Long-term results of tricuspid valve replacement and the problem of prosthetic valve thrombosis

Observations in 71 patients having tricuspid valve replacement over a 14-year period are described. The operative mortality rate was 10% and the actuarial survival rate was 73% at 5 years and 47% at 10 years. Survival was unaffected by the number of valves replaced or the type used (27 Starr-Edwards, 32 Björk-Shiley, 8 Lillehei-Kaster, and 4 porcine xenografts). Complications were common: 3 deaths were related to anticoagulation and 1 was due to a systemic embolus. Six patients required permanent pacing.There was a very high incidence of thrombosis of the prosthetic tricuspid valve. Twenty percent of the tilting disc valves thrombosed, compared with 4% of the Starr-Edwards valves (p < 0.05). Symptoms of thrombosis were usually insidious, and its diagnosis was often delayed. There was a continuing risk of this complication, and presentation occurred up to 12 years after the original operation. Thrombolytic therapy with streptokinase was successful in 1 of 2 patients. Replacement of the thrombosed prosthetic valves was carried out without mortality in 8 patients.     

The impact of imaging on the surgical management of biliary cystadenomas and cystadenocarcinomas; a systematic review

BackgroundBiliary Cystadenomas (BCA) are considered to be benign but may transform to Biliary Cystadenocarcinomas (BCAC). The aim of this systematic review was to assess the diagnostic work-up and necessity of complete surgical resection.MethodA systematic literature search was performed in Embase.com, Medline (Ovid), Cochrane Central, Web-of-Science and Google Scholar. Articles reporting on diagnostic work-up or outcome of various treatment strategies were included.ResultsFifty-one articles with 1218 patients were included: 971 with BCA and 247 with BCAC. Patients with BCA were more often female (91% vs 63.8%, p < 0.001). On radiologic imaging BCAC more often had calcifications (p = 0.008), mural nodules (p < 0.001) and wall enhancement (p < 0.001). Reported treatment strategies were resection, enucleation, or fenestration/marsupialization. Recurrence was reported in 5.4% after resection for BCA and 4.8% after resection for BCAC. Recurrence after fenestration/marsupialization varied from 81.6% to 100% for both BCA as BCAC. Mortality rate was 0 in patients with BCA and 24% in BCAC.ConclusionDue to the difficulty in accurately diagnosing these biliary cystic lesions and the availability of different surgical approaches, patients with suspected BCA or BCAC should be treated in a center specialized in liver surgery with state-of-the-art imaging and all surgical techniques to prevent mismanagement of this rare disease.     

Concealed bypasses of the atrioventricular mode in patients with paroxysmal supraventricular tachycardia revealed by intracardiac electrical stimulation and verapamil

Thirteen patients with paroxysmal Supraventricular tachycardia were studied with use of His bundle electrograms and programmed intracardiac stimulation. No patient had evidence of either the Wolff-Parkinson-White or Lown-Ganong-Levine syndrome. During ventricular pacing at a rate of 90 to 180 beats/min retrograde conduction time increased by an average of 80 msec in eight patients; in the remaining five patients the average increase was only 9 msec. The tachycardia was terminated in all 13 patients after intravenous administration of verapamil, 10 mg. This drug acts predominantly on the atrioventricular (A-V) node, and during termination of an A-V nodal reciprocal tachycardia both the antegrade and retrograde conduction times would be expected to be prolonged. During termination of the tachycardia antegrade conduction was prolonged by an average of 43 msec and retrograde conduction by an average of 79 msec in eight patients. However, in five patients antegrade conduction was prolonged by an average of 101 msec and retrograde conduction by an average of only 3 msec. The minimal effect of this drug on retrograde conduction and the minimal increase in retrograde conduction during ventricular pacing in these five patients is strong evidence for the presence of an A-V nodal bypass that was not apparent from the surface electrocardiogram. The potential hazards should atrlal fibrillation occur and allow rapid antegrade conduction in an A-V nodal bypass are discussed.     

