Multifocal retinopathy in Borna disease virus infected rabbits. Experimental infection of rabbits with Borna disease virus led in all cases to a multifocal retinopathy that paralleled the clinical neurologic symptoms. The retinal changes always became evident first in the lower anterior quadrant of the eye. Infectious virus and antigen were detected in altered and unaltered regions of the retina. Individual chorioretinal lesions showed destruction of the pigment epithelium and the photoreceptors and perivascular inflammation close to small choroidal veins. Because of maximal antigen accumulation and the focal destruction of the retinal pigment epithelium we consider this cell layer to be the initially damaged structure.


Number of type of inflammatory cells in conjunctiva of asymptomatic contact lens wearers. Biopsy specimens were taken from the upper tarsal conjunctiva of eight asymptomatic contact lens wearers and quantitative histology was determined and compared to histology from 15 normals and 55 patients with contact lens-induced giant papillary conjunctivitis. No abnormalities were detected in the asymptomatic contact lens wearers. One or more of the three tissue characteristics of giant papillary conjunctivitis--(1) mast cells in the epithelium, (2) eosinophils in epithelium or substantia propria, and (3) basophils in epithelium or substantia propria--was found in all patients with this syndrome, but none was present in any of the eight asymptomatic lens wearers. Trauma occurring over months or even years does not induce histologic alteration in the upper tarsal conjunctiva; the surface changes seen previously by scanning electron microscopy in asymptomatic lens wearers are secondary to trauma, not early aspects of the giant papillary conjunctivitis syndrome.


Interstitial keratitis caused by American (mucocutaneous) leishmaniasis. A 58-year-old man with American (mucocutaneous) leishmaniasis had the unusual ocular complication of interstitial keratitis. Although the parasite was not identified, clinical laboratory and histologic findings were compatible with leishmaniasis, and tests ruled out other causes. Ulcerative areas improved after treatment with 1 g of amphotericin B.


Infection after sponge implantation for scleral buckling. In one series of 900 explant scleral buckling procedures, 31 had to be removed over seven years because of contamination. Of 1,000 explants from a parallel series, 27 had to be removed. In the second series, requirement of a sterile conjunctiva preoperatively and the use of prophylactic antibiotics postoperatively did not significantly reduce the rate of infection.


Foveal hypoplasia and bilateral 360-degree peripheral retinal rosettes. A 24-year-old woman had bilateral pendular nystagmus, foveal hypoplasia, 360-degree peripheral retinal rosettes, and hypoplastic ora serrata of nongenetic origin. Kinetic perimetry revealed a generalized constriction of the field. Flicker perimetry revealed general depression of the critical flicker frequencies in the entire field. A slight increase of the threshold for light sensitivity after dark adaptation was noted from 10 to 30 degrees. Haidinger brush phenomenon was abnormal. Color vision was normal. The electroretinogram revealed mild abnormalities in the photopic flicker response. The visual-evoked response, recorded by local macular stimulation, was abnormal. The relationship of foveal hypoplasia to peripheral retinal rosettes in this case may have been caused by an intercurrent infection during the late stages of embryogenesis.


Idoxuridine and bacterial corneal infection. Corneas of 20 rabbits were treated with idoxuridine or a bland ointment before and after their inoculation with Staphylococcus aureus. The rabbit corneas treated with idoxuridine had a significantly more severe keratitis and yielded significantly greater numbers of S. aureus on culture than the rabbit corneas treated with the bland ointment.


Primary radiation therapy for meibomian gland carcinoma. Three patients with Meibomian gland carcinoma were treated initially with irradiation. This therapy was palliative in one case that eventually required orbital exenteration because of recurrent disease. A second patient was clinically tumor-free ten months after treatment when he died of a myocardial infarction. The third patient has shown no evidence of recurrent disease in the 25 months since treatment.


Optic atrophy in acute intermittent porphyria. A 24-year-old woman developed bilateral blindness after recovery from coma secondary to acute intermittent porphyria. Gradual return of vision in the right eye with a permanent unilateral visual field defect and optic atrophy followed. We believe the pathophysiologic mechanism was spasm of the vessels supplying the optic disk leading to ischemia and infarction of the optic nerve.


Oculomotor nerve regeneration after aneurysm surgery. A 57-year-old woman had symptoms of oculomotor nerve palsy first appearing one year before successful surgical ligation of a saccular aneurysm arising from the right posterior cerebral artery. During the subsequent postoperative period of two years, oculomotor nerve functions improved as the result of regeneration. Extensive morphometric evaluation of the regenerated nerve was compared to the normal side at the light microscopic level. The affected nerve showed a reduction in the transverse area (62%), estimated number of fibers (49%), and mean diameter of myelinated axons (23%). The normal g-ratio of axon to total diameter was almost constant at 0.64, but on the regenerated side it increased to 0.73. An increase in unmyelinated axons and connective tissue endoneurium was evident at the ultrastructural level. The significance of these marked quantitative changes was compared to the partial return of oculomotor nerve function.


Removal of preretinal blood during vitrectomy. To remove preretinal blood from the posterior pole, balanced salt solution is irrigated into the eye through a 21-gauge needle. The needle previously used for infusion is used as a port of exit. I have treated seven patients with this method without harmful effects.


Errors in the diagnosis of malignant melanoma of the choroid. We reviewed our consultations and enucleations for suspected choroidal melanomas from 1954 through 1977. Among 876 eyes enucleated here during that period, 203 contained malignant melanomas; among these were 172 with melanomas of the choroid. Eighteen additional eyes contained melanomas of the anterior uvea. Six melanomas were clinically unsuspected. These unsuspected cases represented 2.6% of the 233 eyes in this series of enucleated eyes that were removed because of painful glaucoma, and 3.2% of the 190 uveal melanomas. Our study included eyes enucleated elsewhere after a clinical diagnosis of malignant melanoma was made here. Six of 224 eyes enucleated for clinically suspected melanoma were found to have mimicking lesions, a misdiagnosis rate of 2.7%. Two additional eyes were misdiagnosed as having simulating lesions before histologic confirmation of malignant melanoma after enucleation elsewhere.


