Studies comparing the metabolic clearance rate of 11 beta,17,21-trihydroxypregn-1,4-diene-3,20-dione (prednisolone) after oral 17,21-dihydroxypregn-1,4-diene-3,11,20-trione and intravenous prednisolone.

The MCR of prednisolone (11 beta,17,21-trihydroxypregn-1,4-diene-3,20-dione) and the absorption of prednisone (17,21-dihydroxypregn 1,4-diene-3,11,20-trione) were studied in five normal subjects and four patients. Plasma and urinary prednisolone were measured by a competitive radioassay. The MCR was determined after iv administration of 30 mg nonisotopic prednisolone using one-compartment (MCR1) and two-compartment (MCR2) analyses. These values were compared with the MCR determined after oral administration of nonisotopic prednisone (MCR0). MCR1 and MCR2 were closely correlated, indicating the applicability of first order kinetics to the study of prednisolone metabolism. In subjects with normal gastrointestinal function, MCR0 was consistently lower than MCR2 (mean MCR2 = 0.175 liters/h.kg; MCR0 = 0.145 liters/h.kg). In two patients with steroid malabsorption, the MCR0 was significantly greater than MCR2. Knowledge of the expected relationship between MCR0 and MCR2 allowed quantitation of the degree of malabsorption. With or without impaired absorption, the absorptive process was essentially complete by the time of the peak plasma concentration. Estrogen therapy lowered the MCR0, and high prednisone dose increased the MCR0. Those effects and the effects of iv prednisolone administration on the MCR are explained by the effects of plasma protein binding of prednisolone. These studies demonstrate the usefulness of the oral MCR determination in the evaluation of steroid absorption and metabolism.


Metabolic clearance rates of the subunits of human chorionic gonadotropin in man.

Highly purified preparations of the alpha- and beta-subunits of hCG (hCG alpha and hCG beta) were injected iv in normal subjects. After rapid injection, the disappearance of both subunits from serum was nonlinear when plotted on a semilog graph. A two-component exponential curve was fitted for each subject, and the curve parameters were used to estimate the MCR, apparent initial volume of distribution (Vd), and half-times of disappearance of the rapid and slow phase for each subunit. The Vd of hCG beta was indistinguishable from that of hCG alpha (1958 +/- 131 vs. 1729 +/- 99 ml/m2, respectively). The rapid phase half-time for hCG beta was significantly longer than that of hCG alpha (41.2 +/- 1.7 vs. 13.0 +/- 0.9 min; P less than 0.001), and the slow phase half-time of hCG beta was also significantly longer than that of hCG alpha (236 +/- 41 vs. 76 +/- 19 min; P less than 0.01). The estimated MCR of hCG alpha was 49.7 +/- 1.6 ml/min.m2; this value was significantly greater than that of hCG beta (19.0 +/- 0.7 ml/min.m2; P less than 0.001). No significant differences between sexes in parameters determined for the subunits were observed. Continuous infusion of subunits at a rate of 2.7 microgram/min achieved a steady state blood level of hCG beta that was significantly greater than that of hCG alpha (59.1 +/- 7.8 vs. 24.4 +/- 0.7 ng/ml; P less than 0.02) and gave a MCR of hCG alpha that was 3 times greater than the MCR of hCG beta (72.2 +/- 4.9 vs. 21.6 +/- 2.8 ml/min.m2; P less than 0.001). We conclude that the hCG subunits have similar Vds, but since hCG alpha has much shorter half-times of disappearance in both rapid and slow phases, the MCR of hCG alpha is much greater than that of hCG beta.


A seasonal variation study of 25-hydroxyvitamin D3 serum levels in normal humans.

A population residing in the approximate area of Kalamazoo, MI (latitude north, 42 degrees 17' 29''; longitude west 85 degrees 35' 14''), was examined to determine the influence of seasonal variation on human 25-hydroxyvitamin D3 serum levels. Males and females, ranging in age from 16--64 yr of age and judged normal based on laboratory evaluation and physical examination, participated in the 12-month study. Measurement of 25-hydroxyvitamin D3 serum levels was made by high performance liquid chromatography. A correlation coefficient of 0.776 (P = 0.003) was obtained by comparing average monthly 25-hydroxyvitamin D3 serum levels to average monthly temperatures. A comparison of approximated monthly amounts of sunlight to average monthly 25-hydroxyvitamin D3 serum levels produced a correlation coefficient of 0.747 (p = 0.005). In addition, changes in 25-hydroxyvitamin D3 levels for the population examined fitted a model that demonstrated a relationship to sex and a highly significant periodic relationship to time.


