Liver-lung scan in the diagnosis of right subphrenic abscess. To assess the value of liver-lung scanning in the diagnosis of right subphrenic abscess, 148 scans were reviewed against corresponding charts. Of 91 scans with adequate clinical data, overall scanning error was 19.3% with 14 false positive and 3 false negative scans. Among 49 scans (of the initial group of 91 studies) with presence or absence of actual pathology proved by surgery and/or autopsy, there were 3 true positive, 12 false positive, 29 true negative, and 3 false negative scans. Analysis of data indicated (1) lower accuracy of scan interpretations than generally reported, (2) low specificity for positive scans and high specificity for negative scans, (3) correlations of false interpretations with atypical degrees of liver-lung separation and with scanning defects in liver and lung, and (4) failure of rereading significantly to improve accuracy of interpretation.


Pyloric-sphincter studies in peptic-ulcer patients: pylorus in peptic ulcer. Pyloric pressure was assayed by a manometric procedure in the basal state and after intraduodenal infusion of HCl. 13 control subjects, 11 patients with benign gastric ulcer, 8 with duodenal ulcer, and 2 with coexistent gastric and duodenal ulcers were studied. Mean resting pyloric pressure in gastric-ulcer patients (5.17 +/- 0.71) mm Hg) was significantly lower than controls (9.40 +/- 0.85 mm Hg) and did not increase after HCl perfusion into the duodenum. Mean basal pyloric pressure in duodenal-ulcer patients (11.30 +/- 1.57 mm Hg) did not differ significantly from controls and increased after intraduodenal perfusion of HCl to 15.72 +/- 2.40 mm Hg. The two patients with coexistent ulcers had manometric patterns similar to gastric-ulcer patients. Decreased pyloric-sphincter pressure in gastric-ulcer patients may be the mechanism responsible for the increased duodeno-gastric reflux observed in these patients.


A functional description of the canine choledochoduodenal flutter valve. Forward- and reverse-opening pressures of the choledochoduodenal junction were measured in anesthetized, vagotomized dogs. Mean reverse-opening pressures were found to be significantly greater in most cases including those following the intraductal administration of vasoactive agents which are known to significantly influence mean forward-opening pressures. The polypeptides CCK-PZ and CCK-C8 were ineffective in reducing mean forward-opening pressures regardless of the route of administration. Previously published observations have indicated that mean forward-opening pressures are also unaffected by nervous activity. It is concluded that the canine choledochoduodenal junction possesses the physical and functional properties of a passive flutter valve during duodenal relaxation.


Prognostic value of spontaneous hyponatremia in cirrhosis with ascites. Spontaneous hyponatremia in cirrhosis with ascites is generally considered to be due to an impaired renal ability to excrete free water, to be a contraindication of diuretics, and to be a bad prognostic sign. These concepts are reviewed in this paper. 55 cirrhotics with ascites were divided into three groups. Group I consisted of 13 patients with hyponatremia and very low free-water clearance CH2O, 0.07 +/- 0.26 ml/min). These patients also had poor renal function: low inulin clearance (CINU, 40.6 +/- 25.9 ml/min) and paraaminohippurate clearance (CPAH, 383 +/- 275 ml/min). Group II consisted of 8 patients who also had hyponatremia. CH2O, CINU, and CPAH in these patients were fairly high: 5.85 +/- 1.53 ml/min, 85.7 +/- 26.2 ml/min, and 651 +/- 294 ml/min. These values are similar to those o7 +/- 4.27 ml/min, 94.7 +/- 33.1 ml/min, and 598 +/- 199 ml/min. Hyponatremia in Group I could be related to the impaired free-water clearance. The mechanism of hyponatremia in Group II patients is not clear. Patients with hyponatremia and low CINU and CPAH had a negative response to diuretics and a poor prognosis. Patients with hyponatremia but with relatively good renal function had a good prognosis, similar to Group III patients. They responded to diuretics with no worsening of their hyponatremia.


Intramural barium in ischemic colitis: a new radiographic finding. Two cases of ischemic colitis are presented, demonstrating a new radiographic finding of intramural dissection of barium. Colonoscopic findings were compatible with that diagnosis. Deep, discrete ulcerations were observed during the healing process. Both patients recovered and prolonged retention of the intramural barium was seen.


Endoscopic retrograde pancreatography: analysis of the normal pancreatogram. Thirty-five pancreatograms were selected from 62 which were obtained during endoscopic cannulation of the papilla of Vater with retrograde injection of radiopaque medium. Pancreatograms were selected on the basis of the quality of the study and on the absence of any clinically demonstrable pancreatic disease. Measurements were made of the main pancreatic duct (MPD) in the head, body, and tail, as well as the length of the duct. Although there is a wide range of normal, practical reference figures for the diameters of the main duct in the head, body, and tail are 3, 2 and 1 mm, respectively. The length averages 15.4 cm. No correlation was found between the measurements and the body surface area, age, or sex of the patient. Comparisons are made with other autopsy and endoscopic studies, and attention is focused on the salient anatomic features, including normal points of narrowing of the duct, the accessory pancreatic duct (APD), and the main pancreatic duct branches (MPDB).


The occurrence of new mutants in the X-linked recessive Lesch-Nyhan disease. In a population at equilibrium for a sex-linked lethal, one-third of the genes for that lethal must arise anew each generation. Therefore, one-third of all cases of Lesch-Nyhan disease, a severe X-linked recessive lethal disorder, should be new mutants. To test this hypothesis, we have collected 47 families, 20 with a single proband and 27 with multiple affected males in which the patients' mothers and other female relatives had been studied for heterozygosity. Available carrier detection tests identify heterozygous for HPRT deficiency in hair roots and skin fibroblasts. Only four mothers were found not to be carriers. This result deviates significantly from expected (P less than .001). Statistical tests for ascertainment effects indicated absence of bias for multiple proband families but strong bias in favor of families with many heterozygous females. When the analysis was limited to single proband families, the deviation from expected was still significant (P less than .01). The incidence of new mutants among the heterozygous mothers, as determined by the ratio of +/+ to +/- maternal grandmothers, should be one-half (see Appendix). Of all 20 maternal grandmothers studied, five were +/+ and 15 were +/- (P less than .05). Considering only the single proband families, the ratio of 5 +/+ to 8 +/- was not significantly different from expected. In four of the five cases in which the heterozygous mother of an affected individual was a new mutation, the age of her parents was considerably higher than the mean parental age in the population. This raises the possibility of a paternal age effect on X-linked mutations. There appears to be a true deficiency of new mutatnts among males but not among females. Data on additional Lesch-Nyhan families are needed before conclusions regarding a possible higher mutation rate in males can be drawn.


Application of the lod method to the detection of linkage between a quantitative trait and a qualitative marker: a simulation experiment. Simulation experiments were performed to assess the power of the lod method for detecting linkage between a quantitative trait and a qualitative marker. Using family data on the Amy2-Duffy linkage, it was found that linkage detection is feasible in certain limited circumstances. The same qualitative data yielded no evidence for a significant difference in male and female recombination fractions.


Analysis of deoxyribonucleic acid replication in human X chromosomes by fluorescence microscopy. The genetically inactive, late-replicating human female X chromosome can be effectively distinguished from its more active, earlier-replicating homologue, when cells are grown according to the appropriate BrdU-33258 Hoechst protocol. Results obtained from a fluorescence analysis of DNA replication in X chromosomes are consistent with those from previous autoradiographic studies, but reflect additional sensitivity and resolution offered by the BrdU-Hoechst methodology. Both qualitative and quantitative differences in 33258 Hoechst fluorescence intensity, reflecting alterations in replication kinetics, can be detected between the two X chromosomes in female cells. The pattern of replication in the single X chromosome in male cells is indistinguishable from that of the early female X. Intercellular fluctuations in the distribution of regions replicating early or late in S phase, particularly with reference to the late female X, can be localized to structural bands, suggesting multifocal control of DNA synthesis in X chromosomes.


The karaite community of Iraq in Israel: a genetic study. Ninety-eight of 136 (72%) individuals at least 6 years of age from a small isolate of the Karaite community, known to have lived in Iraq since the tenth century, were examined. In Iraq this group maintained a highly inbred existence but married Karaites from Egypt after their immigration to Israel in 1951. Observations of several unique gene frequencies for blood group and isoenzyme markers, not described among other Jewish groups, are explicable by isolation and genetic drift in a very small community.


A third type of serum cholinesterase deficiency in Eskimos. A new type of serum cholinesterase deficiency with less than 10% of the normal activity was found in an Alaskan Eskimo. The new type of deficiency appeared to be allelic with two types previously described in this population.


Esterase D in South American Indians.

Esterase D in South American Indians. Significant variation in the frequency of Esterase D isoenzymes was found in 1,070 individuals belonging to eight South American Indian tribes. The Es D1 allele shows frequencies varying from .36 to 1. A region of low prevalence of this allele seems to exist in northern Brazil, involving the Parakanan, Gorotire, and Krahó. The intratribal variation observed in eight Yanomama villages located in Brazil was not exceptional.


The frequency of "rare" protein variants in Marshall islanders and other Micronesians. Blood specimens from a sample of 373 Marshall Islanders were studied with reference to variants of 23 serum proteins and erythrocyte enzymes. Six of the traits studied exhibited genetic polymorphisms (adenosine deaminase, phosphoglucomutase1, acid phosphatase, 6-phosphogluconate dehydrogenase, haptoglobin, and group specific component). There were in addition four "rare" variants (albumin, transferrin, lactate dehydrogenase, and galactose-1-phosphate uridylyltransferase) involving nine persons, among 8,503 determinations. The frequency of rare variants in Micronesians was compared with the frequencies in West European Caucasians and Amerindians. There are many difficulties in such comparisons, and although the observed values for the three ethnic groups differ by a factor of three (the Micronesians exhibiting the lowest frequency), it is felt that no firm conclusions concerning differences between ethnic groups can be drawn at this time.


The inheritance of fingerprint patterns. Analysis of the fingerprints of 571 members of the Habbanite isolate suggest inherited patterns and pattern sequences. A genetic theory has been developed; it assumes that the basic fingerprint pattern sequence is all ulnar loops and that a variety of genes cause deviations from this pattern sequence. Genes that have been proposed include: (1) a semidominant gene for whorls on the thumbs (one homozygote has whorls on both thumbs, the other has ulnar loops on both thumbs and the heterozygote usually has two ulnar loops or one ulnar loop and one whorl); (2) a semidominant gene for whorls on the ring fingers which acts like the gene for whorls on the thumbs; (3) a dominant gene for arches on the thumbs and often on other fingers; (4) one or more dominant genes for arches on the fingers; (5) a dominant gene for whorls on all fingers except for an ulnar loop on the middle finger; (6) a dominant gene for radial loops on the index fingers, frequently associated with an arch on the middle fingers; and (7) a recessive gene for radial loops on the ring and little fingers. These genes may act independently or may show epistasis.


