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Biomedical subjects

L Harrison

Publications and source records attributed to L Harrison.

At least 145 records · Page 8Linked to original sources
PubMed1986

Interaction between HLA antigens and immunoglobulin (Gm) allotypes in susceptibility to type I diabetes.

HLA-A,B,C and DR typing was performed on 108 Caucasian type I diabetic patients, 68 being Gm typed. The expected association with B8, B18, Bw62, DR3 and DR4 was observed as well as an excess of DR3/4 heterozygotes. DR2 was decreased in frequency. In the total patient group, no Gm association was observed but when the patients were subgrouped according to HLA type, HLA/Gm interactive effects were seen. An increase in Gm(1,3;5) was observed in DR3 positive, DR4 negative patients. This association occurred predominantly in females (compared with DR4 and DR3/4 patients of the same Gm phenotype who were predominantly male). Further genetic heterogeneity was identified within DR3/4 patients. Within this group, Bw62 was increased (strongly suggestive of Bw62-DR4 haplotypes) within B8, Gm heterozygotes compared with B8, Gm homozygotes. This finding can be interpreted as indicating a three-way interaction between genes on two HLA haplotypes and Gm-linked genes. These results reflect the genetic heterogeneity and complexity of insulin-dependent diabetes mellitus and explain in part the previous failure of simple genetic models to adequately explain inheritance patterns observed.

Diabetes Mellitus, Type 1↗
PubMed1986

Immobilization of sperm by condoms and their components.

Condoms and other rubber products immobilize sperm, but the mechanism is unknown. Sperm motility and eosin Y exclusion were measured following exposure of samples of semen to latex condoms of various types. Sperm motility was markedly reduced by exposure to all latex condoms, but eosin Y exclusion was unchanged. While there appeared to be some variability between semen samples and in time to complete immobilization of all sperm, condoms from one batch were similar. The immobilizing effect was not altered by prewashing the condom with buffer, chelating agent or acid. After immobilization, motility was not recovered by sperm washed in buffer, mixed with normal mid-cycle cervical mucus, or exposed to caffeine or adenosine triphosphate after demembranation with detergent. Studies with components of condoms indicated that raw latex and zinc dimethyl- and dibutyl-dithiocarbamate accelerators immobilized sperm within 30 min. In contrast, silicone rubber had no effect on sperm motility for up to 4 h. Enhancement of the sperm immobilizing effect might improve the contraceptive efficacy of condoms, while a useful non-toxic sperm collecting device for semen analysis, artificial insemination or in vitro fertilisation might be developed by omitting the toxic components from the rubber.

Contraceptive Devices, Male↗
PubMed1985

Ventricular arrhythmias following one-stage and two-stage coronary reperfusion: evidence for both reentry and enhanced automaticity.

We studied the effects of reperfusion in 60 dogs following a 30-45 minute period of left anterior descending coronary artery occlusion using electrocardiograms and composite electrogram recordings. One-stage reperfusion in 14 of 15 dogs produced ventricular arrhythmias which degenerated into ventricular fibrillation within 60 seconds. The onset of ventricular arrhythmias was associated with continuous electrical activity in epicardial and intramural electrograms recorded from the reperfused zone. Vagal slowing during reperfusion (64 +/- 8/min) did not prevent ventricular fibrillation (eight of eight dogs) and escape beats were often followed by one or more coupled ectopic beats associated with continuous electrical activity. Rapid atrial pacing (270/min) also did not prevent the appearance of ventricular arrhythmia with associated continuous electrical activity and ventricular fibrillation (six of six dogs) nor did 4 mg/kg lidocaine (15 of 16 dogs). In another group of 15 dogs reperfusion was performed in two stages resulting in no ventricular fibrillation but in 8 of 15 dogs ventricular arrhythmias were observed beginning within two minutes after reperfusion and lasting 20-30 minutes. These ventricular arrhythmias were not associated with continuous electrical activity in any of the recorded leads. Atrial pacing suppressed ventricular arrhythmias and idioventricular rate averaged 157 +/- 10/min versus 55 +/- 10/min pre-reperfusion control. The earliest site of activation indicated automatic foci arising in the subendocardium of the reperfused zone. Lidocaine (2-4 mg/kg) rapidly (less than 90 sec) restored normal sinus rhythm and suppressed automaticity (72 +/- 11/min) as did left anterior descending artery reocclusion (52 +/- 6/min). We conclude that both reentry and enhanced automaticity play a role in ventricular arrhythmias due to reperfusion. Lidocaine (2-4 mg/kg) suppresses automatic but not reentrant ventricular arrhythmias in this experimental setting.