Oscillations in reverse triiodothyronine levels in serum of healthy infants aged 0 to 130 hours.

rT3 was measured by RIA in sera from 273 normal healthy infants between 0--130 h of age. The curve for the mean rT3 level plotted against age was polyexponential in shape and showed superimposed oscillations with a period of about 16 h, similar to the curves for T4, T3, and TSH previously found for the same group of subjects (J Clin Endocrinol Metab 47: 61, 1978). The ratio of concentrations of rT3 to T4 remained approximately constant, with a mean value of 0.016 over the age range of 3--130 h. These observations suggest that the variations in rT3 levels in newborn serum during the first few days of life are largely accountable by variations in T4 substrate concentrations.


Comparison of thyroid stimulators and thyroid hormone concentrations in the sera of pregnant women.

To clarify the role of various thyroid stimulators in normal human pregnancy, we measured serum TSH, chorionic TSH (hCT), hCG, bioassayable thyroid-stimulating activity, T4, T3, T3 uptake, free T4 and free T3 indexes, free T4, and free T3 by dialysis in 339 serum samples from pregnant women at various intervals of pregnancy and in 40 normal female controls. Serum T4 and T3 and free T4 and free T3 indexes were significantly elevated throughout pregnancy in comparison with controls. Free T4 concentration was elevated after 10 weeks of pregnancy and free T3 concentration was elevated at 13--20 weeks. Bioassayable thyroid-stimulating activity was elevated from 9--16 weeks when serum hCG concentrations were highest. Serum TSH levels were significantly lower at 9--12 weeks compared with the rest of pregnancy. hCT was detected in only 35% of sera tested; the mean detectable value was 0.60 +/- 0.04 (SE) microU/ml; only 15% of the detectable values exceeded 1 microU/ml. The level of hCG correlated with bioassayable thyroid-stimulating activity (P less than 0.01). The data indicate that hCT is not a significant thyroid stimulator. We propose that hCG, as a weak thyroid stimulator, causes a modest rise in free thyroid hormone levels early in pregnancy which in turn causes a modest reduction in pituitary TSH secretion.


Comparison of physiological and pharmacological tests of growth hormone function in children with short stature.

We studied 30 short-statured children to investigate their 24-h integrated serum concentration of GH (ICGH) and its diurnal pattern and to compare this data with their responses to standard stimulation tests for GH release. Eight patients with normal stimulation tests had a mean (+/- SD) ICGH value of 8.0 +/- 3.8 ng/ml (range, 4.5--16.4), and all had several secretory peaks greater than 12 ng/ml. Nineteen patients with abnormal responses (peak, less than 10 ng/ml) had a mean ICGH value of 2.7 +/- 1.9 ng/ml (range, less than 0.8 to 7.0); this was significantly lower than that of control subjects and patients with normal stimulation tests. However, 5 of these patients had normal ICGH values. Three patients with borderline stimulation test responses (10--12 ng/ml) had normal ICGH values (3.2, 3.4, and 11.9 ng/ml). Of the 22 patients with either abnormal or borderline stimulation tests, 14 had an ICGH result below the range of normal. Of these 14, 11 had no secretory peaks greater than 10 ng/ml, whereas 3 had peaks between 10--12 ng/ml. The 8 other patients had ICGH results in the normal range. Despite significant correlation (r = 0.668), integrated GH values did not correlate with stimulation tests in a minority of the patients, the status of whom remains to be determined by long term response to exogenous GH therapy.


In vivo metabolism of progestins. V. The effect of protocol design on the estimated metabolic clearance rate and volume of distribution of medroxyprogesterone acetate in women.

