The group assessment of interpersonal traits (GAIT): differentiation of measures and their relationship to behavioral response modes. GAIT performances of undergraduates were rated by peers and professsional clinical psychologists from video tape. Two additional measures; Potential for Clinical Effectiveness, and Insight into the Client's Problem, were included with GAIT measures of Openness, Empathy, Acceptance, and Outgoing and were also rated. GAIT ratings of Empathy, Acceptance, Potential for Clinical Effectiveness were not well differentiated. The behavioral response modes of each participant in the Understander's role were analyzed and correlated with GAIT measures, Potential and Insight. Empathy was correlated with reflecting feelings and advice-giving questions and negatively correlated with dysfunctional questions and silence. Acceptance was correlated with nonverbal attending behavior and negatively correlated with dysfunctional questions. Outgoing was positively correlated with information-gathering questions and total questions. Insight was correlated with reflecting feelings and negatively correlated with silence. An Understander who was rated high on Potential for Clinical Effectiveness was active, made statements about or asked questions pertaining to the Discloser's feelings, asked advice giving questions, tended to have infrequent silences during the interaction, and did not ask digressive or dysfunctional questions. Finally, the importance of Outgoing suggests the salience of an activity dimension in judged Clinical Potential.


Theoretical and applied inputs in mental health center research. Successful implementation of projects in mental health centers aimed at meeting programmatic needs and exploring theoretical issues encounter a number of difficulties. These include time, staffing and funding. While researchers may be interested in complex theoretical questions, agencies require data collected quickly, at minimum cost, and utilizing limited personnel. This paper discusses a model for conducting significant theoretical and applied research in mental health centers. A project undertaken in a mental health center is described to illustrate the model.


Knowledge assessment of mental health advisory boards. Informed citizen advisory boards are vital to the operation of community mental health programs. In order to provide relevant educational experiences, a continuing education program conducted a survey of the self-judged level of knowledge of a sample of board members in a large city. The sample consisted of 57 respondents representing 16 of 19 city mental health centers and the three federally funded community health centers located in the city. The results indicated areas of strength and weakness. Also, knowledge assessments differeed in relation to years of experience on advisory boards. Several suggestions are made about designing curricula for mental advisory boards.


Intake dispersal patterns: a community mental health study. This paper is a descriptive research effort aimed at identifying a profile of the client who is not accepted for community mental health services. A review of 100 closed intakes revealed significant correlations by chi-square analysis between the following items: referral source and units of service; referral source and disposition, referall source and presenting problem, referral source and age; and age and units of service. Some ideas on the different services available through a multidisciplined agency as compared to a single-disciplined agency are discussed. Conformation of the intuitive impression that clients who call in for services themselves are more likely therapy candidates is statistically affirmed. Discussion includes ideas on the value and effect of community outreach to clarify referral procedures. Implications for practice are also presented.


Adrenocortical carcinoma in two children with subsequent primary tumors. Two 13-month-old children with adrenocortical carcinoma were treated surgically; each developed a second primary tumor, four and seven years later, and died shortly thereafter. Adrenocortical carcinoma is a rare childhood tumor. Second primary tumors in children are also uncommon. The coupling of two unusual events in each child is thought to represent genetic predisposition since potentially carcinogenic therapeutic modalities were not employed in treating their original tumors and neither patient exhibited an immune defense deficit.


The physical working capacity of healthy black children. The exercise performance of 170 black boys and girls, 7 to 14 years of age, was evaluated on a mechanically braked bicycle ergometer. The protocol is simple to perform in the hospital or in the field with normal children or children with heart or pulmonary disease. The results of the physical working capacity at a heart rate of 170 beats per minute (PWC170), a submaximal workload, are comparable to values previously recorded in California children. For a given body surface area, boys and girls younger than 10 years of age had similar PWC170 but boys 11 years and older had a greater capacity than girls of similar age or body surface area. There was a significant correlation between PWC170 and total work performed for boys (r = .81) and girls (r = .69).


Mixed connective tissue disease in childhood. Relationship Sjögren's syndrome. Mixed connective tissue disease (MCTD) seems to be a distinct entity that has some manifestations of systemic lupus erythematosus, scleroderma, polymyositis, and Sjögren's syndrome and is serologically characterized by the presence of an antibody to ribonucleoprotein. We report the cases of three children with MCTD with high titers of antibody to ribonucleoprotein. Two fulfilled criteria of lupus erythematosus, two had polymyosis; all three had suggestive features of scleroderma, fulfilled criteria for the diagnosis of juvenile rheumatoid arthritis, and had Sjögren's syndrome. Additional superimposed features of another connective tissue disease should arouse suspicion of MCTD. All three of our patients responded adequately to corticosteroid treatment that makes recognition of this entity by the pediatrician all the more important.


Tracheostomy decannulation.

Tracheostomy decannulation. Tracheostomy in pediatric patients involves major morbidity that is often reflected in prolonged decannulation difficulty. A review of 123 consecutive pediatric tracheostomies shows that 44 patients experienced such difficulties. Among those patients suffering decannulation delay, subglottic stenosis had developed in 39%, tracheal granuloma in 25%, fused cords in 11%, and temporary laryngeal abductor failure in 25%. Although the overall incidence of decannulation failure is high, more than 60% of those patients affected respond to treatment when diagnosis is prompt and accurate. In this regard, the laryngologist may play a central role in the management of the pediatric decannulation process.


Basilar artery migraine. A review of 30 cases. Thirty patients with basilar artery migraine were followed up for a period of six months to three years. The mean age of onset was 7 years. The patients were seen with recurrent transient attacks of neurological disturbances localized to the vertebrobasilar arterial tree. Attacks often included pulsatile cephalagia. A history of migraine was present in 86% of the families studied. The majority of family members with migraine were female and on the maternal side. Permanent neurological residua developed in only one patient. There was a tendency for attacks to be more severe with an older age of onset. Basilar artery migraine is a migraine variant that may affect children from late infancy through adolescence.


Recurrent pseudocyst from a ventriculoperitoneal shunt. An unusual abdominal mass. A 4-year-old girl developed a recurrent abdominal pseudocyst from a ventriculoperitoneal shunt. There was no infection of the peritoneum or CSF. Diagnosis of this unusual abdominal mass was made roentgenographically by direct injection of soluble contrast material under antiseptic conditions into the shunt tubing. Ultrasonography was confirmatory. Management included excision of the cyst and removal of the shunt catheter from the peritoneal cavity.


Measles revaccination. Persistence and degree of antibody titer by type of immune response. During a measles immunization campaign 203 children were enrolled in an antibody response study. Of this group, follow-up clinical data and sera samples were available from 125 children three weeks after immunization and from 90 children ten months later. Seventy-six of the children had been previously vaccinated, ten had a history of measles and 39 denied vaccination or illness. Twenty-six of the children had prevaccination hemagglutination inhibiting antibody titers of less than 5. Of this group 12 had a primary immune response (IgM measles antibody) with geometric mean titers (GMT) of 90 and 40 three weeks and ten months respectively after vaccination. In contrast, the other 14 children with initial titers of less than 5 had secondary immune responses (only IgG measles antibody) with GMTs of 28 and 9 three weeks and ten months after vaccination. Since the antibody responses in these children who had previously been stimulated by measles antigen were modest and transient, it is suggested that booster immunization may not be effective in preventing future secondary vaccine failures. Also noted in this study was a poor correlation between historical data and actual measles antibody.


Prothrombin complex concentrates. Use in treatment of hemophiliacs with factor VIII inhibitors. The development of factor VIII inhibitors has been a major problem in the management of hemophiliacs. The use of prothrombin complex concentrates (PCC) has been advocated as a method of overcoming this problem. We utilized PCC in the treatment of nine hemophiliac patients who had significant levels of inhibitor. Acute bleeding episodes were successfully treated in all nine patients. Single infusions of PCC were usually adequate for control of joint and soft tissue bleeding episodes, while multiple infusions were usually required for more serious hemorrhages. In addition, programs of repeated infusions were used to heal chronically inflamed joints in three patients. The only side effect of treatment was one episode of asymptomatic elevation of liver function values that resolved spontaneously. There were no thrombotic events associated with the PCC infusions. Therapy with PCC is recommended for the management of hemophiliacs with factor VIII inhibitors.


Disproportionate growth of the lower extremities. A major determinant of short stature in Turner's syndrome. The relationships between the height (H), sitting height (SH), and the lower segment (H-SH) were studied in a group of 21 patients with Turner's syndrome. The SH/H ratio was markedly abnormal (0.55), equivalent to that of 6-year-old normal girls. The abnormality in ratio was a result of markedly shortened lower extremities. Further, there was a significant inverse correlation between SH/H-SH ratio and height such that patients with the most shortening of their legs were the shortest. The degree of abnormality in lower segment, therefore, is a major determinant of stature in Turner's syndrome.


Daily alcohol consumption and fatal coronary heart disease. For a series of 568 married white men who died from coronary heart disease (CHD) and an equal number of matched controls, information was collected on a large number of variables, including daily alcohol consumption. The crude matched pair ratio estimate for any versus no daily drinking was 0.6 (95% confidence limits 0.4 to 0.7). After controlling for additional confounding variables the risk ratio for any versus no daily alcohol consumption was 0.6 (0.5--0.8). This preventive effect was restricted to light drinkers, defined as those who drank less than or equal to 59.2 ml (2 oz) of alcohol daily. These data provide strong evidence against a causal role of daily alcohol consumption in fatal CHD and are consistent with a small preventive effect of any versus no daily drinking which is attributable only to light but not heavy drinkers.


Cost considerations and sample size requirements in cohort and case-control studies. Three methods for incorporating cost considerations into sample size determination for cohort and case-control studies are considered. It is found that when the costs of obtaining exposed and nonexposed subjects or of obtaining case and control subjects differ, an improvement in design can be achieved.


Urban-rural differences in coronary heart disease in a low incidence area. The Puerto Rico heart study. This report explores coronary heart disease (CHD) risk factors and the incidence of new CHD events developing over a two and one-half year period in 8793 urban and rural Puerto Rican men aged 45--64 years. Rural men had a lower average blood pressure, serum cholesterol, blood sugar, heart rate and relative weight than urban men. They were more active physically and although more of them smoked, they smoked fewer cigarettes than urban dwellers. The age-adjusted CHD incidence rate for urban men was 1.5 times that of rural men. Among rural areas the most rural had the lowest incidence. Among urban areas there was a suggestive trend of increasing incidence with degree of urbanization. Differences in conventional risk factors, while substantial, do not entirely explain the modest differences in incidence. There also appeared to be a relation with geographic mobility. Urban men who had always lived in the same area had an incidence rate as low as that for rural men whereas recent rural migrants to urban areas had the highest rates of all.


