Metronidazole-resistant strain of Clostridium perfringens isolated from a clinical specimen.
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Aged↗
Biomedical subjects
B Faris
Publications and source records attributed to B Faris.
Candida parapsilosis: an unusual organism causing prosthetic heart valve infective endocarditis.
We report a case of Candida parapsilosis prosthetic heart valve infective endocarditis in a 67-year-old man. The infection was successfully treated with liposomal amphotericin B (AmBisome) and flucytosine. Surgical replacement of the infected valve was necessary. Recurrence was prevented with oral fluconazole 400mg daily as maintenance therapy. The patient remained well after 2 years of follow-up.
Aged↗
Inhibition of the pacemaker current: a bradycardic therapy for off-pump coronary operations.
BACKGROUND: The accurate performance of coronary anastomoses on the beating heart requires some form of myocardial immobilization that can be achieved pharmacologically. Different classes of drugs can be used to induce bradycardia, but the most effective in this setting of off-pump operation has not yet been determined. METHODS: Fifty-six isolated buffer-perfused rabbit hearts were divided into seven equal groups. Control hearts were continuously perfused throughout the experimental time course. A second group of hearts underwent 60 minutes of potassium arrest (at 37 degrees C) followed by 1 hour of reperfusion. The following pharmacologic approaches were tested in the remaining five groups: short-acting beta-blockade (esmolol, 6 x 10(-3) mol/L and 3 x 10(-4) mol/L), opening of adenosine triphosphate-dependent potassium channels (nicorandil, 10(-3) mol/L and 10(-5) mol/L), and inhibition of the pacemaker current, which largely accounts for the diastolic depolarization of sinoatrial node cells (S 16257-2, 3 x 10(-6) mol/L). Each drug was infused at a constant rate for 60 minutes, after which hearts were perfused for 1 additional hour with drug-free buffer. Heart rate and isovolumic measurements of function and coronary flow were serially taken during and after drug infusion. RESULTS: The worst recovery of systolic and, moreover, diastolic function was yielded by potassium arrest. Neither esmolol nor nicorandil was able to induce a significant bradycardia. However, nicorandil did not impair function which, conversely, was markedly depressed after esmolol therapy. Significant bradycardia (p < 0.0001 versus corresponding baseline values and versus all other groups) was only achieved with pacemaker current inhibition, which was otherwise associated with an excellent preservation of contractility, diastolic function, and coronary flow. CONCLUSIONS: Inhibition of the pacemaker current seems to be an effective approach for inducing intraoperative bradycardia without compromising left ventricular function or flow.
Adrenergic beta-Antagonists↗
[Coronary surgery on the beating heart under extracorporeal circulation in high-risk patients. An acceptable compromise?].
Coronary artery surgery with cardioplegia in high risk patients carries a risk of myocardial ischaemia and, without cardiopulmonary bypass, is not always technically feasible. The authors assessed an alternative, surgery on the beating heart with haemodynamic assist by cardiopulmonary bypass in 43 consecutive patients with poor left ventricular function (mean ejection fraction: 0.26), evolving myocardial ischaemia or acute myocardial infarction, old age (mean: 79.5 years) and comorbid conditions. Results were assessed mainly on clinical criteria. In addition, 9 patients had pre- and post-cardiopulmonary bypass measurements of markers of myocardial ischaemia (troponine Ic) and systemic inflammation (interleukines 6 and 10, elastase). In 6 cases, right atrial biopsy was analysed for expression of messenger ribonucleic acid coding for heat shock protein (HSP) 70; the data were compared with those of patients operated under warm blood cardioplegia. There was one cardiac death and one myocardial infarction. Myocardial conservation was confirmed by the minimal increase in troponine Ic levels and the significant increase in HSP 70 in RNA suggesting myocardial adaptation to stress. On the other hand, the minimal concentrations of mediators of inflammation were not significantly changed. In selected high risk patients, coronary revascularisation on the beating heart under cardiopulmonary bypass could be a valuable alternative. It conserves the potentially deleterious effects of cardiopulmonary bypass but peroperative global myocardial ischaemia, an important factor in the aggressivity of cardiac surgery, is eliminated.
