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Biomedical subjects

M Pfister

Publications and source records attributed to M Pfister.

66 records · Page 4Linked to original sources

[Possibilities for increasing the elimination rate of Bonnecor].

Bonnecor is excreted in rats both via urine (3/4) and bile (1/4). It was the aim of this study to find out suitable methods for detoxication of a poisoning with this antiarrhytmic drug. In vivo methods intended to enhance the renal excretion of Bonnecor (forced diuresis, changes in urinary pH-values, peritoneal dialysis) are not qualified for therapeutically relevant increase of Bonnecor elimination. Relating to this Bonnecor is quite comparable with other antiarrhythmic drugs or dibenzazepine derivatives. The hemoperfusion can be recommended for the therapy of a Bonnecor overdosage as a propping up of symptomatic methods of intensive care, which are precendentally indicated. Therefore the therapy of a Bonnecor poisoning seems to be more promising compared to intoxications with other antiarrhythmics. Among the adsorbents tested, the resin Wofatit UH91 is most suitable to remove Bonnecor from the organism. If hemoperfusion equipments are not available, hemodialysis can also be used for acceleration of Bonnecor elimination, although its effectivity is only one third of that of hemoperfusion.

Animals↗

Study of parameters involved in specific immunoadsorption of apolipoprotein B.

A therapeutic immunoadsorption system on immobilized and anti-apolipoprotein B as a plasma cholesterol lowering procedure was optimized. Several antibodies were compared and highest adsorption capacity was obtained with goat polyclonal antibodies. Optimum quantities of antibodies to be immobilized on the gel and quantities of apo-B to be applied to columns were determined. The amount of antibodies released from immunoadsorbents can be minimized by treatment with a 0.005% glutaraldehyde solution with an acceptable reduction rate of adsorption capacity. Each phase, adsorption and desorption respectively, were well-defined and synchronized so two columns could be used in parallel in an automated procedure. In these conditions, the immunoadsorption system can efficiently, specifically and safely remove cholesterol and has to be subjected to clinical trials.

Animals↗

A private red cell antigen, Jones, causing haemolytic disease of the newborn.

Two previously unpublished low-incidence antigens, Jones and Hol., are identical. The antigen is a dominant, autosomally inherited character that segregates independently from the loci for the ABO, MNS, Duffy and Yt blood group systems and is different from previously published infrequent antigens. The antigen is apparently unaffected by enzyme treatment and is well developed on red cells of neonates. The antibody reacts best by indirect antiglobulin testing, is IgG and has caused haemolytic disease of the newborn. This private blood group antigen, named Jones, has been assigned the ISBT number 700047.

Adult↗

[Periodic nocturnal ventilation using an Emerson chest respirator as an alternative to permanent tracheostomy with positive pressure ventilation in patients with idiopathic scoliosis and severe global respiratory insufficiency].

Sustained success was achieved in treating a 40-year-old patient who had had severe progressive thoracic kyphoscoliosis since childhood and developed cardiorespiratory failure with terminal alveolar hypoventilation and hypoxemia due to acute pulmonary infection. On emergency admission to this hospital mechanically controlled ventilation by tracheostomy tube produced a remarkable improvement in cardiorespiratory function. Weakness of the respiratory muscles made complete disconnection from ventilatory support impossible. Instead of positive pressure ventilation by tracheostomy tube with resultant patient invalidity, nighttime external negative pressure ventilation with an Emerson chest respirator was started leaving the patient free for daytime activity. This type of ventilation is a simple, effective and well tolerated long-term treatment at low cost. The patient has been using it nightly at home for over 6 months and no problems have arisen. These findings show that intensive care is indicated in patients with severe thoracic kyphoscoliosis and cardiorespiratory failure since long-term treatment of terminal hypoventilation and cardiorespiratory failure is possible with a cheap and simple nocturnal ventilation system.

Adult↗

Modification of adriamycin toxicity in rats fed a high fat diet.

Rats fed a diet containing a high percentage of butter, cholesterol, cholic acid and proply thiouracil (HFD) showed weight loss and developed hyperlipidemia, marked fatty infiltration of the liver, moderate elevation of SGPT, degenerative changes of the heart muscle, bradycardia, alterations of the QRS complex in the electrocardiogram, and initial hemoconcentration followed by moderate anemia. Treatment with adriamycin (18 X 1 mg/kg i.p.) resulted in significant augmentation of the cardiotoxic effects of this drug demonstrated by electrocardiographic measurements and myocardial histopathology. Adriamycin-induced atrophy of the lymphatic tissue was seen only in rats fed HFD and not in animals receiving ground chow. Adriamycin levels in the heart after single i.p. injection were higher in rats receiving HFD. This effect was present already after 10 days on HFD. At this time histopathological liver changes were present and SGPT was elevated. It is concluded that the increase in adriamycin toxicity is, at least in part, due to diminished excretion by the liver. These experimental findings are in accordance with clinical observations which have identified liver disease as one of the important risk factors for the development of adriamycin cardiomyopathy.