The metabolism of the synthetic progestin, [3H]medroxyprogesterone acetate (MPA), was studied in women using a single injection technique. Computer-implemented analysis was used to calculate the MCR (MCRMPA) and volume of distribution (VoMPA) from the steroid disappearance curve. The value of an objective curve-fitting technique was demonstrated. The effect of protocol design (number and frequency of samples) on these metabolic parameters was evaluated. The estimation of VoMPA was most sensitive to alterations of experimental design and biological variability, while MCR was less easily effected. The MCRMPA of 1668 +/- 146 (SEM) liters/day was lower than that for progesterone but higher than that of another synthetic steroid, dexamethasone. Treatment of women with MPA or aminoglutethimide, two drugs known to increase the rates of testosterone and dexamethasone metabolism, respectively, did not alter MCRMPA. From these observations we conclude 1) with the single injection technique it is difficult to estimate Vo of compounds such as MPA which are rapidly metabolized and 2) the MCRMPA was higher than expected and less susceptible to drug-induced changes than the clearance of other steroids.


Effect of adrenal suppression with dexamethasone in essential hypertension.

The 24-h integrated plasma concentration of aldosterone (IC-ALDO), PRA (IC-PRA), and cortisol (IC-F) were measured in 34 male patients with uncomplicated mild essential hypertension and 15 matched normal controls using a portable 24-h continuous nonthrombogenic blood withdrawal system. The hypertensive were subsequently given 0.5 mg dexamethasone three times per day, resulting in suppression of their urinary excretion of 17-hydroxycorticosteroids and free cortisol. The diastolic blood pressure of the hypertensives fell during adrenal suppression from 104 +/- 5 to 96 +/- 8 mm Hg (mean +/- 1 SD; P less than 0.0001). The systolic pressure fell from 150 +/- 16 to 148 +/- 17 (P greater than 0.01). Baseline values for IC-F, IC-ALDO, and IC-PRA were similar in hypertensive subjects and normal controls. After treatment with dexamethasone for 8 weeks, IC-F in the hypertensives decreased from 7.8 +/- 2.1 to 0.7 +/- 0.6 microgram/dl (P less than 0.0001). There was no associated change in IC-ALDO or IC-PRA. Thus, the fall in diastolic blood pressure in response to dexamethasone was associated with suppression of IC-F, without demonstrable changes in other endocrine or biochemical factors measured.


Effect of parathyroidectomy on serum 1 alpha,25-dihydroxyvitamin D and intestinal calcium absorption in primary hyperparathyroidism.

Serum concentration of 1 alpha,25-dihydroxyvitamin D [1,25(OH)2D] and intestinal absorption were measured before and after parathyroidectomy in 11 patients with primary hyperparathyroidism. Serum 1,25(OH)2D was high preoperatively (P less than 0.001) and normal postoperatively. Ca absorption was elevated preoperatively (P less than 0.001) and decreased significantly after parathyroidectomy (P less than 0.001). However, 5 of 11 patients had a persistent hyperabsorption of Ca postoperatively, despite normal serum 1,25(OH)2D. The results suggest that factors other than 1,25(OH)2D contribute to the maintenance of high intestinal Ca absorption in hyperparathyroid patients in the postoperative state.


Circulating big human prolactin: conversion to small human prolactin by reduction of disulfide bonds.

The heterogeneity of circulating human PRL (hPRL) in sera of patients with hyperprolactinemia was studied by exclusion chromatography on Sephadex G-100. Big hPRL, which elutes between the void volume and the elution position of monomeric small hPRL, is stable upon rechromatography but is almost entirely converted into small hPRL after reduction with 0.5% mercaptoethanol. These results suggest that the existence of circulating big hPRL is dependent upon the formation of interpolypeptide disulfide bonds and does not represent a classical biosynthetic precursor of hPRL.


Serological response of chickens to Salmonella thompson and Salmonella pullorum infections.

Chickens were experimentally infected with Salmonella thompson (serogroup C, paratyphoid) and Salmonella pullorum (serogroup D). Five serological methods and one cultural method were used in detecting the infections. The microantiglobulin test was superior to all other methods for detection of paratyphoid (S. THOMPSON) infection and was followed in efficacy by the microagglutination test, rapid serum plate test, cloacal swab culture, macroscopic tube agglutination test, and rapid whole-blood test, in that order. Birds infected with S. pullorum showed much higher agglutinin titers than the birds infected with paratyphoid. The microagglutination and microantiglobulin tests were not significantly different for detection of pullorum infection and were followed in efficacy by the rapid serum plate, macroscopic tube agglutination, rapid whole-blood, and cloacal swab culture tests, in that order. The cloacal swab culture test was totally inadequate for the detection of pullorum infection.