Anterior polar cataracts associated with bilateral retinoblastoma. A 13-month-old girl had bilateral congenital cataracts at four days after birth. At age 4 months the cataract in her right eye was observed by her mother to enlarge and change in color. Examination of the fundus disclosed a large yellow mass. The eye was subsequently enucleated and histopathology confirmed the diagnosis of retinoblastoma associated with anterior polar cataract. On routine examination at age 13 months multiple tumors were observed in the fundus of the left eye, and were successfully treated by external beam irradiation. This is the second case reported.


Amaurosis fugax associated with SC hemoglobinopathy and lupus erythematosus. A 23-year-old woman with SC hemoglobinopathy and systemic lupus erythematosus had recurrent amaurosis fugax in her right eye. Extraordinary retinal vascular events were observed and photographed during the amaurotic attacks. Prednisone therapy halted the attacks. We believe a focal lupus vasculopathy involving the central retinal artery caused the amaurosis fugax.


Hereditary pigmented paravenous retinochoroidal atrophy. A father and son with pigmented paravenous retinochoroidal atrophy demonstrated the classical fundus appearance of bilateral sharply circumscribed patches of retinochoroidal atrophy and pigmentation along the retinal veins. Our patients, and the preponderance of males in previously reported cases of this disease, suggest the possibility of Y-chromosome mediated male-to-male transmission. Electrophysiologic findings in our patients included elevated dark-adaptation thresholds, slightly reduced electroretinographic amplitudes, slightly prolonged a- and b-wave implicit times, and (in Case 1) abnormal electro-oculographic ratios. These findings indicate a diffuse tapetoretinal degeneration, and suggest that pigmented paravenous retinochoroidal atrophy is another incomplete form of retinitis pigmentosa.


Clinical evaluation of an inexpensive ultrasound oculometer for ocular biometry. We measured anterior chamber depth and axial length in 200 human eyes with the Echo-Oculometer and the Digital Biometric Ruler. There was good agreement between measurements with the two instruments. The echo-Oculometer is much less expensive than any other instrument available for measuring ocular axial length and satisfactorily provides information for calculation of power of intraocular lenses.


Superficial punctate keratitis of Thygeson associated with scarring and Salzmann's nodular degeneration. A 59-year-old woman with superficial punctate keratitis of Thygeson was observed for 14 years. The patient was treated intermittently with topical corticosteroids and artificial tears. Immediate symptomatic relief was followed by multiple recurrences and exacerbations. This case was atypical because of its prolonged clinical course and development of permanent, subepithelial corneal scarring, and elevated lesions resembling Salzmann's nodular degeneration.


Lymphocyte stimulation by yeast phase Histoplasma capsulatum in presumed ocular histoplasmosis syndrome. We measured skin reactions serum antibody, and lymphocyte stimulation to Histoplasma antigens in a series of patients with presumed ocular histoplasmosis syndrome and in controls. The most sensitive test, lymphocyte stimulation to H. capsulatum sonicate, also correlated with severity of the disease. Lymphocyte stimulation to Histoplasma may be a useful adjunct to the monitoring of presumed ocular histoplasmosis syndrome.


Hazards of bilateral intraocular lens implantation. Seven patients had bilateral intraocular lens implantation performed with a short interval between procedures, using intraocular lenses of unproven design or deficient quality control All seven patients suffered severe visual impairment, some to the level of legal blindness in both eyes. Lenses with unproven design characteristics should never be implanted in both eyes of a patients. The interval between the first and second procedure, even when using lenses of proven design and quality, should be long enough to insure the long-term successful outcome of the first procedure.


Vitamin A-responsive punctate keratopathy in xerophthalmia. Slit-lamp examination of 78 cases of xerophthalmia and 29 controls matched for age, sex, and locale indicated a direct correlation between the presence, density, and extent of punctate epithelial keratopathy and the severity of corneal and noncorneal involvement. Only 7% (four or 58) of control eyes but 60% (six of ten) of cases with confirmed night blindness, 75% (47 of 63) of eyes with conjunctival xerosis, and all eyes with corneal xerosis (47) were affected. Within one week of high-dose systemic vitamin A therapy all affected corneas had improved. None of ten patients receiving low-dose systemic therapy showed any improvement over a two-month period, whereas 61% of involved corneas actually deteriorated in the interim. Punctate epithelial keraptopathy appears to be the earliest corneal manifestation of xerophthalmia, and is already present in the vast majority of cases classically considered free of corneal involvement.


Talc emboli and retinal neovascularization in a drug abuser. A 38-year-old male drug abuser had multiple emboli in the retinal circulation of the posterior pole of both eyes. He showed widespread peripheral retinal capillary nonperfusion and neovascular proliferation at the junction of perfused and nonperfused retina. The emboli were considered to be talc particles from the intravenous administration of suspensions of oral medications. The presumed mechanism of development of neovascularization in this case was the filtering out of the particles by the retinal vasculature with vaso-occlusion, ischemia and subsequent retinal neovascularization.


Gentian violet keratoconjunctivitis.

Gentian violet keratoconjunctivitis. A case of bilateral keratoconjunctivitis caused by self-instillation of a 1% aqueous solution of gentian violet was complicated by a secondary uveitis and gram-negative conjunctivitis. The patient was treated with cycloplegics and specific antibiotics and after resolution of the bacterial infection, a mild topical corticosteroid was used. After six months the patient had completely recovered from the keratitis, but bilateral corneal vascularization, had unilateral posterior synechiae, corneal scarring, and cataract formation were present. Cationic dyes such as gentian violet appear to be toxic to the ocular surfaces and tend to produce severe intraocular inflammation.


Vertical endothelial cell disparity.

Vertical endothelial cell disparity. Endothelial cell counts were performed postoperatively in superior, central, and inferior areas of the cornea in 59 patients. No regional differences were found in a series of 23 preoperative control cataract eyes. A definite, large density disparity was noted in 58 of the 59 postoperative corneas studied. Disparity was high nine years as well as two weeks postoperatively. These data indicated that necessity for accuracy of positioning in postoperative comparison studies and the necessity for regional cell counts before secondary surgical procedures.


