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Biomedical subjects

M Lehmann

Publications and source records attributed to M Lehmann.

At least 127 records · Page 7Linked to original sources
PubMed1997

Type 2 helper T cell-type cytokines and the development of "infectious" tolerance in rat cardiac allograft recipients.

CD4-targeted therapy with a nondepleting RIB-5/2 mAb abrogates accelerated (< 36 h) rejection in presensitized LEW rats and results in permanent acceptance of LBNF1 cardiac allografts in conjunction with the features of infectious tolerance. This study examined the role and functional significance of the Th1 and Th2 cytokine network and systemic host allospecific Ab (allo-Ab) responses in the development of the infectious tolerance pathway in this model. Long term survival of cardiac transplants in rats treated with the tolerizing RIB-5/2 mAb regimen was accompanied by profound depression of Th1 (IL-2 and IFN-gamma) and Th2 (IL-4, IL-10) cytokines at the graft site, as shown by competitive template reverse transcription-PCR and immunohistochemistry. In contrast, the expression of Th2-type cytokines was selectively up-regulated after transfer of infectious tolerance by spleen cells into new generations of primary and secondary test recipients. Donor-specific circulating IgM allo-Ab responses were diminished throughout, and the switch from IgM to IgG allo-Ab was completely prevented in tolerant hosts, as shown by flow cytometry. The demonstration that treatment with cytolytic anti-CD4, but not anti-CD8, mAb recreated rejection of test cardiac allografts with simultaneous down-regulation of IL-4 mRNA/protein expression underlines the importance of this cytokine in the development of infectious tolerance. Hence, this report documents distinct cytokine elaboration patterns in animals tolerized by CD4-targeted therapy compared with those rendered tolerant by putative regulatory Th2-like cells. The mechanism of tolerance in anti-CD4 mAb-treated hosts appears distinct from that operating in the absence of mAb, when the tolerant state is being transferred in an infectious manner to new cohorts of test recipients.

Adoptive Transfer↗
PubMed1997

Induction of donor specific transplantation tolerance to cardiac allografts following treatment with nondepleting (RIB 5/2) or depleting (OX-38) anti-CD4 mAb plus intrathymic or intravenous donor alloantigen.

The nondepleting monoclonal antirat CD4 antibody, RIB 5/2, has been shown to modulate, but not eliminate, the CD4+ T cells and to prolong survival of rat skin, renal, or cardiac allografts when serially administered after transplantation. In the present study, we compared the efficacy of recipient pretreatment with a single dose of nondepleting RIB 5/2 or depleting OX-38 anti-CD4 monoclonal antibody plus donor alloantigen given intravenously or intrathymically 21 days before transplantation on the survival of completely MHC-mismatched rat cardiac allografts. Intraperitoneal injection of a single dose (20 mg/kg) of RIB 5/2 resulted in a decrease in CD4 surface molecule expression on peripheral CD4+ T cells without cell elimination as shown by FACS analysis. The nonspecific effect of a single dose of RIB 5/2 mAb had resolved by 21 days after treatment as evidenced by the almost complete recovery of normal surface CD4 molecule expression. Cardiac allografts transplanted immediately or 21 days after a single dose of RIB 5/2 alone were uniformly acutely rejected. On the other hand, recipients treated with depleting anti-CD4 OX-38 (20 mg/kg) acutely rejected cardiac allografts transplanted 21 days later, but indefinitely accepted all grafts transplanted on the same day. In contrast, combined treatment with i.v. donor splenocytes (25 x 10(6)) plus nondepleting RIB 5/2, but not with depleting anti-CD4 mAb, OX-38, resulted in survival for more than 100 days in 75% of recipients of donor specific, but not third party, cardiac allografts transplanted 21 days later. Irradiation (3000 rads) of the i.v. donor splenocytes combined with RIB 5/2 abrogated their tolerizing effect. When donor antigen was given intrathymically, both RIB 5/2 and OX-38 resulted in indefinite tolerance to cardiac allografts transplanted 21 days later. The failure of exogenous administration of high dose (180,000 IU/injection) rIL-2 for 10 days to reverse the unresponsiveness of i.v. SC plus RIB 5/2 pretreatment suggests that this tolerant state is not due to a deficiency of IL-2. In vitro studies showed marked inhibition of MLC responsiveness and cytolytic T cell activity in tolerant recipients that cannot be reversed by the addition of IL-2. Thus, pretransplant intravenous donor alloantigen combined with a dose of nondepleting anti-CD4 mAb, RIB 5/2, which alone has no significant effect, induced donor specific cardiac allograft tolerance.