Animals↗
PubMed1984

Mechanisms of ventricular arrhythmias in multivessel coronary disease: the effects of collateral zone ischemia.

We studied 15 anesthetized dogs with 4-day-old anterior wall infarctions caused by previous ligation of the left anterior descending coronary artery. Left circumflex artery (LCA) stenosis induced an average 41% decrease in collateral-dependent flow to the surviving anterior wall (epicardium) and only a 10% decrease to the normal posterior epicardial wall. Electrogram changes in 12 dogs consisted of fractionation and delay of anterior wall electrograms leading to bridging electrical activity between sinus beats and ventricular ectopic beats in five dogs. No similar electrogram changes were noted in posterior wall recordings. Ventricular paced beats induced ventricular tachycardia arising from the anterior wall in four dogs only after LCA stenosis. LCA stenosis in anterior myocardial infarction may be arrhythmogenic because of increased sensitivity of the surviving tissues, which have been electrically deranged by the ischemic/infarction process.

Angina Pectoris↗
PubMed1984

Nitrofurantoin unmasking peripheral neuropathy in a type 2 diabetic patient.

It is well documented that patients with preexisting renal dysfunction are at increased risk of having nitrofurantoin-induced peripheral neuropathy develop. A diabetic patient whose condition was controlled by diet alone had peripheral neuropathy develop four days after starting nitrofurantoin therapy for the treatment of a urinary tract infection.

Aged↗
PubMed1983

Food items and food groups as risk factors in a case-control study of diet and colo-rectal cancer.

The contributions of food items and food groups as risk factors in a previously reported case-control study of diet and colo-rectal cancer have been analyzed. The study included 348 patients with colon cancer, 194 with rectal cancer, 542 neighbourhood controls individually matched to the cases on the basis of age and sex and a second control series of 535 surgical hospital controls frequency matched to the cases. For colon cancer, as in the previous analysis, the major risk factor was saturated fat, individual food items or groups failing to make a significant contribution to the risk. In particular there was no protective effect of dietary fibre and, for cruciferous vegetables, only a minor protective effect in females. No individual cruciferous vegetable made an important contribution to this effect. For rectal cancer, on the other hand, a significant effect of saturated fat, independent of other food items or groups, was only found for females in the highest consumption category. For males, consumption of eggs, beef and veal significantly increased risk but not consumption of pork, while for females, there was a non-significant increase in risk with consumption of eggs, no increased risk with consumption of beef or veal and a significantly increased risk with consumption of pork. There was no protective effect of dietary fibre or of cruciferous vegetables for rectal cancer, but in females, there was a significantly increased risk for consumption of beer, though this was somewhat reduced when controlled for consumption of saturated fat. There was no indication of an effect of alcohol in either sex or of beer in males. Thus, these results confirm the previous report in showing a significant effect of saturated fat in increasing risk of colon cancer but suggest a contribution of meats to risk of rectal cancer.

Canada↗
PubMed1983

Mechanisms of spontaneous and induced ventricular arrhythmias in the 24-hour infarcted dog heart.