A fetal-infant life table based on single births in Norway, 1967--1973. The study is based on 440,452 single births occurring in Norway, 1967--1973, with known gestational age. The information was collected through a notification system known as "Medical Registration of Births," covering all births occurring in Norway, and the data are made available through the Medical Birth Registry of Norway, which allows for linkage between births and infant deaths. The life table describes the experience of women still pregnant at a gestational age of 16 completed weeks, and states for each subsequent week the number of pregnancy terminations, the outcome, and the number of women still pregnant. Seven outcomes of pregnancy are considered: fetal death prior to labor, fetal death during labor, death within 24 hours, death 1--6 days, death 7--27 days, death 28 days--1 year, and survival of one year or more. The data in the life table provide information on the probability of pregnancy termination in each week of gestation (after 16 completed weeks), and the probabilities of the various outcomes. The fetal-infant life table is considered as an extension of descriptive perinatal statistics and is of value in monitoring health changes and in comparing perinatal mortality between populations. It also provides information on time of pregnancy termination and outcome, which has some clinical applications.


Agreement rates between oral contraceptive users and prescribers in relation to drug use histories. A comparison between prescriber records and patient-reported oral contraceptive histories obtained during a case-control study of thromboembolism and oral contraceptive use served as the basis for evaluating the extent of agreement between these two sources of information. Agreement between oral contraceptive user and prescriber was highest on the name of the most recently-used product (89% agreement), and dropped to 62.5% on the name of the product taken before the more recent one. For total duration of oral contraceptive use (to within one month of hospital admission), agreement (defined as differences not exceeding one month) was 36%, while 39% showed the users reporting longer duration of use, and 25% showed users reporting shorter duration. Cases showed a higher rate of agreement with prescriber records than the controls on both the name of the product and the total duration of use. Disagreement from prescriber records in the direction of reporting longer duration of use was 45% for the controls compared to 27% for the cases. These results indicate that while user information in connection with the most recently used oral contraceptive can be acceptable in studies employing the case-control research strategy, user reports about previous oral contraceptive use may be less useful.


Oral contraceptives and breast disease. An epidemiological study. A case-control study of the relationship between use of oral contraceptives and cancer of the breast, cancer of the corpus uteri, cancer of the ovary, and benign breast diseases was undertaken among women in the age group 20--44 years who had been admitted to several large hospitals in Connecticut. No significant association was seen between use of oral contraceptives and breast cancer. It was found that the longer a woman had used sequential oral contraceptives, the lower her relative risk of benign breast disease. Use of combination oral contraceptives, however, did not appear to influence the risk of benign breast diseases. The numbers of cases with cancer of the ovary and of the corpus uteri in this age group were too small for any conclusions to be reached.


Multivariate analysis for matched case-control studies. A multivariate method based on the linear logistic model is presented for the analysis of case-control studies with pairwise matching. This technique enables one to investigate the effect of several variables simultaneously in the analysis while allowing for the matched design. The odds ratio is used as the basic measure of risk. One is able to control for variables which are not matching variables while investigating the odds ratio for a particular factor, and to estimate the change in the odds ratio as the level of one or more interval variables changes. The computing methods used for obtaining maximum conditional likelihood estimates of the parameters of interest are modifications of standard programs for logit regression.


The effect of high-sodium and low-sodium intakes on blood pressure and other related variables in human subjects with idiopathic hypertension. Nineteen patients with hypertension in whom all known causes of blood pressure elevation had been ruled out were classified as "salt-sensitive" or "nonsalt-sensitive" from the changes in blood pressure with changes in sodium intake from 9 meq to 249 meq/day. With the diet containing 249 meq sodium per day, there were no statistically significant differences in plasma sodium, potassium, chloride, aldosterone, cortisol or renin activity, or in urinary potassium, aldosterone or 17-hydroxycorticosteroids between the two groups. The "salt-sensitive" patients retained more sodium on the high-sodium diet than did the patients who were not sensitive to salt ("nonsalt-sensitive"); accordingly, sodium induced more weight gain in the salt-sensitive patients.


Late prosthetic valve endocarditis: clinical features influencing therapy. To assess the clinical features which might influence therapy, we studied 43 patients with late prosthetic valve endocarditis (LPVE). Twenty patients (47 per cent) survived. Of patients with streptococcal LPVE 61 per cent (11 of 18) survived compared to 36 per cent (nine of 25) of the patients with nonstreptococcal LPVE (p less than 0.10). Among patients with new regurgitant murmurs 33 per cent (nine of 27) survived versus 69 per cent (11 of 16) with such murmurs (p less than 0.03). Of patients with moderate to severe congestive heart failure (CHF) 16 per cent (three of 19) survived compared to 71 per cent (17 of 24) with mild or no CHF (p less than 0.001). The concurrence of two of these three features, i.e., nonstreptococcal etiology, a new regurgitant murmur or moderate to severe CHF, was associated with a mortality rate of 50 to 90 per cent. Persistent fever during therapy, a regurgitant murmur, atrioventricular conduction disturbances and relapse frequently reflected myocardial invasion. In view of the poor outcome with medical therapy and late reoperation, early surgical intervention should be considered when two of the three features noted are present or when myocardial invasion is suspected.


Resistance to endogenous norepinephrine in Bartter's syndrome: reversion during indomethacin administration. In five patients with Bartter's syndrome, mean (+/-SE) plasma norepinephrine concentrations increased from 324 +/- 75 pg/ml with the patients in the supine position to 550 +/- 100 pg/ml, 753 +/- 104 pg/ml and 808 +/- 116 pg/ml after 2,5 and 10 minutes, respectively, in the standing position, levels significantly higher than normal. Plasma epinephrine concentrations were indistinguishable from normal. One patient was shown to resistant the pressor (but not the metabolic) effects of intravenously administered norepinephrine prior to treatment with reversion to normal pressor responsiveness during indomethacin administration. Similarly, that patient's exaggerated endogenous norepinephrine response to standing (10 minute plasma value of 1,110 pg/ml) reverted to normal (10 minute value of 462 pg/ml) during indomethacin administration. Thus, patients with Bartter's syndrome exhibit a hyperadrenergic state consisten with resistance to endogenous, as well as exogenous, norepinephrine. Since the metabolic responses to intravenously administered norepinephrine were normal in the patient studied, norepinephrine resistance would appear to be limited to the vasculare system. Reversion of norepinephrine resistance during administration of an inhibitor of prostaglandin synthesis suggests that this hyperadrenergic state is not a primary pathogenetic abnormality in Bartter's syndrome.


Early detection of hypersensitivity pneumonitis in office workers. Symptoms of hypersensitivity pneumonitis in three employees in an office building led to an investigation  of their work environment. An open spray water air cooling system was implicated when inhalation challenge with the spray water caused acute illness in one of them. A questionnaire survey of the 4,023 co-workers identified 48 other suspect cases, and laboaratory studies confirmed hypersensitivity pneumonitis in three additional workers of this group. A significant change in pulmonary function, occurring only after exposure to the work environment, was the most useful laboratory finding and was found in five workers with no other pulmonary abnormalities, but not is asymptomatic workers or controls, since five of the six patients with hypersensitivy pneumonitis worked in offices cooled by the spray water system and since three had positive responses to inhalation challenge, use of the spray water system was discontinued. The affected workers improved after they were removed from the office complex.


Irreversibly sickled cells and red cell survival in sickle cell anemia: a study with both DF32P and 51CR. For 25 subjects with sickle cell anemia the mean red cell life span measured with Di-isopropylfluorophosphite-32P (DF32P) was 17.32 +/- 4.51 days. Performed simultaneously, the half life (T1/2 of radioactively-labelled chromium 51Cr) was 10.11 +/- 2.82 days (14 subjects). Eight additional subjects, or more than 30 per cent of those studied using both red cell tags, had 51Cr red cell survival curves better described by two exponents than by one, apparently due to two different rates of 51Cr elution from the red cells. This finding limits the value of quantitative data obtained by this procedure. A negative correlation was found between the mean red cell life span measured with DF32P-tagged cells and the proportion of irreversibly sickled cells in venous or capillary blood. A similar negative correlation was found between the red cell half survival time measured with 51Cr-tagged cells and the proportion of irreversibly sickled cells. These data are compatible with the view that repeated sickling and, in particular, the formation of irreversibly sickled cells play a distinct role in the pathogenesis of hemolysis in sickle cell anemia.


The effect of normalization of serum complement and anti-DNA antibody on the course of lupus nephritis: a two year prospective study. A prospective study was carried out in 25 patients with systemic lupus erythematosis (SLE) on the effect of normalizing serum complement (CH50) and anti-DNA antibodies on the course of lupus nephritis. In 16 of the 25 patients, CH50 was maintained within the normal range for two years. Urinary protein excretion increased or remained low in all 16. Repeat renal biopsies were performed in 10 of these 16, and disclosed either stabilization of glomerular disease or diminution. In the nine patients in whom CH50 could not be normalized with tolerated doses of drugs, urinary protein excretion increased or remained increased. Repeat renal biopsies in six of these nine patients were carried out and showed worsening of glomerular disease in five. No clear-cut correlation was found between urinary protein excretion or renal disease and the serum levels of anti-DNA antibody. We conclude from these observations that continuous normalization of CH50 by drug therapy in patients with SLE is associated with stabilization or diminution of lupus nephritis.


