Search PubMed⌕ Search

Biomedical subjects

M J Walker

Publications and source records attributed to M J Walker.

At least 181 records · Page 10Linked to original sources

The actions of felodipine on arrhythmias and other responses to myocardial ischaemia in conscious rats.

The antiarrhythmic activity of felodipine was investigated in conscious chronically prepared rats subjected to coronary artery occlusion. By deliberate high or low placement of an occluder, either large or small occluded zones were produced. In rats with small occluded zones (SOZ), felodipine i.v. (0.2 mumol/kg slow injection + 0.01 mumol/kg per min infusion, and 12.2 mumol/kg slow injection) possessed slight antiarrhythmic activity. In rats with large occluded zones (LOZ), similar doses of felodipine had little antiarrhythmic activity. Felodipine produced a dose-dependent reduction in blood-pressure and delayed the development of ECG signs of ischaemia (ST elevation). The occluded zone size was not reduced by felodipine, although some myocardial salvage (8-17%) may have occurred in SOZ rats. It is concluded that felodipine, at doses producing severe hypotension associated with vasodilatation, possesses little antiarrhythmic activity.

Animals↗

Soft tissue sarcomas of the adult head and neck.

From 1969 to 1983, 53 adult patients with head and neck soft tissue sarcomas were evaluated and treated by the Division of Surgical Oncology at the University of Illinois. The most common anatomic location was the neck (36%), and these patients had the highest 5-year disease-free survival rate (67%). Fibrosarcoma was the most common histologic type (26%); patients with aggressive fibromatosis had the longest mean survival time (93 months). The mean overall survival time was 58.7 months, and the disease-free 2-year, 5-year, and 10-year survival rates were 68%, 54%, and 28%, respectively. Wide excision was the treatment of choice, with adjuvant radiotherapy or chemotherapy, or both, used in selected patients. In all of the long-term survivors, the tumors were either well-differentiated or less than or equal to 5.0 cm in diameter. It is apparent that aggressive therapy of such tumors can provide good long-term results.

Adolescent↗

Tuberculous meningitis in children in the Western Cape. Epidemiology and outcome.

The incidence of tuberculous meningitis in children was determined using hospital records as well as local authority notifications. One hundred and eighty-five cases occurred over a 3-year period. The age-specific incidence in the 0-14-year-old group was 7,5/100 000. In only 28 cases was the disease at an early stage when treatment was commenced. Young age and late-stage disease at presentation were associated with a poor outcome. The associated morbidity and mortality rates were high; the mortality rate was 24%, and nearly 50% of patients were left with a residual disability.

Adolescent↗

Addison's disease in a puppy.

Low serum cortisol levels in a young puppy, following adrenocorticotrophic hormone (ACTH) stimulation, were used to establish a clinical diagnosis of Addison's disease. This was likely to have been congenital although studies of adrenocortical function in close relatives showed no evidence of a genetic origin for the condition. Autoantibody to canine adrenal tissue was not present. Further investigations are necessary to establish the role of autoantibody in canine hypoadrenocorticism. The diagnosis of primary adrenocortical hypoplasia was confirmed at post mortem examination.

Addison Disease↗

The steroid hormone receptors in tumors of adipose tissue.

The clinical evidence suggests that the steroid hormones may influence the biologic course of tumors of soft tissue. In an attempt to characterize the possible steroid hormone dependency of soft tissue, we studied the incidence and distribution of cytosolic receptors for the steroid hormones in benign and malignant tumors of adipose tissue origin. All specimens were assayed for the steroid hormone receptors by charcoal dextran technique and analyzed by the method of Scatchard. The results show a high incidence of cytosolic estrogen and glucocorticoid receptors in tumors of adipose tissue origin except in lipoma and well differentiated liposarcoma. The binding parameter of these receptors suggests that the receptors may be responsive to physiologic steroid hormonal milieu.

Adipose Tissue↗

Pelvic exenteration.

Sixty-eight patients at the University of Illinois, Cook County, and the West Side Veterans Administration hospitals underwent pelvic exenteration for advanced pelvic malignancies during the 15-year period from 1969 to 1984. Thirty-two had colorectal cancers, eleven cervical, seven bladder, and six vulvar; in twelve the cancers were in miscellaneous pelvic sites. Forty-five exenterations were done with intent to cure, and twenty-three for palliation of patients with bulky, necrotic tumors that had caused symptomatic fistulae, local sepsis, chronic bleeding, or severe localized pain. The total 30-day postoperative mortality was 4.4% (3/68). The 5-year survival rate of patients who underwent curative exenteration was 33% (median 27 months). Pelvic exenteration appears to be a feasible surgical procedure for a variety of advanced malignancies as well as for palliation of severely symptomatic patients.

