Electrophysiologic studies in tricuspid atresia.

Five patients with tricuspid atresia underwent His bundle studies with the recording catheter placed close to the mitral valve ring. Right atrial pacing and measurement of the refractory periods were performed in three. The prolonged intraatrial conduction time found in all patients is thought to be caused by a hypertrophied and dilated right atrium with increased internodal distance due to stretching of internodal pathways. The A-H interval was normal in all; the H-V interval was short in three and normal in two. The pattern of left axis deviation in the group with a short H-V interval is thought to be due to early origin of the posterior branches of the left bundle branch from the bundle of His and early activation of the posteroinferior parts of the left ventricle. The pattern of left axis deviation in the group with a normal H-V interval may be related to the previously reported anomalous course of the left bundle. Atrial pacing produced a normal response. The refractory periods were within normal range, suggesting functional integrity of conduction through the atrioventricular node and bundle branches.


Systemic and pulmonary hemodynamic effects of saralasin infusion in hypertension. Predictability of plasma renin status from hemodynamic changes.

Hemodynamic measurements were obtained before and after 30 minutes of saralasin infusion in 26 fasting adults with hypertension (25 men and 1 woman). Nine showed a depressor response with a decrease in mean intaarterial pressure greater than 20 mm Hg. Ten were nonresponders and seven had an agonistic response with an increase in mean arterial pressure of greater than 10 mm Hg. Heart rate, pulmonary arterial and wedge pressures and pulmonary vascular resistance were nearly identical in the three groups and remained unchanged. Cardiac index decreased from a mean of 2.76 +/- 0.14 (standard error of the mean) to 2.48 +/- 0.1 liters/min per m2 in the nonresponders (P less than 0.02) but remained unchanged in the groups with a depressor or an agonistic response. The mean systemic vascular resistance decreased from 2,406 +/- 303 to 1,839 +/- 265 dynes sec/cm5 in the group with a depressor response (P less than 0.001) and increased in nonresponders (less than 0.02) and those with an agonistic response (P less than 0.01). However, regardless of the response of mean arterial pressure, systemic vascular resistance decreased only in the 10 patients with a plasma renin activity greater than 5 ng/ml per hour (8 from the depressor response group and 1 each from the nonresponse and agonistic response groups). It is concluded that (1) classification based soley on the response of aterial pressure to saralasin ignores important hemodynamic changes; (2) the response of cardiac index--no change in the patients with a depressor response and a reduction in nonresponders--suggests that endogenous angiotension II supports cardiac output in these groups; (3) a decrease in systemic vascular resistance is better than  a decrease in mean arteiral pressure as a predictor of the status of the plasma renin activity; and (4) lack of change in pulmonary vascular resistance suggests that endogenous angiotension II plays an insignificant role in maintaining the resistance of the pulmonary vasculature.


Scanning electron microscopy of microcorrosion casts; intracranial and abdominal microvasculature in domestic animals.

The use of methyl methacrylate corrosion casts prepared for portions of the vascular system has made it possible to examine numerous and extensive areas of microscopic structures on a 3-dimensional scale with the scanning electron microscope. By this means we have examined the arterial microvasculature of intracranial vessels among three domestic animal species. In addition, these vessels have been compared with the terminal branches of abdominal arteries in the dog. The results of this study suggest that the sphincteric control mechanisms of the vessels in the two regions may be structurally different from one another. In the case of the intracranial vessels, the terminal portion of the arteriole is continued by a precapillary arteriole composed of a chain-like series of muscular constrictions. This is most suitably described as a precapillary sphincter area, which terminates at the capillary. In the abdominal vessels, the precapillary arteriole is generally followed by a single precapillary sphincter at the origin of the capillary. These morphological characteristics may account, in part, for the difference in response of vessels in these two regions in hypovolemic shock.


Hypertrophy of astroglial processes in the dentate gyrus of the senescent rat.

Quantitative electron microscopic analysis of the supragranular zone of the dentate gyrus molecular layer has shown that the number and volume fraction of profiles of astroglial processes are significantly increased in senescent rat relative to young adults. These ultrastructural modifications, which are not associated with significant age-related changes in the number of astrocytes or in the width of the molecular layer, may result from a formation of new astroglial processes and/or elongation of existing ones. In either case, the increase in the number and volume fraction of astroglial process profiles is an indicator of age-related astroglial hypertrophy. Hypertrophy of astroglial procecesses, which seems to develop with advanced age as a response to partial deafferentation of neurons, may compensate for a decrease in the dendritic volume fraction, thereby preventing changes in the dimensions of the dentate gyrus molecular layer in senescence.


Quantitative morphology and environmental responses of the pineal gland in the collared lemming (Dicrostonyx groenlandicus).

Collared lemmings from Churchill, Manitoba, and their descendants were studied in captivity to define neuroendocrine and related histophsiological characteristics and responses, particularly in relation to photic and temperature conditions. Relatively great pineal size (0.1755 +/- 0.0167 mm3, or 3.08 +/- 0.30 = pineal volume in mm3 X 10(3)/body weight in gm; N = 16) shown in this arctic rodent is consistent with the suggestion that pineal size and significance may tend to be greater in more northern (higher latitude) species. Total number of nucleated cells per pineal averaged 137,000 +/- 10,500. Pinealocytes (105,000 +/- 8,700/pineal) and other cell types were present in relative numbers typical of mammalian pineal glands, and were not numerically correlated with age, sex, or location or circumstances of birth and early postnatal life. Chronic exposure to warmer (21-27 degrees C) in comparison with colder (-9 to -6 degrees C) environments, whatever the illumination, led to greater pinealocyte activity, as shown especially by nucleolar diameter, throughout most of the nine regions of the organ analyzed cytologically (all regions combined: P less than 0.001). Increased pinealocyte activity in chronic darkness was suggested by similar evidence (P less than 0.01), but in comparison with the thermal effects, was less marked and more variable in different regions of the organ. These and other findings of this study indicate that the Dicrostonyx pineal organ is morphologically unique, relatively large in size, and cytologically responsive to environmental conditions.


Morphological development of the epithelium of the embryonic chick intestine in culture: influence of thyroxine and hydrocortisone.

A culture system with defined medium has been utilized to elucidate the role of thyroxine (T4) and hydrocortisone (HC) in growth and differentiation of the epithelium of embryonic chick duodenum during the third week of development. Duodenal explants maintained a basically normal morphology for 48 to 72 hours, but during subsequent culture, muscle and mesenchyme deteriorated, previllous ridges shrank, the epithelial surface became pitted, and the tissue lost weight. These degenerative processes were retarded by addition of HC to the culture medium. Previllous ridges of cultured duodenum failed to develop into true villi and ridge growth was subnormal. Epithelial mitotic counts were increased by T4 or HC, as compared to cultured control tissue, but dropped below values in vivo, by 72 hours in culture. Epithelial differentiation proceeded more rapidly in duodenum cultured without hormones than in vivo. Increase in cell height, flattening of the epithelial surface, attainment of uniform staining of the brush border with periodic acid-Schiff, increase in microvillar density, and formation of a terminal web were accelerated by 24 to 48 hours in culture. In the presence of T4, cell height and microvillar growth were stimulated further, reaching the state found at 19 to 21 days in vivo.


Developemnt of the human optic disc: light microscopy.

Human embryonic and fetal optic discs were studied in semi thin sections stained with silver and toned with gold, in a series ranging from 7 to 21 weeks of gestation. The observations suggest that Bergmeister's papilla forms by proliferation of glial cells in the optic disc rather than by sequestration of retinal glia by axons growing through the region. A possible stimulus for such a glial proliferation is hypothesized to be traction on the anterior face of the disc exerted through the primary vitreous. The formation of the glial sheath of the hyaloid artery also appears to be a consequence of traction from the primary vitreous.


Shunting in intracranial microvasculature demonstrated by SEM of corrosion-casts.

The use of methyl methacrylate corrosion-casts has made it possible to examine the intracranial microvasculature on a three-dimensional scale with the scanning electron microscope. By this means we have compared regions of four cerebral and cerebellar arteries among three domestic animal species. The results of this study suggest that there are from one to three different levels of interarteriolar anastomosis between branches of the same or adjacent vessels. In the horse and ox anastomoses were demonstrated (1) at the level of the precapillary arterioles, (2) along the arterioles, and (3) between small pial arteries. In the dog only the first-named anastomoses were evident in this study. These morphological characteristics may explain in part, the shunting mechanism by which hypoxia may be reduced among intracranial capillary networks.


The effects of continuous direct current on the growth of the antler.

The long-term application of low levels of cathodal direct current to the growing deer antler produced abnormal branching patterns and antlers which grew in atypical directions. The experimental antlers were significantly reduced in length when compared to control antlers.


A relationship between crude fiber and digestibility of wheat milling fractions in rats.

Rat feeding studies were used to measure the dietary fiber content of wheat milling fractions, white and whole wheat breads, and wheat-based breakfast foods. Straight line correlations were established for the relationships between dietary fiber (y) and crude fiber (x) where y = 4.17x--0.27 (r = 0.997, P less than 0.01). Dietary fiber values ranged from 1.1% (flour) to 53.4% (bran), dry weight basis.


The nutritional and metabolic effects of a carbohydrate-rich diet in a glycogen supercompensation training regimen.

It has been suggested that glycogen depletion followed by a protein-fat diet and a carbohydrate-rich diet improves performance. This study was designed to determine the nutritional and metabolic effects of a carbohydrate-rich diet in a glycogen supercompensation training regimen. Four male subjects participated in a 5-week protocol of which the first 3 weeks were devoted to a control period and the last 2 weeks to the experimental phase of the study. The variables measured before, during, and following the experimental phase included anthropometric and basal metabolic rate measurements, urinary and serum analysis for vitamins, SMA 12/60 blood profile and aerobic performance (VO2max). Results indicated an appreciable modification of the metabolic and nutritional profile of the subjects as a result of the diets. During the protein-fat diet there was a decrease in serum glucose and resting respiratory quotient and an increase in cholesterol, blood urea nitrogen, riboflavin, and N1-methylnicotinamide excretion. Subsequent to the carbohydrate-rich diet there was an increase in triglycerides and vitamin C, riboflavin, and thiamin excretion while there was a decrease in serum blood urea nitrogen, and N1-methylnicotinamide excretion. Aerobic performance was slightly decreased and the mean postexercise lactate levels were slightly higher after the carbohydrate-rich diet. It was hypothesized that the reduced niacin intake during the carohydrate-rich diet may hamper the aerobic oxidative pathways.