Effects of interferon on the cAMP-adenylate cyclase system of human, mouse, and bovine thyroid tissue

This report studied the action of interferon on the thyroidal adenylate cyclase-cAMP system. It was found that human interferon did not increase cAMP levels in human or bovine thyroid slices during a 60-min incubation. Mouse interferon also had no effect on cAMP levels in mouse thyroidal lobes over the 60-min incubation, nor did it increase adenylate cyclase activity in mouse homogenates.     

Measurement of the circulatory effects of dobutamine, a new inotropic agent, in patients following cardiac surgery

The use of an extractable aortic electromagnetic flow probe to provide a continuous on-line display of ascending aortic flow and cardiac output following open heart surgery is described. Utilizing this equipment, the hemodynamic actions of dobutamine and isoprenaline are compared in 14 patients immediately following cardiac surgery. The study confirmed an inotropic action produced by dobutamine at a heart rate 10 to 15 per cent lower than isoprenaline, with less peripheral vascular action. Arterial and coronary sinus blood analyses revealed little difference in the myocardial metabolic actions of either drug. Because inotropic drugs produce only relatively small increases in stroke volume in this group of patients, the rise in cardiac output caused by these agents is more dependent on the effects upon heart rate rather than improved myocardial contractile state and consequently dobutamine has little advantage over isoprenaline in this situation.     

Hemodynamic effects of newer antiarrhythmic drugs

The aim of antiarrhythmic drug therapy is to terminate or suppress specific arrhythmias and improve cardiovascular function. Short-term studies of the new Class I drugs encainide, mexilitine, and tocainide have demonstrated only minor falls in cardiac index with modest rises in mean aortic pressure. In contrast, disopyramide has been shown to depress myocardial function in both animals and patient studies. Heart failure may be precipitated by therapy with disopyramide and electromechanical dissociation has been reported. Class II agents with beta-adrenergic blocking actions all produce a degree of myocardial depression. Atenolol resembles propranolol in patients with coronary artery disease in its hemodynamic effects, whereas acebutolol is less of a depressant, resembling practolol. The Class III agent amiodarone has only a mild depressant effect associated with a reduction in afterload and an increase in coronary blood flow. The Class IV agent verapamil, which is a calcium channel blocker, has potent myocardial depressant actions and causes peripheral vasodilatation. Hypotension, heart failure, and shock have been precipitated particularly in patients receiving beta-blocking drugs concurrently. While all the new antiarrhythmic drugs currently studied will cause some degree of hemodynamic depression in an appropriately high concentration, present investigations suggest that particular caution needs to be taken when disopyramide, aprindine, atenolol, and verapamil are administered either acutely by the intravenous route or chronically by the oral route.     

The effect of ingestion of meat on hepatic extraction of insulin and glucagon and hepatic glucose output in conscious dogs

The effect of ingestion of protein on hepatic extraction of insulin and glucagon and hepatic glucose output were investigated in conscious dogs. The ingestion of meat stimulated both insulin and glucagon secretion but the glucagon response was much more rapid and greater than that of insulin. Secretion of glucagon demonstrated a biphasic pattern while insulin release was monophasic. The fractional hepatic extraction of glucagon increased gradually from the basal value of 15 +/- 3% to a peak of 36 +/- 5% at 90 min, and that of insulin increased from the basal level of 41 +/- 2% to 54 +/- 4% at 45 and 60 min. The increased hepatic extraction of glucagon and insulin after meat ingestion may be explained by neural or hormonal signals from the gut. The blood glucose and hepatic glucose output did not increase significantly despite the significant decrease of the portal vein insulin to glucagon molar ratio as well as the significant decrease of the molar ratio of the hepatic uptake of these hormones. The absence of greater hepatic glucose production despite the augmented glucagon secretion and decreased portal vein insulin to glucagon molar ratio could reflect down regulation by glucagon.     

