The utility of aprindine blood levels in the management of ventricular arrhythmias.

Sixty-four patients with a history of ventricular tachycardia and ventricular fibrillation refractory to conventional therapy received aprindine to abolish recurrent episodes of symptomatic ventricular tachycardia. Fifty-six patients became asymptomatic and were followed up for a mean period of 23 months. Aprindine dose was adjusted to minimize adverse reactions but still control arrhythmia. Survival analysis was performed for the group with aprindine levels greater than 1.5 micrograms/ml and the group with levels of 1.5 micrograms/ml or less. At the end of the study, 65% of the patients with a high level were alive and asymptomatic as compared with only 35% of the patients with a low level (p less than 0.036). In patients at risk of recurrent sudden cardiac death, high aprindine levels maintained after abolition of symptomatic ventricular tachycardia were associated with improved survival.

Results of a randomized prospective trial of intraaortic balloon counterpulsation and intravenous nitroglycerin in patients with acute myocardial infarction.

A randomized prospective clinical trial compared combined treatment with intraaortic balloon pumping and intravenous nitroglycerin for 4 to 5 days with routine clinical management in 20 patients with extensive myocardium at risk for infarction as evidenced by a thallium defect score of 7.0 units or greater. No significant differences in mortality or clinical outcome were observed between the 10 patients receiving the combined treatment and the 10 receiving routine management. In 14 patients two-dimensional echocardiograms obtained 6 to 24 hours after the onset of symptoms and at follow-up 6 to 16 days later (after completion of combined intraaortic balloon pumping plus nitroglycerin therapy) were analyzed to determine whether infarct segment or noninfarct segment lengths were affected by therapy. Among these 14 patients, 5 (3 receiving the combined therapy and 2 receiving routine management) demonstrated an increase in infarct segment length of greater than 1.0 cm. Mean infarct segment length increased 0.30 +/- 0.44 cm in patients receiving the combined therapy and 0.29 +/- 0.36 cm in patients on routine management (p = NS). In contrast, noninfarct segment length increased greater than 1.0 cm (mean increase 1.20 +/- 0.39) in five of seven patients on routine management but in none of 7 patients receiving intraaortic balloon pumping plus nitroglycerin therapy (mean decrease 0.22 +/- 0.20 cm) (p less than 0.05). No significant differences were noted in left ventricular ejection fraction, as measured by gated blood pool scintigraphy, or thallium perfusion defect score in a comparison of day 1 (pretreatment) with day 4 thallium or day 7 to 14 gated blood pool scintigrams. Thus, in patients with extensive myocardium at risk, it is unlikely that a reduction in mortality or a significant improvement in myocardial perfusion or ventricular function can be obtained by early intervention with intraaortic balloon pumping in combination with nitroglycerin. Although this combined therapy failed to prevent infarct segment lengthening (infarct expansion), the combined afterload-lowering effects of intraaortic balloon pumping and nitroglycerin did appear to prevent dilation or remodeling of noninfarcted segments during the first 2 weeks after acute myocardial infarction.

Early discharge following acute myocardial infarction. Long-term follow-up of randomized patients.

Long-term follow-up was obtained on 138 patients who participated in a prospective, randomized study comparing two weeks with three weeks of hospitalization following uncomplicated acute myocardial infarction. Follow-up information was available on 123 (89%) of all randomized patients. The mean follow-up period was 35 months for those patients who died and 99 months for those who survived. No differences were found between the two groups with respect to survival, cardiac-related deaths, frequency or severity of angina pectoris, subsequent myocardial infarction, incidence of congestive heart failure, number of ventricular aneurysms, or subsequent medical therapy. A significantly greater number of survivors in both groups stopped smoking and had a normal initial heart size than those who died. This long-term follow-up study further supports the conclusions of earlier short-term studies that two weeks of hospitalization is safe in patients with uncomplicated acute myocardial infarction.

The effects of L-dopa on in vitro and in vivo calcitonin release from medullary thyroid carcinoma.

