The autonomous nodule of the thyroid: correlation of patient age, nodule size and functional status. In light of new techniques for measuring circulating thyroid hormones and for studying the thyroid gland, we present our experience with 35 patients with solitary autonomous nodules of the thyroid to define more precisely the clinical course of patients with this disorder. The patients ranged in age from 19 to 80 years and 31 of the 35 were female. Younger patients were generally euthyroid and sought attention because of a thyroid mass; virtually all older patients were hyperthyroid. Eighteen had obvious clinical features of hyperthyroidism and 5 over age 70 had apathetic hyperthyroidism; all 5 of the elderly and 13 of the 18 under age 70 had elevated thyroxine (T4) and triiodothyronine (T3) levels. Isolated elevation of T3 and elevated basal metabolic rate were observed in 5 previously untreated clinically hyperthyroid young patients. In each of these, thyroid uptake of 131-I was not suppressible with exogenous T3 and BMR was elevated in those tested. Two elderly patients, who had previously been treated for conventional hyperthyroidism with radioactive iodine, had T3 toxicosis when hypoethyroidism recurred. There was a strong positive correlation between the age of the patient, the size of the nodule and the thyroid functional state. The mean area of the nodules projected on 131-I rectilinear scan for euthyroid patients was 5.1 cm2. The mean area of the nodules in hyperthryoid subjects was significantly higher, 13.4 cm-2 in patients with T3 toxicosis and 19.3 cm-2 in subjects with conventional hyperthyroidism. Progression from a euthyroid state to hyperthyroidism was observed four patients. One of these became thyrotoxic within days after an injection of iodinated contrast medium. Spontaneous resolution of nodules occurred in two patients.


Culdoscopic ligation as an outpatient procedure. The increasing demand for abortion and sexual sterilization has caused the need to perform such operations on an outpatient basis. The University Department of Obstetrics and Gynaecology, Singapore, started a prospective study of culdoscopic ligation as an outpatient procedure in November, 1972. To date, over 600 operations have been performed. Analysis of the first 405 cases showed a low complication rate of 2.4 per cent. This study showed that culdoscopic ligation performed in the hospital outpatient is safe and feasible.


Sickle cell anemia- clinical manifestations in 100 patients and review of the literature. The clinical and hematological features of 100 patients with sickle cell anemia are reviewed. The heart was enlarged and a murmur was heard in nearly 80 percent of patients. Pneumonia and pulmonary infarction occurred in 43 percent and 12 percent of patients, respectively. Musculoskeletal involvement included the hand-foot syndrome (15 percent), leg ulcers (55 percent), aseptic necrosis ofbone (11 percent), and osteomyelitis (4 percent). Symptoms and signs related to the gastrointestinal system included jaundice (55 percent), hepatomegaly (50 percent), splenomegaly (23 percent), hepatitis (11 percent) and gallstones (9 percent). Three patients underwent cholecystectomy and three patients had their spleens removed. Pyelonephritis occurred in 17 patients, priapism in five and hematuria in seven. Nineteen women had 39 pregnancies, of which 35 resulted in the birth of healthy infants. At least 328 painful crises occurred in 73 patients. There were also 13 hemolytic crises, eight sequestration crises, and five aplastic crises. A trail of alkali therapy in 33 crises in children failed to produce beneficial effects greater than hydration and analgesics alone as used in the control group. Laboratory findings in the 100 patients were comparable to those previously reported in the literature. The renal concentrating defect in most patients was confirmed.  There were six deaths: hepatic coma secondary to post-transfusion hepatitis, thrombosis of inferior vena cava, congestive heart failure, exsanguination from erosion of the pancreaticoduodenal artery, extensive bronchopneumonia, and pulmonary infarction.


The effects of self-monitoring by patients on the control of hypertension. The effects of self-monitoring of blood pressure on the control of hypertension were examined in this study. Failure of patients to comply with treatment is presumably attributable in part to the fact that hypertension usually is asymptomatic until complications develop. Self-monitoring might make visible an otherwise asymptomatic condition, and thereby increase motivation. One hundred hypertensive patients beginning outpatient treatment were randomly assigned to experimental and control groups. Subjects were given a sphygmomanometer and instructed in its use. Both groups were given similar antihypertensive medications. After six months of treatment, mean systolic pressure was significantly lower (11.4 mm Hg, p smaller than 0.05) in the experimental than in the control subjects. However, the mean baseline systolic pressure in the control group was 3.9 mm Hg less than that of the experimental group. If this value is substracted from the difference between the last mean systolic pressures in the two groups, the 7.5 mm Hg difference is seen as a very modest effect of self-monitoring. Diastolic blood pressure was insignificantly lower for experimental subjects. Compared to the potent effectiveness of drugs in reducing blood pressure, self-monitoring was of little value.


Observations on a model of the biology of carcinoma of the cervix: a poor fit between observation and theory. The role of the mathematical model is to express the biological theory in the form of a set of numerical predictions which can be reconciled with data. We have fitted the model implicit in current theory, and the predictions from that do not fit the observed facts. Either the theory or the observed facts (or both) are wrong. If the facts are right, then our final model (Model II) points to the changes in the theoretical concept which are necessary. Increasing conversion from carcinoma in situ to invasive carcinoma with age must be accepted and explained. The fall in prevalence of dysplasia and carcinoma in situ before the major onset of invasive cancer must be fully appreciated and explained. The regression of carcinoma in situ to dysplasia or normal in large numbers must be accepted and explained either biologically or by error in categorization, or both.


Amniotic fluid creatinine in pregnancies complicated by diabetes. Amniotic fluid (AF) creatinine concentrations, determined in 353 samples from 167 pregnancies complicated by maternal diabetes, are similar to those found at comparable gestation in uncomplicated pregnancy. Added maternal vascular disease significantly raises AF creatinine to such a degree that overestimation of fetal (renal) maturity is a clinical hazard if based solely on this parameter. Relative concentrations of creatinine in AF and maternal plasma (AF/MP ratio) are related to gestational age. Failure of AF creatinine to rise consistently on successive serial samples accompanies an increased risk of perinatal death in the pregnancy complicated by diabetes, four of five deaths in the present series following declines in this measurement.


Reduction of cervical resistance by prostaglandin suppositories prior to dilatation for induced abortion. Several recent reports citing increased rates of prematurity among women who have had induced first-trimester abortion suggest that forceful cervical dilatation may result in cervical incompetence in future pregnancy. There appear to be conflicting clinical impressions regarding the effectiveness on cervical softening and the reduction of cervical resistance produced by various prostaglandins. The development of the Electronic Force Monitor which is capable of precise measurement of the forces encountered in overcoming resistance during dilatation provided objective evidence with which to evaluate the effects of vaginally administered prostaglandin E2 and F2alpha suppositories. Suppositories were administered 3 hours prior to cervical dilatation, after which suction curettage was performed. Compared to the nonmedicated control group, patients receiving PGF2alpha suppositories exhibited greatly reduced cervical resistance, in some cases permitting direct introduction of the suction curette without need for any preliminary dilatation. Those patients receiving PGE2 suppositories showed an intermediate degree of cervical softening.


A comparison of methods for collecting clean-catch urine specimens in a clinic population of obstetric patients. A descriptive study comparing the use of the gram-positive skin cleansers Zephiran and hexachlorophene to Prepodyne, a gram-negative cleanser, was performed upon 1, 469 specimens from patients attending the prenatal clinic of a large university hospital. The period prevalence rate of symptomatic and asymptomatic bacteriuria in 1, 350 patients was 11.5 per cent. Group teaching compared to individualized teaching of the patients to collect their own aliquots did not appear to have a measurable effect upon the levels of bacteriuria. Significant differences were found at p equals 0.05 between all the serially sampled groups using the different cleansers. No significant difference was found between the two groups using only hexachlorophene when compared for differences between patient-collected and nurse-collected specimens; nevertheless, the patient-collected specimens had greater proportions of low bacterial counts than those collected by the nurses. This study indicates that carefully instructed patients in large clinic populations are more efficient than the nurses when they collect their own midstream specimens, using an adequate cleansing agent. An analysis of the rates disclosed that Zephiran cleansing had high contamination levels, whereas Prepodyne significantly reduced contamination of the specimens. However, the possible reduction of the rate of 10-5 specimens to 9.1 per cent in the group using Prepodyne did not rule out the possibility of reduced specificity, and the hazard of false-negative results occuring with the use of gram-negative skin cleansers requires further study.


Fetal stress from methadone withdrawal.

Fetal stress from methadone withdrawal. A pregnant patient in the midtrimester of pregnancy was begun on a methadone detoxification program. The fetal neurobiologic response was monitored by serial amniotic fluid amines (epinephrine and norepinephrine). The detoxification program showed a marked fetal response of the adrenal gland (E) and sympathetic nervous system (NE) that was blunted when the methadone dose was increased. Detoxification during pregnancy is not recommended unless the fetus can be biochemically monitored.


Fetal crown-rump length and biparietal diameter in the second trimester of pregnancy. This study examines the relationships between fetal size (biparietal diameter and crown-rump length) and gestational age among subjects aborted by hypertonic saline in the second trimester of pregnancy. With a confidence of 90 per cent, biparietal diameter can be used to predict gestational age within plus or minus 2 weeks, and crown-rump length can be used to predict gestational age within plus or minus 3 weeks.


Hydatidiform mole with coexistent fetus. Eight cases of hydatidiform mole with coexistent fetus are presented with special considerations of diagnosis and management. Although the incidence of this condition was one in 22,000 pregnancies, it is emphasized that the combination of a mole with a fetus should be included in the differential diagnosis of patients who have signs and symptoms of gestational trophoblastic disease in the presence of a fetus. Recommended treatment is immediate termination of the pregnancy. Appropriate follow-up with a sensitive and specific gonadotropin assay is required to differentiate minimal tumor activity rom normal levels of pituitary luteinizing hormone. None of the patients in this series developed maligant trophoblastic neoplasia.


