Coagulation and the hypertensive diseases of pregnancy.

The coagulation and fibrinolytic systems were investigated in a group of patients with essential hypertension during pregnancy, and the findings were compared with those of normal gravid women. Patients with essential hypertension exhibited the following significant differences: shortened partial thromboplastin times, thrombocytopenia, and decreased antithrombin III levels. Euglobulin lysis times and assays for fibrin breakdown products suggest that essential hypertension is not associated with changes in the fibrinolytic mechanism. Until more sophisticated studies can be performed on such patients, it cannot be concluded that the increased coagulability observed in pregnant patients with essential hypertension represents a state of intravascular coagulation.


Enhanced prediction of pregnancy-induced hypertension by combining supine pressor test with mean arterial pressure of middle trimester.

Both the impact of the mean arterial pressure of the second trimester (MAP-2) on the development of pregnancy-induced hypertension (PIH) and the accuracy of the supine pressor test (SPT) for the prediction of PIH have been demonstrated. Despite good over-all predictability of the SPT, a large percentage of false positive SPT's have been reported, ranging from 6 to 60% with an average of 34%. In an effort to reduce the incidence of false positive SPT's and provide a more accurate method for identifying those primigravidas at risk for PIH, weekly or biweekly SPT's were performed. There were 251 SPT's performed on 97 primigravidas between 28 and 32 weeks' gestation. Along with the performance of serial SPT's, each subject's MAP-2 was calculated. Those primigravidas with an MAP-2 greater than 85 mm. Hg or two or more positive SPT's had a greater incidence of PIH (45 and 46%, respectively). Of greater significance, those women who exhibited both an MAP-2 greater than 85 mm. Hg and two or more positive SPT's had an 88% chance of developing PIH. These results were highly significant (chi square = 9.7, p less than 0.005).


Evaluation of an impedance measurement technique for uterine contraction recording.

An electronic system for the detection of uterine contractions by impedance measurement was evaluated in 30 subjects during the first stage of labor. The advantage of the system was patient comfort and ease of application of the recording electrodes. Simultaneous recordings of uterine contraction activity with conventional extra- or intra-uterine recording systems were made. The available evidence from this study indicated that 82 to 84% of the uterine contractions were accurately detected and that the onset and end of each uterine contraction is a reliable parameter of impedance measurement.


Maternal ingested methadone, body fluid methadone, and the neonatal withdrawal syndrome.

The relationship between the quantity of methadone ingested by the pregnant mother, the quantity of methadone in maternal and neonatal body fluids, and the subsequent neonatal withdrawal course was studied. The severity of the neonatal withdrawal syndrome was found to be related to the total dose of methadone ingested by the mother during the last 12 weeks of pregnancy (p less than 0.02), the maternal dose of methadone at delivery (p less than 0.01), and the intrapartum serum methadone levels (p less than 0.01). The cord blood levels of methadone were consistently lower than the maternal serum levels. Amniotic fluid methadone levels were not constantly related to maternal or neonatal serum methadone levels. Concentrations of methadone 10 to 60 times greater than that of cord blood were found in neonatal urine.


Changes in the conduction of the fetal electrocardiogram to the maternal abdominal surface during gestation.

A technique for recording high-quality vectorcardiograms from the fetus in utero is described. A study was conducted to clarify conflicting views on the mechanism of fetal electrocardiogram (FECG) signal transmission to the maternal abdominal surface during the latter half of gestation. The results of this study support the view that a general pattern of uniform conduction of FECG currents exists between 20 and 28 weeks' gestation in most subjects, that signal magnitudes decrease markedly between 28 and 34 weeks' gestation and conduction tends to behave as if it is nonuniform through the maternal abdominal volume, and that a preferred signal pathway, possibly through the oronasal cavities of the fetus, appears to develop after 34 weeks' gestation and continues until term. Two different abdominal FECG lead systems are recommended on the basis of these findings which should maximize the accuracy of FECG monitoring of the preterm fetus.


Effect fo potential placental surface area reduction on fetal growth.

This investigation was undertaken to study the effect of reduction of placental surface area on fetal growth. The right horn of the bicornuate uterus was removed in nonpregnant ewes, the ewes were bred and 11 out of 15 became pregnant. Near term, under experimental conditions, maternal and fetal blood gases, pH, uterine and umbilical blood flows were measured or calculated. Fetal, placental membrane, uterine, and cotyledonary weights and number of cotyledons were recorded. The experimental hemi-hysterectomized group was compared to a control group of 14. Results show that: (1) weight per cotyledon was significantly greater (p less than 0.01) in the hemi-hysterectomized series than in the controls, (2) loss of a significant number of placentation sites was compatible with the production of term-sized fetuses, (3) since the difference between the number of cotyledons in the hemihysterectomized and control groups is significantly less than the number of implantation sites removed, the efficiency of implantation is improved, and (4) there were no changes in blood flows, PO2, PCO2, and fetal oxygen consumption.


Fetoscopy in continuing pregnancies.

A total of 34 fetoscopic procedures were performed in 28 patients whose fetuses were at risk for hemoglobinopathies (22 cases) or short-limbed dwarfism (three cases). An adequate sample of fetal blood for study of globin-chain synthesis was obtained in 23 of the 25 cases (92%), and valuable diagnostic information was obtained in all three cases at risk for an anomalous fetus. Six patients elected to terminate their pregnancies based on the studies, and in the 22 patients continuing their pregnancies there have been no losses. Thus far, data from this series suggest that fetoscopy is associated with low maternal and fetal morbidity.


Pattern of increase in circulating prolactin levels during human gestation.

Serum prolactin concentrations, determined serially at weekly intervals from the fifth week of gestation, increase in an approximately linear pattern. It is suggested that in human gestation the increase in prolactin secretion is related to supramaximal estrogen augmentation at all times and is a functional reflection of hypertrophy and hyperplasia of pituitary lactotrophs.


Diagnostic peritoneal lavage for blunt trauma in pregnant women.

Twelve pregnant women underwent diagnostic peritoneal lavage for suspected blunt abdominal trauma. Peritoneal lavage was both safe and accurate. The lavage was negative in four patients. Two of these patients survived without clinical evidence of abdominal injuries. The absence of abdominal injuries was confirmed at autopsy in the two patients who subsequently died. Peritoneal lavage was positive for hemoperitoneum in eight patients. All eight had significant abdominal injuries.


Ultrastructure of the placental villi, chorion laeve, and decidua parietalis in normal and hypertensive pregnant women.

The fine structure of the placental villi, chorion laeve, and decidua parietalis from normal and hypertensive pregnant women is described. Placental villi from hypertensive women revealed an increase in syncytial degeneration and fibrinoid deposition. Also noted were greater numbers of cytotrophoblast cells. On the other hand, there were no morphologic differences detected in the cellular and noncellular elements of the chorion laeve and decidua parietalis between normal and hypertensive subjects. Secretory granules were observed in both the placental villi and the chorion laeve.


Urinary excretion of calcium in late pregnancy and its relation to creatinine clearance.

The distribution of the values for the daily urinary excretion of calcium during the last trimester of pregnancy was skewed toward high values in 1,034 women in Bradford, England. The logarithms of the values had a Gaussian distribution. The 95% range of this log-Gaussian distribution was 0.75 to 15.5 mmoles (30 to 620 mg.) per day. Nearly 20% of the values exceeded 8.75 mmoles (350 mg.) per day, which is the reported upper limit of the 95% range for nonpregnant women. Creatinine clearance is known to increase during pregnancy, and a prospective investigation in 112 pregnant Caucasian women in a hospital showed a highly significant correlation between calcium excretion and creatinine clearance. It is suggested that the increase in calcium excretion during pregnancy is due to the increase in glomerular filtration rate.


Fetal cardiac structure: identification and recognition. A preliminary report.

A rapid sonographic method of fetal cardiac structure identification with the use of gray-scale processing is reported. The characteristic ultrasonographic image display is analyzed as to fetal anatomy.


Fetal heart rate acceleration in response to acoustic stimulation as a measure of fetal well-being.

The search for better means of testing for antepartum fetal well-being is a major objective of perinatal medicine. This preliminary report explores the use of a 2,000 c.p.s. pure-tone auditory stimulus for "nonstress" testing, a comparison with the oxytocin challenge test (OCT), and a correlation with fetal outcome. Instead of waiting, when the fetus may be inactive or "sleeping," for a positive fetal heart (FHR) response following a fetal kick or movement, a rapid "nonstress" test may be performed by evoking an FHR acceleration after the application of a five-second auditory stimulation at 105 to 120 db. When FHR acceleration evoked exceeded 15 b.p.m., the subsequent OCT was always negative. Suspicious or positive OCT's were frequently obtained when no response to auditory stimuli occurred. Subsequent outcomes as well as safety and potential applications of this rapid test which may eliminate the need for many OCT's are discussed.


Amniotic fluid testosterone in the prenatal determination of fetal sex.

In the field of genetics, a rapid and accurate test for the prenatal determination of fetal sex, especially in cases of sex-linked disorders, is desirable. Amniotic fluid testosterone was measured by the radioimmunoassay technique in 37 samples obtained at saline abortion between 16 and 19 weeks' gestation. Final confirmation of fetal sex was obtained from fetal gonadal histology. In pregnancies with male fetuses, the mean amniotic fluid testosterone value of 27.6 ng. per 100 ml. was significantly higher (p less than 0.001) than the mean value of 9.6 ng. per 100 ml. found in pregnancies with female fetuses. The range for pregnancies with male fetuses was 15.5 to 41.3 ng. per 100 ml. and for those with female fetuses 5.7 to 15.1 ng. per 100 ml. With a coefficient of variation of 5 to 8% considered for the method of assay, there was an area of potential overlap from 12 to 18 ng. per 100 ml., giving a predictive error of approximately 16%. For patients in whom the results are clearly outside the area of overlap, this test is of value as a preliminary screen in the prenatal determination of fetal sex, especially in X-linked disorders.


Vitamin levels in low-birth-weight newborn infants and their mothers.

The cord blood of 50 normal-birth-weight neonates (more than 2,500 grams) and 50 low-birth-weight neonates (less than 2,500 grams) and the respective mother's blood were analyzed for folate, vitamin B6, riboflavin, nicotinate, pantothenate, thiamin, biotin, vitamin B12, vitamin A, and beta-carotene concentrations at parturition. No mothers had received supplemental vitamin intake. Except for vitamin A and beta-carotene, maternal vitamin levels were lower than those of neonates in all instances. Vitamin levels in the blood of low-birth-weight neonates were the same of those of normal-birth-weight infants except for significantly lower folate, vitamin B12, and pantothenate levels.


