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Biomedical subjects

M J Buckley

Publications and source records attributed to M J Buckley.

At least 91 records · Page 5Linked to original sources
PubMed1994

(+/-)-Epibatidine elicits a diversity of in vitro and in vivo effects mediated by nicotinic acetylcholine receptors.

(+/-)-Epibatidine, exo-2-(6-chloro-3-pyridyl)-7-azabicyclo-[2.2.1] heptane, is a novel, potent analgesic agent that acts through nicotinic acetylcholine receptor (nAChR) mechanisms. This study sought to establish whether (+/-)-epibatidine, like (-)-nicotine, also displays a wide diversity of behavioral responses that are known to be elicited by nAChR activation or whether it demonstrates subtype selectivity for its interactions with nAChRs.(+/-)-Epibatidine displaced [3H](-)-cytisine binding to the alpha 4 beta 2 nAChR subtype in rat brain membranes with high affinity (Ki, 43 pM). The compound was approximately 5000-fold less potent (Ki = 230nM) in the displacement of [125I] alpha-bungarotoxin binding from the alpha-bungarotoxin-sensitive nAChR subtype present in rat brain but was a potent inhibitor (Ki, 2.7 nM) of [125I] alpha-bungarotoxin binding to the nAChR subtype in Torpedo electroplax, which is similar to that present in the neuromuscular junction. Functionally, (+/-)-epibatidine enhanced 86Rb+ flux in IMR 32 cells with an EC50 value of 7 nM. It was some 3000-fold more potent than (-)-nicotine (EC50 value, 21,000 nM) and was approximately 150-fold more potent (EC50 value, 0.4 nM) than (-)-nicotine (EC50 value = 60 nM) in increasing [3H]dopamine release from rat striatal slices. Remarkably, (+/-)-epibatidine was 40% to 50% more efficacious than (-)-nicotine in both functional assays. Both functional effects were blocked by the nAChR channel blocker, mecamylamine (100 microM). (+/-)-Epibatidine was 300 to 1000 times more potent than (-)-nicotine in the reduction of body temperature and locomotor activity in mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗
PubMed1994

Operation for recurrent ventricular tachycardia. Predictors of short- and long-term efficacy.

The success of ventricular operation in ablating drug-refractory ventricular tachycardia secondary to ischemic heart disease varies with surgical technique, the presence of certain identified risk factors, and patient selection biases. Forty-eight patients with drug-refractory ventricular tachycardia secondary to ischemic heart disease underwent directed ventricular operation. All patients had previous myocardial infarction, and 46 of 48 patients had a left-ventricular aneurysm. Mapping was done in 81% of patients. Patients underwent a combination of subendocardial resection, aneurysmectomy, and cryoablation. The operative mortality rate was 8%. Age greater than 65 years was the only risk factor for operative mortality. Forty-one patients underwent postoperative programmed electrical stimulation. In 26 patients (63%) tachycardia was noninducible, whereas it was inducible in 15 patients (37%). Stepwise logistic regression identified septal and inferior focus location as the most significant predictors of outcome. Septal focus location was a significant (p = 0.008) predictor of surgical success whereas inferior focus location was a significant (p = 0.015) predictor of surgical failure. Other identified independent risk factors for surgical failure were (1) use of cardioplegia, (2) lack of a completed intraoperative endocardial map, and (3) decreased ejection fraction. This generated model to predict success or failure had a sensitivity of 93.3% and a specificity of 92.4%. The success of ventricular operation is affected by the presence of certain risk factors. In the management of those patients at high risk for failure, other surgical options such as the placement of implantable cardioverter-defibrillator electrode patches at the time of ventricular operation or the alternative placement of a palliative implantable cardioverter-defibrillator should be considered.

Cardiac Pacing, Artificial↗
PubMed1993

Linopirdine (DuP996) facilitates the retention of avoidance training and improves performance of septal-lesioned rats in the water maze.

The behavioral effects of 3,3-bis(4-pyridinylmethyl)-1-phenylindolin-2-one [linopirdine (DuP996)] were investigated on retention of the inhibitory avoidance test in normal mice and acquisition of spatial discrimination in the two-platform water maze task in septal-lesioned rats (a model of cholinergic dysfunction characteristic of Alzheimer's disease). Linopirdine significantly enhanced retention of the inhibitory avoidance response in mice (0.026 mumol/kg) and also reduced the number of errors made by septal-lesioned rats in the water maze to a level comparable to sham-operated animals. At this dose, no effects were observed on septal-lesion-induced hyperactivity in an open field or in unoperated rats tested in the elevated plus-maze anxiolytic test. This study extends previous findings of facilitatory effects of linopirdine on memory and demonstrates improved spatial learning in septal-lesioned rats. As the facilitatory effects on memory are not accompanied by a reduction in the hyperactive state present in septal-lesioned animals, a dissociation between cognitive and noncognitive effects of linopirdine can be differentiated in septal-lesioned rats.