The in vivo and in vitro effects of the dopamine precursor L-dopa on basal and stimulated calcitonin release from medullary thyroid carcinoma have been studied. In six studies of five patients, including 7- to 8-h control and test periods, oral L-dopa depressed basal calcitonin secretion by an average of 35%; the peak effects occurred within 30 min of drug administration and lasted for as long as 4 h. In seven of eight patients with medullary thyroid carcinoma (three infused with calcium and five with pentagastrin), L-dopa inhibited to varying degrees peak levels of stimulated calcitonin release and total calcitonin secretion; basal calcitonin levels, where directly tested, also again generally fell after L-dopa by an average of 50%. In a short term organ culture system using medullary thyroid carcinoma tissues, calcitonin secretion into the medium was linear with time for 2 h and could be stimulated by dibutyryl cAMP and pentagastrin. L-Dopa, in concentrations from 0.5--3.0 mM, inhibited basal calcitonin secretion (ranging from 25--55%). Addition of the L-dopa decarboxylase inhibitor, alpha-methyldopa, abolished the inhibitory effects of L-dopa. Another L-dopa decarboxylase inhibitor, carbidopa, stimulated calcitonin secretion in vitro; this effect may be independent of the L-dopa decarboxylase-inhibiting properties of this drug since alpha-methyldopa alone did not stimulate calcitonin secretion. It is concluded that the amine precursor L-dopa inhibits calcitonin release in patients with medullary thyroid carcinoma; the in vitro studies suggest that a portion of this effect may involve direct metabolism of L-dopa to dopamine in the tumor tissue itself. The importance of considering the uptake of amine precursors and the subsequent metabolism of these compounds as a modulating site for peptide hormone release from peripheral endocrine tissues is stressed.

Growth standards for poor urban children in nutrition studies.

In order to estimate the importance of a variety of environmental and dietary factors as determinants of growth in a group of 123 poor Peruvian urban children between 2 and 19 years old, we found it necessary to express anthropometric measurements in units that were not age- or sex-dependent. Height quotient and weight quotient for each child were calculated from height and weight ages derived from the 50th percentile of the Boston reference data for the appropriate sex. Only 5% of the children had heights above the Boston 50th percentile (height quotient greater than 100) and 18% had weights above the 50th percentile (weight quotient greater than 100), but 88% had weights that were appropriate or excessive for height (weight/height quotient greater than or equal to 1.00). Some CATch-up" gains in relative height and weight were apparent in preschool children but more impressive gains in both linear and ponderal growth, relative to the Boston data, were evident between 8 and 13.5 years in girls and 10 and 17 years in boys. When the same quotients were calculated for a much larger sample from the same socioceonomic level it seemed likely that this last peak was due to earlier puberty and sexual maturation, and that quotients derived from the Boston data would have different meanings at different ages, making them inappropriate for further statistical analysis. New quotients for the study population, derived from the larger Peruvian group, did not have sex- or age-dependent trends. Racial and regional differences in patterns of growth must be taken into account in the interpretation of anthropometric and nutritional data.

Urban-rural differences in the growth of Peruvian children.

The growth characteristics of children from four villages in northern Peru were compared with those of poor urban children in the capital city, in whom short stature but generally satisfactory weight for height relationships after infancy had been demonstrated. Height for age and weight for age fell more rapidly during infancy in the rural than in the urban children of both sexes. Rural girls caught up with the urban girls in height during childhood but did not match them in weight until late adolescence. Their weight to height ratios were consistently lower after 1 year of age, most strikingly between 2 and 5 years of age, and did not approach or match those of the urban girls until adolescence. Rural boys did not catch up with the urban boys in height or weight (differences in height were not statistically significant between 6 and 10 years, however) and their ratios remained consistently lower until late adolescence, most strikingly in early childhood and during puberty. Such urban-rural and sex differences, if typical and current, might well call for very different remedial measures at different ages in each of the populations.