Evaluation of conventional diagnostic tests for detection of recurrent carcinoma of the cervix.

The use of routine diagnostic tests to evaluate patients periodically after treatment for carcinoma of the cervix has been reviewed. Of 169 patients treated at Brooke Army Medical Center for carcinoma of the cervix, 73 were evaluated after their treatment by a group of six diagnostic tests referred to collectively as an oncologic survey. The survey consisted of an intravenous pyelogram (IVP), chest roentgenogram, barium enema, cystoscopy, proctoscopy, and bone scan. Although 16 patients developed recurrent tumor, the oncologic survey detected only three recurrences that had not already been suspected by physical examination. Only the IVP and chest roentgenogram were of sufficient benefit to suggest their routine use for the detection of recurrent cancer. The other tests included in the oncologic survey were not beneficial when used routinely and should be reserved to evaluate patients otherwise suspected of recurrent cancer.


Psychosocial function in women treated for vaginal agenesis.

The psychosocial functioning of 23 women treated both surgically and nonsurgically for vaginal agenesis was assessed by means of a retrospective questionnaire. Subjects were also physically examined to evaluate anatomic outcome. It was concluded that the patients psychological adjustment before treatment and the sensitivity of her family and medical advisors during treatment took precedence over anatomic results in the eventual resolution of this disorder. Sexual function, emotional stability, self-image, and choice of marital partner in these women are described in some detail and are, in general, far healthier than had been depicted in earlier psychological reports.


Androstenedione metabolism in patients with endometrial cancer.

The plasma concentration of androstenedione and the instantaneous conversion of androstenedione to estrone was increased in patients with endometrial cancer as compared to postmenopausal control subjects. Moreover, the per cent of estrone derived from androstenedione was increased in the cancer group.


Pituitary-ovarian relationships preceding the menopause. I. A cross-sectional study of serum follice-stimulating hormone, luteinizing hormone, prolactin, estradiol, and progesterone levels.

Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, estradiol, and progesterone concentrations were measured in 58 ovulating women in different age groups (20 to 29, 34 to 39, 40 to 44, and 45 to 50 years) at five- to seven-day intervals through a single menstrual cycle and in 18 postmenopausal women sampled weekly five to six times. The over-all hormone patterns were similar in four premenopausal groups. However, mean serum FSH levels increased with age and significantly higher concentrations were found in the 40 to 50 years group than in the 20 to 29 year group. Serum LH levels did not show a similar rise with age, although follicular LH levels in the oldest group were higher than in the 20 to 29 year group. Prolactin and estradiol concentrations did not change with age prior to the menopause, but luteal progesterone levels were lower in the three older premenopausal groups than in the 20 to 29 year group. Postmenopausal women showed elevated FSH and LH, decreased prolactin, and negligible estradiol and progesterone levels. There was an over-all significant linear correlation between prolactin and estradiol concentrations. It appears that the menopause is preceded by several years of rising gonadotropin, predominantly FSH, levels. During this period, ovarian estrogen production appears to be maintained and ovulation continues, but luteal progesterone levels decline. It is likely that these premenopausal alterations in pituitary-ovarian relationships reflect depletion of ovarian follicles.


Comparison of central corneal endothelial cell numbers with peripheral areas.

Using a specific fixation device on a group of patients, we compared corneal endothelial cell count areas above, below, and temporally with the central corneal cell counts. Although younger patients, the central cornea mirrored the peripheral cell counts; peripheral counts were similar in each group. Patients with intraocular lenses had fewer cells than patients with uneventful cataract extraction, and the central cornea was representative in the cataract group. Only in the intraocular lens group was there a small difference between central endothelial cell counts and the temporal and inferior cell counts; but even this difference was significantly less than that seen in patients with intracapsular cataract extraction.


Mechanisms of failure in the repair of large retinal tears.

An analysis of large tears treated over a decade revealed that while dialyses responded well to circumferential buckling, horseshoe tears responded poorly. A circumferential intrusion of the globe augmented the redundancy of the posterior edge of long tears and predisposed to leaking radical folds. Tears up to 70 degrees responded favorably to radical buckles, often without drainage of subretinal fluid. Beyond 70 degrees and initial procedure with cryopexy and a gas tamponade without buckling reattached the retina occasionally, and if not, would at least reduce the problem to one manageable by local buckling techniques with a more favorable prognosis.


Cycloscopy and fluorescein cycloscopy of the ciliary process.

A new gonio-cycloscope that magnifies an object up to 1.5 times was designed to observe the ciliary process and chamber angle. As a result of aging, the ciliary process became hypertrophic and more branched with discoloration. Leakage of fluorescein from the ciliary process decreased as intraocular pressure artifically increased, stopping completely at 50 mm Hg or more. Water drinking accelerated fluorescein leakage, while oral glycerol diminished it.


An ultrasonographic study of the persistence of buckle height three years after segmental sponge explants.

We studied a consecutive series of rhegmatogenous retinal detachments treated with segmental silicone sponge explants and cryotherapy, with or without drainage, approximately three years postoperatively by ultrasonography to determine the degree and persistence of the height of the buckle measuring 1.5 to 3 mm remained in all patienst examined clinically and ultrasonographically at three years or later. Five of these patients reexamined one year later demonstrated no loss of buckle height between the third and fourth postoperative years. By comparison, in a small group of patients examined early in their postoperative course (2.5 to 4 months), the buckles were only slightly higher than in the group studied at three years. Buckle height thus appeared to stabilize relatively quickly postoperatively and to persist at least three years. We believe encapsulation of the sponge by scar tissue must contribute to the long-term maintenance of buckle height.


Late complications following cryotherapy of lattice degeneration.

We observed 341 patients who had received cryotherapy for lattice degeneration in order to identify possible late complications. Sequelae such as retinal tears posterior to an operculum or flap tears within treated areas showed that treatment did not necessarily prevent subsequent vitreous traction. Moreover, the newly created flap tears may extend beyond the treated area and can cause retinal detachment. Even scleral buckling did not necesserily prevent further traction. Therefore, we concluded that when cryotherapy is used to treat lattice degeneration, an adequate margin of surrounding retina should be treated and the treatment should extend to the ora serrata.


Engelmann's disease.

A 5-year-old boy with diaphyseal dysplasia who exhibited marked involvement of the cranial bones developed marked disk edema in a one-year period. We believed the optic canal was being rapidly compromised by bony proliferation and vision was threatened. Selective bone studies, including tetracycline labeling, demonstrated a rapid accretion of bone 1 1/2 to two times the expected rate for his age. We performed bilateral unroofing of the optic canals with additional temporal decompression of the left orbit. Limited unroofing of the right eye proved to be inadequate and only with additional extensive temporal decompression was the disk edema of the left eye reversed. Tomograms taken one year after surgery revealed regrowth of bone in the optic canal and orbital roof. The usefulness of bony decompression of the orbits in Engelmann's disease is requestionable.


Vitelliform macular degeneration.

Six patients had macular vitelliform lesions similar to those in Best's vitelliform foveal dystrophy but all had normal electro-oculograms (EOG) and no familial involvement. Two patients had an exudative form of degenerative chroidopathy. The remining four had vitelliform lesions of unknown etiology. Fluorescein angiography demonstrated slight hyperfluorescence through rarefied retinal pigment epithelium but no leakage occurred from perifoveal retinal capillaries. The diagnosis of vitelliform foveal dystrophy should be restricted to those patients who have the morphologic lesions, and abnormal EOG, and a contributory family history.


Complications of cobalt plaque therapy of choroidal malanomas.

We treated a small series of patients with choroidal malanomas with radioactive cobalt plaques. To assess the effectiveness of radiation, we performed radioactive phosphorus (32P) uptake determinations before and after treatment. The 32P results did not tumor destruction. In five of seven patients with posterior pole melanomas, radiation retinopathy developed after treatment with resultant decrease in vision.


Bilateral retinal vasculitis associated with clotting disorders.

We found distinct alterations of the clotting and fibrinolytic mechanisms in a 27-year-old man who suffered from typical bilateral vasculitis, clinically and fluoroangiographically manifest as obstruction of the central retinal veins. The partial thromboplastin time was slightly increased, a partial clot lysis occurred after one hour, the plasminogen level was markedly low, and alpha2-macroglobulin was decreased, as were factor XII and IgG. Kallikrein was absent. Similar changes, though not so pronounced, were also found in the patient's son and in his brother.


Retinoblastoma in a patient with a 13qXp translocation.

An infant girl with failure to thrive and bilateral retinoblastoma had a translocation of the long arm of chromosome 13 to the short arm of the X chromosome, and possible loss of a portion of the q 14 band. The lack of other major organ malformations in this patient emphasized the importance of considering chromosomal aberrations as a possible etiology of retinoblastoma in patients with nonspecific psychomotor retardation.


Bilateral retinal hemorrhages and disk edema in migraine.

A 27-year-old patient with severe migraine developed bilateral disk edema and retinal hemorrhages during a prolonged attack of his illness, lasting at least two months. The combination of bilateral disk edema and diffuse superficial retinal hemorrhages was considered to be a manifestation of prolonged valsalva efforts accompanying the migraine attack and of not persistent raised intracranial pressure.


Papilledema in endemic typhus.

A 21-year-old women developed severe bilateral papilledema during an acute febrile disease. Her optic disk margins were blurred and the disks were elevated up to 5 diopters. Splinter hemorrhages, cotton-wool exudates, cytoid bodies, and sheathing of veins were also present. The pyrexia was caused by murine typhus diagnosed by serologic tests. These tests revealed that Proteus OX-19 agglutination titer rose to 1:12800, and a positive complement fixation test titer was 1:640 with Rickettsia mooseri antigens. Neurological examination results, skull roentgenograms, brain scan, electroencephalogram, and the cerebrospinal fluid were all within normal range, thereby excluding intracranial hypertension. After the patient's recovery from the rickettsial disease, the papilledema abated gradually until her fundi reverted to normal.


Eye position of strabismus patients under general anesthesia.

We studied the change in eye position under general anesthesia in 317 patients undergoing strabismus surgery. We used the prism cover test to measure preoperative eye position, and the prism reflex test (Krimsky's method) to measure the eye position under general anesthesia. Almost all patients had divergence under anesthesia. We calculated a linear equation and curve to relate the eye position under anesthesia to the preoperative eye position. Patients with a normal amount of divergence (within one standard deviation of the mean) had a higher rate of successful surgical results than those with an abnormal amount of divergence under anesthesia (greater than one standard deviation from the mean).


