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Biomedical subjects

M Lehmann

Publications and source records attributed to M Lehmann.

At least 163 records · Page 9Linked to original sources
PubMed1996

Physical responses to different modes of interval exercise in patients with chronic heart failure--application to exercise training.

METHOD: In exercise training with chronic heart failure patients, working muscles should be stressed with high intensity stimuli without causing cardiac overstraining. This is possible using interval method exercise. In this study, three interval exercise modes with different ratios of work/ recovery phases (30/60 s, 15/60 s and 10/60 s) and different work rates were compared during cycle ergometer exercise in heart failure patients. Work rate for the three interval modes was 50% (30/60 s), 70% (15/60 s) and 80% (10/60 s) of the maximum achieved during a steep ramp test (increments of 25 w/10 s) corresponding to 71, 98 and 111 watts on average. Metabolic and cardiac responses to the three interval exercises were then examined including catecholamine levels and perceived exertion. Parameters measured during interval exercise were compared with an intensity level of 75% peak VO2, determined during an ordinary ramp exercise test (increments of 12.5 W.min-1). RESULTS: (mean +/- SEM) (1) In all three interval modes, VO2, ventilation and lactate did not increase significantly during the course of exercise. Mean values during the last work phase were between 754 +/- 30 and 803 +/- 46 ml.min-1 for VO2, between 26 +/- 3 and 28 +/- 1 l.min-1 for ventilation and between 1.24 +/- 0.14 and 1.29 +/- 0.10 mmol.l-1 for lactate. (2) In mode 10/60 s, heart rate and systolic blood pressure increased significantly (82 +/- 4 --> 85 +/- 4 beats.min-1; 124 +/- 5 --> 134 +/- 5 mmHg; P < 0.05 each), while in mode 15/60 s catecholamines increased significantly (norepinephrine 0.804 +/- 0.089 --> 1.135 +/- 0.094 nmol.l-1; P < 0.008; epinephrine 0.136 +/- 0.012 --> 0.193 +/- 0.019 nmol.l-1; P < 0.005). (3) In all three modes, rating of leg fatigue and dyspnoea increased significantly during exercise but remained within the range of values considered 'very light to fairly light' on the Borg scale. (4) Compared to an intensity level of 75% peak VO2, work rate during interval work phases was between 143 and 221%, while cardiac stress (rate-pressure product) was significantly lower (83-88%). CONCLUSION: All three interval modes resulted in physical response in an acceptable range of values, and thus can be recommended.

Chronic Disease↗
PubMed1996

Influence of different exercise protocols on functional capacity and symptoms in patients with chronic heart failure.

This study compares hemodynamic, metabolic, and gas exchange responses, catecholamine levels, and symptoms in 35 male patients with chronic heart failure (CHF) ([mean +/- SD] age 53 +/- 11 yr; ejection fraction 24 +/- 11%) during three differently graded exercise test protocols. On three consecutive days patients performed cycle ergometry supine, with prolonged steps (prol BE) and right heart catheterization, ramplike cycle ergometry sitting (ramp BE), and ramplike treadmill walking (TMW). As in routine clinical practice, the prol BE was terminated when pathologic central hemodynamics and/or increased symptomology occurred, and ramp BE and TMW due to increased symptomology and/or physician's decision. During prol BE at ventilatory threshold (VT) the VO2 (8.6 +/- 1.8 ml.kg-1.min-1) was lower than during ramp BE (9.3 +/- 2.1 ml.kg-1.min-1) (P < 0.017) and TMW (11.8 +/- 2.3 ml.kg-1.min-1) (P < 0.0001). Prol BE, ramp BE, and TMW also differed significantly with respect to ventilation (22 +/- 7 l.min-1; 26 +/- 6 l/min-1; 29 +/- 7 l.min-1; P < 0.01) and heart rate (100 +/- 15 beats.min-1; 103 +/- 18 beats.min-1; 110 +/- 16 beats.min-1; P < 0.017). No differences were found in lactate levels, catecholamine levels, and ratings of leg fatigue and dyspnea. At test termination, the peak VO2 during prol BE (100.8 +/- 3.3 ml.kg-1.min-1) was lower than during ramp BE (13.3 +/- 4.1 ml.kg-1.min-1) (P < 0.0001) and TMW (14.7 +/- 3.4 ml.kg-1.min-1) (P < 0.0001). Peak norepinephrine value during ramp BE (4.531 +/- 2.788 nmol.l-1) was higher than during prol BE (3.707 +/- 2.262 nmol.l-1) (P < 0.001). Among the three tests, no significant differences were found for peak values of heart rate, lactate, and ratings of dyspnea. Although the VO2.kg-1 at VT was significantly higher during ramp BE and TMW compared to prol BE (P < 0.001), the values expressed as a percent of peak VO2.kg-1 were significantly lower (70 +/- 4%; 72 +/- 6%; 79 +/- 3%; P < 0.017). A systematic effect on aerobic capacity with reduced peak values during ramp BE and TMW was demonstrated when test termination was based primarily on pathological findings of central hemodynamics from prol BE.