O serotyping of Providencia stuartii isolates collected from twelve hospitals.

A collection of 829 isolates of Providencia stuartii, mostly from urological specimens of patients in 12 hospitals, were O serotyped. Hospitals varied in serotype distribution, but most isolates (97%) fell into one or another of 14 O types of P. stuartii. One type (O63) was found in 10 hospitals, and six types (O4, O17, O25, O52, O55, O56) were found in 5 or more hospitals. These seven types were more common than others and included 753 (91%) of the isolates. Only four isolates agglutinated in Providencia alcalifaciens antisera and, for increased efficiency in serotyping, it is recommended that separate schemes be employed for P. stuartii and P. alcalifaciens. Strains endemic in different hospitals may differ in serotype and give rise to nosocomial infections that are clinically recognizable when infections occur in obvious clusters. Nosocomial infections occurring in low frequency among patients not located close to each other in the hospital may be detected with the aid of serotyping.


Two strains of Vibrio species with unusual biochemical features isolated from ear tracts.

A strain of vibrio cholerae Heiberg type II, not agglutinable with any of the eight antisera corresponding to Heiberg's groups, and a nonmotile, methyl red-positivs of chronic external otitis.


Detection of group D and viridans streptococci in blood by radiometric methods.

A prospective study was conducted to evaluate the radiometric detection of group D and viridans streptococci in blood, using three media preparations, Bactec 6A and 6B isotonic media and 8B hypertonic medium. All enterococci tested were detected by the 6A and 6B media. However, the 6A medium failed to detect 76% of the Streptococcus bovis isolates and 57% of the viridans streptococci, whereas all S. bovis isolates and 95% of the viridans streptococci were detected with the 6B formulation. No improvement in detection was noted in comparing the 6B and the 8B hypertonic media. The importance of adequate detection of this group of organisms, especially in patients with endocarditis, is discussed.


Two forms of Staphylococcus aureus in blood of patients with staphylococcal sepsis.

Two distinctly different and stable forms of Staphylococcus aureus were isolated from the blood of each of two patients with staphylococcal sepsis. In each case, one form was hemolytic and the other nonhemolytic, although both had the same biochemical reactions, phage types, and antibiotic susceptibilities, and both were virulent for mice. Variant forms of S. aureus may be selected in vivo by host factors and may be responsible for causing and/or perpetuating infection.


Characterization of a Haemophilus paracuniculus isolated from gastrointestinal tracts of rabbits with mucoid enteritis.

The isolation, characterization, and identification of a microorganism isolated from gastrointestinal tracts of rabbits with mucoid enteritis are described. The isolated organism did not grow on standard media. This organism grew around colonies of Staphylococcus aureus and Lactobacillus desidiosus and around disks saturated with diphosphopyridin nucleotide (factor V) on brain heart infusion agar. The growth of this organism was also observed on media supplemented with beta-nicotinamide adenine dinucleotide. The organism appeared as gram-negative, pleomorphic rods or coccobacilli. It was positive for urease, oxidase, catalase, glycosidases, porphyrin, and indole, and it fermented glucose and sucrose. All of these characteristics suggest that the organism is a member of the genus Haemophilus. Because of its isolation from rabbits and differences in some characteristics from other species of this genus, the name Haemophilus paracuniculus is proposed for this organism.


Comparison of four plating media for isolating Vibrio cholerae.

Two brands of thiosulfate citrate bile salts sucrose agar and Monsur taurocholate tellurite gelatin (TTG) agar were compared with two newly developed media, sucrose tellurite teepol agar and Vibrio parahaemolyticus agar for isolation and identification of Vibrio cholerae. The thiosulfate citrate bile salts sucrose and TTG agars were the best selective media, whereas sucrose tellurite teepol agar was the poorest. Both TTG and sucrose tellurite teepol agars were good for use in follow-up serological tests, whereas only TTG agar could be used for follow-up oxidase tests. In our opinion TTG agar has more advantages for cholera research laboratories routinely culturing large numbers of patients for cholera on a daily basis and where media needs can be accurately predicted. In contrast, in smaller clinical laboratories or in laboratories investigating epidemics, thiosulfate citrate bile salts sucrose agar is best because it is commercially available and easy to prepare and can be used to distinguish colonies of suspect V. cholerae from V. parahaemolyticus.