Inadvertent substitution of acetohexamide for acetozolamide.

In three cases acetohexamide (Dymelor), an oral hypoglycemic agent, was mistakenly given to patients instead of acetazolamide (Diamox), which had been prescribed for their glaucoma. A  number of similarities, including the fact that both medications are 250-mg white tablets, with similar generic and brand names which are generically repackaged medications juxtaposed on the pharmacist's shelf, predispose to the inadvertent substitution of one medication for the other. In one instance a systemic hypoglycemic reaction resulting in head trauma and confusion ended in an emegency hospital admission following the substitution of acetohexamide for acetazolamide.


A modified vitreous scissors.

A new vitreous scissor combines an immobile shaft and hook with a sliding cutting blade; the blade is angled to trap the vitreous band while it is being cut. A tweezer-action handle is used. This scissors cuts dense membranes while producing only minimal traction on the retina.


Patient responses to gas-permeable hard (Polycon) contact lenses.

Forty-six patients who were unable to wear polymethylmethacrylate (PMMA) contact lenses, owing mainly to corneal edema and associated symptoms, were fitted with gas-permeable hard Polycon lenses of the same dimensions. Thirty-one patients (67%) wore the POLYCON lenses successfully. Thirteen (28%) did not, because of discomfort. For 2 patients, the results were unknown. None of the 46 patients exhibited observable edema with the POLYCON lenses. For a group of 5 patients (10 eyes), mean corneal thickness change after 8 hr of lens wear was insignificant. Oxygen transmissibility of these lenses is approximately 5.0 X 10(-11) (cm2 X ml O2)/(sec X ml X mm Hg), a value less than that for hydrogel lenses which produce more edema. It is predicted that gas-permeable hard lenses will eventually replace PMMA lenses.


Development of the modified Frostig Test.

We developed a screening version of Marianne Frostig's Developmental Test of Visual Perception, which we call the Modified Frostig Test. It was designed to guide optometrists educators, and psychologists in screening kindergarten or first grade children for possible visual perception problems.


A personality profile of "Gold Retinoscope" winners: 1961-1975.

Fifteen Gold Retinoscope winners, each judged the most outstanding student in his/her graduating class of the School of Optometry, University of California at Berkeley, were compared with samples of optometry students, Academy Fellows, and non-Academy optometrists. Although most Gold Retinoscope winners had entered optometry school with low to average grades, their grades and clinical performance in optometry school were outstanding. When compared with other optometry students and optometrists in practice, these outstanding students were distinguished by greater self-confidence, initiative, and motivation to achieve. It is suggested that these personality traits were important contributors to their superior achievement.


Mathematical model for predicting dioptric effects of optical parameter changes in the eye.

Changes in refractive status induced by contact lenses have been attributed to changes in various intraocular comonents. Limitation of previous mathematical attempts to quantify the effects of changes in these components are discussed. A series of simple ray-tracing equations is developed which avoids these limitations and provides a practical means of relating calculations to clinical measurements.


Refractive error distribution in a profoundly retarded population.

The refractive errors distribution of 103 profoundly retarded individuals (10 of zero to 20) was determined. This distribution was skewed in the direction of myopia. Since no such data were available for any other profoundly retarded population, direct comparison with other studies was not possible. However, a significant difference in mean spherical equivalent was found between the profoundly retarded of this study and the combined severely and profoundly retarded of two earlier studies.


Vision training for presbyopic nonstrabismic patients.

Home vision training was prescribed for 161 presbyopic patients (ages 45 to 89) who had vision-related symptoms and convergence insufficiency or visual skills deficiencies. Most patients required 10 weeks or less of treatment, the longest treatment period being 15 weeks. Elimination of the symptoms and improved responses on certain optometric tests was achieved by 92% of the patients. Evaluation 3 months after therapy indicated that 77 patients required additional training, the older patients requiring it more often, to retain the initial improvement.


Diseases of the uvea - 1975 review.

Papers relating to central serous choroidopathy and clinically similar conditions in the 1975 literature on the uveal tract are reviewed. This disease entity is examined for aspects relevant to optometric practice. Conditions that must be differentiated from central serous choroidopathy are outlined along with diagnostic techniques that may improve detection and diagnosis by optometrists.


Appliances for treatment of oral sensori--motor disorders.

Cerebral palsied children with predominant oral sensori-motor disorders were treated with functional appliances. Clinical experience with the coordination and the synchronization of interdependent functional chains is reported. Reasonable therapeutic success in control of drooling, masticatory and swallowing defects as well as of perioral dysfunction, dysphonia and dysarticulation suggests a wider use of such functional methods.


Serum glucose and lactic acid concentrations during prolonged and strenuous exercise in man.

Serum glucose and lactic acid levels were determined in 20 young volunteers prior to and following marches with increasing back pack loads (30 and 35 kg) and distances (6 and 12 km). The drop in serum glucose levels correlated well with the degree of effort. A significant mean drop in serum glucose level of 10.3 mg% was detected only in the group carrying 35 kg for a distance of 12 km. In this group, objective physiological parameters as well as subjective grading of the march's difficulty indicated the effort to be strenuous. Serum lactic acid level did not change significantly following any march. Serum glucose level may serve an indicator for determination of work's duration and intensity, determination of optimal distances for untrained hikers and of optimal loads to be carried for various distances.


Variation in dental occlusion and arches among Melanesians of Bougainville Island, Papua New Guinea. I. Methods, age changes, sex differences and population comparisons.

Population studies of malocclusion lack comparability because of the subjective criteria employed in the definition of malocclusion. Alternatively, individual characteristics of occlusion can be quantified and compared within and between populations. Measurements were taken from the dental cases of 319 male an 359 female Melanesians from Bougainville, Papua New Guinea. The cross-sectional age changes from 12 to 68 years of age included an increase in intermolar arch width, a decrease in arch length and intercanine arch width, and increased crowding and malalignment. Neither age nor sex accounted for a large proportion of the differences among individuals. When compared to industrialized groups, the Bougainville population had a slight reduction in variance for most characteristics. Only the sagittal molar relationship was markedly less variable on Bougainville. The results emphasize that a quantitative evaluation of individual occlusal variables may reveal differences within and between populations not detected when simple malocclusion frequencies are reported.


Sexual dimorphism and mechanics of the human hip: a multivariate assessment.

The present research was undertaken to determine the effects of sexual dimorphism in the human pelvis and femur on the mechanics of human locomotion. The analysis was based on six biomechanical variables determined from 25 male and 32 female skeletal remains from the Dickson Mound site. Discriminant function analysis indicates that the mechanical variables which primarily contribute to dimorphism are the moment arm of the gluteus medius and the torque produced by the abductors at the hip. These mechanical aspects of hip function produce greater pressure on the femoral head in females.


Eskimo craniofacial morphology, cold stress and the maxillary sinus.

A determination of the capacity of the maxillary sinus was made for eight Eskimo populations, one Mongolian population and one American white population. Statistical analyses reveal strong and significant correlations of the mean temperature of the coldest month where these populations live with differences in mean maxillary sinus volume (MSV) values. Results indicate that maxillary sinus volume in Eskimo populations decreases in colder areas. These changes may be due to commensurate structural ramifications of internal nasal anatomy variation, specifically of the inferior concha (maxilloturbinal) and inferior meatus. A review of the physiological, morphological and cultural responses of the Eskimo to cold suggests that only the facial area as a whole, and the internal nasal apparatus in particular, sustain significant cold exposure. The "cold-engineered" hypothesis of Mongoloid craniofacial form (Coon et al., '50) finds little support in the anthropological research and literature.


Principal component analysis of the elongation of metacarpal and phalangeal bones.

A hypothesis that the first principal component computed from the covariance matrix of logarithms reflected the specific growth rates of corresponding bones was taken to analyze the growth pattern of the tubular bones of the hand. The total length of 19 tubular bones of the right hand was measured on standardized radiographs of Japanese children (33 boys, 33 girls). Metacarpals in boys and bones of the fifth digit in girls showed higher growth coefficients. The second, third and fourth proximal, and the third and fourth middle phalanges showed lower coefficients for both sexes. These observations suggest the signs of proximal row dominance in boys and of fifth ray dominance in girls in the elongation of the hand bones. A marked sex difference was found in the fifth middle phalanx. In girls the growth coefficients of this bone was much larger than any other bones, but was moderate in boys.


The deflecting wrinkle on the teeth of Icelanders and the mongoloid dental complex.

Three local populations from Northeast Iceland are surveyed for the occurrence of the deflecting wrinkle of the metaconid on second deciduous and first permanent lower molars. The trait occurs more frequently on dm2 than on M1, and no sexual dimorphism is found, as expected. However, the frequencies are clearly within those predicted by the Mongoloid dental complex for Mongoloid populations. It is therefore suggested that the inclusion of the deflecting wrinkle in the Mongoloid dental complex be re-evaluated, and the racial diagnostic value of the trait taken with reservation.


Intra and intertribal genetic variation within a linguistic group: the Ge-speaking indians of Brazil.

A total  of 562 individuals living in four villages of two Brazilian Indian tribes (Cayapo and Krahó) was studied in relation to blood groups ABO, MNSs, , Rh, Lewis, Duffy, Kidd and Diego; haptoglobin, Gc, acid phosphatase and phosphoglucomutase types. These results were compared with those obtained previously among the Xavante, and the inhabitants of three other Cayapo villages, all of whom speak Ge languages; the ranges in gene frequencies observed in a representative series of South American Indians from all over the continent were also compiled. The Ge Indians are characterized by low frequencies of RZ, medium frequencies of R1, R2, R0, or r, Jka and PGM1/1, and high frequencies of Gc2 and ACPA when compared  with  other South American tribes. Genetic distance analyses based on six loci indicate that the intratribal variability observed among Cayapo is of the same order of magnitude as those obtained among the Xavante and Krahó, being much less pronounced than those observed among the Yanomama and Makiritare. The intertribal differences within this linguistic group are much less pronounced than those encountered among tribes that speak more differentiated languages.


Corrigenda to "estimation of stature from long limb bones of American Whites and Negroes," American Journal Physical Anthropology (1952).

The amount of disparity between the lengths of the radii and ulnae of 177 Negro female skeletons of the Terry Collection was questioned. An error was found and corrections have been made in the relevant statistics and tables.


Membrane permeability of isolated lung cells to nonelectrolytes.