Adult↗
On-pump, beating-heart coronary artery operations in high-risk patients: an acceptable trade-off?
BACKGROUND: Current cardioplegic techniques do not consistently avoid myocardial ischemic damage in high-risk patients undergoing coronary artery bypass grafting. Alternatively, revascularization without cardiopulmonary bypass is not always technically feasible. We investigated whether an intermediary approach based on maintenance of a beating heart with cardiopulmonary bypass support but without aortic cross-clamping might be an acceptable trade-off. METHODS: Thirty-seven consecutive patients underwent coronary artery bypass grafting (with an average of two grafts per patient) in a pump-supported, non-cross-clamped beating heart. Inclusion criteria were poor left ventricular function (18 patients; mean ejection fraction, 0.25), evolving myocardial ischemia or infarction (11 patients, 5 of whom were in cardiogenic shock), and advanced age (3 patients; mean age 79.5 years) with comorbidities. Results were assessed primarily on the basis of clinical outcome. In addition, measurements of plasma levels of markers of myocardial damage (troponin Ic) and systemic inflammation (interleukin-6, interleukin-10, elastase) were done in 9 patients before and after bypass. In 6 patients, right atrial biopsy specimens were taken before and after bypass and processed by Northern blotting for the expression of messenger ribonucleic acid coding for the cardioprotective heat-shock protein 70. These biologic data were compared with those from control patients who underwent warm cardioplegic arrest within the same time span. RESULTS: There was one cardiac-related death (2.7%), one Q-wave myocardial infarction, and no strokes. Four other deaths occurred from noncardiac causes, yielding an overall mortality rate of 13.5%. Limitation of myocardial injury was demonstrated by the minimal increase in postoperative troponin Ic levels (3.3 +/- 1.0 micrograms/L versus 6.6 +/- 1.5 micrograms/L in controls; p < 0.05) and the finding that heat-shock protein 70 messenger ribonucleic acid levels (expressed as a percentage of an internal standard) were significantly increased after bypass compared with pre-bypass values (279% +/- 80% versus 97% +/- 21%; p < 0.05). In the control group (cardioplegia), end-arrest values of heat-shock protein 70 messenger ribonucleic acid were not significantly changed from baseline (148% +/- 49% versus 91% +/- 29%), a finding suggesting a defective adaptive response to surgical stress. Conversely, peak levels of inflammatory mediators were not significantly different between the two groups. The eight grafts to the left anterior descending coronary artery that were assessed angiographically, by transthoracic Doppler echocardiography, or both methods were patent with satisfactory anastomoses. CONCLUSIONS: In select high-risk patients, on-pump, beating-heart coronary artery bypass grafting may be an acceptable trade-off between conventional cardioplegia and off-pump operations. It is still associated with the potentially detrimental effects of cardiopulmonary bypass but eliminates intraoperative global myocardial ischemia.
Adult↗
Failure of preconditioning to improve postcardioplegia stunning of minimally infarcted hearts.