Comparison of four culture media for isolation of Mycobacterium avium complex from porcine tissues.

The efficiency of four culture media was compared for the isolation of Mycobacterium avium complex from 197 procine tissues. In 82 tissues with microscopic granulomas and acid-fast bacilli, a significantly greater number of isolates were obtained on Middlebrook 7H10 medium with sodium pyruvate than on Stonebrink medium, Herrold egg yolk agar medium, or Lowenstein-Jensen medium (P=0.01). In 46 tissues in which no microscopic granulomas or acid-fast bacilli were observed, a significantly greater number of isolates were made on Middlebrook 7H10 medium or Herrold egg yolk agar medium than on Stonebrink medium or on Lowenstein-Jensen medium (P=0.01). The time required to grow M. avium complex on Lowenstein-Jensen medium was significantly greater than the time required to observe growth on Stonebrink, Middlebrook 7H10, or Herrold egg yolk agar medium (p=0.001).


Selective and differential medium for isolation of Clostridium difficile.

Clostridium difficile is a recognized cause of pseudomembranous (antimicrobial agent-associated) colitis and may be one of the causes of antimicrobial agent-induced diarrhea. A selective and differential agar medium that contains cycloserine, cefoxitin, fructose, and egg yolk (CCFA) was developed to facilitate the isolation of C. difficile from fecal specimens. Quantitative cultures of 16 stock strains of C. difficile on this medium (and on a medium containing cycloserine, fructose, and egg yolk) yielded counts equivalent to those obtained on blood agar; other media selective for clostridia, including Clostrisel agar, reinforced clostridial agar plus 0.2% para-cresol, and egg yolk-neomycin agar (the latter was inoculated with cultures subjected to prior heat shocking), were also tested and found to be inhibitory to the growth of C. difficile. Of 28 fecal or colostomy effluent specimens cultured on the above media, 14 yielded C. difficile. CCFA was found to be the most sensitive and selective of these media for the recovery of C. difficile. Colonies of C. difficile growing on CCFA had distinctive morphological and fluorescent properties which were sufficient for presumptive identification. CCFA should provide a rapid method for the screening of fecal specimens from patients with antimicrobial agent-associated diarrhea or colitis for C. difficile.


Detection of enteric campylobacteriosis in children.

Campylobacter fetus subsp. jejuni was recovered as the sole bacterial pathogen from 31% of 0- to 8-month-old children with acute gastroenteritis and from 5% of asymptomatic children (P less than 0.05). In children 8 to 24 months old, the respective recovery rates were 38 and 40%. With the exception of one case of simultaneous bacteremia, the clinical course of the symptomatic infection was benign and rarely lasted more than a week. The isolates were sensitive to most commonly used antibiotics. Several isolates shared antigenic determinants with C. fetus subsp. intestinalis. A bacteriophage specific for C. fetus subsp. jejuni lysed 73% of the strains. Several phage-resistant isolates carried a phage that lysed the stock strain of C. fetus subsp. jejuni (NADC 917).


Incidence of "oxidase-variable" strains of Aeromonas hydrophila.

Certain strains of Aeromonas hydrophila are oxidase negative when grown on gram-negative selective and differential media. Of 100 strains of A. hydrophila examined, 8 were found to possess this characteristic. Information is provided on how to detect these common variants of A. hydrophila.


Enterotoxin production by Staphylococcus aureus strains isolated from cases of chronic osteomyelitis.

Of 264 Staphylococcus aureus strains selected at random from 3,978 strains isolated from chronic osteomyelitis patients, 79 were found to produce enterotoxin. A majority of the strains (65%) were nontypable by phages belonging to the international phage set for human strain typing. The significance of these strains and their circulation among the population is discussed, especially from the standpoint of their possible role in the development of osteomyelitis.


Septicemia caused by DF-2.

Fatal septicemia due to an unidentified gram-negative rod developed in a 60-year-old alcoholic. Infection due to this organism has been reported only rarely in the medical literature. Like Pasturella multocida, this organism is related to dog bites, is gram negative, and is sensitive to penicillin.


