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Biomedical subjects

M Pfeiffer

Publications and source records attributed to M Pfeiffer.

At least 73 records · Page 4Linked to original sources
PubMed1997

Tacrolimus: a superior agent to OKT3 for treating cases of persistent rejection after intrathoracic transplantation.

Acute myocardial rejection refractory to treatment still contributes significantly to patient death after intrathoracic transplantation. A historical series of 25 patients who received OKT3 (5 mg/day for 10 days) was compared with our current experience with 14 patients treated with tacrolimus (0.1 mg/kg/day targeting whole blood concentrations of 13 to 18 ng/ml): all 39 patients having persistent rejection unresponsive to treatment at the time of conversion. Mean periods of follow-up were 842.9 days and 342.6 days, respectively. Actuarial 1-year patient survival rates were 64.0% and 76.2% for the OKT3 and tacrolimus treatment groups, with most of the deaths in the OKT3 group occurring early (p = 0.064). Causes of death for patients receiving OKT3 included acute rejection (n = 5), infection (n = 3), carcinoma (n = 2), multiorgan failure (n = 1) and graft vessel disease (n = 1). The two deaths in the tacrolimus treatment group were the result of infections. Eighty percent of patients treated with OKT3 subsequently experienced further rejection episodes, in many cases necessitating methotrexate therapy. In contrast, only one patient (7.1%) from the tacrolimus group was diagnosed with rejection after conversion (p < 0.001). In conclusion, when compared with OKT3 therapy, a switch in baseline immunosuppression from cyclosporine to tacrolimus seems to be markedly more effective, as well as being safe for the treatment of persistent acute rejection.

Actuarial Analysis↗
PubMed1996

Effect of specimen fixation method on pullout tests of pedicle screws.

STUDY DESIGN: Experimental axial pullout tests of a new type of pedicle screw were done on cadaveric lumbar vertebrae. The manner in which specimens were secured in the testing apparatus was varied to determined influence of specimen fixation method on the maximum pedicle screw pullout force. OBJECTIVES: To determine the appropriateness of embedding (i.e., potting) spinal specimens in polymer resin (e.g., bone cement or Plastic Padding [Plastic Padding Ltd., High Wycombe, Buckinghamshire, England]) for axial pullout tests of pedicle screws. Several different specimen fixation methods were examined to make recommendations for the standardization of future experimental testing protocols. SUMMARY OF BACKGROUND DATA: Axial pullout of transpedicular screws, although not a likely clinical mode of failure, is a popular experimental testing mode for evaluating screw-bone biomechanics. A wide variety of techniques for securing a vertebral specimen to counter the axial pullout force has been reported (including the use of polymer resin) with a correspondingly wide range in the resulting axial pullout strengths. The possible influence of the specimen fixation method on pedicle screw axial pullout strength has not been addressed previously. METHODS: Axial pullout tests of pedicle screws (DDS, Plus Endoprothetik, Rotkreuz, Switzerland) from the pedicles of 21 isolated lumber vertebral bodies were done using a Model 810 MTS Universal Testing Machine (MTS Systems, Inc., Minneapolis, Minnesota). The specimens were secured in a custom-made vise fixture either as is or after the vertebral bodies were potted in Plastic Padding up to the pedicle origin. Some of the potted specimens were wrapped first in latex to prevent polymer resin intrusion, and the others were unprotected. Pullout tests were attempted on both the left and right pedicles of each specimen, and the maximum pedicle screw pullout force was recorded. Measurement of bone mineral density by means of dual energy x-ray absorptiometry, in addition to macroscopic and scanning electron microscopy histologic analyses, microradiography, and energy dispersive X-ray spectroscopy, was done post-test to assist in the interpretation of the data. RESULTS: The maximum pedicle screw pullout force was found to be dependent on both the bone mineral density and the mode of fixation of the vertebrae. Embedding in polymer resin without protection of the specimen (i.e., latex wrapping) led to several instances of well-documented polymer resin intrusion; in these specimens, mean maximum pedicle screw pullout force was significantly greater than that of specimens secured without polymer resin and that of embedded specimens for which intrusion did not occur. CONCLUSIONS: Polymer resin intrusion can have a significant effect on the biomechanical characteristics of the bone-pedicle screw interface. When polymer resins are used to secure vertebral specimens for in vitro biomechanical tests of the bone-pedicle screw interface, it is important to either prevent intrusion (e.g., with a latex wrapping) or document post-test (e.g., through the methods described in this article) that intrusion did not occur for the specimens included in the analysis.