BACKGROUND: Ischemic preconditioning is an effective means of reducing myocardial infarct size, but its ability to attenuate stunning after an episode of surgically relevant global ischemia remains elusive. Likewise, the role played by adenosine in this setting has not been established conclusively. This study was designed to address these two issues. METHODS: Thirty isolated, crystalloid-perfused rabbit hearts were subjected to 60 minutes of normothermic potassium arrest and 60 minutes of reperfusion. They were divided into three equal groups. The first group had no prearrest intervention and served as a control. In the second group, ischemic preconditioning was achieved with 5 minutes of zero-flow ischemia followed by 5 minutes of buffer reperfusion before arrest. In the third group, the hearts were first infused for 5 minutes with the nucleoside transport inhibitor draflazine (10(-6) mol/L), the efficacy of which was demonstrated by reversal of the normally high inosine to adenosine ratio in the coronary effluent. These hearts subsequently were given 2 additional minutes of ischemic (zero-flow) preconditioning followed by 5 minutes of reperfusion before arrest. During reperfusion, function was measured serially under isovolumic conditions. Myocardial necrosis was estimated from the release of creatine kinase after the initial 5 minutes of reflow, and the planimetrically determined extent of infarction was determined by triphenyltetrazolium chloride staining. RESULTS: Baseline hemodynamic data were comparable among the three groups. Neither ischemic preconditioning alone nor ischemic preconditioning with draflazine-induced enhancement of endogenous adenosine levels improved postischemic recovery of function over that seen in control, untreated hearts. These results correlated with a minimal amount of infarction in the control group (on average, <10% of the left ventricle), which was not reduced further by either preconditioning regimen. CONCLUSIONS: These data support the idea that, in the absence of substantial necrosis, ischemic preconditioning does not ameliorate postischemic stunning, which leads to the question of its usefulness in clinical cardiac operations. Although, in this model, protection was not potentiated by increasing endogenous concentrations of adenosine, it remains a worthwhile goal to identify the final effectors of the signaling pathway accounting for the otherwise demonstrated cardioprotective effects of preconditioning because of the potential for these mediators to act as effective antiischemic agents.
Adenosine↗
Warm blood cardioplegia in high risk patients.
OBJECTIVE: Despite overall good clinical results, cardiac surgery in high risk patients, such as those with poor left ventricular function or heavily hypertrophied myocardium, is still challenging. This study was designed to assess the efficacy of warm blood cardioplegia (WBC) in these two subgroups of patients. METHODS: Fifty-two patients, with an ejection fraction less than 50%, who underwent surgical revascularization, and 36 patients, with marked left ventricular hypertrophy (LVH), who were operated on for aortic valve replacement (AVR), were consecutively studied. All of them received continuous retrograde 'warm' blood cardioplegia. Results were assessed on clinical outcomes and compared with those predicted from a risk-stratifying index which has been previously validated in a large multicenter population-based study (Ontario score). RESULTS: For cardiac revascularization, the rates of overall hospital mortality, Q-wave infarctions and inotropic use were respectively 5.8%, 9.6% and 21.1%, comparing favorably with those of the Ontario Group. For aortic valve replacement, the incidence of hospital mortality and Q-wave infarction was 2.8%. CONCLUSIONS: By virtue of the study design, these data cannot conclusively establish the superiority of warm blood cardioplegia over other methods of myocardial protection. However, they support the safety of this technique, and suggest that these subgroups of high risk patients might represent the elective indication for aerobic arrest.
Aged↗
[Valvular homografts].
Renewed interest in heart valve homografts is related to recent advances in viability. Increased viability is achieved by collecting explanted hearts from multi-organ donors and cryopreservation. Right access is usually used in case of hereditary cardiopathy to resect or repair the aortic, mitral and tricuspid valves. Life-long anticoagulant treatment can thus be avoided. Current mid-term and long-term results are very promising.
Heart Valve Diseases↗
Influence of temperature on neutrophil trafficking during clinical cardiopulmonary bypass.
