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The outcome of 30 consecutive patients with active aortic prosthetic valve endocarditis and root abscesses treated by the technique of homograft aortic root replacement with reimplantation of the coronary arteries is detailed. The principles of this technique are the removal of all abscesses and infected areas likely to drain into the infected mediastinum, excision of infected tissues down to healthy noninfected tissue and replacement with an antibiotic-impregnated homograft aortic root. All patients had evidence of progressive cardiac failure and ongoing sepsis. Mean patient age (+/- SD) at the time of operation was 42 +/- 18 years. The mean number of previous aortic valve replacements per patient was 1.6 +/- 0.7; 14 patients (47%) had undergone greater than or equal to 2 previous replacements. At operation, aortic root abscesses were found in all patients; abscess extension to adjacent structures and partial valve dehiscence had occurred in 23. In-hospital death occurred in 9 (30%) of the 30 patients. The 21 hospital survivors have been followed up for a mean of 66 +/- 42 months (range 9 to 144). Overall, 17 (81%) of the 21 hospital survivors have remained free of major adverse events (recurrence of endocarditis, need for reoperation or death). The results of our study suggest that homograft aortic root replacement should be considered favorably in the treatment of patients with aortic prosthetic valve endocarditis and root abscesses.

The relation of treatment adherence to mortality after a myocardial infarction was investigated among 2175 participants in the Beta Blocker Heart Attack Trial, which had data for measures of treatment adherence, clinical severity, and the psychological and social features that may influence post-infarction mortality. Overall, patients who did not adhere well to treatment regimen (ie, who took less than or equal to 75% of prescribed medication) were 2.6 times more likely than good adherers to die within a year of follow-up (95% confidence interval, 1.2, 5.6). Poor adherers had an increased risk of death whether they were on propranolol (OR = 3.1) or placebo (OR = 2.5). Furthermore, this increased risk of death for poor adherers was not accounted for by measures of the severity of myocardial infarction, sociodemographic features (eg, race, marital status, education), smoking, or psychological characteristics (high life-stress or social isolation).

The introduction of a sharply angulated catheter through an arterial sheath for percutaneous coronary arteriography was associated in 7 cases with dissection of the iliac arteries; this extended to the lumbar aorta at the level of the coeliac axis. The catheter tip should be introduced gently and preferably straightened out with a good length of guide wire to avoid this complication.

Mice were immunized with human intrinsic factor, and their lymph node cells were fused with a myeloma cell line by standard hybridoma techniques. Eleven of the resulting 227 hybridomas secreted immunoglobulin G capable of binding to intrinsic factor-cobalamin complex. Cloning by limiting dilution gave 6 clones secreting anti-intrinsic factor antibodies that bound human intrinsic factor-cobalamin complex with affinities of 13-116 nM; 3 antibodies also bound rabbit intrinsic factor-cobalamin complex. Five antibodies inhibited to some degree the binding of cobalamin by intrinsic factor, and 2 also prevented attachment of intrinsic factor-cobalamin complex to guinea pig ileal receptors. Anti-rabbit intrinsic factor antibodies specifically precipitated a peptide of molecular weight 53,000, corresponding to the molecular weight of rabbit intrinsic factor from homogenates of rabbit gastric mucosal explants biosynthetically labeled with [35S]methionine and from culture medium in which the explants were incubated. Indirect fluorescence immunocytochemistry with the antibodies in human and rabbit gastric mucosal sections showed intense selective staining of parietal cells. These results (a) document species differences between human and rabbit intrinsic factors not previously demonstrable with polyclonal anti-intrinsic factor sera; (b) confirm earlier evidence that cobalamin binding and receptor functions occur at separate sites in intrinsic factor; and (c) provide a useful approach to studying structure-function relations of the intrinsic function molecule.

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.