Mixtures of viable endothelial and epithelial cells were separated by enzymatic digestion from rabbit lung and recovered by centrifugation. The cells were mixed with an extracellular marker and packed by centrifugation into small-diameter polyethylene tubing and pulsed with tritiated water and 14C-labeled alcohols. Calculation of diffusion coefficients for the packed cell column (D), intracellular material (D2), and extracellular fluid (D1) was based on a local steady-state one-dimensional diffusional model. Permeability coefficients were: tritiated water, 288 X 10(-5) cm s-1; methanol, 385 X 10(-5) cm s-1; ethanol, 214 X 10(-5) cm s-1; propanol, 277 X 10(-5) cm s-1; and hexanol, 1255 X 10(-5) cm s-1. The permeability coefficients of these aliphatic alcohols show a minimum at ethanol with hexanol having the highest value of all substances tested. The results support the concept of parallel aqueous and lipid pathways for small solutes in the plasma membrane. Study of the permeability properties of isolated lung cells can provide information on the cellular pathway in the transcapillary transport of water and solutes in the lung.


Protein transport across cerebral vessels during metrazole-induced convulsions.

The effects of pentylenetetrazole-induced convulsions on cerebrovascular permeability for horseradish peroxidase were studied in locally anesthetized, artificially respired, paralyzed cats. Horseradish peroxidase circulated for 1, 2.5, 5, 10, 30, and 60 min and accumulated in medium-size, i.e., arterial or venous, blood vessel walls. Cerebral neuropil was permeated earliest in thalamic nuclei including medial and lateral geniculate nuclei. No tight junctions containing horseradish peroxidase were found. With 1.0 and 2.5 min circulation of horseradish peroxidase, arterial adventitia and basement membranes contained more peroxidase than surrounding interstitial space in contrast to veins and capillaries. Convulsions increased the number of endothelial vesicles containing horseradish peroxidase in arteries, veins, and capillaries but total number (stained plus unstained) of endothelial vesicles was increased slightly only in capillaries. We conclude that increased permeability is initially at the arterial level, although veins may also become permeable. The role of the endothelial vesicles in transit or protein in and out of the nervous system is not clear.


Mechanical properties of tracheal smooth muscle: effects of temperature.

The effect of temperature on the isometric tetanic myogram was studied in isolated canine tracheal smooth muscle (TSM). At 37 degrees C and 27 degrees C no significant change occurred in maximum tetanic tension (PO). At 17 degrees C a significant reduction was seen Values of Q10 for contraction time (tPO) were almost halved, whereas those for rate of tension development (dP/dt) were almost doubled. The effect of the same temperatures on the force-velocity (F-v) relationships was also studied. All three F-v curves were described by the Hill equation, (P + a) (v + b) = (PO + a)b. Vmax and b decreased with decreased temperature, with Q10's demonstrating they were dependent on active processes. Finally, the decreased dP/dt of the myogram at lower temperatures was felt to be the probable result of decreased contractile element velocity because no decrease in series elastic component stiffness was demonstrable, there being instead an increase in stiffness at lower temperatures.


Adrenergic control of pineal N-acetyltransferase activity: developmental aspects.

The activity of pineal N-acetyltransferase in the neonatal rat does not exhibit the large daily rhythm seen in the adult and is intermediate between the low day and high night adult values. These intermediate values appear to result from adrenergic stimulation. Blockade of adrenergic receptors or of catecholamine synthesis results in a decrease in enzyme activity in vivo. In vitro studies provide additional evidence of a completely developed postsynaptic adrenergic control system for pineal N-acetyltransferase activity at birth. Our observations indicate that the appearance of a circadian rhythm in pineal N-acetyltransferase at the end of the first week of life reflects the development of presynaptic mechanisms and structures necessary for the control of catecholamine release and uptake. These events follow the developmental appearance of the postsynaptic mechanisms required to mediate the adrenergic-cycle AMP regulation of pineal N-acetyltransferase activity, which can be detected prior to birth.


Esophageal manometry in the opossum.

The opossum esophagus is commonly used as an animal model of the human esophagus. We used esophageal manometry in normal animals to provide basal data about normal esophageal motor functions in vivo in this species. At rest, separate and distinct high pressure zones can be recorded at the level of the lower esophageal sphincter, diaphragmatic hiatus, aortic arch, and upper esophageal sphincter. Each zone demonstrates a characteristic pattern of pressures in the radii of the coronal section and a characteristic response to swallowing. The hiatal and aortic zones can be mistaken for the esophageal sphincters. Pressures in the sphincters fall with swallowing. Peristalsis is not bolus-dependent and occurs with 98% of swallows. Pressures generated by peristalsis are greater in the middle of the esophagus than at the ends. Values for resting lower esophageal sphincter pressure and the characteristics of peristalsis were reproducible between different studies in the same animals.


Effect of thyroparathyroidectomy of calcium metabolism in rats: role of 1,25-dihydroxyvitamin D3.

Thyroparathyroidectomy (TPTX) decreases plasma calcium, bone formation and resorption, and tubular reabsorption of calcium. It also reduces the production of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] which very likely results in the decrease in the intestinal calcium absorption (Vna) observed after TPTX. We have examined whether the influence of TPTX on plasma calcium and bone calcium fluxes could be corrected by doses of 1,25-(OH)2D3 (2 X 13 pmol/day ip), which just normalize Vna. The study was made by calcium balance and 45Ca kinetics in rats receiving a normal supply of vitamin D3. The results show that in TPTX rats physiological doses of 1,25-(OH)2D3 increased plasma calcium and decreased plasma phosphate. Calcium retention was not fully corrected because 1,25-(OH)2D3 increased urinary calcium excretion. The deposition into and the release of calcium from bone were enhanced by 1,25-(OH)2D3 but remained lower than in pair-fed sham-operated animals. Thus, in as much as the diminished renal production of 1,25-(OH)2D3 in TPTX is entirely responsible for the reduced Vna, the decrease in 1,25-(OH)2D3 could only partly explain the effect of thyroparathyroidectomy on bone calcium fluxes.


Magnesium-fluoride interrelationships in man. I. Effect of fluoride on magnesium metabolism.

Metabolic balances of fluoride and magnesium were determined in man in control studies and during fluoride supplementation. The studies were carried out during three intake levels of calcium (200, 1,400, and 2,200 mg/day) and during two intake levels of phosphorus (800 mg and 1,400 mg/day). The intake of about 10 mg fluoride per day, given as NaF, resulted in a two- to threefold increase of the urinary and fecal fluoride excretion. However, during the high fluoride intake, the urinary magnesium remained about the same, the fecal magnesium increased slightly, and the magnesium balances did not differ significantly. This was the case whether fluoride was given during a low or high calcium intake in the absence or presence of added phosphorus. Similar results were obtained with large doses of fluoride (40-45 mg/day) given to patients with osteoporosis. The studies have shown that supplemental fluoride ranging from 10 to 45 mg/day did not affect the magnesium balance during calcium intakes that ranged from 200 to 2,200 mg/day and during phosphorus intakes that ranged from 800 to 1,400 mg/day.


Gluconeogenesis in the suckling rat.

Gluconeogenesis from lactate was increased more than twofold in perfused livers and isolated hepatocytes from 10- and 15-day-old suckling rats compared with adult rats and was not increased by fasting. Glucagon (10(-19)-10(-7) M) induced minimal activation of gluconeogenesis in hepatocytes from such animals even though it promoted accumulation of cAMP. Suckling rats had low plasma insulin levels and high plasma glucagon levels. The presented very low insulin/glucagon ratios were associated with high liver cAMP levels. Contrary to the situation in adult rats, glucagon levels fell with fasting. Insulin levels fell proportionally further so that the insulin/glucagon ratios declined. On the basis of these findings, it is proposed that the high glucagon and low insulin levels in young suckling rats result in high liver cAMP levels with resultant maximal stimulation of hepatic gluconeogenesis so that it cannot be further increased by fasting or exogenous glucagon. It is also suggested that milk is an important stimulus to the hyperglucagonemia of suckling rats in view of its high protein and low carbohydrate content.


Effect of insulin, glucose, and controlled diabetes mellitus on human jejunal function.

The effects of serum insulin concentration, serum glucose concentration, and of insulin-dependent diabetes mellitus on human jejunal glucose, Na, and H2O absorption were assessed. Triple-lumen perfusion studies were carried out in 20 nondiabetic and 9 insulin-requiring diabetic male volunteers. In seven normal subjects, sequential elevation of serum insulin concentrations from 20 muU/ml to 50 and 100 muU/ml for 2 h each, with maintenance of constant serum glucose levels, failed to significantly alter glucose, Na, and H2O absorption. Absorption of glucose, Na, and H2O was similar when the serum glucose concentration was maintained at 125 and at 250 mg/100 ml. Glucose absorption results during 26 perfusion studies in 20 control subjects were compared with results obtained during 20 perfusion studies in 9 diabetic subjects. Glucose concentrations in isotonic perfusates were 25, 40, or 75 mM. Na and H2O absorption rates were similar in both groups. Regression lines relating glucose load or geometric mean study segment glucose concentration to glucose absorption were also comparable. These results indicate that insulin-requiring diabetics absorb glucose, Na, and H2O normally.


Effect of lumenal contents on colonic cell replacement.

Recent studies have shown that the rate of colonic cell renewal can be altered through fasting and refeeding, which produces a marked depression and transient stimulation, respectively. In the present study, the role of physical versus nutritional stimulation in the colonic fasting-refeeding response and the renewal of the functional colonic compartment were evaluated via a nondestructive colonic ligation procedure. The results reported herein suggest that physical stimulation by lumenal factors is in part required to initiate the colonic hyperplasia seen after refeeding. Blood-borne nutritional factors, in the absence of physical stimulation, cannot alone stimulate colonic cell production. Additional evidence is presented which suggests that this physical stimulation may be manifested through the lumenal distension produced by the newly ingested food materials. The results are discussed from the viewpoint of influencing the functional colonic compartment and physiological capacity.


Stimulation of renal phospholipid formation during potassium depletion.