BACKGROUND: The adhesion of neutrophils to endothelial cells and their subsequent transendothelial migration play a major role in inflammatory damage elicited by cardiopulmonary bypass (CPB) because these events are linked to the release of cytotoxic proteases and oxidants. However, the patterns of neutrophil trafficking in relation to systemic temperature during clinical CPB have not yet been characterized. METHODS AND RESULTS: Twenty case-matched patients undergoing warm (31.8 +/- 0.4 degrees C) or cold (26.3 +/- 0.5 degrees C, P < .0001 versus warm) bypass were studied. Blood samples were simultaneously collected from the right and left atria before, at the end of, and 30 minutes after CPB. Plasma levels of C3a, P- and E-selectins, elastase, and interleukin-8 were determined by immunoassays. The results demonstrate: (1) a rise in C3a, reflecting complement activation, (2) a fall in soluble E-selectin consistent with an increased adhesiveness of activated neutrophils, (3) a rise in soluble P-selectin expected to enhance endothelial adhesion of these neutrophils, (4) a rise in elastase, suggesting an adhesion-triggered neutrophil degranulation, and finally (5) a rise in interleukin-8 that is likely to promote transendothelial migration of adherent neutrophils. All of these changes occurred in the two groups of patients and were significant compared with prebypass values. However, in none of the groups was there a significant difference between right and left atrial values for any of the markers. The single difference between cold and warm bypass patients was a significant reduction of elastase release in the cold group (P < .001 versus the warm group). CONCLUSIONS: Clinical CPB is associated with biological changes suggesting the occurrence of neutrophil trafficking. Hypothermia provides only partial protection through a reduced release of elastase. Overall, these results reinforce the rationale for the development of therapeutic strategies targeted at blunting the neutrophil-mediated component of bypass-induced inflammatory damage.
Body Temperature↗
Metabolic and functional evidence that retrograde warm blood cardioplegia does not injure the right ventricle in human beings.
BACKGROUND: Retrograde warm blood cardioplegia is now recognized as an effective method of myocardial protection, but concerns persist about its ability to adequately preserve the right ventricle. METHODS AND RESULTS: A total of 75 patients in whom warm blood cardioplegia was continuously given through the coronary sinus were included in this three-part study. Part 1, which involved 30 patients undergoing coronary artery bypass grafting operations, was designed to assess whether the right ventricle incurred a greater degree of anaerobic metabolism than the left ventricle during warm arrest. Immediately before aortic unclamping, antegrade perfusion was resumed and, within 1 minute of washout, blood samples were simultaneously taken from the right ventricle and coronary sinus and assayed for lactate. There was no significant difference in lactate concentrations between the two sampling sites (right ventricle, 2.53 +/- 0.1 mmol/L; coronary sinus, 2.47 +/- 0.1 mmol/L). Part 2 focused on recovery of function. A complete set of postoperative hemodynamic measurements was obtained in 15 among the 30 patients enrolled in part 1 and compared with that obtained in 15 case-matched patients who received conventional cold antegrade crystalloid cardioplegia. Postoperative right ventricular stroke work index was not significantly different between the two groups (retrograde warm, 4.6 +/- 0.2 g.m-1.m-2; antegrade cold, 4.8 +/- 0.2 g.m-1.m-2). Part 3 was also targeted at functional end points but in 30 additional patients undergoing reoperative mitral valve replacement and consequently deemed to be at higher risk of right ventricular ischemia. Fifteen patients who received retrograde warm cardioplegia were compared with 15 case-matched control subjects in whom antegrade cold crystalloid cardioplegia was used. In keeping with data of part 3, postoperative right ventricular stroke work index was not significantly different between the two groups (retrograde warm, 6.9 +/- 0.4 g.m-1.m-2; antegrade cold, 7.7 +/- 0.5 g.m-1.m-2), nor was there a difference in clinical outcomes or biological recoveries of hepatic function. CONCLUSIONS: Inadequate protection of the right ventricle associated with the use of retrograde warm blood cardioplegia does not appear to be a clinically founded concern since this technique preserves right ventricular function to the same extent as conventional antegrade cold cardioplegia does.
Aged↗
Histological and microbiological assessment of the role of microorganisms in chronic anal fistula.
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Anal Canal↗
Long-term neonatal rat aortic smooth muscle cell cultures: a model for the tunica media of a blood vessel.