Effect of a high protein (meat) intake on calcium metabolism in man.

The effect of a high protein (meat) intake of 2 g/kg on the calcium excretions and retention and on the intestinal calcium absorption was studied in man. In the control study the protein intake averaged 1 g/kg. The studies were carried out during a low calcium intake of 200 mg/day and a normal calcium intake of 800 mg/day. Two additional studies were carried out during a calcium intake of 1100 mg/day and one during a 2000 mg calcium intake. During the high protein-low calcium intake and during the 800 mg calcium intake the urinary calcium did not significantly increase. It increased moderately in two studies during the higher calcium intakes, however, these excretions decreased with time to control levels. The lack of a significant increase of the urinary calcium in the majority of the studies is probably due to the higher phosphorus content of the high protein intake. The calcium absorption, determined with 47Ca, the fecal calcium and calcium balances did not differ significantly during the high protein intake. In studies carried out during a low protein (meat) intake of 0.5 g/kg the urinary calcium changed little and the fecal calcium, the 47Ca absorption, and the calcium balance remained unchanged.


Nutritional status of elderly residents in Missouri.

Nutritional assessment of white persons over 59 who participated in the 1973 Missouri Nutrition Survey was based upon biochemical measurements, dietary intakes using food frequency histories, anthropometric measurements, and a dental examination. There were three major nutritionally related problems: poor dental health, obesity, and anemia. The mean for DMF, periodental index, and oral hygiene index for males was 20.5, 4.9, and 3.9, respectively; for females, 17.6, 3.6, and 2.5. Over one-half of both sexes were edentulous. Of the women 59% were greater than 119% of desirable weight compared to 22% of the men. Using guidelines from the Ten-State Nutrition Survey, the following percentages of men had low blood levels: 20, hemoglobin and serum iron; 2, plasma vitamin A; 6, plasma carotene; 1, serum vitamin C; and 0, serum albumin. The percent of women with low biochemical levels were: 11, hemoglobin; 10, serum iron; 7, plasma vitamin A; 1, serum vitamin C; and 2, serum albumin. None of the subjects had low or deficient levels of erythrocyte glutathione reductase. One-half of the women compared to one-fifth of the men had consumed diets with one or more nutrients below 67% of the 1974 Recommended Dietary Allowances.


Comparison of the conventional lecture method and the self-instruction method for teaching clinical pathology.

Two separate courses in clinical pathology were presented to two groups of second-year medical students. The first (large) group was taught by the conventional lecture method; the other (small) group, by a self-instructional method for roughly half of the course, followed by the conventional lecture method for the second half of the course. The effectivenesses of the two methods were compared, based on performances on the final written examination. It was found that the self-instructional method was as effective as the conventional method in teaching clinical pathology, at least in teaching basic principles and interpretive clinical chemistry, as judged by the performances of the two groups. Surprisingly, the two groups differed significantly in performances on the portion of the course taught by similar methods.


Population screening for beta-thalassemia minor. Report of cooperative trials based on two approaches.

In a cooperative intrastate program based upon experience with sickle-cell anemia screening, the authors explored the feasibility of applying hemoglobin electrophoresis for detection of beta-thalassemia gene carriers. Initially, blood samples collected in capillary tubes were analyzed by cellulose acetate electrophoresis with densitometric quantitation of hemoglobin A2 (Hb A2), followed by selective spectrophotometric quantitation. This approach proved insufficiently specific or reproducible. Follow-up hematologic and family studies of presumptive beta-thalassemia gene carriers indicated that coordinate measurement of erythrocytic indices and Hb A2 values would have discriminated a subpopulation with a high incidence of beta-thalassemia trait more specifically. This approach was tested prospectively by the use of 731 venous blood samples collected in a county with a large population of Mediterranean ancestry. Of 31 individuals (4.2%) with presumptive thalassemia trait, 13 returned for a repeat testing, and the initial results for 11 were confirmed. These findings lend support to an empirical screening sequence suggested by Pearson (erythrocytic indices followed by Hb A2 quantitation), but they also indicate that a significant subpopulation of beta-thalassemia gene carriers with limited phenotypic expression may elude detection in any single-pass approach.


The value of the bone-marrow biopsy in the diagnosis of hairy cell leukemia.

Twenty-six patients with hairy cell leukemia have been evaluated clinically at Stanford University Medical Center and the M. D. Anderson Hospital and Tumor Institute since 1973. Only four patients had obvious leukemia and readily identifiable hairy cells in the peripheral blood. The remaining patients were pancytopenic, and hairy cells in peripheral blood were difficult to recognize. In 20 of the latter patients the marrow aspirates were unsuccessful or nondiagnostic. Bone-marrow biopsy was the primary method of diagnosis in 18 cases and proved the most reliable and pertinent diagnostic procedure in identifying this disorder. A well-defined water-clear rim of cytoplasm surrounding and separating the hairy cell nuclei was the main histologic feature, in contrast to the lack of visible cytoplasm and close appositon of lymphocytes in chronic lymphocytic leukemia or poorly differentiated lymphocytic lymphoma. The uniformity and blandness of the nuclei distinguished hairy cells in tissue sections from the cells of histiocytic lymphoma and acute myeloid leukemia. Awareness of the importance of the histologic appearance of the bone-marrow biopsy in hairy cell leukemia is essential in establishing an accurate diagnosis.


An evaluation of blood smears made by a new method using a spinner and diluted blood.

Blood smears were prepared with the use of a spinner, which rotated with a fixed velocity for a fixed time. All blood samples used for spun smears were diluted with a fixed ratio of buffered isotonic saline solution. Distribution of cells in these smears was found to be random. The average number of cells per unit area was substantially uniform from place to place on the same slide and on multiple slides made with the smae sample. The distribution of leukocytes by type was also iniform. For different blood samples, the average number of cells per unit area in the smears correlated well with the measured cell concentrations per unit volume in the samples for leukocytes, erythrocytes and platelets. Leukocyte differential counts on replicate spun smears using the same bloods also agreed to within the sampling error. They similarly agreed with differential counts on pulled smears made from undiluted samples of the same bloods. With few exceptions, erythrocytic morphology on the spun smears was comparable to that on the good areas of pulled smears made with undiluted samples of the same bloods. Nearly all the spun smears were suitable for both viual and fully automated hematologic examination for leukocytes, erythrocytes, and platelets. This was true over nearly the whole area of each spun slide. In these ways this spinner method makes smears whose consistently high quality is little affected by either the properties of the blood sample or the skill of maker.


Reassessment of the "class" concept of disk susceptibility testing. Cephalothin disks versus minimal inhibitory concentrations with eleven cephalosporins. Am J Clin Pathol 70: 909--913, 1978. Studies were carried out to determine whether susceptibility or resistance to 11 cephalosporins could be predicted reliably from the results of tests with a single cephalothin disk. The cephalosporins were tested with a microdilution technic and with a standardized disk test. Strains susceptible to a cephalothin disk were predictably susceptible to all other cephalosporins. However, 2--12% of the strains were resistant to cephalothin disks but were susceptible to the more active parenteral drugs cefoxitin, cephamandole, cefuroxime, and BL-S786. Because of differences in antimicrobial activities, the cephalosporins could be divided into three subgroups for purposes of susceptibility testing: one subgroup includes the majority of cephalosporins and may be represented by tests with cephalothin, the second subgroup inclues three active parenteral drugs (cephamandole, cefuroxime, and BL-S786) and may be represented by tests with cefuroxime, and the third subgroup consists of cefoxitin, a cephamycin with a unique broad spectrum of activity. Until the drugs in the second and third subgroups are released for general therapeutic use, the practice of testing only one cephalosporin disk appears to be a reasonably reliable procedure.


An improved assay method for serum vitamins A and E using fluorometry.

A micromethod for assay of serum vitamins A and E with the use of fluorometry is described. The procedure is a modification of previously described methods eliminating two potentially hazardous reagents, hexane and lithium aluminum hydride, as major components. Comparison with previous methods using n-hexane shows good agreement, as well as satisfactory precision.


Permanent records of microchromatography of hemoglobins.

In the general hematology laboratory, quantitation of hemoglobin A2 by the microchromatographic method is superior to the method of elution from cellulose acetate membranes. A permanent record of microchromatographic patterns for the detection of hemoglobins S and C at birth can be easily obtained by using a photocopying machine and a flat mirror. These copies can be stored for comparison with definitive results when the children are retested at 6 months of age or later.


So-called extraskeletal Ewing's sarcoma. Report of a case with ultrastructural analysis.

The light and the electron microscopic features of an extraskeletal round-cell tumor resembling Ewing's sarcoma are described. Ultrastructural observation revealed features similar to Ewing's sarcoma of bone. Variable agrees of nuclear complexity are described. These soft tissue tumors are probably composed of undifferentiated mesenchymal cells; there is no ultrastructural evidence to indicate the cell of origin.


Microcytic normochromic anemia associated with iron storage by hypernephroma.

A renal-cell carcinoma was discovered and resected in a 38-year-old female patient who had microcytic normochromic anemia. During treatment with ferrous gluconate, the anemia regressed temporarily but reappeared with the onset of metastases to the abdominal lymph nodes. Heavy deposits of hemosiderin were observed in tumor cells in the resected kidney and lymph nodal metastases. It is postulated that the anemia resulted from metabolic diversion and storage of iron by the tumor cells.


Social norms and helping in a community of limited liability.

The social norms constraining interpersonal helping (formal and informal) were studied by the analysis of interviews of 348 persons in the Chicago area. The findings showed that only half the respondents who received help from family and friends believed that they had a right to such help. Three-fourths of those persons receiving help from professional practitioners believed they had a right to such help. There was a definite relationship between the kinds of rights and the kinds of duties reported by those who believed they had such rights and duties. The relationship was significantly different in personal helping among families and friends from what it was in professional helping processes with practitioners.


Help-seeking: a review of the literature.

Help-seeking encompasses a complex set of issues. The present survey appraises the empirical work covering three topics: the people who seek help, the role of the social network in the help-seeking process, and the outcome of the helping interaction. Included are reviews of where people turn for assistance, the type of problems for which they seek help, the kind of aid provided, and conditions influencing satisfaction with help received. Future research directions are presented with special emphasis on implications for effective delivery of services.