Adolescent↗
PubMed1996

Lung cancer chemotherapy. Response-survival relationship depends on the method of chest tumor response evaluation.

In a previous study we found that tumor responses as assessed by CT scan and fiberoptic bronchoscopy are sometimes discordant. We hypothesize that the response-survival relationship might vary according to the method of tumor response assessment. In a multivariate analysis of survival using the landmark method, we evaluated the prognostic significance of tumor response assessed by CT scan or fiberoptic bronchoscopy together with bronchial tumor location and histology of bronchial biopsies at restaging. A total of 133 lung cancer patients (50 small cell lung cancers and 83 non-small cell lung cancers) were entered in controlled chemotherapy trials and prospectively evaluated for chest tumor response by CT scan and fiberoptic bronchoscopy (FOB). Only 106 patients were fully evaluable for response by both methods. For these patients, a statistical concordance was observed between the two tests (kappa = 0.271; p < 0.001). There was a significant correlation between response and survival whatever the test used. However, only CT scan evaluation resulted in a classification showing that the more unfavorable the response stage was, the worse the survival became with no intersection between survival curves. Cox's hazard model demonstrated that CT-evaluated progression, proximal bronchial location at second FOB (intermediate, main bronchus or trachea) and positive histologic status at restaging were all prognostic determinants of poor survival. In conclusion, CT-evaluated response led to the best response-survival relationship as this method classified patients into four groups with different outcomes. Fiberoptic bronchoscopy should be avoided in patients who were found to have no endobronchial lesion during the pretreatment staging. For patients with pretreatment assessable endobronchial lesions, the decision of a second FOB depends on the results of CT restaging: FOB is probably unnecessary in patients for whom progression is disclosed by CT scan. In patients for whom CT scan discloses tumor response or stabilization, bronchial tumor location and histology of bronchial biopsies at second FOB are independent prognostic factors.

Adenocarcinoma↗
PubMed1996

Cytokeratins as serum markers in lung cancer: a comparison of CYFRA 21-1 and TPS.

We examined two recently described cytokeratin markers, CYFRA 21-1 (cytokeratin fragment recognized by KS 19-1 and BM 19-21 antibodies) and TPS (specific M3 epitope of the tissue polypeptide antigen), in 405 lung cancer patients (91 small-cell and 314 non-small-cell lung cancers) and 59 patients presenting with nonmalignant pulmonary disease. Sensitivity-specificity relationship, as analyzed by receiver operating characteristic curves, demonstrated a higher accuracy of CYFRA 21-1 in comparison with TPS in both small-cell and non-small-cell lung cancers. Thresholds of 3.6 ng/ml and 140 U/L for CYFRA 21-1 and TPS respectively gave a 90% to 95% specificity. Sensitivity of CYFRA 21-1 was the highest in squamous-cell carcinomas (0.61) and the lowest in small-cell lung cancers (0.36), whereas sensitivity of TPS did not vary significantly according to histology (overall sensitivity, 0.40). In non-small-cell lung cancers, both serum CYFRA 21-1 and serum TPS distributions varied significantly according to Mountain's stage of the disease, nodal status, tumor status, and performance status, inasmuch as the worse each above-mentioned variable became, the higher the median and interquartile serum marker level was. Neither CYFRA 21-1 nor TPS was able to accurately discriminate between stage IIIa (marginally resectable) and stage IIIb (unresectable) non-small-cell lung cancers, however. In both small-cell and non-small-cell lung cancers, univariate survival analyses demonstrated that either a CYFRA 21-1 level over 3.6 ng/ml or a TPS level over 140 U/L significantly indicated a poor survival rate. In the whole population, taking into account other significant variables, Cox's model analysis demonstrated that a poor performance index, an advanced stage of the disease, the presence of metastases, elevated serum lactate dehydrogenase, and high serum CYFRA 21-1 (odds ratio, 1.74; 95% confidence interval, [1.33-2.27] were independent prognostic variables. We concluded that CYFRA 21-1 is a significant determinant of survival. Other applications of cytokeratin markers in lung cancer are still limited.