Long term follow-up study of a trachoma vaccine trial in villages of Northern India. A field trial of two high titer bivalent trachoma vaccines was done in a rural area of Northern India in children under the age of 6 years. Three months later 310 of the original 451 children in the study received a booster vaccination of either of the two vaccines or a placebo. Both the sucrose gradient purified and the Genetron purified vaccine protected against trachoma infection for one year. Significant protection for two years was found only with the gradient vaccine. A 12-year follow-up study located and examined 201 subjects that had received booster vaccine. It was found that 31, 27, and 28% of the individuals in each of the three groups (two vaccine and placebo) had evidence of mostly minimally active trachoma. Additionally, from 6 to 10% of the subjects in each group had signs of mild to moderate potentially blinding sequelae. The results showed no protection by either vaccine, and there was no evidence of adverse effects from the vaccines.


The ophthalmologic manifestations of sinus histiocytosis with massive lymphadenopathy. Of 113 cases of sinus histiocytosis with massive lymphadenopathy, 13 patients had ophthalmic infiltrates. Eleven of the 13 had infiltrates in the orbital soft tissues, and five of these patients also had eyelid disease. One patient had infiltrates only within the eyelid, and one without disease in the orbit or eyelid had extensive infiltrates in the uveal tract. The microscopic differential diagnosis included a variety of lymphoreticular malignancies, storage diseases, histiocytosis X, rhinoscleroma, tuberculosis, and inflammatory pseudotumor of the orbit. These 13 patients with ophthalmic disease were similar clinically and pathologically to patients with sinus histiocytosis with massive lymphadenopathy who did not have ophthalmic disease.


Leiomyoma of the orbit.

Leiomyoma of the orbit. A 5-year-old boy had a one-year history of inability to adduct the left eye and redness. Examination showed a medial orbital mass indenting the globe without proptosis. A well-encapsulated mass was removed surgically. On light microscopy it seemed to be a neurofibroma. Transmission electron microscopy showed that the tumor was composed of cells with cigar-shaped nuclei, cytoplasmic and plasmalemmal densities, fine filaments, surface-connected vesicles, and basement membrane. These features were characteristic of leiomyoma.


Prostaglandins in human tears.

Prostaglandins in human tears. We detected small quantities of prostaglandin F in tear fluid of patients with clinically normal conjunctivae. The prostaglandin F levels were significantly increased in tear fluid or patients with acute vernal conjunctivitis and chronic trachoma. We could not determine the source of prostaglandin in tears.


An ultrastructural, cytochemical, and autoradiographic study of the mucous membrane of the human cervical canal with reference to subcolumnar basal cells. This study presents a detailed ultrastructural examination of the human endocervix with evidence for the differentiation of subcolumnar basal cells into mucus-secreting cells and ciliated columnar cells. Cytochemical studies in which peroxidatic activity was used indicate that there are two cell types in the endocervical mucosa which can be distinguished by different localization of reaction product. It may be that estrogen sensitivity accounts for such differences. Autoradiographic investigations demonstrated that glandular cells and subcolumnar basal cells synthesize DNA in premenopausal and postmenopausal women. In addition, subcolumnar basal cells actively synthesized RNA, reflecting their ability for further growth and development.


Role of endothelium and hypercholesterolemia in intimal thickening and lipid accumulation. In experiments reported here we tested the hypothesis that persistent absence of endothelium favors intimal thickening, lipid accumulation, and atherosclerosis. Rabbit aortas were de-endothelialized with a balloon catheter at Day 0. Initially, all rabbits were fed a diet low in lipid. Some rabbits (Group I) were continued on a diet low in lipid for 8 to 20 weeks after de-endothelialization. Beginning 4 to 9 weeks after de-endothelialization, other rabbits were fed semisynthetic lipid-rich diets (Group II) or cholesterol-supplemented diets (Groups III) for 4 to 20 weeks. Lipid accumulation in all groups was significantly greater in the re-endothelialized intima than in adjacent intima lacking an endothelial lining. In aortas of Groups I, II, and III the degree of intimal thickening was significantly greater in re-endothelialized areas than in adjacent areas lacking endothelium. Intimal thickness was enhanced in re-endothelialized areas of hypercholesterolemic rabbits of Group III compared with normocholesterolemic rabbits of Group I but not in areas lacking endothelium. Thus, results of these experiments do not support the hypothesis that the absence of endothelium particularly favors intimal thickening and intimal lipid accumulation. Results indicate that intima covered by regenerated endothelium is significantly thicker and more likely to accumulate lipid.


Cell interactions in the initial contact between cultured melanoma cells and syngeneic macrophages. Thioglycolate-induces peritoneal macrophages from melanoma-bearing mice (immune macrophages) or from control mice (control macrophages) were cultured with syngeneic melanoma cells (P51) to determine the surface characteristics of the effector cells during interaction and destruction of the target cells. After a short culture period (3 hours), immune macrophages had extensive connections via filopodia and ruffled membranes to the surfaces of the melanoma cells; control macrophages did not exhibit the same behavior. A dense region in the cytoplasm immediately beneath the macrophage plasmalemma was observed at the point of contact with the target tumor cell. With longer periods of culture (24 hours), effector cells began phagocytosis of the target cells; immune macrophages, however, had more fine filopodial connections and were more cytostatic than were controls. These observations indicate that one of the initial mechanisms of tumor cell destruction was contact-induced lysis, with phagocytosis playing a minor part.


Pneumatosis pulmonalis: a complication of the idiopathic respiratory distress syndrome. Interstitial emphysema of the lung is a well-recognized complication of the idiopathic respiratory distress syndrome. Its incidence has increased with the recent more aggressive therapy for this disease, and persistence of the emphysema in a large number of patients has been observed. This report describes the clinical complications, changes in the roentgenographic pattern, and, particularly, the characteristic morphologic findings in these patients, which delineate persistent pulmonary emphysema as a distinct entity.