The incidence and types of ventricular arrhythmias were evaluated in 14 dogs, 24 hours after occlusion of the left anterior descending coronary artery. After induction of anesthesia and left thoracotomy, standard electrocardiographic leads and electrograms from the His bundle and the left ventricular endocardium and epicardium (both infarct and normal zones) were recorded. Spontaneous ventricular tachycardia presumably due to abnormal automaticity was consistently observed (average rate 154 +/- 26 beats/min). These arrhythmias were irregular and multiform. In this same group of dogs 3 ventricular paced beats at rates above 300 beats/min induced rapid and uniform reentrant ventricular tachycardias (average rate 345 +/- 17 beats/min) that were difficult to terminate by premature beats or overdrive pacing. During this sustained ventricular tachycardia, continuous electrical activity was recorded from composite electrodes on the epicardial surface overlying the infarcted zone. Such interectopic activity was not observed during the spontaneous, automatic arrhythmias. Two of the 14 dogs showed only ventricular fibrillation in response to the provocative stimuli. These data confirm previous findings that 24 hours after acute myocardial infarction in the dog heart multiform ventricular rhythms can result from enhanced automaticity. In addition, it was found that ventricular tachycardia can be induced in the same dog heart by a standard ventricular pacing procedure. Continuous electrical activity bridging the interectopic intervals only during the latter tachycardia provides strong evidence for the reentrant basis of these induced arrhythmias. These experimental findings are comparable to the 2 different forms of ventricular arrhythmias described clinically, at the same stage of myocardial infarction. The direct myocardial recordings also provide new insights into the phenomenon of entrainment of tachyarrhythmias by overdrive pacing.

Animals↗
PubMed1983

Localization of septal pacing sites in the dog heart by epicardial mapping.

To examine whether different septal pacing sites could be distinguished by their epicardial activation patterns, six to eight stimulating electrodes were placed throughout the septum in seven open chest dogs. Unipolar electrograms were obtained from 52 epicardial electrodes during pacing from each stimulating electrode and isochronous epicardial maps were constructed. The location of each stimulating electrode was found by dissection, and its distance from the overlying epicardium was measured. To allow comparison among epicardial maps, the septum was conceptually subdivided into nine regions to which stimulating electrodes were assigned. Epicardial activation patterns from the same region were similar and these patterns allowed the region containing a stimulating electrode to be identified in many cases. Three other variables were found to have additional localizing value. There were: 1) the time from the stimulus to epicardial breakthrough, 2) the duration of epicardial activation, and 3) the area of epicardium activated in the first 5 ms after epicardial breakthrough. For those stimulating electrodes that could not be localized by their epicardial activation patterns, the distance of the stimulating electrode beneath the epicardium was well fit from these three variables by multiple regression (correlation coefficient [r] = 0.97). Thus, using all the previous factors, localization of septal pacing sites was possible in the noninfarcted dog heart by epicardial mapping.

Animals↗
PubMed1983

Analysis of interectopic activation patterns during sustained ventricular tachycardia.

We analyzed the patterns of interectopic continuous electrical activity recorded within interectopic intervals of sustained ventricular tachycardias. These arrhythmias were induced in dogs that were studied 4 days after left anterior descending coronary artery occlusion. Standard ECG leads and electrograms from the His bundle and left ventricular epicardium, both infarct and normal zone, were recorded. In 19 of 24 dogs with transmural myocardial infarction, one to three ventricular paced beats induced sustained ventricular tachycardia, characterized by continuous electrical activity between the initiating and spontaneous ectopic beat and between successive ectopic beats recorded from the epicardium over the infarct zone but not from the normal epicardium. Continuous activity consisted of discrete potentials that were reproduced in each cardiac cycle, suggesting slow conduction within a reentrant circuit. The interectopic activity was divided into three distinct temporal periods, delineated by potentials occurring at the initial portion, the mid-interectopic portion and terminal portion or exit of the slow conduction segment of the presumed reentrant circuit. In some cases, sustained ventricular tachycardia was induced only if an appropriate initial potential was engaged. Spontaneous termination of the sustained ventricular tachycardia was associated with Wenckebach-like block of conduction in the initial or exit potential. Ventricular pacing caused alteration of the interectopic patterns and resulted in cessation of the arrhythmia. Procainamide produced dose-dependent slowing of the ectopic rate due to depression of conduction in the mid-interectopic portion of the continuous electric activity. Inducibility of the sustained ventricular tachycardia was inhibited by decremental conduction in this compartment of the presumed reentry circuit. The present study uses a preparation showing sustained ventricular tachycardia that is stable and regular. Functional analysis of the various portions of the continuous electrical activity during sustained tachycardias allows further insight into the mechanisms of initiation and termination of sustained ventricular tachycardias. The ability to localize the effect of antiarrhythmic drugs on specific portions of a possible reentrant circuit may provide important correlative data for the analysis and interpretation of detailed epicardial mapping studies.