Adult↗

The effects of ablations in the central nervous system on arrhythmias induced by coronary occlusion in the rat.

The role of the central nervous system (CNS) in arrhythmogenesis in the 4 h period following occlusion of a coronary artery was investigated in rats by use of CNS ablations and other procedures. Ablations in the CNS included pithing, spinalization and decerebration combined with acute and chronic surgical preparation and noradrenaline/adrenaline infusions. All procedures involving acute surgery reduced the incidence and severity of the arrhythmias induced by occlusion. Such reductions were most marked in the second (0.5-4 h post-occlusion) arrhythmic period. The observed reductions in arrhythmias could not be explained in terms of involvement of the CNS or adrenoceptor activation. When circulating leucocytes, platelets and serum potassium were measured in a group of pithed rats before and after occlusion, reduced levels (20-50%) of both leucocytes and platelets occurred while serum potassium levels rose by 50-100%. Arrhythmias following coronary occlusion may depend in part on factors in the blood such as leucocytes, platelets and serum potassium and these factors may be altered by acute surgery.

Animals↗

Melanoma of the head and neck.

Cutaneous melanoma of the head and neck accounts for approximately 20 per cent of all melanomas. Variation in the incidence of melanoma by sex and by subsites within the head and neck is related to exposure to sunlight. Study of the precursor skin lesions of individuals and families at high risk for melanoma are providing new insights into the biology of melanoma. The clinical importance of such information is earlier diagnosis and treatment. With microstaging techniques it has become apparent that in many instances the primary tumor can be excised safely with narrower margins than were thought necessary in the past. The role of elective lymph-node dissection remains controversial, but when it is performed a complete dissection is recommended. Improvement in adjunctive methods of treatment is needed, but significant palliation can be achieved, with occasional long-term survival.

Adult↗

Antiarrhythmic actions of verapamil against ischaemic arrhythmias in the rat.

The actions of intravenous verapamil against arrhythmias induced by occlusion of a coronary artery were investigated in conscious rats. Verapamil (2-20 mg kg-1, i.v. given pre-occlusion) dose-dependently reduced arrhythmias in rats with either large or small occluded zones at an ED50 of 6 mg kg-1. This dose was effective when given immediately post-occlusion. Severe arrhythmias, as opposed to PVC, were preferentially reduced. In conscious, and pentobarbitone-anaesthetized rats, verapamil (6 mg kg-1) had different effects on electrically-induced arrhythmias, and the ECG, from an equi-effective anti-arrhythmic dose of quinidine (20 mg kg-1, i.v.). Quinidine decreased following frequency, but increased threshold current and pulse width, whereas verapamil did not. Both drugs increased P-R interval, but only quinidine increased QRS and Q-T intervals. Thirty minutes post-occlusion, the verapamil content of tissue and blood was determined after a 6 mg kg-1 dose given pre- or post-occlusion. Measurable levels of verapamil were found in both normal and ischaemic myocardium. Plasma and plasma water concentrations were 3.6 +/- 0.8 mumol l-1 and 0.6 +/- 0.1 mumol l-1 (mean +/- s.e. mean), respectively following post-occlusion administration vs. 2.7 +/- 1.2 and 0.24 +/- 0.04 for pre-occlusion administration. Plasma water concentrations were close to IC50 values for inhibition of contractility in rat atria and ventricles. Similar concentrations depressed slow action potentials induced in rat ventricles by raised K+ We suggest that the ability of verapamil to prevent severe ventricular arrhythmias following myocardial ischaemia in the conscious rat is largely due to the calcium antagonist effects of the drug.

Action Potentials↗

Intracellular potential changes following coronary occlusion in isolated perfused rat hearts.

A method of perfusing rat ventricles has been developed which permits the recording of intracellular potentials from up to 10 cell layers below the endocardial surface. Intracellular potentials from all layers remained the same for up to 1.5 h before occlusion. Regional occlusion of flow was produced by occluding the left anterior descending coronary artery and then intracellular potentials were recorded from normal and occluded cells for up to 2 h after occlusion. Immediately after occlusion, marked changes in potentials were recorded from occluded tissue. The greatest change was in the duration of the action potential which showed a marked shortening. There was also a reduction in the maximum rise rate and action potential height with smaller falls in resting membrane potential. Changes were greatest in the deeper cells (layers 6-10) and least in superficial subendocardial cells which were always superfused with perfusion fluid. Occlusion increased the number of quiescent cells (no action potential) as well as the number of cells showing aberrant action potential configurations (e.g., double peaks). Similar changes in intracellular potentials following occlusion were also recorded from the subepicardial surface of anaesthetized rats in situ. Arrhythmias induced by occlusion were similar to those seen in conscious rats following occlusion of a coronary artery.