Pharmacy personnel activities and costs in decentralized and centralized unit dose drug distribution systems. Pharmacy personnel activities and labor costs directly associated with concurrent decentralized and centralized unit dose drug distribution systems in the same institution were compared. A work-sampling observation technique was used for the activity survey. Analysis of the data showed that: (1) the activities of pharmacy personnel vary significantly between the decentralized and centralized systems, (2) pharmacists in the decentralized area spent a significantly greater portion of their productive time performing therapy-related activities than did those pharmacists in the centralized system, (3) multiple staffing patterns associated with the centralized unit dose system afforded a significantly greater participation in educational activities by all pharmacy personnel staffing that area, (4) dispensing activities accounted for most nonpharmacist personnel time in both systems, and (5) based on cost/unit dose and existing staffing patterns, there was no appreciable difference in personnel labor costs associated with the two systems. However, it was determined that a considerable cost difference could be expected if the decentralized system's hours of service were equivalent to those associated with the centralized system.


Digoxin tablets--a review of the bioavailability problems. A review is presented of the more significant aspects of recent bioavailability studies on digoxin tablets that have led to the identification of variations among commercially available tablets and of the correlation of the methods commonly used in such bioavailability evaluations. Pharmacopeial requirements for tablet-to-tablet uniformity of content do not automatically yield uniformity of bioavailability. In vitro dissolution rate of digoxin tablets generally has been shown to correlate with in vivo bioavailability, and this has led to new governmental and pharmacopeial requirements for digoxin tablets. However, some recent reports have shown that in vitro dissolution rate may not always correlate well with bioavailability. The relevance and significance of digoxin tablet bioavailability to clinical effects and therapeutics are briefly discussed.


Nursing attitudes toward oral liquid unit dose packaging. Nurses' attitudes toward three types of oral liquid unit dose packages--glass, plastic and aluminum--were determined. Thirty nurses who previously had not used unit dose packaging on their units were asked to evaluate the three types of packaging. The nurses preferred both aluminum and plastic over the glass containers; there was no significant difference in attitude toward the plastic and aluminum packages.


Unit dose radiopharmaceutical service as a component of total pharmacy practice. A unit dose radiopharmaceutical distribution system as a component of total pharmacy services is discussed. The radiopharmacy functions of compounding, calibrating and distributing are rotated on a weekly basis among the staff pharmacists. The elution process and departmental policies and procedures are described. The pharmacist's unique expertise for preparing radiopharmaceutical doses is discussed.


Evaluation of drugs by the medical letter. The operation of The Medical Letter on Drugs and Therapeutics, a biweekly newsletter on drug evaluations for physicians and other health personnel, is described. Included are a discussion of the history and current organization of the publication, method of writing reports, financing, and relations with the pharmaceutical industry. The future of The Medical Letter, in light of more stringent FDA procedures and the fewer new drugs being marketed, is discussed also.


Improved pharmacy services through pharmacist participation in medical rounds. The participation by pharmacists in medical rounds in a 250-bed pediatric hospital with centralized unit dose drug distribution and i.v. admixture programs is discussed. A redistribution of responsibilities enabled pharmacists to attend physician work rounds on each medical service. Nursing-pharmacy rounds were set up for services which had no scheduled physician work rounds. As a result, the amount of medication waste due to late order changes, which had previously been a problem, was reduced by 0.54 cents per patient day. Pharmacist participation in medical rounds increased his clinical expertise and supplied him with the clinical data necessary to make more informed recommendations to physicians.


Motivation of the hospital pharmacist.

Motivation of the hospital pharmacist. Some theories of how management can motivate employees to perform effectively, and the application of these theories to hospital pharmacy practice, are discussed. Types of extrinsic and intrinsic rewards and how they can best be allocated to encourage greater productivity are described. Management must be consistent and credible in its reward allocations in order to maintain the expectation of employees that increased effort will result in rewards. It is important also that management ascertains what employees interpret as desirable rewards.


Effect of hyperthyroidism on hypoprothrombinemic response to warfarin. Clinical observations and studies regarding hyperthyroidism and enhanced response to warfarin are reviewed. The reported cases of increased sensitivity to warfarin in hyperthyroidism are summarized, and possible mechanisms for this disease-drug interaction are discussed. Most recent studies indicate that the activity of warfarin is enhanced in hyperthyroidism because of increased catabolism of vitamin-K-dependent clotting factors.


Novel method for the determination of pediatric dosages. A method by which safe and effective pediatric dosages can be estimated is presented. The method is based on the facts that drugs distribute into body water compartments and that these compartments are significantly different between pediatric and adult populations. The method discussed is tested using data reported in the literature.


Gas-solid chromatography of isopropyl alcohol samples. A study was conducted to analyze the accuracy of the procedure used by a hospital pharmacy to make solutions of 70% isopropyl alcohol and to determine the amount of evaporation of the alcohol which may take place when the containers of these solutions are repeatedly opened. Twenty-five samples of 70% isopropyl alcohol were obtained from eight hospital wards. All the containers had been in patient care areas for over one month and were less than one-half full. Six of the samples were randomly chosen for gas-chromatographic analysis. The results show that gas chromatography for the quantitative analysis of isopropyl alcohol is highly reliable and suitable for the analysis of very large or very small samples. There was no significant amount of evaporation of isopropyl alcohol despite the length of time the solutions had been on the hospital wards.


A modified ortho-toluidine reagent for glucose analysis. A micromethod for the determination  of glucose using a modified ortho-toluidine reagent is described. The proposed method correlates well with the original o-toluidine method. The reaction follows Beer's Law over a wide range of concentrations. The modified reagent contains 75 per cent less glacial acetic acid than the original ortho-toluidine reagent. The color intensity of the Schiff's base is two to three times higher than the original reagent.


Antimicrobial susceptibility testing of anaerobic bacteria. Antimicrobial therapy of anaerobic infections is usually predicted on the basis of known patterns of susceptibility of anaerobic bacteria to antimicrobial agents rather than on results of in vitro tests of individual isolates. Routine susceptibility testing of anaerobic bacteria is not recommended, but there are instances of serious infection, i.e., endocarditis, or specific infecting organisms, e.g., Bacteroides fragilis, when in vitro testing of the specific infecting organism is indicated. No standard method has yet been accepted. Methods presently recommended are agar dilution or broth dilution tests. Other methods currently being evaluated are agar (disc) diffusion, broth-disc, and simplified broth and agar dilution tests. The advantages and limitations of the various methods are discussed.


Retraining of inactive medical technologists - Whose responsibility? A survey was conducted to determine if inactive female medical technologists wish to reactivate, what degree of retraining they feel necessary to do so, and their willingness to pay for such experience. A corollary purpose was to determine the need for inactive technologists, the hiring practices employed, the existence of institutionally sponsored retraining programs, and the institutional views toward providing such programs. Findings revealed that inactive medical technologists wish to return to the field, feel the need for retraining, would prefer a hospital retraining site, and are willing to pay for their retraining. Institutions expressed a need for inactive medical technologists but are most willing to hire individuals who have been retrained. A plentiful supply of new graduates effectively negates this preference in the more densely populated areas. Hospitals and universities are varied in their opinions as to who should provide retraining programs. Few have instituted retraining programs due to high expense and limited availability of financing.


Contract method of individualized instruction applied to clinical bacteriology. An experiment using individualized instruction in clinical bacteriology in a medical technology hospital program is described. Individualized instruction is reviewed as well as the Duluth contract method which was used. The results of this experiment were favorable and the study concludes that students would profit if individualized instruction were used in a medical technology clinical program.


A ventilation system for processing areas in histopathology laboratories. A ventilation system designed for use in our tissue processing laboratory at the National Center for Toxicological Research is illustrated. To facilitate the large volume of research tissue processed daily for our histology labs we use ten Autotechnicon Ultras that process a total of 100 mice daily. This number of tissue processors presents a problem of adequate ventilation.


Serum viscosity and hyperviscosity syndrome in IGG multiple myeloma - the relationship of Sia test and to concentration of M component. The Sia test has been used for a long time for the diagnosis of macroglobulinemia, but its significance in myeloma is not known. It has recently been reported that the majority of sera in immunoglobulin G (IgG) myeloma with hyperviscosity syndrome are Sia-positive.


Delayed hemostatic changes following cardiopulmonary bypass. A variety of hemostatic abnormalities has been reported in patients following open-heart surgery. Since surgery itself may induce changes in the coagulation system, the analyses of postoperative coagulation assays in the bleeding patients may be extremely difficult to interpret without an understanding of the coagulation dynamics in the nonhemorrhagic postoperative patients. Thus, we studied the pattern of change in several coagulation assays performed on 36 consecutive patients before and during the first two postoperative weeks. Approximately one third of the patients has some clotting abnormality before surgery. Shortened prothrombin time (PT) and activated partial thromboplastin time (APTT) were observed within the first three postoperative days. Only following warfarin therapy (initiated on the third postoperative day) was significant prolongation of PT and APTT observed. During the 14 postoperative days, fibrinogen levels and fibrinogen degradation products progressively increased without prolongation of the thrombin time or decrease in the euglobulin clot lysis time. On the first postoperative day, the platelet count and platelet adhesiveness values were significantly less than before surgery (p less than 0.01 and p less than 0.05). Over the following two weeks, the platelet count and platelet adhesiveness returned to normal. Although there was slight lengthening of the Ivy bleeding time on the first postoperative day, this assay was never abnormal. Thus, we conclude that the following cardiopulmonary bypass there is (1) probably activation of circulating procoagulants, (2) progressive increase in fibrinogen levels, (3) activation to the fibrinolytic system, and (4) transient thrombocytopenia with a superimposed platelet defect.


