collagen production by human dermal fibroblasts in vitro, we assessed the effects of gamma-IFN treatment on the skin and on pulmonary function in patients with systemic sclerosis. Fourteen patients entered the study, and nine completed the 12-month trial. Fifty micrograms/day of gamma-IFN was administered subcutaneously 3 days per week. At the end of the 12-month treatment period a significant improvement was observed in total skin score, and blood gas analysis showed a significant increase in Pa O2 during therapy with gamma-interferon. Other clinical parameters (dysphagia, Raynaud's phenomenon, cardiac involvement) were not altered significantly. No serious adverse effects were noted. These results suggest a beneficial effect of gamma-IFN on the cutaneous fibrotic abnormalities and on lung fibrosis in systemic sclerosis.

Adult↗
PubMed1991

Similar frequency of autoantibodies against pneumocytes type II and Clara cells in patients with interstitial lung diseases and healthy persons.

Several experimental findings suggest an association between interstitial lung diseases and autoantibodies. Antibodies against lung tissue including pneumocytes type II in patients suffering from idiopathic pulmonary fibrosis (IPF) were reported in recent years. In this investigation the serum of 103 persons (10 with IPF, 23 with M. Boeck, 18 with rheumatoid arthritis (RA) and 52 healthy controls) was examined for autoantibodies against pneumocytes type II and Clara cells by indirect immunofluorescence on human lung tissue. These antibodies against both cell types are an additional proof for common antigens in pneumocytes type II and Clara cells. The autoantibodies were present in similar frequency in the 4 groups (IPF: 20%, M. Boeck: 26.1%, RA: 22.2% and 23.1% of the healthy controls). So no significant association was found between the antibodies and the interstitial lung diseases. A role of the antibodies in the pathogenesis of the diseases, however, can not be excluded by this study. A possible role as parameter of development of interstitial lung diseases should be subject to further investigations in form of a prospective follow up study.

Adult↗
PubMed1991

Pathogenetic significance of reactive oxygen species in diffuse fibrosing alveolitis.

Excessive release of reactive oxygen metabolites (ROM) from lung inflammatory cells has been claimed to be of major pathogenetic significance in diffuse fibrosing alveolitis. In the present study, the content of oxidized methionine residues [Met(O)] as a percentage of total methionine (Met) in BAL-derived proteins was used to assess the biologic effect of ROM. In addition, procollagen-III-peptide was measured in BAL fluid as a marker of fibroblast activation. We investigated bronchoalveolar lavage (BAL) samples from seven control patients without evidence of interstitial lung disease and from 42 patients with fibrosing alveolitis caused by idiopathic pulmonary fibrosis (IPF), n = 20, or by collagen vascular disease (CVD), n = 22. Met(O) was elevated in the patients with IPF or CVD compared with that in the control subjects (8.86 +/- 1.26 and 8.13 +/- 1.44% versus 3.36 +/- 0.49%, p less than 0.01 and p less than 0.05, respectively; mean +/- SEM). A positive correlation was found between percentage of neutrophils in BAL and Met(O) in both groups separately and combined (IPF, r = 0.84; p less than 0.001; CVD, r = 0.44; p less than 0.05; IPF and CVD, r = 0.60; p less than 0.001), whereas an inverse relationship existed between Met(O) and the percentage of alveolar macrophages in BAL (IPF, r = -0.59; p less than 0.01; CVD, r = -0.24; NS; IPF and CVD, r = -0.41; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Phase I trial of intravenous vinzolidine (LY 104208) given on a biweekly dosing schedule.