Animals↗
PubMed1997

Monitoring high-intensity endurance training using neuromuscular excitability to recognize overtraining.

The minimal rectangular current pulse that produces a single contraction of reference muscles at different pulse durations has been recommended as a marker of the neuromuscular excitability (NME) of skeletal muscles. NME is improved in well-trained, non-fatigued endurance athletes and deteriorates after prolonged heavy exercise and high-volume overtraining. The hypothesis was tested that a deterioration in NME also indicates an early stage in the overtraining process during high-intensity endurance training. Six subjects participated for 40-60 min per day in a 6-week, 6-days-per-week, intensive, steady-state and interval training program using a cycle ergometer. Training was stopped each day on volitional exhaustion. On day 7 of each week training was of low intensity for about 30-40 min. Submaximum and maximum power output were significantly increased after 3 weeks, but there was no further improvement, rather a deterioration after week 6 compared to week 3. Even after 2 weeks of regeneration no supercompensation was evident, rather a decrease in maximum power output. NME was slightly improved after 3 weeks, but deteriorated after 6 weeks, and was again normalized after 2 weeks of regeneration. The discrepancy between normalization of NME and still-deteriorated performance ability after 2 weeks of regeneration reflects additional significant, and probably central mechanisms that explain persistent performance incompetence. Deterioration in NME may indicate an early stage in the overtraining process during high-volume as well as high-intensity endurance overtraining, but normalization does not necessarily indicate sufficient regeneration.

Adult↗
PubMed1997

DNA aneuploidy, S-phase fraction, nuclear p53 positivity, and survival in non-small-cell lung carcinoma.

Inactivation of the p53 gene plays a key role in tumour biology, probably through a disturbed cell cycle control and an increased genetic instability in p53-inactivated tumours. To learn more about the relationship between p53 alterations, proliferation and genetic instability (DNA aneuploidy) in lung cancer patients, specimens of 220 surgically resected lung carcinomas with clinical follow-up information were examined by immunohistochemistry (p53; CM1) and flow cytometry. Nuclear p53 positivity--found in 49.5% of the tumours--was associated with both high S-phase fraction (SPF) and DNA ploidy aberrations. SPF was higher in p53-positive tumours (15.9 +/- 10.2) than in p53-negative tumours (10.3 +/- 8.7; P = 0.03). The rate of p53 positivity was higher in 101 DNA-aneuploid and DNA-multiploid tumours (55%) than in 27 diploid and peridiploid carcinomas (33%; P = 0.0512). These results are consistent with an in vivo role of p53 inactivation for increased proliferative activity and development of genomic instability in lung cancer. There was no association between SPF and prognosis. Although prognosis was worse in DNA-aneuploid and multiploid tumours than in diploid, peridiploid and tetraploid carcinomas (P = 0.029), DNA ploidy was not an independent predictor of poor prognosis in multivariate analysis. These data show that DNA-flow cytometry has little prognostic value for patients with resected non-small-cell lung carcinoma.

Aneuploidy↗
PubMed1997

Effects of exercise training and activity restriction on 6-minute walking test performance in patients with chronic heart failure.

