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Biomedical subjects

P Allen

Publications and source records attributed to P Allen.

At least 145 records · Page 8Linked to original sources

Carpentier-Edwards supra-annular porcine bioprosthesis. Clinical experience and implantation characteristics.

The investigational Carpentier-Edwards supra-annular valve was implanted in 592 patients from November, 1981, to February, 1984 (aortic valve replacement in 286, mitral valve replacement in 259, and multiple valve replacement in 47, for a total of 638 prostheses). A previous cardiac operation had been performed in 77 patients (13%). Concomitant procedures were performed in 202 patients (34.1%), including coronary artery bypass in 163 patients. The patient evaluation was 98.6% complete. The early mortality was 7.4% (44 patients) and the late mortality was 6.2% per patient-year (41 patients). The valve-related causes of late mortality were thromboembolism (five), anticoagulant-related hemorrhage (one), and prosthetic valve endocarditis (one). The overall patient survival, including operative death, was 85% at 2 years. The linearized occurrence rate for valve-related complications was 5.6% per patient-year (37 events)--thromboembolism 2.7% per patient-year (18) anticoagulant-related hemorrhage 1.2% (eight), prosthetic valve endocarditis 0.8% (five), and periprosthetic leak 0.9% per patient-year (six). There were no cases of primary tissue failure or structural failure. At 2 years, the freedom from valve-related complications was 86.9%, from valve-related mortality, 98.7%, and from valve-related mortality and reoperation, 97.7%. This valve is fixed in glutaraldehyde at low pressure and is designed to improve durability. It has provided a low incidence of valve-related complications without structural failure. The structural design of the prosthesis does not always conform to the anatomy of bicuspid aortic valves.

Bioprosthesis↗

Sympathoadrenal function during cardiac operations in infants with the technique of surface cooling, limited cardiopulmonary bypass, and circulatory arrest.

The sympathoadrenal response to surface cooling, limited cardiopulmonary bypass, and deep hypothermic circulatory arrest was investigated in 22 infants undergoing correction of congenital heart defects. Surface cooling to 26 degrees C was associated with a significant rise in plasma epinephrine and norepinephrine levels. Both levels fell during the period of core cooling on bypass, presumably because of hemodilution. Following the period of circulatory arrest there was a rise in both catecholamine levels that correlated nonlinearly with the duration of circulatory arrest. The catecholamine levels remained high after rewarming until the chest was closed. The results suggest that this type of surgical procedure produces severe sympathoadrenal stress. The extremely high values found in the postarrest period in some patients, who had had a long period of arrest (greater than 40 minutes), may indicate hypoxic stress. The biological effect of high circulating plasma catecholamines during hypothermia is difficult to assess. The heart rate response to plasma catecholamine levels tended to diminish on cooling in our patients.

Cardiopulmonary Bypass↗

Plasma and red cell levels of thioridazine and clinical response in schizophrenia.

The relationship of plasma and red blood cell (RBC) levels of thioridazine to clinical response in schizophrenia was evaluated in a fixed-dose study. Steady-state plasma and RBC levels of thioridazine, mesoridazine, and sum of thioridazine and mesoridazine, determined by gas-liquid chromatography, were not significantly correlated with clinical response as measured by improvement on the Brief Psychiatric Rating Scale. RBC thioridazine levels were not substantially more strongly correlated with clinical response than plasma levels.

Adult↗

Hypertrophy without contractile dysfunction after reversal of pressure overload in the cat.

