Thrombotic thrombocytopenic purpura due to rifampicin.
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Humans↗
Biomedical subjects
R E Clark
Publications and source records attributed to R E Clark.
Barbiturates impair cerebral metabolism during hypothermic circulatory arrest.
Barbiturates have been used as a method of cerebral protection in patients undergoing open heart operations. Phosphorus 31 nuclear magnetic resonance spectroscopy was used to assess barbiturate-induced alterations in the cerebral tissue energy state during cardiopulmonary bypass, hypothermic circulatory arrest, and subsequent reperfusion. Sheep were positioned in a 4.7-T magnet with a radiofrequency coil over the skull. Nuclear magnetic resonance spectra were obtained at 37 degrees C, during cardiopulmonary bypass before and after drug administration at 37 degrees C and 15 degrees C, throughout a 1-hour period of hypothermic circulatory arrest, and during a 2-hour reperfusion period. A group of animals (n = 8) was administered a bolus of sodium thiopental (40 mg/kg) during bypass at 37 degrees C followed by an infusion of 3.3 mg.kg-1 x min-1 until hypothermic arrest. A control group of animals (n = 8) received no barbiturate. The phosphocreatine/adenosine triphosphate ratio, reflecting tissue energy state, was lower during cardiopulmonary bypass at 15 degrees C in the treated animals compared with controls (1.06 +/- 0.08 versus 1.36 +/- 0.17; p < 0.001). Lower phosphocreatine/adenosine triphosphate ratios were observed throughout all periods of arrest and reperfusion in the barbiturate-treated animals compared with controls (p < or = 0.01). Thiopental prevented the increase in cerebral energy state normally observed with hypothermia and resulted in a decrease in the energy state of the brain during hypothermic circulatory arrest and subsequent reperfusion. These results suggest that thiopental administration before a period of hypothermic circulatory arrest may prove detrimental to the preservation of the energy state of the brain.
Adenosine Triphosphate↗
Iron chelation in myocardial preservation after ischemia-reperfusion injury: the importance of pretreatment and toxicity.
Oxygen-derived free radicals have been implicated in myocardial ischemia-reperfusion injury. It has been proposed that deferoxamine, an iron chelator, improves myocardial preservation by reducing the iron-catalyzed production of the hydroxyl radical. The objectives of this study were to define the appropriate timing of iron chelation therapy and the dose-response properties of deferoxamine. Isolated working rat hearts were subjected to 25 minutes of normothermic global ischemia. Deferoxamine was given as pretreatment (n = 39; doses of 10 or 30 mg/kg), added to cardioplegic solution (n = 43; doses 0.46 to 1.90 mmol/L), or administered upon reperfusion (n = 52; doses 0.15 to 0.76 mmol/L) and compared with saline controls (n = 25). Deferoxamine pretreatment improved survival at each dose from a control value of 44% to 71% and 72% (p less than 0.05), respectively. A cardioplegia dose of 0.46 mmol/L improved survival from 48% to 75%. Higher doses reduced survival and implied a toxic effect. Reperfusion therapy did not alter survival. Regardless of time of administration, deferoxamine did not improve ventricular function or adenosine triphosphate levels. Deferoxamine given as pretreatment 1 hour before ischemia at doses of 30 mg/kg, and perhaps as low as 10 mg/kg, significantly improved survival. The addition of deferoxamine to cardioplegic solution was safe and may be protective at approximately 0.50 mmol/L; however, toxicity should be considered at concentrations greater than 0.76 mmol/L. These data support the postulate that iron catalysis is involved in the production of oxygen-derived free radicals during ischemia-reperfusion injury. We conclude that pretreatment before ischemia is an important component of iron chelation therapy in myocardial preservation.
Adenosine Triphosphate↗
Nicardipine: myocardial protection in isolated working hearts.
