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Biomedical subjects

A Maitland

Publications and source records attributed to A Maitland.

At least 19 recordsLinked to original sources
PubMed2001

Is ischemia involved in the pathogenesis of murine cerebral malaria?

Sequestration of parasitized erythrocytes in the central nervous system microcirculation and increased cerebrospinal fluid lactate are prominent features of cerebral malaria (CM), suggesting that sequestration causes mechanical obstruction and ischemia. To examine the potential role of ischemia in the pathogenesis of CM, Plasmodium berghei ANKA (PbA) infection in CBA mice was compared to infection with P. berghei K173 (PbK) which does not cause CM (the non-CM model, NCM). Cerebral metabolite pools were measured by (1)H nuclear magnetic resonance spectroscopy during PbA and PbK infections. Lactate and alanine concentrations increased significantly at the terminal stage of CM, but not in NCM mice at any stage. These changes did not correlate with parasitemia. Brain NAD/NADH ratio was unchanged in CM and NCM mice at any time studied, but the total NAD pool size decreased significantly in the CM mice on day 7 after inoculation. Brain levels of glutamine and several essential amino acids were increased significantly in CM mice. There was a significant linear correlation between the time elapsed after infection and small, progressive decreases in the cell density/cell viability markers glycerophosphocholine and N-acetylaspartate in CM, indicative of gradual loss of cell viability. The metabolite changes followed a different pattern, with a sudden significant alteration in the levels of lactate, alanine, and glutamine at the time of terminal CM. In NCM, there were significant decreases with time of glutamate, the osmolyte myo-inositol, and glycerophosphocholine. These results are consistent with an ischemic change in the metabolic pattern of the brain in CM mice, whereas in NCM mice the changes were more consistent with hypoxia without vascular obstruction. Mild obstructive ischemia is a likely cause of the metabolic changes during CM, but a role for immune cell effector molecules cannot be ruled out.

Adenosine Triphosphate↗
PubMed2001

Medtronic Mosaic porcine bioprosthesis: midterm investigational trial results.

BACKGROUND: The midterm clinical and hemodynamic performance of the Medtronic Mosaic porcine bioprosthesis was evaluated in a regulatory trial. METHODS: In nine Canadian centers, 802 bioprostheses (560 aortic and 242 mitral) were implanted between September 1994 and April 1999 in patients with a mean age of 70 years. RESULTS: Survival for aortic valve replacement at 4 years was 84.4%+/-3.1%. Freedom from valve-related or unexplained death was 95.6%+/-1.9%; structural valve deterioration, 100.0%; reoperation, 96.2%+/-1.7%; major thromboembolism, 96.1%+/-1.8%; and major antithrombotic-related hemorrhage, 96.4%+/-1.7%. Echocardiographic derived mean systolic gradient was 13.4 mm Hg at 4 years with an indexed effective orifice area of 0.7 to 0.8 cm2/m2. A significant decrease in left ventricular mass was shown over time in all valve sizes. Survival for mitral valve replacement at 4 years was 79.2%+/-6.8%. Freedom from valve-related or unexplained death was 96.5%+/-3.4%; structural valve deterioration, 100%; reoperation, 97.0%+/-3.2%; major thromboembolism, 95.7%+/-3.8%; and major antithrombotic-related hemorrhage, 95.0%+/-4.2%. Echocardiographically measured averaged mean diastolic gradient was 4.5 mm Hg. CONCLUSIONS: The Medtronic Mosaic bioprosthesis is safe and effective in both the aortic and mitral positions. The valve has low gradients in both positions and excellent left ventricular mass regression in the patients with aortic valve replacement.

Adult↗
PubMed2001

Endothelin receptor blockade improves endothelial function in human internal mammary arteries.