Biodegradable polylactate as a steroid-releasing polymer: intrauterine administration of d-norgestrel. Polylactate film containing 30 per cent or 4.5 mg. of d-norgestrel was fixed around a plain T-IUD and the device was inserted into the uterine cavity. Norgestrel was gradually released into the systemic circulation, blood levels being highest during menstruation. Plasma estradiol and progesterone determinations revealed that cyclic ovarian function was maintained during the intrauterine administration of norgestrel; however, marked local effects on the endometrium resulted. The amount of menstrual bleeding was reduced.


The effect of actinomycin D on estrogen-induced uterine blood flow. The effect of actinomycin D on estrogen-induced uterine blood flow was studied in four nonpregnant, oophorectomized sheep, utilizing electromagnetic flow probes chronically implanted around the uterine arteris. Two hours after the intravenous injection of 1 mug of estradiol-17beta per kilogram of body weight, incorporation of [3H]-uridine into RNA was two- to threefold higher (2.7 plus or minus 0.4 S.E.M.) in the control horn than the uterine horn that had received an intra-arterial injection of actinomycin D. Actinomycin D had no effect on the estrogen-induced increase in uterine blood flow.


Effects of fetal sex and weight and placental weight on maternal serum progesterone and chorionic gonadotropin concentrations. A prospective study of 268 normal pregnant women at term was undertaken in which serum concentrations of progesterone (P) and chorionic gonadotropin (HCG) were determined zero to four days before spontaneous labor. Neither HCG nor P changed significantly during these four days, although they were not measured serially in most women. There was no correlation between the HCG level and either the placental or infant weight, infant sex, or maternal serum progesterone concentration. The maternal serum P level was slightly but significantly correlated with the weight of the placenta (r equal to  0.24; p smaller than 0.001) but not with the fetal weight or infant sex. Thus, although the mass of trophoblastic tissue contributed in part to P concentration, other intracellular factors such as the cyclic adenosine monophosphate system are probably more important regulating mechanisms.


Suprapubic vs. periumbilical amniocentesis. Amniocentesis has assumed a major and increasing role in the proper management of highrisk pregnancies but the procedure is not without complications. This study was undertaken to compare the suprapubic with the periumblical or "small-parts"approach. A total of 308 amniocenteses were included. The suprapubic method had fewer failures and fewer complications. The rate of premature rupture of the membranes was identifical with both approaches; in fact, following either type of amniocentesis, the percentage of premature ruptured membranes was no differnet from the anticipated spontaneous rate. In all cases of premature rupture of the membranes there were no cases of respiratory distress syndrome, maternal infection, or neonatal infection.


Relationship between cortisol and lecithin/sphingomyelin ratios in human amniotic fluid. Amniotic fluid was obtained from 85 women during the last trimester of gastation and analyzed for cortisol by a radioimmunoassay procedure and for lecithin/sphingomyelin (L/S) ratios by a combined thin-layer chromatography densitometer scanning technique. A total of 114 samples were examined. Cortisol values ranged from 38 to 438  ng. per milliliter; L/S ratios ranged from 0.3 to 9.2. Comparison of cortisol levels with L/S ratios by multiple regression analysis gave an "r" value of 0.371. From less than 32 weeks' gestation to 41 or 42 weeks there was an increase in cortisol levels from 139 plus or minus 124 to 290 plus or minus 78 ng. per milliliter whereas the L/S ratios increased from 1.8 plus or minus 2.3 to 3.9 plus or minus 2.0. These data indicate that there is no good correlation between cortisol and L/S ratios in the samples of amniotic fluid analyzed.


Discordant severe cranial defects in monozygous twins. Three cases of monozygous male twins having exencephaly, anencephaly, and acephaly, with their cotwins being normal, are reported. Monozygosity of the twins was demonstrated by pathologic examination and in one case corroborated by blood group antigen testing. A constellation of abnormalities including adrenal hypoplasia in one of a pair of monozygous male twins with chorionic vascular anastomoses, together with the unusual racial background in each case, are in support of the possibility that environmental factors may play an etiologic role.


Effect of folic acid supplement on birth weights of infants. Earlier observations from this Institute have indicated that the infants born to mothers receiving folic acid supplements in addition to iron during pregnancy were heavier than those born to mothers receiving iron alone. Since birth weights are influenced by maternal factors like height and parity, a trial was carried on in matched controls with iron and iron and folic acid during the last 12 to 16 weeks of pregnancy. Simultaneously, placental function was also assessed. The effect of the folic acid supplements was more marked on first born children. Incidence of small-for-dates births was half in the iron and folate-supplemented group as compared with the iron-supplemented group. The heights of mothers did not make any difference on the effect of folate supplement. The improvement in the birth weights seem to have been brought about by increase in placental size, cell number, and protein content in the folate supplement group. In view of multivariant deficiency and practical problems in implementing food supplement programs to expectant mothers, supplements of folate and iron to expectant mothers in large scale may bring about an improvement in the incidence of pregnancy anemia and also reduce the infant morbidity and mortality rate due to the high incidence of low-birth weight babies.


Oral conception and uterine size-ultrasonic study. The effect of oral contraceptives on uterine size has been examined by B-mode ultrasonography. The subjects were 39 women (mean age 21) with regular menstrual cycles. None of them had taken the pill previously. The combined pill (E-con or Neo-Primovlar) was prescribed for 21 and the progestogen-only pill (Exluton) for 18 of the participants. The uterine size  was measured with the help of B-scanning prior to the pill and after it was taken for three and six months. All three ultrasound examinations were carried out on the same day of the cycle plus or minus one day). No difference can be observed between the three measurements of uterine size either in the women on the combined pills or those on th progestogen-only pill (p greater than 0.05). The study will be continued. So far six women have been examined by ultrasound after having taken oral contraceptives for 12 months. Uterine size has remained unchanged in each case.


Mangement of vaginal carcinoma after hysterectomy. Vaginal carcinoma after hysterectomy occasionally has developed into an invasive lesion. Three cases, all treated differently, are described. The means of preventing further disease and for differently treating the vaginal lesion are discussed. Radiotherapy is recommended for invasive lesions and surgery or surveillance for noninvasive lesions.


Erythrocytosis due to erythropoietin-producing uterine fibromyoma. Erythrocytosis has been observed to occur infrequently in association with uterine fibromyomas. Study of this case revealed erythrocytosis prior to surgery and a remission was noted after myomectomy. Elevated erythropoietin activity in this patient's serum was demonstrated. The erythropoietin activity in the tumor tissue extract was 10 times higher than in the control tissue extract. We postulate that the tumor itself was responsible for the erythrocytosis observed. The mechanisms proposed to explain polycythemia in such a tumor were revised and our conclusion is that the tumor produced the erythropoietin autonomously and is not subjected to feedback control mechanism.


Construction of shoulder and breast prostheses. The usual surgical treatment for patients who have osteogenic sarcoma of the humerus is forequarter amputation. Hence, a prosthetic shoulder is needed in order to compensate for the resulting deformity. Occasionally, female patients must also undergo a radical mastectomy and as a result require a comination breast-shoulder prosthesis. The occupational therapy staff at M.D. Anderson Hospital and Tumor Institute devised a procedure for the construction of shoulder and/or breast prostheses. Methods of fabrication and problems encountered are discussed. As medical treatments improve and survival times are lengthened, more cancer patients will require rehabilitation services. This article may provide assistance for therapists who are faced with similar problems in the rehabilitative process.


The effectiveness of master's degree programs for occupational therapists. Are graduates of master's degree programs in occupational therapy satisfied with the content of their programs and the results of their studies? Are these programs commensurate with the needs of the occupational therapy profession in the development of skilled practitioners, educators, administrators, and researchers. These two questions provided the framework for an investigation to determine the needs, trends, strengths, and weaknesses of graduate study in occupational therapy in the United States today. The responses of 100 occupational therapists from 12 universities, 61.4 per cent of those who received questionnaires, were tabulated and analyzed. The results presented a composite picture of master's degree programs in occupational therapy and other graduate programs such as education, vocational rehabilitation, and special education. The conclusions suggest that requirements of the master's programs encourage independent inquiry, provide for the individual's academic needs, and prepare researchers. However, the programs are only partially fulfilling the requirements of the profession for skilled practitioners and educators.


Peer review & record review systems.

Peer review & record review systems. This paper describes the implementation of both peer review and record review systems as initiated at the University Hospitals of Cleveland occupational therapy department. Peer review evaluations can be used to ascertain a therapist's need for continuing education in a specific area, to evaluate and improve standards of practice, to gather statistics on professional objectives, and to develop Professional Standards Review Organization criteria. The system of peer review stimulated an improvement in documentation of services provided by occupational therapists, as well as in critical self-awareness of individual strengths and weaknesses. A separate method of record review was instituted to provide a basis for evaluating individual performance for either recognition or disciplinary purposes. Unlike peer review, record review results become incorporated into the therapist's personnel record.


AOTA Human Resources Project. The education study. This article is the second in a series describing the American Occupational Therapy Association's Human Resources Project. The project, comprised of several interrelated studies, is aimed at identifying the supply of occupational therapists and assistants in the United States as of December 1973, and at describing the projected requirements for their services. The present report describes the initial phase of the Education Study, the objective of which is to define the total supply of occupational therapy manpower, regardless of membership status in the AOTA.


Some considerations of ocular rotations. Our eyes and their extraocular motility muscles are a marvelously engineered system for external data gathering. On teleological grounds alone, it would appear that ocular versions and rotations take place, in many cases, along geodesics of least energy and that paths of higher energy are only taken for reasons of binocular near vision. This paper examines ocular versions and rotations from this viewpoint and "explains" Listings' and Donders' laws and also uses a model eye to demonstrate some resulting consequences. Finally, a common misconception about eye movements is laid to rest, and a suggestion made for further laboratory corroboration.


A supplementary technique for balancing refraction. The customary technique for balancing the refractive (subjective) correction lenses requires the subject to compare the clarity of two images. If there is an inequality in the best acuity attainable for each eye, this technique does not give valid results. An alternate technique is described that does not depend upon maximal acuity for each eye.


Comparison of soflens contact lenses (polymacon) with hard contact lenses and spectacles. A study, comparing Soflens TM contact lenses (polymacon) with hard contact lenses and spectacles, and using 150 male and female patients, has been done. Volunteers qualified for the study if they had healthy eyes and had worn one type of corrective lenses for six months before they were interviewed and examined. During each patient's examination, his type of correction was not known. Such matters as visual acuity, corneal measurements and average wearing time were considered. (Soflens contact lenses were felt to be safer than hard contact lenses.)