The effectiveness of the calcium antagonist nicardipine in protecting the ischemic myocardium was evaluated using the hemodynamic recovery of isolated working rat hearts subjected to hyperkalemic cardiac arrest followed by ischemia at 37.5 degrees C and 10 degrees C. Rat hearts (n = 51) received 20 mL of cardioplegia and were subjected to 27 minutes of ischemia at 37.5 degrees C. Group A (control) did not receive nicardipine. Groups B through F received nicardipine in the cardioplegia with total doses ranging from 2 micrograms to 6 micrograms. Group A had 46% survival of ischemia, whereas groups C (3 micrograms) and D (4 micrograms) had survival rates of 88% and 100%, respectively (p less than 0.05). The recovery of aortic flow after ischemia was 35% in group A, compared with 76% in group B (2 micrograms) and 81% in group D (p less than 0.05). Group A had 49% postischemic recovery of cardiac output, whereas groups B and D had 82% and 85% recovery (p less than 0.05). The postischemic recovery of stroke volume was 48% in group A compared with 84% in group B, 87% in group D, and 73% in group E (5 micrograms) (p less than 0.05). Additional rats were exposed to 210 minutes of ischemia (n = 41) or 240 minutes of ischemia (n = 56) at 10 degrees C. Control groups did not receive nicardipine, whereas treatment groups received nicardipine in the cardioplegia with total doses ranging from 1.4 micrograms to 6.4 micrograms. There were no significant differences in the survival of ischemia or the recovery of function after ischemia at 10 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Acute severe postischemic myocardial depression reversed by triiodothyronine.
The purpose of this study was to determine the effects of triiodothyronine (T3) on postischemic left ventricular performance and high-energy phosphate content in a severe injury model. Isolated working rat hearts (n = 63) received 20 mL of hyperkalemic NIH No. 1 cardioplegia and were subjected to 20 minutes of ischemia at 37 degrees C. Treated hearts were reperfused with T3-supplemented modified Krebs-Henseleit buffer. Control hearts did not receive T3 supplementation. All treated hearts (n = 44) performed work after ischemia, whereas 26% (5/19) of the control hearts were not able to perform any left ventricular work after ischemia. Comparisons with preischemic values demonstrated significant progressive hemodynamic recovery with increasing concentrations of T3 (0, 0.06, 0.15, and 0.60 ng/mL) with concomitant recovery of left ventricular stroke work index (63%, 72%, 89% [p less than 0.05], and 99% [p less than 0.05], respectively). There were corresponding increases in recovery of aortic flow, systolic pressure, cardiac index, and stroke volume index (p less than 0.05). There were no significant changes in coronary sinus flow or heart rate in any group compared with preischemic values. Comparisons of postischemic high-energy phosphate concentrations also demonstrated no change between treated and untreated groups (p greater than 0.05). We conclude that administration of T3 in a severe left ventricular injury model significantly augments rapid ventricular recovery with no change in postischemic high-energy phosphate concentrations.
Acute Disease↗
Isochromosome (6p) in Waldenstrom's macroglobulinemia.
Cytogenetic data on two cases of previously treated Waldenstrom's macroglobulinemia (WM) are presented. An i(6p) was identified in 60 and 56% of bone marrow (BM) metaphases from each patient, respectively. In both cases, i(6p) occurred as part of a complex karyotype but was also observed as the sole abnormality in a proportion of metaphases. The literature on the cytogenetics of WM and the relevance of i(6p) is discussed.
Chromosome Aberrations↗
Reversible lesions of the cerebellar interpositus nucleus during acquisition and retention of a classically conditioned behavior.
Previous lesion, recording, and stimulation studies have implicated the cerebellum and its associated circuitry as essentially involved in classical conditioning of discrete, somatic muscle responses. In 2 experiments, the interpositus nucleus of the cerebellum was assessed for the plasticity associated with learning and memory of the nictitating membrane (NM) response by using local cooling as a reversible lesion technique. In well-trained animals (Experiment 1), NM conditioned responses (CRs) were abolished during cooling of the interpositus but reappeared when the interpositus returned to body temperature. This cooling-warming protocol could be repeated many times. Cooling could be prolonged (one session, approximately 1 hr) with recovery of NM CRs as tested on the next day. Multiple-unit recordings related to learning were also absent in the interpositus and red nucleus during cooling. In naive animals (Experiment 2), both behavioral and unit CRs did not develop while training with cooling. There was no evidence of savings when training continued without cooling: Behavioral and unit CRs developed as if the animals were still naive. These results support the idea that the interpositus nucleus of the cerebellum is the critical locus for learning and memory of this classical CR.