Pulmonary morphology in a multihospital collaborative extracorporeal membrane oxygenation project. I. Light microscopy. This report presents the light microscopic morphology found at autopsy in 59 patients who participated in an organized controlled trial of extracorporeal oxygenation as therapy for acute respiratory failure. Observations were recorded as objectively as possible and were analyzed by computer. The experimental therapy produced no specific alteration in the observed pulmonary lesions. Many of the lesions tabulated had significant correlation coefficients with time, all of which were higher when correlated with the duration of respiratory failure than with the duration of the entire acute illness. The rapid progression of the lesions to fibrosis is emphasized as is the predilection of both early and late lesions to involve alveolar ducts to a far greater degree than the distal alveolar spaces. A unifying mechanistic hypothesis consistent with these observations, as well as others, is that the lesions may result as much from oxygen damage as from the original acute illness.


Myelin deficiency (md): a neurologic mutant in the Wistar rat. Myelin deficiency (md), a newly discovered neurologic mutation in the Wistar rat, is transmitted by an X-linked, recessive lethal gene. Male rats are affected, and the first symptom is a head tremor recognizable at 12 to 15 days of age. The tremors become generalized within a few days and disappear when the animal is at rest. In the later stages, from 17 to 21 days of age, the slightest disturbance will precipitate a generalized seizure. Pups die within 30 days after birth. The only gross postmortem change is a gray color of the spinal cord instead of its normally white appearance. Microscopic findings reveal total lack of myelin formation at all levels of the central nervous system.


Pulmonary neutral fat embolism in dogs.

Pulmonary neutral fat embolism in dogs. Twenty-two adult dogs were each given a single, 30-minute injection of 1.5 ml/kg body weight of pure triolein, and their pulmonary, hepatic, renal, and cerebral morphology was observed for 1, 2, 3, 4, 5, 6, 15, 24, and 48 hours; 3,4, and 5 days; 1 and 2 weeks; and 1 month after the injection. A picture of massive capillary occlusion by lipid droplets was followed by rapidly resolvable inflammatory pneumopathy of granulomatous type, leaving a normal lung at the end of the experiment. The cleaning of the capillaries may be attributed to the mechanical action of the blood flow and to the inflammatory reaction with evacuation of necrotic cells via the bronchial route. Transient pulmonary edema is attributed to increased pulmonary arterial pressure. There was no intravacular coagulation. The few pulmonary lesions observed after the triolein injection suggest that the chemical theory of neutral fat hydrolysis by pulmonary lipase and the toxicity of free fatty acids that are released should be reconsidered.


Absence of neutral protease and alkaline phosphatase in neutrophils of a case of hairy cell leukemia. Enzymaticaly homogeneous fractions of lymphocytes, monocytes, and neutrophils were isolated by zonal centrifugation from peripheral blood of a patient with hairy cell leukemia, or leukemic reticuloendotheliosis, LRE,(with leukopenia, neutropenia, lymphocytosis, and massive splenomegaly). To detect enzymatic deficiencies, the cells were analyzed quantitatively for six leukocytic enzymes on three occasions: 1) before splenectomy, 2) 5 days after splenectomy, and 3) 6 weeks after splenectomy. Before splenectomy, the patient's cells showed moderate deficiency of beta-glucuronidase in lymphocytes and monocytes; server to modorate deficiency of lysozyme and myeloperoxidase in monocytes and granulocytes; and complete absence of neutral protease and alkaline phosphates in neutrophils. Full restoration of neutral protease and a three-fold rise in alkaline phosphatase activities occurred in the patient's neutrophils 5 days after splenectomy. Lysozyme and myeloperoxidase returned to normal in both monocytes and neutrophils of the patient. Six weeks following splenectomy, the alkaline phosphatase activity again disappeared from patient's neutrophils, although neutral protease remained normal. The patient's lymphocytes were unresponsive to PHA and PW mitogen before splenectomy but became responsive 6 weeks postoperatively. Monocytic transfomation into macrophges was supressed before and after splenectomy. The findings indicate that developmenally, in lymphocytic leukemia, a biochemical defect involves the patient's monocytes and neutrophils much more severely than it affects the leukemic lymphocytes. Functionally, the results partly explain the susceptibility of LRE patients to microbial infections.


In vivo demyelination induced by intraneural injection of anti-galactocerebroside serum: a morphologic study. Intraneural injection of rabbit anti-galactocerebroside (anti-GC) serum produced focaldemyelinative lesions in rat sciatic nerves. Recipient rats developed a sensory motordeficit of the toes and feet on the side injected with anti-GC serum. Schwann cellabnormalities in recipient nerves were apparent by 20 minutes, followed by myelinsplitting and vesiculation over the next 8 hours. Macrophages first appeared in moder-ate numbers by 15 hours, and degraded myelin was completely phagocvtized by 5 days.An acute inflammatory reaction consisting of endoneurial edema, polymorphonuclearcell infiltration, and fibrin extravasation also was prominent. In vivo demyelinativeactivity of rabbit anti-GC serums was removed by pre-incubation with GC or central orperipheral nervous system myelin and was also lost when the serums were heated at 56C for 30 minutes and injected into nerves of rats previously injected with cobra venomfactor. Anti-GC antibodies are present in the serum of rabbits with experimentalallergic neuritis (WNV-EAN) and encephalomyelitis (WM-EAE) produced, respectively,by immunization with whole peripheral nerve or brain white matter and may play arole in the pathogenesis of demyelination in GC-induced EAN, WN-EAN, or WM-EAE.


The public and private sector: a developing partnership in human services. Historically, public and private providers of health and welfare services have functioned in separate, often incompatible, arenas. Drawing from the experience of a private child mental health center, the authors suggest that a more coordinated and collaborative approach would benefit both the public and private sectors, as well as their client populations.


The varieties of readmission: the case against the use of recidivism rates as a measure of program effectiveness. The many kinds and functions of rehospitalization--frequently having little, if anything, to do with the recidivist's psychiatric status per se--are examined. It is suggested that the use of recidivism rates may blind evaluators, program planners, and practitioners to the multiplicity of dynamics involved in the rehospitalization process.