Early diagnosis of vulnerability in cancer patients. The newly diagnosed CA patient faces psychosocial as well as physical problems. To assess the impact of diagnosis, and to find significant clues for later emotional distress, 163 new patients with CA of the breast, colon, lung, Hodgkin's disease, and malignant melanoma were evaluated by interviews, psychological testing, and personality inventories, then followed regularly for six months. Vulnerability was but one parameter that measured emotional distress and faltering capacity to cope with concurrent problems. It was found that the more vulnerable patients had more symptoms when first diagnosed, and that systemic symptoms were more significant than the type of CA or the staging. High vulnerability patients were generally pessimistic, anticipating little recovery and practically no support from significant others. They had more marital problems, tended to suppress feelings, but often had a history of depression. Denial in itself did not mean vulnerability. Indecision about treatment and regrets about the past were more indicative of future emotional problems than was delay. Most patients showed little denial throughout the period of observation, but more vulnerable patients tended to vacillate between denial and acceptance. By learning to listen and ask tactful questions, this information can be elicited by the physician who can then intervene effectively.


Characteristics of bacterial endocarditis in heroin addicts in Detroit. Over 24 months (January 1972-December 1973) 48 intravenous heroin users were admitted to Detroit General Hospital with 50 episodes of bacterial endocarditis (B.E.). Staphylococcus aureus (25 cases), enterococci (13 cases), and Pseudomonas aeruginosa (5 cases) were the usual pathogens, accounting for 86 per cent of these illnesses. Occasional episodes were due to other streptococci or diphtheroids which were susceptible to penicillin G. Staphylococcal and pseudomonas endocarditis usually involved the tricuspid valve, while enterococci affected aortic or mitral valves. Pre-existing valvular heart disease was not the sole determinant of the site of infection.


Aortic regurgitation and pigmentation - unusual features of Noonan syndrome. A patient with typical features of Noonan's syndrome showed aortic regurgitation and widespread diffuse hyperpigmentation, features not previously associated with this syndrome. Detailed endocrine and dermatological studies failed to delineate the cause of hyperpigmentation. In addition to mild aortic regurgitation, cardiac catheterization revealed mild left ventricular dysfunction, probably due to primary myocardial disease. Other interesting findings included lymphedema and sexual infantilism despite normal testosterone levels.


Drug addiction in pregnancy and the neonate. Drug addiction during pregnancy has been managed in two ways: the detoxification program and the methadone-maintenance treatment program. In the detoxification program, there have been few complications for the mother and child except for low birth weight, meconium-stained amniotic fluid, and an increase in breech presentation. The methadone-maintenance treatment program at this time is the most satisfactory approach to the treatment of heroin addiction. The complications of pregnancy in this program are similar to those of the average obstetric population. Low birth weight at term is still frequent for those on methadone maintenance. The problem of multiple drug abuse, including heroin, cocaine, alcohol, tranquilizers, and amphetamines, requires more attention. The characteristics of the withdrawal syndrome and its treatment in infants are described. Excessive weight loss and irritability are commin in these infants. Of the many drugs available for the treatment of the newborn withdrawal syndrome, diazepam is currently favored. The long-term effects of intrauterine drug exposure, the withdrawal syndrome, and treatment are generally unknown. Schedules for management of adult narcotic, alcohol, and barbiturate abuse and newborn narcotic withdrawal are suggested.


Conization as only treatment of carcinoma in situ of the uterine cervix. Knife conization was performed in 2,099 cases with abnormal vaginal smears. The frequency of complications was low. Carcinoma in situ was diagnosed in 1,500 cases and follow-up showed that conization was curative in 87%. The curative rate was depending on whether the resection margins were free of pathologic epithelium or not. If smears were repeatedly negative the first year after conization a new diagnosis of cancer was made in 0.4%. It was not possible to decide whether these lesions were residual changes or true recurrences. Treatment of carcinoma in situ by conization has so far reduced the frequency of invasive cervical cancer by 60%.


Ultrastructural studies on the endometrium of women wearing TCu-200 intrauterine devices by means of transmission and scanning electron microscopy and x-ray dispersive analysis. Endometrial biopsies obtained from 12 young women wearing TCu-200 intrauterine contraceptive devices from six to 12 months were studied by means of transmission and scanning electron microscopes as well as with the use of rubeanic acid stains and x-ray dispersive analysis. Six biopsies were taken at Day 10 and six were taken at Day 20 of the menstrual cycle. The aim was to investigate epithelial and stromal changes possibly related to copper deposition. The main changes were located in the cell organelles at Day 10 of the cycle. The mitochondria disclosed vacuolization of the matrix and myelin figure formation in 70 to 80% of the epithelial cells. There were also increased numbers of lysosomes. There were similar alterations of secretory endometrium in only a few cases. Instead, there was an increased number of mitochondria, and most of them were dividing. Rubeanic acid stains as well as energy-dispersive x-ray analysis failed to reveal significant amounts of copper in the various cell organelles studied. The above observations seem to indicate that there is a definite alteration of the mitochondria of epithelial cells which may result in impairment of respiratory mechanisms and energy production, rendering the endometrial environment inhospitable to the fertilized egg. These changes are thought to be reversible. The absence of copper is explained on the basis of a rapid turnover of the endometrium or to a problem in sampling common to this methodology.


Familial dextrocardia, divergent strabismus and situs inversus of optic disc. A family is described in which three of four siblings have major congenital cardiac defects in association with ocular abnormalities. The eldest sibling has isolated dextrocardia and the second has total situs inversus. The fourth child has both atrial and ventricular septal defects, with pulmonary hypertension and right ventricular hypertrophy. The mother and third sibling have normal hearts but exhibit a number of ocular defects. The principal ocular anomalies demonstrated in this family are divergent strabismus, bilateral situs inversus of the optic disc, and myopia. The hereditary aspect of these multiple findings is discussed.


The effect of meperidine analgesia on midtrimester abortions induced with intra-amniotic prostaglandin F2alpha. To determine whether increased amounts of meperidine significantly affect the induction of abortion with intra-amniotic prostaglandin F2alpha, 42 midtrimester subjects were treated with an identical dose schedule of PFG2alpha and one of two dose schedules of meperidine. Although the group that received more mepridine reported severe pain less frequently, their mean and median induction-to-abortion times, cumulative abortion rate, uterine contractility, and complications were not significantly different from those of the group that received less meperidine.


A case of Buerger's disease causing ischemic colitis with perforation in a young male. A case of Bueger's disease causing ischemic colitis with perforation in a 32-year-old male is presented. Abdominal angiography demonstrated occlusion of the vasculature supplying the involved transverse colon. The association of Buerger's disease with ischemic colitis is emphasized.


Perinatal vitamin D metabolism. III. Factors influencing late gestational human serum 25-hydroxyvitamin D. Sera were obtained during the last trimester from both black and white women receiving prenatal care for determinations of calcium, magnesium, and 25-hydroxyvitamin D (25-OHD). The mean serum 25-OHD concentrations were 15.4 +/- 5.9 ng, per milliliter (S.D.) in February (n = 56) and 42.1 +/- 13.9 ng.per milliliter in August (n = 61). There was no significant racial difference in serum 25-OHD in February or August. No seasonal difference in calcium was noted but magnesium concentrations were lower in August. No correlation existed between serum 25-OHD and serum calcium or magnesium, parity, time from last pregnancy, maternal age, or social class. Concentrations of 25-OHD showed weak correlations with vitamin D intake (r = 0.32) and duration of gestation (r = 0.26) in the winter only. These data suggest that, regardless of race, ultraviolet exposure is the major determinant of maternal serum 25-OHD concentration in St. Louis. Dietary intake and and other factors may be important during periods of decreased ultraviolet exposure.


Pycnodysostosis: some aspects concerning kinetics of calcium metabolism and bone pathology. A 23-year-old white woman suffering pycnodysostosis whose parents and five siblings were unaffected was investigated. Chromosomal morphology was normal. Histologic examination of a biopsy specimen obtained from the distal phalanx of the left thumb, corresponding to an area on an x-ray film of osteolysis, showed a fibrous dysplasia-like picture. Kinetic studies of calcium metabolism revealed that exchangeable pool size, turnover, and bone accretion rate were all decreased. Intestinal calcium absorption was investigated simultaneously by a double isotope technique and by deconvolution of the plasmatic specific activity curve of 47Ca given per os. Results obtained by both methods coincided in that values were found to be similarly increased. Endogenous fecal calcium was also determined and revealed a similar increase. Some physiopathological implications of these findings are discussed.


The effect of various vasoactive compounds upon the uterine vascular bed. The effects of various vasodilators on the uterine vascular bed were investigated in nonpregnant, oophorectomized sheep with chronically implanted flow probes and catheters inserted into branches of the uterine arteries. A 1 mug dose of estradiol-17beta (0.224 muM) produces a maximum uterine blood flow response after intra-arterial injection. Adenosine (24 muM) and bradykinin (0.02 muM) were observed to increase blood flow to levels achieved by 1 mug of estradiol-17beta. Acetylcholine, isoproterenol, and histamine were less potent in their vasodilator activity. Atropine, propanolol, and diphenhydramine did not inhibit the increase of uterine blood flow induced by estrogens.


Aspects of the normal psychology of pregnancy: the midtrimester. In this study of nonpregnant women were compared with pregnant women. A set of feelings and attitudes along with questions relevant to the anatomy and physiology of parturition were the measures of comparison. The pregnant women and the nonpregnant women had almost identical feelings and attitudes. There were, however, three exceptions to this general condordance. They were: (1) the nonpregnant women's regard of pregnancy as a depressive and withdrawing experience, (2) a greater fear for the fetus among the nonpregnant women, and (3) higher scores on a pregnancy information inventory among the pregnant women.


A high-risk pregnancy management protocol. A simple hihg-risk pregnancy management protocol is presented. Three basic quantitative tests of fetal-placental function are utilized. The advantages and proper application and interpretation of these laboratory tools are discussed. Perinatal outcome is analyzed in the initial 225 high-risk pregnancies managed according to the protocol. Over 94% of the infants achieved 5 minute Apgar scores of 8 or above. The corrected perinatal mortality rate was only 8.8 per 1,000 live births.


Cortisol levels in umbilical cord plasma in relation to labor and delivery. Cortisol was determined by a competitive protein-binding method in umbilical cord plasma from pregnancies of 37 or more weeks' gestation. In 162 cases of vaginal delivery following spontaneous labor the mean +/- S.E. of cortisol values was 7.43 +/- 0.29 mug per 100 ml. of plasma. This cortisol level was not significantly different from that observed in 51 cases of vaginal delivery after oxytocin-induced labor (6.53 +/- 0.49 mug per 100 ml.) or in 47 cases of delivery by emergency cesarean section following labor (6.21 +/- 0.66 mug per 100 ml.). The mean cortisol level in cases of elective cesarean section with no prior labor (4.67 +/- 0.60 mug per 100 ml.) was significantly less than the value for vaginal delivery after spontaneous or induced labor. The cord plasma and amniotic fluid concentrations of cortisol in a pregnancy complicated by fetal anencephaly and terminated at 44 weeks by induction were normal. It is concluded that labor and vaginal delivery resulted in a significant increase in cord plasma cortisol levels but there was no significant difference between spontaneous and induced labors. These findings do not support the hypothesis that a surge in fetal cortisol production immediately precedes and initiates spontaneous labor in human pregnancy.