Animals↗
PubMed1992

Intraoperative aortic dissection.

Intraoperative aortic dissection is a rare but potentially fatal complication of open heart operations. If the dissection is promptly recognized and repaired, however, the outcome may be significantly better. In this study, we reviewed the hospital records of patients with dissection of the aortic arch occurring as a complication of a cardiac operation at Massachusetts General Hospital and Mt. Auburn Hospital from January 1980 through June 1990. During this period, 14,877 surgical procedures with the use of cardiopulmonary bypass and aortic cannulation were performed, and 24 patients (0.16%) with iatrogenic aortic dissection were identified. Dissection was discovered intraoperatively in 20 patients and postoperatively after complications developed in 4. Of the 20 patients whose injuries were discovered intraoperatively and repaired, 4 (20%) died. Of the 4 whose injuries were discovered after operation, 2 (50%) died. The primary cause of death was ventricular dysfunction resulting from myocardial ischemia. Dissections originated at the aortic cannulation site in 10 patients, at the cross-clamp site in 8, at the site of the partial-occlusion clamp in 7, at the proximal anastomosis in 1 patient, and as a result of direct injury in 1. Three of these patients had simultaneous injuries at the aortic cannulation site and at the heel of the partial-occlusion clamp. Two techniques of repair were used: primary repair and patch or tube graft insertion. There were two deaths in the patients who underwent primary repair and four deaths in patients requiring graft replacement. Although it is uncommon, intraoperative aortic dissection can be a lethal complication of cardiac operations.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Postinfarct ventricular septal defect repair: effect of coronary artery bypass grafting.

Between June 1968 and April 1991, 75 patients who had undergone coronary angiography underwent repair of a postinfarction ventricular septal defect. Group 1 (n = 33) includes patients who had two- or three-vessel serious (> 75% narrowing) proximal coronary artery disease and underwent complete revascularization in addition to repair of the ventricular septal defect. Group 2 (n = 19) patients also had two- or three-vessel coronary artery disease but bypass grafting was not performed; only the ventricular defect was repaired. Group 3 (n = 23) patients had only single-vessel coronary artery disease that corresponded to the region of the infarct; they underwent ventricular septal defect repair only. Follow-up of hospital survivors was 96% complete at a mean of 86.2 months (range, 1 to 288 months). Hospital mortality after ventricular septal defect repair was 21.2% in the cohort with bypassed coronary artery disease (group 1), 26.3% in those with unbypassed disease (group 2), and 26.1% in those with only single-vessel coronary artery disease (group 3) (p = 0.88). With follow-up after 5 and 10 years, the actuarial survival was 72.2% +/- 8% and 47.8% +/- 10%, respectively, in the bypassed group, 29.2% +/- 11% and 0%, respectively, in the unbypassed group, and 52.2% +/- 10% and 36.5% +/- 11%, respectively, in the cohort with single-vessel disease. Bypassing associated coronary artery disease significantly increased long-term survival when compared with patients with unbypassed coronary artery disease (p = 0.0015).

Aged↗
PubMed1992

Blunt injuries of the thoracic aorta.

We managed 51 patients with thoracic aortic injuries caused by blunt trauma between 1977 and 1990. Forty-nine injuries were located in the upper descending aorta and one each in the ascending aorta and aortic arch. Three patients arrived moribund and underwent thoracotomy for resuscitation, and all died. The diagnosis was confirmed by aortography in 48. One patient died of aortic rupture, 1 died of hypoxemia, and 1 refused operation and died. Forty-four patients had aortic repair, 42 with graft insertion. Gott shunts were placed in 23 with 3 cases of paraplegia (13%). Simple cross-clamping was used in 19 with 1 case of paraplegia (5.2%). We found statistically significant differences between the cross-clamp times of patients without paraplegia compared with those in whom paraplegia developed in both the shunt and no-shunt groups. Logistic regression analysis showed that the only factor significantly associated with paraplegia was cross-clamp time. There were two postoperative deaths (4.4%). Seven patients had medical therapy initially and aortic repair was delayed to allow other injuries to stabilize. Before aortic repair, 18 patients had intraarterial pressure monitoring and 34 received beta-blockers or antihypertensive drugs. We conclude that aortic repair with graft insertion is usually successful in nonmoribund patients, simple cross-clamping is associated with a relatively low risk of paraplegia, the incidence of paraplegia is directly associated with the duration of cross-clamp time, and selected patients can be managed medically while awaiting aortic repair.