Potassium depletion induces increased membrane phospholipid formation and renal growth in rats. To determine the mechanism by which potassium depletion augments phospholipid formation, the metabolism of radioactive choline, a precursor of choline-containing phospholipids, was studied in renal slices. Cortical and medullary tissue from potassium-depleted and control animals accumulated extracellular choline and sequentially converted it to phosphorylcholine, cytidine diphosphocholine (CDP-choline), and choline phosphoglyceride, thereby demonstrating that renal cells can utilize the Kennedy pathway for phospholipid synthesis. [14C]Choline uptake into intracellular fluid was increased in cortical slices from potassium-depleted animals. The apparent Km and Vmax of the kinase reaction which converts entering [14C]choline to [14C]phosphorylcholine were unchanged during potassium depletion. The rate of [14C]phosphorylcholine conversion to [14C]CDP-choline was also unchanged. In contrast, the Vmax of [14C]choline phosphoglyceride formation from [14C]CDP-choline was increased, whereas the apparent Km for this reaction was unchanged. These results indicate that increased renal choline phosphoglyceride formation during potassium depletion can occur via the Kennedy pathway and appears to be mediated by increases in choline uptake and the rate of CDP-choline incorporation into phospholipid, the first and last steps of the pathway.


Renal extraction, filtration, absorption, and catabolism of growth hormone.

Renal handling of homologous labeled rat growth hormone (125I-rGH) was studied in the intact rat and in a filtering and nonfiltering isolated perfused rat kidney preparation. Plasma disappearance rate, renal accumulation, renal clearance (C), glomerular sieving coefficient (GSC), absorption rates, and fate of absorbed hormones were determined. 125I-rGH is extensively filtered (GSC approximately 0.6) and subsequently absorbed by the tubular epithelium (C/GRF less than 1%). The absorption process of 125I-rGH has a high capacity and is inhibited by iodoacetate. Absorbed 125I-rGH is catabolized and a detectable product of catabolism (125I-monoiodotyrosine) is returned to the circulation. A nonfiltering kidney preparation with adequate renal perfusate flow was developed to study the contribution of the peritubular side to the renal handling of small proteins. Experiments in the nonfiltering kidney show that renal accumulation, extraction, and catabolism of 125I-rGH from the peritubular side is minimal when compared to that occurring from the luminal side. The ratio of the renal extraction rate of 125I-rGH in the isolated kidney and the mean plasma disappearance rate of 125I-rGH in the intact rat was 0.67, demonstrating that the kidneys account for the major fraction of the total plasma turnover of GH in the rat.


Histamine H1- and H2-receptor vasodilation of canine intestinal circulation.

Studies were conducted in anesthetized dogs to determine whether the mesenteric vasodilator response to histamine is mediated by H1 receptors alone or whether H2 receptors are also involved in the response. Evidence favoring a role for both receptors included: 1) the vasodilator response to histamine was inhibited by either the H1-receptor antagonist, tripelennamine, or the H2-receptor antagonist, metiamide; 2) both the H1 agonist, 2-methylhistamine, and the H2 agonist, 4-methylhistamine, induced dilator responses in the mesenteric circulation; and 3) two temporal patterns of vasodilation could be distinguished, namely a transient spike and subsequent fade of blood flow (seen with either the H1 agonist or with histamine after H2-receptor blockade) and a sustained and stable increase in flow (seen with either the H2 agonist or with histamine after H1 blockade). Metiamide appeared to be a potent inhibitor of the mesenteric vasodilator response to histamine at least equal to tripelennamine.


Renal energy metabolism and sodium reabsorption after 2,4-dinitrophenol administration.

2,4-Dinitrophenol (DNP) (10 mg/kg body wt i.v.) increased renal cortical and outer medullary heat production rates and oxygen consumption by 70-90% in anesthetized dogs over a 90-min observation period without exerting any natriuretic effect. To examine whether DNP inhibited proximal reabsorption and increased distal delivery, ethacrynic acid (3 mg/kg body wt) was infused during maximal DNP effect. Sodium reabsorption fell by 14 +/- 6% in the cortex and 55 +/- 8% in the outer medulla, not significantly different from control experiments without DNP. Conversely, after ethacrynic acid administration, DNP had no additional natriuretic effect. Since DNP did not stimulate renal anaerobic metabolism (no lactate release), the effect of DNP was examined during hypoxia induced by intravenous infusion of NaCN (0.2 mumol/kg body wt-min) until renal metabolic rates fell. Subsequent infusion of DNP reduced tubular sodium reabsorption from 90 +/- 2 to 78 +/- 6%. Thus, DNP may raise renal metabolic rates by 70-90% without inhibiting sodium reabsorption, but, under conditions of hypoxia, DNP reduces sodium reabsorption and increases sodium excretion.


Aldosterone and postprandial renal excretion of sodium and potassium in sheep.

When sheep rapidly eat a meal of dry feed a period of antinatriuresis and antidiuresis is rapidly initiated and lasts for 2-3 hrs. This is followed by a postprandial period of natriuresis and diuresis. This study tested the hypothesis that the postprandial natriuresis was due to a reduction in the secretion of aldosterone. In unanesthetized ewes of about 50 kg body wt, measurements were made of sodium and potassium excretion beginning in the terminal phase of the feed-induced antinatriuresis and continuing through the period of postprandial natriuresis. Aldosterone, given by constant infusion at a physiological dose (10 microgram/h), inhibited the natriuresis. Spironolactone, a competitive inhibitor of aldosterone given as a single intravenous injection of 5 mg/kg body wt, did not significantly increase the natriuresis. These results support the stated hypothesis. Neither aldosterone nor spironolactone had a significant effect on potassium excretion. This finding supports earlier view that aldosterone has only a small role in the homeostatic control of potassium excretion in sheep.


Feedback control of glomerular filtration rate in isolated, blood-perfused dog kidneys.

Micropuncture studies were done in isolated, blood-perfused dog kidneys to investigate the intrarenal nature of tubuloglomerular feedback regulation of nephron filtration rate. Collections were made at early proximal tubular sites during alterations in flow through the loop of Henle to elicit the feedback response. Renal blood flow in the 10 isolated kidneys averaged 4 ml/ min-g kidney after an initial vasoconstriction. Filtration rate was 0.52 +/- 0.12 ml/min-g kidney for the period 90-120 min, but progressively fell after 120 min, as did fractional sodium reabsorption and PAH extraction. The feedback regulation of nephron filtration rate was demonstrated during the first 3 hrs of perfusion even with subnormal renal function. The feedback response expressed as the percent reduction of early proximal flow rate when loop of Henle flow was elevated from 0 to 45 nl/min was 41.3 +/- 4.5 (for the first 90 min), 35.3 +/- 7.5 (90-120 min), 24.3 +/- 6.8 (120-150 min), and 26.6 +/- 7.7% (150-180 min). After 180 min, the feedback response was no longer demonstrated. These results show that feedback-induced changes in nephron filtration rate are achieved in the absence of nervous system influences.


Ontogeny of glycine transport in isolated rat renal tubules.

Isolated renal tubule preparations were made from newborn Sprague-Dawley rats and used to study initial entry rate kinetics of glycine. The results were compared to those obtained in the isolated tubule preparation from the adult rat kidney. While initial rates of glycine uptake were identical for newborn and adult tubules, significant differences in influx kinetics were demonstrated. Of the two apparent transport Km systems shown to be present in the newborn tubule, the high-affinity, low-capacity system accounts for about 40% of total glycine  uptake at physiologic concentrations. The high-affinity, low-capacity system of the adult tissue accounts for about 10% of total uptake at the same concentration range. The data lend strength to the argument against the concept that the physiologic hyperglycinuria of the newborn rat is due to either impaired ability to concentrate glycine intracellularly or to absence of one or more transport mechanisms for glycine.


Glycerol-induced acute renal failure in the two kidney Goldblatt rat.

One to four weeks after the left renal artery was clipped and the contralateral kidney was left untouched in Sprague-Dawley rats (two-kidney Goldblatt preparation), the clips were removed under ether anesthesia and 10 ml/kg body wt of either 150 mM NaCl (control) or 50% glycerol in water (experimental) were injected intramuscularly. The next day the rats were anesthetized (sodium pentobarbital) and the renal function of both kidneys was measured, after which the renal cortical renin content was measured by incubation of tissue homogenate with angiotensinase-free rat renin substrate. Radioimmunoassay was used to determine the rate of angiotensin I production. Compared with controls, both kidneys of glycerol-injected rats had reduced GFR (left 28, right 18% of controls), increased percentage of fractional water excretion (left 5, right 6 times controls), and increased percentage of fractional Na excretion (left 3, right 4 times controls). Despite large differences in renal renin (left 28, 676, right 1,329 ng angiotensin I/h per mg protein), the extent of renal failure produced by glycerol was equal in the left and right kidneys. These results are inconsistent with the hypothesis that renal renin content is directly related to the severity of glycerol-induced renal failure in rats.


Indirect measurement of total exchangeable potassium.

A technique is described for the indirect measurement of total exchangeable potassium (Ke) that involves neither the rapidly decaying radioisotopes of potassium nor a total body counter. Total exchangeable sodium (Nae) and total body water (TBW) are measured by isotope dilution. Ke is calculated from Ke = R (TBW) - Nae, where R is the ratio of the sodium plus potassium content divided by the water content, in a sample of whole blood. In 19 normal rats and four rats with uremia there was an insignificant difference between the indirect determination of Ke and its direct measurement by carcass analysis. A similar insignificant difference was recorded between the indirect determination of Ke and its direct measurement by potassium-42 dilution in 15 normal dogs, five dogs with uremia, 14 dogs in an hyposmolar state, and in 20 patients. In 25 normal volunteers, Ke was determined indirectly. The regression of Ke on TBW and the 95% confidence intervals of this population was similar to published data in which Ke was determined by potassium-42 dilution. The indirect measurement of Ke was, therefore, validated experimentally.


Cross-linking of actin and fibrin by fibrin-stabilizing factor.

Fibrin-stabilizing factor is known to cross-link fibrin monomers. This study was undertaken to explore whether a similar interaction might occur between actin and fibrin. Purified actin and fibrinogen were labeled with 131I and 125I, respectively. The interaction of actin and fibrin, under different conditions, was evaluated by gel electrophoresis. The data show that actin and fibrin are cross-linked in the presence of fibrin-stabilizing factor.


Effects of prostaglandins and endoperoxide analogs on canine saphenous vein.

Contractile effects of prostaglandins (PGs) have not been widely studied in the canine saphenous vein, as in vitro model for venous function. We studied responses to two PG endoperoxide analogs (PGEA) and to monoenoic and bisenoic PGs of the A, B, E, and F series in helical strips of canine saphenous veins. Isometric changes in force were measured. All agents elicited marked contractions. PGEA were several orders of magnitude more potent than either primary PGs or other venoconstrictors, including norepinephrine. E- and A-types PG had unusual concentration and contraction at high concentration. B-types PG evoked a biphasic contractile response. Bisenoic PGs tended to be more potent than monoenoic PGs of the same type. These results show that canine saphenous veins are highly responsive to PGs and PGEA. These data suggest that these substances could influence venous tone in vivo. However, PG-induced changes in venous tone would depend on which PG or intermediate was present, on PG concentration, and on the prior state of venous tone.