On the nature of accommodative micropsia. Both an increase in convergence and an increase in accommodation result in a decrease in the apparent size of objects of a fixed retinal image size (micropsia). The present study demonstrates that the accommodative micropsia produced by a minus sphere lens is due to the retinal image minification introduced by the lens and to the change in convergence accompanying accommodation. The accommodative act itself apparently does not result directly in micropsia.


Peripheral visual response time and retinal luminance-area relations. Button pressing response time was measured in five trained subjects to the onset of small visual stimuli imaged across the horizontal retinal meridian at 10 degrees arc intervals from 90 degrees arc right to 90 degrees arc left of the line of sight. Four stimulus luminance conditions were presented at each peripheral retinal location, a low luminance condition (approx. 2.6 ft-L),  a high luminance condition (arox. 22.2 ft-L), and two conditions in which luminance was varied systematically from low to moderately intense levels from one side of the visual field to the other. The  two variable luminance conditions were included to see if it is possible to compensate for the progressive decrease in retinal stimulus image area caused by the apparent pupil. The results indicated that response time to stimuli imaged within approximately 70 degrees arc from the fovea does not differ significantly when all possess about the same luminance. Mean response time is significantly faster to stimuli imaged beyond about 70 degrees arc from the fovea when their luminance is increased by an amount equal to the foveal stimulus luminance multiplied by the cosine of the angle between the peripheral stimuli and the line of sight. These data are discussed in relation to previous psychophysical data and to possible response mechanisms.


Predicting aniseikonia in anisometropia. In estimating the amount of aniseikonia that may be present in any given case of anisometropia, it is usual to apply the "rule of thumb" approach. The "rule" states that for each diopter of anisometropia, the amount of aniseikonia to be expected is 1 1/2 to 2 percent. The rule is based upon an average value computed for theoretical amounts of aniseikonia in many possible situations that can occur, some of which have little likelihood of being found in everyday clinical practice. Applied to many cases of anisometropia that are common, the rule leads to extreme overstimates and is grossly misleading, often resulting in the mishandling of patients. In this paper, a number of typical cases are dealt with in the refutation of the use of "the rule."


Corneal edema and vertical striae accompanying the wearing of hydrogel lenses. Changes in corneal thickness and the ocurrence of vertical striae were monitored on 27 patients who wore both the "F" and "N" series Bausch and Lomb Soflens-TM (polymacon) contact lenses. Changes in corneal thickness were observed with both lenses; however, the "N" series lens caused slightly more corneal swelling. Vertical striae occurred in about 50% of the patients and was correlated with the development of corneal edema. In most cases where significant corneal edema was measured, it was possible to observe the edema using the biomicroscope.


Effects of hyperbaric air pressure on keratometry. Following reports of vision blur by scuba divers at depth below 100 feet, keratometric readings were taken on volunteers inside a hyperbaric chamber at the USAF School of Aerospace Medicine. It was found that as the pressure within the chamber increased, the corneal reading showed an increased dioptric value. This change in refractive condition also occurred in measurement on test steel balls. Whether this dynamic response was due to increased atmospheric index, or displacement of instrument optics, was explored.


Driving with a bioptic telescope: an interdisciplinary approach. Six low vision patients were fitted with bioptic telescopes in order to obtain driver's licenses. They were given intensive coordinated training to prepare them for the complexities of driving a motor vehicle.


A clinical and epidemiological evaluation of tonometry as a screening test. Because of their differences in emphasis, clinical practitioners and clinical epidemiologists often employ different terms and concepts in comparing and rating health screening tests. The apparent inconsistency of a high error rate (96 to 99% over-referrals) yet good test sensitivity and specificity (40% and 95% respectively) for tonometry can be explained by a complete analysis of tonometric screening, encompassing both the clinical and epidemiological view-points. This paper reviews basic terminology, explains the clinical and epidemiological approaches, and demonstrates both of these methods of analysis in a comprehensive evaluation of tonometry using real data from recent clinical investigations.


Racial differences in color vision: do they exist? The present experiment investigated the possibility that variation in fundus pigmentation among individuals may be related to differential color sensitivity. Fifty black and white observers representing a wide range of skin (and fundus) pigmentation made direct heterochromatic brightness matches for a white standard field against each of five chromatic comparison fields. Results indicated that pigment (i.e., racial) differences in color vision do not exist, as measured by the two psychophysical methods used. The data showed that the heterochromatic matches were less reliable for the more saturated colors, violet and red, and also that the psychophysical methods used to obtain the matching data differentially influenced the results for the more saturated colors.


Juvenile glaucoma - a case report.

Juvenile glaucoma - a case report. A case report of incipient juvenile glaucoma is presented. Clinical data obtained during the optometric examination indicating possible glaucoma were confirmed by an ophthalmological evaluation. Early detection of glaucoma in the young adult may help prevent significant visual impairment and disability in his later years. Screening patients of all ages for glaucoma is recommended.


A nomogram for computing BP/IOP ratios.

A nomogram for computing BP/IOP ratios. Clinical estimates of ocular blood flow, based on a comparison of systemic blood pressure and intraocular pressure, appear to be better predictors of glaucomatous visual field loss than are tonometric estimates alone. One index of ocular hemodynamic status is the blood pressure/intraocular pressure ratio (BP/IOP). A nomogram is presented to aid in calculating this index.


The accommodative response in amblyopia. The accommodative response of normal and amblyopic subjects was measured over a range of stimulus values from two to seven D with a laser optometer incorporating the Badal system. The stimulus and response were found to be linearly related for both normal and amblyopic eyes, but the response of the amblyopic eye to the higher values of stimulus was reduced.


Pattern and depth discrimination from random dot stereograms. The discrimination of depth and pattern was investigated using random dot stereograms. For all four subjects, the psychometric function for depth judgments (probability of correct response) was clearly superior to pattern judgments over a range of ten crossed or uncrossed binocular disparity values. Degrading the visual images, either monocularly or binocularly, with various convex lens power (fogging lenses) reduced both depth and pattern discrimination across all disparity values, rather than simply increasing the thresholds. The results are discussed with reference to current theories of stereopsis, and the question of the hierarchial processing of depth and pattern information is considered.


Ray tracing through a toric refracting surface. A procedure has been developed for tracing a ray through a toric refracting surface. The surface is defined in terms of a rectangular coordinate system. The ray is specified by the rectangular coordinates of a point through which it passes and its direction-cosines.


The effect of stimulus duration and monocular viewing on the "oblique effect" in peripheral vision. Luminance thresholds were obtained for narrow bars of light in vertical, horizontal and oblique orientations. From 5 degrees to 60 degrees into the periphery, a small but significant elevation in threshold was found for stimuli in oblique orientations. The monocularly obtained data replicate an earlier report using binocular presentations and a stimulus duration of 100 msec. When exposure time was 10 msec or 500 msec, this effect of orientation broke down. Theoretical implications are discussed.


Hysterical amblyopia: electrodiagnostic and clinical evaluation. Six hysterical amblyopes and six controls, matched for age and sex, were evaluated as to acuity, color vision, visual fields, dark adaptometry and visual evoked responses (VER). Although the hysterical amblyopes all showed reduced acuity and constricted visual fields, no statistically significant differences were found for the dark adaptation final thresholds when compared to the control group. VERs to stimuli which were varied with respect to brightness, color, frequency and pattern, did not statistically differentiate hysterical amblyopes from the control group. The results appear to indicate the intactness of the visual pathways up to and including cortical area 17 in hysterical amblyopia.


Adverse effects of commonly used systemic drugs on the human eye. Part III. Four tables are presented listing the adverse effects of commonly used drugs on the human eye. Both brand names and generic names of drugs are used. The optometrist using the tables can look up either the drug (to find the adverse effects) or the symptom (to find the drugs that might cause it).


National health and optometry--a survey of public attitudes. A stratified probability sample of the Houston, Texas population was interviewed to assess public opinion of national health care and public awareness of vision care and its role in a national health care system. Over 80% of the population surveyed are in favor of a national health care bill, with a large percentage of the population favoring inclusion of vision care. Demographic trends are reported as they relate to various questions in the survey, and comparisons are made to a similar questionnaire one year earlier.


Analysis of photometric data.

Analysis of photometric data. This paper describes how information about the configuration of the cornea can be derived from the raw data obtained with telecentric photokeratometers, and how such data can be expressed and used. It also deals with the interrelations of the different ways of expressing the data.


Corneal curvature and refractive error changes associated with wearing hydrogel contact lenses. To determine if there are corneal curvature and refractive error changes associated with hydrogel lens wear, 27 patients wearing F series Bausch & Lomb SOFLENS-TM contact lenses were examined regularly for nine months. During the first month of lens wear, a mean corneal steepening of 0.23 DK plus or minus 0.18 and an increase in with-the-rule toricity were found, which persisted during the following eight months of wear. A mean increase in myopia of 0.35 DS plus or minus .211 DS was found after nine months of lens wear for five randomly selected patients. This amount of change was statistically significant and was highly correlated with the observed corneal steepening. Their lenses were removed after nine months of lens wear. Both corneal changes and the increase in myopia persisted during the 14 days after lens removal. If long term studies with larger samples show similar results, the effect of hydrogel lenses on corneal curvature and refractive error will have to be considered in the decision to fit this type of lens.


The birefringence fallacy.

The birefringence fallacy. In recent years it has become common for the birefringence pattern of a thermally toughened glass lens to be examined, and for a judgmental opinion of the impact resistance of that lens to be based on the regularity of the observed pattern. Laboratory experiments were carried out to determine the validity of this practice. Commercially available and specially-generated lenses were subjected to modified heat treatments in the laboratory. The birefringence patterns were then examined and the impact resistances determined: these were then compared with those of control groups, tested simultaneously. In these experiments there was no correlation between impact resistance and regularity of birefringence pattern. Reliance on such a correlation for assessing strength is therefore thought to be unjustified and, in some cases, even dangerous. Replication of this work by others is suggested.