Cultured neonatal rat aortic smooth muscle cells have been used to study the synthesis and accumulation of extracellular matrix components in many laboratories. These cells are capable of accumulating large amounts of insoluble elastin in the extracellular matrix and can be maintained in culture for long periods of time without subcultivation. This study examined the elastin and collagen contents of such cells in culture for 5, 21 and 43 weeks. The percent elastin and collagen observed in the 43-week cultures were strikingly similar to that seen in the intact neonatal rat aorta. It should be noted that the percent collagen varied significantly between 5 weeks and 43 weeks, whereas that for elastin remained relatively constant throughout the same time course. Histological examination demonstrated that the elastin fibers in the extracellular matrix of the cultures were arranged in a pattern similar to the elastic lamellae of the aortic tunica media. Data presented here suggest that these cells in culture mimic the donor tissue from which they were derived with respect to elastin and collagen content as well as elastic fiber arrangement, and possibly represent an organotypic culture of the medial layer of a blood vessel.
Animals↗
In-situ hybridization of tropoelastin mRNA during the development of the multilayered neonatal rat aortic smooth muscle cell culture.
Cultured neonatal rat aortic smooth muscle cells are active in synthesizing and depositing large amounts of elastin in their extracellular matrix, making this an ideal system for studying elastogenesis. In this study, the ability of individual cells to synthesize tropoelastin was examined by in-situ hybridization methods. One-micron semi-thin epoxy resin-embedded transverse sections of cells cultured 1, 2, 3 and 4 weeks showed an increase with time in both the number of cells with hybridization signal and the signal intensity; tropoelastin mRNA hybridization signal intensity decreased thereafter up to 8 weeks in culture. In longitudinal sections through the early cultures (1-week), we observed mitotic cells with no detectable hybridization signal, and non-mitotic cells with either no, little or high signal intensity. These data suggest that mitotic cells do not synthesize tropoelastin, and that there is a strong correlation between the hybridization signal intensity and the rate of tropoelastin synthesis. These data also suggest in-situ hybridization methods can detect which cell(s) contain tropoelastin mRNA, their location in the multilayer, and variations in signal intensity. We conclude it is possible to correlate hybridization signal intensity with variations of tropoelastin mRNA levels within individual cells of the cultured smooth muscle cell multilayer.
Animals↗
The effect of beta-aminopropionitrile on elastin gene expression in smooth muscle cell cultures.
When beta-aminopropionitrile (BAPN) is added to neonatal rat aortic smooth muscle cell cultures there is a decrease in insoluble elastin accumulation with a concomitant increase in tropoelastin and tropoelastin fragments in the culture medium. The experiments described here examine the biological significance of this fragmentation. BAPN, as well as purified tropoelastin fragments isolated from spent medium of cells grown in the presence of BAPN, were added to cultures. A decrease in elastin mRNA was observed in cultures grown in the presence of BAPN and also in those cultures to which the purified tropoelastin moieties were added. These studies indicate that the inhibition of lysyl oxidase by BAPN prevents elastin crosslinking which results in an increase in tropoelastin moieties, thus leading to a down regulation of the steady state levels of elastin mRNA.
Aminopropionitrile↗
A controlled precursor add-back model of elastogenesis in smooth muscle cell cultures.
Neonatal rat aortic smooth muscle cell cultures are capable of synthesizing and accumulating relatively large amounts of insoluble elastin in the extracellular matrix. There are two major soluble elastin molecules in these cultures, one of 77 kDa (protropoelastin) and the other of 71 kDa (tropoelastin). We examined the ability of the cell culture system to insolubilize exogenously added soluble elastin precursor moieties into the elastin matrix. To accomplish this, cultures were allowed to develop an enriched elastic fiber matrix for approximately two weeks in first passage. This accumulated matrix then served as the "substrate" for the exogenously added precursor elastin molecules. Culture-derived radioactive soluble elastin was added to the "substrate" cultures and the presence of radioactivity in the insoluble elastin as well as in the lysine-derived crosslinks unique to elastin (desmosines) was measured. When purified [3H]-valine radiolabeled protropoelastin was used, more than 15% of the radioactivity added was detected in the alkali-resistant insoluble elastin within 24 hours. After an initial 4-hour incubation of the cells with [3H]-lysine-labelled soluble elastin, most of the radioactivity in the insoluble elastin was associated with the lysine and only a negligible amount was detected in the desmosines. However, during a 16-day chase period, the ratio of radioactive desmosines to lysine increased dramatically, suggesting that not only insolubilization, but crosslinking occurs as well. The add-back system described herein should provide a means to probe the molecular properties of protropoelastin and increase our understanding of the mechanisms of elastic fiber formation.