Fifteen years after treatment: a follow-up study of comprehensive vocationally-oriented psychotherapy. The fourth follow-up study of adolescent delinquent boys treated in a community-based program that combined job placement, remedial education, and psychotherapy indicates that the better overall adjustment of the treated group, compared to untreated controls, is maintained well into adulthood. It reaffirms the importance of developing sound, innovative means of reaching adolescents in crisis, and suggests the value of a full-scale replication of the original program.


Conceptualizing structure in a day treatment program for delinquent adolescents. While effective limit-setting is essential to the treatment of delinquents, the burden of providing the necessary structure is likely to be too great for the staff worker to sustain on his own. A program is described in which structure was conceptualized as existing simultaneously at different levels--the physical space, the programmatic organization, and the worker-patient bond--thereby providing programmatic support to the worker in his relationship to patients.


Broken homes, parental psychiatric illness, and female delinquency. Fifty-nine families with delinquent daughters were compared with 59 families, matched on socioeconomic class, with daughters of the same age who were not delinquent. The frequency of broken homes was found to be the strongest distinguishing factor between probands and controls. Parental disabilities appeared to play a part in the incidence of delinquency among girls, particularly when the disabilities result in a broken home.


Differential effects of television programming on preschoolers' cognition, imagination, and social play. Three groups of preschoolers were exposed over two weeks to daily programs of Misterogers Neighborhood, Sesame Street, or a control series of nature and animal films. Specific hypotheses about the effects of program format upon recall of content and upon subsequent behavior were tested. The apparently more slow-paced format and other characteristics of Misterogers were found to yield positive changes, especially for less imaginative children, in imaginative play, affect, concentration, and social interaction.


Working wives and housewives: do they differ in mental status and social adjustment? Matched groups of working wives and housewives drawn from a community sample did not differ on current and past psychiatric symptoms, diagnosis, treatment, and social functioning. They did differ markedly on enjoyment in and satisfaction from their work. The working women derived considerably more satisfaction from their outside jobs than either they or the housewives did from their work in the home.


Family relationships and morale among people 65 years of age and older. The interrelationship of specific types of family relationship--marital and parent-child relations in particular--among older adults is examined. Findings suggest that caution must be exercised when generalizing about the importance of family relationships in the lives of older adults, and that future inquiries should focus on the qualitative aspects of family relations. Suggestions for professionals dealing with older people are offered.


Prosocial behavior and psychopathology in emotionally disturbed boys. Relationships between dimensions of problem behavior and observations of prosocial behavior were explored among a sample of emotionally disturbed boys. Results indicate that anxious/inhibited boys are more likely than less inhibited boys to engage in prosocial behavior. This may be due to their greater empathy in observing the needs of others or, alternatively, to an effort at ingratiation or an overreaction to social distress. The latter possibility suggests that prosocial behavior may reflect or compound the interpersonal difficulties of anxious/inhibited boys.


Fathers, children, and joint custody.

Fathers, children, and joint custody. This survey of 40 middle-class divorced fathers, focusing on father's perceptions of their relationship with their children, suggests that those with joint custody are more likely than those with visitation rights to continue to have a high degree of involvement in and influence on their children's growth and development. It is argued that children of divorce, as do children of intact families, need loving relationships with two parents, and that joint custody arrangements should be encouraged.


Shared parenting after separation and divorce: a study of joint custody. Intensive case studies of four families in which divorced parents have maintained joint custody of their children suggest that this arrangement works well under certain conditions. Components of a successful joint custody arrangement are considered, limitations are discussed, and support is urged for divorcing parents interested in establishing joint custody.


The role of some birth-related variables in father attachment. Forty-six middle-income couples planning different childbirth methods--natural hospital delivery; home delivery; hospital delivery with anesthesia--were studied from the sixth month of pregnancy until six months after the birth. The father's participation in the birth and his attitude toward it were found to constitute the most significant variable in predicting father attachment. prenatal education and structuring of the birth environment are suggested to obtain maximum participation and involvement of fathers.


Effects of the nursing mother-infant dyad on the family. The voluminous literature on breast-feeding is characterized by a narrow, if not exclusive, focus on the mother-infant dyad. This paper describes how the dynamics of the nursing couple can best be understood within the broader context of the family. One father's conflictual reactions to breast-feeding, and the subsequent effects on his nursing wife, are described.


Husbands' problems with breast-feeding.

Husbands' problems with breast-feeding. This paper discusses the importance of educating prospective parents about the stresss thay may be experienced by the father of a nursing infant. Husbands' negative reactions to breast-feeding are considered, and means of alleviating husbands' stress are suggested.


Postural reflexes in man.

Postural reflexes in man. In 40 adult patients stabilized on the tilt table, no evidence was found that the amount of activity at rest in spastic muscles depends on the position of the head in space. The influence of postural labyrinthine reflexes (Magnus) was not confirmed. The activity in spastic extensor muscles was significantly higher (t greater than 1%) in the prone position. The activity in spastic flexor muscles was higher (t greater than 1%) in the supine position. Extralabyrinthine forces (tonic stretch reflexes and exteroceptive reflexes) are assumed to be decisive in these changes. In the same group of patients, the symmetric deep neck reflexes were examined. The patient actively flexed his head forwards or backwards. Significant increase in the activity at rest in spastic extensor muscles on dorsal flexion of the head in the prone position was found (t greater than 1%). Significant increase in the activity at rest in spastic flexor muscles on ventral flexion of the head in the supine position was also found (t greater than 5%). The phenomena of irradiation are assumed to be decisive in these changes. In another group of 27 adults the asymmetric deep neck reflexes (Magnus and De Kleijn) were examined. The patient actively turned his head either to the left or to the right, while his arms were raised (Hoff-Schilder maneuver). When the degree of rotation of the head was slight, the trunk and arms deviated in the same direction. When the rotation of the head was extreme, and reached behind the shoulder, the trunk and arms often reversed the direction of deviation. The effect of asymmetric deep neck reflexes was not confirmed. Visual perception and the mechanism of focusing are assumed to be decisive in these changes. The head turns toward the object of interest in the visual field by the mechanism of eye-centering (Bender) and influences the position of the trunk and motor patterns of the upper extremities (motor principle "eyes-hand").


