Differential inactivation of mitochondrial monoamine oxidase by stereoisomers of allenic amines.
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Biomedical subjects
Publications and source records attributed to R L White.
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During a 3 1/2-year period (January 1978 through June 1981), 245 patients in a university hospital became colonized or infected with methicillin-resistant Staphylococcus aureus. During the first 18 months, the incidence of colonization and infection was only 0.05%. After a focal outbreak of methicillin-resistant S aureus in the burn unit, acquisition of the organism by patients on other wards increased significantly. Nonburn patients acquired the organism more often during time periods when newly admitted burn patients acquired methicillin-resistant S aureus. After the burn unit was closed, acquisition of the organism among nonburn patients on adult surgical and medical services decreased significantly. A questionnaire survey of other institutions disclosed that large outbreaks of this infection occurred more frequently in hospitals with burn units. These studies suggest that the occurrence of methicillin-resistant S aureus infections in burn units may lead to increased transmission of the organism to nonburn patients and that control of the infection in such units may reduce spread of the organism to patients without burns.
The outcome of treatment for Hodgkin's disease has been determined for 407 patients treated in 1973. A two-level random sampling assures that these results are representative of the national practice. Actuarial analysis of recurrence-free survival at four years is: Stage IA, 80%; Stage IIA, 75%; Stage IIIA, 60%; combined Stages IB, IIB, and IIIB, 50%. Factors significantly associated with recurrence include stage, histology, age, chemotherapy, new patient load, part-time practice, treatment technique, treatment machine, treatment simulation, work up score, treatment score, and facility of treatment. Major treatment complications by stage ranged from 4-12%; complications are significantly associated with disease location, patient age, and the presence of coexisting disease.
MRSA strains have become increasingly prevalent in the United States and are now an important cause of nosocomial infections in many large, medical school-affiliated hospitals. In affected institutions, from a few percent to 50% of all hospital-acquired S aureus infections are caused by MRSA strains. It has been suggested that the overall incidence of nosocomial S aureus infections may not increase in hospitals where MRSA strains have become epidemic or endemic and that MRSA strains merely replace methicillin-susceptible strains as a cause of hospital-acquired infections. Several recent studies lend support to this theory. Thompson et al [1] reported that the overall incidence of nosocomial S aureus-associated bacteremias and postoperative wound infections in a university hospital did not increase during a period when MRSA strains caused a significantly greater proportion of such infections. Similarly, Linnemann et al [2] found that the overall incidence of nosocomial S aureus-associated bacteremias did not change during a four-year period when the incidence of MRSA-associated bacteremias increased appreciably. At the University of Mississippi Medical Center, MRSA strains have been recovered from patients with increased frequency since an outbreak of MRSA infections occurred in the burn unit in June 1979 [3]. Continuing surveillance has revealed that the incidence of nosocomial MRSA infections was significantly higher in 1980-1982 than during 1979 (P = 0.002 by Mann-Whitney U test). MRSA strains accounted for 11% of nosocomial S aureus infections in 1979, 38% in 1980, 50% in 1981, 36% in 1982, and 32% in early 1983.(ABSTRACT TRUNCATED AT 250 WORDS)
After a long developmental effort, we can now fabricate, using thin-film techniques, both rigid modiolar multielectrodes and flexible scala tympani multielectrodes which we believe appropriate for long-term implantation in human subjects. In vitro and in vivo life tests are in progress to confirm this expectation.
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A series of 5-phenyl-2-furamidines has been synthesized and evaluated for antidepressant activities. Substitution in the phenyl ring with a nitro (4) or an amino (12) group in the ortho-position resulted in an increase in antidepressant activity. Both 4 and 12 antagonized tetrabenazine-induced ptosis in rodents and inhibited norepinephrine (noradrenaline) uptake into crude synaptosomes of whole mouse brain at doses or concentrations comparable to those of the tricyclic antidepressants. However, these compounds did not possess the anticholinergic and antihistaminic activities common to tricyclic antidepressants. In addition, they lacked monoamine oxidase inhibitory activity. The 5-phenyl-2-furamidines represent a new chemical class of antidepressants and may be useful for depressive patients who cannot tolerate the compromising side effects of the tricyclic antidepressants and monoamine oxidase inhibitors.
