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Biomedical subjects

J Behr

Publications and source records attributed to J Behr.

At least 91 records · Page 5Linked to original sources
PubMed1996

Effects of serotonin on different patterns of low Mg(2+)-induced epileptiform activity in the subiculum of rats studied in vitro.

The subiculum is an epilepsy-prone area within the hippocampal complex that receives a dense serotonergic innervation from the raphe nuclei. We investigated the effect of 5-HT on epileptiform activity in this region with intra- and extracellular recordings. Our data suggest that 5-HT has predominately inhibitory effects on epileptiform activity in the subiculum but in some cases could also function as a disinhibitory agent. As the subiculum is an important output station of the hippocampal complex the serotonergic innervation might influence the spread of epileptic seizures.

Animals↗
PubMed1996

Spread of low Mg2+ induced epileptiform activity from the rat entorhinal cortex to the hippocampus after kindling studied in vitro.

Extracellular recordings were performed in in vitro combined hippocampal-entorhinal cortex (HC-EC) slices obtained from control and amygdala kindled rats to investigate the spread of epileptiform activity from the entorhinal cortex (EC) to the hippocampus (HC). Epileptiform activity was induced by lowering extracellular Mg2+ concentration. In control slices epileptiform activity was in most slices characterized by intericatal discharges and short recurrent discharges in areas CA1 and CA3 and by early seizure like events and late recurrent discharges in the EC and the subiculum. In spite of well preserved anatomical pathways in the combined HC-EC slice in which most of the fibre connectivity between the EC and the dentate gyrus (DG) is intact, seizure like events and late recurrent discharges generated in the EC had only moderate effects on the epileptiform activity in areas CA3 and CA1. In contrast in HC-EC slices obtained from kindled rats epileptiform activity generated in the EC spread to the DG and the areas CA3 and CA1. Kindling facilitates the propagation of seizure like events and late recurrent discharges through the HC-EC slice and appears to alter the filtering function of the DG.

Amygdala↗
PubMed1996

Late pulmonary impairment following allogeneic bone marrow transplantation.

The pulmonary function of 88 consecutive leukemic patients who had undergone allogeneic bone marrow transplantation (BMT) was studied beforehand, at 3 months, at 6 months, and annually thereafter until 5 years after grafting. The parameters for function which are indicative for obstructive and restrictive lung disease deteriorated in all patient groups during the first 3 to 6 months after BMT but partially recovered within one year. Long-term decline in lung function was similar in all patient groups, and neither the onset nor the magnitude of pulmonary dysfunction was related to the occurrence of pulmonary impairment within 6 months after grafting. Multivariate analysis was then employed to assess predictors for long-term pulmonary disease. Despite the obvious effect of chronic graft versus host disease on the course of lung function, it was in itself not a significant predictor of long-term pulmonary outcome. Rather, the conditioning regimen turned out to be indicative; compared with busulfan, fractionated total body irradiation was demonstrated to be clearly superior with a lower incidence of both restrictive and obstructive long-term lung impairment. Our data indicate a previously unknown long-term side effect of busulfan conditioning.

Adult↗
PubMed1996

Spirometrically controlled high resolution computed tomography - quantitative assessment of density distribution in patients with diffuse fibrosing alveolitis.

STUDY OBJECTIVE: Lung density assessed by high resolution computed tomography (HRCT) is sufficiently sensitive for the diagnosis of interstitial lung disease, but may be hampered by uneven disease distribution. We determined the mean and subpleural density values in patients with diffuse fibrosing alveolitis (FA) and evaluated the diagnostic accuracy of both parameters, expressed as post-test odds ratios. MATERIALS AND METHODS: Pulmonary HRCT was performed on 21 FA patients and compared to scans of 27 healthy volunteers. The HRCT procedure was standardized by taking 3 scans at the carina +/- 5 cm, and by defining inspiration levels at 50% vital capacity. Mean lung density (MLD) and subpleural lung density (SLD) were calculated for all participants. RESULTS: MLD and SLD values for healthy subjects were significantly higher compared with the patient group. Odds ratios were 7.8:1 and 3.9:1 for SLD and MLD, respectively, demonstrating a superior discrimination power of SLD in the diagnosis of FA. CONCLUSION: Diagnostic accuracy of quantitative HRCT measurements in FA was improved by the separate evaluation of subpleural lung density, which is a better indicator of the presence or absence of lung fibrosis than is mean lung density.