Action Potentials↗

Limb salvage in extremity soft-tissue sarcoma: combined modality therapy.

Thirty-two consecutive patients with high-grade soft-tissue sarcoma of an extremity were treated preoperatively with concomitant intra-arterial infusion of Adriamycin (doxorubicin) (10 mg/m2 daily for 10 days) and radiotherapy (2500 rad [25 Gy] in 10 fractions in 2 weeks). En bloc resection was then performed. Postoperatively, depending on the surgical specimen findings, radiotherapy was given to a dose ranging from 5000 rad (50 Gy) in 5 weeks to 6000 rad (60 Gy) in 6 weeks equivalent continuous schedules. No residual tumor was found in 28% of the surgical specimens and only minimal tumor in 41%. A functionally intact limb was preserved in 30 patients (94%). Local recurrence developed in one patient (3%). The actuarial overall survival at three years was 70% and disease-free survival 57%.

Adult↗

Effects of halothane anesthesia compared with fentanyl anesthesia and no anesthesia during coronary ligation in rats.

The effects of halothane and fentanyl anesthesia on responses to ligation of a coronary artery in chronically prepared rats were compared with responses in conscious animals. A total of 86 rats were used; 24 were ligated under halothane anesthesia, 18 under fentanyl, and 23 were left conscious. Three other groups (each of seven rats) were identically prepared but not ligated. Non-ligated rats were left conscious or anesthetized with halothane or fentanyl. Ligation was performed with the aid of a permanently implanted snare around the left anterior descending coronary artery. The responses to ligation that were measured were: arrhythmias, blood pressure changes, heart rate changes, ECG changes, mortality rate, occluded zone, and infarcted cardiac tissue mass. It was found that 1% halothane anesthesia starting 30 min before and continuing for 4 h after permanent ligation, had an overall beneficial effect, when compared with controls. Fentanyl (200-1,000 micrograms/kg, iv) had no overall beneficial effect, compared with conscious controls. Halothane reduced arrhythmias and mortality rates, when compared with controls, while fentanyl did not. Halothane produced lower blood pressures, fewer ECG changes, and lower heart rates than those seen in conscious or fentanyl anesthetized rats. The occluded and infarcted zones produced by ligation were not influenced by the two anesthetics.

Anesthesia, General↗

Effects of halogenated hydrocarbon anesthetics on responses to ligation of a coronary artery in chronically prepared rats.

Responses to ligation of the left anterior descending coronary artery (blood pressure, heart rate, ECG, arrhythmias, myocardial tissue loss, and mortality) were investigated in chronically prepared rats anesthetized with one of various halogenated hydrocarbon anesthetics. Halothane (inhaled concentrations of 0, 0.25, 0.5, 1.0, and 2.0%) reduced arrhythmias, mortality, and "S-T" segment changes in the ECG in a dose-related manner. The most effective antiarrhythmic concentrations were 0.5 and 1.0%. Other halogenated hydrocarbon anesthetics (chloroform, enflurane, isoflurane, methoxyflurane, and trichlorethylene) were investigated at minimal anesthetic concentrations. Of these, only chloroform and enflurane reduced arrhythmias. However, both increased mortality as a result of nonarrhythmic causes. At one-half anesthetic concentrations, chloroform (0.25%) and enflurane (0.75%) were not antiarrhythmic and mortality resulting from nonarrhythmic causes was not increased. In the chronically prepared rat, halothane at anesthetic and subanesthetic concentrations has antiarrhythmic actions against ligation-induced arrhythmias, reducing mortality. Of the other halogenated hydrocarbons tested, only enflurane and chloroform had antiarrhythmic actions, however, mortality was high with both agents because of accompanying cardiovascular depression.

Anesthesia↗

Effects of aspirin and prostacyclin on arrhythmias resulting from coronary artery ligation and on infarct size.