Inhibitory postsynaptic currents (IPSCs) recorded at cholinergic synapses between identified neurons of the buccal ganglia of Aplysia decay exponentially. IPSC decay has been ascribed to a receptor-channel-dependent kinetic process, rather than to changes in subsynaptic acetylcholine (ACh) concentration, but is prolonged by the anticholinesterase eserine. Our data are consistent with a direct effect of 1.6 X 10(-4) M eserine on an elementary channel process. IPSC decay remains single exponential during eserine prolongation, suggesting that eserine slows the kinetic process responsible for decay, rather than substituting an additional kinetic process. In either control sea water or eserine, noise spectra computed from currents induced by pressure ejection of ACh are fitted by the sum of two Lorentzians. The slow corner frequency f1 is reduced from 6.3 to 3.5 Hz by eserine, consistent with a direct eserine action on receptor-channel kinetics, whereas apparent single-channel conductance was unchanged. Both IPSCs and ACh noise recorded in the same cells were comparably slowed by eserine. In eserine, decay time constant tau agreed with noise f1; however, tau and f1 in control sea water differed by 31%. The discrepancy may be accounted for by invoking an additional component to the recorded noise spectra, perhaps produced by synaptically active choline. In addition to the direct effect on kinetics, prolonged exposure to eserine produces a slow extra component to the IPSC decay tail.
The biosynthesis of isopenicillin N from delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine in a cell-free system has been correlated wih O2 consumption by two methods, involving the use of an oxygen-electrode and an n.m.r. spectrometer respectively. The results are consistent with a 1 : 1 stoichiometric ratio for the dioxygen consumed to the isopenicillin N formed.
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The MS-2 system (Abbott Diagnostics, Division of Abbott Laboratories, Dallas, Tex.) is an automated system capable of rapid antimicrobial susceptibility testing. However, the short incubation periods used by the device may adversely affect its ability to detect slowly growing resistant organisms. Shortly after the introduction of the MS-2 system into the University of Mississippi Medical Center clinical microbiology laboratory, we noted discrepancies between the MS-2 and the disk diffusion susceptibility reports when methicillin-resistant Staphylococcus aureus isolates were tested. Subsequently, we determined the susceptibilities of 75 such isolates by the MS-2 and Kirby-Bauer disk diffusion methods and measured the minimum inhibitory concentrations of methicillin, oxacillin, and cephalothin for 33 of the 75 isolates by standardized agar dilution techniques. There was only 47% overall agreement between the MS-2 and disk diffusion methods when methicillin was tested and 15% agreement when cephalothin was the test drug. There was 93% or more overall agreement between the two methods when other antimicrobial agents were tested. The minimum inhibitory concentration of methicillin was greater than or equal to 16 micrograms/ml for all 33 isolates evaluated by the agar dilution method. A comparison of the MS-2 and agar dilution results revealed an overall agreement of 49% when the susceptibilities to methicillin were determined. The MS-2 system reported that multiple methicillin-resistant S. aureus isolates obtained from a single patient were either resistant, intermediate, or sensitive to methicillin. Inconsistent results were also obtained when a single isolate was tested simultaneously in 10 cuvette cartridges. We conclude that the MS-2 system does not reliably detect methicillin and cephalothin resistance among S. aureus.
One hundred-twelve females with stage I-III breast carcinoma were treated primarily with radical megavoltage irradiation. The loco-regional area received 50 Gy/5 weeks with a boost to the primary site of 10 Gy/1 week to 20 Gy/2 weeks. Local control rates were as follows: 94 per cent in stage I, 86 per cent in stage II and 69 per cent in stage III. Survival rates were comparable to those reported by other authors. Complications correlated with disease stage and extent of radiation fields.