Adult↗
PubMed1996

Low Mg2+ induced epileptiform activity in the subiculum before and after disconnection from rat hippocampal and entorhinal cortex slices.

The subiculum is an area within the hippocampal complex which participates strongly in ictaform activity generated in the entorhinal cortex (EC). To study the properties of epileptiform activity with intra- and extracellular recording techniques in the subiculum, combined slices containing the EC, subiculum and hippocampus were prepared with and without surgical disconnection of the subiculum from the EC and area CA1. For induction of epileptiform activity extracellular magnesium was lowered. After acute disconnection of the subiculum from the cornu ammonis and the EC, seizure like events similar to those in the more intact preparation did develop. These were characterized by slow negative field potential shifts and, in intracellular recordings by sustained depolarization shifts lasting for 10-43 s. This activity could develop into late recurrent discharges of 1-2 s. These data indicate that the subiculum may be an important zone for epileptogenesis in temporal lobe epilepsy.

Animals↗
PubMed1996

Bronchoalveolar lavage for evaluation and management of scleroderma disease of the lung.

Fibrosing alveolitis (FA) is a frequent and often fatal complication of systemic sclerosis (SSC). Alveolar inflammation has been recognized as a primary event in the pulmonary manifestation of SSC. To evaluate the significance of the alveolitis in SSC, we performed bronchoalveolar lavage (BAL) and correlated the generated data with changes in lung function over time. Seventy nine SSC patients with pulmonary involvement were followed for 56.8 +/- 3.1 wk (mean +/- SEM) with a repeat lung function test at the end of the follow-up period. During follow-up, 38 patients were treated with a systemic immunosuppressive regimen. For evaluation, patients were assigned to two groups according to whether their BAL cell differential was normal (inactive BAL) or abnormal (active BAL: i.e., polymorphonuclear leukocytes > 5% and/or lymphocytes > 15%). Active BAL was associated with more severe lung function impairment than was inactive BAL, and patients with active BAL deteriorated during follow-up if untreated. In contrast, treated patients with active BAL stabilized or improved. In summary, active alveolitis as characterized by BAL is associated with progressive pulmonary disease in SSC patients, and a significant positive effect of immunosuppressive therapy on the course of pulmonary disease was observed in patients with active BAL.

Bronchoalveolar Lavage↗
PubMed1996

Characterization and quantification of alveolar monocyte-like cells in human chronic inflammatory lung disease.

This flow cytometric study was designed to identify, characterize and quantify alveolar monocyte-like cells in healthy volunteers and in patients with chronic inflammatory lung disease. Cells were obtained by bronchoalveolar lavage (BAL) from 19 patients with sarcoidosis, 29 with idiopathic pulmonary fibrosis, 10 with extrinsic allergic alveolitis, 19 with collagen vascular disease, and from 10 healthy volunteers. By taking advantage of the distinct electro-optical features of alveolar macrophages (AMs) and monocyte-like cells, the numbers of alveolar monocyte-like cells were counted, the cell dimensions calculated, and the densities of antigens on the surface of alveolar monocyte-like cells and AMs were compared. By using a panel of monoclonal antibodies detecting CD11b, CD14, CD16, and human leucocyte antigen-DR (HLA-DR), the immunophenotypes of these cells were selectively characterized. In the BAL fluid of patients with chronic inflammatory lung disease, significantly increased numbers of alveolar monocyte-like cells were detected that exhibited an immunophenotype intermediate between blood monocytes and mature AMs. Positive correlations were found between numbers of monocyte-like cells and expression of the monocyte-associated surface antigens CD11b and CD14 on total AMs; in contrast, an inverse relationship existed between monocyte numbers and expression of the macrophage-associated surface antigens CD16 and HLA-DR. When the patients were assigned to two groups according to the percentage of BAL monocyte-like cells being lower or higher than 13% (= mean value of the controls +2SD), it could be demonstrated that a high percentage of BAL monocyte-like cells was associated with significantly reduced lung function parameters. In summary, our flow cytometric data strongly support the view that considerable numbers of blood monocytes are recruited to the bronchoalveolar space in patients with chronic inflammatory lung disease.

Adult↗
PubMed1996

Cardiorespiratory responses to incremental exercise in patients with systemic sclerosis.