Validity of the laser refraction technique for determining cylindrical error. Employing a laser refraction technique, spherical error was determined for each of three meridans in 50 eyes. The measurements were used to calculate spherical error and cylindrical axis and power, and the findings were compared with standard methods of measurement. Correlations between the laser and non-laser methods indicated that the laser technique is a valid method for determining spherical error. Correlations between the findings for laser and non-laser cylindrical measurements were not high enough to warrant use of this laser technique in clinical practice. Differential laser validity findings for against-the-rule astigmatism are also discussed.


Training a patient to drive with telescopic lenses. An interdisciplinary approach to licensing partially-sighted individuals to drive is presented. The model includes the participation of optometry, special education, and the department of motor vehicles.


The Myopter viewer: an instrument for treating and preventing myopia. A new instrument has been developed for utilization in attempts at myopia therapy and control. The inventor discusses instrument design and treatment procedures, and suggests an explanation for the movement of juvenile eyes from hypermetropia into myopia.


A protocol for hypertension screening and referral. The current nationwide attack on hypertension, with its emphasis on early detection and prevention, has served to reinforce optometry's commitment to vision-related health screening and referral. The current status of this multidisciplinary program is reviewed, and the major risk factors are presented, in a hypertension screening/referral form designed to improve the screening/referral process.


Development of the triadic junction in skeletal muscle fibers of fetal and postnatal rats. Electron microscope examinations of the developing triadic junction in fibers from leg muscles of fetal and postnatal rats reveal a range of complexity from no structural connections across the space between apposed membranes of T and SR to all of the junctional structures visible in adult rat muscle fibers. In triads showing no connections, faintly stained projections from the apposed membranes of T and SR are seen. The simplest form of junctional structure is a series of faintly stained strands that make connections across the space between apposing membranes. Junctional structures stained more intensely show periodic bridges traversing the space plus an intermediate dense line (intermediate density) running parallel to the apposed membranes of T and SR and bisecting the space between apposed membranes. The intermediate density is continuous across the periodic bridges and interbridge spaces and it appears to be connected to the apposed membranes of T and SR. It is suggested that projections from T and SR are precursors of the connections and that the projections interact to form the intermediate density. It is also suggested that bridge and interbridge junctional structures might form compartments isolated from the sarcoplasm and thus enhance the flow of electrical current from T to apposed SR by reducing low-resistance shunting of current flow into the sarcoplasm,


Electrical activity in muscle pain.

Electrical activity in muscle pain. The concept of muscle pain-spasm-pain vicious cycle has been challenged on the basis of inability to find electrical activity in the presence of palpable changes in fibrositic muscle. We produced muscle pain in the wrist extensor and paravertebral muscle groups of seven healthy subjects by injection of hypertonic saline (0.3 ml of 6% NaCl solution). The time course of the integrated muscle action potentials, roughly paralleled the time course of the developed pain in all but one subject for each muscle group. EMG recordings were made on one subject using both surface electrodes with amplifier sensitivity of 10 muV/cm and needle electrodes with an amplifier sensitivity of 100 muV/cm. Sequential recording showed clear evidence of electrical activity from the surface electrode and high sensitivity whereas the combination of the needle electrode with lower sensitivity showed no electrical activity whatever. We conclude that even mild muscle spasm is accompanied by muscular hyperactivity which can be evaluated by appropriate EMG techniques. There appears to be no reason to challenge the widely accepted concept of pain-spasm-pain as stated by Travell, Rinzler and Herman.


Excretion of Na and H2 O and hypertension after adrenal enucleation or compression. An attempt was made to analyze the participation of the several independent variables that must contribute to the reproted inability of large male adrenal-enucleate rats withintact kidneys to normally excrete sodium following a light oral sodium load. This was prompted by a desire to understand whether the phenomenon was improtant to development of adrenal-regeneration hypertension (ARH). The results indicated that sdoium retention required the presence of both  kidneys as it was not evident in unilaterally nephrectomized rats. The failure of ARH to develop in rats having both kidneys argues against a cause-and-effect relationship between the two phenomena. Sex does not appear to be important to sodium retention. Various fasting periods were employed, but  with none of them did rats with a single kidney exhibit sodium retention. Since the conditions necessary to elicit imparied sodium  excretion are incompatible with the induction of ARH and those essential to development of ARH prevent significant sodium retention, the two must be considered as independent manifestations of distrubed glandular function.


Absorption of trace metals in the zinc-deficient rat. The effects of zinc deficiency on the whole-body absorption and intestinal content of Zn, Cd, Cu, Co, Fe, Mn, and Cr were determined in the rat 1 h after oral administration of the isotopes. Both the absorption and intestinal content of Zn and Cr were increased in zinc-deficient rats, and the intestinal content of Feand Co was also increased in the zinc-deficient animals. Zinc administered orally with Cr decreased both absorption and intestinal content of the isotope in zinc-deficient rats. Chromium administered orally with Zn decreased intestinal content and absorption of Zn in zinc-deficient rats. Fractionation of mucosal supernatants by gel filtration showed that both zinc and chromium eluted in the same low molecular weight fraction. The elution patterns of zinc and cadmium from that of zinc-supplemented animals. These experiments provide some insight into the specificity of the zinc absorption pathway and present some explanations for the interaction or lack of interaction among trace elements.


Temperature responses of lambs after centrally injected prostaglandins and pyrogens. It has been proposed that pyrogens may produce their febrile response by the release of prostaglandins in the hypothalamus. To test this theory, prostaglandin E1 (PGE1) was injected into a lateral ventricle in dosages of 2-200 ug into conscious newborn lambs, ages 4-168 h. Fiifteen of 40 injections were followed by rises in rectal temperature but the remainder were followed either by no change or by falls. Temperature responses did not appear to be related to age and a variation in responses to the same dosage of PGE was  often observed. Some lambs were able to develop fevers in response to intravenous bacterial pyrogen yet did not develop fever after intraventricular PGE 1. Intraventricular bacterial pyrogen (3 ng) produced no change in body temperature, whereas three of four injections of 300 ng pyrogen caused fever. The results suggest that the newborn lamb may be able to develop a fever independently of the central involvement of PGE1. Alternatively, the intraventricular approach may not be useful  for the study of the central control of body temperature in the newborn lamb.


Carbohydrate metabolism and its response to catecholamines as modified in alkalotic rat. Metabolic activities and their responses to catecholamines were studied in fasted rats exposed to simulated altitudes. Analysis of hepatic levels of gluconeogenic intermediates revealed the inhibition of gluconeogenesis between glyceric acid 3-P and fructose 6-P associated with a rise of the ratios of redox pairs such as lactate to pyruvate in livers of alkalotic rats. Inhibition of gluconeogenesis was indicated also by the suppressed incorporation of glutamate 14C into blood glucose. Since no activation was detected on glycolytic pathway of skeletal muscles, marked hyperlactacidemia during alkalosis appeared to result from the suppression of hepatic gluconeogenesis. Most of metabolic actions of epinephrine and isoproterenal known to be mediated via the beta receptor were significantly reduced but not completely abolished during alkalosis. Exceptionally, hyperinsulinemia induced by isoproterenol was completely  reversed and replaced by hypoinsulinemia during alkalosis. Despite hypoinsulinemia, hyperglycemia induced by glucose load decreased more rapidly in alkalotic than in normal rats. In view of the fact that the adrenergic alpha receptor is involved in theinhibition of insulin secretion, the observed irregular modifications of catecholamine actions could be explained on the basis of a postulate that the adrenergic alpha-receptor functions are potentiated in alkalosis.


Local specialization at ileocecal junction of the cat and opossum. In 10 cats and 10 opossums, serial transverse strips of muscularis propria 2 mm wide, from about 1.5 cm above to about 1.5 cm below the ileocecal mucosal junction, were separately stretched to discover the relationship between length and tension and were separately subjected to electrical field stimulation. In both species, ileal strips showed stimulus relaxations, sometimes accompanied by contractions after the stimulus trains (off responses), whereas colonic strips generally did not. These responses were abolished by tetrodotoxin, 3 times 10-7 M in the opossum, 3 times 10-6 M in the cat. Length-tension slopes were greatest just above the ileocecal junction where stimulus relaxation occurred. Tetrodotoxin at 3 times 10-7 M raised basal tension in ileal strips in both species and in colonic strips only in the cat. Muscle of the ileocecal junction resembles that of the esophagogastric and gastroduodenal junctions in showing a relatively high degree of resistance to stretch and prominent neurogenic stimulus relaxation. However, the ileocecal junction, in contrast, also possesses a tonic inhibitory innervation.


Changes in vascular ionic content and distribution across aortic coarctation in the dog. Eight dogs were subjected to 80-90 percent coarctation of thoracic aorta, which produced a mean blood pressure gradient of 40 mmHg; six normal dogs were used as controls. Proximal aorta was compared with distal aorta, and carotid and femoral arteries removed after coarctation were compared against the contralateral vessels removed before coarctation. After 4 wk of coarctation, proximal aorta contained more total and intracellular Na (derived from 24Na fluxes and space measurements), more Mg, Cl, hydrolyzable SO4 equals to, and H2O than distal aorta. Hydrolyzable SO4 equals to was also higher in proximal than in distal noncoarcted aorta. Carotid arteries removed after coarctation had higher total and "noninulin" Na, higher Ca, and similar hydrolyzable SO4equals to and total hexosamine than the contralateral normal vessels. Aortic coarctation had no effect on ionic composition of femoral arteries. The data suggest that an increase in intravascular pressure has direct effects on vascular ionic composition. Although ionic changes may vary in different vessels, increased intracellular Na seems to be the most consistent finding.


Respiratory fluctuations in pupil size.