1 The effects of pretreatment with aspirin, and of prostacyclin (PGI(2)) infusions, on responses to myocardial ischaemia and infarction produced by ligation of a coronary artery were investigated in conscious rats.2 Surgical preparation, under halothane anaesthesia, consisted of implanting exteriorized aortic and jugular cannulae, ECG leads and a polypropylene/polyethylene occluder for the left anterior descending coronary artery. Ligation of the coronary artery was performed six to nine days after surgery.3 Aspirin pretreatment consisted of 100 mg/kg given intravenously 1 or 36 h before ligation. PGI(2) infusions (10-400 ng kg(-1) min(-1), i.v.) were begun 2 min before ligation and continued for 4 h afterwards.4 ECG, blood pressure, heart rate and arrhythmias were recorded starting 30 min before, and continuing for 4 h after, ligation. Twenty-four hours after ligation, in surviving animals, the heart was removed for estimation of occluded and infarcted zones.5 Some treatments provided antiarrhythmic and other protection in the first 30 min post-ligation. By 4 and 24 h post-ligation, protective effects were lost.6 Both aspirin pretreatment and low doses of prostacyclin reduced arrhythmias occurring within 30 min of ligation. The highest dose of prostacylin (400 ng kg(-1) min(-1)) was arrhythmogenic.7 None of the treatments influenced the amount of cardiac tissue occluded or infarcted by ligation.8 The conclusions from this study in conscious rats were that acute aspirin pretreatment and low doses of infused prostacyclin have limited beneficial actions which are mainly confined to the earliest post-ligation period.

Animals↗

The effect of modification of sympathetic activity on responses to ligation of a coronary artery in the conscious rat.

1 Ligation of a coronary artery was performed in conscious rats whose sympathetic system activity had been altered by various treatments. 2 beta-Adrenoceptor blockade with acute (0.2 mg kg-1 plus 0.1 micrograms kg-1 min-1) or chronic (50-60 mg kg-1 daily for 12 days) propranolol treatment had little effect on arrhythmias, or other responses to ligation. 3 Abrupt withdrawal of chronic propranolol two days before ligation was also without effect. 4 Reduction of sympathetic activity acutely with labetalol (5 mg kg-1), or chronically with adrenomedullectomy and 6-hydroxydopamine treatment, accentuated the adverse effects of ligation. 5 The results of this study suggest that, while activity of the sympathetic system is not detrimental during ligation in the conscious rat, it may be important for survival.

Adrenalectomy↗

Effects of prostaglandin E2, propranolol and nitroglycerine with halothane, pethidine or pentobarbitone anaesthesia on arrhythmias and other responses to ligation of a coronary artery in rats.

The effects of various cardiovascular drugs (prostaglandin E2 (PGE2), propranolol and nitroglycerine) and anaesthetic regimens (halothane, pethidine and pentobarbitone), upon the outcome of coronary artery ligation in acutely prepared rats were determined. Effects upon arrhythmias, blood pressure, heart rate, mortality, ECG and the size of the occluded zone were determined for each drug in the presence of each anaesthetic. PGE2 and nitroglycerine had no statistically significant effects on the outcome of ligation whatever the anaesthetic. Propranolol had limited antiarrhythmic actions. The anaesthetic used had major effects upon the outcome of ligation, regardless of the cardiovascular drugs administered. Pentobarbitone anaesthesia resulted in the highest mortality, and most arrhythmias. Pethidine-N2O anaesthesia was associated with fewer arrhythmias. Halothane-N2O anaesthesia markedly decreased the incidence and severity of arrhythmias, independent of the cardiovascular drug. It was concluded that the anaesthetic used can have a major influence on ligation-induced arrhythmias in acutely prepared anaesthetized rats.

Anesthetics↗

Responses to ligation of a coronary artery in conscious rats and the actions of antiarrhythmics.

A method for ligating the left anterior descending coronary artery in conscious rats and measuring the resultant cardiovascular responses, arrhythmias, cardiac tissue loss, electrocardiogram (ECG), and mortality is described. Analyses of such responses identified statistically acceptable measures for which precision and interrelationships were defined. Responses to ligation were a variable function of the amount of ligated myocardial tissue. For example, arrhythmia score was a linear function of the square root of the occluded zone size. To test the ability of the model to detect beneficial drugs, verapamil, lidocaine, disopyramide, and quinidine were given. Low doses of verapamil (0.2 mg/kg i.v. + 0.3 mg X kg-1 X h-1), and of disopyramide (10 mg/kg) had few antiarrhythmic, or other actions, whereas high doses of verapamil (20 mg/kg) and disopyramide (40 mg/kg i.v. repeated) were markedly antiarrhythmic as measured by all indices. Quinidine (20 mg/kg i.v. repeated) was also antiarrhythmic but less so than high dose disopyramide and verapamil. Lidocaine (10 mg/kg i.v. + 5 mg X kg-1 X h-1) reduced the incidence of ventricular flutter and fibrillation. High-dose verapamil and quinidine, but not disopyramide, increased the number of nonarrhythmic deaths and the incidence of atrioventricular conduction defects.

Animals↗