Social and psychological correlates of help-seeking behavior among urban adults.

Drawing from a longitudinal survey of 1,106 urban adults aged 20 to 70, the present study investigated whether persons who sought help from informal and/or formal support systems for major troublesome life changes were distinguishable from those who handled problems without assistance in terms of demographic background, personal resources, social networks, or psychological barriers to help-seeking. Generally, nonseekers who felt self-reliant and respondents who sought assistance from informal associates exclusively seemed well prepared to manage bothersome transitions, crises, or role-related strains. Nonseekers who were reluctant to ask for assistance as well as help-seekers who only contacted professionals were comparatively more at risk.


The relationship of life event interpretations to helping interactions: a case study.

When people seek help for a stressful event, they believe they lack the necessary resources to cope with the event; therefore, they seek those resources. Before deciding which resources are necessary, they must first assign meaning to the event. That meaning affects the helping interaction--the resources sought, helper selected, and relationship with the helper. One case was selected to illustrate the nature of the relationship between the interpretation of a stressful event and the subsequent helping interaction. The discussion of the case focuses on: (a) an illustration of substitution and modeling processes; (b) the desirability dimension as applicable to the prospect, process, and outcome of an event; (c) the function of intimacy in the resolution of a problem event, and (d) the reinterpretation of an event at critical points between the event's occurrence and its resolution.


Seeking help for parental concerns in the middle years.

This study focuses on a single problem--parents' concerns about their late adolescent and adult children--and traces the decision to seek assistance from the parental concerns which prompt it to the relief which may follow it. The extent of parents' concerns about their 16- to 35-year-old children was strongest when the family was in the midst of launching and the oldest child was 21 to 25. While parents reporting more concerns were more likely to be distressed, parental distress also differed by sex and parental optimism, especially at earlier family stages. Women and more pessimistic parents were more distressed. At later stages, these had little impact. Among help seekers, greater distress was associated with lesser use of family members and greater use of formal helpers. Parents with a strong sense of personal mastery were more likely to use formal helpers, particularly where lower income would otherwise predispose against use of formal help. Kind of help received rather than choice of helper was the strongest contributor to reported relief.


Does help help? The adaptive consequences of obtaining help from professionals and social networks.

This study reports on a longitudinal analysis of changes in adaptation associated with seeking help on a representative sample of Chicago area adults who had experienced one of three transitions or four crises during the interval between 1972 and follow-up 1976--77 interviews. For each event, respondents are classified into three groups according to their help-seeking behavior: those who went to professionals, those who went only to their social networks, and those who had the event but sought no help. Nine measures of adaptation are used: symptoms of anxiety and depression and strains and stresses in four role areas. Statistical controls equate the groups on demographic characteristics, perceived stress, personal resources, access to help, and elapsed time since the event. There are no consistent statistical significant differences among the groups. No evidence is found that help-seeking has positive adaptive consequences. The findings are not likely to result from an inadequate sample, outcome measures, or statistical controls, but could result from insufficient information on the kind, quality, and duration of the help provided.


Ventilatory lung function studies in Pacific Island Micronesians.

In the first study of ventilatory lung function in people of the Micronesian race, observations in 182 normal subjects (117 males and 65 females) between the ages of 15 and 80 years were used to calculate regression equations for FVC, FEV1, and FEV1%. Mean values of FVC and FEV1 were found to be lower than those reported for Caucasians and Polynesians, but similar to Melanesians, Negroes and Chinese. Values of FEV1% were comparable among all races. The three Oceanic races showed a smaller reduction of FVC and a larger reduction of FEV1% with increasing age than did Caucasians. Although the biological significance of this variability of ventilatory function in different races is uncertain, the definition of racial norms is already proving useful in studies of pulmonary airway disease among Oceanic peoples.


Relationship of oxygen uptake capacity, serum uric acid and glucose tolerance in males and females, age 10-69.

Age 10-69, 793 males and 80 females were tested on the treadmill as they walked at 4.83 km per hour (3.27 km per hour in subjects 60 years and older). Every three minutes, the grade was increased 3%. Maximal oxygen uptake (VO2max.) and related measurements were recorded during the third minute at each grade. Subjects age 10-39 exercised to exhaustion and VO2max. was measured. In subjects age 40-69, VO2max. was estimated from sub-maximal VO2 and heart rate. The sum of four skinfolds, serum uric acid (SUA) and one-hour glucose tolerance were also measured on these subjects. Body fatness was positively correlated with SUA and blood glucose and negatively correlated with VO2max. Age was negatively correlated with VO2max. and positively correlated with blood glucose. After removing the effects of age, weight and fatness, the correlation of VO2max. and SUA was low. Similarly, there was little or no correlation between VO2max. and blood glucose after the effects of age, weight and fatness were removed.


Chronic disease in former college students. XVII. Sociocultural mobility as a precursor of coronary heart disease and hypertension.

The relationship between sociocultural mobility and subsequent coronary heart disease (CHD) and hypertension (HT) was studied in a cohort of 13,728 male former Harvard University students examined in 1939-1950. All 13,728 were followed for CHD mortality, while 8852 returned self-administered mail questionnaires in 1962 or 1966 and in 1972 which queried for doctor-diagnosed myocardial infarction (MI), angina pectoris (AP) and HT. For each of 98 cases of fatal CHD, 78 cases of MI and 48 cases of AP, four controls were randomly selected. One control was selected for each of 319 HT cases. Significant negative associations between father's occupational status and risk of combined fatal CHD and MI and between geographic mobility and risk of HT were noted in univariate analysis. These associations persisted with stratification by individual confounding factors and by a multivariate confounder-summarizing score. Intergenerational mobility, as indicated by occupational status of the father, was associated with a 1.5 times increased risk of fatal CHD and MI. Intragenerational geographic mobility was associated with a slightly reduced risk of HT.


Estimation of multiple relative risk functions in matched case-control studies.

A linear logistic model used to estimate multiple risk functions in both cohort and case-control studies is adapted for sampling plans wherein each case is matched with R controls. The resulting methodology substantially liberalizes current practice by permitting simultaneous analysis of multiple discrete and continuous risk factors. Interactions among risk factors, and between risk factors and matching variables, may be explored. Data from two studies of oesophageal cancer, one conducted among Singapore Chinese and the other on the Caspian littoral of Iran, illustrate the methods.


Erythema chronicum migrans and Lyme arthritis: epidemiologic evidence for a tick vector.

Forty-three residents of 12 contiguous Connecticut communities were identified who had the onset of erythema chronicum migrans, Lyme arthritis, or both during the summer and fall of 1977. Nine of them (21%) remembered having been bitten by a tick at the site of the initial skin lesion a median of 12 days (range 3-20) before onset; one patient brought in the tick for identification (Ixodes scapularis). Compared to 64 of their neighbors, significantly more patients had cats and farm animals, and had noted ticks on their pets and tick bites on themselves. The incidence of the illness during 1977 was 2.8 cases per 1000 residents in the three communities on the east side of the Connecticut River, compared to 0.1 cases per 1000 residents in the nine communities on the west side, a difference of almost 30-fold. Taken with the results of a concomitant acarological study on both sides of the river, these findings support the hypothesis that erythema chronicum migrans and Lyme arthritis are tick-transmitted, specifically by I. scapularis.


Erythema chronicum migrans and lyme arthritis: field study of ticks.

Ticks were collected during 1977 in communities east of the Connecticut River where there was a high incidence of erythema chronicum migrans and Lyme arthritis and were compared with collections from a similar area 20 km west of the river where cases of the disease were rare. Ixodes scapularis was much more abundant on the east side than on the west. Immature I. scapularis were 13 times more abundant on white-footed mice (Peromyscus leucopus), and adult I. scapularis 16 times more abundant on white-tailed deer (Odocoileus virginianus) in the east than in the west communities. In addition, all active stages in the life cycle of this tick--larvae, nymphs, and adults--both males and females, were found on humans (mostly patients) in the east communities. Both nymphs and adults were abundant on dogs and cats in this area. Attempts to recover an etiologic agent from ticks were unsuccessful.


Cardiovascular mortality in Mormons and non-Mormons in Utah, 1969--1971.

Cardiovascular mortality in the State of Utah is among the lowest in the United States. The religion of 72% of the state residents (Mormon) proscribes the use of tobacco and alcohol; a large number of Mormons adhere to this proscription. This study analyzed the 6108 cardiovascular disease deaths between 1969--1971 in Utah of members in the Mormon Church. For both sexes, Mormons had 35% less mortality than expected from US rates for ischemic heart disease, while non-Mormons were not significantly different from US whites. These results support the relationship between cigarette smoking and mortality from cardiovascular disease. Mormon men also had lower mortality from hypertensive heart disease and Mormon women from rheumatic heart disease than non-Mormons in Utah.


Differences between respondents and non-respondents in a population-based cardiovascular disease study.

The differences in cardiovascular health status between participants and non-participants were examined in a population-based cardiovascular study. Telephone interviews with non-respondents revealed generally more cardiovascular disease but less hyperlipidemia and family history of cardiovascular disease. Non-respondents did not differ regarding known hypertension, diet or drug therapy for hyperlipidemia, or egg use. Non-respondents were more likely to be cigarette smokers. Because the amount of non-respondent bias in the study was small while the response rate was high, respondents were generally representative of the target population. However, the observed differences could have produced spuriously high estimates of risk factor prevalence, low estimates of disease prevalence, and biased relative risks if the non-response rate and/or the baseline differences had been considerably larger.


Noncancer deaths in cancer and noncancer lineages.

Starting with white probands who were potential milk donors in a program of human milk collection, a series of 2411 family health histories were obtained of the first degree relatives of the probands' parents. A lineage is defined as the parents and siblings of a parent of the proband as well as the parent. 2090 cancers were identified in the 31,939 people. Of the 21,712 persons without cancer in the parents' generation, age-specific death rates were significantly higher in those lineages with at least one cancer. This was true in infants, children and adults for both males and females (p less than 0.001). Cancer may be linked to other morbid conditions by a commonality of heredity, family environment, or perhaps both as necessary antecedents--neither sufficient by itself.


Emergence of a new arbovirus disease in Brazil. II. Epidemiologic studies on 1975 epidemic.