Respiratory fluctuations in pupil size. Regular fluctuations in pupil size of the cat were measured and the properties, nervous pathways, and origin of these oscillations were investigated. The rhythm of pupil movements under control conditions appeared to be either locked to the central respiratory cycle or to the artificial ventilatory cycle. These movements were only seen in lightly anesthetized or tranquilized cats, but not in alert or deeply anesthetized cats (ether, halothane or pentobarbital). The fluctuations proved to be independent of sympathetic innervation but related to variations in parasympathetic outflow. At least two sources for pupil oscillations appeared to be involved: central respiratory activity and respiratory blood pressure fluctuations that modulated pupil width via sinoaortic baroreceptors. Lung movements per se, as a third possible factor, did not modulate pupil width, whereas electrical stimulation of the afferent lung vagi did; therefore the role of this mechanical factor is not clear. A review of the pertinent literature shows that in the organism there are many phenomena exhibiting respiratory oscillations. It seems likely that these oscillations have the same origin as the respiratory pupil fluctuations.


Passage of glucose through the cell membrane of capillary endothelium. The mechanisms of glucose passage through the cell membrane of vascular endothelium were studied in vitro with a preparation of pure blood capillaries isolated from the rete mirabile of the eel swimbladder. In countertransport experiments, no competition for a common carrier could be detected between D-glucose and 3-O-methylglucose or between D-glucose and L-glucose. In the endothelial cells, inward and outward fluxes of labeled sugars were not changed when studied against concentration gradients of corresponding unlabeled sugars. The distribution of 3-O-methylglucose-14C and L-glucose-14C at equilibrium between intracellular and extracellular water was not modified by reducing their specific activity in the medium over a wide range. The addition to the medium of phlorizin 10-5 or 10-7 M, 3-O-methylglucose 60 mM, or L-glucose 60 mM did not reduce the rate of glucose utilization by the capillary tissue. The temperature coefficient for glucose uptake between 27 and 37 degrees C averaged 1.4. Insulin had no effect on the initial rate of 3-O-methylglucose-14C entry into cellular water. It is concluded that in the eel capillaries the mechanism of glucose passage into the vascular endothelial cell is compatible with the kinetics of free diffusion.


Kaluresis and diuresis after administration of antidiuretic hormone to hyperkalemic dogs. Dogs infused with 2 meq KCl/kg per h exhibit electrocardiographic evidence of prelethal cardiotoxicity in about 3 h when serum potassium reaches a level between 10.2-10.5 meq/liter. During this time, their urine output of 30 ml/h is equal to the volume of KCl infused. Studies of the potassium distribution in these animals indicate that 20 percent of the infused ion is added to the extracellular fluid and red blood cell mass, 20 percent is excreted in the urine, while the remaining 60 percent is unaccounted for and presumably transferred to intracellular fluid. Dogs treated with moderately large doses of antidiuretic hormone intramuscularly before and during KCl infusion delay development of prelethal cardiotoxicity for about 5 h, with serum potassium levels comparable to those of untreated dogs. In addition, treated animals display a considerable diuresis and kaluresis with urine volumes nearly 4 times that of the volume infused. The potassium ion distribution in animals given antidiuretic hormone is much different from that of untreated dogs, with 55 percent of the infused ion found in the urine, about 15 percent in extracellular fluid and red blood cell mass, and only 30 percent presumably transferred to intracellular fluid. Transfer of potassium to intracellular fluid was calculated to be 3.1 plus or minus 0.7 meq/kg in antidiuretic-hormone-treated animals and 3.8 plus or minus 0.7 meq/kg in untreated (control) animals. Since these values are, within experimental error, quite comparable, it is possible that antidiuretic-hormone-induced kaluresis and diuresis are involved in protecting some animals from the effects of hyperkalemia by delaying the attainment of cardiotoxic blood levels.


Valinomycin shortening of action potential of embryonic chick hearts. The effects of valinomycin, an agent known to increase the K+ conductance (gK) of lipid bilayer membranes and to be an uncoupler of oxidative phosphorylation, were examined on young (3 days old) and old (15-19 days old) embryonic chick hearts. In the old hearts, valinomycin produced pronounced shortening of the action potential plateau, and often only the spike component remained. The rate of rise of the action potential was usually not affected (slightly diminished sometimes). Addition of dimethylsulfoxide (2 percent), the vehicle for the valinomycin, did not cause shortening of the plateau. The diminution of the plateau by valinomycin at 1 mug/ml was usually obtained after incubation for 1 h; larger doses produced prominent effects within 15 min. The threshold concentration was about 0.1 mug/ml. Cooling, isoproterenol, Ba++, Sr++, and tetraethylammonium partially relengthened the plateau shortened by valinomycin. Lowering of external K+ also lengthened the plateau slightly in the presence of valinomycin. Young embryonic hearts were more resistant to valinomycin, and it was necessary to incubate with 20-40 mug/ml for 1-2 h to produce a significant diminution in plateau. In both young and old hearts, the resting potential was not increased by valinomycin, even though young hearts have a low resting potential (similar to minus 40 mV) mainly because of a low gK. These results suggest that the kinetics of the changes in gK during the action potential plateau may be more greatly affected by valinomycin than the steady-state gK of the resting membrane. In addition to such a direct effect on the sarcolemma, valinomycin could also exert an indirect effect by blocking the slow inward current through ATP depletion.


Phosphorylated beta-guanidinopropionate as a substitute for phosphocreatine in rat muscle. To evaluate phosphorylated beta-guanidinopropionate (beta-GPAP) as a substitute for phosphocreatine (PC), hypoxic tibialis anterior muscles were stimulated to contract isometrically in situ until twitch tension fell to 25 percent of the peak value. Muscles from rats fed beta-guanidinopropionic acid (beta-GPA) failed to exhibit the staircase phenomenon, and they developed 28 percent less tension than control muscles. In control muscles lactate increased from 0.75 to 20.99, ADP increased from 0.89 to 1.20, ATP decreased from 5.09 to 2.73, and PC decreased from 15.78 to 1.52 mumol/g. In muscles from rats fed beta-GPA, lactate increased from 0.85 to 14.31, ADP increased from 0.86 to 1.05, ATP decreased from 2.69 to 1.71, PC decreased from 0.73 to 0.30, and beta-GPAP decreased from 30.34 to 19.45 mumol/g. From these measurements, the use of high-energy phosphate was calculated to be reduced 32 percent in muscles from rats fed beta-GPA. The relationships between the use of high-energy phosphate was calculated to be reduced 32 percent in muscles from rats fed beta-GPA. The relationships between the use of high-energy phosphate and tension development confirm experimentally the ability of beta-GPAP to substitute for PC as a source of energy to sustain muscle contraction.


Inhibition of renal vasoconstriction by elevated ureteral pressure. These experiments were prompted by the observation that elevated ureteral pressure inhibited renal vasoconstrictions elicited by electrical stimulation of "defense regions" of the central nervous system (DNS) in cats. Experiments were designed to detect the relative contributions to this inhibition of CNS reflexes and interactions between autoregulatory and neural controls of the renal circulation. Cats were anesthetized with either chloralose or pentobarbital. Renal blood flow was measured electromagnetically. Elevated ureteral pressure lowered prestimulus renal vascular resistance. Renal vasoconstrictions elicited by electrical stimulation of the CNS or the peripheral renal nerves and by infusion of catecholamines into the renal artery were equally inhibited by elevated ureteral pressure. Equal inhibition of CNS and renal nerve-evoked vasoconstrictions suggested that a reflex was not involved. Equal inhibition of vasoconstrictions elicited by renal nerve stimulation and by catecholamine infusions suggested that elevated ureteral pressure acted primarily at a postsynaptic site. Inhibition of prostaglandin synthesis by indomethacin diminished, but did not abolish, the ureteral pressure-induced inhibition of neurogenic vasoconstrictions.


Distribution of H+ and HCO3 minus between CSF and blood during metabolic alkalosis in dogs. In anesthetized, paralyzed dogs ventilated to maintain a normal PaCO2, metabolic alkalosis was induced and held constant over 6 h by infusion of sodium bicarbonate. Determination of pH, PCO2, (HCO3 minus), and (lactate) in cisternal and lumbar cerebrospinal fluid (CSF) and in arterial plasma together with measurement of the CSF/plasma DC potential differences permitted calculation of the electrochemical potential difference (mu) for H+ and HCO3 minus; measurements were made prior to induction of metabolic alkalosis at pHa equal to 7.40, as soon after induction as stable arterial values were achieved and 3, 4.5, and 6 h thereafter. A steady state for ion distribution was reached by 4.5 h. Values of mu for H+ and HCO3 minus returned to +0.1 and +0.9 mV of control at 6 h for cisternal CSF and +0.6 and minus 0.4 mV for lumbar CSF. This return of muH+ and muHCO3 minus close to control in the steady state is compatible with passive distribution of these ions between brain extracellular fluid and blood.


Liver uptake of amino acids and carbohydrates during a single circulatory passage. The uptake of 14C-labeled amino acids and carbohydrates by liver following rapid injection into the portal vein was measured relative to a simultaneously injected highly diffusible reference, tritium-labeled water, (3HOH). A 0.25-ml bolus of buffered Ringer solution containing 1-2 muCi of the 14C-labeled test substance and 3-6 muCi of 3HOH was administered by rabid portal injection in anesthetized rats. Circulation was terminated after a single passage of the bolus through the hepatic microvasculature and the tissue was immediately macerated, solubilized, and subjected to liquid scintillation counting. Liver uptake indices (LUI) were calculated from the ratio of 14C to 3H in liver tissue relative to the same ratio in the injection mixture. LUI's of five carbohydrates were measured: sucrose (24.3 percent), inulin (27.7 percent), D-mannitol (80.2 percent), D-glucose (96.8 percent) and L-glucose (26.7 percent). The LUI for cholic acid was 127.1 percent. Among 18 amino acids tested, the LUI's were the highest for the acidic ones (L-aspartic acid, 100.0 percent and L-glutamic acid, 86.4 percent) and lowest for the basic ones (L-arginine, 37.4 percent and L-lysine, 31.4 percent). Stereospecificity for glucose and alanine uptake, saturation kinetics for glutamic acid (Km equal to 4.8 mM) and aspartic acid (Km equal to 2.7 mM), and cross-inhibition among uptake of the acidic amino acids were observed. These findings confirmed the applicability of a technique which was originally developed for studies of amino acid uptake in brain to characterization of transport systems in liver.


