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Biomedical subjects

K O'Brien

Publications and source records attributed to K O'Brien.

At least 127 records · Page 7Linked to original sources

Protection of the myocardium during ischemic arrest. Dose-response curves for procaine and lignocaine in cardioplegic solutions.

The dose-response curve of procaine or lignocaine (lidocaine) added to the St. Thomas' Hospital cardioplegic solution was investigated with an isolated working rat heart preparation. In the absence of any cold cardioplegic protection, hearts failed to recover after as little as 30 minutes of ischemia. A single infusion (20 degrees C) of the basic St. Thomas' Hospital cardioplegic solution allowed hearts to recover to 60% or more of their preischemic control aortic flow after a 120 minute period of ischemia. Addition of procaine to the cardioplegic solution either increased or reduced the apparent protective properties of the solution with a bell-shaped dose-response curve being obtained. The optimum procaine concentration was 0.05 mM/L. At this concentration the protection afforded by the St. Thomas' Hospital solution was increased by up to two thirds. Substitution of lignocaine for procaine resulted in a similar dose-response curve with its optimum also at 0.05 mM/L. If a similar optimum exists for the human heart, the doses in current clinical use would appear to be too high. These results argue for determining the dose-response characteristics of all substances used in cardioplegic solutions.

Animals

Cross-linking studies of the self-association properties of apo-A-I and apo-A-II from human high density lipoprotein.

The state of self-association of the apoprotein components of human high density lipoprotein have been studied by use of the cross-linking reagent dimethyl-suberimidate. Analusis of the cross-linked products was carried out by soduim dodecyl sulfate-gel electrophoresis and by agarose column chromatography in 6 M guanidine hydrochloride. Apo-A-I was found to exist as a monomer at low concentration, but associates to tetrameric and pentameric forms at concentrations of 0.5 mg/ml or higher. The self-association was found to be ionic strength-dependent, with association promoted by the presence of salt. Apo-A-II was also found to associate, but the major oligomeric form observed was dimeric (Mr = 34,000), and the association was less dependent on ionic strength than for apo-A-I. Cross-linking in the presence of various concentrations of guanidine hydrochloride showed that apo-A-II self-association persisted at higher concentrations of the denaturant than for apo-A-I. Studies of the effect of temperature demonstrated that the self-association of both proteins was diminished at temperatures above 30 degrees C. Recombination of apo-A-II with phospholipid resulted in the formation of particles which yielded primarily trimers upon cross-linking. This suggests that phospholipid binding causes major reorganization of the self-associated forms of apo-A-II.

Amino Acids

Congenitally bicuspid aortic valves. Clinicogenetic study of 41 families.

The families of 41 patients with surgically proved isolated bicuspid aortic valves were examined. There were 275 first degree relatives of whom 220 were living, and 188 (85.5%) of these were examined. Seven first degree relatives were found to have aortic valve disease, and in a further 11 there was 'doubtful' evidence of bicuspid aortic valves. In 6 families there was more than 1 affected member and in an additional 7 families there was 1 or more 'doubtful' first degree relative. The minimum family incidence was therefore 14.6 per cent, or 31.7 per cent if 'doubtful' cases were included. The inheritance is most probably multifactorial, but occasionally the condition may occur as an autosomal dominant. The difficulties of diagnosing bicuspid aortic valves before the development of obstruction of left ventricular outflow were encountered and are discussed. The association of a bicuspid aortic valve with asymmetric septal hypertrophy, hypertrophic cardiomyopathy, and Marfan's syndrome was also noted.

Aortic Valve

Monte Carlo calculations of the energy response of lithium dosemeters to high energy electrons (less than 30 MeV).

Monte Carlo calculations of the energy response of LiF dosemeters have been carried out to help resolve the discrepancy between the measurements of Holt, Edelstein and Clark (1975) and those of Paliwal and Almond (1975) and others. It is concluded that the assumptions used by Holt et al. are largely responsible. They assume, in converting energy deposition in an air-filled ionization chamber to energy deposition in water, that as electrons penetrate a medium they are monoenergetic and the energy is given by Harder's expression (ICRU 1972). The assumption gives poor results as the stopping power for electrons in air is strongly energy dependent, and the energy spectrum has been significantly broadened. The Monte Carlo calculations are also used to criticize the electron cavity theories of Almond and McCray (1970), Burlin, Snelling and Owen (1969) and Holt et al. (1975), and to suggest as an alternative a slightly modified version of the Bragg-Gray theorem.

Electrons

Ebstein's anomaly. Genetic study of 26 families.

The families of 26 patients with Ebstein's anomaly were examined. There were 120 first-degree relatives, 100 of whom were living, and 93 of these were examined. Information was available on 14 of the 20 who had died. No case of Ebstein's anomaly was found among the first-degree relatives, but 2 had ventricular septal defects and another, who died at 7 months, was said to have had congenital heart disease. In more distant relatives there were 6 with congenital heart disease, including 2 with ventricular septal defects and 2 with Fallot's tetralogy.

Ebstein Anomaly

Long-term hemodialysis for patients over 50.

Hemodialysis can hodl end-state renal failure at bay and enable patients to lead a relatively normal life-regardless of their age. In a 10 year retrospective study of 574 patients, the 154 patients over 50 had about the same survival rates as younger persons for the first three years of dialysis. After that, the older patients had higher mortality. Patients who dialyzed themselves at home-with a relative or friend to help-had much better results than those who were dialyzed at the center. This in part reflects the selection process, since patients with severe medical problems usually weren't allowed to try self-dialysis. Older patients did particularly well on home dialysis, which was attributed to their maturity and dependability. Older patients with cardiac instability may require carefully monitored dialysis at the center and frequent blood transfusions. In general, though, patients over 50 needed fewer transfusions and fewer days in the hospital than younger patients.

Aged

Association of secundum atrial septal defect with abnormalities of atrioventricular conduction or left axis deviation. Genetic study of 10 families.

A genetic analysis was made of 10 families in which the propositi had a secundum atrial septal defect associated with abnormal atrioventricular conduction (first, second, or third degree heart block) or unexplained left axis deviation or a combination of these conduction disturbances. Diagnostic information was available on 51 (81%) of the first degree relatives. Three of the families appeared to be examples of a new syndrome which, with variable expression, was inherited as a non-sex-linked autosomal dominant. The main features were a secundum atrial septal defect; disease of the conducting tissue, which in some cases was progressive; unexplained left axis deviation; and unexpected death. These families did not seem to be examples of the Holt-Oram syndrome, for the upper limbs were clinically and radiologically normal in the 19 members examined. The importance of recognizing this syndrome is the occurrence of progressive disease of the conducting tissue and the risk of sudden death. When, therefore, unexplained left axis deviation or prolonged atrioventricular conduction is found in association with a secundum atrial septal defect all available relatives should be examined. In the remaining seven families there was only one affected first degree relative out of 39 examined. He was the son of one of the propositi and had paroxysmal coronary sinus rhythm with an intact atrial septum.

Adolescent