Liver abscess caused by Haemophilus paraphrohaemolyticus.

Haemophilus paraphrohaemolyticus was isolated in pure culture from a liver abscess in a 73-year-old man.


In vivo regulation of secretion of bronchiolar Clara cells in rats.

We used ultrastructural morphometric methods to study the in vivo regulation of secretion in bronchiolar Clara cells of rats. The Clara cells studied were located in airways with an internal diameter of 0.21 +/- 0.06 mm (mean +/- SD) at a transpulmonary pressure of 20 cm H2O. We found that pilocarpine caused a 50% decrease in the volume density of secretory granules of Clara cells in 60 min and that atropine blocked this effect. Isoproterenol produced a similar fall in volume density and this was blocked by propranolol. Propranolol also blocked the effect of pilocarpine. The fall in volume density of the secretory granules produced by pilocarpine and by isoproterenol occurred without any change in the surface-to-volume ratio of the granules. This indicates the change in volume density reflected a decrease in number rather than in size of the secretory granules. The observation that propranolol blocks the secretory response to pilocarpine as well as the response to isoproterenol suggests a dual in series cholinergic adrenergic regulation of secretion in bronchiolar Clara cells in rats.


Production of erythrocytes that contain fetal hemoglobin in anemia. Transient in vivo changes.

Serial microscopic immunodiffusion assays of F cells, i.e., erythrocytes that contain fetal hemoglobin (HbF), in four individuals recovering from anemia demonstrate initial increases in the percentage of circulating reticulocytes that contain HbF (F reticulocytes) and subsequent increases in the percentage of mature erythrocytes that contain HbF (F erythrocytes). In one individual responding to therapy for iron-deficiency anemia, the average percentage of F reticulocytes increased from 4.8+/-1.1 to 16.0+/-2.8% (mean+/-SD), while the mean level of F erythrocytes increased from 3.5+/-0.7 to 7.2+/-0.6%. Two normal children with transient erythroblastopenia exhibited F reticulocyte percentages of 71.3+/-6.7 and 41.5+/-1.5%, respectively, when erythropoiesis resumed. With recovery these values fell to finally measured values of 33.7+/-4.7 and 12.6+/-1.1%, respectively. In an adolescent with sickle cell anemia, F-reticulocyte percentages fluctuated between 0.6+/-1.1 and 34.0+/-2.8% and paralleled the rise and fall of total reticulocytes associated with therapy for a nasopharyngeal carcinoma. Such findings suggest that first, the production of F cells and non-F cells are separately regulated. Second, F-cell production is preferentially stimulated during escape from erythropoietic suppression and selectively depressed at the start of suppression. Third, during escape from erythropoietic suppression, F-cell production in vivo resembles that reported for in vitro cultures of erythroid stem cells. Fourth, individuals with sickle cell anemia, like individuals without hemoglobinopathies, can change their relative level of F-cell production.


Collecting duct sodium reabsorption in deoxycorticosterone-treated rats.

In vitro studies of isolated, perfused, cortical collecting tubules have demonstrated that prior chronic deoxycorticosterone acetate (DOCA) treatment increases sodium reabsorption in this nephron segment, yet sodium balance in vivo is maintained. To evaluate the effect of chronic DOCA treatment on collecting duct sodium reabsorption in vivo, we compared fractional sodium delivery (FD(Na)%) out of the superficial late distal tubule with the fraction of sodium remaining at the base and the tip of the papillary collecting duct during extracellular fluid volume expansion in untreated, salt-treated, and DOCA-salt-treated rats. In untreated rats, FD(Na)% to the distal tubule was 6.5+/-1.0%, and to the base was 8.7+/-1.6% (Delta2.2+/-0.9%, P < 0.05). FD(Na)% to the tip was 4.9+/-1.1%, significantly less than FD(Na)% to the base (Delta3.7+/-1.1%, P < 0.01). In salt-treated rats, FD(Na)% to the distal tubule was 8.3+/-0.8%, and to the base was 10.4+/-1.1%. FD(Na)% to the tip was 5.9+/-0.6%, significantly less than FD(Na)% to the base (Delta 4.6+/-1.0%, P < 0.005). In DOCA-salt-treated rats, FD(Na)% to the distal tubule was 16.1+/-2.6% and to the base was 9.5+/-1.9% (Delta 6.6+/-1.7%, P < 0.005). FD(Na)% to the tip was 5.9+/-1.2%, also significantly less than FD(Na)% to the base (Delta 3.6+/-1.1%, P < 0.01). We conclude that (a) in DOCA-salt-treated rats, sodium delivery to the end of the superficial distal tubule is greater than in untreated or salt-treated rats; (b) in DOCA-salt-treated rats, sodium delivery to the end of the superficial distal tubule is greater than to the base of the papillary collecting duct, suggesting stimulation of sodium reabsorption in the cortical and(or) outer medullary collecting duct; and (c) sodium reabsorption by the papillary collecting duct is unaffected by chronic DOCA-salt treatment in the volume-expanded rat.