Why does anyone still use desiccated thyroid USP? The effect on thyroid status of changing from thyroid USP to sodium L-thyroxine was evaluated in 40 patients. With thyroid, abnormally high triiodothyronine (T3) levels were seen in 36 of 38 patients receiving doses of 90 to 240 mg; compared to sodium L-thyroxine, 0.15 to 0.2 mg, the serum T3 was higher (289 +/- 15 ng/dl versus 176 +/- 9 ng/dl, p less than 0.0005) and the thyroxine (T4) lower (7.4 +/- 0.3 microgram/dl versus 11.6 +/- 0.5 microgram/dl, P less than 0.01). Thyrotoxic symptoms occurred in six patients and diminished or disappeared after the change to sodium L-thyroxine, suggesting that the raised T3 level with thyroid may have undesirable effects in some patients. The T4 level, because it is low whether symptoms are present or not, may inadvertently suggest the need for higher dosage of desiccated thyroid in patients who have already received adequate replacement. The dose of sodium L-thyroxine was adequately assessed by measurement of both T4 and T3 levels. Thyroid USP should be discontinued as thyroid medication since it produces thyroid hormone levels that are misleading estimates of thyroid function and can cause thyrotoxic symptoms.


Circulating immune complexes in Hodgkin's disease. Levels of circulating immune complexes (CIC) in the serum of patients with Hodgkin's disease were measured by the Raji cell radioimmunoassay. Elevated levels of immune complexes (mean value of 49 microgram/ml +/- 21 SE) were detected in 20 of 40 (50 per cent) untreated patients. After treatment, the level of CIC was normal (less than 15 microgram/ml) in 39 of 41 patients. Recurrent disease developed in two of the 39 patients with normal post-treatment levels of CIC and in one of the two patients with elevated post-treatment levels during the follow-up period of six months to six years. Elevated levels of CIC were detected in patients with Hodgkin's disease in stages I, II and III but not in stage IV. No significant correlations were found in the frequency of elevated levels of CIC or the values observed, and the presence or absence of symptoms (fever, sweats, weight loss) or the histologic subtype of the tumor. Our data indicate that the measurement of CIC by the sensitive and specific raji cell assay may prove useful in the management of patients with Hodgkin's disease. In particular, serial measurement of the level of CIC could be employed to monitor the response to treatment and to detect recurrent diseases.


Mid-systolic click and mitral valve prolapse following mitral commissurotomy. Five patients with rheumatic mitral stenosis were observed to have mid-systolic clicks with murmurs of mitral regurgitation at various intervals after mitral commissurotomy. In two patients echocardiography showed an unusually rapid posterior deflection of the mitral valve coinciding exactly with a systolic nonejection click. It is speculated that the shortened, fused chordae tendineae, compromised by mitral commissurotomy, rigidly hold the valve leaflets fixed at the onset of systole. During systole, ventricular conformational changes, in the face of marginal coaptation of thickened and fibrotic mitral leaflets, allow the mitral valve to be forced abruptly towards the left atrium with great velocity. This is manifested by a loud systolic click and, in some patients, a near vertical posterior systolic deflection of the mitral valve on the echocardiogram. The systolic click may occur without echocardiographic or angiographic evidence of mitral valve prolapse. Unusually loud mid-systolic clicks can be heard in patients with rheumatic heart disease after mitral commissurotomy and may be accompanied by a distinctive echocardiographic appearance of the mitral valve.


Plasmapheresis and immunosuppressive agents in antibasement membrane antibody-induced Goodpasture's syndrome. Four patients with rapidly progressive glomerulonephritis and pulmonary hemorrhage (Goodpasture's syndrome) induced by circulating anti-glomerular basement membrane (GBM) antibodies were treated with immunosuppressive agents and varying amounts of plasma exchange. All four patients showed progressive decreases in circulating anti-GBM antibody during therapy. Two patients with established renal failure before therapy showed no improvement in renal function but had a remission from pulmonary disease. In two other patients, renal failure developed early in the course of therapy and required maintenance hemodialysis. Later, their renal function improved coincident with a decrease in circulating anti-GBM antibody. Aggressive measures to reduce the levels of circulating anti-GBM antibody may have a salutory effect on the clinical course of the disease, particularly when undertaken early.


Vascular reactivity to angiotensin II infusion during gestation. We serially tested 26 healthy, young, nulliparous patients, while they were maintained in the left lateral recumbent position, during a four-week interval (29 to 32 weeks), with progressive increments of angiotensin-II (A-II) 2.0 to 15.0 ng. per kilogram per minute). Blood pressure was recorded with an ultrasound device. All patients were followed through delivery. Three patients (12 per cent) developed pregnancy-induced hypertension (PIH); only one of these demonstrated enhanced vasoreactivity prior to PIH. Conversely, 13 patients who did not develop PIH demonstrated enhanced vasoreactivity at least once during the testing interval. Comparison of results obtained from one week to the next was evaluated in 57 test pairs; discordant data, i.e. reaction to less than 8 ng. per kilogram per minute one week and nonreaction the next, was observed in 17 pairs (30 per cent). We conclude that assessment of the risk of PIH, with the use of the diastolic pressor response to infused A-II, is unreliable.


Effect of oxytocin and oral prostaglandin E2 on uterine contractility and fetal heart rate patterns. The incidnce of uterine contractility and of abnormalities of fetal heart rate (FHR) pattern was determined in a series of 2,834 monitored gravid women with singleton pregnancies producing mature infants in vertex presentation. Those subjected to uterotonic agents for induction or augmentation of lbaor had significantly more tetanic contractions, baseline hypertonus, and coupling of contractions. Similarly, significantly more variable and late FHR decelerations occurred in stimulated labors, and these were concentrated primarily in those receiving oxytocin. The overall incidence of FHR decelerations associated with the use of prostaglandin E2 (PGE2) was comparable to that encountered in unstimulated labor. The similarity between the contractions of spontaineous labor and those labors produced by PGE2 is noted.


Vasoconstrictive effects of prostaglandins in sheep placental circulations. Changes in the uterine and umbilical circulations after intra-aortic injection of prostaglandin E2 (PGE2) or protaglandin F2alpha (PGF2alpha) to either the fetus or the mother have been examined in 13 ewes at late gestation. PGF2alpha vien to either the fetus or the mother is vasoconstrictive in both uterine and umbilical circulations. PGE2 given to the fetus results in a dissociated response with vasodilation of the uterine circulation and vasoconstriction of the umbilical circulation. PGE2 given to the mother causes a uterine contraction that precludes specific hemodynamic analysis. Therefore, exposure of either maternal or fetal ovine circulation to exogenous prostaglandins in associated with acute changes in both placental circulations. Similar responses to pertubations in endogenous prostaglandin levels may exist in pregnant sheep.


Changes in cervical compliance at parturition independent of uterine activity. A new animal model has been developed to measure intrinsic changes of cerivcal compliance during spontaneous parturition or exposure to hormonal manipulation. Intermittent measurements of cervical compliance and continous measurements of uterine and cervical pressure were made during the last month of gestation of nine pregnant ewes. Cervical compliance increased abruptly and dramatically during spontanous and dexamethasone-induced parturition. Maternal progesterone supplementation at parturition inhibited uterine contractions but not the increase in cervical compliance, demonstrating the independence of the two events. The cervix was found to contract rhythmically and vigorously with a gradual decrease in activity as parturition approached.


Cardiac output and uterine blood flow in the pregnant ewe. Fifteen pregnant ewes were studied to determine what fractions of the increases in maternal cardiac output and oxygen consumption found in pregnancy were due to the concomitant increases in blood flow to and oxygen consumption of the uterus and its tissue contents. Maternal cardiac output rose at term to 6.65 +/- 0.47 L. per minute, a value 40 per cent above the postpartum level. Uterine blood flow, which had increased at term to 1.62 +/- 0.15 L. per minute, represented 24 per cent of maternal cardiac output above postpartum levels. Maternal oxygen consumption at term was 259 +/- 11 c.c. per minute, a value 33 per cent above the postpartum level. Uterine oxygen consumption, which had increased at term to 57 +/- 4 c.c. per minute, represented 22 per cent of maternal oxygen consumption and accounted for 87 per cent of the increase in maternal cardiac output above postpartum levels. These data indicate that in the ewe most of the pregnancy-associated increases in maternal cardiac output and oxygen consumption are due to the demands of the uterus and its tissue contents.


Initiation of human parturition. X. Substrate specificity of phospholipase A2 in human fetal membranes. The substrate specificity of phospholipase A acitivty of fetal membranes and uterine decidua was investigated with the use of synthetic substrates, and emphasis was on the specificity of fatty acid esters in the sn-2 position of glycerophospholipids. Rat liver mitochondria were also used as an enzyme source for the substrate specificity studies. Phosphatidylethanolamine was found to be hydrolyzed more rapidly than was phosphatidycholine by the phospholipase A activities of human fetal membranes and uterine decidua and of rat liver mitochondria. The phopholipase A2 in fetal membranes preferentially effected the hydrolysis of phosphatidylethanolamines containing specific fatty acids in the sn-2 position in the following order: arachidonic acid greater than oleic acid less than palmitic acid. No remarkable specificity for arachidonyl esters in the sn-2 position of phosphatidylethanolamines was observed for the phospholipase A activities of human uterine decidua or rat liver mitochondria. The results of this study are consistent with the view that human fetal membrane phospholipase A2 that preferentially hydrolyzes the phosphatidylethanolamines that contain arachidonic acid in the sn-2 position is, in part, responsible for the highly selective accumulation of free arachidonic acid in the amniotic fluid of women in labor.


Effect of obesity on conversion of plasma androstenedione to estrone in postmenopausal women with and without endometrial cancer. The purpose of this study was to ascertain if a relationship exists between the transfer constant of conversion of plasma androstenedione to estrone ([rho]AE1BU) and total body weight or excessive body weight in 50 postmenopausal women, of whom 25 had adenocarcinoma of the endometrium and 25 had no endometrial disease. The [rho]AE1BU ranged from 0.015 to 0.129 in these 50 women. The [rho]AE1BU in the women with endometrial cancer was 0.051 +/- 0.006 (mean +/- S.E.), whereas that in the women with no endometrial disease was 0.039 +/- 0.004. These values are not significantly different (p greater than 0.05). The body weights of these 50 women ranged from 104 to 430 pounds. The weight of the patients with endometrial cancer was 234 +/- 16 pounds (mean +/- S.E.), and that for the women with no endometrial disease was 194 +/- 12 pounds. A statistically significant correlation (p less than 0.001) was found between [rho]AE1BU and body weight and between [rho]AE1BU and excessive body weight in both groups of women. Moreover, obesity and aging appear to act in concert to potentiate the conversion of plasma androstenedione to estrone in extraglandular sites since the [rho]AE1BU is considerably greater among obese postmenopausal women than among comparably obese premenopausal women.