Adolescent↗
PubMed1991

The safety of intraaortic balloon pump catheter insertion through suprainguinal prosthetic vascular bypass grafts.

To determine the safety of intraaortic balloon pump catheter insertion for critical coronary ischemia through suprainguinal prosthetic bypass grafts, we examined our experience of 19 intraaortic balloon pumps placed through grafts in 17 patients by means of surgical exposure (8) or the percutaneous (11) approach. Fourteen intraaortic balloon pumps were placed through matured grafts at a time remote (2 to 13 years; mean, 7 years) from their vascular bypass surgery. Five were inserted through nonmatured grafts during the same hospitalization as their vascular reconstructive surgery (1 to 12 days; mean, 4 days). One patient, a day after an aortoiliac bypass, died during an urgent, surgical intraaortic balloon pump insertion for cardiogenic shock. All other patients had prompt reversal of their cardiac ischemia. Decreased limb perfusion developed during use of the intraaortic balloon pump in three patients, all of whom had their intraaortic balloon pump placed percutaneously through mature grafts. Two of these required surgical thrombectomy. Ten intraaortic balloon pump insertions in eight patients survived the hospitalization and were followed for a mean of 24 months (range, 2 weeks to 64 months). No localized groin or graft infections were identified. No bleeding complications or pseudoaneurysms occurred. Thus in patients with unstable, severe, cardiac disease, intraaortic balloon pumps can be safely placed through indwelling suprainguinal bypass grafts.

Aged↗
PubMed1990

Preclinical evaluation of an "instant" 99mTc-labeling kit for antibody imaging.

This communication presents information on the quality and stability of a new conjugate of 99mTc to an anticancer antibody fragment and results of animal imaging and distribution studies. Clinical studies have proved that this labeled antibody can image tumors within 2 hours of i.v. injection. It is produced using an "instant kit," merely requiring addition of [99mTc]pertechnetate to a lyophilized vial containing the fragment and a pertechnetate-reducing agent. Within 5 min of addition of pertechnetate to the vial containing the fragment, [99mTc]pertechnetate is reduced and quantitatively bound to an intrinsic high-affinity receptor present in the Fab'. The Fab'-bound 99mTc is completely stable to challenge with diethylenetriaminepentaacetic acid and human serum albumin. Minimal oxidation and release of 99mTc bound to the fragment were observed when the labeled fragment was incubated for 24 h at 37 degrees C. Animal biodistribution studies were consistent with the known metabolic elimination of a radiolabeled Fab' fragment by the kidney. Tumor localization studies in athymic nude mice bearing xenografts of human colonic carcinoma (GW-39) predicted the positive results later demonstrated in clinical studies.

Animals↗
PubMed1990

The effects of mechanical strain on osteoblasts in vitro.

The effect of mechanical strain on bone is important to the field of oral and maxillofacial surgery. Oral and maxillofacial surgeons are involved on a daily basis with problems including alveolar ridge resorption, implant stability, craniofacial growth, and bone resorption related to trauma and pathology. To understand and control these effects on bone, it is important to examine the effects of mechanical strain on the osteoblasts. This series of experiments provides the changes in alkaline phosphatase, collagen synthesis, and protein synthesis in osteoblast-like cell subjected to mechanical strain.

Alkaline Phosphatase↗
PubMed1990

Surgical coronary revascularization in survivors of prehospital cardiac arrest: its effect on inducible ventricular arrhythmias and long-term survival.

In a selected subgroup of 50 survivors of cardiac arrest, the impact of surgical myocardial revascularization on inducible arrhythmias, arrhythmia recurrence and long-term survival was examined. The effects of several clinical, angiographic and electrophysiologic variables on arrhythmia recurrence and survival were also analyzed. All patients had a prehospital cardiac arrest and severe operable coronary artery disease and underwent myocardial revascularization. Preoperative electrophysiologic study was performed in 41 patients; 33 (80%) had inducible ventricular arrhythmias. Of 42 patients studied off antiarrhythmic drugs postoperatively, 19 (45%) had inducible ventricular arrhythmias. Thirty patients with inducible arrhythmias preoperatively underwent postoperative testing off antiarrhythmic drugs; arrhythmia induction was suppressed in 14 (47%). By multivariate analysis, the induction of ventricular fibrillation at the preoperative electrophysiologic study was the only significant predictor of induced ventricular arrhythmia suppression by coronary surgery (p less than 0.001). Inducible ventricular fibrillation was not present postoperatively in any of the 11 patients who manifested this arrhythmia preoperatively. In contrast, inducible ventricular tachycardia persisted in 80% of patients in whom preoperative testing induced this arrhythmia. Patients were followed up for 39 +/- 29 months. There were four arrhythmia recurrences; one was fatal. There were three nonsudden cardiac deaths and three noncardiac deaths. By life-table analysis, 5 year survival, cardiac survival and arrhythmia-free survival rates were 88%, 98%, and 88%, respectively. Depressed left ventricular ejection fraction and advanced age were predictive of death (p = 0.015 and 0.026, respectively) and cardiac death (p = 0.037 and 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗
PubMed1990

Orbital emphysema causing vision loss after a dental extraction.

