Wenckebach periods with repetitive block: evaluation with His bundle recording

Two patients are reported in whom repetitive block of two consecutive P waves occurred during Wenckebach beating induced by atrial pacing. His bundle recordings revealed block proximal to H in the first case, suggesting inhomogeneous conduction in the A-V node. In the second case, long cycle lengths were produced in the His-Purkinje system due to A-V nodal Wenckebach periods. The long cycles prolonged refractory periods in the His Purkinje system so that subsequent beats (short cycles) were blocked distal to H.The repetitive block of consecutive multiple atrial impulses could result in unexpected degrees of ventricular asystole during usually benign Type I second-degree A-V block.     

The effects of two years of mestranol treatment on carbohydrate metabolism

Twenty-nine menstrual age women who had a hysterectomy and oophorectomy were treated cyclically with 80 μg of mestranol per day for 2 yr. Their carbohydrate metabolism was evaluated prospectively by doing a 3 hr oral glucose olerance test after a 100 g glucose load and measuring both blood glucose and plasma insulin levels. The tests were performed before drug treatment and after 2 yr of drug use. Those women that had a “normal” predrug test had some carbohydrate metabolism changes at the 2 yr test with significant elevations of the fasting, 1 and 2 hr blood glucose values, and also significant elevations of the 2 and 3 hr plasma insulin values. Those women with a “borderline abnormal” predrug test had no significant change in either parameter of carbohydrate metabolism however a trend toward similar changes was noted.     

Hyperkalemic hyperchloremic metabolic acidosis in sickle cell hemoglobinopathies

This report describes the occurrence of hyperkalemic hyperchloremic metabolic acidosis in six patients with sickle cell hemoglobinopathies. Three patients had sickle cell anemia, two had sickle cell trait and one had S-C disease. In all patients, decreased renal potassium excretion was demonstrated by the finding of a fractional potassium excretion lower than that of control subjects with comparable glomerular filtration rates. Two patterns of impaired urinary acidification were discerned. Four patients had a urinary pH above 5.5 in the presence of systemic acidosis and, thus, were classified as having distal renal tubular acidosis. The remaining two patients had very low rates of ammonium excretion despite intact capacity to lower urinary pH below 5.5 during systemic acidosis; this pattern was ascribed to selective aldosterone deficiency. Sickle cell hemoglobinopathies should be included in the differential diagnosis of hyperkalemic hyperchloremic metabolic acidosis.     

The pathogenesis of hyperchloremic metabolic acidosis associated with kidney transplantation

The mechanism of persistent hyperchloremic metabolic acidosis developing after kidney transplantation was investigated in six patients. In five patients in whom acidosis failed to lower the urine pH below 5.5, an infusion of sodium sulfate also failed to lower the urine pH. Neutral phosphate infusion failed to increase the urine minus blood (U-B) carbon dioxide tension (pCO₂) difference normally in these patients. This abnormal response to both maneuvers indicates the presence of a tubular defect for distal hydrogen ion secretion. In the remaining patient, spontaneous acidosis lowered the urine pH below 5.5 and increased the U-B pCO₂ normally with the administration of phosphate, demonstrating that this patient's distal capacity for hydrogen secretion was intact. The plasma aldosterone level was low in this patient, and thus he had the acidification defect characteristic of aldosterone deficiency. Hyperkalemia developed in two patients; both were aldosterone-deficient, and they had a low fractional potassium excretion in response to stimulation with sodium sulfate or acetazolamide. In all but one patient, who lost his kidney to accelerated rejection, chronic rejection developed. Homogeneous deposition of complement (C3) along the tubular basement membrane was found in three patients. Our data suggest that a secretory type of distal renal tubular acidosis can be an early sign of the immunologic process that leads to chronic rejection.     

Aorticopulmonary septal defect and interrupted aortic arch: a diagnostic challenge

A report of a rare case of aorticopulmonary septal defect and interrupted aortic arch is presented with cardiac catheterization, cineangiocardiographic and autopsy findings. Emphasis is placed on the masking of the Interrupted arch by the presence of an aorticopulmonary septal defect and patent ductus arteriosus.     