Patients with systemic sclerosis are known to have histologic pulmonary abnormalities despite normal chest radiograph or conventional pulmonary function or both. In an attempt to detect early features of lung involvement in progressive systemic sclerosis, we investigated patients with systemic sclerosis using cardiopulmonary exercise testing. We have studied 78 patients who fulfilled the American Rheumatism Association criteria for the classification of systemic sclerosis, and according to the classification of LeRoy, 44 had limited cutaneous systemic sclerosis and 34 had diffuse cutaneous systemic sclerosis. A significantly decreased diffusing capacity (65 +/- 3% of that predicted) was present only in the group with diffuse cutaneous systemic sclerosis. The patients with lung involvement showed a significant reduction in exercise capacity (54 +/- 3% of that predicted) and in oxygen uptake (70 +/- 3% of that predicted). Additionally, we could demonstrate an increased functional dead space ventilation (0.34 +/- 0.02) and widened alveolar-arterial oxygen difference during exercise (44 +/- 3 mm Hg). By cardiopulmonary exercise testing, 12 of the 78 patients (15%) with normal single-breath diffusing capacity for carbon monoxide had increased dead space to tidal volume ratio. Our results suggest that occult pulmonary impairment may be present in patients with normal pulmonary function and that cardiopulmonary exercise testing enables detection of such impairment. Our study results show the limitations of resting data in predicting abnormalities during exercise in patients with systemic sclerosis.

Adult↗
PubMed1996

Phase I study of high-dose etoposide phosphate in man.

Etoposide is a widely used cytotoxic agent with a broad spectrum of activity in human malignancies. This agent has been incorporated into many transplant regimens although toxicity occurs because of its poor water solubility and toxic excipients. Etoposide phosphate, a water soluble prodrug of etoposide, has been studied at conventional dosages in man and shown to have advantages over the parent compound. We have extended our previous experience with this new agent to evaluate the levels needed in transplantation protocols. This phase I study of intravenous high-dose etoposide phosphate over 2 h on days 1 and 2 was designed to determine whether or not dose linearity between the amount of etoposide phosphate administered to patients and generation of etoposide in vivo as seen with conventional dosages of this agent would be present at transplant-dose levels. In addition, the toxicities of these dose levels with the short infusion schedule were defined. A conservative dose escalation scheme was chosen based upon prior knowledge of etoposide. Thirty-one patients (19 male, 12 female) with CALGB performance status 0-1 with a variety of solid tumors entered this study. The patients were treated with dose levels of etoposide phosphate given as the etoposide-equivalent doses of 250, 500, 750, 1000, 1200, 1400, and 1600 mg/m2/day in 250-400 ml of normal saline given as an intravenous infusion over 2 h on days 1 and 2 every 28 days. After the maximal tolerated dose level was determined on this schedule, additional patients received etoposide phosphate as a 4 h infusion on both days in an attempt to reduce toxicities. G-CSF (5 micrograms/kg/day) was administered subcutaneously to all patients from day 3 until the WBC > or = 10000/microliters. Nonhematologic toxicity was considered to be dose limiting. Serial plasma samples for pharmacokinetics were obtained from patients on day 1 of cycle 1. For the 2 h infusion, the maximum tolerated dose of etoposide phosphate was 1000 mg/m2/day x 2 with dose limiting mucositis. In the small number of patients studied, the maximum tolerated dose was reached for the 4 h infusion at 1400 mg/m2/day of drug, again due to mucositis. Other toxicities, despite the rapid infusion schedule, were modest with transient mild headache being most common. At the highest doses etoposide phosphate was efficiently and rapidly dephosphorylated to etoposide. Etoposide generated by dephosphorylation of etoposide phosphate had plasma disposition curves characteristic of etoposide administered parenterally. One partial response occurred in a patient with small cell lung cancer. Etoposide phosphate can be rapidly infused in modest fluid volumes at dosages required for transplantation protocols with minimal acute side-effects. On a 2 h schedule, mucositis becomes the dose limiting nonhematologic toxicity. Mucositis seems to correlate with peak dose levels of the drug rather than total drug administered. On a 4 h infusion schedule given sequentially for 2 days, the maximum tolerated dosage could be increased 40% compared to the 2 h schedule. The relative ease of administration and the rapid conversion of this prodrug into etoposide should make it useful in high-dose therapy settings.

Adult↗
PubMed1995

Reproducibility of quantitative, spirometrically controlled CT.