Eighteen hospitalized patients with severe chronic heart failure (ejection fraction [mean +/- SEM] 21% +/- 1%) underwent 3 weeks of exercise training (interval bicycle ergometer and treadmill walking training exercises) and 3 weeks of activity restriction in a random-order crossover trial. Before and after exercise training and after activity restriction, a 6-minute walking test was performed to determine the maximum distance walked, hemodynamic and cardiopulmonary responses, norepinephrine levels, and ratings of leg fatigue and dyspnea while walking. A ramp test on bicycle ergometer (increments of 12.5 W/min) was performed before and after exercise training and activity restriction to determine peak oxygen uptake. After training, the maximum distance walked was increased by 65% (from 232 +/- 21 m at baseline to 382 +/- 20 m; p < 0.001), whereas after activity restriction (253 +/- 19 m) there was no significant difference compared with baseline. No significant differences in hemodynamic and cardiopulmonary parameters (with the exception of the ventilatory equivalent for carbon dioxide and perceived exertion) or norepinephrine levels were observed during walking tests. Improvement in maximum distance walked correlated significantly with training-induced increase in peak oxygen uptake measured during bicycle ergometry (r = 0.47, p < 0.05). The lower the maximum distance walked at baseline, the more pronounced the training-induced prolongation of maximum distance (r= -0.73; p < 0.001). These data support the value of exercise training in patients with severe chronic heart failure for improving maximum distance walked, as documented by the 6-minute walking test. The impairment of walking test performance during activity restriction suggests a need for long-term exercise training programs.

Activities of Daily Living↗
PubMed1997

Tolerance to heart and kidney grafts induced by nondepleting anti-CD4 monoclonal antibody (RIB 5/2) versus depleting anti-CD4 monoclonal antibody (OX-38) with donor antigen administration.

BACKGROUND: The monoclonal antirat CD4 antibody RIB 5/2 has been shown to modulate the CD4 glycoprotein without eliminating the affected T cells. We have shown that the administration of multiple doses of RIB 5/2 during the peritransplantation period prevents the rejection of rat kidney allografts. METHODS: We compared the efficacy of a single intraperitoneal dose of 20 mg/kg RIB 5/2 plus donor antigen (25 x 10(6) spleen cells [SCs]) given by either an intrathymic or an intravenous route with the depleting anti-CD4 monoclonal antibody (mAb) OX-38 plus antigen 21 days before a major histocompatibility complex (MHC)-mismatched Lewis (RT1l) to Buffalo (RT1b) rat cardiac or renal allograft. By delaying the transplantation for 21 days, recovery from the nonspecific effects of the antibody treatment allowed the demonstration of donor antigen-specific tolerance. RESULTS: OX-38 mAb given with intrathymic SCs induced tolerance to heart but not kidney grafts, whereas OX-38 given with intravenous SCs failed to prolong survival of either heart or renal allografts. In contrast, RIB 5/2 mAb administration, when combined with alloantigen given by either intravenous or intrathymic routes, induced tolerance to heart allografts, whereas only alloantigen given by the intravenous route with RIB 5/2 resulted in tolerance to renal grafts. CONCLUSIONS: Concomitant administration of intravenous donor alloantigen and the modulation of CD4+ recipIent cells by nondepleting RIB 5/2, rather than elimination of these CD4+ cells with depleting mAb OX-38, is a more potent method for the induction of allograft tolerance.

Animals↗
PubMed1997

[Explanatory factors for length of stay in the postoperative intensive care unit].

OBJECTIVES: Because of the increasing role of post-anaesthesia care in anaesthetic activity, the explicative value of various factors on post-anaesthesia length of stay (POLS) was tested. STUDY DESIGN: Retrospective study. PATIENTS: Population of 38,655 patients admitted to the post-anaesthesia care unit (PACU) between 1990 and 1994. METHOD: Multivariate analysis (semiparametric Cox model) of POLS. RESULTS: Overall 71% of the patients stayed less than four hours in PACU. Average POLS did not vary with years. Eleven variables were related to POLS, with an odds-ratio (OR) between 0.75 and 0.77 (negative link) or between 1.22 and 2.77 (positive link). A comparison of the OR for years 1990 to 1994 indicated major variations for the following three variables: neurosurgery, mechanical ventilation in PACU, low occupancy rate in the PACU at the time of discharge. CONCLUSION: POLS are linked with various factors whose changes in explicative value can be analysed chronologically. However, other methods remain necessary in order to evaluate the impact of organisational modifications, as the introduction of objective criteria for discharge.

Anesthesia↗
PubMed1997

Two new regulatory elements controlling the Drosophila Sgs-3 gene are potential ecdysone receptor and fork head binding sites.