Animals↗
Chromosome aberrations following cytotoxic therapy in patients in complete remission from lymphoma.
The frequency of chromosome aberrations in the peripheral blood of patients successfully treated for Hodgkin's disease (HD) and non-Hodgkin's lymphoma is compared with that seen in age-matched haematologically normal subjects. Findings are considered in relation to risk factors associated with the development of secondary myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML). Overall aberration frequencies were not significantly increased in patients compared with normal subjects. However, there were differences in aberration type. The frequency of exchanges was significantly higher among patients (P less than 0.01) and the frequency of gaps lower (P less than 0.0005). The mean frequency of exchanges was also greater in patients receiving multiple compared to single courses of therapy (P less than 0.0005) and in patients receiving radiotherapy or combined modality therapy compared to chemotherapy alone (P less than 0.005 and P less than 0.0005). Four patients had aberration frequencies greater than 2 SD above the patient mean. One of these was also found to have a mutation of the ras oncogene. None of the patients has yet developed secondary MDS/AML.
Antineoplastic Combined Chemotherapy Protocols↗
Dangers in the evaluation of instructional media.
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Computer-Assisted Instruction↗
Competition and community mental health agencies.
Community mental health agencies (CMHAs) provide most of the institutional outpatient treatment in the United States. A great deal of this care is given to clients at prices below the actual cost of the service. As the number of mental health providers increases, the question of how competition shapes the performance of CMHAs becomes more important. We use a two-stage least-squares model to examine how competition from other outpatient facilities, psychiatrists, and health maintenance organizations (HMOs), coupled with demographic, economic, and organizational factors affects subsidized care in CMHAs. Our analysis shows that competition from psychiatrists and HMOs reduces the number of subsidized visits that CMHAs provide and that agencies in urban areas and those initiated with federal funds provide more subsidized care. By restricting access to outpatient treatment, competition may have adverse long-term consequences for potential clients and for state mental health authorities.
Ambulatory Care↗
Pretreatment with nicardipine preserves ventricular function after hypothermic ischemic arrest.
Calcium antagonists have a protective effect on postischemic myocardial function when included in normothermic cardioplegia solutions. This effect varies with the calcium antagonist, but is generally lost under hypothermic conditions. The hypothesis tested was that a calcium antagonist would increase postischemic myocardial performance if given before the onset of hypothermic arrest. Isolated working rat hearts were used with an oxygenated modified Krebs-Henseleit buffer solution as a perfusion media. Rats were pretreated with 1 of 9 doses of a nicardipine solution (0 to 100 micrograms/kg, intraperitoneally) 20 minutes before excision of the heart. Nicardipine is a light-stable, water-soluble calcium antagonist with minimal myocardial depressant effects. The hearts were arrested for 25 minutes at 37 degrees C or 93 minutes at 24 degrees C with 20 mL of cardioplegia solution containing 0.05 mmol/L CaCl2. Postischemic performance and adenosine triphosphate content were used as determinants of efficacy. Eighty-three percent of 101 treated hearts recovered in contrast to a mortality of 50% in the 24 nontreated hearts. Pretreatment with 25 micrograms/kg significantly increased (p less than 0.05) the percent recovery (compared with the nontreated group) of the following variables of cardiac function: systolic pressure, 74% to 96% (37 degrees C), 76% to 90% (24 degrees C); cardiac output, 61% to 90% (37 degrees C), 62% to 84% (24 degrees C); stroke work, 49% to 95% (37 degrees C), 50% to 92% (24 degrees C); and adenosine triphosphate, 76% to 87% (37 degrees C), 58% to 68% (24 degrees C). Progressive increases in postischemic function at 37 degrees and 24 degrees C were seen as the dose of nicardipine was increased from 0 to 25 micrograms/kg and decreased function was seen with a pretreatment dose greater than 25 micrograms/kg of nicardipine. Pretreatment with nicardipine significantly improved postischemic myocardial performance under hypothermic conditions and should be administered or at least not discontinued before cardiac operations.