Aged↗
PubMed1996

Standardized evaluation of long-term results after anterior lumbar interbody fusion.

A total of 113 patients, excluding those with tumor, spondylitis, and idiopathic scoliosis, underwent anterior lumbar interbody fusion (ALIF) with autologous iliac crest graft between 1984 and 1991 at our department. The proportion of these who were failed back patients was higher than that reported in the literature. Evaluation of functional outcome was feasible in 80 patients, utilizing Oswestry and Marburg scores, which were closely intercorrelated. The overall results yielded an improvement in the Oswestry score of 35.7 percentage points. A subset of 52 patients who were evaluated twice, showed the same results at an average of 6.6 years as they did at 2.3 years following surgery. Functional results showed a weak correlation with postoperative height loss of the intervertebral space. Influencing factors for the functional result were: postoperative compensation claim, age, and obesity. Of the professional people involved, 19.4% did not return to any occupation. Patients satisfied with the result had significantly greater functional improvement. Younger patients with additional dorsal distraction prior to ALIF for reduction of severe spondylolisthesis fared better than patients with ALIF alone. The rate of complications was low and did not contribute to the postoperative functional result. On the basis of these results further prospective studies have been designed and are currently underway.

Adolescent↗
PubMed1996

Comparative investigation of drug delivery of collagen implants saturated in antibiotic solutions and a sponge containing gentamicin.

Collagen implants of various structures and a gelatine sponge were placed in five different antibiotic solutions until complete saturation occurred. The antibiotics were chosen to represent different drug classes (gentamicin sulphate, cefotaxim, fusidic acid, clindamycin, vancomycin). The collagen implants saturated with antibiotic solution and a lyophilized collagen sponge containing gentamicin sulphate were eluated in 0.066 M phosphate buffer (pH = 7.4) at 37 degrees C. The total eluation period is 7 d with buffer changes every 24 h. The antibiotic delivery by the collagen implants and the lyophilized sponge containing gentamicin sulphate is complete after a maximum of 4 d. If an implant that has a protective effect against wound infections over a period of 24-48 h is required, the materials described here are suitable. However, where treatment in infected areas should ensure antibiotic cover for 5-10 d, neither collagen materials immersed in antibiotic solutions nor collagen sponges containing gentamicin are suitable.

Anti-Bacterial Agents↗
PubMed1996

[Aspiration-induced lung complications following emergency endoscopy in upper gastrointestinal hemorrhage: incidence and localization by thoracic radiography].

PURPOSE: Determination of incidence and mortality of pulmonary pathologies arising after gastroscopy for acute bleeding, of left to right ratio of pulmonary findings in postgastroscopic chest films, and determination of a possible relationship between bleeding activity and frequency of aspiration. METHODS: 174 patients with emergency gastroscopies for upper gastrointestinal haemorrhage with pre-/postendoscopy chest films, retrospective analysis. Of the pulmonary findings, infiltrates and atelectases were considered. RESULTS: After emergency gastroscopy, 16% of patients had infiltrates or atelectases at chest radiography. Mortality within 30 days in the study group was 18%, and 39% among the subgroup with radiologically proven pulmonary complications. The distribution of chest findings between left and right side was 1:1,3. In the subgroup with gastroscopic signs of bleeding the share of postgastroscopic pulmonary findings was slightly superior to that of patients without direct signs of bleeding; however, the difference was statistically not significant. CONCLUSION: Endoscopy-related aspirations do not seem to account for an increased rate of pulmonary complications after emergency gastroscopy.

Adult↗
PubMed1996

Effects of gamma-aminobutyric acid (GABA) agonists and GABA uptake inhibitors on pharmacosensitive and pharmacoresistant epileptiform activity in vitro.