Effect of extragastric and truncal vagotomy on pancreatic secretion in the dog. In four dogs with chronic pancreatic and gastric fistulas, dose-response studies of pancreatic bicarbonate and protein secretion were done with intravenous infusions of secretin, octapeptide of cholecystokinin (OP-CCK), and 2-deoxyglucose (2-DG). The pancreatic response to a meal and to duodenal perfusion of graded concentrations of HCl, sodium oleate, and tryptophan were also studied. These observations were repeated after division of both the hepatic and celiac vagal branches to produce extragastric vagotomy, and subsequently after transthoracic truncal vagotomy. The responses to secretin, OP-CCK, and to duodenal perfusion of HCl were either unaltered or only slightly decreased by either extragastric or truncal vagotomy. Basal pancreatic secretion and the responses to duodenal perfusion of oleate and tryptophan were markedly depressed by extragastric vagotomy. These findings indicate that tonic vagal activity contributes to basal pancreatic secretion but has little effect on the response of the pancreas to secretin or CCK or on the release of secretin from the intestine. The decreased pancreatic response to intestinally perfused oleate and tryptophan seen after extragastric vagotomy could be caused either by interruption of reflex paths between gut and pancreas or by interference with CCK release. Extragastric vagotomy reduced pancreatic responses to a meal and to 2-DG and subsequent truncal vagotomy caused still further reduction, possibly, at least in part, by depressing release of antral gastrin.


Alterations in hepatic chromatin template availability during infection. Hepatic chromatin was isolated from rats at various times after inoculation with either live or heat-killed bacteria. The chromatin was assayed under conditions that allow determination of the DNA template available to support in vitro transcription. Both a fulminant Diplococcus pneumoniae and a milder Salmonella typhimurium infection produced time-related increases in hepatic chromatin template availability when compared to chromatin isolated from rats inoculated with heat-killed bacteria. Both timing and magnitude of increased template availability correlated with the severity of the infection. The earliest change observed was a 50 percent rise in availability noted 4 h after inoculation with D. pneumoniae. This preceded the onset of fever, as well as other known heaptic consequences of systemic infection. After 24 h of infection the maximum rise of 90 percent occurred. Similar changes developed during S. typhimurium infection, but were slower in onset and smaller in magnitude. Adrenalectomy prior to infection enhanced the severity of the disease but markedly blunted the increase in template availability. The data are consistent with the hypothesis that systemic infection regulates the hepatic metabolic response to infection through transcriptional control and that a permissive or stimulatory action of glucocorticoids is involved in the increases in template availability effected.


Kinetics of Na+ uptake and transcellular transit by the pancreas. 22Na uptake into strips of rabbit pancreas was measured for up to 10 min. The uptake curve was characterized by the presence of two plateaus separated by an inflexion point; a first "plateau" or an approximation of steady-state uptake was observed between 1 and 3 min; betwen 3 and 4 min the slope of the uptake curve increased again, finally decreasing to a new and higher steady-state uptake between 4 and 6 min. The data suggest that the first part of the uptake curve (from 0 to 3 min) represents uptake into most if not all cells, and the second part (from 3 to 10 min) represents the sum of "quasi" steady-state cellular uptake and of the equilibration of the ductal compartment in series with the cells. In this model a substantial delay (2.5-3.25 min) elapses between the filling of cellular and ductal compartments which is apparently of intracellular origin, implying restricted Na+ diffusion within the cytoplasm and an intracellular Na+ gradient. If this model is correct, then the mean transit time for Na+ across the whole organ should be approximately 3-4 min and be primarily the result of transcellular transit. The mean transit time for Na+ across the whole organ in vitro was measured and found to be 3.5 min on the average. The step that accounts for most of this time appears to be the transepithelial transit of Na+.


Hypothalamic stimulation induces acid secretion, hypoglycemia, and hyperinsulinemia. Electrical stimulation of the posterior hypothalamus brought about an increase in plasma insulin accompanied by a fall in blood glucose. If glucose fell below 55 mg/100 ml, gastric secretion of HCl ensued. The same relationship between acid secretion and glucose was observed when hypoglycemia was induced by intravenous injection of insulin. Stimulation outside the posterior hypothalamus did not give either a fall in glucose or an increase in gastric acid secretion. It is concluded that posterior hypothalamic stimulation causes gastric acid secretion by inducing insulin release and a consequent hypoglycemia.


Cyclic changes in ionic composition of digesta in the equine intestinal tract. Effects of diet and time after feeding on osmolality and inorganic ion content of gastrointestinal digesta were studied in 24 ponies. Animals, fed either a conventional or a low-protein, high-cellulose diet, were sacrificed 2, 4, 8, or 12 h after a meal. Animals fed the conventional diet showed cyclic variations in the ionic composition and osmolality of digesta with time after feeding. The most marked variations were seen in the contents of the stomach and small colon. However, results also indicated a cyclic appearance and disappearance of Na in large intestinal contents that correlated with net appearance and disappearance of volatile fatty acid (VFA) and H2O. Since Na and VFA were the major solutes absorbed from the cecum and colon, the ionic composition and water content of large intestinal digesta appeared largely dependent on the rate of microbial digestion. Although the large intestine of animals fed the experimental diet contained approximately twice the quanity of Na, K, Cl, VFA, and H2O, COMPENSATORY ABSORPTION BY THE MOre distal segments of colon resulted in little additional loss of these in the feces.


Dynamic analysis of gravimetric response of isolated dog hindlimb. Previous gravimetric studies of transcapillary fluid movement have been based on capillary filtration coefficient (CFC) estimates. In these studies only a single CFC value is estimated for the entire isolated vascular bed. We have analyzed the dynamic gravimetric responses of isolated dog hindlimb to venous pressure steps and found it possible to estimate two different CFC values. Under control conditions, one CFC value averaged .0049 ml/mmHg min per 100g tissue wt, whichagrees with results of previous investigators. The other CFC value averaged 90304, which is very close to estimates we have previously made by an independent frequency-response methods. Changes in hindlimb properties to intra-arterial infusions of acetylcholine, papaverine, isoproterenol, and norepinephrine were also studied. Drug infusion results and the presence of similar dynamic components in experiments on gracilis muscle support the existence of inhomogeneous pathwaysin tissue, which lead to fluid-exchange nonuniformity.


Effects of flow rate and potassium intake on distal tubular potassium transfer. Potassium transport was studied across proximal and distal tubular epithelium in rats on a normal, low- and high-potassium intake during progressive loading with isotonic saline (150 mM) or a moderately hypersomotic urea (200 mM) sodium chloride (100 mM) solution. Free-flow micropuncture and recollection techniques were used during the development of diruesis and tubular fluid (TF) analyzed for inulin-14C, potassium (K) and sodium (Na). Tubular puncture sites were localized by neoprene filling and microdissection. During the large increase in tubular flow rates (10 times): 1) fractional potassium reabsorption fell along the proximal tubule, 2) TFk along the distal tubule remained constant and independent of flow rate in control and high-k rats; thus, net potassium secretion increased in proportion to and was limited by flow rate. 3) In low-K rats TF k fell; with increasing flow rates distal K secretion was not effectively stimulated. 4) Distal tubular sodium reabsorption increased in all animals with flow rate, but tubular Na-K exchange ratios varied greatly. It is suggested that whenever sodium delivery stimulates distal tubular potassium secretion it does so by 1) increasing volume  distal tubular potasssium secretion and by 2) augmenting the transepithelial electrical potential difference (lumen negative).


Effects of graded solute diuresis on renal tubular sodium transport in the rat. Sodium transport was studied across proximal and distal tubules of rats undergoing progressive intravenous loading with either isomotic saline or urea (200 mosmol)-saline (100 mosmol) solutions. Free-flow as well as recollection micropuncture techniques were used, and tubular fluid (TF) samples were analyzed for inulin-14C and sodium (Na). With administration of progressively larger intravenous saline loads, the delivery of fluid and sodium into the distal tubule rose. Concomitantly, the normally observed decline of tubular sodium concentrations along the distal tubule became attenuated until it was abolished at the highest infusion rates of saline solutions. Absolute reabsorption rates of Na across the distal tubule increased in proportion to tubular flow rate, and no tubular maximum (Tm) was observed. It is suggested that the delivery of increased amounts of sodium to the normally unsaturated later parts of the distal tubule and the elevated tubular sodium concentration after saline loading account for the observed stimulation of distal tubular net sodium transport. The extent of transport stimulation is also subject to control by the amount of urea accumulation along the distal tubule. As the latter declines, sodium reabsorption is proportionately enhanced.


Renal glutaminases: Diamox inhibition of glutamyltransferase. Ammonia (NH3) production by the rat kidney was studied after an acute administration of acetazolamide (Diamox). Diamox reduced renal ammonia release (renal vein NH3 + urine NH3 - arterial NH3) 60 PERCENT IN The intact functioning kidney. Ammonia production by whole-kidney homogenates was decreased by Diamox, confirming the drug's action as inhibiting glutaminase activity. Additional studies demonstrated the inhibited glutaminase was localized in the cytoplasm; the glutaminase activity of the mitochondrial fraction was unaffected by Diamox. Isolated perfused kidneys from Diamox-treated rats confirmed that the drug reduced ammonia production by inhibiting glutamyltransferase; in addition, inhibition was shown to be of a competitive nature. We therefore conclude that cytoplasmic glutamyltransferase is the major producer of ammonia in the nonacidotic rat kidney and that it is competitively inhibited by Diamox.


Hemodynimic effects of systemic and central administration of clonidine in the monkey. Systemic and regional hemodynamic changes were measured in restrained, conscious rhesus monkeys with indwelling arterial and venous catheters before and after clonidine (5 and 15 mug/kg) was slowly infused intravenously or smaller doses (2 mug/kg) were injected into a lateral cerebral ventricle. Dye-dilution cardiac outputs and the complete distribution of cardiac output were obtained intermittently with the use of the radioactive microsphere method. After the higher intravenous dose and the intraventricular injection, systemic arterial pressure was significantly lowered for 30-45 min. Both of these groups had similar changes in the redistribution of cardiac output and blood flow that outlasted the hypotensive period. Blood flow was maintained or increased in the hepatic and renal arteries at the expense of skin; flow to skeletal muscle and brain also decreased during the first hour. These data support previous studies that indicate that the primary action of clonidine is in the central nervous system and, in addition, add new information about the regional blood flow changes evoked by clonidine.