Evidence for in vivo compartmentation of amino acids between blood cells and plasma in man with liver disease during constant infusion of L (U-14C) tyrosine

L (U-¹⁴C) tyrosine tracer was infused at a constant rate for 8 hrs in a series of five patients with liver disease on two occasions, the first when diet consisted of intravenous glucose, and the second when aminoacids were added. Plateau labelling of both plasma and intracellular blood cell free tyrosine was obtained by 6 hr of each infusion. However, the intracellular specific activities were on average 50% lower (p < 0.05) when diet was glucose alone, and 54% lower (p < 0.01) when glucose and aminoacids were given. Change in diet did not significantly affect these differences. The results provide evidence for significant in-vivo compartmentation of aminoacids between plasma and blood cells in man with liver disease, and indicate that whole blood cannot be used in the conventional measurement of whole body protein     

Validation of a practical in vivo insulin dose-response curve in man

To adequately investigate the state of insulin resistance, an insulin dose-response curve should be constructed so that insulin sensitivity (right shift of dose-response curve) and insulin responsiveness (maximal response) can be determined. This paper describes and validates in man a practical in vivo insulin dose-response curve technique, using a modification of the euglycaemic clamp described by De Fronzo et al. Insulin action at steady state was expressed as metabolic clearance rate of glucose (MCR_G) rather than overall rate of glucose disappearance (M or Rd). MCR_G was chosen because at plasma insulin concentrations >25μU/ml it was shown (n = 5) not to be altered by changes in blood glucose concentration (MCR_G 379 ± 23 and 408 ± 19 ml/m²/min; at plasma glucose concentrations 5.4 ± 0.3 and 10.2 ± 0.7 respectively), whereas Rd was critically dependent on the prevailing blood glucose concentration (Rd 2007 ± 128 and 4124 ± 219μmol m²/min respectively). MCR_G was demonstrated to be stable over a 6 hr period (n = 7) and to be reproducible (n = 4). Insulin dose-response curves (MCR_G Versus insulin concentration) were performed on two obese and seven normal weight individuals. The insulin dose-response curves were linearized, allowing accurate prediction of the maximal MCR_G, as compared to the experimentally determined maximal response (r = 0.953 p < 0.01). The use of this transformation obviates the need to employ very high insulin infusion rates to determine the maximal insulin response. In conclusion, the technique permits, in a single 6 hr study, a precise insulin dose-response curve to be constructed for accurately determining insulin sensitivity and responsiveness.     

Nature and biologic activity of “extrapancreatic glucagon”: Studies in pancreatectomized cats

After total pancreatectomy concentrations of circulating immunoreactive glucagon (IRG) were elevated (255 ± 37 pg/ml, mean ± SEM; n = 20) in comparison to unoperated cats (119 ± 27 pg/ml). Plasma glucagon concentrations were determined in an assay regarded as specific for pancreatic glucagon. The nature of this extrapancreatic IRG was further examined in the following studies. Arginine (0.45 gm/kg i.v.) caused a marked elevation of IRG in normal animals but did not cause a consistent elevation of IRG in 6 pancreatectomized cats. Whereas somatostatin (20 μg/kg/hr i.v. for 1 hr) in 10 pancreatectomized cats caused a reduction in IRG from 195 ± 45 to 64 ± 22 pg/ml (p < 0.02), blood glucose did not change. Moreover, insulin (0.22 U/kg/hr i.v. for 1 hr) failed to reduce blood glucose levels in 6 pancreatectomized cats despite a fall in IRG from 269 ± 87 to 150 ± 62 pg/ml (p < 0.05). Glucagon (4 ng/kg/min i.v. for 1 hr) given during the second hour of somatostatin infusion failed to raise blood glucose in 7 untreated pancreatectomized cats. However, when euglycemia was achieved by prolonged insulin therapy in 2 pancreatectomized animals, extrapancreatic IRG became completely suppressed and a hyperglycemic response to exogenous glucagon was restored. Although extrapancreatic IRG appeared identical to pancreatic glucagon by immunoassay, Sephadex G50 chromatography of plasma from 4 pancreatectomized animals showed that 40%–90% of the IRG was of approximately 9000–10,000 molecular weight. Only 10%–60% was of molecular weight corresponding to pancreatic glucagon, i.e., 3500. This contrasted with normal cats, in whom more than 90% of IRG was of molecular weight 3500. The excessive secretion of extrapancreatic IRG is probably related to insulin deficiency since it is reversed by prolonged insulin therapy. The circulating material is heterogeneous and would correspond in molecular size to pancreatic glucagon and a larger molecular weight glucagon precursor. The lack of a consistent response to arginine and predominance of 9000–10,000 molecular weight material could be due to chronic hyperstimulation of true A cells situated in the upper gastrointestinal tract or other extrapancreatic sites; on the other hand, these results could suggest that the cell of origin of extrapancreatic IRG is distinct from the A cell. A major role for extrapancreatic glucagon in the hyperglycemia of diabetes is not evident in these studies, though hepatic glycogen depletion and a reduced rate of peripheral glucose utilization in the operated animals may have reduced the impact on blood glucose levels of changes in IRG. It is possible that extrapancreatic IRG contributes to the poor response to exogenous insulin and glucagon seen in untreated pancreatectomized animals.     