Bundle branch block. Demonstration of the incomplete nature of some "complete" bundle branch and fascicular blocks by the extrastimulus technique

The incomplete nature of some electrocardiographic “complete” bundle branch and fasclcular blocks is demonstrated using the atrial extrastimulus technique. Patient 1, with a QRS pattern of “complete” left bundle branch block, manifested a QRS pattern of right bundle branch block at a shorter coupling interval, indicating that the left bundle could conduct. Patient 2, with a QRS pattern of right bundle branch block and “complete” left anterior hemiblock, manifested a pattern of left posterior hemiblock at a shorter coupling interval, indicating that the left anterior fascicle could conduct. Patient 3, with a normal QRS complex, showed left bundle branch block at shorter coupling intervals and then a pattern of right bundle branch block as the coupling interval was further decreased, indicating that functional left bundle branch block was incomplete. This demonstration of partial bundle branch block depends on a discordance of conduction time and refractory period, the bundle or fascicle with depressed conduction (incomplete block) having a shorter refractory period than the more normally conducting bundle or fascicle. This discordance may be related to the development of trifascicular block in patients with bifascicular block and a normal H-V interval. It is a predisposing factor in the complex patterns of aberrant conduction seen during supraventricular tachyarrhythmias with varying cycle lengths.     

The conduction system in rheumatoid arthritis with complete atrioventricular block.

Rheumatoid arthritis, of the peripheral type, or the ankylosing spondylitis type, with complete atrioventricular (A-V) block^1–11 or other conduction disturbances^12–18 has been sporadically reported. Very few conduction system studies have been done in these cases.^{3, 7–9, 17, 18} The present report deals with a comprehensive serial section study of the conduction system in a case of the peripheral type of rheumatoid arthritis with complete A-V block.     

Frequency response of fluid-filled catheter-micromanometer systems used for measurement of left ventricular pressure

The resonant frequencies of five commonly used fluid-filled catheters connected to a solidstate microdisplacement pressure gauge were 18 to 33 per cent higher than those obtained with a conventional manometer. Four catheters had a flat amplitude response to 26 Hz. or more at the 10 per cent amplitude distortion level. The dynamic response characteristic of certain fluid-filled catheters used with microdisplacement pressure gauges allows one to record high fidelity left ventricular pressure curves.     

Effect of ethanol and its metabolites on glucose mediated insulin release from isolated islets of rats.

Effects of ethanol and its metabolites, acetaldehyde and acetate, on insulin secretion were studied in isolated islets from normal rats. Addition of ethanol to the incubation media inhibited glucose mediated insulin release in a dose related manner. Prior exposure of islets to ethanol during the preincubation period had no influence on subsequent insulin response to either glucose or glucose plus ethanol. Acetaldehyde inhibited while sodium acetate potentiated insulin response to glucose. It is concluded that ethanol has a direct inhibitory effect on glucose mediated insulin release from rat islets.     

The effect of diet on thermogenesis in acquired lipodystrophy.

We tested the effect of variation of intake of carbohydrate, fat, protein, and total calories on the metabolic rate and thyroid hormones in an 18-yr-old female with total acquired lipodystrophy and a 23-yr-old normal female control subject. The lipodystrophic subject's resting metabolic rates, when expressed as W/m² body surface area, were elevated and varied directly with the caloric intake. The metabolic rates were highest after 3 days of the protein-supplemented diet and lowest after a 3 day fast. Serum triiodothyronine (T₃) concentrations of the lipodystrophic subject were within the normal range but varied directly with the caloric content of the diet. T₃ was highest during the period of protein supplementation and lowest after the 3 day fast. The resting metabolic rate rose beyond the normal range in the control subject only after 3 days of the protein-supplemented diet and fell to low normal values after the 3 day fast. In contrast to the finding in the lipodystrophic subject, T₃ concentrations were stable after each 3–6 day dietary alteration. We conclude that there is relative metabolic lability in the lipodystrophic subject, and this may be related to the diminished capacity to store energy as fat. Metabolic rates, when calculated as W/kg estimated lean mass, were normal in the lipodystrophic subject, consuming reduced amounts of food (1800 cal/day). The role, if any, of T₃ in modulating these processes is unclear. The subject with lipodystrophy may demonstrate a form of dietary-induced thermogenesis.     