The growth of adipose tissue in children and adolescents. Cross-sectional and longitudinal studies of adipose cell number and size.

Adipocyte size and number were determined in 288 subjects ranging in age from 4 mo to 19 yr. The study was performed in 110 obese and 178 non-obese subjects. 4-yr, longitudinal, follow-up studies were also performed in 132 subjects. The results demonstrate that the contribution of cell number and size to the growth of the fat depot in nonobese children varies with age. Deviations from this normal development were observed in obese children shortly after 1 yr of age. By 11 yr of age obese children exceeded the mean cell number found in nonobese adults. Indeed, obese subjects displayed more rapid and earlier elevations in both cell number and size, which were maintained throughout the study. Thus obese children display both quantitative and qualitative differences in fat tissue development when compared to nonobese children. The data indicate that the rate and type of adipose tissue cellular development one encounters in children may play a role in the development of the enlarged fat depots found in obese subjects.


Further studies of the frequency and significance of the Tgamma-chain of human fetal hemoglobin.

A further study of the Tgamma-chain in a variety of conditions has revealed its presence in the cord bloods of ethnic groups previously unstudied. Heterozygous newborn average 17-19% Tgamma-chain while the mean value in four presumed homozygotes was 31%. The Tgamma-chain is readily detectable in beta-thalassemia of various ethnic groups (although infrequent in Blacks) as well as in deltabeta-thalassemia. Studies of a few families have provided an opportunity to determine whether or not certain individuals are heterozygous or homozygous for the Tgamma-gene. The Tgamma-chain has not been detected in the human fetal hemoglobin that is synthesized in increased amounts in persons with the hereditary persistence of fetal hemoglobin. Although the Tgamma-chain is detectable in sickle cell anemia, its frequency appears to be lower than in normal individuals. By focusing upon the relationship of the percentage of Tgamma-chain to the sources of human fetal globulin from determinants in cis and in trans, the conclusion has been reached that the Tgamma-chain is the product of a mutant Agamma-locus which should be named the TAgamma-chain.


Protective activity of antibodies to exotoxin A and lipopolysaccharide at the onset of Pseudomonas aeruginosa septicemia in man.

Serum antibodies to exotoxin A and type-specific lipopolysaccharide were measured by passive hemagglutination in 52 patients with Pseudomonas aeruginosa septicemia. Their comparative protective activities were evaluated by relating the titers of each at the onset of bacteremia to subsequent outcome. High acute serum antitoxin and antilipopolysaccharide titers (log2 reciprocal mean titers greater than 5) were associated with survival (76% of 17 with high vs. 46% of 24 with low antitoxin titers, P = 0.05; 85% of 13 with high vs. 48% of 29 with low antilipopolysaccharide titers, P = 0.03). In contrast, neither antibody titer was significantly associated (P less than or equal to 0.05) with patients' age or sex, severity of underlying disease, presence of leukopenia, steroid or immunosuppressive therapy. Despite a correlation between acute titers of the two antibodies (r = 0.33, P = 0.06), they appeared to protect independently and additively. Whereas 75% of 8 patients with high antitoxin titers and only 38% of 16 with low titers survived with low antilipopolysaccharide titers (P = 0.10), 100% (6/6), 73% (8/11), and 38% (6/16) survived, respectively, when both, one, or neither antibody was present in high titer (P = 0.01). Furthermore, the association between high acute serum antitoxin titers and survival was more pronounced in patients with rapidly fatal underlying disease (P = 0.06) and leukopenia (P = 0.12) than in more favorable prognostic and immune categories. These data indicate that serum antibodies to exotoxin A and lipopolysaccharide are found in most patients with P. aeruginosa septicemia and both are protective. Both antibodies may have therapeutic or prophylactic potential, whereas serum antiexotoxin A antibodies may be particularly beneficial in compromised hosts.