OBJECTIVE: Endothelial dysfunction, specifically endothelium-derived contracting factors have been implicated in the development of arterial conduit vasospasm. The potent vasoconstrictor endothelin-1 (ET-1) has received much attention in this regard. The present study was designed to evaluate the role of ET-1 in the development of endothelial dysfunction in human internal mammary arteries (IMA). To this aim, we examined the effects of specific and non-specific ET-receptor antagonists on endothelial function (assessed using acetylcholine (ACh)-induced vasodilation) in segments of IMA obtained during coronary artery bypass graft (CABG) surgery. METHODS: Vascular segments of IMA were obtained from 51 patients undergoing elective coronary artery bypass graft (CABG) surgery and in vitro endothelium-dependent and -independent responses to ACh and sodium nitroprusside (SNP) were assessed. Isometric dose response curves (DRC) to ACh and SNP were constructed in pre-contracted rings in the presence and absence of bosentan (ET(A/B) receptor antagonist, 3 microM), BQ-123 (ET(A) antagonist, 1 microM) and BQ-788 (ET(B) antagonist, 1 microM) using the isolated organ bath apparatus. Percent maximum relaxation (%E(max)) and sensitivity (pEC(50)) were compared between interventions. RESULTS: ACh caused dose-dependent endothelium-mediated relaxation in IMA (%E(max) 43+/-4, pEC(50) 6. 74+/-0.12). In the presence of bosentan, BQ-123 and BQ-788 ACh-induced relaxation was significantly augmented (%E(max) bosentan 60+/-3, BQ-123 56+/-4, BQ-788 53+/-5 vs. control 43+/-4, P<0.05) without affecting sensitivity. The effects of these antagonists were endothelium-specific since endothelium-independent responses to SNP remained unaltered. Furthermore, the beneficial effects were independently and maximally mediated by ET(A) and ET(B) receptors (%E(max) BQ-123 56+/-4 vs. BQ-788 53+/-5 vs. bosentan 60+/-3, P>0. 05). CONCLUSIONS: These data uncover, for the first time, beneficial effects of ET receptor blockade on endothelial-dependent vasorelaxation in human IMA.

Acetylcholine↗
PubMed2000

Tetrahydrobiopterin improves endothelial function in human saphenous veins.

OBJECTIVES: Diminished production of nitric oxide has been linked to saphenous vein endothelial dysfunction. Tetrahydrobiopterin is an obligate cofactor for the oxidation of L -arginine by nitric oxide synthase in the production of nitric oxide by endothelial cells. The objective of the present study was to examine whether the exogenous addition of tetrahydrobiopterin improves endothelial function in saphenous veins from patients undergoing coronary artery bypass graft operations. METHODS: Vascular segments of saphenous veins were obtained from 17 patients undergoing elective coronary artery bypass grafting, and in vitro endothelium-dependent and endothelium-independent responses to acetylcholine and sodium nitroprusside were assessed. Isometric dose-response curves were constructed in precontracted rings in the presence and absence of tetrahydrobiopterin (0.1 mmol/L) with the use of the organ bath apparatus. The percentages of maximum relaxation and sensitivity were compared between interventions. RESULTS: Acetylcholine caused dose-dependent endothelium-mediated relaxation in saphenous veins. In the presence of tetrahydrobiopterin, acetylcholine-induced relaxation was significantly augmented (percentage maximum relaxation, 16.8% +/- 2.9% vs control 7.5% +/- 1.8%; P =.003) without an effect on agonist sensitivity. These effects were endothelium-specific because endothelium-independent responses to sodium nitroprusside were preserved. CONCLUSIONS: These data uncover beneficial effects of acute tetrahydrobiopterin addition on endothelial function in human vessels. Because endothelial dysfunction has been implicated in the development of graft failure, studies aimed at chronic delivery of tetrahydrobiopterin would be useful in determining the contribution of this cofactor toward saphenous vein atherosclerosis.

Acetylcholine↗
PubMed2000

Dichloroacetate (DCA) reduces brain lactate but increases brain glutamine in experimental cerebral malaria: a 1H-NMR study.

Recent findings that levels of brain lactate and alanine were elevated in murine cerebral malaria led us to investigate the effect of dichloroacetate (DCA; 60 mg/kg), an activator of pyruvate dehydrogenase, on the levels of brain metabolites, and on the survival of mice infected with Plasmodium berghei ANKA which normally causes lethal cerebral malaria. DCA significantly reduced brain lactate and alanine levels when administered to infected mice, had no effect on the TCA cycle-related metabolites glutamate, GABA and aspartate and was associated with increased brain glutamine levels: 40% of mice thus treated survived the normally lethal infection.

Animals↗
PubMed1996

Aortic arch interruption associated with ruptured cerebral aneurysm.

The authors present a case of aortic arch interruption in an adult, an anomaly that was discovered coincidentally during angiography for ruptured cerebral aneurysm. The presentation in adulthood with rupture of the aneurysm and the successful surgical treatment of both abnormalities are unusual.

Adult↗
PubMed1995

The cutting edge: surgical education for medical students and a patient care system.

This paper describes computer-assisted instruction designed for medical students on their clinical surgery rotation. Patient care systems continue to evolve; incentives for physician participation should include educational benefits and clinical practice guidelines. Sometimes overlooked in the rush to develop expert systems are medical students, who do not have the depth of knowledge inherent in decision support. Foothills Hospital in Calgary, Canada, uses the TDS HC4000 patient care system, where physicians and medical students enter their orders directly on the terminals. The Surgical Patient Care Program was developed to help students learn the basics of peri-operative patient management. The Program runs on the HC4000 and consists of a collection of order sets with appended educational information to guide students in their automated order selection. Unlike other instructional programs, which use fictitious patients, students enter real orders on real patients. Tracking of usage indicates that the Program is popular with students, who each access it an average of 20 times per week. An ongoing study will determine any educational benefit by measuring student performance at Foothills Hospital against a control group at another hospital, which does not have a computerized patient care system.