Adenosine Triphosphate↗
Aortic regurgitation after left ventricular myotomy and myectomy.
Five hundred twenty-five patients with hypertrophic cardiomyopathy underwent left ventricular myotomy and myectomy (LVMM) from 1960 to 1990. Four hundred ninety-six had nonregurgitant trileaflet aortic valves before LVMM. In 19 (4%) of these patients, aortic regurgitation developed after LVMM. Age of the 19 patients ranged from 10 to 58 years (mean age, 35 +/- 3 [+/- standard error of the mean]]. Seven were male and 12, female. Five patients underwent LVMM followed immediately by aortic valve replacement or valvuloplasty. Aortic regurgitation developed in 14 patients at a later date. The average New York Heart Association functional class improved from 3.2 +/- 0.1 to 1.3 +/- 0.1 (p less than 0.05, Student's t test) after operation. The average peak systolic left ventricular outflow tract gradient at rest and with provocation decreased from 65 +/- 8 to 14 +/- 5 mm Hg (p less than 0.05) and 108 +/- 9 to 45 +/- 7 mm Hg (p less than 0.05), respectively, 6 to 8 months after operation. Aortic regurgitation occurred in 7 of the 14 patients at 6 months or less after operation, and 3 required operative repair. In the other 7 patients, aortic regurgitation developed 3 years or more after LVMM, and 3 of them also required operative repair. All 12 patients in whom aortic regurgitation developed at operation or within 6 months postoperatively had either a very small aortic annulus (less than or equal to 21 mm, 5 patients), a low mitral-septal contact lesion (greater than or equal to 35 mm below the aortic annulus, 3 patients), or both (4 patients).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Triiodothyronine: to be or not to be, that is the question.
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Animals↗
Magnesium ion is beneficial in hypothermic crystalloid cardioplegia.
The role of magnesium ion and its relation to the calcium concentration of cardioplegic solutions was reexamined in this study. Isolated rat hearts were used with an oxygenated modified Krebs-Henseleit bicarbonate buffer as perfusion medium. The hearts were arrested for 20 minutes at 37 degrees C or 90 minutes at 24 degrees C. Treatment groups received one dose of nine possible cardioplegic solutions containing magnesium (0, 1.2, or 15 mmol/L) and calcium (0.05, 1.5, or 4.5 mmol/L). Ninety-six percent of the 75 magnesium-treated hearts recovered, regardless of the calcium concentration, in contrast to a 52% recovery rate in the 69 hearts that did not receive magnesium. The addition of 15 mmol/L Mg2+ to a cardioplegic solution containing no magnesium but 0.05 mmol/L Ca2+ significantly increased (p less than 0.01) the percent recovery of the following parameters of cardiac function: systolic pressure, 74% to 93% (37 degrees C), 64% to 98% (24 degrees C); cardiac output, 76% to 101% (37 degrees C), 71% to 102% (24 degrees C); stroke work, 64% to 104% (37 degrees C), 52% to 99% (24 degrees C); and adenosine triphosphate level, 75% to 83% (37 degrees C), 58% to 90% (24 degrees C). There were significant reductions (p less than 0.03) in percent recovery (37 degrees C and 24 degrees C) of cardiac output, stroke work, and adenosine triphosphate level in the groups that contained 0 or 15 mmol/L Mg2+ as the calcium concentration was increased from 0.05 to 4.5 mmol/L.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenosine Triphosphate↗
Reoperation for persistent outflow obstruction in hypertrophic cardiomyopathy.