Relationship between cortisol levels in umbilical cord plasma and development of the respiratory distress syndrome in premature newborn infants. The aim of this study was to determine whether there is a decrease in fetal cortisol levels associated with the respiratory distress syndrome (RDS). Eighteen newborn infants of less than 37 weeks' gestation who developed moderate to severe forms of RDS did have a significantly lower (P less than 0.02) mean cord plasma cortisol concentration at birth than that observed in 67 unaffected infants of similar gestational age; mean values +/- standard errors were 3.36 +/- 0.42 and 5.58 +/- 0.43 mug per 100 ml, respectively. However, whether or not RDS developed in neonates appeared to depend more upon the degree of prematurity (with a 71.5% incidence in gestations of less than 32 weeks compared to 17.1% in those of 32 to less than 37 weeks) than upon cortisol levels at delivery. Bood cortisol levels in the first days of life of four infants with RDS were considerably increased in comparison to those at birth. Mean cord plasma cortisol concentrations increased with duration of pregnancy, with the previously observed value for term infants (of 37 or more weeks) being approximately twice that for infants of less than 32 weeks' gestation. These findings appear to justify carefully controlled studied with antepartum glucocorticoid administration with the aim of reducing the incidence of RDS in premature newborn infants.


Acute posterior multifocal placoid pigment epitheliopathy. Thirteen cases of acute posterior multifocal placoid pigment epitheliopathy occurred in young adults or older children. In ten there was a characteristic, possibly infectious syndrome that preceded the onset of ocular manifestations by a few weeks. One patient developed cerebrospinal fluid lymphocytosis and a cerebral vasculitis coincident with the ocular changes. Extensive evaluations for viral and other infectious etiologies in this and other cases were unrevealing. An inflammatory reaction was observed in the anterior chambers of most patients, and cells were noted in the anterior vitreous bodies of a few patients. In one instance a serous detachment of the retina occurred adjacent to the optic disk. Our findings and others support the conclusion that the fundus lesions resulted from a multifocal choroiditis primarily involving the choriocapillaris and affecting the pigment epithelium and retina secondarily. The data also suggested that the choroiditis may be associated with a more widespread vasculitis occurring as an immune reaction to an earlier systemic infection.


Severe solar maculopathy associated with the use of lysergic acid diethylamide (LSD). A 23-year-old man sustained severe macular damage by sun gazing during a hallucinogenic drug-induced state. Sequential fundus photography and fluorescein angiography documented prominent focal injury to the retinal pigment epithelium.


Primary retinal detachments without apparent breaks. In a prospective study of 415 consecutive eyes operated on for retinal detachment, there were no apparent retinal breaks in 41 eyes. Examination of the most likely site for breaks during, or shortly after, cryotherapy was helpful in detecting tiny breaks in several cases. All detachments without apparent breaks were operated on with a three-step operation: we applied two rows of confluent cryotherapy to all retinal breaks, drained subretinal fluid, and used buckles just anterior to the equator. Surgical cure, defined as reattachment for at least six months, was achieved in 93% of eyes with apparent breaks, and in 85% of eyes without apparent breaks. The latter figure increased to 91% when the seven patients with preoperative massive preretinal retraction were excluded.


The architecture of the choriocapillaris at the posterior pole. The afferent and efferent vessels as well as the choriocapillaris in the human posterior pole, studied in flat preparations, paraffin sections, and Epon sections, formed relatively discrete units of organization which we called lobules. A lobule is a segment of the choriocapillaris supplied centrally by a precapillary arteriole and demarcated peripherally by a ring of postcapillary venules. Observations on the choroidal phase of fundus fluorescein angiography indicated that blood entering a lobule did not intermingle with blood from adjoining lobules. The choriocapillaris in the posterior pole of the human eye, with its supplying and draining vessels, appeared as a mosaic of adjoining lobules that function independently.


Ghost cells as a cause of glaucoma.

Ghost cells as a cause of glaucoma. Clinical and investigative evidence indicated a glaucoma caused mainly by degenerated red blood cells, or ghost cells. These ghost cells, with altered shape, color, and pliability, accumulated in the vitreous cavity after hemorrhage. Following disruption of the anterior hyaloid face, they passed into the anterior chamber and caused severe glaucoma. In the anterior chamber, the tiny, khakicolored cells, circulating slowly, were frequently mistaken for white blood cells. They covered the trabecular meshwork or filled the inferior angle with a pathognomonic khaki-colored layer. They were identified by phase-contrast microscopic examination of anterior chamber aspirates. The decreased pliability of these degenerated cells seemed to account for their inability to pass easily through the human trabecular meshwork and, therefore, to cause severe glaucoma.


Experimental iridectomy with bipolar microcautery. Peripheral iridectomy was performed in pigmented rabbits after the application of bipolar microcautery to the iris surface. At low doses of cautery, no increase in postoperative inflammation or complications was noted clinically or pathologically in control eyes. High doses of cautery resulted in an increased incidence of postoperative inflammation, corneal opacity, hyphema, iris prolapse, lens changes, and poor wound healing.


Acute glaucoma in hemorrhagic fever with renal syndrome (nephropathia epidemica). Bilateral eyelid edema, chemosis, conjunctival injection and hemorrhages, shallowing of the anterior chamber with transitory myopia, and acute glaucoma were observed in three patients with hemorrhagic fever with renal syndrome (nephropathia epidemica). One patient had anterior uveitis with posterior synechiae. Two patients had congestion of retinal venules and retinal edema, and one patient had small retinal hemorrhages. Fluorescein angiography revealed early leakage of the conjunctival capillaries and delayed filling of the lower retinal arterioles with retinal edema. The acute glaucoma subsided rapidly. The myopia disappeared slowly with a gradual deepening of the anterior chamber after onset of the diuretic phase of the illness. In nephropathia epidemica, the transitory shallowing of the anterior chamber, myopia, and acute glaucoma are due to lesions in the small blood vessels of the ciliary body, resulting in its swelling, with relaxation of the zonules and forward movement of the lens.


Relative afferent pupillary defect in glaucoma. Seven patients with asymmetrical open-angle glaucoma had relative afferent pupillary defects. This defect may have occurred during any stage of glaucoma, but the presence of this sign may be indicative of the earliest onset of optic nerve damage in patients with ocular hypertension. Although the presence of an afferent pupillary defect should suggest the consideration of a neurologic lesion, glaucomatous damage may be the sole explanation for this phenomenon.


Glycerol and hyperosmolar nonketotic coma. Hyperosmolar nonketotic coma occurred in a 29-year-old diabetic man with chronic renal failure after the repeated use of oral glycerol for treatment of acute neovascular glaucoma. Treatment with intravenous hypotonic saline, albumin, and packed red blood cells together with insulin and bicarbonate was successful in overcoming the coma.


Endothelial damage associated with intraocular lenses. We examined the corneal endothelium of five patients with the clinical specular microscope before and at intervals after combined cataract extraction and intraocular lens implantation. There was a severe loss of endothelial cells postoperatively in all five patients despite clear, thin corneas. We observed no significant endothelial regeneration (increased number of cells) or continued cell loss during 15 weeks of postoperative observation. The clinical specular microscope was useful in assessing the endothelial effects of ocular surgical procedures.


Comparative toxicity of intraocular irrigating solutions on the corneal endothelium. Isolated rabbit and human corneas were perfused in vitro with Plasma-lyte 148 solution and with a glutathione bicarbonate Ringer's solution. The corneal swelling rate and ultrastructure were compared to corneas perfused with three commonly used intraocular irrigating solutions. Corneas perfused with Plasma-lyte 148 swelled at a rate of 47 mu/gr and the endothelial cells separated from each other and showed extensive damage after three hours of perfusion. By comparison, corneas perfused with 0.9% NaCl increased in thickness by 98 mu/hr, lactated Ringer's by 39 mu/hr, balanced salt solution by 24 mu/hr, and glutathione bicarbonate Ringer's solution by 4 mu/hr. These results indicate that endothelial cell damage and increased corneal thickness observed during perfusion was related to the incomplete composition of 0.9% NaCl, Plasma-lyte 148, and lactated Ringer's and that endothelial cell damage can be prevented if the intraocular irrigating solution contains concentrations of inorganic and organic constituents that are similar to those in aqueous humor.


Corneal endothelial degeneration and fibrous proliferation after plana vitrectomy. A 45-year-old woman with juvenile-onset diabetes had persistent corneal edema after a pars plana vitrectomy and lensectomy procedure. Phase contrast and electron microscopic observation of the patient's cornea revealed extreme attenuation of the endothelial cell layer and abnormal collagenous and basement membrane material interposed between Descemet's membrane and the endothelium. Endothelial fibrous proliferations in this case were consistent with the development of ultrastructurally identical fibrous proliferations in many other situations involving dysfunction of the corneal endothelium.


Autofluorescence of the human diabetic lens in vivo. We studied the in vivo measurements of the autofluorescence of the clear lens in 80 juvenile diabetics and 25 young healthy subjects. When the diabetes was of seven years' duration or more, no overlap with the control subjects was found. The pathologic autofluorescence of the diabetic lens showed a positive correlation with age and the duration of diabetes.


Tissue, tear, and serum IgE concentrations in vernal conjunctivitis. Abnormal upper tarsal tissue from four patients with vernal conjunctivitis stained immunofluorescently contained abundant IgA-, IgD-, and IgE-forming plasma cells in two of four patients. These were absent in normal upper tarsal conjunctiva. The IgE levels of paired tear-serum samples of 11 patients with vernal conjunctivitis and ten control subjects were 130 ng/ml in patients that did nor differ significantly from the normal tear IgE value of 61 ng/ml. The serum IgE means of 1,031 ng/ml for patients and 201 ng/ml for normal subjects differed significantly (P less than .05). Tear and serum IgE values correlated significantly for both groups (P less than .01 for patients, P less than .05 for normal subjects). These findings are consistent with a hyperplasia of IgA, IgD, and IgE antibody-forming cells in tarsal conjunctiva of some patients with vernal conjunctivitis, and tear IgE levels being a function of serum IgE levels.