We identified two regulatory elements in the upstream region of the Drosophila Sgs-3 gene which are both able to bind the ecdysone receptor (EcR/USP) and the product of the fork head gene. Interestingly, only one of the EcR/USP binding sites is able to recognize in vitro-translated EcR/USP, which provides evidence for the existence of different receptor forms having different DNA binding specificities. Deletions of the elements lead to a reduced accumulation of Sgs-3 mRNA without altering the temporal expression profile of the gene. The data are consistent with the hypothesis that the ecdysone receptor directly contributes to the transcriptional activation of Sgs-3 by binding to at least one of the two elements. Since also the Sgs-4 gene is controlled by a functional EcR/USP binding site, a direct participation of EcR/USP in the formation of regulatory complexes may be of general importance for the hormonal control of Sgs genes.

Animals↗
PubMed1997

Physiological characterization of a microbial sensor containing the yeast Arxula adeninivorans LS3.

The yeast Arxula adeninivorans LS3 is a suitable organism for use as part of a microbial sensor. In combination with an amperometric oxygen electrode the sensor offered a possibility for the physiological characterization of this yeast. About 300-400 measurements could be carried out with a single Arxula sensor. The microbial sensor was remarkably stable for over 35 days, when kept at 37 degrees C during the operation time and at room temperature overnight. The physiological characteristics of Arxula adeninivorans LS3 obtained with the sensor technique were identical to the data obtained with the conventional techniques. However, the sensor technique makes it additionally possible to quantify the physiological data. So the substrates ribose, citric acid, glycerol, oil and benzoate produced signals lower than 10% in comparison to the glucose signal. Fructose, xylose, sucrose, maltose, gentianose, glucosamine, glutamic acid, tryptophan, butyric acid, lauryl acid and propionic acid reached 10-70%, galactose, alanine, glycine, lysine and methionine signals were similar to the glucose signal whereas acetic acid, ethyl alcohol, capron acid, capryl acid and caproic acid reached the highest signals up to 434%.

Amino Acids↗
PubMed1997

Validation of the acetylene rebreathing method for measurement of cardiac output at rest and during high-intensity exercise.

The use of the acetylene rebreathing method to estimate cardiac output (CO) during high-intensity exercise, which may be influenced by recirculation of acetylene, has not been validated. This study was designed to validate the acetylene rebreathing method to measure CO during high-intensity exercise using the direct Fick method. CO was measured at rest and during exercise at 25%, 50%, 75% and 90% of the nine subjects' maximum oxygen uptake (VO2max) by the direct Fick and acetylene rebreathing method. CO measured by the acetylene rebreathing method correlated with work rate (r = 0.90, P < 0.01) and with oxygen uptake (r = 0.94, P < 0.01). The correlation coefficient of CO between both methods was r = 0.91 (P < 0.01). There was no significant difference in CO measured by each method at rest as well as at each work rate. The difference in CO between each method was greater at lower CO than at higher CO. At 90% of VO2max, the CO measured by acetylene rebreathing was nearly identical to that measured by the Fick method. It can be concluded that acetylene rebreathing for measurement of CO is valid not only at rest but also during exercise, especially during high-intensity exercise.

Acetylene↗
PubMed1997

Interval training in patients with severe chronic heart failure: analysis and recommendations for exercise procedures.

This study analyzes a new exercise training procedure, which includes interval exercise training on cycle ergometer (IntCT) (30-s work phases/60-s recovery phases) and on treadmill (60-s work and recovery phases each). Training was applied for 3 wk in 18 patients with severe chronic heart failure (CHF) ((mean +/- SEM) age 52 +/- 2 yr, ejection fraction 21 +/- 1%). Peak VO2 was increased from 12.2 +/- 0.7 to 14.6 +/- 0.7 ml-kg-1 min-1 owing to training (P < 0.001). A specific steep ramp test (work rate increments 25 W.10 s-1) was developed to derive exercise intensity for work phases in IntCT, which was 50% of the maximum work rate achieved. Steep ramp test was performed at the start of the study to determine the initial training work rate, then weekly to readjust it. Since the maximum work rate achieved from this test increased weekly (144 +/- 10 W -->172 +/- 10 W-->200 +/- 11 W; P < 0.001), the training work rate also increased (72 +/- 4 W-->86 +/- 6 W-->100 +/- 7 W; P < 0.001). Physical responses to IntCT were measured. There was no significant change in heart rate, blood pressure, and ratings of perceived exertion (RPE) using a Borg Scale between the first and the third week of training (heart rate 88 +/- 3 b.min-1; blood pressure 115 +/- 4/80 +/- 2 mm Hg; leg fatigue 12 +/- 1; dyspnea 10 +/- 1). Mean lactate concentration (1.70 +/- 0.09 mmol-1-1) indicated an overall aerobic range of training intensity. When compared with the commonly used intensity level of 75% peak VO2 from an ordinary ramp test (work rate increments 12.5 W.min-1), the performed training work rate was more than doubled (240%; P < 0.0001) while cardiac stress was lower (86%; P < 0.01). Values of norepinephrine and epinephrine as well as of RPE corresponded to those measured at 75% peak VO2. Interval exercise training is thus recommended for selected patients with CHF as it allows intense exercise stimuli on peripheral muscles with minimal cardiac strain. Using a steep ramp test, training work rate can be determined and readjusted weekly during initial training period.