1. Lowering of the extracellular Mg(2+)-concentration induces various patterns of epileptiform activity in combined rat entorhinal cortex-hippocampal brain slices. After a prolonged period of exposure to Mg(2+)-free medium seizure-like events in the entorhinal cortex change to a state of late recurrent discharges which cannot be blocked by clinically available antiepileptic drugs. This late epileptiform activity thus represents a useful model to test the effects of new anticonvulsant substances. 2. A mechanism possibly underlying the development of sustained seizure-like activity is the loss of synaptically released gamma-aminobutyric acid (GABA). Drugs which increase the amount of GABA available in presynaptic endings might thus be useful in the treatment of these therapeutically complicated forms of epilepsy. 3. Therefore, we studied the effects of various substances increasing GABA-mediated inhibition on early and late forms of epileptiform activity. GABA and the GABAA receptor agonist muscimol blocked both the pharmacosensitive discharges in the hippocampus and entorhinal cortex as well as the late recurrent discharges in the medial entorhinal cortex. The GABAB receptor agonist baclofen blocked the recurrent short discharges very potently, but did not consistently block seizure-like events and late recurrent discharges in the entorhinal cortex. 4. GABA uptake blockers showed a differential potency to block the various discharge patterns. Whereas nipecotic acid and beta-alanine suppressed all forms of epileptiform activity albeit at high concentrations (1-5 mM), tiagabine was much more potent in blocking the hippocampal recurrent short discharges and the seizure-like events in the medial entorhinal cortex, but could not block the late recurrent discharges. 5. Our data support the idea that prolonged neuronal overactivity might result in a loss of synaptically available GABA. Selective block of uptake into glia cells or substitution of the transmitter may therefore be an efficient strategy for the treatment of severe prolonged epileptic discharges whereas block of neuronal GABA uptake fails to counteract synchronized discharges in this situation.

Animals↗
PubMed1996

Family burden of schizophrenia and bipolar disorder: perceptions of relatives and professionals.

OBJECTIVE: The study compared the burden that specific problem behaviors of patients with schizophrenia or bipolar disorder placed on relatives and evaluated the accuracy of mental health professionals' judgment of the burden. METHODS: A questionnaire was developed to assess the burden of 20 common problem behaviors associated with manic, positive, and negative symptoms. The questionnaire was given to 48 relatives of patients with schizophrenia or bipolar disorder. In addition, 39 mental health professionals completed separate questionnaires indicating the amount of burden they believed relatives experienced due to these behaviors. RESULTS: Relatives of patients with bipolar disorder rated manic symptoms as more burdensome than did relatives of patients with schizophrenia, but relatives of patients in the two groups did not differ in their ratings of burden associated with positive or negative symptoms. Professionals' perceptions of the burden associated with manic symptoms were relatively accurate, but they tended to underestimate the burden of positive and negative symptoms experienced by relative of patients with bipolar disorder. CONCLUSIONS: Psychiatric diagnosis may be of limited value in understanding the burden relatives experience due to specific psychiatric symptoms. Professionals are encouraged to assess the burden that is associated with specific problem behaviors regardless of psychiatric diagnosis.

Activities of Daily Living↗
PubMed1996

The quantitation of metabolites of quercetin flavonols in human urine.