Defective gastrointestinal recovery after irradiation in W/Wv mice. W/Wv mice are white, sterile, and have macrocytic anemia, all due to defective function of pertinent stem cell compartments. Sterility and coat color reflect stem cell failure during embryogenesis, while anemia results from a defective hematopoietic stem cell system which is active throughout life. Studies of radiation damage and recovery were undertaken to determine if the stem cell compartment of the intestinal mucosa, also active throughout life, is likewise affected. W/Wv mice "cured" of their hematopoietic defect, and normal littermates were exposed to 1,250 rads of whole-body irradiation. Mean survival time of controls was 8.4 plus or minus 0.31 days compared to only 5.85 plus or minus 0.18 days (P = LESS THAN0.001) FOR W/Wv. Incorporation of 3HTdR into mucosal cells of controls was minimum 2 days after exposure and exceeded nonirradiated levels by day 3, W/Wv values were lower than controls on days 2-4 and never significantly exceeded nonirradiated values. Changes in gut weight followed the same pattern. These studies suggest that the W/Wv defect involves stem cells of the gut and that the defect is a failure to proliferate and/or differentiate.


Free-feeding patterns of rats: effects of pyrogen and dietary protein content. Infusion of bacterial pyrogen (Priomen) was accompanied by an increase in body temperature, an increase in heat production, and a decrease in the voluntary food intake ofrats fed high-as well as low-protein diets. The magnitude of this pyrogen-induced depression of food intake was comparable for both diets. However, in rats fed high-protein diets, this decrease was additive to that normally seen following administration of such diets. These data indicate that the control of food intake cannot be explained in terms of a behavioral the more regulatory response.


Kinetics of renin-antirenin reaction: micromethods for the assay of renin and antirenin. Indirect micromethods were designed for the assay of human renin (lower limit 0.25 times 10-4 U and of antirenin to human renin (lower limit 3 times 10-4 U), with the rat used for the bioassay of the angiotensin produced by the action of renin on renin substrate. This made possible the assay of unusually small amounts (0.01 mu1) of serum for antirenin. The Michaelis-Menten concept of a dissociating complex can be applied to the antireninrenin reaction: the rate constants for the formation and for the breakdown of the complex were k1 equal to 1.65 (ml/U antirenin per min) and k3 equal to 1.97 times 10-3 (U inactivated renin/U antirenin per min), respectively; the apparent Michaelis constant was 12 times 10-4 (U renin/ml). A second method of analysis was also applied by assuming the formation of a rather tight complex, with antirenin functioning as an irreversible inactivator of renin. Both methods of analysis yielded practically the same rate constant (k1 equal to 1.65 and k1 equal to 1.71), but the treatment according to the Michaelis-Menten equation affords a slightly better fit of the experimental data (accuracy equal to plus or minus 15.5 percent) than the second method of calculation (accuracy equal to plus or minus 21.6 percent).


Release of antirenin to human renin by anaphylactic shock or by antihypertensive agents. In dogs that have had repeated intravascular injections of small doses of human renin, even for long periods, the development of antirenin to human renin in the blood has not been previously noted, and their pressor response (30 mmHg) to 1 U of human renin has remained unchanged for years. In such dogs, however, a profound, abrupt fall of the systemic blood pressure, due to an anaphylactic reaction to human renin, or to the infusion of depressor agents, such as Arfonad, histamine, or diazoxide, resulted in the appearance in the blood of an inhibitor specific for human renin. This inhibitor was suddenly released into the blood-stream from the tissues in which it presumably had been stored, and it persisted, in a relatively high concentration, in some animals for months. It did not occur in dogs that had not previously received many injections of human renin. This study has shown that the inhibitor has all of the properties of antirenin to human renin. It abolished the pressor response to hog, dog, and rat renin or to angiotensin and norepinephrine. It inactivated human renin, but not dog renin, duringits incubation with renin substrate to form angiotensin.


Adrenergic mechanisms in cerebral circulation of the goat. The effects of electrical stimulation of the cervical sympathetic nerves and tyramine on cerebral blood flow (CBF) were investigated in 13 unanesthetized goats in which electromagnetic flow probes had been previously implanted on the internal maxillary artery. Nerve stimulation (1.5-12 cycles/s) produced frequency-dependent reductions in CBF, a decrease of 50 percent occurring with the highest frequency. Injections of tyramine (50-500 mug) into the internal maxillary artery produced dose-dependent reductions in CBF, a decrease of 36 percent occurring with the highest dose. Both reserpine and phentolamine diminished the vasoconstriction induced by nerve stimulation and tyramine. Cocaine partially abolished the effects of tyramine and did not alter those of nerve stimulation. In addition, phentolamine produced cerebral vasodilatation, which was greatly reduced by previous treatment with reserpine. These results show that sympathetic stimulation and tyramine produce cerebral vasoconstriction by the release of the transmitter from the perivascular nerve endings, and they suggest the presence of a tonic sympathetic activity in the cerebral vessels.


Polyuria and imparied ADH release following medial preoptic lesioning in the rat. Studies were carried out in the rat to detemine if hypothalamic lesions which caused polydipsia and polyuria had their effect mediated through an alteration of the ability of the neurohypophyseal system to release ADH. Rats with medial preoptic lesions hadincreased water intake while on ad libitum access to water and slightly impaired ability to conserve water following dehydration, but with no impairment of urine-concentrating ability. These were associated with an increase in plasma osmolality both during ad libitum fluid intake and after dehydration. Urinary ADH excretion was at leastas great as in shamoperated controls during ad libitum water intake, but failed to increase during dehydration in spite of a marked increase in plasma osmolality. Pituitary ADH content did not differ from control animals either during ad libitum water intake of after dehydration. Animals with lesions in the lateral preoptic and septal areas did not differ from control animals during ad libitum fluid intake and after dehydration even though lateral preoptic lesions produced polydipsia. In all animals, lesions were remote from the supraoptic nuclei, which showed no histological evidence of damage. It is concluded thatareas of the central nervous system away from the supraoptic nuclei are involved in the regulation of both water intake and ADH release.


Depression of pulmonary 5-hydroxytryptamine uptake by metabolic inhibitors. Energy requirements for uptake of 14-C labeled 5-hydroxytryptamine ([14-C]5-HT) were studied in isolated guinea pig lungs, ventilated with 95% O2-5% CO2 and perfused in a recirculating system with Krebs-Ringer-bicarbonate solution containing 4% bovine serum albumin and 5 mM glucose. After 14 min preincubation with various inhibitors, lungs were perfused for 30 min with 0.25 times 10- minus 6 M [14-C]5-HT. Aliquots of perfusate were analyzed for [14-C]5-HT and metabolic products. Control lungs had a fractional serotonin clearance of 0.57 plus or minus 0.04. The rate of removal of [14-C]5-HT was inhibited 96% by imipramine, 88% by chlorpromazine, and 65% by ouabain, but was unaffected by iproniazid. Anoxia and cyanide each inhibited uptake by 68%. Omitting glucose from the perfusate reduced uptake by 30%. 2-Deoxyglucose and iodoacetate decreased the rate of [14-C]5-HT removal by 44 and 70%, respectively. Uptake was not affected by lung weight gain nor by changes in lung mechanical properties produced by [14-C]5-HT. [14-C]5-HT uptake by guinea pig lung requires a metabolic source of energy providing additional evidence for transport by an active process.


Electrolyte excretion and free-water production during onset of acute diuresis. The concentration of major urinary solutes was studied in ureteral urine collected at 15- to 30-s intervals at the onset of acute diuresis induced in anesthetized dogs either by high-ceiling diuretics (mainly ethacrynic acid) or by osmotic diuretics. Phosphate/inulin clearance ratios remained unchanged; potassium/inulin clearance ratios rose rapidly. Principal attention is given to the mechanisms underlying a transient rise in urinary sodium and chloride concentrations during the onset of diuresis. When the data are corrected for washout artifacts from the pelvis and ureter, it can be shown that the initial collection periods are associated with a transient increase in free-water production and by the simultaneous secretion of urea from the interstitium into the tubular fluid. The former coincides in time with the rise in urinary chloride concentration and represents an augmentation of water reabsorbed in the collecting duct, which is relatively impermeable to chloride. Both responses are quantitatively consistent with the transition from a hyperosmotic to isosmotic medullary interstitium.


Development of glomerular perfusion rate and nephron filtration rate in rats 17-60 days old. The development of filtration rate and perfusion rate in superficial nephrons has been studied in 17- to 60-day-old rats with micropuncture and microsphere techniques. Recordings have also been made of total renal blood flow (RBF), cardiac output (CO), arterial blood pressure, and hematocrit. Sincle-nephron glomerular filtration rate (SNGFR) as well as glomerular perfusion rate (GPR) and RBF described a similar developmental pattern with a slower rise from 17 to 30 days of age and a faster rise thereafter. No plateau was observed. The quotient between SNGFR and GPR was constant from at least 22 days of age. Since the hematocrit was also constant after 22 days this implies a constant filtration fraction. On the basis of those findings it is suggested that GPR is the main determinator for the development of GFR. The fraction of cardiac output perfusing the kidneys increased continuously in 17- to 60-day-old rats, suggesting that the increase in RBF and GPR is due to intrarenal factors: renal vasodilatation and increase in renal vascular volume.


Micromanipulation of pressure in terminal lymphatics in the mesentery. The terminal lymphatics are a network of highly previous vessels that are distributed in a loose association with the blood capillary bed, in particular along with the collecting venules. The base-line pressure in these lymphatics is close to atmospheric, but after they converge to form valved collecting channels PL is increased with a pressure differential of 1-2 cmH20 built up across each valve. This increment in lymphatic pressure is clearly related to the presence of one-way valves, the contractile activity of the collecting channels, and the comparative impermeability of these channels. The pressure differential required to draw fluid from the interstitium into the lymphatics would appear to reside in the vasomotor activity of the collecting channels, although the data do not rule out changes in Pt coincident with net capillary filtration or absorption.