Alberta↗
PubMed1993

Comparison of biphasic and monophasic shocks for defibrillation using a nonthoracotomy system.

A comparison of defibrillation thresholds was made using biphasic and monophasic shocks delivered by a nonthoracotomy lead system in 2 clinically distinct groups of patients. The first group were patients receiving an implantable cardioverter-defibrillator who were studied before surgery with their chests closed. The second group were patients undergoing coronary artery bypass grafting (CABG) who were studied before surgery with their chests open but reapproximated. Biphasic defibrillation thresholds (stored energy) were significantly (p < 0.001) less than monophasic ones in subjects with the implantable cardioverter-defibrillator (12.3 +/- 5.3 vs 21.1 +/- 9.3 J) or CABG (14.6 +/- 7.1 vs 24.2 +/- 12.6 J). These values are less than were previously reported with a similar nonthoracotomy lead configuration. There were no significant differences between the 2 groups in all measurements derived from corresponding shock waveforms, although impedance tended to be greater in patients with CABG. However, subjects with CABG had greater left ventricular ejection fractions and did not have history of potentially lethal ventricular arrhythmias. Despite these differences, the conclusion that biphasic shocks are more effective would have been made in a study of either group alone. It is concluded that patients with CABG who have not had preceding potentially lethal ventricular arrhythmias may be a potential source of surrogate subjects for defibrillation research such as epicardial mapping, which requires that the chest be open.

Coronary Artery Bypass↗
PubMed1993

A randomized comparison of a bipolar steroid-eluting electrode and a bipolar microporous platinum electrode: implications for long-term programming.

Differences in acute and chronic pacing thresholds were compared in patients receiving either the Medtronic Model 4004 steroid-eluting lead or the Medtronic Model 4012 microporous platinum lead. Patients (n = 35) were randomized at the time of implant to receive either a steroid-eluting (n = 17) or a microporous (n = 18) lead. Pacing thresholds were determined within 24 hours and at 2, 4, 6, 12, 24, and 52 weeks postimplant. By 2 weeks postimplant, pacing thresholds measured at 0.8, 1.6, 2.5, 3.3, and 4.2 V were significantly lower in the steroid lead group compared to the microporous lead group (P < 0.05). At 24 weeks, the voltage threshold at 0.3 msec was 0.8 V in 88% of patients with a steroid lead whereas this threshold was only observed in 33% of patients with the microporous lead (P < 0.01). At 52 weeks the pacing energy measured at 1.6 V, twice pulse duration threshold, was significantly lower in the steroid lead group (0.81 +/- 0.59 microJ) compared to the microporous lead group (1.25 +/- 0.60 microJ, P < 0.05). Thirteen patients in the steroid lead group and 9 patients in the microporous lead group have been programmed at a pulse amplitude of 1.6 V since the 24-week follow-up visit. These patients have been followed for a minimum of 6 months without documented failure to capture. This study shows that pacemaker/lead systems with stable chronic low thresholds can be safely programmed to low pulse amplitude settings. This practice will prolong the longevity of pulse generators.

Aged↗
PubMed1992

Expression of metalloproteinases and their inhibitors in primary pulmonary carcinomas.

Nine primary pulmonary carcinomas, one metastatic carcinoma, and two malignant pleural mesotheliomas have been analysed for the expression at the mRNA level of metalloproteinases (MPs) and tissue inhibitors of MPs (TIMPs). In situ hybridisation showed TIMP-1 and TIMP-2 transcripts predominantly over tumour stroma and gelatinases evenly distributed over both stromal and tumour cells. While both TIMP-1 and TIMP-2 were expressed in non-neoplastic lungs (NNL) as well as in carcinomas, stromelysin 3 (ST3), 92 kDa gelatinase and interstitial collagenase were expressed only by carcinomas. Expression of these MPs by carcinomas was independent of histologic type and such tumour features as fibrosis or necrosis. The consistent expression of ST3 by all of the carcinomas examined and absence of its expression in NNL indicates that ST3 production is likely associated with the malignant phenotype. However, since 92 kDa gelatinase and interstitial collagenase transcripts were found in some but not all tumour samples, their expression is not a uniform feature of pulmonary carcinomas. The possible prognostic significance of the expression of the latter two enzymes by carcinomas remains to be established.

Aged↗
PubMed1991

Not all neonatal hearts are equally protected from ischemic damage during hypothermia.