Estrogen attenuation of the development of hypertension in spontaneously hypertensive rats.

To examine the effects of estrogen on the development of high blood pressure in rats with a genetic predisposition toward hypertension, we administered to rats of the spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) strains 0.05 mg mestranol daily from ages 4 to 13 wks. Control animals of each strain received corn oil placebos. Systolic blood pressure was measured by a microphonic tail-cuff technique twice a week after the rats were 6 wks of age. Estrogen treatment in SHR was associated with a significant reduction in the level of hypertension attained, but estrogen treatment had no effect on blood pressure in WKY. Estrogen prevented normal growth in SHR and WKY, but this effect (reproduced in another group of SHR and WKY by restriction of food intake) was not related to the lower blood pressures seen in estrogen-treated SHR. Thus, it appeared that estrogen administration attenuated the rise in blood pressure normally seen in SHR and that this attenuation was independent of the estrogenic effect on body weight.


Reflex effects on circulation and respiration from contracting skeletal muscle.

Isometric exercise induced by ventral root stimulation in the anesthetized cat caused heat rate (HR) to increase from 199 +/- 6 beats/min to 206 +/- 6 (P less than 0.001); mean arterial pressure (MAP) from 99 +/- 5.3 mmHg to 112 +/- 5.8 (P less than 0.001); and left ventricular dp/dt at developed pressure of 25 mmHg from 3,960 +/- 204 mmHg/s to 4,380 +/- 220 (P less than 0.001), while end-diastolic pressure remained unchanged. Respiratory volume (RV) increased from 755 +/- 71 ml/min to 1,160 +/- 123 (P less than 0.001). These changes were abolished by cutting the dorsal roots receiving afferents from the exercising muscle. Beta-adrenergic blockade with propranolol (1 mg/kg) abolished the changes in heart rate and contractile state; however, changes in MAP and RV still occurred. Induced isometric exercise causes a small rise in HR with a more marked increase in MAP, the contractile state of the left ventricle and RV. In this preparation the cardiovascular and respiratory changes reflexly originate from contracting skeletal muscle as proven by section of the corresponding dorsal roots, and the cardiovascular changes are mediated in part by activation of beta-adrenergic receptors in the heart.


In situ measurement of papillary muscle dynamics in the dog left ventricle.

In five open-chest dogs, pairs of ultrasonic dimension gauges were implanted in the anterior papillary muscle and in a circumferential subendocardial segment of the anterior left ventricular free wall, and simultaneous recordings were made with intracardiac pressure. The average shortening of the anterior segment in isovolumetric systole was 6% of end-diastolic length (EDL), with a total shortening of 19%. In the papillary muscles, isovolumetric shortening averaged 2%, total shortening was 10%, and shortening velocity was only 0.60 length/s. With acute pressure and volume overload, or inotropic interventions, changes in EDL were relatively less in papillary muscles than in the free wall. During acute occlusion of the anterior descending coronary artery, shortening of anterior segments and papillary muscles was replaced by holosystolic lengthening, and occlussion of the circumflex artery produced augmentation of shortening in  both these regions, with lengthening of the posterior papillary muscle. The present study documents shortening of the anterior left ventricular papillary muscle throughout systole that is substantially less than that of the circumferential free wall, and demonstrates severe papillary muscle dysfunction with systolic elongation during regional ischemia.


Loss of regional ventricular postextrasystolic potentiation after coronary occlusion in dogs.

Postextrasystolic potentiation following coronary artery occlusion was studied serially using pairs of ultrasonic crystals to measure regional myocardial function in control, marginally ischemic, and ischemic segments of the left ventricle in dogs. Prior to coronary occlusion (CO), percent shortening in control (normal) segments increased by an average of 51.4 +/- 4.6% in the beat after a premature ventricular contraction (post-PVC beat), and this response changed little after coronary occlusion. During the 1st min after CO, in ischemic segments, systolic expansion developed but was replaced by active shortening in post-PVC beats; however, after 3 min of CO (average) and thereafter, there was no net positive shortening in post-PVC beats. In marginally ischemic segments early after CO, hypokinesia developed, but there was marked augmentation of percent shortening (208.6 +/- 32.6%) which persisted in post-PVC beats even after 2 h. It is concluded that loss of postextrasystolic potentiation occurs rapidly in ischemic regions after CO and is not indicative of irreversible damage; partially ischemic regions retain this mechanism for prolonged periods.


Effect of isoproterenol on relation between maximal rate of contraction and maximal rate of relaxation.

The relaxing effect of two positive inotropic interventions was studied in the isolated rat heart beating at constant rate and perfused at constant coronary flow. Experiments were performed under isotonic or isometric conditions during heart perfusions with Ca2+, 3.5 X 10(-3) M, and with isoproterenol, 10(-7) to 10(-8) M. Changes induced in maximal velocity of contraction (+L or +T) and maximal velocity of relaxation (-L or -T) were analyzed as the ratio between both maximal velocities (+L/-L or +T/-T). For similar increments in the amount of the apex-to-base shortening or in developed tension during Ca2+ or isoproterenol perfusions, the effect on the maximal velocity of relaxation differed for each intervention. High Ca2+ perfusion increased velocities of contraction and relaxation proportionally without significant changes in their ratio. Isoproterenol increased -L or -T more than +L or +T and the ratio showed a significant fall both in isotonic and isometric experiments (+L/-L, -0.33 +/- 0.11 and +T/-T, -0.38 +/- 0.09; P less than 0.01). The relaxing effect of the beta agonist seems to be related to the activation of the protein kinase system since perfusions with dibutyryl 3',5'-cAMP had a greater effect on the relaxation of the hearts.


Non-uniform strain distribution in papillary muscles.

Measurements of surface strains were made on small segments of intact papillary muscles of cats and rabbits. The measured strain is found to be non-uniform, both along the length and across the diameter of the papillary. This observation introduces difficulty in interpreting the data from experiments on the mechanics of the papillary muscle.


A closed-chest canine model for cross-sectional echocardiographic study.

Cross-sectional echocardiography has been limited in the intact dog due to the intervening lobes of the left lung. Previous echo studies of the canine heart have utilized implanted transducers, catheter-tip transducers, or opened-chest preparations. The pericardial cradle technique described in this paper provides an acoustical window for echo studies of the entire heart in the closed-chest dog that has several advantages over these prior preparations. The left lung was retained by attaching the pericardium to the thoracic wall in a simple prestudy operation. Cross-sectional real-time echocardiographic studies have been performed on 52 anesthetized animals that were prepared in this manner. The studies were video taped for frame-by-frame analysis.


Ingestive behavior after intracerebral and intracerebroventricular infusions of glucose and 2-deoxy-D-glucose.

Direct infusions of 2-DG into the lateral hypothalamic area (LHA), the ventromedial hypothalamus (VMH), the dorsal hippocampus, the amygdaloid complex or the caudate nucleus were all ineffective in eliciting drinking or feeding in satiated rats. However, 2-DG (but not D-glucose) infused into the lateral ventricles of satiated rats elicited feeding preceded by an initial burst of drinking, which could be blocked by prior intraventricular infusion of the alpha-adrenergic antagonist, phentolamine, by the serotonergic blocker, methysergide, but only slightly by the dopaminergic receptor blocker, spiroperidol. The feeding response was totally blocked by phentolamine but not by methysergide or spiroperidol. These results show that 1) intraventricular administration of 2-DG can induce feeding, as well as drinking, supporting the hypothesis of cerebral glucoreceptors for the initiation of feeding behavior; and 2) local cytoglucopenia in the LHA, the VMH, or other limbic structures is not sufficient to initiate feeding. It is hypothesized that a specific pattern of cerebral glucoprivation rather than local glucoprivation, or an action of 2-DG on the presynaptic membrane of noradrenergic "feeding neurons" could be the mechanisms of 2-DG-induced feeding.


Oxygen exchange in a simulated trout gill secondary lamella.

The complex blood flow patterns occurring in a trout secondary lamella were computed from a theoretical electrical model consisting of a two-dimensional array of unitary resistances representing the blood channels of the lamella. Estimates of oxygen uptake from water to blood were made by means of the standard conductance equations for oxygen and values from the literature for blood and water PO2's in trout. The results were plotted as contour charts of blood and water PO2, O2 transfer, and blood flow. According to the results of various manipulations of this model, oxygen exchange across a given lamella will be largely unaffected by changes in the overall shape of the lamella. However, the model predicted that oxygen exchange would be greatly reduced if 1) the basal pillar cell channels were denied access to the respiratory water flow, 2) pillar cell contraction were to force blood into the larger-diameter marginal channels, or 3) the blood flow rate were to be increased, regardless of a concomitant increase in water flow. These predictions are discussed in terms of current theories of gas exchange in teleost gills.


Levels and reduction.

This paper addresses the problem of reconciling pluralism with reductionism, i.e., acknowledging both the variety of the world and the need and possibility to explain it. First the various kinds of monism and pluralism that litter the scientific and philosophical literature are examined cursorily. Then certain maligned notions are examined, mainly those of novelty, self-assembly, level, and levels "hierarchy." They are shown to be amenable to analysis and even mathematization. Then the logic of reduction is analyzed. Two kinds of reduction are distinguished: full or straight, and partial or roundabout. And three stands on reduction are examined: anti-, radical, and moderate reductionism. The former is dismissed for being obscurantist and the second for being quixotic. Moderate reductionism, aiming at the (partial) reduction of higher levels to lower ones without skipping any intermediate levels, is adopted. Finally moderate reductionism is found to be consistent with a certain variety of pluralism, characterized as naturalistic.


Evidence for enhanced uptake of ATP by liver and kidney in hemorrhagic shock.

It has been shown that infusion of ATP-MgCl2 proved beneficial in the treatment of shock; however, it is not known whether this effect is due to improvement in the microcirculation or direct provision of energy or a combination of the above or other effects. To elucidate the mechanism of the salutary effect of ATP-MgCl2, we have now examined the in vitro uptake of ATP by liver and kidney of animals in shock. Rats were bled to a mean arterial pressure of 40 Torr and so maintained for 2 hrs. After the rats were killed, liver and kidney were removed and slices of tissue (0.3-0.5 mm thick) were incubated for 1 h in 1.0 ml of Krebs-HCO3 buffer containing 10 mM glucose, 5 mM MgCl2, and 5 mM [8-14C]ATP or 5 mM [8-14C]ADP, or 5 mM [8-14C]AMP, or 5 mM [8-14C]adenosine in 95% O2-5% CO2 and then homogenized. Tissue and medium samples were subjected to electrophoresis to separate and measure the various nucleotides. The uptake of [14C]ATP but not that of [14C]ADP or [14C]adenosine by liver and kidney slices from animals in shock was 2.5 times greater than the corresponding uptake by control slices. Thus, the beneficial effect of ATP-MgCl2 in shock could be due to provision of energy directly to tissue in which ATP levels were lowered.