Effect on maximal strength of submaximal exercise in Duchenne muscular dystrophy. Four Duchenne muscular dystrophy patients, with quadriceps of at least antigravity strength, exercised one quadriceps submaximally 4 or 5 days per week for six months. The exercise was done under supervision and consisted of extending one knee from 90 degrees to full extension using the Cybex isokinetic exerciser. The other side was not exercised at all. The two sides were tested for maximal isokinetic strength monthly for twelve months and at 18 and 24 months after the beginning of the study. On the average, the exercised leg had a greater maximal torque both during and after the exercise period until the torques on both sides decreased to zero. The results indicate that submaximal exercise has no negative effect and may be of limited value in increasing strength in Duchenne muscular dystrophy.


EMG comparison of quadriceps femoris activity during knee extension and straight leg raises. Both knee extension and straight leg raises have been used to rehabilitate atrophied quadriceps musculature following knee immobilization. A comparison of the tension developed during these two exercises was made in each of the three surface quadriceps muscles (quadriceps femoris, vastus lateralis, vastus medialis) at three different levels of activity (20%, 50%, and 80% of 1RM). Integrated EMG (m Volt-seconds) was used to measure tension developed during a seven second contraction. Tension developed was significantly greater during a seven second contraction. Tension developed was significantly greater during knee extension than during straight leg raises at each exercise intensity. For both exercises and at all three exercise levels, the vastus lateralis was the most active; the vastus medialis was the least active. The difference between knee extension and straight leg raises became greater with increasing levels of activity. Therefore, unless contraindicated by chondromalacia of lack of knee flexibility, knee extensions should be used for post-surgical knee rehabilitation. The greater tension development would lead to a more rapid return of strength, and therefore quicker rehabilitation.


Relation between force and fatigability of red and pale skeletal muscles in man. Experiments were performed to test the effect of muscular fatigue on the relationship between smoothed rectified electrical activity (SREMG) and force in human muscles of different fiber compositions. Fatigue was shown to be produced by failure of a mechanism distal to the neuromuscular junction in three muscles tested: biceps brachii, triceps brachii, and adductor pollicis. Fatigue produced changes in SREMG in first dorsal interosseous, suggesting an effect at or proximal to the neuromuscular junction. Fatigue produced changes in the SREMG-force relationship only at high force levels in the pale triceps and biceps brachii, but produced a change throughout the force range in the red adductor pollicis. It is suggested that muscle units composed of pale fibers fatigue selectively in mixed muscles containing many such units, while fatigue effects are more difficult to produce and are distributed more uniformly in predominantly red muscles.


Digital beat-to-beat cardiotachometer.

Digital beat-to-beat cardiotachometer. A beat-to-beat cardiotachometer counting from 27 to 199 beats per minute has been constructed using digital integrated circuits. Power consumption is reduced, and accuracy enhanced, by incorporating a programmed read-only memory. This circuit technique can be employed for other devices, such as digital thermometers, in order to circumvent a nonlinear relationship between voltage and the physiological variable.


Hyperpolarization in mouse parathyroid cells by low calcium. Intracellular microelectrodes were used to record the resting membrane potential of mouse parathyroid cells in vitro. The mean value of the membrane potential in 2.5 mM calcium was -20 mV. Exposure to low-calcium solutions (1.5 mM) caused rapid hyperpolarization to a mean value of -50 mV. The relationship between extracellular calcium and the membrane potential was sigmoid, and the transition between high and low intracellular potentials occurred between 1.5 mM and 2.25 mM calcium. Magnesium, manganese, and lanthanum reversed the low-calcium hyperpolarization. In 1.5 mM calcium solutions, the relationship between external potassium (greater than 10 mM) and the membrane potential was 46 mV per 10-fold change in extracellular potassium. In 2.5 mM calcium solutions, the resting membrane potential was independent of the external potassium concentration. It is concluded that the resting membrane potential of mouse parathyroid cells is highly sensitive to the extracellular concentration of calcium and calcium-like ions. With the low-calcium secretory stimulus, hyperpolarization is accompanied by the development of strong dependence of the resting membrane potential on extracellular potassium levels.


Cellular augmentation of polymorphonuclear leukocyte chemotaxis. The density of neutrophils influences the number of cells that will respond to a chemoattractant, endotoxin-activated serium. When fewer than 3 x 10(5) polymorphonuclear leukocytes (PMN) were placed in the top compartment of a modified Boyden chemotaxis chamber, the cellular response was weak. Complete membrane penetration by activated neutrophils rarely was observed. When this number of PMN was exceeded, however, both the number of cells and the percentage of neutrophils responding to the leukoattractant increased. The density of cells required for effective chemotactic response to occur was such that intimate cell-to-cell contact was suggested. This indicated that PMN exerted a kinetic influence upon one another. Extracts of disrupted PMN induced an otherwise insufficient number of neutrophils to respond to the chemotactic stimulus. The active component was isolated in the cytoplasmic fraction (postcentrifugation, 100,000 x g, 60 min) of PMN, but was not present in other subcellular fractions. This cytoplasmic augmentor of chemotaxis (CACh) increased random mobility of neutrophils, but was not, itself, a chemotactic factor. These findings suggest that PMN cooperate in their response to a leukotactic stimulus.


Properties of motor units of the frog iliofibularis muscle. The tension developed by single motor units of the iliofibularis muscle of the frog Litoria aurea was recorded in response to single-shock and repetitive stimulation of motor axons. The majority of units in each muscle, 13 on the average, were of the twitch type; an additional 4 units were slow or tonic. It appeared that slow units comprised a single homogeneous population, but two types of twitch units could be recognized: small fatigue-resistant units with long twitch times to peak (20--40 ms) and larger, fatigable units with briefer times to peak (16--27 ms). Evidence from a comparison of unit tetanic tensions indicated the presence of polyneuronal innervation of both slow and twitch muscle fibers. The relatively low incidence of polyneuronal innervation of twitch fibers in iliofibularis, when compared with a muscle like sartorius (9), was attributed to the difference in lengths of muscle fibers in the two muscles. It was argued that slow muscle fibers probably receive a multiterminal as well as polyneuronal innervation, with the terminals of any one axon lying widely spaced along the muscle fiber.