Animals↗
PubMed1982

Evaluation of a self-administered dietary questionnaire for use in a cohort study.

A self-administered diet questionnaire designed for use in a cohort study has been assessed in comparison with a detailed quantitative diet history previously used in and validated for case-control studies. One hundred fifty-eight women aged 40 to 59 were asked to complete the self-administered questionnaire and 123 returned it by mail. Of these women, 50 were interviewed at home using the detailed diet history. Estimates of intake of major nutrients other than fat and fatty acids are comparable from the two methods although in general, estimated intake from the self-administered questionnaire was higher than the diet history. The difference in intake of fat and fatty acids was largely but not completely accounted for by differences in amounts of added fat recorded. It is concluded that when applied to large numbers of women in a cohort study, the self-administered questionnaire is feasible to administer and will be sufficiently accurate in estimating nutrient intake as compared to estimates from a detailed, interview-type diet history.

Adult↗
PubMed1982

Mechanisms of bradycardia-induced ventricular arrhythmias in myocardial ischemia and infarction.

Experimental and clinical cases have been described in which bradycardia, i.e., heart rates below 60 beats/min or slowing of the heart rate, resulted in lethal ventricular arrhythmias during various stages of myocardial ischemia and infarction. The present study was designed to determine the relationship of lethal ventricular arrhythmias and slow heart rates. In 18 dogs anesthetized with sodium pentobarbital, the left anterior descending (LAD) coronary artery was ligated. Standard ECGs, His bundle electrograms and composite electrograms from intramural and epicardial areas in ischemic and normal zones were recorded during the first 3 hours of ischemia. Vagosympathetic trunk stimulation caused varying degrees of slowing and bradycardia. Of the 18 dogs, slowing of the heart rate or marked bradycardia induced ventricular ectopic beats coupled to the sinus beats in two, sustained ventricular tachycardia in two, and ventricular fibrillation in two. In another group of six dogs studied 17-25 days after LAD ligation, one dog showed sustained ventricular tachycardia in response to vagal-induced bradycardia. In all acute or chronic cases of arrhythmias after LAD ligation, continuous electrical activity was recorded on one or more of the electrograms within or overlying the ischemic or infarcted zones. This bridging electrical activation, which is indicative of slow conduction, provided strong presumptive evidence for reentry as the mechanism of lethal or potentially lethal ventricular arrhythmias triggered by bradycardia in the setting of myocardial infarction.

Animals↗
PubMed1981

The transition to ventricular fibrillation induced by reperfusion after acute ischemia in the dog: a period of organized epicardial activation.

Ventricular fibrillation was induced in eight of 10 open-chest dogs by reperfusion after a 15-minute occlusion of the proximal circumflex coronary artery. Simultaneous recordings were made from 27 epicardial electrodes spaced over both ventricles. Analysis of the initial 1.5--2.5 seconds of the transition from sinus rhythm or ventricular tachycardia to fibrillation revealed that ventricular activation occurred in an orderly, rapidly repeating sequence in all hearts. Each activation from arose near the border of the ischemic-reperfused region and passed across the nonischemic portion of the ventricles to the opposite side of the heart as a single, organized wavefront. As the arrhythmia progressed, the time between the appearance of successive activation fronts on the epicardium decreased. Concurrently, the time for each activation front to traverse the ventricles increased. The stimulation increase in rate of appearance and decrease in conduction velocity for each successive cycle resulted in overlapping cycles in which a new activation front arose from the ischemic-reperfused region before the previous front terminated over the right ventricle. The overlap between successive activation fronts increased as the arrhythmia continued. Thus, ventricular activation during the transition to ventricular fibrillation arose near the border of the ischemic-reperfused region and was organized as it passed across the nonischemic tissue, but the body surface ECG appeared disorganized because of variable spacing between successive, coexistent activation fronts.

Acute Disease↗