Animals↗
Measurement of urinary desmosine by isotope dilution and high performance liquid chromatography. Correlation between elastase-induced air-space enlargement in the hamster and elevation of urinary desmosine.
The accuracy of methods employed to measure the elastin-specific crosslinks, desmosine (DES) and isodesmosine (IDES), has been called into question because contaminants in the urine may cause elevated values. In the present study urine samples were spiked with a known amount of [14C]DES and refluxed in 6 N HCl. Sephadex G-15 chromatography of the hydrolyzed urine employed to remove contaminants. DES and IDES were quantified by high performance liquid chromatography (HPLC) as well as by amino acid analysis. The amount of isotope recovered was used to determine losses during the overall procedure and the isotope dilution to calculate the amounts of endogenous DES and IDES originally present in the urine. Because similar values were obtained by both methods, the more rapid HPLC method was used for all succeeding analyses. In one experiment, the DES amounts in urine collected from hamsters for 3 days after intratracheal treatment with human neutrophil elastase (300 micrograms) or porcine pancreatic elastase (300 micrograms) were 0.212 +/- 0.012 (mean +/- SEM, two measurements on a single pool) and 0.816 +/- 0.005 (two measurements) microgram per hamster per day, respectively. Urine from control hamsters had a mean value of 0.074 +/- 0.008 (eight measurements) microgram per hamster per day. The HNE- and PPE-treated hamsters had mean linear intercept values of 119 and 159% of control values, respectively, giving a positive correlation between increase in airspace size and elevation of urinary DES.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Sandra Coney and the National Women's Hospital affair.
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Female↗
Role of tropoelastin fragmentation in elastogenesis in rat smooth muscle cells.
Neonatal rat aortic smooth muscle cell cultures produce two major soluble elastin molecules termed protropoelastin (77 kDa) and tropoelastin (71 kDa). Cell layer extracts are protroproelastin-enriched, while protropoelastin, tropoelastin, and significant amounts of discrete elastin fragments (Mr of 66,000, 61,000, 56,000, and 45,000) are present in preparations from the medium of these cultures. To determine the role of the various elastin molecules in the metabolism of elastin in neonatal rat aortic smooth muscle cell cultures, the amino termini of these proteins were sequenced. All soluble elastin components present in the medium were purified as a single peak by high performance liquid chromatography; further separation of the components was achieved by polyacrylamide gel electrophoresis and electroblotting. The bands were excised and sequenced. The amino-terminal sequences of protropoelastin, tropoelastin, and the 66-kDa, 61-kDa, and 56-kDa fragments were identical: Gly-Gly-Val-Pro-Gly-Ala-Val-Pro-Gly-Gly. This sequence is identical with published amino-terminal sequences of tropoelastins from several other species. As expected, when the cell cultures were pulsed with [3H]valine, all the soluble elastin molecules were radioactive, while only protropoelastin appeared radioactive after [35S] cysteine pulsing. Since cysteine is present only in the carboxyl-terminal end of the molecule, all the data indicate that the cleavage of the elastin fragments identified in the culture are occurring at the carboxyl end of protropoelastin. These results are consistent with the original hypothesis that a precursor-product relationship exists between the 77-kDa and 71-kDa soluble elastin molecules. Based on known tropoelastin sequences and the molecular weights of the discrete fragments, additional fragmentation of protropoelastin and/or tropoelastin most likely occurs at the lysine/alanine-enriched domains presumably involved in cross-link formation.
Amino Acid Sequence↗