In April, 1975, an outbreak of human encephalitis caused by Rocio virus, a new flavivirus, occurred in the coastal region of southern São Paulo, Brazil. The epidemic started during the second half of March, 1975, and ended in June, 1975. A total of 465 cases with 61 deaths were recorded, and the overall attack rate was 15 per thousand population. The mortality rate was two per thousand inhabitants and the overall case-fatality rate was 13%. However, the case-fatality rate was markedly decreased when adequate hospital care was provided. The number of cases in the 15--30 years age group was higher than in the other age groups and the rate was higher in males than in females. Lack of evidence of person-to-person transmission, based on a study of families involved in the epidemic and on the antigenic relationship to other mosquito-borne flaviviruses, suggested that the virus was transmitted by a vector and that wild animals were involved in the virus cycle.


The use of logistic regression for modelling risk factors: with application to non-melanoma skin cancer.

Logistic regression was used to estimate the "relative" risk of basal and squamous skin cancer for such factors as cumulative lifetime solar exposure, age, complexion, and tannability. In previous reports, a subject's exposure was estimated indirectly, by latitude, or by the number of sun days in a subject's habitat. In contrast, these results are based on interview data gathered for each subject. A relatively new technique was used to estimate "relative" risk by controlling for confounding and testing for effect modification. A linear effect for the "relative" risk of cancer versus exposure was found. Tannability was shown to be a more important risk factor than complexion. This result is consistent with the work of Silverstone and Searle.


Case-control studies: a sequential approach.

A sequential approach to the design of a matched pair case-control study is proposed as an alternative to fixed sample plans when information on case-control pairs is acquired sequentially in time. The method described is that of Wald using the Sequential Probability Ratio Test (SPRT) for comparing two binomial populations. The test is an open, non-truncated procudure. Several tables are presented for the average sample numbers needed under the sequential plan and fixed sample plan for selected Type 1 and 2 errors, alternative relative risks of interest and exposure probabilities in case and controls. A hypothetical example is presented to illustrate the use of the method and discussion is given as to the possible advantages and disadvantages of the sequential approach to case-control studies.


The number of families required for detecting the familial aggregation of a continuous attribute.

A formula is presented and graphs are displayed that provide the approximate power of a test for intraclass correlation. The results are useful for estimating the number of families required for detecting the familial aggregation of a continuous attribute.


Causes of perinatal mortality excess in prolonged gestations.

The study sought to determine what proportion of the perinatal mortality excess associated with prolonged gestations was due to placental insufficiency. Using data from a large prospective study of pregnancy, the perinatal mortality rate was 20.9/1000 births for post-term and 11.7/1000 for term infants. Only a quarter of the perinatal mortality rate excess in the post-term pregnancies was due to disorders related to inadequate uteroplacental perfusion, i.e., abruptio placentae, large placental infarcts and marked placental growth retardation. Twenty-six per cent of the mortality excess was due to congenital malformations, 19% to amniotic fluid infections, 8% to Rh erythroblastosis fetalis and the remaining 22% to a variety of other disorders. The post-term mortality excess due to congenital malformations was in infants who had hypoplastic adrenal glands, a well-known cause of prolonged gestation. The 4205 placentas of the post-term infants did not show any significant increases in those microscopic lesions that are characteristic of uteroplacental under-perfusion.


Case report. Brucella canis bacteremia: a case with negative B canis agglutinins.

Naturally acquired Brucella canis infection is believed to be uncommon, but is not readily diagnosed. A 55-year-old woman developed fever, abdominal pain, malaise, weakness, and anorexia eight weeks after her dog delivered stillborn pups. Blood cultures yielded B canis. Specific B canis agglutinins were negative initially and remained negative during convalescence. Therapy with tetracycline and streptomycin was successful but was associated with a probable Jarisch-Herxheimer reaction.


Case report. Cardiobacterium hominis: review of prior infections and report of endocarditis on a fascia lata prosthetic heart valve.

The clinical spectrum of disease caused by Cardiobacterium hominis, a small, gram-negative coccobacillus, is little known to physicians. From analysis of a new case of C hominis endocarditis on a fascia lata aortic valve, and from review of all previous reports of infection due to this microorganism, a remarkably consistent clinical picture emerged. C hominis only causes endocarditis, affects middle-aged individuals with structurally abnormal, left-sided cardiac valves, and follows a subacute course associated with the frequent occurrence of mycotic aneurysms and embolic phenomena. The methodology and therapeutic importance of identifying this organism and separating it from the closely related Actinobacillus actinomycetemcomitans, Eikenella corrodens, and Haemophilus aphrophilus is emphasized. Either penicillin alone or penicillin plus an aminoglycoside is recommended for therapy.


Temporal stability of the dark focus of accommodation.

The temporal stability of the dark focus of accommodation (the refractive power of the eye in total darkness) was examined using a laser optometer. It was found that dark focus does not vary greatly in most subjects over a period of 2--3 weeks. Intrasubject ranges varied from 0.08--2.92 over that period, with a mean range of 1.07 D. Theoretical and practical implications of these findings are discussed.


Renin stimulation during clonidine therapy in "low renin" essential hypertension.

Plasma renin activity (PRA) was measured during the administration of clonidine (0.1 mg twice daily) to 11 patients with essential hypertension. After eigth weeks a trend toward an increase in PRA was noted. This increase was significant in "low renin" subjects (less than 1 ng Al/ml/hr, n = 7) in whom PRA (ng/ml/hr +/- SEM) rose from a control value of 0.7 +/- 0.1 to 2.0 +/- 1.1 at one week, 5.6 +/- 2.1 at four weeks, and 4.4 +/- 1.0 at eight weeks (p less than 0.05). In contrast, in a small group of "normal renin" patients (n = 4), PRA did not change significantly but tended to decrease on clonidine therapy from 9.2 +/- 3.4 at control to 3.3 +/- 2.0 at one week, 3.4 +/- 0.6 at four weeks, and 4.7 +/- 1.7 ng Al/ml/hr at eight weeks. Plasma renin substrate and serum and urinary electrolytes did not change significantly in either group and blood pressure reduction was comparable in the two groups. A strong negative correlation (r = -0.84, p less than 0.001) was found between changes in creatinine clearance and changes in PRA. Previous studies have implicated alpha-adrenergic receptors as the site of clonidine actions on blood pressure and renin release. The observed renin stimulation during chronic administration of clonidine to "low renin" patients with essential hypertension may imply an altered intrarenal alpha-receptor function in "low renin" essential hypertension.


Changes in retinal correspondence following surgery for intermittent exotropia.

An intermittent exotrope of 54delta had harmonious anomalous correspondence when squinting and normal correspondence when bifoveally fixating. Measures of the angle of deviation (H) and angle of anomaly (A) were made at the first postoperative dressing 6 hr after surgery (H = 8--14delta esotropia, A = 0--54delta exo) and at several times over a 2.5-mo period during which a second operation was performed. The final result was 3delta of exophoria with normal correspondence when fusing and harmonious anomalous correspondence (A = 3delta exo) when fusion was disrupted. The change in angle of anomaly created by the surgery cannot be explained by changes in fusional vergence. Halldén's "sensory-fusion" mechanism, which is based on diplopia resulting from stimulation of disparate retinal points, is more useful in explaining the obtained results.


Treating infant esotropia: a case report.

A case study is presented of a child who had a constant left esotropia since birth. The patient was first seen at age 8 mo, after an ophthalmological opinion had suggested immediate surgery. The therapy and its success are discussed.


Baroreflex function in uremic and hypertensive man.

Human hypertension has been related to abnormalities of autonomic blood pressure regulation. In order to characterize a possible defect, we have studied several aspects of reflex autonomic circulatory control in normal subjects, patients with primary hypertension, and two types of subjects with uremia and elevated blood pressure. Phenylephrine infusion (a measurement of baroreceptor response to high pressure stimulus) resulted in similar hemodynamic changes in all types of subjects. However, all groups of patients exhibited significantly different hemodynamic responses to amyl nitrite inhalation (an index of baroreceptor response to low pressure stimulus). These results suggest that patients with uremia and those with primary hypertension differ from each other and normal subjects regarding baroreceptor reflex function. Furthermore, one type of uremic patient may have a neurogenic component to their hypertension similar to experimental animals following surgical section of afferent baroreceptor nerves.


Staphylococcal infections in a hemodialysis unit.

Experience with Staphylococcus aureus infections in a hemodialysis unit in which arteriovenous fistulas were used routinely for dialysis is reviewed, including an epidemic involving multiple bacteriophage types. Most infections involved the fistula site and were associated with bacteremia, although bacteremia without an obvious fistula infection did occur. Despite recurrent bacteremia, endocarditis was not documented, and patients did not develop teichoic acid antibodies as measured by an immunodiffusion technique. Patients with fistula infections responded to antibiotic therapy and did not require removal of the fistula except in two patients whose fistulas ruptured. Patients with shunt infections had to have their shunts removed to control infection. The epidemic developed after the hemodialysis unit was moved into a larger area to facilitate an increasing number of patients and after diabetic patients were admitted to the dialysis program. Both autoinfection and cross-infection contributed to the epidemic, which resolved with improvements in aseptic techniques. A culture survey indicated that the nasal carriage of staphylococci was not unusually high during the epidemic. This report emphasizes that staphylococcal infections remain a problem in continually changing hospital environments.


Development of amphotericin B-resistant Candida tropicalis in a patient with defective leukocyte function.

Emergence, during therapy, of fungi resistant to amphotericin B is purportedly rare, as fungi with altered cell membrane ergosterol content are considered too fragile to survive normal host defenses. Progressive amphotericin B resistance arose in a strain of Candida tropicalis isolated repeatedly from the urine of a patient with pyelonephritis. The most resistant isolate (R-2) lacked cell membrane ergosterol, the usual attachment site for amphotericin B, and was not inhibited by greater than 500 micrograms/ml of the drug. R-2 infected and killed embryonated eggs, but was unable to produce progressive renal infection in steroid-treated mice because of a reduced capacity to produce pseudomycelia. Persistent infection of the patient by this altered fungus was attributed to defective leukocyte candidacidal activity, especially marked in autologous serum, and to defective Candida-related cell-mediated immunity. A literature review suggests that amphotericin B resistance may not be as rare as many authorities have indicated. It is apparent that few laboratories routinely monitor fungi for amphotericin B susceptibility. In patients with defective antimicrobial defenses, amphotericin B-resistant fungi may survive, produce progressive infection, and require alternative chemotherapy for eradication.


Clinical implications of the rare thyroid carcinoma which is indistinguishable from a follicular adenoma.