To determine whether a causal relationship exists between the myocardial hypertrophy and the deficits in myosin ATPase activity and contractile function that have been associated with chronic, experimental pressure overload, we studied contractile function, myosin ATPase, and isomyosin pattern in a model of severe pressure overload in which the pressure overload was surgically relieved but hypertrophy persisted. Severe hypertrophy, contractile dysfunction, and pump failure were produced in the cat right ventricle by tight pulmonary arterial banding. In two groups of cats banded for 2- and 7-wk periods, right ventricular mass doubled, and contractile function was severely depressed compared with controls. In another group of cats subjected to severe right ventricular pressure overload for 4 wk, pressure overload was reversed by removal of the pulmonary arterial band. After a 4-wk recovery period for this group, right ventricular mass remained markedly increased, but contractile function had returned to normal. Changes in neither isomyosin composition nor myosin ATPase activity were found regardless of contractile function. Thus, following reversal of a right ventricular pressure overload severe enough to cause pump failure and a twofold increase in right ventricular mass, muscle contractile function can return to normal even when severe hypertrophy persists. Furthermore, changes in myosin isozyme composition or ATPase activity do not explain the changes in contractile function.

Adenosine Triphosphatases↗

Adsorption of plasma from tumor-bearing hosts over protein A--containing nonviable Staphylococcus aureus Cowan I: possible mechanism of antitumor reactions.

Adsorption of autologous plasma over nonviable Staphylococcus aureus Cowan I (SAC) followed by reinfusion of the plasma causes regression of (a) chemically induced rat mammary adenocarcinomas (MA), and (b) canine transmissible venereal tumors (TVT) and spontaneously occurring dog tumors. Animal data are more impressive than that from trials in humans. Nine of 41 patients receiving perfusions of adsorbed plasma showed some partial objective response. Eight of these nine patients received multiple perfusions over a period of time. Twenty-one of 41 patients showed subjective responses. Adsorption of autologous plasma over non-protein A--containing S. aureus Wood 46 caused regression of MA. Adsorption of normal rat plasma with SAC, and infusion of this adsorbed plasma into mammary tumor--bearing rats, caused regression of MA. Intravenous infusion of purified protein A alone caused regression of both rat MA and canine TVT. Superimposed on this observation is the finding that, during plasma adsorption, bacterial moieties leach from SAC. It is possible that the immunostimulation observed in plasma-perfused hosts is due to the removal of plasma blocking agents on one hand, and introduction of the bacterial agents on the other.

Adenocarcinoma↗

Effect of frequency of plasma adsorption over protein A-containing Staphylococcus aureus on regression of rat mammary adenocarcinomas: modification of antitumor immune response and tumor histopathology.

Adsorption of the plasma of Sprague-Dawley rats having 7, 12-dimethylbenzanthracene (DMBA)-induced primary mammary adenocarcinomas with protein A-containing Staphylococcus aureus Cowan I (SAC) and reinfusion of the adsorbed plasma caused significant (p less than 0.05) regression of mammary adenocarcinomas. Adsorption of plasma was done at different intervals--weekly, biweekly, and on alternate days. Of these protocols, alternate-day adsorptions induced very fast (within a week) tumor regression (p less than 0.001). Other protocols also produced tumor regression; however, the effect was delayed. In long-term studies, the responding animals showed fewer tumor nodules than did the untreated controls. The plasma of the treated animals showed (a) a reduction in blocking activity, (b) an increase in antibody- and complement-mediated cytotoxicity, and (c) potentiation of the cytotoxic activity of peripheral blood mononuclear cells (PBMCs). Histopathological analyses of biopsied sections of tumors from treated animals showed (a) disruption of tumor cell architecture, (b) loss of glandular structure, (c) shrinkage of epithelial cells, and (d) moderate mononuclear cell infiltration. Thus, adsorption of the plasma of DMBA tumor-bearing rats with SAC allows an indigenous immune mechanism to function against autochthonous tumors to control their growth and cause regression.

Adenocarcinoma↗

Attitudes to research ethical committees.