The use of high-speed air-cooled rotary cutting instruments is common in dental practices. When used near open wounds, the forced air can lead to subcutaneous emphysema and involvement of vital structures. This case highlights the unfortunate episode of orbital emphysema with optic nerve damage after a pneumatically cooled drill was used in the removal of a mandibular second molar.

Adult↗
PubMed1990

Hemodilution in orthognathic surgery.

The patient population for elective orthognathic surgery usually comprises young, healthy patients, in whom homologous blood transfusions should be avoided. Homologous transfusion poses substantial, potentially preventable risks to this patient population. In addition to autologous predonation, acute intentional hemodilution is an alternative that potentially avoids the use of homologous blood. Indications and contraindications for its use as well as initial results in two patients are presented. Further data and experience are required before this technique can be recommended for routine use.

Adolescent↗
PubMed1990

Late results with Carpentier-Edwards porcine bioprosthesis.

From 1977 to 1984, 429 patients underwent aortic valve replacement (AVR), and 339 underwent mitral valve replacement (MVR) with a Carpentier-Edwards bioprosthesis. Early mortality for AVR was 4.6% (isolated AVR, 1.9%) and for MVR was 5.3% (isolated MVR, 4.1%). Follow-up was 99.3% complete at a mean of 5.9 years. Actuarial event-free rates at 10 years for AVR and MVR were, respectively, 1) for structural valve deterioration, 91.4 +/- 3.2% versus 75.1 +/- 4.0% (p less than 0.01); 2) for nonstructural dysfunction, 100% versus 97.8 +/- 1.6% (p = NS); 3) for thromboembolism, 90.6 +/- 2.3% versus 87.3 +/- 2.6% (p = NS); 4) for anticoagulant-related bleeding, 95.3 +/- 1.1% versus 88.6 +/- 2.4% (p = 0.05); 5) for endocarditis, 87.8 +/- 5.7% versus 90.6 +/- 2.4% (p = NS); 6) for reoperation, 91.0 +/- 2.5% versus 74.4 +/- 3.7% (p less than 0.01); 7) for valve-related mortality, 76.1 +/- 6.9% versus 71.4 +/- 5.2% (p = 0.01); 8) for permanent physical impairment, 85.0 +/- 3.0% versus 71.5 +/- 3.6% (p less than 0.01); and 9) for combined operative mortality, valve-related mortality, and reoperation, 68.7 +/- 6.4% versus 51.5 +/- 4.9% (p = 0.01). No structural valve dysfunction was observed in any AVR patient whose valve was inserted after age 70. Age at operation was the only factor that predicted structural valve deterioration (p less than 0.01).

Actuarial Analysis↗
PubMed1989

Systolic and diastolic interaction in the assessment of left ventricular function following surgical cardioplegia.

Using regionally implanted sonomicrometry crystals, we have evaluated a new index of regional function (normalised systolic shortening [NSS]) which integrates the systolic and diastolic properties of the left ventricle. Eight dogs (group I) were subjected to standard cardiopulmonary bypass and 45 min of hypothermic (10 degrees C), hyperkalaemic (25 mEq) crystalloid cardioplegia. Seven dogs (group II) underwent occlusion of the left anterior descending (LAD) coronary artery 5 min prior to initiation of cardiac arrest. The occlusion was released after 20 min, before the second cardioplegia infusion. Sarnoff left ventricular (LV) function curves were performed pre-arrest and 20, 40 and 60 min after removal of the cross-clamp. Regional assessment of myocardial function showed 55% +/- 3%, 70% +/- 3% and 70% +/- 5% recovery in the LAD region and 52% +/- 2%, 83% +/- 3% and 88% +/- 4% recovery in the circumflex (Cx) region of group I. In group II the LAD region recovered 27% +/- 1%, 31% +/- 3% and 38% +/- 3% and the Cx region showed 61% +/- 3%, 55% +/- 1% and 65% +/- 5% recovery. Comparison of the new index of ventricular function to standard indices of regional and global function demonstrate that the latter underestimate the degree of myocardial dysfunction after cardioplegic arrest, particularly in situations of acute regional myocardial ischaemia and uneven myocardial protection. The utilization of this index should provide a better standard for the more accurate assessment of interventions designed to decrease myocardial injury during cardioplegic arrest.

Animals↗