The inadequacy of the standard pathologic criteria for identifying certain well-differentiated thyroid follicular carcinomas from follicular adenomas in rare instances is illustrated by four cases. The excised thyroid nodule in these patients appeared to be adenoma, but subsequent local spread in the neck or distant metastases disclosed the actual malignant nature of the lesions. This observation is not intended as a basis for more extensive operations for adenoma, but rather as an indication for close, long-term observation. Postoperative, lifelong suppressive therapy with thyroid hormone is suggested for all patients with a diagnosis of follicular adenoma.


The immunoglobulin allotypes (Gm and Km) of twelve Indian tribes of Central and South America.

The Gm and Km immunoglobulin allotypes are presented, for the first time, for six South American Indian tribes (Baniwa, Kanamari, Kraho, Makiritare, Panoa, and Ticuna) and one Central American tribe (Guaymi). Additional allotype information is presented for five previously reported South American tribes (Cayapo, Piaroa, Trio, Xavante and Yanomama). The distributions of the Gm and Km allotypes among all the tribal populations tested to date are reviewed and evidence is presented for the presence of a north (high)-south(low) cline in Km frequency. The wave theory of the populating of the South American continent was tested by an examination of the distribution of six alleles (Gmax;g, Gma;b0,3,t,Dia,Rx,TFDChi, and 6PGDC), absent in some populations but with polymorphic proportions in others. The present, limited, data failed to confirm the theory.


Bilateral asymmetry of human skeletal non-metric traits.

The use of non-metric skeletal traits to compute population distance statistics assumes strong genetic control of trait expression. An investigation of bilateral asymmetry frequencies of human cranial and postcranial non-metric traits shows that asymmetry is common. This suggests that environmental stress, as well as the genotype, is important in controlling trait frequencies.


Discrete dental traits in four Tlaxcaltecan Mexican populations.

Seven hundred dental casts from four Tlaxcaltecan Indian populations of Mexico were analyzed for the incidence of ten discrete dental traits. The populations are of known historical origin, with Cuanalan and Saltillo transplanted from the Valley of Tlaxcala approximately 400 years ago. Given this temporal and geographical separation of these transplanted populations from the parental gene pool, statistically significant morphological divergence was observed. However, varying degrees of admixture with Spanish and possibly African colonists have complicated the interpretation of the results. Shovelling of incisors was shown to be the best discriminator of group differences. Mandibular molar patterns and mandibular incisor extension indicate that Cuanalan is closest to Saltillo while the valley communities. Tlaxcala and San Pablo, are closest to each other.


The dentition of New Britain West Nakanai Melanesians. VIII. Peopling of the Pacific.

The dental crown morphology and size of 48 male West Nakanai, New Britain, Melanesians is described and compared with other Pacific and Asian dental samples. The West Nakanai dentition is like those of other Melanesians, much less like those of Polynesians and Micronesians, and very dissimilar to teeth of modern and Neolithic Southeast Asians. It is suggested that the origin of the modern Melanesian dental pattern (large but simplified teeth) was probably in Melanesia, not Southeast Asia as the orthodox view of a Hoabinhian-Australmelanesian relation claims.


Differences between populations in body shape of children and adolescents.

Growth is marked by changes in body shape as well as increase in body size. It is suggested that changes in body shape in childhood and adolescence be analyzed by least squares fit lines for one dimension on a second at successive ages. These are preferred during childhood to the traditional indices of anthropologists because body proportions change with growth, and one can identify the direction of the change and observe which body dimension is changing, or if both are. Furthermore, populations may be compared by analysis of covariance for different patterns of growth related to sex and ethnic groups. Analysis of a number of populations have demonstrated clear differences between the sexes and between populations for the following body proportions: sitting height to leg length, arm length to leg length, biacromial width to biiliac width.


Sexual dimorphism in the growth of the cranium.

The major sexual dimorphisms in body size appear at puberty but, by then, 95% of the growth of the cranium is completed. As sexual dimorphism in the cranium is as great as for other parts of the body, this suggests that it must appear at an earlier age, and that cranium/body size ratios for the two sexes will vary during growth. Results from a longitudinal study of Montreal children are used to investigate this phenomenon. The effect is expressed quantitatively by proportional growth and growth velocity curves, based on the final size of boys, which show that the dimorphism indeed makes an early appearance. The data are also analyzed on an age scale relative to the ages of peak growth velocity in stature, derived from the individual growth curves. This shows that although there is a minor pubertal spurt in growth for the external cranial dimensions of boys, it contributes relatively little to the final dimorphism in cranial size. To summarize this aspect of growth, an index of cephalization is calculated: head length X head width/stature. Cross-sectional standards for the change of the mean index with age show a linear decline for boys and girls until puberty, with a constant difference between them. After puberty, the index becomes equal in the two sexes. Individual development curves for the index are however not linear.


Possible role of gap junctions in activation of myometrium during parturition.

Gap junctions between smooth muscle cells of the myometrium of pregnant rats were found only immediately prior to, during and immediately after parturition by quantitative thin-section and freeze-fracture microscopy. Ovariectomy of 16- to 17-days-pregnant rats resulted in premature termination of pregnancy and the appearance of gap junctions. Methods that prolonged normal pregnancy in rats or maintained pregnancy in ovariectomized animals (progesterone treatment) prevented the appearance of gap junctions. Gap junctions formed in tissues incubated for 24--96 h in vitro without any hormonal influence. We propose that gap junctions are essential for normal labor and delivery for synchronous contraction of the muscle of the uterus. We present a model for control of parturition that may apply to other animals including humans. The model proposes: 1) the possible roles progesterone, prostaglandins, or estrogens may play in initiating gap-junction formation; 2) that the formation of gap junctions is a necessary step in activation of the myometrium leading to labor; and 3) that agents used to stimulate or inhibit labor may do so by affecting gap junctions.


Ionic milieu and control of K permeability in the parotid gland.

The roles of Mg, K, Na, and Cl ions in the biphasic K-permeability response (86Rb release) to receptor activation in the parotid gland were investigated. Both the transient and sustained phases of K release (86Rb release) were unaffected by alterations in Mg concentration. Elevating extracellular K enhanced 86Rb release presumably by decreasing the negativity of the membrane potential. Elevating extracellular K had no effect on the transient or sustained phases of 86Rb release due to carbachol and 1.0 mM Ca. Measurements of responses to carbachol with various substitutes for NaCl suggested that extracellular Cl and ionic strength are important for the K-permeability response. Experiments with LiCl suggested the operation of a Na-Ca exchange similar to that seen earlier in experiments with amylase release. When tetraethylammonium Cl was substituted for NaCl, the cation appeared to block K fluxes directly. Choline Cl, in partial substitution for NaCl, potentiated the sustained phase of response to substance P and, in complete substitution, produced both Ca-dependent and Ca-independent increases in 86Rb release. It was concluded that the 86Rb-release response in relatively (but not completely) insensitive to alteration in the ionic milieu. It was also concluded that Na regulates K permeability in part directly and in part by means of a Na-Ca exchange.


Stimulus-secretion coupling in the rat lacrimal gland.

The role of calcium in stimulus-secretion coupling in the lacrimal gland was investigated. Rat exorbital lacrimal gland slices released peroxidase into the incubation medium after muscarinic or alpha-adrenergic receptor stimulation. In both cases, secretion appeared to involve exocytosis as revealed by electron microscopy. Secretion due to the muscarinic agonist carbachol was inhibited by Ca omission and by lanthanum. Secretion due to the alpha-adrenergic agonist phenylephrine was inhibited by Ca omission at 10(-5) M concentration but not at 10(-4) M concentration. The effects of 10(-4) M phenylephrine could be blocked by lanthanum or by reduction of extracellular Na. Both agonists stimulated 45Ca efflux, but phenylephrine was less efficacious. These results suggest that the agonists may cause exocytosis by stimulating influx of Ca or release of cellular Ca. Sodium may play a role in the Ca-release mechanism.


Relationship of intracellular creatine concentration and uptake to muscle mass in vivo.

Attempts have been made to evaluate the role of intracellular creatine in conditions leading to increased or decreased amounts of contractile protein in rat skeletal muscles. Resting concentrations of intracellular creatine ([Cr]i) and creatine phosphate ([CrP]i) were compared in gastrocnemius and soleus muscles with those immediately after a 20-s tetanic stimulation. The hydrolysis of creatine phosphate was the same after heavily and lightly loaded contractions, suggesting that hypertrophy of isometric exercise is not mediated by creatine. With atrophy after denervation or interruption of sciatic axoplasmic flow [Cr]i also remained unchanged, though [CrP]i and the rate of Cr uptake fell after denervation. The major change in adult red and white muscle bulk with unaltered [Cr]i suggests that the Cr sensitivity found by others in developing muscle in vitro has been supplemented or replaced by other control mechanisms.


Sensitivity of excitable and inexcitable membranes to alpha-dihydrograyanotoxin II.

A variety of excitable and inexcitable preparations have been examined for their sensitivity to the depolarizing action of alpha-dihydrograyanotoxin II. alpha-Dihydrograyanotoxin II was effective in producing membrane depolarization in giant axons from the crayfish (Procambarus clarki) and sartorius muscle fibers from the frog (Rana pipiens) and the salamander (Taricha torosa). The toxin-induced depolarization was reversed by lowering the external sodium concentration. High concentrations of tetrodotoxin and saxitoxin were also effective in reversing the depolarization in the various grayanotoxin-sensitive preparations studied except in the salamander sartorius muscle, in which sodium-dependent action potentials were highly resistant to tetrodotoxin and saxitoxin. In contrast, alpha-dihydrograyanotoxin II was ineffective in changing the resting membrane potential in the muscle fibers of the crayfish (Procambarus clarki and Orconectes virilis) and in the salivary gland giant cells from Drosophila virilis. Of the preparations that were examined, only the membranes that produce a sodium-dependent action potential are sensitive to the depolarizing action of alpha-dihydrograyanotoxin II.


Invaginated membrane in crustacean tonic muscle fibers: estimates of membrane capacitance.