Quantitative spirometrically controlled computed tomography (with 1-mm-thick sections) was performed twice (with a 5-minute break) in 24 adult patients with pulmonary disease to objectively evaluate parenchymal changes in the lung. Twelve measurements of attenuation were made on apical, carinal, and basal scans (right, left, total of each level, total right, total left, total of all three scans), obtained at 50% vital capacity. Since differences in measurements between the first and second examination were not significant, the method provides highly reproducible results.

Adult↗
PubMed1995

Pathogenetic and clinical significance of fibroblast activation in scleroderma lung disease.

Fibrosing alveolitis (FA) is a major and often fatal complication of systemic sclerosis (SSC). The critical role of fibroblasts in the pathogenesis of FA has long been recognized. Characterization of fibroblast activation in the lungs may improve our understanding and the management of this disease. We analyzed bronchoalveolar lavage (BAL) fluid samples from 9 healthy controls and 43 patients with FA caused by lung involvement form SSC. The chemoattractant activity (CAA) of cultured human fibroblasts elicited by native BAL fluid was measured in Boyden chambers. In addition, procollagen III peptide was measured in BAL fluid as a marker of collagen synthesis. CAA (expressed as percentage of the chemoattractant effect of 0.25 ng/ml platelet-derived growth factor; PDGF) was elevated in the SSC patients compared with that of the controls (control: 12.6 +/- 4.0%; SSC: 68.8 +/- 15.2%; p < 0.01). A positive correlation was found between BAL total cell count and CAA (r = 0.60, p < 0.01). An inverse correlation existed between CAA and total lung capacity (r = -0.55, p < 0.05). The patients were followed up for 13.3 +/- 1.4 months (mean +/- SEM). Twenty-seven patients received immunosuppressive therapy, whereas 16 refused therapy. The patients were assigned to two groups according to their CAA being lower or higher than 36% of the PDGF response (= mean value of the controls + 2 SD).

Adult↗
PubMed1995

Increased oxidation of extracellular glutathione by bronchoalveolar inflammatory cells in diffuse fibrosing alveolitis.

An unbalanced oxidative stress is thought to be an important element in the pathogenesis of diffuse fibrosing alveolitis (DFA). The purpose of our study was to investigate the role of reactive oxygen metabolites (ROMs) released from cultured bronchoalveolar inflammatory cells (BA-cells) on glutathione oxidation. We studied bronchoalveolar lavage samples from 10 healthy controls and from 20 patients with diffuse fibrosing alveolitis (all were nonsmokers). BA-cells obtained by bronchoalveolar lavage (BAL) were incubated with 50 microM of reduced glutathione (GSH). Oxidation of GSH to glutathione disulphide (GSSG) by BA-cell derived oxidants was detected as a decline of GSH in the supernatants. Total glutathione (GSHtot = GSH + 2 GSSG) and GSSG in the epithelial lining fluid (ELF), and methionine sulphoxide (Met(O)) content of BAL proteins were determined. In diffuse fibrosing alveolitis the oxidative activity of BA-cells was enhanced, GSHtot and GSH were decreased, whereas the GSSG:GSH ratio was increased. The oxidative activity of BA-cells correlated positively with the GSSG:GSH ratio, but not with the methionine sulphoxide content. The methionine sulphoxide content was elevated in diffuse fibrosing alveolitis and inversely correlated with GSHtot. The methionine sulphoxide content also correlated positively with the percentage of BAL neutrophils. We conclude that BA-cell-derived reactive oxygen species are capable of oxidizing extracellular GSH in vitro. The positive correlation between the BA-cell oxidative activity in vitro and GSSG:GSH ratio in ELF suggests that a similar oxidative effect on extracellular GSH may also occur in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Peripheral airspace dimensions in patients with COPD.

Monodisperse aerosol particles can be used to assess noninvasively intrapulmonary airspace dimensions. Since emphysematic changes in the peripheral lung are difficult to detect with most of the common lung function tests, aerosol-derived airway morphometry was used to assess the peripheral airspace dimensions (EAD800) in 25 patients with COPD and in 36 healthy volunteers. Spirometric and body plethysmographic measurements were performed in all patients. In ten patients, high-resolution CT-derived mean lung density (MLD) was additionally assessed. In healthy subjects, EAD800 was 0.39 +/- 0.05 mm. In patients, EAD800 was significantly increased (0.82 +/- 0.33 mm). In a subset of nine patients with severe alpha 1-antitrypsin deficiency and clinically severe emphysema, EAD800 was even larger (1.14 +/- 0.32 mm). In patients, EAD800 correlated with MLD (r = 0.82), diffusion capacity (DCO) (r = 0.78), and FEV1 (r = -0.75). Since MLD is considered a valid indicator for lung emphysema, the close correlation between EAD800 and MLD suggests that EAD800 reflects enlarged peripheral airspace dimensions in patients with emphysema.

