Rhabdomyolysis associated with lovastatin and erythromycin use.
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Biomedical subjects
Publications and source records attributed to C D Clark.
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The properties of the autonomically regulated chloride current (ICl) were studied in isolated guinea pig ventricular myocytes. This current was elicited upon exposure to isoproterenol (ISO) and reversed upon concurrent exposure to acetylcholine (ACh). ICl was time independent and exhibited outward rectification. The responses to ISO and ACh could be blocked by propranolol and atropine, respectively, and ICl was also elicited by forskolin, 8-bromoadenosine 3',5'-cyclic monophosphate, and 3-isobutyl-l-methylxanthine, indicating that the current is regulated through a cAMP-dependent pathway. The reversal potential of the ISO-induced current followed the predicted chloride equilibrium potential, consistent with it being carried predominantly by Cl-. Activation of ICl produced changes in the resting membrane potential and action potential duration, which were Cl- gradient dependent. These results indicate that under physiological conditions ICl may play an important role in regulating action potential duration and resting membrane potential in mammalian cardiac myocytes.
The Saccharomyces cerevisiae CDC46 protein accumulates in the nucleus of nondividing interphase cells. Soon after the cell has become committed to division, there is a rapid disappearance of CDC46 protein from the nucleus. This shift is not a consequence of variation in total CDC46 protein levels and is associated with DNA replication at the G1-S boundary. We propose that the CDC46 protein, which is required for DNA replication, becomes mobilized quickly from the cytoplasm into the nucleus as mitosis is completed and persists there until the next round of division is initiated. This partitioning of proteins in a cell cycle-dependent manner illustrates a general means of regulating events that must occur only once in each cycle, such as DNA initiation.
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A DNA sequence consisting of the 5-mer AGAGG repeated tandemly 32 times has been detected in a chicken genomic clone and found to be present in about 2000 copies per chicken genome. This sequence was highly susceptible to single-strand specific endonucleases isolated from Aspergillus oryzae (S1) and mung bean, but cleavage by a single-strand specific endonuclease isolated from Neurospora crassa occurred only at a pH below 5.5. Endonucleolytic cutting of the AGAGG sequence by the single-strand specific enzymes required a supercoiled substrate and was independent of ionic strength.
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SMEDI and hog cholera viruses were shown to have marked effects upon the survival of the embryo (from conception to 30 days of gestation), the fetus (from 30 days of gestation until birth), and the neonatal pig (from birth until five days after birth). Embryonic infection was characterized by death and absorption of the embryo and in some instances the return to estrus after an irregular estrous cycle. Embryonic infection also may have been responsible for the development of some abnormal pigs. Fetal infection caused death with mummification of one or more fetuses and occasionally all fetuses in the uterus. Infection established in early gestation produced effects on the fetus which apparently persisted until after birth and varied from a persistent viremia (as in hog cholera infection) to an undefined lack of resistance in the newborn (as in SMEDI virus infection). Hog cholera vaccinal virus was the more virulent of the two virus types and reacted somewhat like rubella virus, in that infection apparently could be established in the fetus even in middle trimester of pregnancy, and possibly later. SMEDI viruses, in contrast, were less virulent and were most pathogenic when the dam was infected during the first 30 days of pregnancy. Immunity against either virus could be established in the nonpregnant gilt and was most effective in preventing intrauterine infections with that virus. However, with as many as 10 enteroviruses (five are known to cause intrauterine infection) it was believed that maintaining a closed breeding herd and introducing new stock into contact with the breeding herd at least 30 days before breeding time might be a safer means of control.
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OBJECTIVE: To evaluate changes in antimicrobial use and expenditures and the rates of selected nosocomial infections due to resistant organisms associated with implementation of an antimicrobial-prescribing improvement program. DESIGN: Before-after trial comparing 1992 (pre-program), 1993 (a transition year), and 1994 (after full implementation of the program). SETTING AND PARTICIPANTS: Academic medical center, all patients and physicians. INTERVENTION: An antimicrobial-prescribing improvement program with prior approval requirement for use of restricted agents. MAIN OUTCOME MEASURES: Antimicrobial use and expenditures, rates of selected nosocomial infection marker events. RESULTS: Between 1992 and 1994, there were substantial decreases in antimicrobial use, from 158,107 to 137,364 defined daily doses, and in expenditures from $2,486,902 ($24.01 per patient day) to $1,701,522 ($18.49 per patient day). After adjusting for changes in purchase prices and census days, we estimated savings attributable to the program of $279,573 in 1993 and $389,814 in 1994. In addition, we found significant decreases between 1992 and 1994 in the rates of enterococcal bacteremia (.34 vs .16 events per 1,000 patient days; P = .016), selected gram-negative bacteremia (.26 vs .11; P = .015), methicillin-resistant Staphylococcus aureus colonization or infection (.66 vs .20; P < .0001), and Stenotrophomonas colonization or infection (.35 vs .17; P = .019). No significant change occurred in rates of nosocomial candidemia or Clostridium difficile toxin-positive diarrhea. Values for 1993 were intermediate between those of 1992 and 1994. CONCLUSION: Implementation of an antimicrobial-prescribing improvement program was associated with substantial savings in antimicrobial use and expenditures and significant decreases in rates of selected nosocomial infections due to resistant organisms.