Lower eyelid reconstruction by tarsal transposition. We reconstructed the lower eyelids of 13 patients using a tarsoconjunctival flap from the upper eyelid. The laterally based pedicle flap permitted a one-stage repair without prolonged occlusion of the eye. The technique was best suited to lesions involving the lateral aspect of the lower eyelid, but can be applied to lesions of the central and medial eyelid. The functional and cosmetic results were equal or superior to tarsoconjunctival advancement flaps.


Anaerobic streptococcal corneal ulcer.

Anaerobic streptococcal corneal ulcer. An anaerobic streptococcus caused a central corneal ulcer in a 10-year-old girl. There were no identifying clinical findings. The lesion healed promptly and satisfactorily with antibiotic therapy.


Field work experience ratings and certification examination scores as predictors of job performance and satisfaction in occupational therapy. The American Occupational Therapy Association's certification instruments, the Certification Examination for Occupational Therapists Registered and the Field Work Performance Report, were examined in terms of their ability to predict future job performance and satisfaction of occupational therapists. A job satisfaction questionnaire was administered to 208 occupational therapists, and their supervisors rated them on a job performance instrument. The resulting correlations between these work adjustment variables and the previously administered certification instruments failed to reveal any predictive ability. Some plausible reasons for these negative results and possible directions for further research into this professional screening process were explored.


Community-based learning in occupational therapy. A community-based field work experience for senior occupational therapy students is described. The program was designed to meet five objectives: to provide students with an effective integration of theory and practice; to allow an application of theoretical concepts to early intervention and prevention programs; to enable students to confront complexities of community service delivery; to allow students to learn new roles in community programs; and to demonstrate the role of occupational therapy within a public health model of service delivery. In addition to these project objectives, placement sites, student roles, and organization of supervision are discussed. Examples are given to illustrate the diversity of student experience. Student and consumer feedback indicated that positive gains had been made toward fulfillment of the project objectives.


The relationship between occupational therapy and physical therapy test scores in children with learning disabilities. Twenty-seven children with learning disabilities associated with perceptual deficits were studied in order to determine what relationship might exist between occupational therapy and physical therapy test scores. Intercorrelations were computed and multivariate models were developed for the occupational therapy test items. Numerous positive relationships were demonstrated between the two groups of test items, consistent with previous clinical and experimental data. One test, however, did not duplicate the other, and both are essential in the evaluation of the learning-disabled child with perceptual deficits. Negative correlations also emerged, which might have been caused by compensation for deficits.


Unusual intranuclear filaments in the circulating lymphocytes of patients with multiple sclerosis and optic neuritis. Mononuclear cells obtained from the peripheral blood of patients with multiple sclerosis (MS) and optic neuritis (ON) were examined by electron microscopy. Unusual intranuclear filaments identical with the so-called paramyxovirus-like filaments were found in circulating lymphocytes from 5 patients with MS and 3 with ON. They were observed in 0.1 to 0.5% of the mononuclear cells. Electron microscopy of the blood cells from 5 other patients with ON, 3 patients with neurologic diseases other than MS, and 4 normal subjects failed to reveal similar structures. The filaments were also absent from blood cells from blood cells from normal subjects during the process of autolysis.


Nonpathogenicity of antiintestinal antibody in the rabbit. Rabbits were immunized with intestinal extract prepared from rabbits, guinea pigs, and germ-free rats. The resultant serum antibody response to intestinal antigen was determined by gel precipitation and direct tissue immunofluorescence. Forty-eight hours prior to sacrifice of each immunized animal, a portion of the duodenum, ileum, and colon were traumatized to bring circulating antibody into contact with the tissue. Sections for histology and direct immunofluorescence were taken from the area of trauma, just adjacent to the area, and 10 cm from it. The humoral immune response, the presence of tissue bound immunoglobulin, and tissue histology were compared. The area of trauma in normal and immunized animals showed the same histologic changes. In each animal, tissue just adjacent to the area of trauma and 10 cm from it were histologically identical. The pathologic alterations in the immunized animals were similar to those associated with malabsorption in man. Direct immunofluorescence of the intestinal tissue revealed bound immunoglobulin in histologically normal and abnormal tissue. Precipitating antibody to intestine was present in the serum of rabbits with normal and abnormal histology. Thus, antiintestinal antibody as dected by precipitation in gel and direct tissue immunofluorescence does not appear to be a factor in the pathogenesis of this model of immunologically induced histologic changes in the intestine.


Localization of platelet prostaglandin production in the platelet dense tubular system. Platelet production of 12L-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and 8-(1-hydroxy-3-oxopropyl)-9, 12L-dihydroxy-5,10-heptadecadienoic acid (PHD), two metabolites of the prostaglandin cyclic endoperoxides PGG2 and PGH2, was found in this investigation to occur primarily in a platelet microsomal fraction consisting almost exclusively of membranes. To further localize the membrane site of platelet prostaglandin biosynthesis, the present study has used a cytochemical technique employing 3,3'-diaminobenzidine as an oxidizable substrate. The reaction product was found to localize in the platelet dense tubular system. Formation of the reaction product was inhibited by aminotriazole. In similar concentrations, aminotriazole inhibited collagen and arachidonic acid aggregation, the second wave of ADP and epinephrine aggregation, but failed to inhibit aggregation by PGG2 and A23187. A study of the mechanism of action of aminotriazole revealed inhibition of formation of HHT and PHD. The results localize platelet prostaglandin biosynthesis to the membranes of the dense tubular system.


Kinetics of epidermal production during epidermal regeneration following abrasion in mice. A technique is presented which allows us to measure total increases in epidermal wet weight on the back of a mouse during epidermal regeneration, thus for the first time permitting us to determine the kinetics of increase of epidermal mass during epidermal regeneration. Within 2 days after removal of the epidermis by abrasion with an emery wheel, in mice in the resting phase of the hair growth cycle, the epidermis begins to be regenerated from the cells of the underlying resting hair follicles. By Day 3 epidermal wet weight is 70% of normal. By Day 4 it is 1.97 times normal and reaches its peak of 3.8 times normal by 5 days. Associated with this increase in epidermal wet weight is a two times increase in the number of epidermal cells per millimeter of interfollicular epidermis. However, the change in the number of cells is not uniform for all types of epidermal cells. Suprabasal cells increase 4.6 times by 7 days, whereas the basal cells actually decrease to 60% of normal levels. Colchicine mitotic count is increased almost 18-fold by Day 3 and remains above control levels for the rest of the experimental period. Many mitoses appear in the suprabasal layers.


Cyclodextrin nephrosis in the rat.

Cyclodextrin nephrosis in the rat. The renal toxicity of the Schardinger dextrins, alpha and beta-cyclodextrin, is manifested as a series of alterations in the vacuolar organelles of the proximal convoluted tubule. These changes begin as an increase of apical vacuoles and the appearance of giant lysosomes. The giant lysosomes characteristic of cyclodextrin nephrosis are notable because of the prominent acicular microcrystals embedded in the lysosomal matrix. Giant vacuoles devoid of acid phosphatase reaction product are found in advanced lesions. The vacuolar apparatus shows advanced changes prior to manifestation of lesions in  mitochondria and other organelles. These observations indicate a role of the vacuologenic apparatus in the nephrotic process. Intracellular concentration of toxin via the lysosomal pathway represents a perversion of the physiologic function of the proximal tubule which ultimately leads to cell death.


Child advocacy: a perspective.

Child advocacy: a perspective. Child advocacy provides a vehicle for building checks into systems that fail children. This paper examines the assumptions underlying child advocacy efforts, the types of child advocacy programs that have developed in the past few years, and the types of strategies used by child advocates.


The impact of the child's deficiency on the father: a study of fathers of mentally retarded and of chronically ill children. Psychological assessments of fathers of mentally retarded, of chronically ill, and of healthy children indicate that the first two groups undergo significant stress associated with their fathering a handicapped child. Some fathers of mentally retarded children appear subject to a pattern of neurotic-like constriction. Differences in the experiences of fathers and mothers of deficient children are discussed, and suggestions for treatment are offered.


The effects of parental divorce: experiences of the child in later latency. This paper discusses the impact of divorce on 31 children in later latency, as observed shortly after the initial parental separation and one year later. The material is part of an on-going clinical study, begun in 1970, of 131 children and adolescents from 60 divorcing families in Northern California.


Relational and behavioral interventions with economically disadvantaged toddlers. Matched groups of children, ages 12-24 months, referred for early social or verbal developmental lags or home-environment problems, participated either in a center-based "relational" or a home-based "behavior modification" intervention. Although both programs accelerated youngsters' intellectual development, there were few differences between groups on the criterion change measures.


Some aspects of adoption in selected samples of adult adoptees. Various aspects of adoption--psychopathology, age at placement, agency versus independent placement, best age to tell child he is adopted, etc.--are studied in three groups of adoptees: biological parent schizophrenic or manic-depressive; adoptive parent schizoprenic or manic-depressive; biological parent with no psychiatric history. Findings raise questions about a number of common assumptions regarding adoptees.


Relationships between symptomatology and SES-related factors in hyperkinetic/MBD boys. Relationships among symptomatology, socioeconomic status, and parenting styles were examined for 113 hyperkinetic/minimal brain dysfunction boys from intact families. Primary symptoms (e.g. hyperactivity) did not vary as a function of SES, but SES-related differences emerged for secondary symptoms (e.g., aggressive behavior, self-esteem deficits) and for parenting variables. Parenting variables were found to be better predictors of secondary symptoms than was SES. Implications for further research are offered.


Sequential withdrawal of stimulant drugs and use of behavior therapy with two hyperactive boys. The separate and combined effects of stimulant drugs, placebos, and behavior therapy were investigated with two hyperactive boys. In each case, sequential replacement of drugs (Ritalin and Dexedrine) with placebos demonstrated placebo effects of the drugs; behavior therapy, alone and in combination with drugs, was effective in controlling hyperactive behaviors. Implications in regard to drugs as treatment of choice are discussed.


Current medical practice and hyperactive children. An extensive questionnaire was completed by 48 physicians, detailing the medical and behavioral information they collect in forming a diagnosis of conditions that have hyperactive behavior as a symptom. Results indicate that diagnoses are made primarily on the basis of behavioral indicators, and indicators and information from the child's personal medical history, rather than from other data collected during the physical exam.