Surface and volume densities of the invaginated membrane components of tonic muscle fibers of crayfish (Orconectes rusticus) were determined by stereological methods. Surface densities of the sarcolemma, sarcolemmal invaginations, T tubules and Z tubules were 2.0, 5.9, 26.3, and 3.3 micron2/100 micron3 of fiber, respectively, and volume densities of the sarcolemmal invaginations, T tubules, and Z tubules were 0.28, 0.29, and 0.08 micron3/100 micron3. The values obtained for surface density show that 95% of the membrane exposed to the extracellular environment is composed of invaginated membrane. Specific membrane capacitance, determined from square-wave pulse analysis and referred to the apparent area of surface sarcolemma, was 30.3 muF/cm2. However, after correction for the extent of invaginated membrane, the specific membrane capacitance was 1.6 muF/cm2.


Mechanism of membrane stabilization by calcium in vascular smooth muscle.

In this study we observed relaxation in helical strips of rat tail artery in response to high concentrations of calcium after contraction induced by 10(-7) g/ml norepinephrine. This action of calcium on vascular smooth muscle contraction is referred to as the "membrane-stabilizing effect" of calcium. The current study demonstrates that changes caused by many of the variables that alter this relaxation induced by calcium parallel changes in relaxation in response to potassium; both are attenuated by ouabain, low sodium, reduced temperature, and low potassium. Relaxation produced by manganese is not similarly affected. Because potassium has been shown to cause relaxation of vascular smooth muscle by increasing the activity of sodium-potassium ATPase, we conclude that the relaxation produced by high concentrations of calcium is dependent on the activity of sodium-potassium ATPase; that produced by manganese is not.


Modification of slow sodium inactivation in nerve after internal perfusion with trypsin.

Crayfish axons, internally perfused and held at depolarized membrane potentials, exhibit an inactivation of sodium conductance with slow kinetics. Restoration of maximum peak early currents requires prepulse hyperpolarizations of up to 1 s duration. Addition of trypsin to the internal perfusate at low concentrations (0.02 mg/ml) causes a rapid and irreversible loss of slow inactivation at the resting potential and a corresponding increase in Na currents to maximum values. After trypsin action, steady-state slow Na inactivation is shifted by 20--25 mV in the depolarizing direction, with no change in fast (h) inactivation. N-ethylmaleimide (NEM), a reagent with a high specificity for sulfhydryl groups, has been shown to induce slow inactivation, modify fast inactivation, and block a fraction of the Na conductance. After trypsin action NEM no longer increases slow Na inactivation but other effects remain. Prior exposure to NEM does not protect axons against the loss of slow inactivation caused by trypsin.


Electron probe microanalysis of red blood cells. I. Methods and evaluation.

The concentrations of potassium, sodium, and iron in human and sheep red blood cells were measured with an electron probe. Cells were prepared for analysis by spraying them on pyrolytic graphite supports. The results obtained with this spray technique agreed well with values measured on similar cells that were prepared for analysis by freezing, sectioning, and freeze-drying. Higher Na concentrations and lower K concentrations were found to be associated with lower cell volumes in human and high-potassium sheep cells. In low-potassium sheep cells the reverse was found, lower Na and higher K concentrations were associated with lower cell volumes. However, the amounts of iron were found to remain relatively constant in all human cells.


Electron probe microanalysis of red blood cells. II. Cation changes during maturation.

To understand the sequence of maturation of membrane transport and hemoglobin production during erythropoiesis, we have measured the K, Na, and Fe content in single mature red blood cells and bone marrow cells of dog using electron probe microanalysis (EPMA). Mature red blood cells of dog are low in potassium (LK) and high in sodium. These cells are derived from erythroblastic stem cells, which are high in potassium (HK) and low in sodium. This change from HK stem cells to LK red cells occurs in the marrow. The ratio of K/Na was found to be less than 0.2 independent of Fe/(K + Na) in circulating red cells. However, a significant number of marrow cells had both low K/Na and low Fe/(K + Na). We conclude that the changes in cation transport properties responsible for the conversion of HK to LK cells occur before the synthesis of hemoglobin in at least some marrow cells.


Amino acid stimulation of oxygen and substrate utilization by cardiac myocytes.

The inclusion of plasma levels of the natural amino acids plus 2.5 mM glutamate and 2.5 mM malate (PAAGM) raised the oxygen consumption and glucose oxidation of isolated cardiac myocytes in phosphate buffered saline. The addition of calcium (1.25 mM) and magnesium (0.66 mM) potentiated the stimulatory effect of PAAGM on glucose oxidation and oxygen consumption, PAAGM did not alter the shape of the dose-response curve for glucose oxidation by the isolated cardiac myocyte preparation. It did increase the amount of glucose oxidation at any given media glucose concentration up to 20 mM. PAAGM also increased the rate of lactate oxidation by the isolated cardiac myocyte preparation. PAAGM did not stimulate the oxidation of octanoate unless there was glucose present in the incubation media as well. Measurements of the concentrations of free amino acids indicated higher levels in myocytes incubated in PAAGM than in myocytes incubated in phosphate buffered saline. The data suggest that substrate metabolism by the isolated cardiac myocyte preparation can be influenced by the presence of plasma constituents that would be available to the myocardium in vivo.


Synthesis of chromogranins and dopamine beta-hydroxylase by perfused bovine adrenal glands.

The incorporation of [3H]leucine into chromogranins and into soluble and membrane-bound dopamine beta-hydroxylase (DBH) was studied in isolated perfused adrenal glands. [3H]chromogranins and [3H]DBH were quantitatively determined by immunoprecipitation. The amounts of soluble [3H]DBH formed were about equal to the amounts of membrane-bound [3H]DBH whereas the amounts of [3H]chromogranin were 5- to 20-fold greater than that of soluble [3H]DBH. On continuous sucrose density gradients, [3H]chromogranin was unimodally distributed after 2- to 20-h chase periods and accumulated in a vesicle having a lower buoyant density than mature chromaffin vesicles. At 2 h both membrane and soluble [3H]DBH were both bimodally distributed whereas after a 20-h chase period the distribution of soluble and membrane [3H]DBH was essentially unimodal and paralleled the distribution of [3H]chromogranin. These studies indicate that [3H]chromogranin, soluble [3H]DBH, and membrane [3H]DBH are synthesized concomitantly, but that each is transported into chromaffin vesicles at different rates.


Adrenocortical metabolism of angiotensin in sheep with adrenal transplants.

Conscious trained sheep with adrenal gland autotransplants in cervical skin loops were used to study adrenocortical metabolism and clearance of angiotensin (AII) administered by constant systemic infusion. For comparative purposes similar experiments were undertaken in five control sheep with skin loops but no cervical adrenal tissue. During AII infusions (0.33 microgram/min for 30 min), loop venous-arterial AII ratios (0.42--0.62 were similar in both groups of sheep. Measured AII clearances across the skin loop in sheep with and without adrenal transplants were 400--600 and 100--150 pg/min, respectively, which correlated with blood flow (r = 0.79), but showed no relation to aldosterone secretion rate. Analysis of AII immunoreactive fragments showed similar proportions of octa-, hepta-, and hexapeptide fractions (64, 26, and 5%, respectively) in adrenal arterial, adrenal venous, and systemic venous plasma. These studies do not support selective heptapeptide uptake or metabolism by adrenal tissue in vivo and indicate that specific adrenal binding of AII is likely to be less than 400 pg/min at arterial AII concentrations approximating 120 pg/ml.


A miniature transducer for recording intestinal motility in unrestrained chronic rats.

An extraluminal strain gage force transducer has been developed for recording gastrointestinal motility in small animals such as rats. Two commercial strain gages are bonded and wires attached to form half a Wheatstone bridge. The device is placed between silicone sheeting and prepared for implantation. As many as six implanted transducers can record simultaneously contractions and tone variations of circular or longitudinal gastrointestinal muscles. The transducers have been implanted in more than 20 rats, with some units lasting up to 4 mo. Furthermore, good relationships exist between intraluminal pressure waves registered by a small intraluminal balloon and gut contractions registered by the transducer. The transducers are a useful and accurate tool for rodent gut motility studies.


Intestinal absorption of zinc: a role for a zinc-binding ligand in milk.

This study examined the proposal that a low molecular weight, zinc-binding ligand (ZBL) in certain milks is important for zinc absorption in the neonatal period. Ten-day-old rats, in which intestinal ZBL is absent, fed (by stomach intubation) 65Zn-labeled ZBL from rat milk, absorbed significantly more 65Zn than those fed free 65ZnCl2 or bovine milk fractions. ZBL from human milk appeared to have an intermediate effect, possibly due to species specificity. 65Zn was found in the ZBL fraction in intestinal mucosa of 10-day-old rats fed rat or human milk fractions, but not in those fed bovine milk or free 65ZnCl2. In contrast, in 18-day-old rats, which have an endogenous intestinal ZBL, there were no differences in zinc absorption, and any of the labeled milk fractions or free 65Zn caused localization of 65Zn in the ZBL fraction of intestinal mucosa. These results support the hypothesis that the intestinal ZBL plays a role in zinc absorption and that in the neonatal period before its development the milk ZBL is valuable for this function. This mechanism may be important in normal human infants as well as in acrodermatitis enteropathica patients.


Role of gastrin in mucosal DNA synthesis after vagotomy and atropine in the rat.

The purpose of this study was to examine 1) the influence of the cholinergic innervation of the stomach on the rate of DNA synthesis in the fundic mucosa of the rat and 2) the possibility that hypergastrinemia might be involved in the response. Repeated injections of atropine in fasting rats increased by 40% the rate of DNA synthesis in the oxyntic gland mucosa. Two weeks after truncal vagotomy, the DNA synthesis rate in oxyntic gland mucosa was increased 64% compared to sham-operated control animals. In the rat colon, atropine administration produced a 56% increase in DNA synthesis compared to saline-injected controls. The injection of pentagastrin in fasting rats also increased the DNA synthesis rate in both stomach and colon, but pentagastrin combined with either atropine or vagotomy stimulated DNA synthesis no more than pentagastrin alone. Cholinergic interruption by atropine or vagotomy elevated endogenous serum gastrin concentrations, indicating that the observed DNA stimulation may be mediated by hypergastrinemia.


Uncoupling of proximal sodium bicarbonate from sodium phosphate transport by bumetanide.