Conduction system examination in a case of spontaneous heart block in a dog

This is a serial-section study of the conduction system in a 2-year-old boxer with electrocardiographic evidence of complete A-V block. The following findings were present: a lack of communication between the atria and the A-V node, atrophy of the A-V node, and tenuous connections between the A-V node and the A-V bundle. These were accompanied by acute degenerative changes in the conduction system. These changes are considered to be the result of arteriolosclerotic heart disease.     

Early vascular modifications induced by asbestos fibers in the hamster cheek pouch

The vascular response of the hamster cheek pouch to direct application of five UICC-standardized types of asbestos fibers was studied in vivo by the transparent chamber technique. The resulting vascular modifications were different from those in studies of the inflammatory process, but similar to changes induced in the cheek pouch by several chemical carcinogens or transplanted malignant tumors. Although definite conclusions may not yet be drawn as to the mechanism and/or significance of the induced vascular response, its relationship to the respective abilities of the various fiber types to induce mesothelial tumors is considered.     

Pathologic measurements in aortic atresia

Detailed autopsy measurements were performed in 13 infants with hypoplastic left ventricle and aortic atresia. Emphasis was placed on the evaluation of changes in the right ventricle, since its function may be important in determining surgical survival. Other important aspects were the ascending aortic and transverse aortic arch diameter, the presence of left atrial obstruction, and the size of the left atrium. The development of improved 2DE and Doppler imaging will permit preoperative and sequential evaluation of these parameters. Measurements performed in this study may serve as a basis for selection of infants for palliative surgery; these procedures are being undertaken more frequently in this hitherto fatal lesion. The measurements may also serve as a basis for noninvasive serial studies of these infants postoperatively.     

Effect of ventromedial hypothalamic lesions on the secretion of somatostatin,insulin, and glucagon by the perfused rat pancreas

Somatostatin, insulin, and glucagon secretion by the perfused pancreas were studied in adult female rats 10 days after ventromedial hypothalamic (VMH) lesions and in sham operated controls to assess the role of their hypothalamic control. Insulin secretion was significantly greater in VMH-lesioned rats both under basal conditions and after stimulation by theophylline and arginine plus theophylline. Basal glucagon secretion was greater in VMH-lesioned rats as was the glucagon response to theophylline alone and in combination with arginine. Basal somatostatin secretion was similar in VMH and control rats but somatostatin secretion induced by theophylline and by arginine plus theophylline was significantly increased in VMH-lesioned rats. Both the pancreatic content and concentration of somatostatin were increased in VMH-lesioned rats. These results indicate the presence of hyperresponsiveness of A, B, and D cells following VMH destruction and provide new evidence for a role of the hypothalamus in the regulation of pancreatic somatostatin secretion.     

Suppression of insulin secretion by protein deprivation in obesity.

The effect of low protein diets on insulin levels was studied in 17 obese, nondiabetic hyperinsulinemic subjects. Their mean weight was 271% of ideal weight. Nine patients were fed a weight-maintaining 3700-calorie diet for 14 days; this diet contained 398 g carbohydrate and 170 g protein. The patients were then fed an isocaloric diet containing only 6 g protein and 587 g carbohydrate for 14 more days. Mean basal insulin levels decreased from 50.4 to 34.7 μU/ml. This decrease was accompanied by a significant decrease in mean plasma glucose. In seven patients who were fed the low-protein diet after a 4-day period of total fast, the low-protein diet prevented the recovery of basal insulin levels decreased during fasting. These findings were in contrast to the apparent recovery of basal insulin levels observed when the control rather than the low-protein diet was refed in 4 patients following a fast. The suppression of basal insulin levels by protein deprivation was not correlated with changes in plasma glucose, glucagon, urinary 17-hydroxycorticoids, or body weight. Although urinary 17-hydroxycorticoids and free cortisol decreased significantly on protein-restricted diets, treatment with cortisol did not prevent the effect of protein deprivation on basal insulin and glucose levels. Plasma levels of branched chain amino acids (valine, leucine, and isoleucine) decreased in parallel to insulin levels on the isocaloric low-protein diets. We conclude that protein-restricted diets can decrease basal plasma insulin levels in obesity even in the presence of sufficient calories to maintain weight and high carbohydrate content. Of the factors investigated that may account for this phenomenon, it is unlikely that glucagon, glucose, or cortisol play a direct role. It is possible that protein as well as carbohydrate plays a role in the development of hyperinsulinemia and insulin resistance in obesity.     