Adult↗
PubMed1996

[Diagnosis and therapy of shoulder instability].

Shoulder instability is based on various acquired or constitutional aspects which determine the therapy and clinical outcome. In order to differentiate between traumatic and atraumatic forms of shoulder instability a careful history has to be taken. A systematic clinical examination is necessary to evaluate the shoulder joint for general laxity or true instability and especially to assess direction and degree of glenohumeral translation. The basic diagnostic imaging includes X-rays in 3 planes. CT-arthrogram and MRI may provide additional information to evaluate the intraarticular pathology. An elective therapy depends on the patients age and demands. Recurrent anterior dislocations are treated by an anatomical reconstruction of the glenohumeral ligament complex. Open or arthroscopic Bankart-repair have been established as the treatment of choice. Conservative treatment is primarily indicated in cases of atraumatic posterior or multidirectional instability. If physiotherapy fails, surgical treatment should be discussed for these patients.

Diagnosis, Differential↗
PubMed1996

Assessment of chronic rejection in permanent accepted renal allografts in anti-CD4 treated rats.

In rats, transient prophylactic anti-CD4 therapy with the nondepleting mAB RIB5/2 prevents acute rejection of MHC-mismatched allografted kidneys and induces long-lasting unresponsiveness. However, little is known about long-term benefits of this prophylactic anti-CD4 regimen. Here we report experimental results of permanently accepted rat renal allografts after prophylactic anti-CD4 treatment in regard to signs of chronic rejection. Kidneys from Wistar Furth donors were orthotopically grafted into bilateral nephrectomized BDIX recipients under the cover of anti-CD4 treatment (20 mg/kg b.w). Kidney function was serially monitored by measurement of serum creatinine and urine protein excretion. After 100 or 300 days respectively renal allografts were harvested, histologically and immunohistologically assessed and intragraft cytokine gene expression determined. Serum creatinine increased in few allografted rats. 30% of the 300-day-old grafts had an increased proteinuria and higher degrees of glomerular sclerosis. In these grafts cellular infiltration was more pronounced. However, no activated leukocytes (IL-2 receptor positive) were detected. Correspondingly, intragraft gene expression of CD3, IL-10 and IFN gamma was low. The results of our study indicate that a prophylactic anti-CD4 regimen diminishes chronic rejection to a level comparable to isografted or naive mass-reduced or ischemic kidneys. Thus, the signs of chronic rejection observed seem to be mainly caused by alloantigen-independent processes.

Animals↗
PubMed1995

Implication of the alpha v beta 3 integrin in the adhesion of the ovarian-adenocarcinoma cell line IGROV1.

Accumulating evidence suggests that integrins, which participate in many complex cellular processes, are important for tumor progression and metastasis. In order to understand the role of these cell-surface receptors and of their ligands in the biological behavior of ovarian tumor cells, we have examined the expression of integrins in the human ovarian-adenocarcinoma cell line IGROV1. These cells expressed the alpha v sub-unit and used it to attach on vitronectin (Vn). A monoclonal antibody (MAb) (69-6-5) specific to alpha v blocked the attachment of IGROV1 cells on Vn and fibrinogen (Fg), but not on fibronectin (FN) and other adhesive ligands. Immunoprecipitation of surface biotinylated cells followed by Western blotting showed that the alpha v sub-unit was associated with beta 3, but not with beta 1, beta 5 or beta 6. When cells were cultivated on glass coverslips or on Vn sub-stratum in serum-free medium, immunofluorescence staining with MAb 69-6-5 revealed the presence of alpha v at cell-cell contacts and at focal contacts, supporting its active participation in adhesion as part of a functional heterodimer. Furthermore, immunofluorescence data showed the presence of Vn as a fibrillar network in IGROV1 cells cultivated on FN-coated slides. These results suggest that alpha v beta 3 and its Vn ligand may play a important role in the behavior of ovarian epithelial tumors.