System for averaging physiological data recorded on film or paper. A simple electro-mechanical system has been constructed to convert photographically-recorded data into a form that can be readily handled by a small, special-purpose averaging computer. Manual tracing of a series of records results in the production of an immediate and highly reproducible average response. The method has proven to be particularly useful in the analysis of electromyograms obtained during various form of locomotion.


Microscopic features and transient contraction of palpable bands in canine muscle. Ten pairs of biopsies were excised from gracilis and semitendinosus muscles of 4 mongrel dogs. These were compared with the histological findings reported in painful spots and muscle hardenings of human muscles. Test biopsies sampled a palpable band. Paired control biopsies sampled a portion of the same muscle where it showed no palpable hardening. Processed sections were randomized and read blind. Sections stained with aqueous toluidine blue showed no convincing metachromasia. Sections stained with trichrome showed no proliferation of endomysial connective tissue. Test sections stained with hematoxylin and eosin showed no proliferation of nuclei and no increase in the number of central nuclei in muscle fibers compared to control sections. No convincing histological difference was found. During surgery under Nembutal anesthesia, rubbing palpation of the exposed muscle elicited a transient contraction of a bundle of muscle fibers several milli-meters in diameter. This corresponded in time and position to the palpable band in the dog muscle. The band-like hardness palpated in these canine muscles appears to be caused by a circumscribed transient muscular contraction rather than histologically demonstrable structural changes.


Interaction of gastrin I, secretin, and cholecystokinin on gallbladder smooth muscle. The effect of cholecystokinin (CCK), the octapeptide of cholecystokinin (CCK-OP), gastrin I, and secretin was studied on guinea pig gallbladder smooth muscle in vitro. Both CCK and CCK-OP stimulated gallbladder contraction, with CCK-OP being more potent. Gastrin I, over a wide dose range, had no effect on gallbladder contractility. Secretin alone also showed no effect on gallbladder smooth muscle but in combination with CCK-OP it produced a noncompetitive type of inhibition. Michaelis-Menten kinetics showed the calculated maximum response of the secretin plus CCK-OP interaction to be less than with CCK-OP alone. There was no change in the dose required to achieve half-maximal response, D50. These studies indicate that: a) CCK-OP has a greater effect on gallbladder contractility than CCK, b) gastrin I has no effect on gallbladder muscle tone, and c) secretin acts as a noncompetitive antagonist of CCK-OP. These findings suggest that gallbladder motor function may be determined in part by the interaction of secretin and CCK rather than solely in response to CCK.


Reflex limb dilatation following norepinephrine and angiotensin II in conscious dogs. Effects of intravenous and intra-arterial norepinephrine (NE) and angiotensin II (AN) were compared in 18 conscious dogs instrumented with Doppler or electromagnetic flow probes on the iliac, mesenteric, and renal arteries, and catheters in the aorta and iliac arteries. NE and AN administered intravenously constricted the mesenteric and renal beds, and constricted the iliac bed when administered directly into the iliac artery. In contrast, intravenous NE and AN caused striking reflex increases in iliac flow and reductions in iliac resistance, respectively, in 12 of 18 dogs studied. The reflex iliac dilatation was not prevented by beta blockade with propranolol, cholinergic blockade with atropine, or prostaglandin synthetase inhibition with indomethacin. However, the responses were abolished by either phentolamine, 1 mg/kv iv, or after local blockade of the limb with either phentolamine, 0.5 mg/kg, or with tripelennamine, 2 mg/kg. The dilatation was not prevented by either bilateral carotid sinus and aortic nerve section or by bilateral vagotomy alone, but was prevented by a combination of these procedures. Thus, intravenous NE and AN cause striking reflex iliac dilatation in the limb in the conscious dog; the afferent arc of this reflex involves both arterial baroreceptor and vagal pathways, while the efferent mechanism involves an interaction of alpha-adrenergic and histaminergic receptors.


Norepinephrine turnover in heart and spleen of 7-, 22-, and 34 degree C-acclimated hamsters. Norepinephrine (NE) turnover rates were measured in hamster (Mesocricetus auratus) heart and spleen tissues after 7-10 wk exposure to 7, 22, and 34 degrees C. The competitive inhibitor of NE synthesis, alpha-methyl-p-tyrosine methyl ester, was injected (200 mg/kg, ip) into acclimated animals. At sequential periods after drug treatment, hamsters were sacrificied by cervical transection, and tissues were removed and frozen. Rate constants, turnover time, and turnover rates were determined from regression analysis of NE tissue decay. Heart NE turnover was highest in cold-acclimated and lowest in heat-exposed animals (.111 and .047 mug/g per h, respectively), control values being intermediate (.081 mug/g per h). NE turnover is inversely related to tissue levels in the myocardium of temperature-acclimated hamsters. Spleen NE turnover was lowest with heat exposure, but spleen tissue levels of NE with heat or cold exposure were not different from control (22 degrees C) measurements. Heat-acclimated hamsters are slightly hyperthermic (Tre, 37.24 +/- .18 C; P, .032) compared to 22 degrees C-maintained controls (Tre, 36.85 +/- .07), but body temperature were unchanged with 7 degrees C exposure. The implication of altered NE synthesis is that sympathetic nerve activity is decreased with heat acclimation and increased with cold acclimation.


Mechanisms of blood vessel constriction during hemorrhage. The contributions of sympathetic nerves, circulating hormones, and passive vascular recoil to vasoconstriction and transcapillary fluid reabsorption in skin and skeletal muscle were examined in the forelegs of 55 pentobarbitalized dogs by using a combined gravimetric and segmental resistance technique. Hemorrhage elicited large increases in forelimb segmental vascular resistances and in the rate of extravascular fluid reabsorption. Only a small part of these responses could be attributed to the passive effects of reducing forelimb perfusion pressure.


Localization of mesenteric hyperemia during digestion in dogs. For localization of the site of post-prandial mesenteric hyperemia, low-fat, low-protein food was placed in either the stomach, duodenum, or jejunum while blood flow was measured in the celiac artery, superior mesenteric artery (SMA), or jejunal vein of anesthetized dogs. Distribution of flow in the jejunal wall was also measured. After intragastric placement of food, celiac arterial flow increased within 5 min and remained elevated for 30-60 min; SMA flow increased within 30 min and stayed up for at least 3 h. Intra-duodenal infusion of digested food increased SMA flow but did not alter celiac flow or flow to an isolated jejunal segment. Placement of digested food into one jejunal segment increased flow to that segment did not affect flow was localized to the mucosal layer. These studies indicate that during digestion, blood flow increases in the mucosa of the intestine when exposed to chyme and is not changed in other areas of the gastrointestinal tract. Postprandial mesenteric hyperemia induced by low-fat, low-protein food is a local phenomenon.


Vascular response to short-term systemic hypoxia, hypercapnia, and asphyxia in the cat. Acute systemic hypoxia, hypercapnia, or asphyxia was produced in ketamine-anesthetized, paralyzed cats by ventilating them for 2-4 min with appropriate gas mixtures. A sustained rise in arterial pressure occurred in all cases. Vascular responses to hypoxia (7% O2, 10%  02, or 14% O2) included muscle constriction, cutaneous (hindpaw) dilatation (no change with 14% O2), renal constriction (unchanged flow), and unchanged intestinal resistance. Asphyxia (hypoxia + 10% CO2) produced a similar pattern, except that intestinal dilatation occurred. Hypercapnia (10% CO2 + 21% O2) produced muscle constriction, renal constriction (unchanged flow), intestinal dilatation, and no change in cutaneous resistance. Intestinal dilatation seemed in all cases a response to elevated CO2 only. Hypercapnia augmented the effects of hypoxia in skin and skeletal muscle. The variation of responses in different vascular beds suggests a patterning of sympathetic discharge, and varying responsivity to local and humoral factors.


Beta-hydroxybutyrate transport in rat brain: developmental and dietary modulations. Transport of beta-hydroxybutyrate (betaHB) into rat brain was estimated from the early rise in brain/serum 14C ratio after subcutaneous injection of [14C]betaHB. Permeability of the D isomer exceeded that of the L isomer. Permeability of either isomer rose throughout suckling (sevenfold) and declined after weaning to the low, newborn values. This age dependence differed markedly from those of cerebral blood flow and cerebral permeabilities of urea, glucose, valine, leucine, and DMO (5,5-dimethyloxazolidine-2,4-dione). Fat-feeding more than doubled cerebral betaHB permeability without significantly affecting cerebral blood flow or the permeabilities of urea, glucose, and DMO. Temperature dependence of betaHB permeability was similar to that of glucose transport. The age and diet dependence of betaHB were not accounted for in terms of body temperature, capillary surface, capillary porosity, or plasma proton concentration. A modulable betaHB carrier seemed indicated. Utilization of betaHB by the brain was signficantly governed by permeability, hence the increased permeability in ketotoc states should contribute to glucose sparing and eventually to protein sparing.


Frequency-force relationships of mammalian ventricular muscle in vivo and in vitro. The change in contractility with increasing heart rate was studied in the left ventricle of dogs and in isolated trabeculae carneae of cats. For some of the studies in situ a transient isovolumic state was created by aortic occlusion. At physiological temperatures the frequency-force relationship is flatter than at room temperature and at the same temperature it is flatter in vivo than in vitro. The frequency-(dF/dt)max relationship is steeper than the frequency-force relationship at both temperatures in vivo and in vitro. The frequency-(dF/dt)max relationship is steeper in vitro than it is in situ, although the discrepancy is less marked than in the case of the frequency-force relationship. It is concluded that "staircase" plays less of a physiological role in adjustment of contractile state in situ than might be inferred from studies of isolated tissue.


Propranolol and pyrogen effects of shivering and nonshivering thermogenesis in rats. Injection of bacterial endotoxin (Piromen) into unanesthetized rats elicited increases in shivering and nonshivering thermogenesis as well as in colonic temperature. In animals exposed to 24-25 degrees C, treatment with propranolol (a beta-adrenergic antagonist) markedly diminished the pyrogen-induced increases in oxygen consumption (heat production) and colonic temperature with little change occurring in shivering activity. In contrast, in rats exposed to mild cold (17-18 degrees C), propranolol did not significantly alter the magnitude of the pyrogen-evoked thermogenesis. Rather in these animals, shivering tended to increase when nonshivering thermogenesis was blocked. These data are interpreted as reflecting differential effects of pyrogen on the pathways controlling the two modes of heat production in the rat.