Determinants of growth among poor children: nutrient intake-achieved growth relationships.

Seven-day individual weighed dietary intakes and anthropometric measurements were determined in 123 children, 2 to 19 yr of age, from 26 poor families in Lima: each included one child who had been malnourished, six were adopting families. Heights and weights were converted to "ages" based on Boston reference data and local data, then to "quotients" as percentages of actual ages. Mineral and vitamin intakes were expressed as amounts per day and per 1000 kcal, calories and protein as percentages of FAO/WHO recommendations for age and height age and of modified recommendations based on size of Peruvian children. Regression analyses identified common sources of nutrients and greater dependence of intakes on body size than on age. Analysis of covariance for sex identified different nutrient-growth correlations. Polynomial regression analysis identified percentage protein from animal sources and percentage fat calories as having significant quadratic as well as linear correlations with achieved growth. In males, multiple regression analysis identified percentage protein from animal sources and beta-carotene intakes as strongly associated with achieved height and weight, and percentage fat calories as strongly associated with weight quotient/height quotient ratios. In females the correlations were not as strong, possibly because a significant percentage had reached the menarche some time before the survey and were probably no longer growing. Nevertheless, calorie intake, as a percentage of the recommendation for height age, was prominent in the regressions for height quotient and percentage fat calories in that for weight quotient. The very strong association of animal protein intake with male height, despite seemingly generous total protein intakes, is difficult to reconcile with current recommendations. The possible role of vitamin A (as beta-carotene) has potentially important implications for food policies.

Determinants of growth among poor children: relation of nutrient intakes to expenditure for food.

The growth status and the nutrient intakes of 123 children from 26 urban poor families in Peru were related to per capita expenditure for food. Children from six better off families were taller and heavier (p less than 0.001), with no difference in weight for height. They had significantly higher calorie and total protein intakes (as percentage of recommended) and higher intakes of animal protein, fat, calcium, carotene, riboflavin, and vitamin C. When macronutrient intakes were expressed as percentages of recommended calorie intakes, correcting for age and relative size, all of the increase in total protein intake was due to animal protein, vegetable protein remaining constant. Almost all of the increase in adequacy of total calories was due to increasing fat intakes, relatively much less to carbohydrate, and this only among the poor families. In this population, as more money becomes available to purchase food, there is an increase in animal protein and fat intakes, over an almost constant vegetable protein and carbohydrate intake. There is a simultaneous increase in consumption of fruits and vegetables, accounting for increases in the carotene and vitamin C intakes.

Prognostic assessment of survivors of ventricular tachycardia and ventricular fibrillation with ambulatory monitoring.

The ability to assess prognosis in patients with serious ventricular arrhythmias treated with antiarrhythmic drugs by the degree of complexity on the 24-hour ambulatory electrocardiogram was evaluated in 59 survivors of ventricular tachycardia (VT) and ventricular fibrillation. After conventional therapy had failed, patients were treated with investigational drugs until symptomatic VT was abolished. A Holter monitor recording, obtained once the therapeutic regimen was established, was graded for the presence or absence of asymptomatic VT. Fifty-two patients were asymptomatic at discharge and were followed for 700 days. Of 44 patients followed for 1 year, none had recurrent syncope or died if asymptomatic VT was absent at 1 month (p less than 0.002). After 700 days, 27 patients (82%) without asymptomatic VT at 1 month were doing well, compared with 11 patients (58%) with asymptomatic VT at 1 month (p less than 0.002). In patients at risk for sudden cardiac arrest, early abolition of asymptomatic VT on ambulatory monitoring can be used to predict a good long-term clinical response.

Predictors of survival after tricuspid valve surgery.