The flavonoid quercetin, or its metabolites, inhibit chemical carcinogenesis in rodents and may have a role in the prevention of human cancers. Quercetin exposure in human populations results from the dietary intake of various plant foods; high concentrations of quercetin are found in apples, onions, tea, and red wine. Determination of the relationship between dietary intake and cancer risk depends on the characterization of quercetin intake. The development and use of biomarkers for quercetin intake may provide a basis for the objective classification of this exposure. One possible biomarker is metabolic products of quercetin. We report the development of a high-performance liquid chromatography (HPLC)-based assay for quantitation of quercetin metabolites in human urine. The metabolites include 3,4-dihydroxyphenylacetic acid (homoprotocatechuic acid), metahydroxyphenylacetic acid, and 4-hydroxy-3-methoxyphenylacetic acid (homovanillic acid). The assay has only two major steps, ether extraction and HPLC analysis, and is suitable for analysis of large sample numbers. Analytical characteristics of the assay include a sensitivity of less than 1 microgram, precision with coefficients of variation < 10%, and metabolite recoveries > 90%. The mean concentrations of 3,4-dihydroxyphenylacetic acid, metahydroxyphenylacetic acid, and homovanillic acid in two human urine samples are approximately 0.7, 4.8, and 2.8 micrograms/ml, respectively. The identification of each metabolite is confirmed by HPLC, UV absorbance scans, and gas chromatography-mass spectrometry analysis. These results verify the occurrence of quercetin metabolites in human urine and the feasibility of quercetin metabolite quantitation, by the assay described herein, for epidemiological studies. Development of the analytical procedure is an essential first step for validation of the metabolites as biomarkers of quercetin intake.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Stimulation of protein phosphatases as a mechanism of the muscarinic-receptor-mediated inhibition of cardiac L-type Ca2+ channels.

Acetylcholine decreases currents through cardiac L-type Ca2+ channels after stimulation with agents which elevate levels of cyclic adenosine monophosphate, such as isoproterenol, but there is still a controversy over the mechanisms of this muscarinic effect. We tested the hypothesis of whether, after isoproterenol stimulation, protein phosphatases are activated by acetylcholine. Whole-cell currents were recorded from guinea-pig ventricular myocytes. The effect of 10(-5) M acetylcholine on currents induced by 10(-8) M isoproterenol was studied in the absence or presence of protein phosphatase inhibitors. Three agents reduced the acetylcholine response: okadaic acid (3 or 9 x 10(-6) M) and cantharidin (3 x 10(-6) M) added to the pipette solution, and bath-applied fluoride (3 mM). In contrast, pipette application of other phosphatase inhibitors, namely the inhibitor PPI2 (1000 U/ml), ciclosporin (10(-5) M), or calyculin A (10(-6) M) did not significantly diminish the acetylcholine effect. Interestingly, there was no correlation between the effects of the compounds on basal Ca2+ current and their interference with the muscarinic response. An activation of type 2A phosphatases by acetylcholine would explain these findings. Indeed, okadaic acid is 3 orders of magnitude more potent in vitro in its inhibition of this isoform (purified from cardiac myocytes) than is calyculin A, while type-1 phosphatases are inhibited equally. The data support the attractive possibility that stimulation of protein phosphatases is part of the signal transduction cascade of Ca2+ channel inhibition by acetylcholine.

Acetylcholine↗
PubMed1995

Experience with the Novacor left ventricular assist system as a bridge to cardiac transplantation, including the new wearable system.

The three components of the Novacor left ventricular assist system, compact controller, battery, and back-up battery, have been miniaturized in the development of the wearable system. Therefore patients can be fully mobilized receiving mechanical circulatory support while awaiting heart transplantation. Between February 1992 and April 1994 a total of eight patients with decompensated heart failure (6 dilated cardiomyopathy, 1 acute myocarditis, 1 ischemic cardiomyopathy) were treated with the Novacor left ventricular assist systems. In the most recent four cases the wearable system (N100P) was used. Patients' ages ranged from 17 to 49 years. In five patients severe failure of the right side of the heart was present at the time of implantation. Hemodynamic stabilization was achieved in all patients during the 2 to 122 days (mean 30.8 +/- 42.5 days) of support. The following parameters were measured on average before and 24 hours after implantation of the left ventricular assist system: mean arterial pressure 70 +/- 11 versus 87 +/- 13 mm Hg (p < 0.05), cardiac index 1.71 +/- 0.42 versus 3.23 +/- 0.74 L/min/m2 (p < 0.05), pulmonary capillary wedge pressure 27.1 +/- 4.4 versus 9.9 +/- 5.2 mm Hg (p < 0.01), mean pulmonary pressure 41 +/- 9 versus 27 +/- 6 mm Hg (p < 0.05), and right ventricular ejection fraction 16.7% +/- 10.3% versus 22.0% +/- 11.6% (not significant). Patients who received the wearable system were capable of managing their own power supply during the bridging period and were able to walk to the hospital park and shopping area. One patient had a serious pulmonary infection, which was treated successfully, and two patients had a cerebrovascular accident, which resolved in one and resulted in a minor residual deficit in the other. All eight patients received a heart transplant. One patient died early after transplantation and seven patients are alive and well. In summary, the wearable Novacor left ventricular assist system provides major advantages regarding quality of life of patients during mechanical circulatory support. However, there is a remaining risk of thromboembolism despite anticoagulation therapy.