Uptake and metabolism of beta-alanine and L-carnosine by rat tissues in vitro: role in nutrition. Uptake and metabolism of the dipeptide L-carnosine (beta-alanyl-L-histidine) and of the free amino acid beta-alanine were studied in scraped mucosal epithelium of jejunum, kidney cortex slices, and intact hemidiaphragm muscle of the rat. These preparations expose plasma membranes with various orientations to amino nitrogen nutrition.


Effects of anesthetic agents on autoregulation of renal hemodynamics in the rat and dog. Controversy has existed over apparent dissimilarities in the autoregulatory capacities of the rat and dog. A protocol was designed to evaluate both the effects of the anesthetic agents. Nembutal (used most commonly in dogs) and Inactin (most frequently employed in rats) and the species peculiarities of these two mammals on autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR). With Nembutal autoregulation of RBF was present in both experimental animals. Inactin impaired RBF autoregulation similarly in both species. With impaired RBF autoregulation similarly in both species. With either anesthetic GFR was autoregulated well in both rat and dog. Comparison of the two species revealed a greater RBF per gram kidney weight and a higher renal perfusion pressure (RPP) at which autoregulation of both hemodynamic parameters was lost in the rat. It is concluded from these studies that 1) the frequent use of Inactin in the rat in large part accounts for the observed lack of autoregulation of RBF in this animal and 2) renal hemodynamic responses are qualitatively similar in rat and dog when the same anesthetic agents are used.


Metabolic response to carbon monoxide by isolated rat lungs. Glucose metabolism was studied in isolated rat lungs ventilated with 95% O2.5% CO2 (control), 95% N2: 5% CO2 (hypoxia), and 95% CO:5% CO2 (carbon monoxide) and perfused for 100-120 min with Krebs-Ringer-bicarbonate buffer, pH 7.4, containing [U-14C] and [3-3H]glucose. The production of 14C-labeled lactate plus pyruvate (L + P) and of 14CO2 represented 48% and 22% respectively, of the total [14C]glucose utilization. The lactate-to-pyruvate ratio (L/P) was 8.7. Tritium was recovered predominantly as 3H2O in the perfusate. Wth carbon monoxide ventilation, L + P production was increased by 357% with an L/P of 52.9, and 14CO2 production was markedly decreased. A 56% decrease in lung ATP content was associated with decreased incorporation of 14C into fatty acids. Compared with CO, changes with N2 ventilation were less marked, indicating that ventilation with CO is a more effective method with which to study inhibtion of oxidative metabolism. The lung exhibits a Pasteur effectbintain ATP content or its supply for synthetic activity.


Modification of aortic barorecptor resetting in the spontaneously hypertensive rat. Aortic barorecptor function was studied in spontaneously hypertensive rats (SHR) of various ages and normotensive Wistar rats. The aortic arch was isolated and perfused, and the activity of the left aortic nerve was recorded. The threshold pressure to elicit barerecptor firing was 80-120 mmHg in normotensive Wistar rats. Resetting of barorecptors (threshold pressure 160-180 mmHg) was found in all untreated SHR of 35-70 wk of age. Resetting of barorecptors was prevented in SHR by starting treatment with antihypertensive agents at the age of 11 wk. Treatment of 32-wk old SHR with antihypertensive agents for 4-6 wk resulted in reversal of barorecptor resetting in 50% animals. The percentage of SHR showing complete reversal of resetting did not increase even when the duration of treatment was tripled. In 52- to 64-wk old SHR, treated with antihypertensive agents, reversal of baroceptor resetting was seen in only 30% animals. It was concluded that baroceptor resetting in SHR was secondary to hypertension. Hypertension, in turn, induced hypertrophy of the tunica media of the aorta. Histological studies showed a close correlation between aortic hypertrophy resetting. Aortic hypertrophy may, therefore, be one of the important factors involved in baroceptor resetting.


Release of prostaglandin F2alpha during splanchnic artery occlusion shock. Prostaglandin F2alpha concentrations were determined in hepatic portal venous plasma of dogs during splanchnic artery occlusion (SAO) shock and in nonshock control dogs. Dogs subjected to SAO shock exhibited a dramatic decrease in mean arterial blood pressure and significant increases in portal venous PGF2alpha and amino-nitrogen concentrations, as well as in cathepsin D and MDF activities. Dogs treated with indomethacin prior to SAO shock did not exhibit a significant increase in portal venous PGF2alpha. Indomethacin had no effect on the increase of plasma amino-nitrogen and only slightly reduced portal venous cathepsin D activity during SAO shock. Nevertheless, indomethacin significantly attenuated the severity of the postrelease hypotension observed in SAO shock and diminished the plasma accumulation of MDF. These studies indicate that prostaglandins are released from the splanchnic region during SAO shock and that this release can be prevented by pretreatment with indomethacin. The role of endogenously released prostaglandins in SAO shock is not clear, but the magnitude of the increase warrants further study.


Regional blood flow in normotensive and spontaneously hypertensive rats. Regional distribution of cardiac output in unanesthetized spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) and Wistar NR male rats (10 each group; average age 21 wk) was determined using two 15-mum microspheres (141Ce and 85Sr) injected 10 min apart through a left ventricular (LV) cannula. Fractional flow distribution was expressed as percentage activity of injected dose (average of the two measurements). Despite differences in body and organ weights, organ flow distribution did not vary between SHR and WKY, except for heart and testes (P less than 0.025). However, differences did not exist between SHR and NR with respect to heart, brain, lungs, spleen, and adrenal flows (P less than 0.05).


Role of distal delivery of filtrate in impaired renal dilution of the hypothyroid rat. Free water clearance (CH2O) was measured during hypotonic saline infusion in Sprague-Dawley and in Brattleboro (DI) rats with 131I-induced hypothyroidism and their age-matched controls. At peak urine flow, which was similar in hypothyroid DI (HDI) and control DI (CDI) rats, inulin clearance (CIn/kg) and CH2O/kg were 23 and 20% (P less than 0.02) lower in HDI. Fractional urine flow and fractional sodium excretion were 30 and 40% (P less than 0.001) higher in HDI. Utilization of distal delivery of filtrate for CH2O, formation was 16% less in HDI (P less than 0.01). Papillary osmolality was not higher in HDI rats. Data in Sprague-Dawley rats were similar to those of the DI rats, indicating that endogenous ADH was effectively suppressed. It is concluded: 1) delivery of filtrate out of the proximal tubule was not diminished in hypothyroid rats in spite of a decrease in CIn; 2) despite a similar delivery of filtrate to the distal diluting site, CH2O formation was less in hypothyroid rats than in controls; 3) these data suggest that a defect in the diluting segment could be unmasked at high rates of filtrate delivered to the distal nephron; 4) this defect could be either due to impaired sodium chloride reabsorption or due to increased backdiffusion of water in the distal nephron.


Placental amino acid uptake. III. Transport systems for neutral amino acids. The human placenta is known to concentrate nearly all amino acids intracellularly for transfer to the fetus. To clarify the mechanism and regulation of this process we have determined the specificity of the principal placental transport systems for neutral amino acids. With the use of competitive inhibition techniques, three transport systems of overlapping specificity have been elucidated. These correspond approximately to the "A", "L", and "ASC" systems of Christensen and associates. In the placenta the specificity of these systems is as follows: A system - alpha aminoisobutyric acid (AIB), glycine, proline, N-methylalanine, alanine, serine, threonine, and glutamine; L system - isoleucine, valine, phenylalanine, BCH, alanine, serine, threonine, and glutamine; and ASC system - alanine, serine, threonine, and glutamine. Placental AIB uptake previously has been shown to increase with preincubation of tissue in vitro. This increase has now been found to be limited to the A system. Activity of the other two systems is essentially unaffected, demonstrating that the transport pathways are separately regulated.


Renal effect of meclofenamate in presence and absence of superfusion bioassay. Systemic blood pressure (SBP), renal blood flow (RBF), renal vascular resistance (RVR), and arterial and renal venous prostaglandin E (PGE) concentrations were determined in pentobarbital-anesthetized dogs.The effect of sodium meclofenamate infused into the renal artery was compared under two sets of conditions. In experiments carried out under control conditions, SBP, RBF, and RVR were stable and meclofenamate caused only a slight decrease in RBF (5.4%) and increase in RVR.


Effect of occlusion duration on reactive hyperemia in sartorius muscle capillaries. Reactive hyperemia was studied in cat sartorius muscle by measurement of venous outflow and capillary red cell velocity following occlusions of 5-120 s. The peak value for volume flow rose in a graded manner as occlusion duration increased, reaching a level of 280% above control following 120 s of occlusion. By contrast, peak values for capillary flow were 200% above control even after short (10-15 s) occlusions and increased moderately thereafter to 280% above control following 120-s occlusions.


Nonshivering thermogenesis induced by repetitive cooling of spinal cord in the rat. The effect of prolonged and repetitive cooling of the spinal cord on the sensitivity to the metabolic effect of exogenous noradrenaline and on the resistance to cold exposure was studied in the white male rat. The spinal cord of 10 animals was cooled for an average of 90 h-9 h/day 5 days/wk - to a level that induced an increase in oxygen uptake of almost 70%. Oxygen consumption was then measured at 30 degrees C before and 1 h after a subcutaneous injection of noradrenaline (0.4 mg/kg). Following the noradrenaline injection, the experimental animals increased oxygen uptake by 71%, while the control ones increased it by only 33% (P less than 0.01). During exposure to -20 degrees C, the experimental animals, despite their increased capacity for nonshivering thermogenesis, did not maintain rectal temperature longer than the control ones, thus showing that other factors also play a significant role in cold adaptation in the rat.


Circadian rhythms of intestinal sucrase and glucose transport: cued by time of feeding. In the rat, under constant illumination, the activities of the digestive enzyme sucrase and the absorptive transport system for glucose follow circadian rhythms on ad lib. and controlled feeding regimens. In response to controlled feeding, (1400-1800 h or 0200-0600 h, EST), both rhythms shift with time and the general level of activities are enhanced. Sucrase activity peaks before feeding and transport activity peaks during feeding. Feeding is a synchronizer for these digestive-absorptive functions, and the maximum activity of a function may occur prior to as well as subsequent to the daily onset of the synchronizer. The rhythms of these functions results from previous days' feeding patterns.