Comparison of free fatty acid and glyceride--fatty acid uptake by human adipose tissue

A comparison has been made of the uptake of palmitate and triglyceride into human adipose tissue. Both substrates are converted into tissue lipid at similar rates over an incubation period of 2 hr; the uptake of triglyceride is proportional to the amount of tissue in the incubation medium. The assimilation of triglyceride by human adipose tissue requires preincubation of the triglyceride emulsion with serum; depends on the presence of glucose in the incubation medium; and radioactivity from glyceryl-tripalmitin-T is incorporated in preference to ¹⁴C-glyceryl-tripalmitin. Fasting reduced both the uptake of triglyceride into tissue lipid and the esterification of palmitate by the tissue. Fluoride (20 mM) significantly inhibits the esterification of palmitate by human adipose tissue without altering the incorporation of triglyceride. At higher concentrations of fluoride (80 mM) there is some inhibition of triglyceride uptake.     

Spontaneous closure of secundum atrial septal defect in infants and young children

The records of 264 pediatric patients with uncomplicated ostium secundum atrial septal defect (ASD) were reviewed. Eighty-seven patients were younger than age 4 years at the time of cardiac catheterization. Subnormal weight gain, frequent pneumonia, cyanosis or tachypnea were present in 26 patients (30%). Of the 36 infants at catheterization, 17 (48%) had the previously described symptoms, including 12 (33%) who had congestive heart failure. Eight of the 36 infants were found to have closed their defect at a subsequent catheterization. Six of 18 patients who underwent cardiac catheterization between 1 and 2 years of age also had spontaneously closed their ASD at subsequent study. Statistical analysis of hemodynamic data revealed no difference (except a smaller shunt size) between ASDs that closed and those that did not in patients who were <4 years at initial catheterization. Analysis of hemodynamic data revealed no statistical differences between groups of patients with an ASD who were younger than and those older than 4 years at time of diagnostic study. Patients with ASDs that closed were significantly different from patients with atrial level shunting thought to be secondary to a valve-incompetent foramen ovale with respect to age at initial study (11 versus 2 months, p <0.001), mean left atrial pressure (7.7 versus 12.3 mm Hg, p <0.02) and difference between mean right and left atrial pressures (1.0 versus 4.2 mm Hg, p <0.01). Because of this high incidence of spontaneous closure of ASD, even in symptomatic patients, intensive medical management rather than surgical correction is recommended for patients with ASD who are younger than age 2 years. Elective surgical repair of ASD diagnosed after age 4 years is recommended because spontaneous closure after that age is probably unlikely.     