Adolescent↗
PubMed1995

[Chemoembolization in primary liver cell carcinoma. Results of a prospective study].

A remarkable progress was made in the palliative treatment of unresectable hepatocellular carcinoma using transcatheter arterial chemoembolization (TAC). The combination of doxorubicin as cytotoxic drug and of Lipiodol as carrier, which is selectively accumulated within the tumors is an effective treatment. Prolonged survival has been demonstrated in several clinical studies. In a prospective trial the effect of regional TAC with temporary ischemia of the liver was evaluated concerning liver function, systemic reactions and tumor response. Temporary ischemia of the liver was well tolerated even in patients with liver cirrhosis. Revascularization of the liver after TAC was observed in all cases. Systemic side effects of the cytotoxic drug were mild. In patients with Child C cirrhosis or tumor volume of more than 60% of the liver no impact of the treatment on the survival time was observed. In the entire patient group a survival rate of 70% after 15 months was achieved.

Aged↗
PubMed1994

Reduction of cyclosporine-induced nephrotoxicity by cilastatin following clinical heart transplantation.

The objective of this prospective, randomized, placebo-controlled, single-blinded study in 28 heart-transplanted patients was to investigate whether the dehydropeptidase inhibitor cilastatin reduces cyclosporine-induced nephrotoxicity. Cilastatin is available only in combination with imipenem, a beta-lactam antibiotic to which it is added for reduction of nephrotoxic side-effects of the antimicrobial agent. Patients received either 100 ml placebo (n = 12) or 100 ml (500 mg) imipenem/cilastatin (n = 16) twice perioperatively, and 4 times daily for the first 7 postoperative days. Serum creatinine and urea, as well as urine concentrations of N-acetyl-beta-D-glucosaminidase, which is directly correlated with tubular cell damage, were used as markers for renal function. Thromboxane B2 and 6-keto-prostaglandin F1-alpha serum concentrations were determined to investigate whether there is an imbalance in synthesis of thromboxane A2 and prostacyclin as a possible mechanism for cyclosporine-induced nephrotoxicity. Two placebo patients and 6 patients receiving imipenem/cilastatin had to be excluded from further analysis. Three of 10 placebo patients required hemofiltration, and 2 of them even required hemodialysis, as compared with none in the imipenem/cilastatin group. Creatinine concentrations increased significantly from the second to the fourth postoperative day in the placebo group, but remained nearly normal in cilastatin patients (P < 0.05 for intergroup comparison on postoperative days 2-4). The same trend was observed in urea and N-acetyl-beta-D-glucosaminidase concentrations, without the difference reaching statistical significance. For thromboxane B2 and 6-keto-prostaglandin F1-alpha no differences between the groups could be found. These results suggest that imipenem/cilastatin can counteract acute cyclosporine-induced nephrotoxicity, which appears to be associated with alterations of tubular cell function. The combined use of cyclosporine and imipenem/cilastatin appears to be advantageous in patients following heart transplantation during the initial postoperative period.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Degeneration model of the porcine lumbar motion segment: effects of various intradiscal procedures.

In an experimental study with 18 minipigs, we have tried to establish a model for the standardized evaluation of mechanical, histological and radiological phenomena of degenerative and reparative processes within the lumbar motion segment. Comparing different operative techniques revealed that the intradiscal application of hyaluronic acid into the nuclear defect is likely to enhance the regeneration process. Using the measurement of disc compliance, a semiautomatic picture analyzer and a new semiquantitative disc score could make future studies more comparable. From this basis, the intradiscal application of hyaluronic acid deserves further evaluation.

Animals↗