Effect of obesity on conversion of plasma androstenedione to estrone in ovulatory and anovulator young women. The purpose of this study was to evaluate the transfer constant of conversion of plasma androstenedione to estrone ([p]AE1BU) as a function of total body weight and excess body weight in ovulatory and anovulatory young adult women. Twenty-four ovulatory and 31 anovulatory women were studied; their weights ranged from 90 to 350 pounds. The [p]AE1BU among these women ranged from 0.006 to 0.048. The extent of conversion of plasma androstenedione to estrone was significantly correlated with total body weight and with excessive body weight in both ovulatory and anovulatory young women. However, the mean [p]AE1BU for the anovulatory women (0.018) was not significantly different from that of the ovulatory women (0.015). Indeed, when the [p]AE1BU values of ovulatory and anovulatory women of similar total body weight or excessive body weight were compared, no difference was found in the extent of conversion of plasma androstenedione to estrone between the two groups.


Contribution of maternal circulation to blood-borne progesterone in the fetus. I. Studies on human subjects. Tritiated progesterone was infused intravenously at a constant rate into three pregnant volunteers in labor, for at least two hours before delivery. Blood samples from a maternal peripheral vein and from unbilical vessels were taken at birth. Comparison of the specific activities of progesterone in these samples indicated that 10 per cent or less of the hormone in fetal circulation is derived from transfer of maternally circulating progesterone. After consideration of reported values of umbilical vein blood flow at term and measured arteriovenous differences in concentrations of progesterone in umbilical vessels, the secretion rate of the placental hormone toward the fetus was estimated to be about 1/10 of the rate of secretion of progesterone toward the maternal circulation. About 1 per cent of the maternally circulating hormone was found to cross the placenta.


Contribution of maternal circulation to blood-borne progesterone in the fetus. II. Studies on sheep. Catheters were placed in maternal and fetal vessels in four ewes in the last month of gestation. Tritiated progesterone (P) was infused at a constant rate into a maternal peripheral vein. Specific activities and endogenous concentrations of P were measured in blood samples drawn from a maternal artery and either a fetal femoral artery or an umbilical vein. Comparison of the specific activities of P in fetal and maternal samples revealed that direct secretion of the placental hormone into the umbilical vein accounted for 90 to 93 per cent of the hormone in the fetal circulation. Estimates of the rates of production of P in the fetal circulation, obtained by multiplying metabolic clearance rates previously reported and concentrations of P in a fetal femoral artery, indicate that placental P is preferentially secreted toward the maternal circulation.


Human fetal respiration. IV. Failure of severe distress to stimulate aspiration of amniotic fluid by the immature human fetus. Reported herein are studies on fetal breathing, specifically the inhalation of labeled amniotic fluid, by immature human fetuses so severely distressed that they subsequently died in utero. Decreased rather than increased amounts of the amniotic fluid label were found in the lungs of the distressed fetuses compared to the amounts in fetuses of comparable weight that were not distressed. We conclude from this study of the immature human fetus that severe distress depresses rather than stimulates aspiration of amniotic fluid.


An in vivo system in man for quantitation of estrogenicity. I. Physiologic changes in binding capacity of serum corticosteroid-binding globulin. A modified method of measuring the binding capacity of corticosteroid-binding globulin (CBG-BC) in serum using 3H-cortisol saturation-charcoal adsorption is described. Forty serum samples per day can be assayed in duplicate, each sample with a heated nonspecific binding blank (60 degrees C.). The interassay coefficient of variation is less than 6 per cent. All age groups of men and women had similar levels of CBG-BC, except postmenopausal women, whose levels were higher (15.9 +/- 0.2 vs. 18.7 +/- 0.8 microgram per 100 ml., mean +/- standard error of the mean, respectively; z = -3.51, p less than 0.001). The variance of serum levels of CBG-BC throughout the menstrual cycle in five women was small (coefficient of variation = 13 per cent) and showed no relationship to the marked and cyclic changes in estradiol levels (coefficient of variation = 73 per cent). In pregnancy the levels of CBG-BC increased linearly after estradiol levels exceeded 1,300 pg. per milliliter and after estrone levels exceeded 500 pg. per milliliter (r = 0.88, p less than 0.001; and r = 0.85, p less than 0.001, logarithmic regression analysis). The findings of this study indicate that serum levels of CBG-BC are relatively constant in men and menstruating women. In pregnancy after a high threshold of endogenous estrogen is reached, CBG-BC increases in a direct dose-response manner as levels of estradiol increase further.


Embryonic development in consecutive specimens from recurrent spontaneous abortions. Although habitual abortion occurs in a relatively small number of patients, its successful management is often difficult. Etiologic factors may be either maternal or embryonic or both; there is much information available on maternal factors but little is known of factors related to the embryo. Information obtained from examining and karyotyping the aborted embryo or fetus may be of considerable importance in determining the possible cause of the abortion and subsequent investigation and counseling of the patient. At least two specimens from over 50 women who have had two or more consecutive spontaneous abortions have been examined and the results show that: (1) Patients aborted conceptuses of the same developmental stage, i.e., embryo or fetus, in consecutive pregnancies. This suggests that investigation should be directed to factors which may be important in the stage of pregnancy indicated. (2) Late abortions were associated with normal fetal development and factors related to the uterine environment. (3) The conceptus in an early abortion was significantly more likely to have a cytogenetic abnormality, suggesting a problem at, or prior to, conception/fertilization. A case study is also included.


Intrapartum fetal asphyxia: a preliminary report in regard to long-term morbidity. This is a preliminary report of a prospective follow-up study of 42 infants who had episodes of intrapartum fetal asphyxia at delivery identified by an acid-base assessment and a control group of 69 babies who had no evidence of intrapartum fetal asphyxia. The newborn infants were mature at delivery. There were no major neurologic disabilities in the asphyxia group. The pattern of physical growth and the mental and physical development indices of the babies of the asphyxia group were similar to those of the control group babies at 12 months of age. Results have not as yet indicated that the mature fetus with at least a terminal episode of asphyxia will exhibit evidence of handicap due to central nervous system injury.


Intrauterine growth retardation: a preliminary report of long-term morbidity. This is a preliminary report of a prospective follow-up study of 88 intrauterine growth-retarded (IUGR) babies and a control group of 97 babies with weights appropriate for gestational age. The characteristic clinical features of IUGR pregnancies were observed in the obstetric patients of the IUGR group. The babies of the IUGR group have a phase of accelerated growth during the 3 months following delivery although they continue to be smaller than the babies of the control group at 12 months of age. No major neurologic abnormalities have been noted in the IUGR babies although behavioral differences were observed during the neonatal period and at 12 months of age. There were lower mental and physical development indices at 12 months of age which were due to the IUGR babies of lowest birth weight and those with a low maternal urinary estrogen index.


Cryosurgery for the treatment of cervical intraepithelial neoplasia. Cryosurgery was used to treat 208 patients with cervical intraepithelial neoplasia. These patients were referred to our Colposcopy Clinic for investigation of an abnormal Papanicolaou smear. Prior to treatment a colposcopically directed biopsy was taken in all cases. The regrigerant used for cryosurgery was nitrous oxide. Included in the 208 patients were 57 with mild dysplasia, 76 with moderate dysplasia, 44 with severe dysplasia and 31 with carcinoma in situ. The cure rates were 100 per cent for patients with mild dysplasia, 95 per cent for those with moderate dysplasia, 96 per cent for those with severe dysplasia and 91 per cent for those with carcinoma in situ. Cryosurgery is an effective method of treating cervical intraepithelial neoplasia, with cures obtained in 199 of 208 patients in this study.


Breech presentation at term.

Breech presentation at term. Of 835 cases of breech presentation occurring from 1964 through 1973, 507 which produced mature singleton babies, were studied. This presentation has a high correlation with prematurity. This report indicates that with the term patient, a rational and competent approach results in reduction of the morbidity and mortality rates to equal those for cephalic presentation.


Cesarean section in the management of breech presentation. In a retrospective analysis of 275 consecutive deliveries of singleton infants in a breech presentation, the liberal use of cesarean section (58.2 per cent) resulted in a corrected perinatal mortality rate of zero for both vaginal and abdominal deliveries of infants weighing over 2,500 grams although perinatal morbidity was greater for vaginal deliveries (5.6 per cent) compared to cesarean section (0.8 per cent). Comparison of perinatal morbidity for delivery of infants weighing between 1,000 and 2,500 grams in a breech presentation suggests that cesarean section is the method of choice for delivery of infants in this weight range in a breech presentation.


Surface-active material in human amniotic fluid. Surface-active fractions similar to the biochemical constituents of the pulmonary surfactant system can be isolated from human amniotic fluid and lung tissue from week 10 of gestation through term. Amniotic fluid yielded 10 mg. per 100 ml. surface-active material at 10 to 28 weeks' gestation and 330 mg. per 100 ml. at term. Fetal lung at 10 weeks of gestation gave 1,233 mg. per 100 ml. and 1,670 mg. per 100 ml. at 4 days after birth. The constituent PC of these surface-active fractions from amniotic fluid and lung contained in excess of 60 per cent palmitoyl residues. PC associated with the surface-active fraction accounted for no more than 15 per cent of the total amniotic fluid concentration of this compound. Minimum surface tensions obtained with these preparations from amniotic fluid ranged from 2.5 dynes per centimeter at 33 weeks to 8.3 dynes per centimeter at 40 weeks. At 14 to 28 weeks, the surface-active fraction from lung gave a minimum surface tension of 18.1 dynes per centimeter and 7.0 dynes per centimeter by 4 days after birth. These findings are consistent with the observation that an increase in the activity or concentration of the fetal lung surfactant system takes place in the last 4 weeks of gestation. Some constituents of this system, or their derivatives which have possibly been altered as a result of biochemical changes, are found in amniotic fluid. We infer that the majority of PC in amniotic fluid is not directly associated with the biochemical constituents of the fetal lung surfactant system.


Falope Ring tubal ligation.

Falope Ring tubal ligation. By minilaparotomy or through the laparpscope, Falope Ring sterilization is accomplished by applying silicone rubber bands to the Fallopian tubes. The applicator and its use are described and 383 cases without any major complication are reported. The major advantage is elimination of thermocoagulation. The occlusion is complete in a short segment and offers theoretical possibilities of tubal reconstruction.