Effect of graded bilirubin loads on bilirubin transport by perfused rat liver. Features of hepatic bilirubin transport were studied with the isolated perfused rat liver. Male Wistar rats weighing 350-400 g were used as liver donors. When bilirubin was constantly infused into the perfusion medium, which contained sheep erythrocytes and 3.0 g/100 ml bovine serum albumin, the maximal excretion rate for bilirubin was 14.4 +/- 1.2 mug/min per g liver. Over a wide range of constant bilirubin infusion rates which went as high as 25.9 mug/min per g liver, there was no effect on bile flow, bile acid excretion, or the pattern of bilirubin conjugates in bile. The hepatic extraction efficiency for unconjugated bilirubin from the perfusate also remained constant averaging 26%. However, when bolus injections of bilirubin were used to produce higher levels of unconjugated bilirubin in the perfusate than could be attained during constant infusion, the disappearance rate of [14C]bilirubin from the perfusate decreased with increasing bilirubin concentrations. This was consistent with saturation of the hepatic removal of unconjugated bilirubin.


Potassium flux in smooth muscle of frog stomach. In frog stomach muscle fibers, normal steady-state K flux, estimated directly from 42K uptake, was 0.17 pmol/cm2 per s at 5 degrees C and 0.63 pmol/cm2 per s at 15 degrees C. Influx characteristics were studied at 5 degrees C, where backflux and diffusional delay effects are minimized. Steady-state K influx was a saturating function of external [K] over the range 0.25-11 mM [K]o; influx at normal and higher [K]o did not differ significantly. Na loading (in K-free or low K solution) strongly stimulated influx, which showed altered saturation kinetics; maximal K influx was a quasilinear function of internal [Na]. Ouabain (10(-4) M) reduced normal and stimulated K influx markedly. Ethacrynic acid (10(-3) M) caused net K loss and Na gain, but increased K influx fourfold; ouabain inhibited the stimulated influx by 50%. These results indicate that K influx depends mainly on cycling of the Na-K pump and is normally limited by Na efflux. Ethacrynic acid may stimulate another mode of pump operation, K-K exchange, and uncouple the normal operation.


Disposition of plasma cholesterol in the pregnant hypocholesterolemic rabbit. Processes that might explain the hypocholesterolemia observed in pregnant rabbits were studied in animals fed a cholesterol-free chow diet. Excretion of endogenous steroids, measured after administration of a single intravenous dose of radioactive cholesterol, averaged 75 mg/day in controls and 96 mg/day in pregnant hypocholesterolemic rabbits. The mass of maternal plasma cholesterol transferred to the fetuses was measured in animals in which a constant plasma cholesterol specific activity was maintained. Placental transfer during the first 28 days of gestation ranged from 2 to 12 mg/day for mothers carrying litters of one to eight fetuses. It is concluded that loss of maternal plasma cholesterol due to placental transfer is small compared to loss by fecal steroid excretion. Because large decreases in plasma cholesterol concentration during pregnancy and increases at parturition were not accompanied by changes in the slopes of the specific activity-time curves, it appears most likely that cholesterol in isotopic equilibrium with plasma cholesterol is temporarily and reversibly sequestered in maternal tissues of the pregnant rabbit.


Mechanism of action of aspirin on canine gastric mucosa. Using an in vivo chambered canine stomach preparation, exposure of the gastric mucosa to 5, 10, and 20 mM aspirin(pH 3.0) resulted in a decrease in electrical potential difference (PD) and in an increase in resistance (R) within 30 min. In vitro, exposure of the mucosal side of the isolated canine gastric mucosa to 5, 10, and 20 mM aspirin (pH 3.0) for 1 h or of 1 mM aspirin (pH 3.0) for longer than 1 h resulted in marked permeability changes, i.e., increases in the undirectional fluxes of Na+ and Cl-, as well as inhibition of net ion fluxes. These concentrations of nonionized aspirin (pH 3.0) also reduced the R and PD. However, 1 mM aspirin (pH 3.0) or 20 mM ionized aspirin (pH 7.4) depresses the active transport of ion, increases R, but does not increase the ionic permeability. Mucosal adenosine triphosphate (ATP) content is reduced by mucosal instillation of aspirin (pH 3.0). These results demonstrate that the initial action of aspirin is inhibition of ion transport which is followed by an increase in permeability.


Renal excretion of uric acid in the rat: a micropuncture and microperfusion study. Free-flow micropuncture experiments were done in rats of three strains infused with small amounts of urate [plasma urate (P urate) = 95 +/- 8 muM]. Urate concentrations in tubular fluid were measured by an accurate chemical fluorometric ultramicromethod. In fluid from surface glomeruli, the glomerular fluid-to-plasma urate ratio [GF/P) urate] was 0.99 +/- 0.03 (n=11), i.e., lower than expected for total ultrafiltrability of plasma urate. Along proximal convolutions, net reabsorption of 55% of filtered urate was demonstrated. Small amounts of urate may have been reabsorbed between late proximal and early distal sites. Net transepithelial movements of urate did not occur in distal tubules or collecting ducts. In microperfusion experiments on proximal tubules, both a reabsorptive flow of urate (loss of perfused [2-14C]urate) and a secretory flow (entrance of cold urate into perfusate) of the same order of magnitude were demonstrated. Neither flow was influenced by simultaneous water movements. Microperfusion of Henle's loops indicated a significant but very small net reabsorption.


Increase in renin release after sionaortic denervation and cervical vagotomy. The role of the vagi in the control of renin secretion was investigated in dogs maintained on a high-salt diet. Renal perfusion pressure was maintained relatively constant by the manipulation of a suprarenal aortic snare. Mean arterial blood pressure (MAP), plasma renin activity (PRA), and packed cell volume (PCV) increased after sinoaortic denervation and cervical vagotomy. Cooling of cervical vagi to 3-5 degrees C had the same effect as vagotomy. There was no change in MAP, PRA, and PCV in sham-operated animals. Propranolol prevented the increase in PRA following sinoaortic denervation and vagotomy, but not that in MAP or PCV. In splenectomized dogs, PCV still showed increases after sinoaortic denervation and vagotomy. It is suggested that the removal of sinoaortic and/or vagal inhibitory effects on the vasomotor center causes increases in sympathetic discharge to the adrenal medulla and the peripheral vessels, and that this in turn leads to the increase in MAP. The increase in sympathetic discharge to the adrenal medulla and the kidney causes the increases in PRA.


Intrarenal calcium in phosphate handling. The intrarenal role of plasma ionized calcium (Ca), on fractional phosphate excretion (FE PO4) was investigated in dogs with control of parathyroid hormone (PTH). In series 1, acute thyroparathyroidectomy was immediately followed by a constant infusion of bovine PTH (0.01 U/kg per min). Subsequent calcium chloride infusions increased Cai in plasma phosphate and decreased in the percentage of ultrafiltrable phosphate. A 20% increase in Cai significantly increased FE PO4 by +3.82 +/- 0.97% (P less than 0.01) when infused intravenously and by +2.62 +/- 1.06% (P less than 0.05) when infused in the renal artery. In contrast, a 75% increase in Cai did not significantly change FE PO4. In series 2, dogs were thyroparathyroidectomized 18 h before experiments, and no PTH infusion was initiated. A bolus of bovine PTH (30 U/kg) increased FE PO4 + 8.9 +/- 0.9% (P less than 0.001) in hypocalcemic dogs, +19.1 +/- 4.4% (P less than 0.001) in normolcalcemic dogs, and +15.5 +/- 1.5% (P less than 0.001) in hypercalcemic dogs. We conclude that increases in plasma calcium potentiate the phosphaturic effect of PTH. This potentiating effect is attenuated in marked hypercalcemia by superimposed hemodynamic and/or metabolic changes.


Hypothalamic and brachial nerve effects on circulation of isolated canine forelimb,. Canine forelimbs were vascularly isolated and perfused at either constant inflow or constant inflow pressure. A comparison of the effects of electrical stimulation of hypothalamic pressor areas and brachial nerves was made on several vascular parameters. During constant pressure perfusion, forelimb resistance increased and total forelimb volume decreased. Additionally active vascular volumes measured with 131I-labeled albumin and 51Cr-labeled red cells decreased significantly. Capillary diffusion capacity product calculated from extraction of 86RbCl also decreased significantly as did the capillary filtration coefficient (CFC). The only significant differences between hypothalamic and brachial nerve stimulation were noted in the larger decreases in active volumes and CFC during the latter stimulations.


Effect of a fixed pyloric opening on gastric emptying in the cat and dog. The effect of preventing pyloric closure on the rate of gastric emptying without alteration of the gastroduodenal junction was studied in six dogs and four cats with gastric fistulas. Each had a Teflon cannula with an internal diameter of 1.0 or 1.25 cm (dog) and 0.6 cm (cat) sewn into the pyloric channel. At the completion of the initial series of tests, the cannulas were removed and the studies repeated. Test meals were 240 and 480 ml of water, acid (120 mM HC1), and hyperosmotic glucose (555 mM) in the dogs and 50 ml of water, acid (100 mM HC1) and fat (20 mM Na oleate) in the cats. Phenol red was used as a nonabsorbable marker. The residual volumes were collected at 15-40 min in the dogs and 15-20 min in the cats. In both species, the rate of emptying of all the meals was unaffected by the pyloric cannula. In the dog, added secretions were greater with the pyloric cannula in place, suggesting reflux of duodenal contents. This study indicates that while the pylorus is unimportant in the gastric emptying of liquids in the dog and cat, it may have a role in prevention of duodenal reflux.


Effect of hemorrhagic shock on renal release of prostaglandin E. The effect of hemorrhage and reinfusion on renal release of prostaglandin E (PGE), arterial [PGE], mixed-venous [PGE], and renal function was observed in anesthetized dogs. Following hemorrhage to 60 mmHg arterial pressure, arterial [PGE] rose significantly from 405 to 740 pg/ml. Renal release of PGE remained near control (8 ng/min), as renal blood flow (RBF) decreased from 4.7 to 2.2 ng/min per gram kidney weight (KW). Mixed-venous [PGE] remained near the control value (960 pg/ml). Reinfusion of shed blood restored RBF to 4.0 ml/min per KW. Renal release of PGE rose significantly to 190 ng/min. Arterial [PGE] remained elevated, but mixed-venous [PGE] was not significantly different from control. Indomethacin, a prostaglandin synthesis inhibitor, caused a significant decrease in renal release of PGE. Arterial [PGE] remained elevated following treatment. The inhibition of PGE release from the kidney by indomethacin indicates that increased renal release of PGE following reinfusion is the result of accelerated PGE synthesis. The data suggest that the elevated arterial [PGE] may be the result of alteration of the handling of PGE by the lung.