Vinzolidine (VZL) is a semisynthetic vinca alkaloid with broad antitumor activity in animal models of malignancy but had unpredictable toxic effects when given orally to humans. To minimize the toxic effects due to potential erratic gastrointestinal absorption, this drug was restudied in man as an intravenous preparation given as a rapid injection every two weeks. The maximum tolerated dose (MTD) on this schedule was 9.0 mg/m2 with unpredictable leukopenia (usually occurring 5-14 days post treatment but appearing erratically), constipation, paralytic ileus, and inappropriate ADH syndrome as major toxicities. Nonhematologic toxicities were dose-limiting. Repetitive dosing at two week intervals was associated with leukopenia at D 14-15 in some but not all patients treated above 5.0 mg/m2 precluding further treatment on schedule. In contrast, the oral MTD of this agent in our prior studies was 45 mg/m2 with no evidence of delayed leukopenia. Intrapatient variability of toxicity was small; interpatient variability of toxicity was substantial and did not correlate with prior therapy. Because of the presence of delayed hematologic toxicity on repetitive dosing schedules, intravenous VZL should be given on a dosing schedule longer than 14 days. No antitumor activity was seen in this study.

Adult↗
PubMed1990

Measurement of pulmonary parenchymal attenuation: use of spirometric gating with quantitative CT.

A new approach to reproducible measurement of lung attenuation and structure by means of respiratory-gated computed tomography (CT) was developed. The patient breathes through a microcomputer-controlled pocket spirometer during the complete CT examination, starting with a measurement of the vital capacity. At a user-selected respiratory level, the CT scan is triggered and air flow is inhibited mechanically. To exclude operator-related reproducibility errors, evaluation is based on semiautomated algorithms that isolate lung parenchyma by fast contour tracing. In a study on one volunteer, measurement of lung attenuation changed by a factor of about 2.6 (-895 to -730 HU) as a function of inspirational status. Reproducibility on the order of 5% or better can be achieved only with tight spirometric control of respiration.

Humans↗
PubMed1990

[Primary metastasizing fallopian tube carcinoma. Case report and overview of current therapy].

Case report a primary metastasizing carcinoma of the fallopian tube with radical operation and 4 cycles of antineoplastic chemotherapy (cisplatin and treosulfan). Tumor markers decreased to normal level following primary treatment and the first chemotherapy cycle. After six months we did and immunoscintigraphy and second-look-laparotomy including the Regaj-procedure. There was a histological complete remission. Additionally we give a review about cytostatic treatment of this cancer the last then years. Radical operation combined with adjuvant chemotherapy is said to be successful.

Adenocarcinoma↗
PubMed1990

[Functional changes in the lower urinary tract after irradiation of cervix carcinoma].

104 patients submitted to primary irradiation for cervix carcinoma were examined by means of urodynamic methods of diagnosis in order to investigate the functional changes of the lower urinary tract induced by therapy. 34 patients could be examined prior to therapy, 19 and 12 patients, respectively, were examined six and 18 months on an average after the treatment. Another group of 70 patients had retrospective check-up examinations with average intervals of five and ten years. Hydronephrosis occurred only as a late result after more than six years in 12% of the irradiated women. The incidence of residual urine, significant bacteriuria, and disturbed sensory function of the bladder was not important. All patients were incontinent two years after the irradiation; 60% of the cases of incontinence were due to the bladder and 40% to the urethra. The increase of urgency incontinence is possibly caused by a radiofibrotic reaction of the bladder, as is shown by correspondent cystometric alterations: the bladder tonicity increased, whereas the bladder capacity decreased. These alterations were only partially reversible. The stress incontinence, however, was found already before the treatment. The maximum urethral closing pressure, which often indicates incontinence due to the urethra, was not modified by the irradiation. An increased stress incontinence, probably caused by advanced age, was found only after six years or later. The problems resulting from functional changes should be taken into consideration in the course of post-therapeutic care, i.e. the patients concerned should be given instructions for a regular bladder training.

Brachytherapy↗
PubMed1990

[Cysto-urethroscopy in the diagnosis of stress incontinence].