Loss of oncogenicity and concomitant increased immunogenicity of murine plasmacytoma cell lines. Murine plasmacytoma cells gradually decrease in oncogenicity with prolonged culture in vitro. Newly established cultures are oncogenic and cause lethal tumors. Subsequently, the cultures are oncogenic but some of the tumors regress. Later in the life of the culture none of the tumors are lethal. The longer the cells are in culture, the less oncogenic they become; eventually the cultures are nononcogenic in normal mice but do cause tumors in irradiated mice. Clones from the cultures vary from being very oncogenic to being nononcogenic. It appears that the nononcogenic cells have a selective growth advantage and become the dominant cell type in the cultures. Nononcogenic cultures are more effective for immunization to subsequent challenge with the original tumor than are the tumor cells or oncogenic cultures and may confer complete protection against lethal tumor challenge in adoptive transfer experiments. Mixtures of nononcogenic and oncogenic cells decrease the tumor-forming ability of the latter when they are injected together in one site or injected separately in two sites.


Ultrastructural changes in the liver in heatstroke. The ultrastructural changes in the human liver 24 to 96 hours after an attack of heatstroke are described. The alterations are most obvious along the vascular pole of the hepatocytes. These consist of degenerative changes or desquamation of sinusoidal lining cells, ballooning or flattening of microvilli, breaks in hepatocyte outer membranes, and electron-lucent vacuoles along the sinusoidal border. Also noteworthy is the appearance, in a number of cases, of basement membranes or ill-defined electron-dense material which may be of basement membrane character. Sinusoidal elements, such as erythrocytes, are found in hepatocytes, and hepatocellular debris appears in sinusoids. The membranes of hepatocytes and sinusoidal lining cells thus seem to be the prime targets of the hepatic injury in heatstroke. Other changes in the hepatocytes include vesiculation of endoplasmic reticulum, detachment of ribosomes, and alterations of mitochondria. Morphologic evidence of intravascular coagulation of intravascular hemolysis is often encountered. A comparison between the findings described here and those in experimental hyperthermia suggests that many of the hepatic changes seen in heatstroke are due to an excessively high tissue temperature per se but that some of the alterations are probably a consequence of complicating factors such as hypoxia, intravascular hemolysis, or disseminated intravascular coagulation.


Structural analysis of hemopoiesis in S1/S1d anemic mice. This study is an ultrastructural analysis of hemopoiesis in S1/S1d anemic mice. The anemia in this strain is caused by a defect in hemopoietic microenvironment which fails to support hemopoiesis. Marrow cellularity is reduced and vascular channels are dilated. Coverage of sinus endothelium by adventitial cells is nearly twice as in normal mice, suggesting a reduced rate of cell traffic into the circulation. Central macrophages are small with little or no interdigitation with erythroid cells and no crystalloid inclusions as seen in normal littermates. The findings suggest that a fundamental abnormality in the central macrophage may be responsible for the defect in hemopoietic microenvironment.


Inhibition of human neutrophil oxidative metabolism and degranulation in vitro by nitroblue tetrazolium and vitamin E. The effect of a mixture of nitroblue tetrazolium (NBT) and vitamin E on the metabolism and ultrastructure of polymorphonuclear leukocytes (PMN) from normal subjects or patients with chronic granulomatous disease (CGD) was determined in vitro. Increasing concentrations of NBT and vitamin E progressively decreased rates of oxygen consumption and 1-14C-glucose oxidation by normal PMN stimulated with particulates to a degree that exceeded either agent alone. NBT-vitamin-E also inhibited vacuole formation and the cytochemical release of myeloperoxidase-positive granules. The depressed oxidative metabolism and degranulation of NBT-vitamin-E-treated control PMN closely approximated the blunted responses of CGD PMN which were similar alone or in the presence of NBT-vitamin-E. In contrast to these effects, the highest concentration of NBT-vitamin-E used in the study did not damage, decrease rates of unstimulated oxidative metabolism of, or impair ingestion of particulates by control or CGD PMN. NBT and vitamin E impose a state on normal PMN which is remarkably similar to that observed in PMN from patients with CGD.


Nephrotoxic nephritis in rabbits. The role of the sympathetic nervous system. The sympathetic nervous system and catecholamines play a major role in fibrin deposition in organs in rabbits after endotoxin administration. Glomerular fibrin deposition is also a key factor in the pathogenesis of nephrotoxic nephritis in rabbits, but the role of the sympathetic nervous system in this type of fibrin deposition has not been defined. We investigated sympathetic nervous system involvement in nephrotoxic nephritis using a model of isolated chemical sympathectomy with 6-hydroxydopamine. Different quantities of pooled nephrotoxic serum were injected intravenously into control and sympathectomized rabbits to produce a known spectrum of pathology in normal rabbits. Animals were killed and their organs were analyzed to ascertain that sympathectomy had been accomplished. Biochemical, immunohistologic, and histopathologic evaluation of the animals, comparing controls and sympathectomized rabbits, revealed no differences in the degree of renal damage for a given quantity of nephrotoxic serum. We conclude that, in the rabbit model, the sympathetic nervous system plays no significant role in the pathogenesis of fibrin deposition and glomerular damage in nephrotoxic nephritis.


The morphology of the Legionnaires' disease organism. The Pennsylvania Department of Health, Bureau of Laboratories, has isolated the Legionnaires disease organism from two patients with Legionnaires' disease proved by serologic techniques. We have studied the morphology which the isolate assumes in yolk sac tissue and on bacteriologic media. The organism was Giménez-positive and gram-variable. Using an indirect immunofluorescent procedure, it was shown to react with convalescent serum samples taken from patients who had Legionnaires' disease. The organism multiplies by binary fission extracellularly and intracellulary; is both coccoid and bacillary in form; and contains characteristic cytoplasm, nucleoids, a cytoplasmic membrane, and a small cell wall of variable size. It may produce spores of unusual appearance. Intracellular replication characteristically occurs within vacuoles. The Legionnaires' disease organism conforms to the morphologic criteria for a prokaryocyte.


Induction of cytochrome P-450 in a selective subpopulation of hepatocytes. The objective of this study was to determine whether the inductive effect of phenobarbital (PB) on liver cytochrome P-450 was the result of the action of this drug on all or some hepatocytes. For this purpose, a light (cell band I) and a heavy (cell band II) subpopulation of hepatocytes were separated from rat liver in a continuous density gradient. To determine the location of these hepatocytes in tissue, [14C]bromobenzene, which binds covalently to centrilobular hepatocytes, was administered. The specific activity (14C dpm/mg protein) was greater in cells of band I than in cells of band II, suggesting a predominant contribution of centrilobular hepatocytes to the lighter cell band. Microsomes were separated from each cell subpopulation after 3 days of PB administration and cytochrome P-450 was measured. Although a fivefold increment in cytochrome P-450 content of light hepatocytes was noted, the content of heavy hepatocytes was similar to that of the respective subpopulation in controls. Concomitantly, PB administered for 3 days induced the smooth endoplasmic reticulum of centrilobular hepatocytes only, as revealed by electron microscopy of whole tissue. These results indicated that PB induces cytochrome P-450 in a selective subpopulation of hepatocytes, most likely located near the terminal hepatic venule.


Magnesium net fluxes and distribution in rabbit myocardium in irreversible contracture. Distribution of magnesium (Mg) in heart muscle was studied by measuring fluxes of Mg and transmembrane potentials as a function of perfusate [Mg2+] after a massive increase in permeability of the sarcolemma was induced in the Langendorff prepared heart from the Nembutal-anesthetized rabbit. After onset of 0 mM [Ca2+] perfusion which produced excitation-contraction (E-C) uncoupling and mechanical arrest, action potentials recorded from subepicardial cells showed an increase in duration and decrease in amplitude, which progressed until no transmembrane potentials could be observed. Restoration of physiological salt solution perfusion after 15 min of [Ca2+]-free perfusion caused an irreversible contracture that was associated with 1) efflux of potassium (K) and myoglobin, 2) perfusate [Mg2+]-dependent flux of Mg, and 3) transmembrane potentials of 0 mV. The magnitude of net efflux of K and myoglobin during contracture was unaffected by perfusate [Mg2+]. During the first 2 min of contracture, net efflux of Mg (mumoles per gram wet muscle +/- SE) was 1.37 +/- 0.09 and 0.48 +/- 0.19 during 0 mM and 2.5 mM [Mg2+] perfusion, respectively; but a net influx of 0.56 +/- 0.23 occurred during 5 mM [Mg2+] perfusion. Total sarcoplasmic [Mg] may correspond to perfusate [Mg2+] of 3.6 mM, which was found by interpolation to prevent any net flux of Mg during contracture. 3.6 mM may, therefore, represent the upper limit of the intracellular free-ionized Mg concentration in rabbit heart.


Glucose metabolism by adult hepatocytes in primary culture and by cell lines from rat liver. The metabolic fate of [U-14C]glucose has been examined in detail in adult rat hepatocytes in primary monolayer culture, as well as in two permanent cell lines--Buffalo rat liver (BRL) and transplantable rat hepatoma (HTC) cells-derived from normal rat liver and from rat hepatoma, respectively. Under defined conditions of incubation, at a glucose concentration of 5.5 mM, the three types of cultured liver cells exhibited pronounced differences in glucose metabolism. Primary cultures, like the intact liver, differed from the cell lines in consuming relatively small amounts of glucose and converting approximately 50% of the total metabolized glucose to lactate. By contrast, the permantent cell lines consumed glucose at a 40-fold greater rate than did primary cultures, converting 80--90% of the carbohydrate to lactate. Oxidative metabolism of glucose carbon also differed among the three types of liver culture. Of the total [U-14C]glucose consumed, primary cultures converted approximately 30% to labeled CO2 per hour, whereas the liver cell lines converted 5--10%. Finally, glucose metabolism in primary culture exhibited adaptation as hepatocytes aged in culture, shifting progressively toward the pattern exhibited by the permanent cell lines. This change occurred over a time course similar to that for other kinds of functional change in hepatocytes in primary culture and thus may be relevant to the general problem of phenotypic alteration in liver cell culture.