Adolescent↗
PubMed1995

[Pulmonary manifestations of systemic scleroderma: pathophysiologic and clinical significance of the activation of lung fibroblasts].

Fibrosing alveolitis (FA) is a common and often fatal complication of systemic sclerosis (SSC). The purpose of this study was to characterize the fibrotic process within the lungs using bronchoalveolar lavage fluid (BALF). We investigated 25 healthy controls (CON) and 85 SSC patients. In 61 patients (72%) lung function tests, clinical, and radiological findings indicated manifest FA, whereas 24 patients (28%) where free of significant lung disease. Of the latter, 12 had pathologic BAL differential cell counts (= subclinical alveolitis; SUB), 12 had normal BAL cytology (NOR). BAL samples were analysed for chemoattractant activity (CAA) for fibroblasts using Boyden chambers. Procollagen-III-Peptide (P-III-P) and Laminin fragment P1 (Lam-P1) were measured radioimmunologically. CAA (expressed as % of the effect of conditioned medium) was increased in FA and SUB (CON: 17.3 +/- 3.2; FA: 40.8 +/- 5.8, p < 0.01 vs. CON; SUB: 58.6 +/- 11.8, p < 0.01 vs. CON; NOR: 23.7 +/- 6.3; n.s.). Lam-P1 [U/ml ELF] was also elevated in FA and SUB patients (CON: 0.90 +/- 0.17; FA: 2.07 +/- 0.48, p < 0.05 vs. CON; SUB: 2.61 +/- 1.14, p < 0.05 vs. CON; NOR: 1.05 +/- 0.35, n.s. vs. CON). P-III-P [U/ml ELF] was elevated in FA patients (CON: 8.3 +/- 1.1; FA: 26.9 +/- 5.5, p < 0.001 vs. CON) but not in SUB or NOR (SUB: 10.2 +/- 0.7, NOR: 7.9 +/- 2.9; n.s.). There was no significant relationship between P-III-P and LAM-P1 values in ELF and serum, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

[Quantitative computerized tomography of the lung--respiration controlled diagnosis of diffuse lung diseases].

STUDY OBJECTIVE: Computed tomography provides measurements of lung attenuation which reflect changes in the air to tissue ratio and can thereby be employed for diagnosis of diffuse lung disease. In this prospective study, we quantitatively analyzed lung density by high resolution computed tomography (HRCT) in 26 healthy volunteers, 15 patients with chronic obstructive pulmonary disease (COPD), and 15 patients with idiopathic lung fibrosis (IPF). The procedure was standardized by examination of 3 scans at the carina +/- 5 cm and by defining inflation levels by %VC using an on-line hand held spirometer. RESULTS: Performance of HRCT at 50% VC provides not only significant and distinguishable group data, but is the easiest to carry out for dyspneic patients. The mean lung density at 50% VC for healthy subjects was -820 +/- 4.2 (mean +/- SEM) Hounsfield units (HU). It was significantly lower (p < 0.01) in COPD patients (-865 +/- 9.2 HU), and considerably higher (-697 +/- 17.8 HU, p < 0.001) in the IPF group. At an inflation level of 20% VC, mean lung density values were similarly distributed, at significantly lower values relative to those at 50% VC, but the procedure was more difficult to perform for patients with dyspnea. In contrast, at 80% VC, lung density values for the COPD and control groups were not significantly different (p = 0.08). The sensitivity to detect COPD was improved by selecting HRCT values lower than -900 HU, which represent the part of the lung with an increased air/tissue ratio. For IPF patients an increase of lung density values above -699 HU was characteristic, indicating a decrease of the air/tissue relationship. CONCLUSION: From our data we propose to perform quantitative HRCT measurements at 50% VC. Diagnosis of diffuse lung disease can be further improved by consideration of specific CT -value intervals. Spirometrically controlled quantitative HRCT is a clinically meaningful tool for the assessment of diffuse parenchymal lung disease.

Adult↗