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.     

The metabolic response and problems with nutritional support in acute tetanus

Thirteen patients with severe tetanus were studied in the first and second week of illness in order to assess metabolic changes and nutritional requirements. Nine required muscular paralysis and subsequent assisted ventilation in order to control spasms. Symptoms and signs of sympathetic overactivity were especially common in the latter groups with a fourfold increase in urinary adrenaline and noradrenaline excretion. Other hormonal and metabolic abnormalities included hyperglycemia, mildly elevated insulin concentrations with no significant rise in cortisol, and glucagon. Evidence of excessive protein catabolism was obtained particularly during the second week of illness, mean urinary nitrogen excretion being 20.5 ± 13.8 g/d. Maintenance of nutrient homeostasis proved impossible with conventional enteral-feeding techniques: high-density feeds exacerbated hyperglycemia and diarrhea; low-density feeds were unable to maintain nitrogen balance (?12.34 g/d in ventilated patients, second week). The results indicate that loss of lean body mass is inevitable in such patients unless the metabolic response can be suppressed or more aggressive forms of nutritional support (eg, total parenteral nutrition including sufficient insulin to maintain normoglycemia) are employed.     

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 QRS scoring system for estimating myocardial infarct size: clinical, angiographic and prognostic correlations

The relation between a QRS score derived from the routine electrocardiogram and left ventricular function was investigated in 181 patients after myocardial infarction. Patients with left ventricular hypertrophy and conduction defects were excluded. The QRS score correlated closely with the severity of wall motion abnormalities and left ventricular ejection fraction. The more severe the dyssynergy, the higher the QRS score (hypokinesia = 3.0; akinesia = 5.4; dyskinesia = 9.1). The left ventricular ejection fraction (percent) = 66 - (3.3 x QRS score) (correlation coefficient [r] = -0.81, probability [p] less than 0.001). With use of this regression equation, the QRS score predicted angiographic left ventricular ejection fraction to within 12% of the angiographic ejection fraction in 29 of 30 additional patients studied prospectively. The QRS score was also related to clinical functional class. The worse the clinical manifestation of left ventricular dysfunction, the higher the QRS score (Killip class I = 3.5; class II = 6.5; class III = 7.1). A QRS score greater than or equal to 7 had a specificity of 97% and a sensitivity of 59% for predicting an ejection fraction of less than 45%. Patients with a QRS score of 7 or greater had severe wall motion abnormalities, higher peak serum creatine kinase levels, higher prevalence of multivessel coronary disease, poor clinical functional class and an unfavorable outcome. The QRS score provides an inexpensive, clinically useful estimate of left ventricular function after myocardial infarction and can identify patients at high risk.     

Ebstein's anomaly in association with anomalous nodoventricular conduction. Pre-operative and intra-operative electrophysiological studies.

A 13 year old girl with Ebstein's anomaly was investigated for refractory paroxysmal tachycardias and ventricular pre-excitation. Intracardiac electrophysiological studies demonstrated that ventricular pre-excitation was due to conduction in an anomalous nodo-ventricular pathway. Tachycardia occurred as a result of re-entry within the A-V node with pre-excitation during tachycardia due to conduction in the nodo-ventricular pathway. These tachycardias were controlled initially by medical therapy but because of increasing frequency of attacks, occasionally requiring D.C. conversion, further electrophysiological studies and epicardial mapping were undertaken. The epicardial surface of the right ventricle and right atrium were mapped during tachycardia. The results of the studies confirmed that a direct anomalous atrio-ventricular pathway was not present and that re-entrant tachycardia did not involve an accessory pathway of this type. A rapid atrial pacing system was implanted and paroxysmal tachycardias have been successfully controlled.     

Specific cross-protection between Schistosoma bovis and S. haematobium induced by highly irradiated infections in mice

Significant levels of resistance against Schistosoma haematobium challenge were developed by mice exposed to highly irradiated (20 krad) cercariae of the homologous species (46-53%) or of the closely related species, S. bovis (34-56%) but not of S. mansoni (-6-28%). This ability to cross-protect reflects the phylogenetic relationships between these species; S. mansoni and S. bovis, as well as S. mansoni and S. haematobium, failed to cross-protect. The cross-protection demonstrated between S. bovis and S. haematobium in mice was non-reciprocal.     

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.     

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.     

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     

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.     

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.     

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.     

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.     

Impaired beta-adrenergic stimulation in the uninvolved ventricle post-acute myocardial infarction: reversible defect due to excessive circulating catecholamine-induced decline in number and affinity of beta-receptors

Left ventricular infarction (AMI) was produced in experimental animals and the contractile response to isoproterenol was tested in the isolated perfused heart preparation. Adenylate cyclase activity, phosphodiesterase activity, and beta-receptor binding characteristics were determined in a sarcolemmal preparation of the right ventricle of the same hearts. Three days post-AMI the dose-response curve for isoproterenol of right ventricular dP/dtmax was significantly depressed, while the inotropic effect of histamine was not impaired. Stimulation of adenylate cyclase activity by isoproterenol was reduced by 70% in the membrane preparation, whereas histamine and NaF stimulation rates were unaltered; phosphodiesterase activity was unchanged. In contrast, beta-receptor binding studies with [3H]-DHA1 indicated 74% loss and 10 times lowered affinity (KD) of the remaining beta-receptors, while specific [3H]-QNB1 binding was unchanged. All of the above alterations were prevented by pretreatment with reserpine or metoprolol. It is concluded that these abnormalities in the nonischemic surviving myocardium post-AMI are the result of specific reversible damage of sarcolemmal beta-receptors due to excessive levels of circulating catecholamines.     

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.     

Randomized controlled trial of intraaortic balloon counterpulsation in early myocardial infarction with acute heart failure

The value of intraaortic balloon counterpulsation in limiting infarct size and improving survival was studied in patients with early transmural myocardial infarction complicated by acute heart failure. Thirty such patients, previously well, were randomly assigned to counterpulsation (14 patients) or standard therapy (16 patients). Counterpulsation was begun 4.8 to 13.7 hours (mean 7.1) after the onset of pain and continued for less than 1 to 11 days (mean 4.5). Peak creatine kinase was 1,794 ± 846 IU/liter (mean ± standard deviation) in patients receiving counterpulsation compared with 1,688 ± 908 for those receiving standard therapy; cumulative creatine kinase was 3,590 ± 1,936 IU/liter for patients receiving counterpulsation and 2,945 ± 1,803 for those receiving standard therapy. Hospital mortality was similar (counterpulsation, 7 of 14; standard therapy, 7 of 16 [p = 0.05 for 25 percent mortality reduction]) as was mortality at follow-up (counterpulsation, 8 of 14; standard therapy, 10 of 16 [p = 0.09 for 25 percent mortality reduction]). Functional class at follow-up examination 1 to 36 months (mean 15) after infarction was also similar in the two groups. Counterpulsation did not appear to modify infarct size or to alter morbidity or mortality when initiated as primary therapy 4.8 to 13.7 hours after the onset of symptoms of myocardial infarction.