Concentration of urine by the hibernating marmot. Studies wer performed with marmots (Marmota flaviventris) of both sexes that had chronic arterial, venous, and bladder catheters. Urine collection was performed during hibernation and urine osmolalities (611.6 not equal to 166.1 SD) were found to be lower than those of aroused animals (1264 not equal to 472.9 SD), but hypertonic to plasma. Peak osmolality of meduallary slices was found to be in the range of osmotic pressures of urine obtained from hibernating or aroused animals. After single injections of a mixture of rho-aminohippurate and inulin, or during constant infusion of inulin, steady-state excretion by hibernators was not achieved for several days. Indirect evidence indicateds that the hibernating marmot is capable of PAH secretion.


Metabolic adaptation of the chick embryo to chronic hypoxia. In a colony of white leghorn chickens maintained at 3,800 m successive generations exhibited an increasing hatchability of fertile eggs incubated at elevation of 3,100m. Embryonated eggs produced by the high-altitude-adapted line (WM) and by genetically similar but unselected stocks at sea level (D) were incubated at 3,100 m and at sea level, and the oxygen consumption was measured on individual eggs after the 17th day of incubation. At sea level, oxygen consumption rates of WM strain were less than that of SL stocks during late embryonic development. At 3,100 m, embryonic respriation of all strains was reduced, but to a much lesser degree in the high-altitude strain. It appears that a decreased metabolic activity of the late embryo coupled with a slower rate of embryonic developement is an important factor in the adaptation of the domestic fowl to high altitude.


Pathway mediating hypotension elicited by stimulation of the amygdala in the rat. Cardiovascular responses were elicited from 372 histologically verified sites in the amygdala and closely adjacent structures in 82 rats under urethan or chloralose anesthesia. Arterial hypotension was elicited at low current intensities from the medial, central, lateral, and basal nuclei of rats under either anesthetic; the hypotension was still elicited in artificially respired paralyzed rats. Stimulation of the cortical nucleus produced variable changes in arterial pressure. The hypotension elicited under urethan was not found to be correlated with changes in the frequency of electrical activity of hippocampus, amygdala, or septum or to be associated with electrical seizures. Hypertension was usually elicited from the medial nucleus at high current intensities and was attributed to current spread to the cortex ventral to the medial nucleus from which hypertension was elicited at low current intensities. Stimulation of the central, basal, and lateral nuclei under chloralose elicited bradycardia. Lesions of the stria terminalis had no effect on the hypotension, whereas lesions of the ipsilateral medial forebrain bundle abolished this response.


Transport of plasma FFA in cats; effect of hypothalamic stimulation. Two tracer methods, repetitive single injection of [3-H]palmitate and continuous infusion of [1 minus 14-C]palmitate, were applied simultaneously to study tracer kinetics of the free fatty acid (FFA) miscible pool in anesthetized cats before, during, and after electrical stimulation of the hypothalamus. The results indicated that the FFA pool of the cat behaved as though it consisted of two compartments which exchange FFA with each other. The data were analyzed according to a two-compartmental mammillary system model. The space of the central compartment which represents the plasma was found to be 74 ml/kg body wt. No anatomical significance could be unequivocally ascribed to the peripheral compartment. The variables of the model system were determined for each cat, and a highly significant positive linear relationship between the net FFA transport (mumol/min) and the total quantity of FFA (mumol) in both compartments was established by a regression analysis of the control data. No significant changes were observed in this relationship during or following hypothalamic stimulation which had a significant effect on the plasma FFA level. This result suggests that hypothalamic stimulation affects FFA mobilization by modifying the rate of FFA inflow into the circulation, while the mechanisms for clearing FFA from the plasma are not altered.


Interaction of respiratory cell discharge patterns and spontaneous resporatory rate. Potentials from single respiratory cells in the inspiratory and expiratory populations of the medulla were recorded by extracellular microelectrodes in spontaneously breathing cats anesthetized with pentobarbital. Experiments were designed to follow alterations in single-cell discharge patterns after modification of the respiratory rate by either barbiturate depression or doxapram activation. Unit activity was quantitated by a computerized mathematical technique based on the sequential arrangement of interspike intervls. From this analysis several discharge parameters were derived which successfully quantitated initial (frequency increase), middle (frequency plateau), and terminal (frequency decrease) phases of spike activity. Discharge parameters were correlated with respiratory rate by the use of linear and curvilinear regression analyses. Theoretical discharge patterns for both inspiratory and expiratory populations were reconstructed at selected respiratory rates by interpolation from regression equations. These data, demonstrating average quantitative shifts in cell activation and deactivation phases as a function of respiratory rate, suggested several possibilities for the modulation of the respiratory frequency.


Estimate of relative thickness of peritubular interstitial space in Necturus kidney. Electrophysiological techniques were used to evaluate volume changes of compartments interposed between the peritubular membrane of proximal tubue cells and capillary wall or peritoneal surface of Necturus kidney. The time courseof potassium-induced peritubular membrane depolarization was measured during a switch from 3- to 90-meq potassium sulfate solution in superfusion as well as in vascular perfusion experiments. When superfusion fluids contained 6, 2, and 0 g dextran/100 ml, mean half times of depolarization in normal kidneys were 4.1, 1.9, and 5.8 s. Decreasing the colloid osmotic pressure of superfusion fluids resulted in a significant increase in half-time values. Similar results were obtained in saline expansion. In controls the mean half time was 4.5s; in saline expansion it was 7.7 s. In vascular perfusions, mean half-time values were 225, 350, 355, and 450 s for dextran concentrations of 6, 4, 2, and 0 g/100 ml, respectively. These results indicate that the half time of depolarization increases significantly as the colloid osmotic pressure of perfusion fluids decreases. Estimates of effective unstirred-layer thickness on the peritubular side of proximal tubular epithelium indicate a decrease by about 25% when vascular colloid osmotic pressure is increased from 0 to 54 mmHg.


Renal sodium reabsorption during saline loading and distal blockade in newborn dogs. The ability of the proximal tubule to respond to saline expansion and varying filtered sodium loads was studied in 27 neonatal dogs aged 1-23 days. Sodium reabsorption beyond the proximal tubule was blocked with ethacrynic acid and chlorothiazide. When puppies received an intravenous load of 0.9% saline for 1.5 h, fractional sodium reabsorption averaged 0.985. After the addition of distal blockade to the saline infusion fractional Na reabsorption fell to 0.512. During distal blockade alone fractional Na reabsorption was 0.701, and after 1.5 h of saline expansion added to distal blockade fractional Na reabsorption fell to 0.493. Thus, there was a significant decrease in proximal tubular fractional Na reabsorption after saline expansion in neonatal dogs, and the high fractional Na reabsorption and low Na excretion during saline loading without distal blockade must be due to a large distal Na reabsorption. When filtered sodium load was varied by raising and lowering the glomerular filtration rate during distal blockade, there was excellent correlation between amount of filtered and reabsorbed sodium (r = 0.92). Thus, glomerulotubular balance exists in newborn dogs when there is no saline expansion.


Uptake and compartmental distribution of fatty acid by rat small intestine in vivo. The uptake and esterification of micellar [3-H]oleate and [14-C] palmitate were uniform along the entire length of the small intestine in vivo. Fatty acids (FA) radioactivity taken up by the small intestine could be described in terms of four functionally distinct compartments analogous to those described in vitro. The KRP-extractable compartment (KEC) and albumin-extractable compartment (AEC) contained reversibly adherent unesterified FA radioactivity, while the tissue free and esterified FA compartments contained irreversibly bound radioactivity. Wheras 27% and 63% of FA uptake were reversibly bound in the KEC and AEC by the most proximal and most distal regions of the small intestine in vitro (15), less than 10% was contained in these compartments in vivo, independent of location. Linear inverse relationships were found betweeen tissue FA esterification and proportion of FA radioactivity present in the KEC,AEC, and the tissue free FA compartment in vivo. These observations allow for the possibility that FA molecules pass through these compartments prior to esterification.


Salicylate, tryptophan, and tyrosine hypothermia. The intraperitoneal administration of sodium salicylate, L-tryptophan, and tyrosine resulted in significant hypothermia when rats were exposed to a 4degree C ambient temperature. Salicylate and tryptophan increased plasma levels of nonprotein-bound tryptophan while total and bound tryptophan were reduced in salicylate-treated rats. Tryptophan  concentrations were unaffected by tyrosine administration. Concomitant with increases in free plasma tryptophan, there occurred significant rises in brain levels of tryptophan in both groups of rats, while brain tyrosine levels were increased in those rats receiving tyrosine. Similarly, significant increments in hypothalamic serotonin levels in rats receiving salicylate or L-tryptophan and increases in hypothalamic norepinephrine in tyrosine-treated rats seem to reflect the increased availability of tryptophan and tyrosine for monamine synthesis. However, alternative mechanisms of hypothermiaseem to be operative since oxygen consumption studies demonstrate dissimilar results for tryptophan and salicylate administration.


Reversible hemodynamic defect in glomerular filtration rate after ischemic injury. In Wistar rats with surface glomeruli 3 h of nearly complete occlusion of the left renal artery resulted in uniform falls (similar to50%) in ipsilateral whole-kidney glomerular filtration rate (GFR) and single-nephron GFR (SNGFR) and in urinary findings consistent with impaired water reabsorption. Since the fall in SNGFR was accompanied by a proportional fall in glomerular plasma flow rate (GPF), and since net ultrafiltration pressure at afferent and efferent ends of the glomerular capillary was unchanged from preischemic levels, these findings suggest that the fall in SNGFR was a hemodynamic consequence of the fall in GPF. To test this hypothesis, GPF was restored to preischemic levels by means of acute infusion of homologous, isoncotic plasma. GPF and SNGFR uniformly increased, on average to preischemic levels, whereas net ultrafiltration pressure at afferent and efferent ends of the glomerular capillary again remained essentially unchanged. These studies demonstrate that the fall in SNGFR in this model of ischemic injury is causally related to the accompanying fall in GPF. Of interest, despite this reversal of the defect in GFR, fractional water reabsorption remained impaired. This restoration of GFR but not reabsorption by plasma infusion abruptly converts this ischemic lesion from nondiuretic to diuretic.