Placental transfer of water and nonelectrolytes during a single circulatory passage. A bolus of a 14C-labeled nonelectrolyte and tritiated water was injected into the maternal arterial system supplying the uterine circulation. Blood was sampled immediately on the fetal side of the placenta from the umbilical vein. A placental transfer index (PTI) was calculated from the ratio of the tracers in the fetal blood divided by the ratio of the tracers in the injectate. Placental transfer was measured for 11 nonelectrolytes in anesthetized guinea pigs and 8 nonelectrolytes in unanesthetized sheep. Placental transfer in both species was determined by molecular weight and lipid solubility. The PTI measured for the lipophilic solutes antipyrine and 1,6-hexanediol were less than 1, and those for methanol and ethanol were greater than 1. We conclude that placental transfer for water and small (mol wt less than 200) lipid-soluble nonelectrolytes is limited  by diffusion as well as by blood flow.


Distribution of ionic sulfate, lithium, and bromide across the sheep placenta. Salts of sulfate, lithium, and bromine were injected or infused intravenously into ewes in the last trimester of gestation. Ewes and fetuses had indwelling catheters; most fetuses were nephrectomized. Concentrations were measured in paired maternal and fetal samples over periods of 4--14 days. Maternal excretion of sulfate was too rapid to permit near equilibration of fetal and maternal plasma concentrations; the results, however, did not support the existence of a large potential difference across the exchange barrier. The concentrations of Li+ (given by continuous infusion) and 82Br- in maternal plasma did not change rapidly. The concentrations of these tracers in fetal plasma rose until they were nearly equal to the maternal plasma concentrations. Steady-state transplacental potentials, calculated by use of the Nernst equation, were 5.2 +/- 2.0 (SEM) mV (n = 26) for Li+ and -2.2 +/- 0.8 (SEM) mV (n = 10) for Br-. Nernst potentials calculated from previously measured maternal and fetal plasma concentrations of Na+, K+, Mg2+, and Cl- were +0.4, +3.6, +0.5, and -1.4 mV. We concluded that, of the total potential difference of about -50 mV (fetus negative) between the fetal lamb and the ewe, only a few mV are dropped across the placental exchange barrier.


Substrate oxidation specificity in different types of mammalian muscle. The maximal capacity of homogenates prepared from cardiac, fast-oxidative-glycogenolytic (FOG) vastus lateralis, fast-glycogenolytic (FG) vastus lateralis, and slow-oxidative (SO) soleus muscle to oxidize pyruvate, palmitate, alpha-glycerophosphate, and acetoacetate was assessed by measuring oxygen consumption under conditions of nonlimiting substrate and cofactors. Pyruvate oxidation varied eight-fold among the muscle types and was highest in cardiac, followed by FOG, SO, and FG muscle. Palmitate was oxidized at 97%, 85%, 77%, and 57% of the relative rate for pyruvate in cardiac, FOG, SO, and FG muscle, respectively. In contrast, alpha-glycerophosphate oxidation rates were highest in FG muscle, followed by cardiac, FOG, and SO muscle. Although cardiac muscle possessed the highest absolute rate for acetoacetate oxidation, it had the lowest capacity relative to pyruvate (19%), whereas SO muscle possessed the highest (61%). FOG and FG muscle had similar relative capacities for this substrate (30%). These results provide further evidence to suggest that mammalian muscle types are differentiated in terms of both mitochondrial mass and substrate oxidation specificity.


Sarcomere motion in isolated cardiac cells. Computerized image-analysis techniques have been employed to examine the sarcomere dynamics of isolated mammalian cardiac myocytes. The cells were prepared by perfusion of adult rabbit hearts with hyaluronidase-collagenase solutions; they exhibited phasic contractions in the presence of 10(-6) M Ca2+. The dissociated cells were visualized by phase microscopy and a video camera interfaced in a minicomputer. Digitized cell images were processed by an algorithm utilizing signal averaging and contrast enhancement to yield data showing individual sarcomere position and shortening vs. time, so that patterns of sarcomere activation could be observed in spontaneously contracting cells. Compared to records of whole-cell shortening and of striation displacement, computerized image analysis provided a much more faithful indication of time course and sequence of sarcomere shortening. Spontaneously contracting cells showed sequential sarcomere shortening beginning at one end and propagating longitudinally with a constant velocity, typically at 100--150 micron/s for beat rates of 40 min-1. Velocities of initial sarcomere shortening appeared to increase with elevated Ca2+. These observations are consistent with a regenerative mechanism of calcium-induced calcium release.


Cation exchange and glycoside binding in cultured rat heart cells. The Na/K-exchange characteristics, ouabain-binding kinetics, and Na pump turnover rates of synchronously contracting monolayers of neonatal rat myocardial cells were studied. The cells exchange Na rapidly (T1/2 = 35 s) with a mean Na flux of approximately 25 (pmol/cm2)/s. The half time (T1/2) of K exchange is much longer (12 min); the mean K flux is 13 (pmol/cm2)/s. Active Na/K transport, as measured by K influx, is relatively ouabain sensitive, and 10(-6) M ouabain produces half-maximal inhibition. Ouabain (10(-2)M) inhibits 60% of the Na efflux and 75% of the K influx. The cells bind [3H]ouabain rapidly (T1/2 = 8 min), but release it very slowly (T1/2 = 11 h), and both the amount bound and the rate of binding were inversely proportional to extracellular K. Specific [3H]ouabain binding demonstrates saturation reaching a maximum of 1.6 x 10(6) molecules per cell at 2 x 10(-7) M [3H]ouabain. From cell surface area and ouabain-sensitive flux measurements, the Na pump density was calculated at 720/micrometer2 with an individual pump turnover rate of 50/s. Thus the studies indicate that despite their neonatal origin, the behavior of the Na pump in these cells is very similar to that in other mammalian tissues.