Adenocarcinoma↗
PubMed1995

Molecular cloning of the isoquinoline 1-oxidoreductase genes from Pseudomonas diminuta 7, structural analysis of iorA and iorB, and sequence comparisons with other molybdenum-containing hydroxylases.

The iorA and iorB genes from the isoquinoline-degrading bacterium Pseudomonas diminuta 7, encoding the heterodimeric molybdo-iron-sulfur-protein isoquinoline 1-oxidoreductase, were cloned and sequenced. The deduced amino acid sequences IorA and IorB showed homologies (i) to the small (gamma) and large (alpha) subunits of complex molybdenum-containing hydroxylases (alpha beta gamma/alpha 2 beta 2 gamma 2) possessing a pterin molybdenum cofactor with a monooxo-monosulfido-type molybdenum center, (ii) to the N- and C-terminal regions of aldehyde oxidoreductase from Desulfovibrio gigas, and (iii) to the N- and C-terminal domains of eucaryotic xanthine dehydrogenases, respectively. The closest similarity to IorB was shown by aldehyde dehydrogenase (Adh) from the acetic acid bacterium Acetobacter polyoxogenes. Five conserved domains of IorB were identified by multiple sequence alignments. Whereas IorB and Adh showed an identical sequential arrangement of these conserved domains, in all other molybdenum-containing hydroxylases the relative position of "domain A" differed. IorA contained eight conserved cysteine residues. The amino acid pattern harboring the four cysteine residues proposed to ligate the Fe/S I cluster was homologous to the consensus binding site of bacterial and chloroplast-type [2Fe-2S] ferredoxins, whereas the pattern including the four cysteines assumed to ligate the Fe/S II center showed no similarities to any described [2Fe-2S] binding motif. The N-terminal region of IorB comprised a putative signal peptide similar to typical leader peptides, indicating that isoquinoline 1-oxidoreductase is associated with the cell membrane.

Amino Acid Sequence↗
PubMed1995

Ecdysone regulation of the Drosophila Sgs-4 gene is mediated by the synergistic action of ecdysone receptor and SEBP 3.

The steroid hormone 20-hydroxyecdysone controls both induction and repression of the Drosophila 'intermolt gene' Sgs-4. We show here that the ecdysone receptor binds to two sites, element I and element II, in the regulatory region of Sgs-4. A functional analysis revealed that element II appears to be of no importance for Sgs-4 expression, while element I proved to be an ecdysone response element that is necessary, but not sufficient, for induction of Sgs-4 expression. Our results provide no evidence that repression of Sgs-4 expression is mediated by one of the two receptor binding sites. In the close vicinity of elements I and II, we detected two binding sites of secretion enhancer binding protein 3 (SEBP 3). Like receptor element I, one of these sites also proved to be necessary, but not sufficient, for expression of Sgs-4. Therefore, induction of Sgs-4 requires binding of both ecdysone receptor and SEBP 3 to a complex hormone response unit, which also contains binding sites for a third factor, SEBP 2. The SEBP 2 sites coincide with binding sites of products of the Broad-Complex locus, which has been implicated recently with transduction of the hormonal signal. Thus, the available data suggest that induction of Sgs-4, and possibly other 'intermolt genes', is a combination of a primary and a secondary response to the hormone.

Animals↗
PubMed1995

Heart rate deflection related to lactate performance curve and plasma catecholamine response during incremental cycle ergometer exercise.