Thirty-two patients with large postinfarction left ventricular aneurysms shown at operation to consist of fibrous tissue are reported. All had angina and/or breathlessness, and none had a history of embolism. Thirty were correctly diagnosed by left ventricular cineangiography. Two of the 3 patients with inferior and 1 with an anterior aneurysm had associated ventricular septal defects, and 3 patients with an anterior aneurysm had mitral regurgitation. All had major coronary arterial lesions and 68 per cent had double or triple vessel disease. The aneurysm was excised in all patients; in 15 this was combined with saphenous vein bypass grafting of coronary arteries supplying surviving myocardium, in 3 with closure of a ventricular septal defect, and in 3 with mitral annuloplasty or replacement. Operative mortality was 6-2 per cent, and 79 per cent of the survivors are asymptomatic with average follow-up period of 18 months after operation.

Composite graft replacement of the ascending aorta and aortic valve was performed in 78 patients over an 8 1/2-year period. Degenerative lesions of the aortic root in Marfan's syndrome (annuloaortic ectasia) was the indication for operation in 56 cases; the other 22 patients had other causes of aortic root dilatation and aortic valve disease. Overall hospital mortality was 8%. Follow-up ranged from 1-9 years (average 5 years). Reoperation was required in six of the 72 hospital survivors. Overall 5-year actuarial survival was 77%, and 85% of the survivors have shown significant clinical and radiologic improvement. Composite graft replacement reduces the risk of aneurysm formation of the sinuses of Valsalva and eliminates paraprosthetic leakage; postoperative hemorrhage is also reduced. It appears to be the method of choice for patients with degenerative lesions in the ascending aorta and valve, particularly annuloaortic ectasia.

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.

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.

Intracavitary recording of monophasic action potentials (MAP) is a sensitive means of detecting the electrophysiological effects of early or subendocardial ischaemia. The effect of nitroglycerin on the MAP was evaluated during pacing-induced angina in seven patients with localized, reversible ischaemia. Recordings from the ischaemic zone demonstrated a decrease in MAP amplitude and an abnormal rate-corrected shortening of MAP repolarization. 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 100 micrograms nitroglycerin. In contrast, 200-300 micrograms intravenous nitroglycerin produced a normalization 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 nitroglycerin on the early electrical changes of pacing-induced ischaemia are thus related to decreased oxygen demand due to cardiac unloading.

An extremely rare congenital abnormality is reported in which the anterior descending branch of the left main coronary artery arises independently from the pulmonary trunk in a young patient who presented with unstable angina. Its clinical presentation, angiographic identification and surgical treatment are described. It appears to be a distinct entity with few of the features of the classical form of anomalous origin of the left main coronary artery.

The effect of cimetidine on gastric acid, pepsin, and intrinsic factor secretion was assessed in normal male subjects. Cimetidine (300 mg) completely inhibited acid, pepsin, and intrinsic factor concentration and output stimulated by betazole. In contrast, basal output of pepsin and intrinsic factor was not inhibited. We conclude that H2-receptor antagonists inhibit betazole stimulation of intrinsic factor output in addition to their well-known inhibition of acid secretion.

The familial occurrence of essential tremor combined with (congenital) nystagmus, duodenal ulceration and a narcolepsy-like sleep disturbance caused by an autosomal dominant gene with high penetrance and fairly uniform expressivity is reported in a family of Swedish-Finnish ancestry. Twelve of 17 affected family members had essential tremor which began between 30-40 years of age and which could be controlled temporarily by alcohol; this resulted in alcoholism in several affected individuals. The most severly affected persons showed cerebellar signs which may reflect a possible pathogenetic relationship of the syndrome to the genetic cerebellar atrophies. Nystagmus, observed in 12 of 17 affected family members (eight of whom were also affected with tremor) usually was congenital and accompanied by refractive errors. Duodenal ulcers occurred almost exclusively in individuals with the neurological syndrome, and preceded its onset in some cases. The ulcer disease therefore seems to be a component manifestation of the syndrome and is interpreted as a pleiotropic effect of the gene which also causes the nystagmus, tremor and sleep disturbance.

In 78 (0.9%) of 8,283 patients without associated congenital heart disease studied by angiography, one or more major elements of the coronary arterial system originated in an ectopic manner. Symptoms attributable to the aberrant vessel more present in 20 of the 78 patients and in 15 patients these anomalies were treated surgically. The hemodynamically significant anomalies which lead to abnormalities of myocardial perfusion are of particular surgical importance. There are 4 major types: 1) aberrant origin of the left anterior descending branch from the pulmonary artery; 2) origin of the left coronary artery from the right aortic sinus; 3) origin of the left coronary artery from the pulmonary artery and 4) severe atherosclerotic occlusive disease in an aberrant vessel. The incidence, angiographic features and surgical aspects of these anomalies are discussed.

