Nifedipine and nocturia.
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Biomedical subjects
Publications and source records attributed to R M Donaldson.
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To examine the effects of restraint on the diagnostic process, 25 physicians were urged to be as economical as possible when requesting diagnostic tests for case report simulations of nine patients who had previously been hospitalized with abdominal pain and weight loss. The results of the tests correctly changed the physicians' initial diagnoses, increased their diagnostic confidence, and led to appropriate management decisions. When restrained, individual physicians needed only 3.0 (1.7 to 4.1) diagnostic procedures per patient to reach management decisions, whereas 6.1 (3.0 to 11) diagnostic procedures had actually been performed. Diagnostic approaches were so diverse, however, that the number of procedures collectively requested by randomly assembled "teams" consisting of four to five "economical" physicians equaled the number of procedures actually performed. Moreover, 20 percent of the procedures requested by "economical" physicians were invasive compared with only 7 percent of those actually performed. These findings suggest that, without uniform diagnostic approaches, "team" management may increase testing despite restraint by individual physicians. Moreover, quests for economy may increase invasive diagnostic testing.
During 24 h of organ culture, rabbit gastric fundic mucosal explants maintain constant tissue levels of intrinsic factor (IF) while steadily secreting this glycoprotein into culture medium. Mucosal explants thus generate in one day an average of 1.8 pmol of new IF per milligram mucosal protein, an amount corresponding to 70% of IF present in explant tissue. Cultured explants also incorporate [35S]methionine into tissue IF and secreted IF at a constant rate. Histamine combined with isobutylmethylxanthine stimulates explants to release IF into the culture medium, but tissue levels of IF are diminished and specific activities of tissue and secreted IF remain the same. Fluorograms of 35S-labeled proteins generated by cultured explants fail to show cobalamin-binding precursors or breakdown products of IF. These findings complement previous morphological documentation of IF synthesis by gastric mucosa. Histamine appears to stimulate IF secretion without altering IF synthesis.
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Highly specialized mechanisms are required for transporting cobalamin (vitamin B12) into and out of mammalian cells. This review describes the key role of the cobalamin-binding proteins in meeting the stringent requirements for transport of this essential nutrient. Also summarized are the various defects capable of impairing intestinal absorption and transcellular transport of cobalamin. Elucidation of these defects proved crucial for our current understanding of normal cobalamin transport mechanisms.
Obstructive coronary artery disease is widespread, fatal, and difficult to treat. Up to now, treatment has hinged on medical or surgical treatment. Transluminal angioplasty of the coronary arteries has been introduced as a simple method of relieving coronary artery obstruction with a high initial success rate and a short period of hospitalization.
Intracavitary recording of monophasic action potentials (MAP) is a sensitive means of detecting the electrophysiological effects of early or subendocardial ischaemia. The effects of nitroglycerin (NTG) on the MAP was evaluated during pacing-induced angina in seven patients with localised, reversible ischaemia. Recordings from the ischaemic zone demonstrated a decrease in MAP amplitude and an abnormal rate-corrected shortening of MAP repolarisation. The "control" right ventricular MAP showed only the expected rate-dependent decrease in duration throughout the pacing stress test. The ischaemic MAP were unchanged following the intracoronary administration of NTG (100 micrograms). In contrast, intravenous NTG (200 to 300 micrograms) produced a normalisation of MAP amplitude and duration in spite of continuous pacing at the angina-provoking rate. These changes were preceded by a fall in aortic pressure (from mean 123/84 to 96/62) and subsequent lowering of the rate-pressure product. The major beneficial effects of NTG on the early electrical changes of pacing-induced ischaemia are thus related to decreased oxygen demand due to reduction in cardiac preload.
We evaluated the clinical application of echocardiography (M and 2D modes) in the assessment of cardiac patients with fever and an underlying valvular abnormality in whom the diagnosis of infective endocarditis was suspected. One or more of the classic clinical features of the disease were present in 50 patients (group A). Vegetations were detected by echocardiography in 17 (47%) out of the 36 patients within this group A who had positive blood cultures. Four (28.5%) of the remaining 14 patients with unequivocal endocarditis clinically and negative blood cultures had demonstrable vegetations on ultrasound. Anatomical complications resulting from the septic process (valve destruction or detachment, aortic root abscess) were visualized in 18 (36%) of the 50 patients in group A. The clinical features of endocarditis were lacking in the other 53 patients with fever and murmur (group B). This group included 12 patients with other sources of bacteraemia besides endocarditis. Unsuspected vegetations were detected only in 2 (3.7%) out of the 53 cases. Thus echocardiography is useful in confirming the clinical diagnosis of infective endocarditis, but only rarely detects vegetations in patients who lack the characteristic clinical features of endocarditis, regardless of whether they have positive negative blood cultures.
The role of increased extracellular K+ concentration ([K+]o) in the production of the early electrophysiological changes induced by myocardial ischaemia, was evaluated by recordings of monophasic action potentials and the paced endocardial evoked response. Changes in the duration of local repolarization and conduction time were evaluated during ischaemia, K+ infusion and hypoxia. Raising [K+]o levels in systemic arterial blood from 3.4 +/- 0.5 mmol l-1 to 5.9 +/- 1.5 mmol l-1 produced a similar shortening of repolarization as was seen during ischaemia. Prolongation of conduction time occurred only when the [K+]o levels rose to 8.8 +/- 1.3 mmol l-1. The conduction time slowing during acute ischaemia was always greater and occurred at lower [K+]o levels than that produced by K+ infusion at rates equivalent to the post-ischaemic myocardial venous effluent. Monophasic action potential amplitude and upstroke velocity were reduced in ischaemia but not markedly affected by the increase in [K+]o. Absolute reduction in repolarization time during K+ infusion was more marked at the apex than at the base in the epicardial recordings. The superimposition of hypoxia on hyperkalaemia resulted in marked slowing of repolarization and conduction time. Many but not all of the early electrophysiological abnormalities of acute ischaemia in the intact heart can be related to raised [K+]o.