Bicycling↗
PubMed1997

Highland mountain hiking and coronary artery disease: exercise tolerance and effects on left ventricular function.

Physical exercise has become a well-established concept in the secondary prevention of coronary artery disease. We investigated the exercise requirements of extensive highland mountain hiking (8.7 km, 470 m to 1220 m over sea level, average incline 8.5%, mean walking velocity < 3 km x h-1) in 11 regularly exercising male patients with history of MI and stable coronary artery disease (CAD; mean age +/- SD:61.0 +/- 3.9 yr) and 9 age-matched male healthy controls (CO; mean age +/- SD:61.2 +/- 5.0 yr). All subjects underwent continuous ECG monitoring; arterial blood pressure and blood lactate concentrations were measured several times during mountain hiking. Before and after exercise, cardiac dimensions and functions were assessed by two-dimensional echocardiography and Doppler echocardiography. The mean exercise levels for heart rate and blood lactate were compared with the corresponding data of a multistage upright cycle ergometry. Clinical manifestations of coronary insufficiency, left ventricular myocardial dysfunction, or cardiac arrhythmias > Lown IIIb were not observed in any case. No significant differences in left atrial and left ventricular dimensions and no changes in systolic left ventricular function compared with the preexercise values were found after the mountain hike tour. Doppler echocardiography demonstrated significant changes in diastolic left ventricular function in CAD, but not in CO. The peak exercise intensity during mountain hiking was equivalent to a workload of 100-125 W (1.25-1.5 W x kg-1 body weight) in a multistage upright cycle ergometry. Extensive highland mountain hiking may be a low risk alternative within the outpatient rehabilitation program for secondary prevention of CAD for MI patients with a cycle ergometric exercise tolerance > 1.5 W x kg-1 body weight.

Aged↗
PubMed1997

A new acid-fast trichrome stain for simultaneous detection of Cryptosporidium parvum and microsporidial species in stool specimens.

The detection in stool specimens of Cryptosporidium parvum and microsporidia, the most frequent parasitic pathogens causing diarrhea in AIDS patients, until now has depended on two different staining methods. However, since double infections occur and minimization of laboratory costs is mandatory, development of a method for simultaneous detection of these parasites appeared desirable. We report on a new, inexpensive, and easy-to-perform staining procedure to demonstrate both acid-fast oocysts of C. parvum and other coccidia, as well as microsporidial spores. This acid-fast trichrome stain yields results comparable to those obtained by the Kinyoun and modified trichrome methods and considerably reduces the time necessary for microscopic examination.

AIDS-Related Opportunistic Infections↗
PubMed1997

Effect of felodipine on regional blood supply and collateral vascular resistance in patients with peripheral arterial occlusive disease.