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 role of non-invasive nuclear medicine procedures in the management of paediatric cardiac abnormalities is reviewed. The studies can be performed at the bedside of the very sick infant using a mobile gamma camera computer system, and provide functional structural information essential for management.

The early electrophysiological patterns of regional subendocardial ischaemia were studied by using the paced endocardial evoked response and simultaneous endocardial monophasic action potential recordings in 16 experiments in open chested dogs. Ischaemia was produced by transient (1-3 min) coronary artery occlusion. Regional subendocardial isochaemia caused asynchronous activation due to differential conduction delay and shortened repolarization as evaluated by the duration of the paced evoked response from 175 +/- (SD) 18.7 ms to 167 +/- 16 ms (P less than 0.001). These changes occurred within 60 s of occlusion and reversed rapidly after release of the occlusion. In simultaneous endocardial monophasic action potentials there was a decrease in plateau amplitude and the duration of repolarization shortened from 180 +/- (SD) 21.2 ms to 167 +/- 20.4 ms (P less than 0.001). The delay in endocardial activation after 2 min ischaemia was 5.5 ms, which is considerably shorter than the conduction delay previously reported in the subepicardial layers. The calcium-channel blocking drug verapamil (infused at 0.4 mg/kg) altered the rate at which shortening of repolarization and asynchronous activation occurred during ischaemia in six experiments. These experiments suggest that intracavitary electrodes could provide earlier and more sensitive detection of regional subendocardial ischaemia and may permit the assessment of therapy on the early electrical changes in the intact heart.

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.

Despite the current availability of physiologic pacing systems, there remain distinct disadvantages associated with their operation. Although in theory the atrial synchronous pacemaker (VDD or DDD) is the ideal system, in practice it performs satisfactorily over a very limited range of heart rates in a limited number of individuals. We describe the TX system which incorporates ventricular pacing and is driven by T wave sensing determined by the QT interval. This pacemaker can distinguish between physiologic and pathologic tachycardias while providing an almost unlimited rate response even in the presence of an unresponsive atrium.

Abnormal tricuspid valve structure and motion resulting from the rupture of a right ventricular papillary muscle were visualised by two dimensional echocardiography. These findings were confirmed at operation. Two dimensional echocardiography appears to be a satisfactory method for evaluating patients with tricuspid regurgitation of sudden onset with a view to surgery.

Since transcobalamin II is the plasma binder of vitamin B12(cobalamin) that mediates delivery of cobalamin to tissues, we measured circulating levels of transcobalamin II after intravenous injection unlabeled cyanocobalamin in 12 control subjects and, because the liver is a major source of transcobalamin II, in eight patients with decompensated cirrhosis. Thirty minutes after injection of cyanocobalamin (200 ng per kilogram of body weight), total transcobalamin II (unsaturated plus cobalamin bound) declined in all 20 subjects to levels that averaged (+/- S.E.) 53.5 +/- 4.6 per cent of initial values. Subsequently, unsaturated transcobalamin II rapidly increased so that by eight hours, total transcobalamin II approached preinjection levels. Rates of regeneration of transcobalamin II were similar in control subjects and patients with liver disease. Unlike total transcobalamin II, total transcobalamin I was unaltered by injection of cyanocobalamin. Moreover, addition of cyanocobalamin to plasma in vitro did not alter measurements of total transcobalamin II. The rapid response of circulating transcobalamin II to cyanocobalamin injection strongly supports a dynamic role for this polypeptide during transport of a relatively large load of cobalamin.