We have studied the endocardial ventricular evoked response which follows delivery of a unipolar stimulus down the sensing electrode. The system uses the same lead for both pacing and sensing and permits recordings of the evoked T wave representing a dominantly local repolarization which follows a pacing-induced depolarization at the same site. In 12 animal experiments and in the course of electrophysiological investigations in 19 patients, we evaluated changes in the morphology and duration of the paced evoked response following drug interventions which alter myocardial refractoriness and repolarization time. These changes paralleled results obtained by simultaneous, paced monophasic action potential recordings, and suggest that myocardial repolarization can be accurately assessed by this new technique, which could overcome some of the difficulties in comparing 'in vivo' experiments with the clinical effects of drugs in man.
The electrophysiological and mechanical events that follow transient therapeutic coronary artery balloon occlusion were analyzed in five patients. A marked (mean, 60 msec) decrease in the repolarization time of the left ventricular ischemic zone (assessed indirectly from endocardial monophasic action potential [MAP] recordings) ensued within 6 to 10 beats of occlusion. Abnormalities in left ventricular relaxation occurred almost simultaneously and preceded contraction abnormalities. A shift in the ST segment in the electrocardiogram (ECG) usually followed within the next 5 to 10 beats. An increase in heart rate (approximately 10 beats per minute) appeared last in the sequence of events. Angina was a variable parameter, frequently absent. Thus, intracavitary recordings of the electrical and mechanical changes are sensitive indicators of the early ischemic changes that follow coronary occlusion, and may be used to assess the effects of therapeutic interventions on events resulting from a myocardial perfusion deficit.
The serial application of electrocardiography and echocardiography to 67 selected patients undergoing valve replacement for chronic severe aortic regurgitation, documented regression of hypertrophy and chamber size within six to twelve months of surgery in all cases experiencing haemodynamic improvement. Those patients who had persistently increased patterns of myocardial hypertrophy and abnormal end-diastolic dimensions in the presence of normal prosthetic (homograft) function usually had persistent, irreversibly depressed myocardial function postoperatively. Preoperative noninvasive and angiographic characteristics could not predict ventricular function after surgery. Thus we could not precisely define what level of depressed ventricular performance or what degree of dilatation and myocardial hypertrophy constituted an irreversible state from this data. Although operative factors such as myocardial protection during cardiopulmonary bypass may influence postoperative cardiac performance, preoperative histological and histochemical data was useful in delineating irreversible morphological and function changes contributing to a depressed cardiac function, and therefore may be of prognostic importance.
Ten patients with late-onset prosthetic valve endocarditis, uncontrolled sepsis, and aortic root abscesses underwent homograft aortic root replacement with reimplantation of the coronary arteries. There were two perioperative deaths. The necrotizing endocarditis was cured in all eight survivors, who have been followed from 6 to 132 months (mean 3 1/2 years). Two of these patients are having symptoms caused by biological valve malfunction; excellent clinical and hemodynamic results have been obtained in the remaining six patients. Homograft aortic root replacement excludes the root abscesses and the weakened infected aortic anulus from the high systemic pressures and permits suturing to a bed of the aortic root in continuity with healthy myocardium. This operation provides an alternative technique to the management of selected patients with active prosthetic infection and destruction of the aortic ring by sepsis.
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A new pacemaker that can adapt the heart rate in response to the patient's metabolic requirements has been developed. This pacemaker uses the QT interval as the indicator of physiological demand. Experience in five patients showed the rate response to exercise to be smooth and progressive and to return gradually to the basic paced rate after activity stopped. Physiological rate responsive pacing resulted in a 45% increase in cardiac output when compared with fixed rate pacing. Similarly, a 57% increase in maximal exercise capacity was noted when rate responsive pacing was compared with conventional pacing at 70 beats/min. This study showed that physiological rate responsive pacing using the QT interval provides a simple means of increasing the heart rate in accordance with the body's requirements.
The origin and early branching of the coronary arteries is fairly constant. Anomalous origin of the coronary arteries, which produced significant abnormalities of myocardial perfusion, were documented in 13 adult patients undergoing investigation because of chest pain. All underwent surgical treatment with relief of the presenting symptoms. They can be divided into four groups: (1) Origin of the left anterior descending branch of the left coronary artery (LCA) from the pulmonary artery (PA) (three cases); (2) origin of the LCA from the anterior sinus. Acute angulation of the ostium and compression of the intramural segment of this coronary produced severe myocardial ischaemia in three patients. (3) Origin of the LCA from the right coronary artery with its proximal segment closely related to the noncoronary sinus (one patient) in whom relief of symptoms was obtained by surgery. (4) Origin of the LCA from the PA with reversal of coronary flow and left to right shunting (six patients). It is concluded that anomalies of the origin of the coronary arteries are rare, but can produce specific clinicopathological entities that can be diagnosed with confidence and corrected surgically. Moreover, the study emphasises the need for angiographic awareness of these coronary anomalies, even in adult patients in whom atherosclerotic disease would be the most likely finding at cardiac catheterisation.
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