This double-blinded, randomized, placebo-controlled study was designed to investigate the acute effect of felodipine on regional blood supply and collateral vascular resistance in patients with peripheral arterial occlusive disease (PAOD). Thirty men with PAOD were treated with a single dose of 5 mg felodipine or placebo. Systolic blood pressure (SBP), Doppler ankle pressure (DAP), calf blood flow (CBF) by venous occlusion plethysmography and calf transcutaneous oxygen tension (tcpO2) were measured during a cycle ergometry. Felodipine reduced SBP significantly (from 149 to 136 mmHg, p < 0.05), while placebo did not. DAP increased slightly but not significantly in both groups. The pressure gradient between SBP and DAP fell significantly in the felodipine group (60 vs 39 mmHg, p < 0.01) but not in the placebo group (59 vs 56 mmHg). There was a trend for lower velocity in tcpO2 decrease during the stress test and higher velocity of tcpO2 increase during recovery from exercise in the felodipine group although the differences between both groups were not significant. In the felodipine group, CBF increased by 35.6% (p < 0.05) whereas it did not change in the placebo group. In conclusion, while lowering SBP, felodipine increased slightly, or at least maintained, the blood supply to the calves in PAOD patients, which probably results from reducing collateral vascular resistance.

Adult↗
PubMed1997

Influence of an unaccustomed increase in training volume vs intensity on performance, hematological and blood-chemical parameters in distance runners.

The hypothesis was tested that high-volume endurance training can be monitored using hematological and blood-chemical parameters as markers of an early stage in the overtraining process. Eight experienced distance runners participated in a prospective, experimental, controlled study. The study consisted of an unaccustomed average 103% increase in training volume (ITV) within 4 weeks (average final volume: 174.6 km per week). A year later, 9 runners performed the additional 4-week control study that consisted of an unaccustomed average 152% increase in intensive training measures (ITI). Average total volume amounted to 61.7 km (week 1) and 84.7 km (week 4). Seven athletes participated in both studies. Simultaneously to performance diagnostics, a comprehensive pattern of hematological and blood-chemical parameters was determined. During ITV, submaximum running performance was improved after 2 weeks, stopped improving between week 3 and 4; maximum performance did not increase rather was decreased after week 4 compared to baseline as indication of an early stage in the overtraining process. During ITI, submaximum and maximum running performances increased continuously. In contrast to ITI, the following parameters decreased significantly during ITV: White blood cell count, serum iron, ferritin, VLDL-(very low density lipoproteins), LDL (low density lipoproteins)-cholesterol, albumin, resting and maximum free fatty acid, maximum lactate, resting, submaximum and maximum glucose, summed amino acid, resting, submaximum and maximum ammonia concentrations, whereas prothrombin time increased significantly. During high-volume endurance training a multifactorial and longitudinal approach considering either a performance incompetence and an individually different range of symptoms and alterations in hematological and blood-chemical parameters can help to recognize an early stage in the overtraining process.

Blood Chemical Analysis↗
PubMed1997

Transrectal ultrasonography in prostatic cancer: interexaminer variability of interpretation.

OBJECTIVE: To compare the variability of transrectal ultrasonographic (TRUS) interpretation for the decision of performing biopsies and the lesions to biopsy. METHODS: We extracted at random from our videotape database 16 records of patients who had undergone biopsies, added 2 normal glands and duplicated 2 of these 18 records. Based on the records, 5 well-trained physicians had to describe the images on the tape, and to decide whether or not to biopsy the prostate. A kappa test was computed between each couple of readers, and for the whole group. The kappa test denotes the agreement between examiners. A value of kappa < 0.20 is considered poor to slight agreement, 0.2-0.40 is considered fair agreement. RESULTS: The agreement between the 5 readers was poor for the biopsy decision (kappa < 0.2) and the difficulty to read the records (kappa = 0.05). The results with the global kappa were similar with a highest value < 0.3. Most of the abnormalities were described in the peripheral zone. The global kappa for the seminal vesicles interpretation is poor, but better for the capsular penetration. CONCLUSION: TRUS has a poor informative value between different practitioners. This poor agreement between different practitioners must lead to more objective ultrasonographic methods.

Biopsy, Needle↗
PubMed1997

Immunohistochemical detection of p53 protein and prognosis of surgically resected non-small-cell lung cancer.

We analyzed the survival of 89 surgically treated patients presenting non-small-cell lung cancer in regard to the accumulation of p53 protein as detected by indirect immunoperoxidase reactivity of PAb1801 anti-human p53 protein. Although the well-known factors such as stage grouping, tumor status, and nodal status were found to be prognostic determinants, the p53 protein accumulation had no effect on either univariate analysis or multivariate analysis of survival.

Adult↗