Assessing the severity of aortic stenosis.
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Biomedical subjects
Publications and source records attributed to B Massie.
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Increased left ventricular filling pressure and reduced cardiac output are two major hemodynamic deficits in pump failure. In patients with chronic heart failure, consequences of these hemodynamic deficits and diminished cardiac reserve are manifested initially during stress and eventually at rest. The purpose of therapeutic interventions include reduction of ventricular filling pressure increase in cardiac output and improvement in cardiac reserve. To achieve these goals, the hemodynamic effects of predominantly venodilators (nitrates), predominantly arteriolar dilators (hydralazine) and the combination of nitrates and hydralazine were evaluated in patients with chronic heart failure at rest: left ventricular filling pressure (mm Hg) control 28, nitrates 17, hydralazine 25, nitrates plus hydralazine 18; cardiac output (liters/min/m2) control 2.1, nitrates 2.1, hydralazine 3.2, nitrates plus hydralazine 3.3; mean blood pressure (mm Hg) control 87, nitrates 85, hydralazine 83, nitrates plus hydralazine 85. These data suggest improved left ventricular performance with a combination of nitrates and hydralazine. Exercise hemodynamics improved in some patients, suggesting that such vasodilator therapy may be beneficial in chronic heart failure.
Patients with mitral valve prolapse (MVP) frequently experience chest pain which may, expecially in older subjects and males, be difficult to differentiate from angina pectoris. Electrocardiographic (ECG) changes, ventricular arrhythmias, metabolic abnormalities and rare reports of myocardial infarction and sudden death further suggest the presence of an ischemic process in these patients. The recognition of accompanying coronary artery disease (CAD) and exclusion of other causes of ischemia, therefore, may be important in determining the prognosis and appropriate therapy for such patients.
Over five years, 13 patients with episodic apparent type II atrioventricular (AV) block associated with sinus slowing were seen. This phenomenon occurred only transiently during an acute illness in eight patients (group I) but recurred chronically in five (groupII). For the group as a whole, the mean spontaneous cycle length was 42% longer during the period of AV block compared with periods of 1:1 AV conduction (800 +/- 116 msec to 1138 +/- 489 msec) (P less than 0.05). Electrophysiologic studies in four group I patients showed no abnormalities, whereas abnormalities in AV nodal conduction and refractoriness or provocation of intranodal Mobitz type II AV block (during carotid massage) were observed in three patients in group II and were totally abolished by atropine. In group I patients, apparent type II AV block was self-limited. In the chronic group, recurrent symptoms required insertion of permanent pacemakers in two patients. Simultaneous type II block and sinus slowing appeared to be related to the effects of increased vagal tone on both nodal structures. Intracardiac pacing is not indicated for patients with transient episodes associated with an acute illness, but may be required for symptomatic patients with recurrent episodes.
Patients with severe left ventricular failure generally have both reduced cardiac output and increased pulmonary and systemic venous pressures. A study was therefore made of the use of combined vasodilator therapy with nonparenterally administered nitrates, which act primarily on venous capacitance vessels and thus reduce preload, and orally administered hydralazine, which acts on arteriolar resistance vessels and thus reduces afterload. Twelve patients with chronic refractory heart failure were given these drugs individually and in combination during continuous hemodynamic monitoring. Heart rate and arterial pressure did not change significantly. Nitrates significantly reduced filling pressures of both ventricles without affecting cardiac index. Hydralazine did not alter filling pressures but dramatically increased cardiac index. The hemodynamic effects of each drug were additive during combined therapy, resulting in a 36 percent (28 to 18 mm Hg) mean decrease in left ventricular filling pressure and a 58 percent (2.1 to 3.3 liters/min per m(2)) mean increase in cardiac index. The seven patients who have continued to receive combined therapy for 3 to 10 months have shown sustained clinical improvement.
The hemodynamic effects of oral hydralazine were investigated in ten patients (nine in NYHA Class IV and one in Class III) with chronic refractory heart failure. With hemodynamic monitoring, adequate oral doses of hydralazine (50 or 75 mg) were determined and then administered every six hours. Hemodynamics were determined at 2-3, 6-8 and 24 hours on hydralazine therapy. Arterial pressure decreased slightly (5%) and systemic vascular resistance decreased significantly (42%). Cardiac and stroke volume index increased by 70 and 66%, respectively, without any significant change in heart rate, pulmonary capillary wedge or right atrial pressure. Hemodynamic improvement was associated with clinical improvement without a major complication. During the follow-up period of 3-7 months, seven of nine patients were in NYHA Class II and one in Class III. One other patient died suddenly six weeks after discharge. These findings suggest that hydralazine in an effective oral vasodilator for the treatment of refractory heart failure.
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As part of an effort to develop a suspension-culture perfusion-based process with high flow rate without the fouling and antibody retention inherent to filter-based cell-separation devices, we have evaluated and contributed to the development of the Centritech Lab centrifuge for the perfusion culture of hybridoma cells in protein-free medium. Culture start-ups showed that cell growth and monoclonal-antibody (MAb) production rates were similar in both a spinner flask and continuous centrifugation coupled to a bioreactor. The centrifuge efficiently separated viable cells from dead ones. Viable-cell recoveries were never below 98%, whereas dead-cell recoveries were usually around 80%. The cell content of the centrifuge supernatant and concentrate was strongly determined by the total amount of cells, viable and dead, in the culture broth, but an influence of the centrifugation parameters (feed rate, times of separation and discharge, and rotor speed) was observed. This understanding of the separation process inside the centrifuge is important and may apply to other similar devices. Monoclonal antibodies were not retained in the bioreactor during centrifugation perfusion. However, whereas similar growth rates were obtained in perfusion cultures using either continuous centrifugation or filtration, MAb concentrations were 35% lower in the former case. Utilization of the centrifuge in an intermittent fashion decreased the daily cell residence time outside the bioreactor, the daily pelleted-cell residence time in the centrifuge, and the frequency of cell passage to the centrifuge. This led to higher viable-cell numbers in the bioreactor and an accompanying increase in MAb concentrations, 225-250 mg of IgM L-1, equal to the performance of filter-based perfusion systems with the same cell line. It was hypothesized that having cells periodically packed at the bottom of the centrifuge insert (up to 800 x 10(6) cells mL-1) is deleterious to the culture by exposing the pelleted cells to prolonged nutrient limitations.
Seven strains of Escherichia coli O55:B5g, isolated from independent cases of infantile diarrhoea, contained similar RColBM plasmids beloning to incompatibility group IncFIII. Suspecting an epidemiological link among all these cases we compared the restriction pattern of the corresponding RColBM plasmids after digestion with endonucleases EcoRI and BglII. These patterns were similar, confirming the suspected relationships among the seven cases of infantile diarrhoea. The patterns obtained with the RColBM plasmids from children were different from those obtained with two RColBM plasmids isolated from adults. The probable source of the seven cases of infantile diarrhoea was identified as a nursery.