Endogenous angiotensin stimulation of vasopressin in the newborn lamb.

The effect of furosemide on plasma renin, vasopressin (AVP), and aldosterone concentrations was studied in 10 control and 6 nephrectomized lambs during the 1st 2 wk of life. In a separate study in 10 newborn lambs, 1-sarcosine-8-alanine-angiotensin II (saralasin acetate, 5 mug/kg per min) was infused alone for 40 min, after which furosemide 2 mg/kg i.v. was injected in association with continuing saralasin acetate infusion. Plasma renin activity increased from a mean (+/-SEM) of 21.3+/-3.4 ng/ml per h in the 10 control lambs to 39.4+/-8.2 ng/ml per h at 8 min (P < 0.001) and remained high through 120 min after furosemide. Plasma AVP and aldosterone concentrations increased from respective mean values of 2.1+/-0.4 muU/ml and 12.8+/-2.5 ng/dl to 9.8+/-2.0 muU/ml (P < 0.01) and 23.0+/-7.7 ng/dl (P < 0.05) at 35 min and 13.8+/-2.1 muU/ml and 23.0+/-4.4 ng/dl at 65 min after furosemide (each P < 0.01). There was an insignificant AVP response in the 10 lambs treated with angiotensin inhibitor: from a mean base line of 4.7+/-0.9 to 8.3+/-2.0 muU/ml at 35 min, and 7.4+/-2.0 muU/ml at 65 min after furosemide. There was no increase in AVP in the anephric lambs. The mean increment AVP response from base line in the newborn lambs without saralasin, Delta 10.8+/-2.0 muU/ml, was greater than in the lambs with saralasin, Delta4.0+/-1.9 (P < 0.05), and greater than in the anephric lambs, Delta3.3+/-2.1 muU/ml (P < 0.05). The mean blood pressure fell 6 mm Hg in the 10 control lambs (P < 0.05), 7 mm Hg in the anephric lambs (P < 0.05), and 16 mm Hg in the lambs treated with angiotensin inhibitor (P < 0.05) by 35 min after furosemide. However, the changes in plasma AVP were not related to the fall in blood pressure. These data support the view that the observed AVP response to furosemide in the newborn lamb was mediated through the renin-angiotensin system.


Effect of atropine on vagal release of gastrin and pancreatic polypeptide.

We studied the effect of several doses of atropine on the serum gastrin and pancreatic polypeptide responses to vagal stimulation in healthy human subjects. Vagal stimulation was induced by sham feeding. To eliminate the effect of gastric acidity on gastrin release, gastric pH was held constant (pH 5) and acid secretion was measured by intragastric titration. Although a small dose of atropine (2.3 mug/kg) significantly inhibited the acid secretory response and completely abolished the pancreatic polypeptide response to sham feeding, this dose of atropine significantly enhanced the gastrin response. Higher atropine doses (7.0 and 21.0 mug/kg) had effects on gastrin and pancreatic polypeptide release which were similar to the 2.3-mug/kg dose. Atropine (0.78 and 2.3 mug/kg) without sham feeding significantly inhibited basal acid secretion and also led to significant increases in serum gastrin above basal levels. The gastrin response to sham feeding with 2.3 mug/kg atropine was significantly greater than the sum of the gastrin responses to sham feeding alone and to 2.3 mug/kg atropine alone, indicating potentiation of vagal gastrin release by atropine. We conclude: (a) Unlike vagally mediated gastric acid secretion and pancreatic polypeptide release which can be blocked by atropine, vagal gastrin release is potentiated by atropine. This observation suggests the existence of a vagal-cholinergic pathway which normally (i.e., in the absence of atropine) inhibits gastrin release. (b) Because atropine (without sham feeding) increased basal gastrin levels, it is likely that the cholinergic pathway which inhibits gastrin release is active even when the vagus nerve is not stimulated by sham feeding.