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Biomedical subjects

M Pfeiffer

Publications and source records attributed to M Pfeiffer.

At least 19 recordsLinked to original sources

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

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

[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

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

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

Medical malpractice reform as a part of health care reform.

It appears that any health care reform will include tort reform. Since health care reform is aimed at reducing the cost of providing health care and since medical malpractice is believed to be a significant portion of that cost, any health care reform bill passed under the current political climate will most likely include provisions for limiting the costs associated with medical malpractice.

Defensive Medicine

Effect of dietary restriction on in vivo somatic mutation in mice.

Dietary restriction is the one experimental variable which has been shown reproducibly to retard ageing. The effect of dietary restriction on in vivo mutation was studied in mice by feeding experimental mice 60% of the amount eaten by control mice and measuring mutations in lymphocytes at the hypoxanthine phosphoribosyl transferase locus at 4 weeks, 6 months and 12 months of age. Dietary restriction markedly decreased the age-associated accumulation of mutations observed in control mice, which suggests that somatic mutation is involved in the ageing process and that the majority of in vivo mutations result from dietary factors.

Aging

[Craniocerebral trauma and aseptic osteonecrosis. Steroid-induced sequelae after therapy of brain edema].

In this publication we present three cases of avascular osteonecrosis (AON) of the femoral head and the talus in adolescent and young adult patients following short-term, high-dose steroid therapy for cerebral trauma. All patients were proven to be free of other risk factors for AON. The latency period between the steroid therapy and the occurrence of AON ranged from 12 to 60 months; steroid therapy lasted for 12 to 16 days with a total dosage equivalent to 2370-7180 mg prednisolone. Our case reports are added to a review of the literature with 14 similar cases reported receiving short-term, high-dose steroid therapy; 2 of them were also after brain trauma. To the best of our knowledge, 1 of our cases shows the longest latency period ever described after such therapy, and all our cases had a shorter therapy time than reported by other authors who have mentioned brain trauma patients. Additionally, bilateral necrosis of the talus due to short-term, high-dose steroid therapy has also not previously been described. Whereas AON is quite common after long-term steroid therapy (e.g., for immunosuppression and rheumatic disorders), our cases prove that serious complications can occur even after a short period of emergency steroid therapy in cerebral trauma, a possibility that is generally unknown. The minimal dosage and the maximum time steroids can be applied to exclude the risk of AON has not yet been determined, although we do recognize that steroids are useful for the prevention of brain edema.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Vertebral body replacement with homologous femoral head transplants.

From 1978 to 1989, we carried out 15 resections of single vertebral bodies, with homologous femoral head transplantation, for malignant and benign lesions of the spine. The advantages of this procedure are compared to fixation with bone cement, autologous bone grafts and other materials. The results are discussed.

Adolescent

[Wound secretions in standard orthopedic surgery interventions using a new kind of closed vacuum drainage. A report of experiences].

One year's experience with 400 closed Redyrob drainage systems in 267 male and female patients has yielded encouraging results, which led to the replacement of the drainage system formerly used in the orthopaedic university clinic in Marburg by the new system. This makes it possible to regulate the suction strength between 0 and 900 mbar and to couple two suction tubes with one container. Drainage without suction and changing of the containers, which may be necessary in the case of large wound surfaces, can be performed without opening the system, which would endanger both patients and clinic personnel. Additional containers were only needed in 2.3%, because of the better filling volume. Thus, the new drainage system also proved to be superior with respect to cost efficiency and disposal. The total amount of wound secretion never exceeded 1620 ml, depending on the type of surgery performed, and there were no cases of infection or bleeding complications. The suction was regulated in 74% of all systems, and after most of the operations for insertion of endoprostheses. The handling of the systems was classed by the staff on the ward as "very good" or "good" in 96% of all cases. These results are discussed in the light of important aspects of wound drainage already mentioned by other authors.

Adult

[Puncture track metastasis after ultrasound-guided fine-needle puncture biopsy. A rare complication?].

Bilaterally enlarged adrenals were diagnosed by ultrasonography in a 57-year-old man with a potentially resectable adenocarcinoma of the lung. Ultrasound-guided fine-needle biopsy of the left adrenal revealed a metastasis, proven cytologically. Chemotherapy was tried but failed to influence tumour growth. Three months later a painful subcutaneous nodule was noted in the area of the previous needle puncture, which on removal proved to be a skin metastasis. The patient died later from the underlying tumour.

Adenocarcinoma