The long-term survival rate of 74 consecutive patients who underwent multiple cardiac valve surgery including tricuspid valve surgery was analyzed to identify predictive preoperative clinical variables. Univariate analysis revealed that male sex (P less than 0.04), symptoms of New York Heart Association functional class IV heart failure (p less than 0.004), ascites or pulmonary edema (p less than 0.01), high preoperative bilirubin level (p less than 0.012), mean pulmonary artery pressure greater than 40 mm Hg (p less than 0.038) and pulmonary vascular resistance greater than 6 Wood units (p less than 0.02) were each associated with an increased risk of death after surgery. Stepwise multivariate analysis indicated that severity of preoperative edema and mean pulmonary artery pressure were the most predictive combination of independent variables. These 2 variables were used to calculate an estimated probability of 1-year survival after surgery for patients with multivalvular cardiac decompensation. Recognition of these preoperative variables should assist the clinician in determining the risk of surgical intervention.

Identification of patients at high risk for complications of intraaortic balloon counterpulsation: a multivariate risk factor analysis.

Risk factors for vascular complications of intraaortic balloon (IAB) counterpulsation were evaluated in 206 consecutive patients. The approach was percutaneous in 105 patients and surgical cutdown in 101. Vascular complications occurred in 42 patients, and of these 21 required surgery. Multivariate analysis demonstrated the following major risk factors for vascular complications: preexisting peripheral vascular disease (PVD) defined as a history of claudication, femoral bruit or absent pedal pulse (p less than 0.01); and the use of the percutaneous approach (p = 0.02). Evidence of PVD was particularly predictive of major vascular complications requiring surgery (p less than 0.01). In patients with evidence of previous PVD, the risk for a major vascular complication was 31% with the percutaneous, and 16% with the surgical cutdown approach. Without PVD, the risk for a major vascular complication was 4 times higher in women (15%) than in men (3.5%), but in the presence of PVD gender had no significant effect (p = 0.03). Age, duration of IAB counterpulsation and indication for insertion were not significant risk factors. It is concluded that (1) without previous PVD, women are at greater risk than men for major vascular complications (due to smaller arterial size); and (2) evidence of previous PVD identifies patients at high risk for major vascular complications with IAB counterpulsation, particularly by way of the percutaneous approach.

The development of catecholaminergic innervation in chick spinal cord.

This combined biochemical and histofluorescent study of the embryonic chick was designed to investigate the temporal and spatial development of noradrenergic pathways in the spinal cord. The sequence of catecholaminergic innervation was analyzed by measuring the specific uptake of [3H]norepinephrine, the levels of endogenous norepinephrine, and the distribution of catecholamine histofluorescence. Uptake studies showed early axons present in all levels of spinal cord by 10 days incubation with subsequent increases of uptake activity appearing in a rostrocaudal fashion. Endogenous norepinephrine values were low until day 14, at which time transmitter levels began to increase, approaching hatched values on incubation day 17. Morphologic studies demonstrated catecholaminergic terminals first in the intermediate gray matter and later concentrated in the ventral and dorsal horns. These observations were interpreted to indicate that: (1) noradrenergic axons are an early descending supraspinal pathway; (2) arborization of this system occurs in a rostral-caudal sequence; and (3) monoaminergic uptake mechanisms develop prior to and independent of neurotransmitter synthesis and storage. The development of this noradrenergic system parallels alteration in spinal cord physiology and refinements in the motility of the embryo.

Evaluation of functional sensation in the hand.

The ability to predict hand function based upon the degree of sensory impairment is required in determining disability rating, evaluating patients for reconstructive surgery, measuring end results of nerve repairs, and following peripheral neuropathies. The present study evaluated the ability of four tests of sensibility to predict hand function. It was found that the moving two-point discrimination test best correlated with the patient's ability to identify objects with the fingertips, p less than 0.001. The time required for object recognition correlated best with the static two-point discrimination test, p less than 0.001. This study also suggests that the most precise prediction of functional sensation in the hand requires the combined use of both these tests.

Rabbit carotid sinus reflex under pentobarbital, urethan, and chloralose anesthesia.