Re-collection micropuncture of late proximal tubular segments and simultaneous clearance studies were performed in chronically thyroparathyroidectomized dogs before and after the intravenous administration of bumetanide. The drug, a new sulfonamide-derivative diuretic, inhibited proximal fractional sodium and fluid transport by 0.12 (from 0.44 +/- 0.04 to 0.32 +/- 0.04, P less than 0.05) and that of bicarbonate by 0.14 (from 0.43 +/- 0.05 to 0.29 +/- 0.07, P less than 0.02). Tubular fluid bicarbonate concentration was unchanged, indicating a reduction in the transport of this ion proportionate to that of tubular fluid. However, unlike sodium and bicarbonate reabsorption, fractional proximal phosphate transport was unaltered (from 0.65 +/- 0.04 to 0.62 +/- 0.04, P greater than 0.40). The drug induced a substantial natriuresis; the percentage of filtered sodium excreted rose from 0.4 +/- 0.1 to 13.1 +/- 2.4% (P less than 0.005). Bicarbonate and phosphate excretion rose more modestly: the percentage excretion of the former ion increased from 0.9 +/- 0.3 to 3.7 +/- 0.08% (P less than 0.005) and that for phosphate doubled (from 3.4 +/- 1.0 to 6.8 +/- 1.3%, P less than 0.025). However, urinary pH did not change. Accordingly, bumetanide uncoupled the transport of sodium bicarbonate from that of sodium phosphate in the proximal convoluted tubule. It is concluded from these data that the action of bumetanide in the proximal convoluted tubule is probably not related either to carbonic anhydrase inhibition or to the impairment of sodium-phosphate-linked transport.


Glomerulotubular balance following saline loading in the developing canine kidney.

Glomerulotubular relationships for glucose were studied in the developing kidney before and after saline loading in 13 anesthetized puppies that were 2-51 days of age and in one adult. When volume expansion, plasma glucose concentrations of more than 500 mg/dl, and changes in sodium excretion (FENa) were avoided, the ratio of maximal tubular reabsorption of glucose (TmGlc)/inulin clearance (CIn) was 3.37 +/- 0.28 (means +/- SD) in the puppies and did not change with age. Following intravenous saline loading (20 ml/kg), TmGlc and sodium reabsorption decreased, CIn decreased, and TmGlc/CIn decreased to 2.97 +/- 0.67. When a volume equivalent to the saline load had been excreted, TmGlc increased, CIn and FENa did not change, and TmGlc/CIn increased to 3.60 +/- 1.00. Splay in the glucose titration curve did not change with age, but the portion of the curve at saturation decreased with saline loading and returned to the control pattern as the saline load was excreted. It is concluded that glomerulotubular balance for glucose obtains from birth in the dog kidney, and that saline loading results in functional glomerulotubular imbalance with glomerular preponderance and alters the appearance of the glucose titration curve.


Blunted norepinephrine natriuresis in the isolated spontaneously hypertensive rat kidney.

In order to characterize the relationship between blood pressure and renal sodium handling in the Kyoto spontaneously hypertensive rat (SHR), we did renal clearance and isolated perfusion studies in SHR and Wistar-Kyoto controls (WKY). Clearance studies revealed no differences in renal function between SHR and WKY. Isolated perfused kidneys from SHR demonstrated a diminished glomerular filtration rate (GFR) compared to WKY kidneys when both were perfused at normotensive pressures. Increasing the perfusion pressures to hypertensive levels by adjusting the perfusate flow rate increased both the GFR and sodium excretion to equivalent values. However, the addition of norepinephrine 15 ng/ml, to the perfusate resulted in a far greater natriuretic response in WKY kidneys than in SHR, despite equivalent increases in perfusion pressures, renal resistances, GFR, and filtration fractions. These results suggest that norepinephrine exerts a direct or indirect inhibitory action on renal sodium transport, and this effect is diminished in SHR kidneys. Additionally, abnormalities in renal sodium transport may play a role in the pathogenesis of hypertension in the SHR.


Glucose-mediated inhibition of phosphate reabsorption in rat kidney.

Clearance, tracer intra-arterial injection, and tracer intratubular microinjection techniques were used on two strains of Wistar rats. In Saclay rats, clearance studies during hyperphosphatemia showed that glucose significantly decreased reabsorption of phosphate; during normal phosphatemia, glucose induced a 25% inhibition both in nondiuretic and in volume-expanded animals; thyroparathyroidectomy did not modify this inhibition. When mannitol was substituted for glucose, no change in phosphate reabsorption was noted. Tracer injection into the renal arteries of [3H]inulin, [14C]glucose, and [32P]-phosphate with or without additional unlabeled glucose or mannitol showed that the presence of glucose significantly increased 14C and 32P urinary recoveries but not mannitol. Intratubular paired microinjections into early proximal tubules of the same tracers with and without glucose showed that addition of sugar also increased the 14C and 32P urinary recoveries. In Munich rats, the effects were much less marked than in Saclay rats. It is concluded that the inhibitory effect of glucose 1) partly results from intrarenal factors, 2) is linked to glucose reabsorption per se but not to a nonspecific osmotic intraluminal effect, 3) is localized on the tubular luminal side, and 4) is subject to strain differences.


Stimulation of adenylate cyclase in isolated rat glomeruli by prostaglandins.

The effect of prostaglandins and various agents on cyclic adenosine 3',5'-monophosphate generation was studied in isolated rat glomeruli. Specific activity of adenylate cyclase in the glomeruli showed a 12-fold increase over the crude homogenate and a fivefold increase over a tubular preparation. Prostacyclin (PGI2) preferentially stimulated adenylate cyclase of isolated glomeruli at a concentration as low as 10(-9) M. Prostaglandins (PGE1, PGE2, and PGA2) and parathyroid hormone (1-34 synthetic PTH fragment) increased adenylate cyclase in glomeruli with maximal stimulation at 2 X 10(-5) M and 2-4 microgram/ml, respectively. No inhibition of PGE2 on PTH stimulation was observed. Isoproterenol (2 X 10(-4) M) caused a small stimulation, while PGF2alpha, arginine vasopressin, and angiotensin II were ineffective. The presence of guanosine triphosphate in the adenylate cyclase assay enhanced basal and PGE2- and PTH-stimulated activity, but had no effect on NaF stimulation. These findings show an effect of prostaglandins and PTH on the glomerular cAMP system and raise the possibility of a physiological action of these agents on the glomerulus.


Cross-circulation study of natriuretic factors in rats with reduced nephron mass.

The importance of humoral factors, including urea, in the adaptations in electrolyte excretion which occur with acute or chronic reduction in nephron mass was studied using isovolemic cross-circulation in 38 pairs of anesthetized rats. After initial clearance studies, donor rats with acute (48 h) three-quarter nephrectomy or sham operation, acute urea loading, or chronic (2-3 wk) three-quarter nephrectomy or sham operation, underwent cross-circulation with normal recipient animals. Donor rats with acute three-quarter nephrectomy caused a marked natriuresis-kaliuresis in normal recipients. Natriuresis resulted from inhibition of tubular reabsorption independent of changes in GFR or renal plasma flow. Urea was a major but not the only factor involved in the cross-circulation natriuresis-kaliuresis. The severity of reduction in nephron mass, as indicated by the GFR of the donor rat, correlated with the increase in electrolyte excretion in the recipient. Donor rats with chronic three-quarter nephrectomy produced a slight but significant natriuresis in recipients which was much less than that seen with acute three-quarter nephrectomy. Since the GFR and blood urea nitrogen level of donors with acute and chronic renal insufficiency were similar, it was evident that the chronicity of reduced nephron mass, through mechanisms that are not clear, had a significant effect on the level of circulating natriuretic and kaliuretic factors in renal insufficiency.


Organic acid secretory pathway and urinary excretion of prostaglandin E in the dog.

Urinary prostaglandin E (PGE) has been utilized as an index of renal PGE production. Recent studies, however, have suggested that the organic acid secretory pathway is a major determinant of endogenous UPGEV (urinary excretion of PGE). The following experiments were designed to quantitatively test this latter view. In clearance studies the administration of para-aminohippurate (PAH) or probenecid (25 mg/kg) failed to alter endogenous UPGEV although PAH clearance fell with probenecid. Comparison of the excretion patterns of exogenously administered [3H]PGE and [14C]inulin after intra-arterial injection into the dog renal artery (Chinard technique) demonstrated both glomerular filtration and secretion of [3H]PGE. Blockade of the organic acid pathway by probenecid (25 mg/kg) abolished [3H]PGE secretion. Indomethacin (1 mg/kg) did not alter the secretion pattern of [3H]PGE, but decreased endogenous UPGEV by over 80%. Because this low dose of indomethacin did not decrease [3H]PGE secretion, it probably decreased endogenous UPGEV by inhibiting synthesis. Thus, these tracer studies do indeed confirm the suggestion that PGE may be excreted by the organic acid pathway. However, the failure of total endogenous UPGEV to fall after blockade of the organic acid pathway would suggest that the component of UPGEV due to this mechanism is quantitatively insignificant.


Calcium and sodium transport by the distal convoluted tubule of the rat.

Calcium and sodium transport were studied in the distal convoluted tubule of the rat by micropuncture and microperfusion techniques. The animals received either control infusions, 0.9% saline at 0.02 ml/min, or chlorothiazide (CTZ), 0.5 mg/min-kg. In free-flow micropuncture, distal calcium reabsorption occurred against an electrochemical gradient; it was 9% of the filtered load in the controls and 13.8% in the CTZ-treated rats. The drug dissociated calcium and sodium transport along the distal tubule. Absolute reabsorptive rates for calcium and sodium, measured in pump perfusion experiments, were proportional to the distal loads. CTZ, acting from the lumen, enhanced net calcium (P less than 0.01) and reduced net sodium (P less than 0.01) reabsorption. In stationary microperfusion experiments, sodium backflux produced rapid establishment of a steady-state concentration of 50 mM. In contrast, net backflux of calcium was negligible. With calcium in the luminal perfusion fluid, there was a concentration-dependent reabsorptive efflux which was not saturated at a luminal calcium concentration of 9.5 mM and which was enhanced by CTZ.


The structure and function of the myocardial cell surface.

External to the lipid bilayer or unit membrane at the surface of the myocardial cell is the glycocalyx. This coat is approximately 50 nm thick and is composed for two layers, the surface coat (SC) and the external lamina (EL). The SC is an integral part of the sarcolemma and many of its glycoproteins penetrate into or through the lipid bilayer. The glycocalyx invaginates with the unit membrane to fill the transverse tubules of the cell. Both layers contain abundant fixed negatively charged sites and a prominent constitutent of both is sialic acid. Removal of sialic acid produces a large specific increase in sarcolemmal calcium permeability without perturbation of potassium permeability. Sialic acid also accounts for a component of negatively charged sites which, with other acidic mucopolysaccharides, contributes to cationic binding at the surface of the cell. Calcium bound at the surface seems to be of importance in the excitation-contraction (EC) coupling sequence whether as a source of "trigger" calcium for the sarcotubular system or as a direct activator of the myofilaments. The bound Ca appears to be in rapid equilibrium with Ca in the vascular and interstitial spaces and is the probable immediate source of the Ca that crosses the sarcolemma. The integrity of the glycocalyx appears to be necessary in the prevention of uncontrolled entry of Ca into the cell.