The correlation between the behaviour of the heart rate/work performance (fc/W) curve and blood lactate ([la]b) and plasma adrenaline/noradrenaline concentrations ([A]/[NA]) during incremental cycle ergometer exercise was investigated. A group of 21 male sports students was divided into two groups: group I, with a clear deflection of the fc/W curve; group II, without or with an inverse deflection of the fc/W curve. The aerobic threshold (Thaer) and the lactate turn point (LTP) were defined. Between Thaer and maximal work performance (Wmax) the behaviour of the fc/W curve as well as the behaviour of [la-]b and [A]. [NA] were described mathematically. The fc, systolic blood pressure (BPs), W, [la-]b, [A] and [NA] at rest, Thaer, LTP, Wmax, after 3 and 6 min of recovery (Re3/Re6) were calculated. A significant difference between the two groups could only be detected for fc at LTP, Re3 and Re6 (P < 0.05). No significant correlation could be found between individual fc/W-behaviour and individual time course of [la-]b, [A] and [NA]. However, a significant correlation was visible between [la-]b/W-behaviour and individual catecholamine response. These results and the fact that the different flattening at the top of the fc/W curve was related to diminished stress-dependent myocardial function led us to the conclusion that it is possible that sympathetic drive is not directly involved in mechanisms of regulation between load dependent fc and myocardial function. In addition, individual fc/W behaviour was independent of BPs and Wmax, or individual conditions of energy supply.

Adult↗
PubMed1995

Unaccustomed high mileage compared to intensity training-related neuromuscular excitability in distance runners.

The influence of a 4-week unaccustomed average 103% mileage increase (ITV, increase in training volume; n = 8; average baseline mileage 85.9 km.week-1, final mileage 174.6 km.week-1) on performance and neuromuscular excitability (NME) was tested in experienced distance runners and controlled 1 year later by a 4-week unaccustomed average 152% increase in tempo-pace and interval-runs (ITI, increase in training intensity; n = 9; baseline 9 km.week-1 final 22.7 km.week-1) with an average total mileage of 61.7 km.week-1 (week 1) to 84.7 km.week-1 (week 4). Seven athletes participated in ITV as (week 4). Seven athletes participated in ITV as well as in ITI. During incremental treadmill test performance at a lactate concentration of 2 mmol.1-1 (2 LP) increased, and at 4 mmol.1-1 (4 LP) performance did not change, whereas total running distance (TD) during the incremental test decreased in ITV compared to an increase in 2 LP, 4 LP and TD during ITI which may indicate that there was an ITV-related overtraining. The NME of the reference muscles vastus medialis and rectus femoris deteriorated in ITV (day 28 compared to 0) compared to constant values during ITI, reflecting an ITV-related overload of neuromuscular structures.

Adult↗
PubMed1995

Cervical cancer screening with cervicography and cytology.

The results of colposcopy and directed biopsies were compared with the cytological findings and cervicography in 1539 asymptomatic outpatients undergoing routine cervical cancer screening in order to compare the accuracy of cervicography and cytology and to assess the potential benefits of the combination of both screening tests. With the new reporting criteria, cervicography looked less sensitive (53% vs. 56%; P = 0.718) and significantly less specific (97% vs. 98%; P = 0.040) than cytology. In comparison with cytology and at the expense of a recall rate of 9%, the combination of both screening tests and to an increase of the sensitivity (77% vs. 56%; P = 0.013) but also to a decrease of the specificity (95% vs. 98%; P < 0.0001) and of the positive predictive value (44% vs. 60%; P = 0.051). When the original reporting criteria were applied to cervicography, the combination of both screening tests led to optimal sensitivity and negative predictive value (100%, respectively) at the expense of an unrealistic recall rate of 20%. Consequently, cervicography should not be considered as an alternative to cytology for cervical cancer screening since its accuracy is not significantly better and its rate of technically defective tests is significantly higher. The combination of both methods increases the sensitivity of cervical cancer screening at the expense of a high recall rate, of which cost effectiveness has to be assessed.

Adolescent↗
PubMed1995

Comparison between exact and parametric distributions of multiple inter-raters agreement coefficient.

The Global Kappa statistic can be used for measuring the degree of agreement between more than two raters. In this paper, we give simple computation formulas in the case of dichotomic and no missing responses in order to describe the exact distribution of Kappa for various sets defined by the number of raters, of different examinations and of positive responses. By programming those computations with the SAS software package, we were able to compare the exact and parametric distributions of Kappa. Although the correlation between parameters is high, a linear regression analysis shows that a strong imbalance between positive and negative responses can lead to misinterpretation of the results when using the parametric method.