Fitting straight lines to experimental data.

The problem associated with use of statistical methods for determining a best linear relationship of the form Y = AX +B have been examined for a condition quite prevalent with experimental research, i.e., when the values of both variables are subject to essentially unknown errors. Under this condition standard least-squares regression analysis underestimates the value of the slope A. A very simple method for determining the best value of the slope and intercept has been introduced which can be used when errors are present in both variables. With this proposed method, the calculated slope is equal to the standard error of Y divided by the standard error of X (with the appropriate sign) and the intercept is found from the mean values of X and Y, i.e., B = Y - AX. The best estimate of the slope is also equal to the slope found with the conventional regression method divided by the absolute value of the correlation coefficient. The line determined with the suggested method can be considered to be a line of symmetry through the data.


Suppression of pineal multiunit response to flash after habenular lesion in quail.

Habenular nuclei were completely destroyed in male photostimulated and nonphotostimulated quail (Coturnix coturnix japonica). Lesion of the nuclei habenulae led to a markedly increased pineal multiunit activity (MUA) pattern in both long and short daily photoperiods compared to control values. Intact, as well as habenular lesioned birds, showed a lower level of pineal MUA under long-day rearing than under short-day rearing. The decrease in pineal firing rates found in controls under repetitive flash-light stimulations was suppressed in quail bearing habenular lesions. Data are compared to results obtained in sympathectomized and blinded birds. It is suggested that some acute photic information might reach the pineal organ through retinal receptors and habenular pathways. However chronic influence of lighting on pineal MUA, mediated by the retina, does not seem to involve habenular or cervical sympathetic pathways in quail.


Blood-brain amino acid transport and content during anoxia and reoxygenation.

The isolated dog brain preparation was used to investigate the dynamics of cerebral amino acid metabolism during perfusion with anoxic blood (PO2 less than 10 mmHg). Significant uptake of histidine and lysine, as determined by arteriovenous (A-V) differences in whole blood samples, was observed during 30 min of cerebral anoxia. The A-V differences determined from plasma samples indicated that uptake of histidine and efflux of glutamic acid and proline had occurred. Nitrogen balance in the preparation appeared to be maintained. Thirty minutes of anoxic perfusion resulted in increased tissue concentrations of five essential amino acids (methionine, histidine, leucine, lysine, and valine) and a decreased tissue level of the essential amino acids threonine and phenylalanine. Taurine, gamma-aminobutyric acid, alanine, glycerophosphoethanolamine and phosphoethanolamine also increased, whereas the aspartic acid concentration declined. When aerobic perfusion was resumed, the total pool of essential amino acids continued to increase and was nearly twice normal after 120 min of reperfusion. The combined concentration of asparagine and glutamine, serine, alpha-aminobutyric acid, and cystathionine also increased during postanoxic perfusion. Only taurine and phenylalanine concentrations returned toward normal.


Relationship between plasma and cerebrospinal fluid insulin levels of dogs.

Several experiments are reported in which insulin or glucose was administered intravenously to anesthetized dogs. Plasma and cerebrospinal fluid levels of glucose and immunoreactive insulin were determined at several intervals before and after the administrations. Intravenous insulin (0.2 U/kg) administered as either a pulse or a 1-h infusion caused a large increase of plasma insulin, but a relatively small increase of cerebrospinal fluid insulin. When endogenous insulin was elevated by the administration of glucose (100 mg/kg), cerebrospinal fluid insulin changed only slightly. A significant correlation was found between steady-state plasma and CSF endogenous insulin levels. The results are interpreted to indicate that the level of insulin in the cerebrospinal fluid reflects basal plasma level plus an integral over time of the insulin response to challenge. The implications of such a system are discussed.


Canine gastric emptying of solids and liquids.

In four dogs, gastric emptying of a digestible solid (50 g of liver tagged with [57Co]-cyanocobalamine and diced into 1-cm cubes), an indigestible solid (40 radiopaque plastic spheres, diameter 7mm), and a liquid (400 ml of either 1 or 10% dextrose tagged with polyethylene[1,2-3H]glycol were simultaneously assessed by quantitating the rate of appearance of the gastric markers in the duodenum. The rate of gastric emptying of cubed liver was similar whether the liver was given alone or with solutions of the rapidly emptying 1% dextrose, but its rate of emptying was slowed by the slower emptying 10% dextrose. Homogenization of the liver speeded its emptying. Moreover, the homogenized liver emptied even faster when dispersed in 1% dextrose and emptied more slowly when dispersed in 10% dextrose, but in both instances the liver emptied at the same rate as the solution in which it was mixed. Indigestible spheres were nearly all retained, whereas the liver and the dextrose were emptied. Our conclusion is that the stomach empties liquids and retains solids for reduction to a smaller size, after which they are discharged at the same rates as the liquid then present in the stomach.


Synthesis of macromolecules by intestinal cells incubated with ammonia.

Mucosal cells isolated from the small intestine of chicks and rats were incubated with concentrations of ammonia normally found in the intestinal tract of mammals and birds. NH4Cl added to the incubation medium increased glucose metabolism in cells from both species. Ammonia stimulated incorporation of precursors into RNA and decarboxylation of orotic acid by cells isolated from chickens, but an increase in incorporation of precursors into DNA was not observed in cells from either species. Cultured embryonic chicken duodena showed increased incorporation of orotate into RNA with NH4Cl added to the medium. Rats immunized against jack bean urease showed lower urease activity per gram of dry intestinal content, lower intestinal weight, lower mucosal cell, and total gut protein and less protein per unit weight of DNA in the mucosal cell fraction. The results are compatible with the conclusion that ammonia PRODUCED IN THE INTESTINE BY BACTERIAL UREASES CAUSES SIGNIFICANT CHANGES IN THE CONTENT OF RNA and protein in intestine cells.


Changes in protein synthesis after trauma: importance of nutrition.

The effect of trauma (femur fracture) on protein synthesis in rats given four different parenterally administered nutrient formulations ("diets") was investigated. Diet I was a maintenance formulation. It contained sufficient amino acids and glucose to keep the rats in nitrogen balance but was inadequate to support growth. Diet II was amino acids only, diet III was severely hypocaloric glucose, and diet IV was diet I minus the amino acids. The rats received parenterally all nutrients for the duration of the 4-5 day study. Twenty-four hours posttrauma, the fractional synthesis rates of liver, lung, heart, kidney, and muscle were estimated by infusing [15N]glycine for 17.5-19 h. (T.P. Stein, J.C. Oram-Smith, M.J. Leskiw, H.W. Wallace, L.C. Long, and J.M. Leonard. The effects of protein  and calorie restriction on protein synthesis in the rat. Am. J. Physiol. 230: 1321-1326, 1976.) Two trends were found: i) on the amino acid-containing diets (I and II), most protein synthesis rates were increased posttrauma. Lung was the exception: no change was found; ii) rats on the amino acid deficient diets (III and IV) showed a decrease in the fractional muscle and lung synthesis rates posttrauma. We concluded that in this rat trauma model the requirement is mostly for amino acid nitrogen posttrauma.


Renal lymph protein in the rat.

Renal lymph and systemic (posterior) lymph were studied in hydropenic rats. As a consequence of the anatomical arrangement of collecting lymphatics near the kidney, mixed renal and systemic lymph tributaries are situated in such a way that sampling pure renal lymph is difficult. Pure renal lymph contains 1.0 +/- 0.1 g/100 ml total protein with an albumin-to-globulin (A/G) ratio of 2.1 +/- 0.1. Mixed renal and extrarenal lymphatic tributaries contain 3.3 +/- 0.2 g/100 ml total protein with an A/G ratio of 1.8 +/- 0.2. Corresponding values in the plasma are 4.9 +/- 0.2 and 1.2 +/- 0.1 g/100 ml, respectively. Previous studies in which the concentration of renal lymph protein was determined as 30-50% of that in plasma were probably in error due to contamination of renal samples by posterior lymph ducts. The amount of systemic and renal lymph mixing is highly variable from one animal to another. Our renal lymph samples in carefully controlled and prepared Munich-Wistar rats contained a total protein uniformly 20% of that in plasma.


Development of chronic perinephritic hypertension in dogs without volume expansion.

The theory of whole body autoregulation to explain the pathogenesis of experimental renal hypertension states that hypertension is initiated in response to an early increase in salt and water retention and a subsequent elevation of the cardiac output. This hypothesis was evaluated in the present study. Dogs (n,5) were made hypertensive by wrapping the left kidney in cellophane and removing the contralateral kidney 3 wk later. One week prior to right nephrectomy, the dogs were volume depleted by placing them on a low sodium intake (less than 3 meq of sodium/day) and giving them a mercurial diuretic for the first 3 days of the diet. This superimposed sodium depletion (negative sodium balance of 137 +/- 17 meq) increased plasma renin activity 3-5 times but did not change arterial pressure or heart rate. Within 2 days after nephrectomy, the mean arterial pressure increased from the control level of 105 +/- 1 to 135 +/- 6 mmHg (P less than 0.005) and pressure remained elevated throughout an additional 4-wk period in which volume depletion was enforced. The present study suggests, therefore, that initial blood volume expansion with such possible consequences as elevated cardiac output are not essential to the pathogenesis of experimental renal hypertension.


Renal hemodynamics in the rat before and during inhibition of angiotensin II.

Renal blood flow (RBF) was measured with a noncannulating electromagnetic flow transducer in anesthetized rats which had been maintained for 3-5 wk on low, normal, or high salt plus deoxycorticosterone diets. After base-line observations, one of two dissimilar inhibitors of the renin-angiotensin system, angiotensin I converting enzyme inhibitor SQ 20881 or the structural analogue [Sar1,Ala8]angiotensin II was administered intravenously. The employed doses of SQ 20881 and [Sar1,Ala8]angiotensin II effectively inhibited the pressor and renal vasoconstrictor responses induced by exogenous angiotensin I and II, respectively, in each dietary group. Both inhibitors vasodilated kidneys in salt-restricted rats; however, neither affected base-line renal hemodynamics in salt-loaded rats. Pressure-flow relationships were evaluated by clamping the aorta to reduce renal perfusion pressure. Renal blood flow was autoregulated between 100 and 140 mmHg with the same efficiency before and during inhibition of angiotensin II in each dietary group. These data indicate that angiotensin II modifies base-line RBF and renal vascular resistance and are consistent with the view that the renin-angiotensin system is not an essential mechanism responsible for autoregulation of RBF in the rat.