Inhibition of insulin release during hypovolemic shock

Hyperglycemia, a frequent occurrence during circulatory failure, is not associated with increased circulating insulin concentrations. In this study, large primates (baboons) were subjected to hemorrhagic hypotension for 2 hr to determine whether hypoinsulinemia was due to decreased pancreatic output of insulin or acceleration of insulin degradation. Within 5 min of the onset of hemorrhage, portal vein insulin, as well as peripheral venous concentrations declined substantially and remained below preshock levels throughout the experiment. Tolbutamide, injected after 60 min of shock, elicited only a minimal rise in portal and peripheral venous insulin levels, when compared to that observed in a group of nonshock animals. The disappearance of immunoreactive insulin from serum in another group of shocked animals was not accelerated beyond that of controls. Phentolamine, when injected after 1 hr of shock in another group of animals, was able to elicit a rise in serum insulin with a subsequent decrease in glucose levels. These studies demonstrate that the hypoinsulinemia of the shock state is due to reduced pancreatic output of insulin, which may be under complex adrenergic control and may play an important role in the glucose intolerance of circulatory failure.     

Instantaneous and continous measurement of 14C-labeled substrate oxidation to 14CO2 by minute tissue specimens: An ionization chamber method

The vibrating reed electrometer and ionization chamber have been adapted for the instantaneous and continuous measurement of ¹⁴C-labeled substrate oxidation to ¹⁴CO₂ by minute quantities of isolated tissues. This modified technique, utilizing a “closed” circulation incubation system, is 10–50 times as sensitive as the previously described “open” circulation techniques. Substrate oxidation curves are described for human erythrocytes and polymorphonuclear leucocytes, canine parietal cells and isolated segments of the rat nephron. This apparatus should prove to be a useful tool for metabolic studies of small quantities of isolated tissue.     

Thyroid abnormalities in children of parents who have Graves' disease: Possible Pre-Graves' disease

We have studied possible premonitory features of Graves' disease among offspring of parents who had this condition. One-hundred-fifty-three children of parents with Graves' disease were examined, as were 129 control children selected on the basis of a negative history for Graves' disease among first-degree relatives. Examination consisted of a physical examination, brief medical history, and determination of a variety of thyroid function and autoimmunity tests. Thirty-six percent of children of parents with Graves' disease had one or more abnormality, as compared to 24% of the control children. The incidence of abnormalities increased with age and were more common in females. The abnormalities in both groups were similar in variety and intensity, and differed mainly quantitatively in frequency. Half of the minor abnormalities detected in the thyroid, including firmness, enlargement, or lobulations, were accompanied by chemical abnormalities such as a high or low T₄ level, abnormal thyroglobulin or triiodothyronine (T₃) level, or the presence of antithyroid antibodies. One quarter of children having some minor abnormality in the thyroid had definite evidence of Hashimoto's thyroiditis. Bioassays for long-acting thyroid stimulator (LATS) were positive in 2 of 95 children of parents with Graves' disease, and in 1 of 49 control children. Assays for thyroid stimulatory immunoglobulins, cell-mediated immunity to thyroid antigens, and thyroglobulin immune complexes were negative. There was a clustering of abnormalities in certain families, suggesting that these families may be prone to develop subsequent clinical illness. During follow-up examination extending over 3 yr, a significant fraction of children lost or modified the original abnormality or developed a new abnormality. During observation, one child developed asymptomatic thyrotoxicosis, one developed exophthalmos, one developed vitiligo, and one had the onset of Hashimoto's thyroiditis. The data suggest that there is a progressive evolution of abnormalities in thyroid function, and that these are especially common within certain families. It may be possible to determine from sequential examinations which children are at risk, with a high degree of probability of developing thyrotoxicosis. The abnormalities found in these children change from year to year and do not represent a necessarily progressive process. The data indicate the presence of a condition that may be called “Pre-Graves' Disease”, a dynamic state of disordered antithyroid immunity, which may lead to overt thyrotoxicosis in some children.