Effects of phloretin and theophylline on 3-O-methylglucose transport by intestinal epithelial cells. Phloretin and theophylline each exert an immediate inhibitory effect on the Na+-independent, facilitated-diffusion transport system for sugar associated with intestinal epithelial cells. Phloretin inhibits approximately 50% more of the total Na+-independent sugar flux than theophylline. Neither agent has an immediate effect on the Na+-dependent, concentrative sugar transport system, although preincubation of the cells with phloretin causes a significant inhibition. The slowly developing effect is correlated with a decrease in cellular adenosine triphosphate (ATP) and an elevation of intracellular Na+. Other agents which elevate cell Na+ also inhibit Na+-dependent sugar influx, even if ATP levels are not depleted. On the other hand, if ATP is depleted by phloretin under conditions in which the cells do not gain Na+, the inhibitory effect on Na+-dependent sugar flux tends to disappear. The slow-onset phloretin effects are due to transinhibition of the Na+-dependent sugar carrier by cellular Na+. When the passive sugar carrier is inhibited by phloretin or theophylline, the concentrative system can establish an enhanced sugar gradient. Because of the secondary metabolic effects of phloretin, theophylline induces a greater gradient enhancement despite its more limited effect on the passive sugar-transport system. Sugar gradients as large as 20-fold are induced by theophylline, in contrast to 12-fold gradients observed in the presence of phloretin and approximately 7- to 8-fold for untreated cells. These results are discussed in terms of conceptual questions regarding the energetics of Na+-dependent transport systems.


Properties of thyroidectomized rat extensor muscle. Basic mechanical and electrical properties of rat extensor muscle were analyzed 4--6 wk after thyroid removal. Isometric twitch tensions in thyroidectomized (Tx) rat muscle varied considerably, with over 60% of the muscles showing abnormally low values and the remainder showing a high twitch force. The duration of the twitch was significantly increased from 137 to 245 ms but contraction and half-relaxation times were not significantly changed. Tetanic force was not effected by thyroidectomy. Electrical properties of the muscle fiber membranes were made exclusively via intracellular techniques. The resting membrane potential was slightly higher in thyroidectomized rats (-79 mV) as compared to sham controls (-78 mV). Both direct and indirect action potentials showed higher overshoots, amplitudes, and rates of depolarization in thyroidectomized rats. The threshold of the indirect action potential appeared at a higher transmembrane potential as compared to sham-operated controls. The input resistance, space constant, time constant, and specific membrane resistance were all significantly increased in thyroidectomized rat extensor muscle, whereas fiber diameter and capacitance were significantly decreased. Estimates of specific ionic conductance show that both potassium and chloride conductance are decreased in thyroidectomized rat muscle.


Reduced triglyceride secretion: a metabolic consequence of chronic exercise. Chronic exercise training is recognized to reduce plasma lipid levels in man and animals, but the mechanism(s) mediating this phenomenon have not been defined. In the present study, we examined triglyceride (TG) production and disposal in vivo in a genetic model of human type IV hyperlipemia, the obese Zucker rat. Utilizing the normolipemic thin littermate as the control, we investigated endogenous production of TG utilizing the Triton methodology and peripheral disposal of an exogenous lipid emulsion utilizing Intralipid injection. In the sedentary state, the hyperlipemic obese Zucker rat demonstrated a threefold elevation in triglyceride secretion rate relative to the normolipemic thin littermate. After a 3-wk period of exercise training, a reduction of basal plasma TG concentration of 42% was associated with a 51% reduction in TG secretion rate, a change adequate to account for the hypolipemic response. Moreover, chronic exercise training also improved the ability to dispose of an Intralipid load. A similar reduction in TG production with reduced TG removal was observed in the thin normolipemic rats, a result that suggests that the lipid lowering response to exercise training may be predominantly mediated by reduced secretion of TG. The possible relationship between reduced TG secretion and alterations in the bihormonal axis of insulin and glucagon are discussed.


Effect of sugar and monoglyceride on fatty acid esterification. The effect of hexose and monoolein on fatty acid esterification was studied in everted rings of rat jejunum. By use of [3H]oleic acid and [U-14C]glucose, esterification via both phosphatidic acid and monoglyceride pathways was quantified. Our results showed that 1) metabolizable sugars stimulate fatty acids esterification regardless of their mode of transport; 2) in the presence of glucose alone, in vitro fatty acid esterification is mediated entirely by the phosphatidic acid pathway; 3) glucose stimulates both esterification pathways in the presence of monoolein; 4) monoolein stimulates only the monoglyceride pathway and has no effect on the phosphatidic acid pathway; and 5) the rate-limiting factor in the presence of monoolein alone is the formation of acyl-CoA, whereas in the presence of glucose alone, the rate-limiting factor is the formation of alpha-glycerophosphate.


Inhibition of lower esophageal sphincter circular muscle by female sex hormones. To determine the effect of estrogenic and progesteronic activity on lower esophageal sphincter (LES) circular muscle, studies were performed on 20 adult opossums. Does-response curves on circular smooth muscle strips from the LES were constructed for gastrin and acetylcholine alone, and with 17beta-estradiol and/or progesterone added. Each female hormone significantly decreased the maximal LES muscle responses to gastrin and acetylcholine. A combination of 17beta-estradiol and progesterone abolished the response to gastrin. In contrast, the male sex hormone, dihydrotestosterone, had no effect. In conclusion, administration of estrogen and progesteron, but not dihydrotestosterone, in vitro reduced LES muscle responses to gastrin and acetylcholine. These studies suggest that the female sex hormones can alter LES function and potentially may be of importance in the pathogenesis of heartburn of pregnancy.


Intestinal O2 consumption and 86Rb extraction during arterial hypoxia. Earlier reports indicated that arterial hypoxia not only dilated intestinal resistance vessels but also increased capillary filtration coefficients. The latter finding was interpreted as reflecting an increased number of perfused capillaries. Because both increased blood flow and increased capillary density would tend to maintain tissue oxygenation in spite of arterial hypoxia, the main purpose of this paper was to determine how effectively intestinal O2 utilization is maintained during arterial hypoxia. Therefore, I perfused isolated loops of canine small bowel at constant arterial pressure. Under this condition, reducing arterial PO2 to a mean value of 46 +/- 2.4 mmHg caused blood flow to increase to 146% of control, and O2 consumption was kept within 26% of control. In gut loops perfused at constant blood flow, arterial hypoxia depressed O2 uptake still further, but measurements of 86Rb extraction confirmed that the density of the perfused capillary bed increased. Thus, the responses of both resistance and exchange vessels tend to maintain O2 delivery to intestinal tissue during arterial hypoxia.


Transport characteristics of isolated newborn rabbit ileum. Segments of ileum from newborn rabbits were mounted as flat sheets in Lucite chambers and transmural fluxes of Na, Cl, and alanine were measured in the absence of electrochemical potential gradients. In the presence of 140 mM Na, the ileum of the newborn exhibited a serosa-positive electrical PD and a corresponding short-circuit current (Isc) which was markedly enhanced by the addition of D-glucose of L-alanine to the mucosal solution. Alanine-induced increments in Isc were a saturable function of the mucosal alanine concentration. In the presence of Na, alanine was actively absorbed, and the net alanine flux was a saturable function of alanine concentration. When the Na in the bathing solutions was completely replaced by choline, Isc declined to near zero, and the response of Isc to mucosal alanine was abolished. In addition, active amino acid transport was abolished in the absence of Na. In the absence of alanine, the isolated ileum of the newborn actively absorbed Na and Cl, and the algebraic sum of the net movements of these ions accounted for Isc. In the presence of alanine, active Cl transport was abolished and Isc was equal to the net Na absorption. These results indicate that the ileum of the newborn rabbit is similar to that of the adult in its ability to actively absorb Na, Cl, and alanine, but differs from the ileum of the adult by having a greater passive permeability to ions and amino acid, and differs particularly with regard to the effect of mucosal alanine on transmural ion transport.


Sexual maturation of male rats in continuous light. Male rats were raised from birth in either continuous light (LL) or in 14 h light/10 h dark per day (LD) at 22 +/- 1 degree C. Food and water were administered ad libitum. Groups of rats were killed by decapitation at 14, 20, 25, 35, 41, 45, 51, 55, 58, 63, and 79 days of age. Testicular (TW), ventral prostate (VPW), and seminal vesicle (SVW) weights were measured. Serum concentrations of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and androgens were quantified by radioimmunoassay. Results indicate no significant change in TW or spermatogenesis. Spermatozoa were first seen in the lumen of 10% of seminiferous tubules at 35 days of age in both LD and LL rats and by 42 days of age, 80% of tubules from both LD and LL rats contained spermatozoa in the lumen. A highly significant depression in accessory structure development (VPW, SVW) was observed as a result of LL exposure. Serum FSH levels in LL rats were depressed on days 45, 51, 55, and 58 but elevated at 79. Serum PRL concentrations were elevated in LL rats on days 41, 55, 58, 63, and 79, whereas serum androgen levels were depressed on days 58, 63, and 79. Results suggest that exposure to LL results in delayed maturation of the accessory structures in the reproductive system of the male rat possibly as a result of reduced FSH or elevated PRL levels, which in turn may modify the rate and pattern of LH and/or androgen secretion.


Adrenal gland in experimental renal hypertension. The effect of total adrenalectomy on the mechanisms of arterial pressure control was studied in uninephrectomized rats with and without renal artery stenosis (Goldblatt one-kidney model). Four groups of rats were prepared and maintained on high-salt intake (1% NaCl): uninephrectomized-KI; KI + adrenalectomy-KIAx; uninephrectomized with renal artery stenosis-GI; and GI with adrenalectomy-GIAx. Over 3 wk blood pressure rose significantly in both GI and GIAx but the degree of increase in GI was greater. Hyponatremia, hyperkalemia, and increased plasma urea nitrogen were observed in both KIAx and GIAx. Plasma renin concentration (PRC) and plasma renine activity (PRA) were markedly increased and plasma renin substrate (PRS) was decreased in both adrenalectomized groups. Infusion of saralasin resulted in significant and similar reductions in mean arterial pressure (MAP) in KIAx and GIAx, but had no effect on MAP in KI and GI. These results allow approximations of the contribution to total MAP of identifiable components, which are: the total adrenal component, the renin-angiotensin system component, which partially compensates for loss of the adrenal secretions, and the independent effect of the renal artery clip. Thus, a multifactorial analysis of GI hypertension is provided.


