Biomedical subjects
Publications and source records attributed to M B Mitchell.
The nonresectional approach to major liver trauma is clearly preferred. Unfortunately, trachotomy with vessel ligation, selective hepatic arterial ligation, perihepatic pack, and fibrin glue are not viable options with high-energy bilobar liver injuries. We have fashioned a balloon tamponade device that has proved very effective for these transfixing hepatic gunshot wounds.
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The establishment of a pneumoperitoneum is essential for laparoscopy. Anatomical features of the umbilicus can be used to reduce associated complications and improve the ease of creating a pneumoperitoneum.
Between April 1988 and February 1989, 877 patients undergoing total hip (394 patients) and total knee (483 patients) replacement surgeries were given warfarin prophylaxis perioperatively and were tested with impedance plethysmography (IPG) approximately 17 days postoperatively (10 days post-discharge) in the outpatient office. There were 69 positive IPG tests (7.8%). Further assessment of patients with positive IPG results using duplex scanning or venography confirmed DVT in 25 of the 69 patients (3.6%) in the popliteal or thigh areas, and ruled out venous disease in 44 patients. All 25 patients were readmitted for anticoagulation therapy with intravenous (IV) heparin and warfarin. There were no cases of pulmonary embolus. This study indicates that IPG testing is a safe and effective method of screening patients for DVT and its potentially fatal sequela of pulmonary embolus. Furthermore, IPG testing has proven to be cost effective, as it is a relatively simple procedure which can be administered by non-professional personnel in the outpatient office setting.
6-[4-[3-[[2-Hydroxy-3-[4-[2- (cyclopropylmethoxy)ethyl]phenoxy]propyl]amino]propionamido] phenyl]- 5-methyl-4,5-dihydro-3(2H)-pyridazinone (3) consists of a mixture of four stereoisomers, i.e., two racemates, as a consequence of the two asymmetric centers contained in the structure. An approximately equimolar mixture of these two racemates exhibits a novel combination of vasodilation and beta-adrenergic antagonist activity. This paper describes the synthesis of each of the four possible stereoisomers of 3 and provides clear evidence for the different pharmacological profile of each of the stereoisomers. The RA,SB isomer 3a has an overall profile slightly better than the complete mixture; the other three isomers all show reduced activity as vasodilators and/or beta-adrenergic antagonists.
Antibodies were raised in rabbits to electrophoretically homogeneous cytochromes P-450 isolated from rat and human liver microsomes. These antibodies were used to compare various forms of rat, rabbit, and human cytochromes P-450 present in microsomes and in purified preparations by using double-diffusion analysis, immunoelectrophoresis, quantitative microcomplement fixation, competitive radioimmune assay and inhibition of enzyme activity toward d-benzphetamine and benzo[a]pyrene. The results indicate that (1) at least some forms of cytochrome P-450 from the three species share certain common immunological determinants, (2) there are immunological differences between cytochromes P-450 isolated from the three species, (3) some immunological differences exist between cytochromes P-450 isolated from rats of different strains, (4) immunologically distinguishable forms of cytochrome P-450 exist within individual human liver samples, and (5) human liver samples obtained from different individuals contain immunologically different forms of cytochrome P-450. Quantitative microcomplement fixation techniques were used to assign immunological distances to different form of rat, rabbit, and human liver microsomal cytochrome P-450. Cross-reactivity was observed in all systems tested, and the extent of immunological similarity was dependent upon the particular assay used.
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1,3,4-Trimethylpyrrole and 1-methyl-3,4-bis(hydroxymethyl)pyrrole were synthesized and labeled with tritium in the C3 and C4 substituents. Both pyrroles were covalently bound to protein, DNA, and RNA when administered to rats in vivo; the level of binding of the trimethyl compound was an order of magnitude higher than that of the diol in liver. Binding of both pyrroles to protein in vitro was catalyzed by microsomal fractions in the presence of NADPH but not NADH, and the enzymatic activation of the trimethyl compound was inhibited by SKF 525-A, CO, anaerobiosis, or reduced glutathione. The microsomal fractions could be replaced by reconstituted systems containing highly purified NADPH-cytochrome P-450 reductase and cytochrome P-450 in catalyzing the activation of the trimethyl compound. These results indicate that cytochromes P-450 can activate pyrroles to more electrophilic species capable of binding irreversibly to biological macromolecules.