We have evaluated an intracardiac technique for the study of the electrophysiological patterns of early or subendocardial ischaemia in man. Simultaneous recordings of the paced endocardial evoked response and monophasic action potentials were obtained during pacing stress testing in 10 patients with reversible myocardial ischaemia. Early patterns of change occurred in both these recordings in response to regional ischaemia. Abnormal rate corrected shortening of the local repolarisation time in the paced endocardial evoked response from the left ventricular ischaemic zone diverging from control non-ischaemic values by a mean of 10.6% was paralleled by decreases in the simultaneous paced monophasic action potentials duration. A differential delay in the local activation time and conduction was also documented by the paced endocardial evoked response and monophasic action potential electrodes. Non-ischaemic control zones showed no changes in the pattern of activation and repolarisation. Disparate repolarisation times and asynchronous activation within the myocardium were thus consistently demonstrated during regional ischaemia. These changes in the endocardial paced evoked response and monophasic action potentials always preceded the appearance and regression of the clinical ischaemia. Intracavitary recordings may thus provide earlier and more sensitive detection of regional ischaemia during cardiac catheterisation or coronary artery surgery. The study of the patterns of activation and response could permit the assessment of interventions on the early electrical changes of ischaemia, and may bridge the gap between in vitro studies and the electrophysiological studies performed upon the intact heart.

Amiodarone is a benzofuran derivative with depressant effects on all electrically active cardiac tissues and important antiarrhythmic properties after long-term dosing. We evaluated its short-term effects on myocardial repolarization and refractoriness in eight patients. The duration of repolarization was evaluated by a new method, the paced evoked-response system, which records the dominantly local repolarization that follows a controlled (paced) depolarization from the same site. Intravenous amiodarone (5 mg/kg) prolonged the latency of the stimulus peak-evoked T wave interval an average of 39.4 msec (+15% of control) 10 min after infusion. In animal experiments these changes correlated well with simultaneous increases in the paced monophasic action potentials obtained with suction electrode catheters. There was also a lengthening of the effective refractory period of the atrioventricular node from 270 +/- 20 to 295 +/- 25 msec. Atrial and ventricular refractoriness were not altered. Amiodarone early activity at the atrial and ventricular level apparently differs from that long-term therapy and appears to favor changes in action potential duration and not changes in refractoriness.

Recent studies have demonstrated problems with the radiodilution assay method for measuring serum cobalamin (vitamin B12) levels. We have found the standard commercial radiodilution kit assay to be totally ineffective in screening for cobalamin deficiency. In a four-month period, 352 patients were screened in a routine clinical laboratory using this kit. None of the serum samples yielded a result below the given normal range of 200 to 1,100 pg/mL. However, when 42 patients with low-normal serum cobalamin levels (200 to 500 pg/mL) were retested by a combination of a modified radiodilution kit, a human intrinsic factor assay, and a microbiological (Lactobacillus leichmannii) assay, 16 (36%) were identified as having serum cobalamin levels that were abnormally low. The diagnosis of cobalamin deficiency may have been incorrectly dismissed in many patients on the basis of test results obtained with these kits, which are in widespread use.

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.

We have evaluated clinically a rate-responsive pacemaker which uses the evoked QT principle as indicator of physiological demand. This pacemaker is microprocessor-based and fully programmable noninvasively through radiofrequency coupling to an external microcomputer. To date this system has been implanted in 15 patients. With this QT sensing pacemaker the rate response to exercise was smooth and progressive, and gradually returned to the basic paced rate after termination of activity. Physiologic rate responsive pacing resulted in significant improvement in exercise tolerance and a 40% increase in cardiac output when compared to fixed-rate pacing in 8 patients. This initial experience confirms the possibility of obtaining a physiological response to exercise using a pacing system dependent only on a unipolar electrode which is independent of the problems of atrial activity and sensing. Rate responsive pacing might prove to be a useful alternative to atrial synchronous systems, and particularly advantageous in those patients whose sinoatrial function is abnormal or who suffer from atrial arrhythmias.

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.

99mTc-labelled phosphates (PyP, IDP and MDP) were compared for their usefulness for the diagnosis of myocardial infarction. The results indicated the superiority of 99mTc-labelled imidodiphosphonate over the other 99mTc-labelled phosphates. At the same time, two mobile gamma cameras were compared with respect to their instrumental characteristics and clinical versalitity and their advantages and disadvantages are reported.