The functional consequences of cholinergic self-inhibitory synaptic potentials (SISPs) upon firing patterns were examined in pairs of electrotonically coupled neurons of Aplysia buccal ganglia. In each neuron, the size of the peak SISP current decrements exponentially with increased number of previous conditioning action potentials (APs). To determine the effect of SISPs on the firing patterns of each cell, AP trains elicited by constant-current steps with the SISP intact were compared to those with the SISP blocked by curare. The SISP prolonged initial interspike intervals, providing an early supplement to accommodation, and produced a 75% increase in the sensitivity of firing frequency vs injected current plots for the first ISI. Firing rates were more regular in the presence of the SISP. However, the efficacy of the SISP, like the size of the underlying current, decrements with repetition. SISP effects were also studied in electrotonically coupled pairs of self-inhibitory neurons. Although the SISP altered the shape of the hyperpolarizing component of coupling potentials, DC coupling between the neurons was unaffected. Firing synchrony in coupled pairs stimulated with long DC pulses was assessed with cross-correlation histograms. In 60 mM Ca2+, the SISP sharpens the central peak of synchrony and deepens the flanking troughs, increasing the probability of synchronous firing within +/- 4 msec by 76%. The major determinants of synchrony were found to be common input, SISP-dependent regularity of firing, and the depolarizing phase of the coupling potential, rather than the SISP-enhanced hyperpolarizing phase.
A series of 3-(aminoacyl)-1-[[[5-(substituted phenyl)-2-furanyl] methylene]amino]-2,4-imidazolidinediones was synthesized and evaluated for skeletal muscle relaxant activity. All compounds were active by the intravenous route, and nine of 11 were active orally. One compound was very active when evaluated by the mouse Straub tail and rotarod tests; its efficacy index (ED50 rotarod/ED50 Straub tail) was 2.0, while its therapeutic index (LD50/ED50 Straub tail) was > 225.
A 24-year-old man had a massive right cerebral infarction after occlusion of the middle cerebral artery trunk by a shotgun pellet that embolized from the heart during external cardiac massage for cardiac arrest. The cerebral infarct was followed by massive edema, uncal herniation, and death.
Forty patients who recently underwent coronary artery bypass graft (CABG) operations had serial hemodynamic and scintigraphic studies. Multidose hypothermic potassium crystalloid cardioplegia was used for myocardial protection and newer techniques in anesthetic management and perioperative patient care were also employed. The method of equilibrium cardiac gated blood pool (GBP) scintigraphy was used to obtain perioperative changes in global ejection fraction (EF) and regional wall motion (RWM). Ninety percent of patients displayed a decrease in EF 2 hours postoperatively when compared to their preoperative values. This change was also associated with a fall in cardiac index (CI) and left ventricular stroke work index (LVSWI). Twenty-four hours postoperatively, EF and CI recovered to preoperative levels, but LVSWI remained depressed. Seven days postoperatively, global EF had improved to a value greater than the preoperative one (50% +/- 3% versus 57% +/- 4%, p < 0.05). Perioperative changes in RWM followed the same pattern as EF, but recovery in this index of regional contractility was faster than EF, since maximal improvement was observed 24 hours postoperatively. Thus transient left ventricular dysfunction is common immediately after CABG, but recent advances in myocardial protection and perioperative management are associated with short-term increases in regional and global left ventricular function documented by noninvasive GBP imaging.
A series of quaternary ammonium salts of dantrolene and clodanolene was prepared and evaluated for skeletal muscle relaxant activity. The quaternary ammonium salts exhibit greater aqueous solubility and, therefore, facilitate intravenous administration. One member of this series, although less effective orally, exhibited greater aqueous solubility than the sodium salt. When administered intravenously, it was a more potent antagonist of skeletal muscle contraction and yielded comparable therapeutic and muscle relaxant efficacy indexes.
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