This study compares results of a second left ventricular myotomy and myectomy (M + M) with those of mitral valve replacement (MVR) as reoperative procedures for persistent left ventricular outflow obstruction after M + M in hypertrophic cardiomyopathy. Comparison of the second M + M group (n = 12) with the MVR group (n = 11) disclosed significant difference (p less than 0.05) in mean age at the initial operation (29 +/- 11 years versus 40 +/- 8 years), interval between operations (46 +/- 57 months versus 18 +/- 13 months), and age at reoperation (33 +/- 10 years versus 42 +/- 8 years); and insignificant differences in mean preoperative functional class, cardiac index, left ventricular outflow gradients at rest or with provocation, and hospital mortality at reoperation (2/12 versus 1/11). At 6 months after reoperation, comparison of results of a second M + M with MVR showed that mean functional class, cardiac index, and left ventricular outflow gradient at rest were similarly improved, but the outflow gradient with provocation was significantly higher in the second M + M group (57 +/- 44 mm Hg versus 14 +/- 9 mm Hg, p less than 0.05). Total follow-up was 108 patient-years (100% complete) with an average of 5.9 years per patient in the second M + M group and 3.4 years per patient in the MVR group. Actuarial survival, including hospital mortality, at 3 and 5 years was 83% and 76%, respectively, after the second M + M, which was similar to 92% and 77% after MVR.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Brain protection during circulatory arrest.
Previous nuclear magnetic resonance studies in this laboratory have shown a beneficial biochemical effect of antegrade cerebroplegia (CP-A) during hypothermic circulatory arrest. This study compared CP-A with other methods of cerebral protection during hypothermic circulatory arrest to assess the clinical utility of this technique. Twenty-three sheep were divided into four groups: systemic hypothermia alone (SYST) and systemic hypothermia combined with external cranial cooling (EXTNL), retrograde cerebroplegia (CP-R), or CP-A. Cardiopulmonary bypass was started, and the sheep were cooled to 15 degrees C and subjected to 2 hours of circulatory arrest. Cardiopulmonary bypass was restarted, and the animals were rewarmed and weaned from cardiopulmonary bypass. Serial neurological examinations were performed and hourly scores assigned until the animals were extubated. Postanesthetic neurological scores improved in all groups throughout the 6-hour recovery period except the CP-R group. The improvement over time for these scores was similar for the EXTNL and CP-A groups and significantly better than for the SYST or CP-R groups (p = 0.004). The CP-A group had 5 of 7 animals with deficit-free survival despite the similarity in recovery of baseline brainstem function. We conclude that both antegrade infusion of cerebroplegia and external cranial cooling confer distinct cerebroprotective effects after a protracted period of hypothermic circulatory arrest when compared with the other methods studied.
Animals↗
Prevention of ischemia-reperfusion injury by the allergy drug lodoxamide tromethamine.
Lodoxamide tromethamine, an orphan antiallergy drug, inhibits degranulation of mast cells that reside in the myocardium and inhibits xanthine oxidase located in myocytes and predominantly in the vascular endothelium. The hypothesis evaluated was that lodoxamide tromethamine would attenuate oxygen free radical damage. Isolated working rat hearts were perfused with Krebs-Henseleit buffer containing 0, 1, 10, 100, or 1,000 mumol/L lodoxamide tromethamine at 37 degrees and 24 degrees C with ischemic times of 22 and 93 minutes, respectively. These ischemic intervals yielded 50% survival and 50% return of function in untreated hearts. Lodoxamide treatment alone at the onset of reperfusion was also studied. Performance end points were aortic flow, pressure, and coronary flow. Biochemical analyses included serotonin collected from coronary effluent as a marker of mast cell degranulation, uric acid for xanthine oxidase inhibition, myocardial adenosine triphosphate, and carbonyl group concentrations. Performance data demonstrated that lodoxamide was beneficial in a log-linear dose response when given continuously at both temperatures. Percent of preischemic values for untreated and maximal responses at 1,000 mumol/L of lodoxamide were as follows: a mortality of 50% in nontreated hearts versus 0%; aortic flow, 47% to 94% (37 degrees C), 46% to 86% (24 degrees C); cardiac output, 60% to 98% (37 degrees C), 58% to 97% (24 degrees C); adenosine triphosphate, 59% to 90% (37 degrees C), 48% to 65% (24 degrees C). Serotonin was undetectable from any hearts. Uric acid concentrations and carbonyl group content did not change with increasing dose. Lodoxamide demonstrated no benefit when given only during reperfusion, suggesting injury occurred at times other than reperfusion.
Adenosine Triphosphate↗
The STS National Database: alive, well, and growing.
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Databases, Factual↗