Effect of endurance exercise training on plasma pancreatic polypeptide concentration during exercise

The effect of exercise on human pancreatic polypeptide (hPP) levels was evaluated in five subjects preceding and following a conditioning program. During 90 min of exercise, the plasma concentration of hPP rose to a peak value five times higher than the resting level. After 2 mo of endurance exercise training, exercising at the same absolute work load resulted in only a twofold increase in hPP levels. Even at a higher work load, plasma hPP levels were significantly lower than the values observed prior to conditioning. These results show that plasma hPP concentrations rise during exercise and the magnitude of this response is significantly lower after 2 mo of endurance exercise training.     

Pacing techniques in the management of supraventricular tachycardias. Part 1. The use of high frequency stimulation (HFS) in the management of paroxysmal supraventricular tachycardia.

Using techniques for programmed electrical stimulation of the heart, seven patients with paroxysmal supraventricular tachycardia have been studied and shown to have a reciprocal mechanism as the most likely basis for the tachycardia. In four patients it was found that the tachycardia could be terminated by single right atrial premature beats and in three patients two right atrial premature beats were required. A variable zone for tachycardia termination was found when single or double stimuli were used and so a system for introducing high frequency stimuli at 100 or 1000 stimuli/sec for a given duration is described. Using this system a wider range of the cardiac cycle could be covered, thereby increasing the likelihood of producing correctly timed premature beats. The results of using this system are presented and its practical usage discussed.     

Actin in Triton-insoluble cytoskeleton of thyroid

Treatment of bovine thyroid with the non-ionic detergent Triton X-100 extracts most of the cell protein and leaves insoluble residue. This Triton-insoluble cytoskeleton consists of five major polypeptides on sodium dodecyl sulfate polyacrylamide gels. One of these polypeptides is actin. Based on DNase inhibition assay, 30% of the total actin is associated with the cytoskeleton as the filamentous form. Thyroid actin from the cytoskeleton has been solubilized by dialysis against a low ionic strength buffer at pH 8.0 and purified to homogeneity by a polymerizing-depolymerizing cycle. The overall purification was about 144-fold with a yield of 10%. Bovine thyroid actin is very similar to actins from other tissues on the basis of: (1) comigration with rabbit skeletal muscle actin during gel electrophoresis in sodium dodecyl sulfate, (2) its amino acid composition, which includes about 1 mole of 3-methylhistidine per 42,000 g, (3) its ability to bind and inhibit pancreatic deoxyribonuclease I, and (4) its ability to form 7-8 nm microfilaments which is similar to that of skeletal filamentous actin. Thyroid actin contains beta- and gamma-isoactins, with isoelectric points more alkaline than the alpha-actin of rabbit skeletal muscle.     

Schistosoma bovis as an immunological analogue of S. haematobium

The host-parasite relationships of Schistosoma bovis and S. haematobium have been compared in normal and T-cell-deprived mice, and have been found to contrast with that of S. mansoni. Deprived mice infected with either of the former two schistosome species survived as long as, or longer than, comparably infected immunologically intact controls, and hepatocytes of infected deprived mice were not damaged in the absence of granuloma formation. S. mansoni-infected deprived mice, however, die earlier than intact controls, and suffer extensive hepatocellular abnormalities. A high degree of cross-reactivity between S. bovis, S. haematobium and S. mansoni antibodies and antigens was noted in immunoprecipitation but a greater degree of homology between S. haematobium and S. bovis egg antigens was demonstrated by enzyme immunoassay (ELISA). S. haematobium and S. bovis thus resemble each other more closely than either resembles S. mansoni, and in view of the apparent antigenic similarities between S. haematobium and S. bovis and the relatively greater ease with which the S. bovis life-cycle can be maintained in the laboratory, the animal parasite may be useful in providing material for further immunological studies of the human infection.     

Tall right precordial R waves in members of a family with hypertrophic cardiomyopathy

We recently observed a family with tall R waves from V1 to V3 in different relatives, regardless of the actual presence and localization of idiopathic left ventricular hypertrophy.