Effect of hypoxia on mechanical function in the neonatal mammalian heart.

The effect of 30 min of hypoxia followed by reoxygenation on mechanical function was studied in isolated, arterially perfused, neonatal rabbit and dog hearts. All studies were performed at a perfusion rate of 2.5 ml/g-min, at a pacing rate of 60 beats/min and at 27 degrees C. The muscles were perfused with Krebs-Henseleit solutions equilibrated with 95% O2 and 5% CO2 (control) or 95% N2 and 5% CO2 (hypoxia). In the newborn rabbit and dog, both the developed tension (DT) and the maximal rate of tension development (dT/dtmax+) decreased during the first 3 min of hypoxia and then recovered to values not different from control. The effect of hypoxia on DT and dT/dtmax+ was inversely related to age in both the rabbit and dog. The equations describing the decline in DT and dT/dTmax+ during hypoxia and the recovery during reoxygenation were best expressed by two or three exponentials. Time to peak tension and half time to relaxation decreased during hypoxia and the decrease was also inversely related to age. The fact that the newborn was able to maintain normal mechanical function during hypoxia suggests that the newborn is capable of maintaining normal myocardial ATP levels due to enhanced flux through the glycolytic pathway.


Effect of hypoxia on myocardial high-energy phosphates in the neonatal mammalian heart.

The effect of hypoxia on myocardial high-energy phosphate content in the newborn, 2-wk-old, and adult rabbit was determined and compared with mechanical function. Studies were done on the ventricular septum arterially perfused with Krebs-Henseleit bicarbonate buffer solution equilibrated with 95% O2 and 5% CO2 (control) or 95% N2 and 5% CO2 (hypoxia) at 60 beats/min and 27 degrees C. In the adult, ATP concentration decreased to 68%, 56%, and 39% of control after 2, 30, and 60 min of hypoxia, respectively. After 30 min of hypoxia, ATP concentration was not different from control in the newborn but decreased to 82% of control in the 2-wk-old. After 2 min of hypoxia, creatine phosphate concentration decreased to 55% and 10% of control in the newborn and adult rabbit, respectively. Lactate production increased significantly during hypoxia and was greater in the newborn than in the adult. The data indicate that the newborn rabbit is capable of maintaining glycolysis and normal levels of myocardial ATP during hypoxia, which ensures normal myocardial mechanical function for longer periods than in the adult.


Sympathetic vasomotor outflows to hindlimb muscles of the cat.

Blood flow to the hindlimb muscles of chloralose-anesthetized, paralyzed cats was monitored with an electromagnetic flowmeter on the femoral artery. The functional pathways of the sympathetic constrictor and dilator innervations to the vasculature of these muscles were determined by measuring changes in vascular conductance during electrical stimulation of 1) ventral roots T12-L7 (exit of preganglionic fibers from the spinal cord and entrance into the sympathetic chain), 2) the distally intact sympathetic chain at successive levels between the L1 and L7 ganglia (presence of caudally running vasomotor fibers in the chain at each level), and 3) isolated sympathetic ganglia L2-L7 (exit of postganglionic vasomotor fibers from the chain at each level). Our results indicate that vasoconstrictor fibers emerge from ventral roots T12-L4 with maximum functional outflow at L1-L3; the fibers course downward through the sympathetic chain to exit from the chain mainly at L5-L7 or below. In contrast, the preganglionic origin of cholinergic vasodilator fibers, tested after blocking the constrictor fibers with bretylium, is limited to ventral roots L2-L5, with maximum outflow at L4. The vasodilator fibers leave the sympathetic chain to enter the spinal nerves at the same levels as the vasoconstrictor fibers.


Reflex responses of abdominal vascular capacitance from aortic baroreceptors in dogs.

The vascularly isolated abdominal circulation of chloralose-anesthetized dogs was perfused at constant flow through the aorta and drained at constant pressure from the inferior vena cava. Changes in resistance were calculated from changes in perfusion pressure and changes in capacitance were calculated by integrating changes in venous outflow. While carotid sinus pressure was constant, a decrease in pressure in the vascularly isolated aortic arch, over the whole range of baroreceptor sensitivity, decreased abdominal vascular capacitance by 2.9 ml-kg-1 (mean, SE +/- 0.42) and increased the abdominal vascular resistance by 35 +/- 7.1%. Decreases in pressure in the vascularly isolated carotid sinuses, while aortic pressure was constant, decreased capacitance by 5.0 +/- 0.62 ml-kg-1 and increased resistance by 72 +/- 15.9%. Responses of capacitance and resistance to changes in aortic pressure were greatest when carotid pressure was held near threshold levels and least when it was held at levels that would maximally excite carotid baroreceptors. The responses to changes in aortic pressure were abolished when the venous nerves were cooled or the splanchnic nerves were cut.


Interrelations between contracting striated muscle and precapillary microvessels.

Arterioles and capillaries in the hamster cremaster muscle were observed during electrical stimulation of striated muscle fibers in order to characterize the microcirculatory basis of functional hyperemia. When contraction was restricted to single muscle fibers, responses were variable and frequently transient. Stimulation of either small bundles of muscle fibers or the entire cremaster muscle resulted in reproducible responses typified by: 1) a latency period, 2) an early, often transient phase of dilation, and 3) a second, slower phase of dilation. The latency varied inversely with contraction frequency, and the magnitude of the dilation varied directly with contraction frequency over the range 1--8/s. With stimulation of single fibers and small groups of fibers, arteriolar vasodilation was highly localized to regions of the arterioles that were in close apposition to the stimulated fibers. The number of capillaries with red blood cell flow increased during contraction, and the increase was graded with contraction frequency. The changes observed suggest that the vascular response during functional hyperemia is a two-part process and that the control processes are influenced by contraction frequency.


Role of oxygen in arteriolar functional vasodilation in hamster striated muscle.

Small isolated groups of striated muscle cells were stimulated in the hamster cremaster muscle. During and after stimulation, oxygen microelectrodes were employed to determine the relationships among arteriolar vasodilation, tissue Po2, and periarteriolar Po2. Localized contraction produced a biphasic arteriolar vasodilation without associated alteration of Po2 on the surface of the arterioles (vascular smooth muscle Po2). In contrast, muscle contraction produced a decline in muscle tissue Po2 that was proportional to the contraction frequency over the range of 1--4 contractions per second. An increase in contraction frequency also produced a graded increase in arteriolar diameter, the magnitude of which was statistically correlated with the steady-state change in tissue Po2. However, arteriolar diameter changes preceded tissue Po2 changes, both with the initiation of functional dilation and during the recovery period. Tissue Po2 was manipulated at rest and during contraction by increasing the Po2 of the superfusion solution. Increasing the tissue Po2 caused a decrease in vascular diameter under both conditions and a reduction in the magnitude of the arteriolar vasodilation during contraction. Restoration of tissue Po2 to resting levels during muscle contraction produced only partial restoration of vascular diameters. The results are consistent with the hypothesis that at least three components are involved in the vascular control process during muscular activity: an early component independent of tissue oxygen levels, a late component independent of oxygen, and a late component associated with a decrease in muscle Po2, without an effect on vascular smooth muscle Po2. The evidence indicated that Po2 of the smooth muscle of the arterioles had no role in the dilation observed.


Transmural myocardial deformation in the canine left ventricular wall.

A biplane cineradiographic technique was used to measure deformation of the myocardium as indicated by small lead spheres implanted into the anterior left ventricular wall of anesthetized dogs. Deformation was resolved into nine separate components for each of the epicardial, middle, and endocardial layers. The data illustrate the mechanical effect of myocardial fiber orientation and the ability of muscle layers to deform differentially. In order to present an overview of all the results, the implications of the deformation components are discussed first separately and then in a coordinated fashion.


Dissociation of energetic state and potassium loss from anoxic myocardium.

Cellular high-energy phosphate levels and 42K exchange were studied in isolated, interventricular rabbit septa at 28 degrees C. Septa were perfused with a modified Tyrode solution that contained glucose as the metabolic substrate. Anoxia was induced by switching to solution equilibrated with N2-CO2 gas. Potassium lost during anoxia by increased efflux from the cells was measured by 42K. Whole tissue levels of ATP, ADP, phosphocreatine, and total creatine were determined. The effects of 20-min anoxic stresses were evaluated in each of four groups of septa: 1) control (perfused with regular solution and paced at 42 excitations/min; 2) E-C uncoupled (by perfusing with solution containing 50 micron Ca2+); 3) quiescent (spontaneous contraction rate less than 1/min); and 4) perfused with high glucose solution (20 mM). Compared to the control group, only quiescence significantly decreased the potassium loss during anoxia; the cellular energetic state was well maintained during stress by both E-C uncoupling and quiescence. The results indicate that the increase in potassium efflux during brief anoxic stress is largely excitation dependent and can be dissociated from contraction and cellular energetic state.


Cellular electrophysiological marker of irreversible ischemic myocardial injury.

Glass microelectrode studies on posterior papillary muscle (PPM) slice preparations from 20 pentobarbital-anesthetized dogs (15 subjected to prior circumflex coronary artery ligation, 5 to sham ligation) have resulted in the definition of an electrophysiological marker of irreversible ischemic injury, namely, findings of areas composed of cells unable to generate a significant resting potential (less than -25) mV), designated "electrically inactive areas." Electrically inactive areas were essentially confined to PPM from dogs with circumflex coronary ligation; the incidence and distribution of the areas was related to duration of ischemia. Correlative phase- and light-microscopic studies demonstrated close correspondence between such areas and morphological evidence of irreversible ischemic injury. Analysis of frequency and distribution of electrically inactive areas permits quantitative assessment of the extent and spatial distribution of irreversible injury. This method has been used to quantitate injury in PPM from dogs that had been subjected to ligation for varying time periods. The potential utility of this method for evaluation of interventions designed to protect against ischemic injury and to assess electrical properties of surviving cells is considered.