To determine the effects of different anesthesias on the performance of the arterial baro-reflex, the open-loop characteristic of the carotid sinus reflex was analyzed in 24 rabbits under anesthesia with pentobarbital (30 mg/kg), urethan (800 mg/kg), alpha-chloralose (80 mg/kg), or a mixture of alpha-chloralose (40 mg/kg) and urethan (0.4 g/kg). For each rabbit and anesthesia, mean systemic arterial pressure and heart rate were measured as carotid sinus pressure was changed in 10-mmHg steps between 40 and 150 mmHg. This set of measurements was repeated four times at 1-h intervals. A logistic function curve was fitted to the carotid sinus pressure-arterial pressure relationship. The parameters of this curve were then analyzed to delineate the specific effects of the anesthesias on the relationship. The main finding was that the response range and the slope parameters under alpha-chloralose anesthesia were significantly smaller than those obtained under the other anesthesias. Propylene glycol, used as the solvent for chloralose, did not affect the reflex control of arterial pressure or heart rate. The reflex under chloralose-urethan anesthesia showed characteristics similar to those under urethan anesthesia. We conclude that although alpha-chloralose has traditionally been used in the dog to obtain strong reflex responses, it weakens the reflex control of arterial pressure in the rabbit.

The effect of right ventricular filling on the pressure-volume relationship of ejecting canine left ventricle.

Acute shifts in the pressure-volume relationship of the left ventricle occur under several conditions. One potential mechanism for this phenomenon is ventricular interdependence, that is, the influence of right ventricular filling on the left ventricle. This mechanism was studied in an isolated cross-circulated ejecting canine heart preparation with balloons sewn into both right and left ventricles and connected to volumetric chambers allowing continuous and accurate simultaneous measurement of right and left ventricular pressures and volume. Sets of left ventricular pressure-volume loops were obtained under a variety of right ventricular volumes. Experiments were repeated with and without the pericardium. Both diastole and systole were studied. We show that in the pericardium-free heart working over a normal range of volumes, the right ventricle exerts little influence on left ventricular pressure. With the pericardium present, there is a small but significant effect of right ventricular volume on left ventricular pressure during systole and diastole. Over a wider range of volumes imposed in the arrested heart, the right ventricle does influence left ventricular pressure even without the pericardium. Thus we have demonstrated that ventricular interdependence is not likely to lead to large acute pressure-volume shifts, either during diastole or systole, except in the presence of considerably above normal right ventricular volumes.

Age-associated alterations in viscoelastic properties of canine aortic strips.

Many studies have delineated the changes in the elastic properties of arterial tissue as a function of age. Despite the fact that viscoelasticity is a prominent feature of these tissues, there is little information or characterization of age-associated changes in viscoelastic properties, over a wide range of smooth muscle activation, particularly in nonhuman tissue where atherosclerosis is not a confounding factor. In the present study, using small sinusoidal length perturbations, we determined the dynamic stiffness properties across a wide range of lengths (stretch ratios from 100 to 135%) and frequencies (from 0.25 to 35 Hz) in strips excised from ascending and descending aortas from six young (2 to 4-year-old) and 12 senescent (10- to 13-year-old) beagles. Studies were performed with the smooth muscle fully activated with calcium and norepinephrine, as well as fully inactivated with cyanide, iodoacetate, and dinitrophenol. There was a cubic nonlinear dependence of stiffness modulus on length only in senescent tissue and, surprisingly, little frequency dependence in tissue of either age. Compared to the young aortas, the three-dimensional surface representing the dependence of stiffness modulus on length and frequency from both the ascending and descending regions of aged aortas was displaced higher on the stiffness axis both with the muscle fully activated and inactivated. This age difference was accentuated at longer lengths. The phase lag between force and length was greater in the young vs. the old strips only in the activated, ascending aortic tissue. We found no age differences in the content of elastin, collagen, or in the collagen/elastin ratio, to account for these mechanical property differences.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship of specific coronary lesions and regional left ventricular dysfunction to prognosis in survivors of sudden cardiac death.