Humans↗
PubMed1995

[Evaluation of tumor response during chemotherapy of bronchial cancer].

Chemotherapy of lung cancer is still an experimental approach requiring careful evaluation. Tumour response (marker of anticancer activity) is not perfectly correlated to survival (marker of chemotherapy efficacy), but its evaluation remains a milestone inasmuch as reporting a wrong tumour response rate might lead to the rejection of active new treatments. This review deals with the method of tumour response measurements and its use during a chemotherapy protocol. Recommendations drawn from the analysis of the literature are: 1) to assess and classify all lesions which can be identified at the beginning of the treatment; 2) to define the target lesions, mainly the ones which can be bidimensionally measured; 3) to use the World Health Organization recommendations for reporting the overall response; 4) to confirm complete response by negative rebiopsies; 5) to avoid second fiberoptic bronchoscopy to patients with stable or progressive disease on CT-scan, and finally; 6) to assess response quality by evaluating response duration and improvement of quality of life.

Antineoplastic Agents↗
PubMed1995

Serum amino acid concentrations in nine athletes before and after the 1993 Colmar ultra triathlon.

The amino acid imbalance hypothesis should explain the fatigue originating in the brain during sustained exercise or over-training as a branched-chain (BCAA)/aromatic amino acids (AAA) imbalance with increased brain tryptophan uptake and 5-hydroxytryptamine synthesis. The serum amino acid profile was determined in 9 ultra-triathletes before and after completing the 1993 Colmar ultra-triathlon to additionally analyse the extent of this amino acid imbalance during such an extreme prolonged contest lasting more than 23 hours. The summed serum concentration of 25 amino acids decreased by 18% from 3962 +/- 846 to 3255 +/- 694 umol.l-1 likely reflecting a catabolic state of the organism with a decrease in 18 individual amino acids by 9-56%, an increase in cystine (+38%), methionine (+24%), tyrosine (+10%), phenylalanine (+12%), free tryptophan (+74%), and constant glutamine, leucine and total tryptophan levels. Since plasma volume increased by approximately 7.6% with a 3.3 kg body mass decrease in the athletes during the ultra triathlon, a decrease in intra-cellular water with an extra-cellular fluid increase is hypothesized. This decrease in cellular hydration state is seen as a protein-catabolic signal.

Adult↗
PubMed1995

Delay in corneal allograft rejection due to anti-CD4 antibody given alone and in combination with cyclosporin A and leflunomide.

Anti-CD4 monoclonal antibodies (mAbs) have been shown to inhibit in vitro T-cell activation and proliferation to both antigens and mitogens. Animals studies have demonstrated the immunosuppressive potency of anti-CD4 mAbs given in vivo for therapy of autoimmune disease and following allografting. Similarly, leflunomide (LF), a new potent immunosuppressive, has been shown to be effective in preventing autoimmune disorders and reactions leading to organ transplant rejection. LF is thought to antagonize cytokine activity, thereby interfering with T-helper-cell-dependent B- and T-lymphocyte proliferation. A new anti-CD4 antibody (RIB 5/2) was investigated alone and in combination with cyclosporin A (CsA) and LF for the treatment of corneal allograft rejection in the rat. Corneal buttons were grafted from Lewis/Brown Norway rats to Lewis recipients. Animals were randomly assigned to the following treatment groups: (1) untreated; (2) CsA at 1.5 mg/kg; (3) RIB 5/2 at 2.5 mg/kg; (4) RIB 5/2 at 2.5 mg/kg and CsA at 1.5 mg/kg; (5) RIB 5/2 at 2.5 mg/kg, CsA at 1.5 mg/kg and LF at 10 mg/kg; (6) RIB 5/2 at 4 mg/kg; (7) RIB 5/2 at 4 mg/kg and CsA at 1.5 mg/kg; and (8) RIB 5/2 at 4 mg/kg, CsA at 1.5 mg/kg, and LF at 10 mg/kg. RIB 5/2 was given intraperitoneally at 24 h before surgery, on the day of grafting, and on postoperative day 1 and was continued every 2nd day until the rat had received ten doses in all (postoperative day 15).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