Bicarbonate transport by isolated perfused rabbit proximal convoluted tubules.

Proximal convoluted tubules were dissected from rabbit kidneys and perfused in vitro in order to investigate the relationship between the reabsorption of fluid and of bicarbonate. Bicarbonate was absorbed when it was initially present in the perfusate. At slow rates of perfusion the mean concentration of total CO2 was 9 mM in collected fluid with 25 mM bicarbonate in the bath. At faster rates of perfusion the mean rate of reabsorption was 13.6 pmol cm-1 tubule length s-1. Absorption of bicarbonate was inhibited to a large but not complete extent by elimination of sodium from the perfusate and bath or potassium from the bath, and by addition of ouabain. It was not inhibited by elimination of the organic solutes from the perfusate nor by elimination of chloride from the perfusate and bath. Considered with previous measurements of fluid absorption these results are consistent with the existence of a linked sodium-for-hydrogen ion exchange mechanism at the luminal border of the tubule cells, but there are other possibilities which are discussed. Additionally, the effect of acetazolamide was investigated. The drug virtually completely inhibited bicarbonate absorption and inhibited fluid absorption by 30-40%.


Relation of distal tubular delivery and reabsorptive rate to nephron filtration.

The tubuloglomerular feedback hypothesis states that filtration rate in a single nephron unit (SNGFR) is controlled or modified through variations in the rate of either distal delivery or tubular reabsorption in that same nephron. We have reexamined this hypothesis by varying the perfusion rate of the late proximal tubule from normal (10 nl/min) to supranormal values (30 nl/min) in a reversible fashion and measured the resultant nephron filtration rate. Three perfusion fluid were utilized: group I, a solution simulating late proximal tubular fluid (11 mM HCO3); group II, a solution with a higher HCO3 concentration (30 mM HCO3); and group III, a solution simulating early proximal tubular fluid. In group I SNGFR was 27.2 nl/min during perfusion from the late proximal tubule at 10 nl/min and fell to 19.8 nl/min during the 30 nl/min perfusion rate. Group II SNGFR was 27.7 nl/min at the 10 nl/min rate and 19.0 nl/min during the 30 nl/min perfusion. Groups I and II then demonstrated a completely reversible tubuloglomerular feedback response. In group III, the SNGFR at 10 nl/min was 26.2 nl/min and 23.4 nl/min at the 30 nl/min perfusion rate and were significantly different. Evaluation of collections of distal tubule fluid in perfused nephrons revealed that increased absolute reabsorption of water and chloride between late proximal and distal tubules was associated with the reductions in SNGFR in the same nephron. A strong candidate for the afferent limb of this system is the change in absolute chloride reabsorption between late proximal and distal tubules.


Effect of basement membrane and colloid osmotic pressure on renal tubule cell volume.

Renal tubule cell volume is thought to be kept constant by a cation pump. When active transport is blocked, intracellular impermeant solutes cause cells to swell. Cell size is then determined by transmembrane hydrostatic and colloid osmotic forces. We studied the importance of passive transmembrane forces in determining cell size in isolated rabbit proximal straight tubules (PST). We blocked active solute transport with ouabain and evaluated subsequent changes in cell size by measuring outer diameter of nonperfused tubules. Tubules in a ouabain and 6 g/100 ml protein bath swelled only 40% above control. However, removal of the tubule basement membrane with collagenase dissipated a transmembrane hydrostatic pressure and caused more swelling. Final cell volume was determined largely by bath protein concentration. Tubules in ouabain and collagenase swelled enormously in hyponcotic protein, moderately in isoncotic protein, and could be shrunk below control in hyperoncotic protein. Intracellular colloid osmotic pressure was estimated to exceed 38 cmH20. We conclude that hydrostatic and colloid osmotic forces are major determinants of cell size in isolated PST treated with ouabain.


Tubular localization of adaptation to dietary phosphate in rats.

The renal tubule of rats adapts its transport capacity for inorganic phosphate (Pi) in response to changes in dietary Pi intake. Tubular localization of this adaptation was studied in rats pair-fed for 10 days a low (LPD), i.e., 0.2 g/100 g, or a high (HPD), i.e., 1.8 g/100 g, phosphorus diet. Free-flow micropunctures under acute Pi infusion were made at elevated but similar filtered loads of Pi: LPD, 6.07 +/- 0.29 (n, 32); HPD 5.34 +/- 0.24 (n, 33) micromol/kidney per min. Fractional excretion of Pi (FEPi) for the whole kidney was: LPD, 0.26 +/- 0.02 (n, 32); HPD, 0.67 +/- 0.02 (n, 33) (P less than 0.001). The fraction of filtered Pi found at various puncture sites suggests that part of the adaptation to dietary Pi occurs in the early proximal tubule. An effect in the later portion of the proximal convoluted tubule cannot be excluded in the present experiments. Furthermore, dietary Pi affects markedly the difference in Pi delivery between distal tubule and final urine. This could be due to a greater adaptive response of deep nephrons. Alternatively, the results could also indicate that an adaptation with a secretory component takes place along the terminal part of the nephrons.


Statistical models for renal micropuncture studies.

Statistical issues relating to data analysis of re-collection micropuncture experiments are presented. In the presence of significant animal-treatment interaction, namely, differential response of each animal at different levels of the treatment, the conventional paired or unpaired t testing would not be entirely appropriate. Accordingly, two analysis of variance (ANOVA) models have been derived for the appropriate paired and unpaired designs of micropuncture experiments. Interactive computer programs have been written for both these analyses, and the results are illustrated with experimental data. An example is presented in which the results are statistically significant with paired t testing and by analysis of variance for unequal number of tubules but not when the animal-treatment interaction is included in the analysis of variance model. To investigate linkage in renal transport mechanisms, we propose the use of partial correlation analysis. Experimental results from our laboratory are used to illustrate these techniques.


Myocardial oxygen consumption: the role of wall force and shortening.

The relationship between the force in the left ventricular wall during systole and myocardial O2 consumption (MVO2) was determined. In addition, the relative influence of the load imposed during shortening and fiber shortening on MVO2 was assessed. For this purpose, 14 servo-regulated, paced, isolated canine hearts were used and the steady-state response in total coronary flow and arteriovenous oxygen difference was measured. For both the isovolumetrically beating and the ejecting ventricle, statistically significant linear relations were observed between MVO2 and the integral of systolic force. These relations were not significantly different from one another, indicating that shortening was not a determinant of MVO2. Moreover, when ejecting an isolumetric beats of equivalent developed force were compared, a difference in MVO2 (deltaMVO2) was found. deltaMVO2 was a function of the force integral difference between these contractions and not fiber shortening. Thus, under the conditions of this experiment, the integral of systolic force that includes developed force and shortening load is the predominant factor regulating MVO2 for any given contractile state, whereas the influence of fiber shortening is negligible.


Chronology and mode of reinnervation of the surgically denervated canine heart: functional and chemical correlates.

This study was undertaken to evaluate functionally the time and pattern of inotropic and chronotropic efferent cardiac reinnervation of the deneravated canine heart and to correlate functional data with regional myocardial catecholamine content and supersensitivity to norepinephrine. Our data indicate that efferent autonomic reinnervation takes place first in the atria, followed by a base-to-apex sequence in the ventricles, and that such reinnervation is functionally effective 9-12 mo after denervation. The return of neural function parallels the return of measurable quantities of myocardial norepinephrine and is accompanied by a decrease in supersensitivity to exogenous norepinephrine. The return to apparently complete functional reinnervation, however, cannot be quantitatively related to myocardial levels of catecholamine. Segmental myocardial supersensitivity to norepinephrine is sequentially reversed during progressive adrenergic reinnervation.


Positive inotropic response to inosine in the in situ canine heart.

Effects of inosine on left ventricular contractile force, circumflex blood flow, heart rate, and arterial pressure were investigated in mongrel dogs. Infusion of 50 ml of 10, 25, or 50 mM inosine into the right atrium over 5 min produced arterial blood inosine concentrations of 20-120 microM. Infusion of inosine concentrations of 10 mM or greater produced statistically significant increases in contractile force and circumflex blood flow (P less than 0.05). The increases in contractile force and circumflex blood flow caused by 50 inosine were approximately 40% and 110%, respectively. No statistically significant increases in heart rate or arterial pressure were observed during infusion of inosine at any concentration. Administration of propranolol (2 mg/kg) in no way altered the effects of inosine on contractile force or circumflex blood flow. Thus, the present study suggests that inosine in concentrations which may be produced in the myocardium during stressful conditions causes a substantial effect on the inotropic state of the heart and that the effects of inosine are not mediated through adrenergic mechanisms.


Cardiac function and metabolism during cholinergic stimulation in the newborn lamb.

This study was designed to assess the influences of cholinergic stimulation on coronary flow (CF), oxygen metabolism (MVO2) and contractility (MC) of the left ventricle in the newborn. Nineteen lambs, 1-7 days of age, were anesthetized with pentobarbital (20 mg/kg) and prepared for continuous measurement of CF, heart rate (HR), aortic (AP) and left ventricular end-diastolic (LVEDP) pressures, dP/dt max, and cardiac output (CO). HR, AP, and CO could be controlled as desired. Simultaneous arterial and sinus blood samples were analyzed for O2 content, hematocrit, pH, PO2, and PCO2. LV MVO2 and %O2 extraction (Ext) were calculated. Acetylcholine (ACh) infusion (30-50 microgram/min-kg) caused an increase of LVEDP (4 cmH2O), but no significant change in dP/dt max or HR with constant AP and CO. CF increased by 44%, but MVO2 per beat was unchanged. Similar changes were observed with constant HR (pace). Suramaximal efferent stimulation of right or left vagus nerves produced bradycardia (77-68 beats/min) but no significant changes in contractility, CF, Ext, or MVO2. These findings were unaltered by beta blockade. The changes elicited by ACh infusion or vagal stimulation were abolished by giving atropine. It is concluded that although cholinergic sensitivity can be demonstrated, vagal stimulation does not importantly influence MC, CF, or MVO2 in the lamb. This may relate to incomplete development of the adrenergic system.