We prospectively evaluated the relationship of specific coronary arterial and left ventricular segments to subsequent clinical outcome in 80 persons who were survivors of sudden cardiac death and had failed conventional antiarrhythmic therapy. There were 68 men and 12 women with an average age of 51 years who were treated with investigational antiarrhythmic agents, rendered asymptomatic, and followed for 16 +/- 14 (SD) months. At the end of the study 48 patients (60%) were alive and asymptomatic while 32 (40%) had experienced either recurrent syncope (five) or sudden cardiac death (27). The independent relationship of clinical and angiographic variables was performed in a univariate fashion using a Kaplan-Meier survival analysis and then multivariate logistic analysis was used to simultaneously consider all clinical and arteriographic variables. The results reconfirmed the importance of ejection fraction and left ventricular filling pressure on outcome. However, coronary arterial and left ventricular segmental analyses provided additional predictive power. Specifically, the survival outcome was found to be inversely related to the degree of proximal left anterior coronary (LAD) arterial narrowing: at 1 year 90% of patients with minimal LAD narrowing were alive/asymptomatic in contrast with 70% who had partial and 40% who had complete proximal LAD obstruction (p less than 0.005). Analysis of the posterobasal left ventricular segment wall motion demonstrated that 100% of patients with minimal dysfunction were alive/asymptomatic at 1 year, whereas only 52% of patients with severe dysfunction were alive (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Interaction of canine carotid sinus and aortic arch baroreflexes in the control of total peripheral resistance.

Interaction of carotid sinus and aortic arch reflex control of total peripheral resistance was studied in eight dogs anesthetized with sodium pentobarbital and placed on constant flow cardiac bypass. Carotid sinus and aortic arch baroreceptor areas were isolated and separately perfused at controlled pressures. Combinations of carotid sinus and aortic arch pressures were delivered at random in steps of 25 mm Hg over the 50-225 mm Hg pressure range, and systemic arterial pressure was measured. Changes in arterial pressure reflected changes in total peripheral resistance. A multiple linear regression showed that both carotid sinus and aortic arch pressures exhibited a sigmoidal relationship with arterial pressure. Independent of carotid and aortic baroreceptor pressures, arterial pressure was found to be a periodic function of time (period = 2 hours) in all dogs. The average carotid sinus reflex open loop gain was found to be 0.231 +/- 0.092, while average aortic arch open loop gain was 0.141 +/- 0.088. The gain of either the carotid sinus or aortic arch reflex was not influenced by the absolute pressure level of the other receptor area. In a separate series of experiments performed in the same dogs, we tested the hypothesis that a nonlinear temporal summation of the reflex control of total peripheral resistance might exist when the inputs to carotid and aortic baroreceptors are changed simultaneously. With both inputs held at the region of maximum gain, 25 mm Hg step changes were imposed first on carotid sinus pressure, then on aortic arch pressure, and then on both simultaneously. A temporal inhibition of the two reflexes showed that simultaneous excitation of both receptors resulted in a smaller reflex response than the sum of individual responses.

Absence of increasing incidence of meningitis caused by Haemophilus influenza type b.

An epidemiologic survey of meningitis caused by Haemophilus influenzae type b in children aged zero to four years during an 11-year period (January 1965-December 1975) was conducted in the Baltimore, Maryland, metropolitan area to examine recent trends in the incidence of this disease. Cases of H. influenzae meningitis were identified at all 19 hospitals in the city and county of Baltimore and all 41 hospitals in the surrounding area. The population at risk (age, zero to four years) was estimated using yearly birth rates provided by the state of Maryland and U.S. Census information for 1960 and 1970. Yearly age-adjusted incidence was calculated; in contrast to previous studies, there was no significant increase in the annual incidence (range, 12-27; mean, 19.3/100,000 population at risk). Previous reports of recent increases in the incidence of meningitis caused by H. influenzae type b may be due to differences in study techniques.