Biological function of metallothionein. V. Its induction in rats by various stresses. Induction of metallothionein (a Zn-binding protein) was investigated in liver and kidneys of rats under the following stresses: cold environment, hot environment, heat burn, strenuous exercise, and CCl4 intoxication. As markers of metallothionein (MT) synthesis, [14C]cystine and 65Zn were injected parenterally into rats, and MT in liver and kidney supernatants was separated on Sephadex G-75 columns. Among stresses tested, the greatest stimulations of MT synthesis in liver were observed under cold (315%), strenuous exercise (302%), and CCl4 intoxication (543%), as evidenced by increased amount of [14C]cystine and 65Zn incorporation into the MT fraction. In contrast to liver, only small responses were observed in MT synthesis in kidneys. There was a general decline in plasma Zn levels in rats under the stresses employed. However, no great differences were observed in Zn levels in whole liver and kidneys. The present study suggests that various unrelated physiological stresses, which are accompanied with a change in Zn distribution, increase the synthesis of MT in liver of rats.


Mechanism of lithium-induced hypercalciuria in rats. Chronic administration of lithium salts is associated with hypercalciuria in the rat. To study the renal and extrarenal mechanisms of this phenomenon, we utilized balance and clearance techniques in rats pair-fed diets with or without Li2CO3 (0.5 meq/day per rat). Lithium induced hypercalcemia (mean +/- SE: 5.40 +/- 0.09 VS. 5.06 +/- 0.05 meq/liter) and hypercalciuria (Ca/creatinine = 0.28 +/- 0.04 vs. 0.13 +/- 0.03) only during feeding. When CaCO2 supplement to a calcium-deficient diet was abruptly withdrawn, hypercalciuria was abolished. However, polyuria and polydipsia persisted. No significant changes in serum phosphate, urine phosphate, sodium, pH, or citrate were observed. Chronic parathyroidectomy (PTX) also abolished this effect. During clearance studies, fasting excretion of calcium was similar between treated and control animals. Superimposed acute PTX resulted in comparable changes, hence arguing against primary changes in renal calcium reabsorption or changes in parathyroid hormone effects on the renal tubule. Thus, lithium produces absorptive hypercalciuria by a mechanism dependent on intact parathyroid glands and adequate diet calcium, but independent of urine sodium, phosphate, or pH. The active component of gut calcium transport may be involved, possibly via alterations of vitamin D metabolism.


LES pressure response to pentagastrin: effect of cholinergic augmentation and inhibition. Studies were performed on the anesthetized adult opossum to examine a) the pressure response of the lower esophageal sphincter (LES) to both bolus injections and continuous infusions of pentagastrin (PG), and b) how this response is affected by either cholinergic antagonism with atropine or cholinergic enhancement with edrophonium, an anticholinesterase. Both the bolus injection and the continuous infusion of PG produced dose-dependent rises in LES pressure. The peak pressure responses occurred at 1 microgram/kg and 32 microgram/kg-h, respectively. Atropine (100 microgram/kg), in a dose that significantly diminished the LES response to exogenous acetylcholine, had no significant effect on PG-induced increases in LES pressure. Similarly, edrophonium (100 microgram/kg) had no effect on the response of the LES to PG stimulation. The Sphincter's response to exogenous acetylcholine was significantly enhanced after edrophonium pretreatment. From these studied, we conclude that PG-induced increases in the LES pressure are due primarily to the direct stimulation of sphincter smooth muscle rather than to activation of excitatory cholinergic neurons.


Regulation of cardiac protein balance by hydrocortisone: interaction with insulin. In fetal mouse hearts in organ culture the rate of protein synthesis was substantially reduced and the rate of protein degradation slightly increased by hydrocortisone in the absence of insulin, but in the presence of insulin the steroid caused a small increase in protein synthesis and a significant reduction in protein degradation. Hydrocortisone promoted the net uptake (or reduced the net release) of branched-chain amino acids independent of insulin and independent of simultaneous changes in protein balance. The specific activities of the lysosomal enzymes cathepsin D and glucosaminidase were reduced by hydrocortisone in all media, whereas the specific activity of creatine kinase increased when the medium contained insulin but decreased in the absence of insulin. It is concluded that hydrocortisone regulates cardiac protein balance via alterations both in synthesis and in degradation. Some of the hormone's myocardial effects are influenced by insulin so that hydrocortisone is anabolic in its presence but catabolic in its absence.


Loss of glucagon suppression of feeding after vagotomy in rats. Infusion of pancreatic glucagon through the hepatic-portal vein decreased short-term food intake in sham-vagotomized but not in subdiaphragmatically vagotomized rats. Measurement of hepatic glycogen storage  showed that vagotomized rats maintain a lower glycogen level than control animals over the four fasting periods evaluated. To determine whether the absence of a glucagon effect on feeding in vagotomized rats was the result of the reduced amount of substrate for glycogenolysis, vagotomized rats were not fasted and control animals were food deprived for 8h to produce comparable hepatic glycogen levels. Hepatic-portal infusion of glucagon into these differentially fasted animals suppressed feeding in control rats but not in vagotomized rats. It is concluded that the ineffectiveness of glucagon in suppressing feeding in vagotomized rats is not due to reduced concentration of hepatic glycogen. Instead, it is likely that glucagon induces glycogenolysis, but the glucose, or some other correlate of glycogen breakdown, loses its ability to produce satiety subsequent to vagotomy.


Acid secretion and motility of isolated mammalian gastric mucosa and attached muscularis externa. A procedure is described for the setting up of a preparation of mammalian gastric mucosa from kitten or ferret. The mucosa is stripped of its outer muscle coats except for a 2-mm strip of circular muscle fibers running across the diameter of the preparation. The connections of this strip to the underlying mucosa are undisturbed. The preparation is immersed on the nutrient side in Krebs-Henseleit solution, gassed with 95% O2 and 5% CO2, and the secretory side contains 5% dextrose, both at 37 degrees C. Acid secretion is determined by a pH stat method and motility is recorded by a strain gauge attached to one end of the muscle strip. Secretory and motility responses are recorded for the three main parietal cell agonists, acetylcholine (ACh), pentagastrin, and histamine. In all cases, concentrations adequate to produce secretory effects also produced modulation of motor activity. In both animals the similarity between the motility responses produced by cholinergic stimulation and pentagastrin was notable.


Interdigestive motor activity of Heidenhain pouches in relation to main stomach in conscious dogs. A great number of studies using Heidenhain pouches have been reported, but most of them have been concerned with secretory activity. Studies on the motor activity of the pouch are few, and our knowledge about it is rather limited. In the present study, therefore, long-term changes in contractile activity of the Heidenhain pouches were recorded simultaneously with those of the main stomach in conscious dogs by means of chronically implanted force transducers. It was found that during the interdigestive state Heidenhain pouches contracted precisely in association with the main stomach. During this time a series of strong contractions arose simultaneously in the Heidenhain pouch and the main stomach, lasted for 24.2 +/- 1.90 min, and then ceased abruptly. Such strong contractions were followed by a long period of motor quiescence lasting for 86.9 +/- 6.06 min. These characteristic recurring episodes in the Heidenhain pouch and the main stomach lasted during the interdigestive state but were inhibited by the ingestion of food or intravenous administration of pentagastrin. These findings indicate that the interdigestive motor activity of the stomach is strongly controlled by a humoral factor(s) rather than the parasympathetic nervous system; however, we also propose a possible role for the sympathetic nervous system for coordinated occurrence of the interdigestive contractions between the Heidenhain pouch and the main stomach.


Factors influencing transepithelial potential difference in mammalian distal tubule. Studies were performed to examine some electrical properties of the mammalian distal tubule. Experiments were performed to evaluate the influence of changes in ion concentration in luminal fluid on transepithelial potential difference. Variations in the concentration of Na+ and K+, near the physiologic range, resulted in only modest changes in potential difference. During changes in Na+ the average slope, deltaV/ln C2/C1, was -1.52 +/- 0.39 mV and during variations in K+ the slope was -5.60 +/- 0.95 mV. Changes in Cl- concentration had no effect on transepithelial potential difference. Since the sum of transferase numbers did not equal 1, it seems likely that potential difference is influenced by a shunt current due to cellular rheogenic pumps. These data, therefore, indicate that variations in ion concentration in tubular fluid of the mammalian distal tubule do not significantly influence the resting transepithelial potential difference, and they suggest that analysis of permselective properties of the luminal cell membrane by transepithelial electrophysiologic approaches is probably invalid.


Effect of phosphate deprivation on renal phosphate transport in the dog. In order to examine the role of dietary intake of phosphate in regulating renal phosphate transport, clearance and micropuncture studies were performed in 25 dogs with various duration of phosphate deprivation induced by low phosphate diet and aluminum hydroxide gel. In phosphate deprivation of 17-41 days duration, the phosphaturic response to extracellular volume expansion (ECVE) was blunted in the intact group and was virtually abolished in the acutely thyroparathyroidectomized (TPTX) group. With longer phosphate deprivation of 53-110 days, no phosphaturia occurred after ECVE or administration of parathyroid hormone (PTH), even with intact parathyroids. These alterations in phosphaturic responses did not correlate with the plasma phosphate but rather with the duration of phosphate deprivation. Fractional proximal tubule phosphate reabsorption was enhanced in phosphate deprivation and the proximal tubule fluid-to-ultrafilterable phosphate ratio appeared to be a good index for the degree of phosphate deprivation. Acute infusion of phosphate to raise plasma phosphate slightly above normal did not completely restore the responsiveness to ECVE. It is concluded that the adaptive response to phosphate deprivation occurs in both proximal and distal nephron segments and that factors other than plasma phosphate are primarily responsible for such an adaptation.


Superficial nephron tubular-vascular relationships in the rat kidney. Silicone rubber injections of methyl salicylate-cleared rat kidneys were performed. In 50 of 56 injections of superficial nephrons with their accompanying blood supply, the efferent vessel and early proximal tubule were closely approximated. In 18 of 21 tubular injections filling through the pars recta, the proximal tubule folded upon itself with early and late proximal segments, in close contact, located over their parent glomerulus, and the midproximal segments separate and located over their parent interlobular artery. The distribution of blood was serially through the early-late proximal region above the glomerulus via a long unbranched efferent vessel, via branches over the capsular surface, via capillaries down through the midproximal region, then into the interlobular vein. The observed anatomical pattern of the superficial nephron appears to permit direct functional interactions between the juxtaposed early and late proximal tubule, and in turn may effect midproximal function via the distribution of blood (modified by early proximal) from the efferent vessel to midproximal convolutions. In addition, the relationship between specific segments of the proximal tubule and specific portions of the postglomerular peritubular blood supply may be important in determining the distribution of peritubular physical forces to these nephrons.