Alanine Transaminase↗

Radioactive labeling and location of specific thiol groups in myosin from fast, slow and cardiac muscles.

1. Based on incorporation of radioactively labeled N-ethylmaleimide, the readily reactive thiol groups of isolated myosin (EC 3.6.1.3) from fast, slow and cardiac muscles could be classified into 3 types. All 3 myosins contain 2 thiol-1, 2 thiol-2 and a variable number of thiol-3 groups per molecule. Both thiol-1 and thiol-2 groups which are essential for functioning of the K+-stimulated ATPase, are located in the heavy chains in all 3 myosin types. 2. The variation in the incorporation pattern of N-ethylmaleimide over the 3 thiol group classes under steady-state conditions of Mg(2+) - ATP hydrolysis allowed different conformations of some reaction intermediates to be characterized. In all 3 types of myosin the hydrolytic cycle of Mg(2+) - ATP was found to be controlled by the same step at 25 degrees C. In all three cases, this rate-limiting step is changed in the same way by lowereing temperature. 3. Using the chemically determined molecular weights for myosin light chains, their stoichiometry was found on the basis of sodium dodecyl sulfate electrophoresis to be 1.2 : 2.1 : 0.8 for light chain-1: light chain-2:light chain-3 per molecule of fast myosin, 2.0 : 1.9 for light chain-1:light chain-2 per molecule of slow myosin and 1.9 : 1.9 for light chain-1:light chain-2 per molecule of cardiac myosin. This qualitative difference in light subunit composition between the fast and the two types of slow myosin is not reflected in the small variations of the characteristics exhibited by the isolated myosins, but rather seems to be connected with their respective myofibrillar ATPase activities.

Adenosine Triphosphatases↗

A second middle eastern kindred with autosomal recessive non-syndromic hearing loss segregates DFNB9.

A second kindred has been identified which supports the previously reported location of DFNB9. Linkage has been established to markers closely linked to DFNB9 which is located on 2p22-p23. The hearing impaired individuals in this highly consanguineous kindred from Eastern Turkey have prelingual profound hearing loss which affects all frequencies. A genetic map of the 2p22-p23 region where DFNB9 resides was generated using marker genotypes available from the CEPH database. All markers were placed on this genetic map using a likelihood ratio criterion of 1000:1. This map suggests that the region for DFNB9 is less than 1.08 cM, 95% confidence interval (0-2.59 cM).

Chromosome Mapping↗

Proinflammatory effects in experimental mesangial proliferative glomerulonephritis of the immunosuppressive agent SDZ RAD, a rapamycin derivative.

BACKGROUND/AIM: The new immunosuppressant SDZ RAD, a rapamycin derivative, inhibits growth factor driven cell proliferation. SDZ RAD designed for transplantation may also be a candidate agent to treat inflammatory kidney diseases. Therefore, we investigated the effects of SDZ RAD in two different animal models of glomerulonephritis, in anti- Thy1.1 nephritis and in acute puromycin aminonucleoside (PAN) nephrosis. METHODS: Eighty-seven male Wistar rats were investigated. Anti-Thy1.1 nephritis: healthy rats (n = 9), SDZ RAD-treated healthy rats (n = 6), nephritic rats (n = 9), SDZ RAD placebo treated nephritic rats (n = 6), SDZ RAD-pretreated nephritic rats (n = 9), and early (n = 6) as well as delayed (n = 6) SDZ RAD-posttreated nephritic rats. PAN nephrosis: healthy rats (n = 6), SDZ RAD-treated healthy rats (n = 6), nephritic rats (n = 12), and SDZ RAD-pretreated nephritic rats (n = 12). In a separate study, 12 male Sprague-Dawley rats were analyzed in anti-Thy1.1 nephritis: healthy rats (n = 3), nephritic rats (n = 3) and pretreated nephritic rats (n = 6). SDZ RAD and SDZ RAD placebo were given at single doses of 2.5 mg/kg body weight per day by gavage. The experiments lasted until days +2 and +9 after induction of anti-Thy1. 1 nephritis and until day +13 in the case of PAN nephrosis. RESULTS: In anti-Thy1.1 nephritis, SDZ RAD demonstrated marked proinflammatory effects in a time-dependent manner, as reflected by severe focal damage to glomerular histology including inhibition of mesangial cell proliferation, reduction of creatinine clearance, and increase in plasma creatinine levels as well as proteinuria. Almost identical results were obtained in both rat strains. In contrary, SDZ RAD ameliorated significantly the development of PAN nephrosis. Animals pretreated by this agent showed a significant reduction of proteinuria and of glomerular invasion of monocytes/macrophages. CONCLUSION: Some caution is warranted for the use of SDZ RAD in inflammatory glomerular diseases, since it accentuated glomerular damage induced by anti-Thy1.1 antibodies.

Animals↗