Despite hypothermia, pediatric cardiac surgeons continue to experience difficulties in providing adequate myocardial protection in newborns. This study examines the effects of deep hypothermia on neonatal heart tolerance to ischemia by measuring metabolic responses and the time to onset of ischemic contracture, or "stone heart." After control right ventricular biopsy specimens were obtained, hearts of newborn pigs (n = 36) were excised and placed in temperature-regulated baths: 37.5 degrees +/- 0.5 degrees C (n = 9), 19.0 degrees +/- 0.5 degrees C (n = 14), and 12.0 degrees +/- 0.5 degrees C (n = 13). With a compliant balloon in the left ventricle to measure pressure, time to onset of ischemic contracture (greater than 2-mm Hg rise) was recorded, and sequential biopsies were done. Data indicated hypothermia significantly (p less than 0.001) prolonged time to onset of ischemic contracture from 29.5 +/- 1.7 minutes (mean +/- standard error of the mean) at normothermia to 150.0 +/- 6.4 minutes at 19 degrees C and to 283.8 +/- 46.4 minutes at 12 degrees C. Lactate buildup at 30 minutes of ischemia was significantly reduced by 70% with hypothermia. Decline in adenosine triphosphate level was significantly reduced by 50% (19 degrees C) and 75% (12 degrees C) with hypothermia. More importantly, a subgroup of hearts in each hypothermia group (n = 5 per group) was identified by 38% to 48% lower adenosine triphosphate stores before ischemia compared with the group means.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1990

Myocardial abscess in a patient with AIDS-related complex: pericardial patch repair.

A hemophiliac with acquired immunodeficiency syndrome-related complex was seen with sepsis related to a ventricular septal abscess. The abscess was debrided and the septum was patched with a single layer of autologous pericardium. The patient recovered and survived 6 months before dying of acquired immunodeficiency syndrome. At autopsy, the septal patch was well healed with no evidence of recurrent endocarditis.

AIDS-Related Complex↗
PubMed1989

Atenolol for the prevention of arrhythmias following coronary artery bypass grafting.

Seventy patients undergoing aortocoronary bypass grafting were randomized, double-blind, to receive either atenolol or placebo. There were 35 patients in each group. Patients received either atenolol 5 mg intravenously or matching placebo within 3 h of the completion of surgery. A second intravenous dose was administered 24 h following the first and then atenolol 50 mg orally or matching placebo was given for six days. Continuous Holter monitor recordings were obtained for the 24 h immediately preoperatively and continuously for eight days postoperatively. No patient received any antiarrhythmic drug preoperatively. Patients who required pharmacological intervention for the management of postoperative arrhythmias were withdrawn as treatment failures. Holter monitor analysis continued for 24 h following withdrawal of a treatment failure. All patients were analyzed according to the intention-to-treat principle. Both groups were comparable with respect to age, sex, severity of coronary artery disease, left ventricular ejection fraction, preoperative use of beta-blockers, bypass time, aortic cross-clamp time, number of grafts per patient and frequency of preoperative arrhythmias. Arrhythmia analysis was done manually. Supraventricular arrhythmias (atrial tachycardia, atrial fibrillation and atrial flutter) were classified as either mild (less than 0.5 mins, less than 140 beats/min), moderate (0.5 to 30 mins, 140 to 180 beats/min), or severe (longer than 30 mins, more than 180 beats/min). Ventricular arrhythmia analysis was performed with respect to isolated PVCs, couplets, triplets and episodes of nonsustained ventricular tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1987

Effects of tricuspid regurgitation on thermodilution cardiac output: studies in an animal model.

The thermal dilution technique (TD) of measuring cardiac output (Q) has been assumed to be inaccurate when the tricuspid valve is regurgitant (TR). The indicator transit time from the right atrium to pulmonary artery (PA) is prolonged and may increase indicator loss to the heart and adjacent tissue. We surgically created TR in four anaesthetized dogs and compared simultaneous cardiac output measurement made with an implanted PA flow probe with intermittent TD cardiac output measurements. We found an excellent correlation (r = 0.98) between the techniques in the normal heart when Q was increased by 100-150 per cent of control values using an intravenous dobutamine infusion. After TR was produced by incorporating the tricuspid valve leaflet within a suture, Q decreased. Dextran 40 was then infused and Q increased significantly. The rate at which Q increased was greater with the TD technique than with the PA flow probe; however, a significant (r = 0.85) linear relationship was still present with TR. The altered thermal waveform detected by the PA thermistor in TR was characterized by a lower peak amplitude and a slower return to baseline. Within the limitations of an animal model, our data suggest that TD cardiac output may be more accurate than previously assumed, particularly in low output states.

Animals↗