Mathematical modeling of transport in structured tissues: corneal epithelium. A computer model has been constructed to describe multi-ionic transport across an epithelium consisting of a transcellular pathway in parallel with a shunt. The model is parameterized to simulate rabbit corneal epithelium. Calculations show that when this tissue is stimulated by epinephrine at open circuit, there is a flux of electrolyte across it into the tears. The magnitude of the flux is sensitive to paracellular resistance, which also affects the potentials across the mucosal cell border and entire epithelium. The electrolyte extrusion rate of the tissue is found to be near zero in the absence of stimulation. More generally, it is shown that for epithelia whose structure is at least as complex as that used  here, the active transport rate of ions exceeds their net flux at short circuit; tracer fluxes in one direction at two polarizations cannot be used to identify active transport or significant tracer interactions; and tracer measurements yield ionic permeabilities only at short circuit and only if the ion is not actively transported.


Permeability changes in Necturus proximal tubule during volume expansion. The permeability of Necturus proximal tubule to hydrophilic nonelectrolytes of varying molecular size was studied under control conditions and during isotonic expansion of the animal's extracellular volume. Transepithelial permeability was measured in perfused tubular segments under conditions of zero net water flux. During volume expansion, tubular permeability to urea increased slightly, whereas mannitol decreased slightly and permeability to sucrose was significantly decreased. Volume expansion had a greater effect on osmotic flow parameters; the NaCl reflection coefficient decreased from 0.64 to 0.47 (summer animals) and from 0.41 to 0.27 (winter animals). Osmotic water flux and hydraulic conductivity increased but only in the lumen-to-capillary direction. Reflection coefficients of nonelectrolytes measured at the apical surface were reduced during volume expansion for probing molecules greater than 3 A in radius and were unchanged for smaller molecules, less than 3 A, suggesting two pore populations. We propose that an increase in tight-junction permeability can account for modification of osmotic flow parameters, whereas the whole thickness of the epithelium, particularly the intercellular space, plays the dominant role in regulation of diffusional permeability.


Generation of transepithelial potentials by isolated perfused reptilian distal tubules. Transepithelial potentials were measured in the most distal segments of garter snake (Thamnophis spp.) distal tubles perfused in vitro. The segments generated high lumen-negative potentials when sodium was in the lumen. The size of the potentials was a saturable function of luminal sodium concentrations between 0 and 32 mM. The potentials were stable with time only when sodium concentrations in the lumen were less than 30 mM. Perfusion with high sodium concentrations resulted in transient potentials. Stable potentials changed markedly when the lumen sodium concentration or the bath potassium concentration was altered suddenly, but they were independent of lumen potassium concentrations and bath sodium concentrations. Amiloride stimulated or inhibited the potentials, ouabain partially depressed them, and ethacrynic acid and cyanide inhibited them slowly and often irreversibly. We conclude that distal transepithelial potentials reflect sodium transport from lumen to bath across a tight asymmetric epithelium which differs from other sodium-transporting epithelia in that stable transepithelial potentials are maintained only with luminal sodium concentrations less than 30 mM.


Techniques for microdrop analysis of fluids (sweat, saliva, urine) with an energy-dispersive X-ray spectrometer on a scanning electron microscope. Volumes of 10(-10) liter of sweat, saliva, and urine were analyzed with an energy-dispersive spectrometer (EDS) X-ray analyzer on a standard scanning electron microscope (SEM). Results of the EDS analysis of diluted and undiluted samples were verified by comparison with results of analyses of the same sample prepared by conventional quantitative methods. Except for Cl in concentrated urines and Mg in low concentrations, good agreement was found between the methods. The analysis provides quantitation of most elements of biological interest present in concentrations of about 1 mM, while it demonstrates good linearity (r greater than 0.99) throughout a wide range of commonly encountered biological concentrations. Reproducibility of the analysis is on the order of 2% and the minimal determinable concentration is generally between 0.5 and 1.0 mM for S, P, K, and Ca and slightly more than 1.0 mM for Mg.


Interaction of descending spinal sympathetic pathways and afferent nerves. With the use of computer-aided techniques, the interaction of descending spinal sympathetic pathways and afferent nerve fibers (cervical dorsal roots and tibial nerve) in regulation of thoracic (T2) preganglionic nerve activity was investigated in anesthetized, vagotomized, and paralyzed cats. High-frequency activation of a sympathoinhibitory pathway (ventrolateral funiculus) depressed the evoked discharges in the T2 preganglionic nerve elicited by stimulation of a sympathoexcitatory pathway (dorsolateral funiculus) and the spinal component of the somatosympathetic reflex. Submaximal evoked responses were also inhibited through baroreceptor reflex activation (blood pressure elevations up to 225 mmHg). Facilitation of the spinal component of the somatosympathetic reflex occurred during stimulation of the excitatory pathway. Carotid occlusion (baroreceptor inactivation) facilitated the submaximal evoked discharges from stimulation of the descending excitatory pathway. These data support the contention that sympathetic nerve activity can be modified by the integration of excitatory and inhibitory impulses at the spinal level.


Norepinephrine metabolism in canine saphenous vein: prevalence of glycol metabolites. To examine the disposition of [3H]norepinephrine ([3H]NE) in adrenergically innervated veins, helical strips of canine saphenous veins were incubated in Krebs-Ringer solution containing D,L[3H]NE (2 X 10(-7) M) for 2 h. [3H]NE and its metabolites were measured in extracts of veins and in superfusate (Krebs-Ringer) collected during basal conditions and during release of [3H]NE evoked by electrical stimulation (1-8 Hz), tyramine (5 X 10(-6) to 5 X 10(-4) M), or high concentrations of potassium (35-100 meq/liter). During basal conditions, the efflux from veins comprised mainly metabolits of [3H]NE, especially 3,4-dihydroxphenylglycol (DOPEG) and 3-methoxy-4-hydroxyphenylglycol (MOPEG); this pattern was unchanged by cocaine treatment, and monoamine oxidase inhibition reduced the formation of DOPEG. During evoked release of NE, the major metabolites in the perfusate were DOPEG, MOPEG, and normetanephrine, and their proportions differed with the stimulus used: O-methylated metabolites in the perfusate always increased more than did the deaminated catechol compounds; DOPEG and MOPEG were released in greater amounts than the corresponding acids; and cocaine treatment caused a higher content of all metabolites except DOPEG. 3-Methoxy-4-hydroxymandelic acid was also formed by the vein but was retained in the tissue.


Effect of activation sequence on MVO2 before and after coronary ligation. In pentobarbital-anesthetized, open-chest dogs with fixed heart rate, cardiac output, and systemic arterial pressure, ectopic ventricular activation originating from apical as compared to basilar regions of either ventricle was associated with small (3--5%) but significantly (P less than 0.005) lower myocardial O2 consumption (MVO2) and thus higher left ventricular (LV) efficiency without change in LV end-diastolic pressure (LVEDP), work index (LVWI), and LV dP/dt. Data obtained during epicardial and corresponding endocardial activation did not differ. During normal ventricular activation, MVO2 remained unchanged but LVEDP was significantly (P less than 0.005) lower, thus yielding higher LVWI and efficiency. MVO2 differences among ectopic sites were abolished after coronary artery occlusion, whereas data obtained during endocardial and epicardial on normal and ectopic activation were not affected. Thus, normal activation resulting in lower LVEDP is most efficient; apical ventricular activation is less efficient at the same MVO2P basilar is the least efficient, because both MVO2 and LVEDP are higher. Ventricular activation sequence changes do not constitute a substantial determinant of MVO2.


Estimation of the filtration coefficient of pulmonary exchange vessels. Filtration characteristics of the exchange vessels in isolated dog lung were studied by calculating the volume conductance (LP,C) with use of different components of the weight-gain curve following changes in capillary pressure. In one series of lungs, capillary pressure was elevated to levels that produced alveolar edema (29.4 +/- 5.3 (mean +/- SD) mmHg), and total alveolar capillary membrane conductances (LP,T) were calculated using different components of the accumulated weight-gain measurements. These conductance values are similar to those found in the literature for studies in which alveolar edema developed and LP,T was calculated using wet-to-dry weight ratios as a measure of filtered volume. In another series of lungs, capillary pressure was altered by only 5.8 +/- 2.5 mmHg, and LP,C was calculated by estimating the initial filtration rate by an extrapolation method LP,C calculated by use of the extrapolation method (0.71 X 10(-11) cm3/dyn-s) was larger than the LP,T reported in the literature, because LP,T is an estimate of the conductance of the alveolar plus the capillary membrane. Also, for the most calculations of LP,T, tissue forces have changed which causes an overestimation of the filtration driving pressure and thus an underestimate of the capillary volume conductance. After estimating both LP,C and LP,T, the maximum volume conductance of the alveolar membrane (LP,a) was calculated to be 0.13 X 10(-11) cm3/dyn-s.


Comparison of carotid artery mechanics in the rat, rabbit, and dog. Cylindrical segments of carotid arteries from rat, rabbit, and dog were studied in vitro in order to compare active and passive mechanical properties, with gross morphology and composition. Pressure-diameter relations were determined under active (norepinephrine) and passive (2 mM EGTA) conditions, and were used to compute values of tangential wall stress, incremental elastic moduli, characteristic impedance, and active smooth muscle responses. The water and connective tissue contents of these segments were also determined. Significant differences were found in the passive mechanical properties of these arteries, with those of the rat being most compliant and those of the dog being the stiffest. These differences were consistent with the connective tissue content of these arteries. The ratio of collagen to elastin was smallest in the rat and largest in the canine carotids. Differences were also demonstrated in the responses to smooth muscle activation. The maximum value of active stress response was essentially the same in the canine and rabbit arteries, both of which were larger than that of the rat carotids. On the other hand, the rabbit vessels produced a larger maximum diameter response than either of the other arteries. Values of incremental elastic modulus were largest at specific values of transmural pressure for the rabbit vessels. This latter fact may make the contractile system more effective in reducing wall diameter in the rabbit arteries in spite of the fact that they did not have the capacity to generate a larger active stress response.