A questionnaire on the attitudes towards the functions of research ethical committees was sent to members of selected research ethical committees in Wessex and some controls. Almost all respondents felt there was a need for ethical review of research projects; 42 per cent thought there was a need for some training before joining a committee; 67 per cent thought the system could be improved and 47 per cent thought that monitoring or follow-up procedures should be adopted. Ethical committees were thought to be purely advisory, as opposed to mandatory, by 33 per cent, and 63 per cent thought they should restrict their review to ethical problems as opposed to scientific or design problems. Views about the function of non-medical members ranged from 'none at all' to 'very important'. Of the 10 controls who were asked whether they would become a member of an ethical committee if asked, seven said that on balance they would and the reasons stated varied from the view that it was a 'very important committee' to the feeling that it was 'a necessary but irksome job'.

Attitude↗

Contractile function, myosin ATPase activity and isozymes in the hypertrophied pig left ventricle after a chronic progressive pressure overload.

Experimental right ventricular pressure-overload hypertrophy in small mammals is associated with early muscle dysfunction, even before the onset of overt pump failure. Experimental results are quite heterogeneous regarding muscle function of the pressure hypertrophied left ventricle. Muscle dysfunction of the right or left ventricle, when found, may be causally related to alterations of myosin ATPase activity and isozyme type. However, the effect of a gradual pressure overload, analogous to that which occurs in human aortic stenosis, on myocardial contractile function and myosin ATPase activity has not been studied in a large animal whose normal myosin isozyme pattern resembles that of man. We therefore studied pump performance, myocardial contractile function, and myosin ATPase activity and isozyme pattern in pigs with severe, gradually applied left ventricular pressure overload. Thirteen weeks after supravalvular aortic banding, 10 pigs grew more than 7-fold in body weight and were found to have an aortic stenosis area of 0.5 +/- 0.1 cm2 with a gradient of 93 +/- 12 mm Hg. Compared with nine control animals, the banded animals had a 67% increase in left ventricular mass relative to body weight without overt pump failure as measured by cardiac index and pulmonary artery wedge pressure. Left ventricular ejection performance, measured as shortening fraction, was maintained except in three animals with extreme hypertrophy, in which depressed ejection performance may have been due to an afterload mismatch, myocardial dysfunction, or both. Myocardial contractile function, determined from the end-systolic stress-diameter relationship, was normal except in two pigs in which ejection performance was depressed and left ventricular mass was more than doubled. Only the slow V3 isozyme of myosin ATPase was found in both normal and hypertrophied pig myocardium, and the ATPase activity was normal in pigs with all degrees of hypertrophy. Thus, in a large animal model of severe, gradual left ventricular pressure overload, in which myosin isozyme pattern remains apparently unaltered, moderate hypertrophy can be associated with normal myosin ATPase activity and contractile function that is normal by current methods of evaluation.

Adenosine Triphosphatases↗

Coronary artery bypass in patients over 65 years of age.

At the Vancouver General Hospital 235 consecutive patients (172 men, 63 women) aged 65 years or older underwent aortocoronary bypass grafting between January 1974 and December 1979; 168 were 65 to 69 years of age and 67 were 70 years or older. Concomitant cardiac procedures were carried out in 65 (valve surgery in 53, resection of ventricular aneurysm in 10, repair of ventricular septal defect in 1, excision of left atrial tumour in 1). A mean of 2.6 vessels per patient were grafted. Early mortality was 7.7%. For patients who underwent bypass grafting alone, the mortality for those 65 to 69 years was 5.1% and for those 70 years or older it was 5.9%. For patients who underwent bypass grafting and a concomitant procedure, the mortality for those 65 to 69 years of age was 3.1% and for those 70 years or older 24.2%. At follow-up (mean 30 months) there were 23 late deaths. The 5-year survival (life-table method) for the whole group was 77% including early deaths and 83% excluding early deaths. Late survival in those aged 70 years or older was similar to that in patients aged 65 to 69 years. Improvement in function was good; 92% of patients were in New York Heart Association functional class I or II at follow-up, where 94% had been in class III or IV before operation. Acceptable operative mortality with good long-term survival and lessening of symptoms support the use of aortocoronary bypass grafting in patients over 65 years of age. Complex procedures in those 70 years of age or older carry a high risk.

Age Factors↗