61 patients with a urinary stress incontinence of different degrees were examined by cysturethroscopy at a bladder volume of 300 ml in supine position and also by lateral urethrocystography in standing position. With increasing subjective stress incontinence, they showed an increasing dilation of the bladder neck in cysturethroscopy and lateral urethrocystography. At the same time the urethral closure pressure at the proximal urethra diminished. These observations offer new possibilities in the diagnosis of urinary stress incontinence.

Cystoscopy↗
PubMed1990

[Diagnosis of irritative-toxic isocyanate asthma with the isocyanate exposure test].

We investigated 10 healthy control subjects, 15 asthmatics without occupational exposure to isocyanate, and 45 "isocyanate workers" with workplace-related respiratory symptoms. In none of the cases did the skin test or the IgE-RAST reveal a type I sensitisation to isocyanate. The investigation programme included a lung function test, provocation with metacholine or acetylcholine, and an isocyanate challenge test under controlled clinical conditions. A total of 17 "isocyanate workers", and 1 asthma patient with no occupational exposure to isocyanate revealed a positive bronchial obstructive reaction to the isocyanate challenge test. In 10 of the patients, the MCH (ACH) test was positive; 2 were chronically obstructive, but 6 patients showed no signs of bronchial hyperreactivity. No significant differences in the severity of the bronchial obstructive reaction induced by isocyanate exposure were observed between patients with and those without bronchial hyperreactivity. In the group of "isocyanate workers", the isocyanate challenge test was observed to be superior to the MCH (ACH) provocation test in terms of sensitivity (0.68 versus 0.62) and specificity (1.0 versus 0.61), this difference being more obvious in the overall group (sensitivity 0.71 versus 0.62; specificity 0.98 versus 0.49).

Airway Resistance↗
PubMed1990

[Pulmonary manifestation of progressive systemic scleroderma: prognostic value of centromere antibodies and antibodies to Scl-70 nucleoprotein].

We examined 74 patients with systemic sclerosis. 21 of them (= 28%) had Scl-70 antibodies in their blood serum and 12 (= 16%) were anticentromere antibody positive, whereas in 41 cases (= 56%) none of these antibodies could be detected. In patients with Scl-70 antibodies lung function tests showed a decrease in vital capacity (p less than 0.05), total capacity (p less than 0.01), and diffusing capacity (p greater than 0.05/n.s.) as compared to ACA-positive patients. A limitation of pulmonary function was seen in 76% of Scl-70-positive patients, in 44% of antibody-negative patients, and in only 33% in the ACA-positive group. A disabling respiratory limitation was found in 14% of Scl-70-positive patients, and in 7% of antibody-negative patients, whereas none of the ACA-positive patients had a higher degree of respiratory insufficiency. We conclude that pulmonary involvement in systemic sclerosis is most frequent and severe in patients with Scl-70 antibodies; it is relatively rare and of minor severity in ACA-positive patients. Antibody-negative patients are in between these extremes.

Adolescent↗
PubMed1989

A controlled clinical trial of baclofen as protective therapy in early Huntington's disease.

We carried out a controlled clinical trial to examine the potential of baclofen to slow the functional decline of patients with early Huntington's disease (HD). The basis of the trial was: (1) the hypothesis that excitatory amino acid neurotransmission mediates the neuronal degeneration of HD, (2) preclinical evidence that baclofen retards corticostriatal release of glutamate and aspartate, and (3) reports that baclofen produces short-term clinical benefits in some HD patients. Sixty patients with early HD were randomized to chronic baclofen, 60 mg/day, or placebo treatments and followed systematically for up to 42 months. Total functional capacity was not favorably influenced by baclofen treatment. Factors that contributed, although nonsignificantly, to a more rapid rate of total functional capacity decline included younger age (less than 35 years), earlier stage (stage I) of illness, paternal inheritance of the HD gene, and baclofen treatment. Our patients declined at a pace slower than that observed in other prospective studies, a finding likely due to selection criteria, avoidance of neuroleptic therapy, and strong psychosocial support.

Adolescent↗