Uptake of unconjugated bilirubin by isolated rat hepatocytes. The mechanism responsible for the hepatic uptake of unconjugated bilirubin was examined in isolated rat hepatocytes from control and phenobartital-pretreated rats. The uptake was extremely rapid and the equilibrium between cell and medium was attained within 60 s with a 100-fold higher concentration in the cell than the medium. The initial velocity of uptake (Vo) exhibited a linear relationship to the bilirubin concentration in the medium. Pretreatment of cells with various metabolic inhibitors had no effect on the uptake of unconjugated bilirubin. Ouabain did significantly decrease Vo, but replacement of sodium ion with choline or lithium had no effect on bilirubin uptake. The organic acids sulfobromophthalein (112 muM) and taurocholic acid (50 (muM) and two steroidal compounds, diethylstilbestrol (50 muM) and spironolactone (50 muM), had no effect on the uptake of bilirubin. It is suggested that bilirubin gains access to the hepatocyte interior by passive diffusion into and through the lipid membrane and that intracellular binding may explain the high degree of bilirubin accumulation associated with the isolated hepatocytes.


Hexose transport and phosphorylation by capillaries isolated from rat brain. Hexose transport and phosphorylation were studied in capillary segments isolated from rat brain. Uptake of 3-O-methyl-D-glucose (3MG) could be inhibited by cytochalasin B, phloretin, and phlorizin, but not by 2,4-dinitrophenol or ouabain. 2-Deoxy-D-glucose (2DG), D-glucose, galactose, and mannose inhibited 3MG uptake, while L-glucose, fructose, and ribose did not. Accelerative exchange diffusion of 3MG was demonstrated. At equilibrium, the intracellular concentration of hexose did not exceed the external concentration, and transport was, therefore, equilibrative rather than accumulative. Transport of 2DG and D-glucose was not rate limiting for metabolism. When incubated in 5 mM D-glucose, the endothelial cells contained a large pool of free glucose. L-Glucose entered capillaries more slowly than other hexoses and served as a marker for simple diffusion of sugars into the cells. Our results suggest that sugar uptake into isolated brain capillaries occurs by a transport system similar to the one responsible for glucose transport across the blood-brain barrier in vivo.


Influence of taurocholate, taurochenodeoxycholate, and taurodehydrocholate on sulfobromophthalein transport into bile. To test the hypothesis that incorporation of sulfobromophthalein (BSP) into mixed micelles could account for the increase in its biliary transport maximum (Tmax) by bile salts, we have compared in hamsters the influence on BSP Tmax of taurocholate and taurochenodeoxycholate (two micelle-forming physiological bile salts) to that of taurodehydrocholate, a bile salt which, in vitro, does not form micelles. In a first series of experiments, it was observed that taurocholate and taurochenodeoxycholate increased the secretion of phospholipid (40 and 53%, respectively), and cholesterol (50 and 110%, respectively), whereas taurodehydrocholate decreased the secretion of phospholipid (-31%) and cholesterol (-43%). This result suggests that, in vivo, taurodehydrocholate or its metabolites do not form mixed micelles. In a second series of experiments, it was seen that the three bile salts induced a similar increase in BSP Tmax (63% with taurocholate, 52% with taurochenodeoxycholate, and 51% with taurodehydrocholate). These results provide circumstantial evidence for the hypothesis that mixed micelle formation is not an important determinant of maximal BSP secretion into bile.


Increased glucagon secretion in protein-fed rats: lack of relationship to plasma amino acids. This investigation was designed to test the hypothesis that protein feeding stimulated glucagon secretion because amino acids liberated during protein digestion function as glucagon secretagogues. Rats were fed high-protein (HP) or control diets for 9--10 days and blood taken from the aorta or portal vein (PV) at 0800, 1300, 1700, 1900, 2100, and 2300 for determination of amino acids, glucose, insulin, and glucagon. Glucose, insulin, and glucagon of control rats showed little change. In HP rats, PV glucose rose during fasting (0800-1700) and declined during feeding (1700-0800), changes that reflected alterations of glucagon and insulin secretion. PV glucagon in HP rats that was elevated 2--4 times rose during fasting, whereas PV and arterial amino acids declined. HP feeding caused enhanced glucagon release that was associated with increased amino acids in PV and arterial plasma, especially the branched-chain group. Although these findings suggest that protein feeding promotes glucagon release because branched-chain amino acids are elevated, these amino acids are known to have little effect on alpha cell function. Thus, we conclude that protein feeding influences glucagon secretion through some mechanism other than increased blood amino acid levels.


Effect of pulseless perfusion on gastrointestinal blood flow and its distribution. The effect of nonpulsatile (NP) arterial perfusion on gastrointestinal organ blood flow and intraorgan flow distribution was studied in 10 anesthetized (pentobarbital) dogs utilizing the radionuclide-labeled microsphere (15 micrometer) technique. Measurements of flow to the stomach, small intestine, and colon were made during a pulsatile perfusion control period and after 1- and 2-h periods of NP perfusion with a centrifugal left ventricular bypass pump (Medtronic). Total gastric blood flow (0.178 +/- 0.021 ml/min per g) as well as the partitioning of that flow between gastric subsegments such as antrum (17% of total gastric flow), body (83%), and mucosa (73%) was not significantly altered during the 2-h period of NP perfusion (P greater than 0.20). Similarly, flow to the intestine showed significant change during NP perfusion. Under conditions of equivalent hemodynamic states (mean perfusion pressure), nonpulsatile arterial perfusion results in no significant alteration in gastrointestinal blood flow or its intraorgan distribution.


Interaction between gastrin, CCK, and secretin on canine antral smooth muscle in vitro. This study compared the actions and interactions of human synthetic gastrin, octapeptide-cholecystokinin (OP-CCK), cholecystokinin (CCK), and secretin on the amplitude of isometric tension developed in strips of dog antral smooth muscle in vitro. Cholecystokinin, OP-CCK, and gastrin produced maximal stimulatory effects at 7.5 x 10(-9), 4.5 x 10(-9), and 3.5 x 10(-9) M, respectively. Secretin alone was ineffective up to 2.5 x 10(-8) M. Observed maximal responses to gastrin, OP-CCK, and CCK tested alone were not significantly different. A submaximal gastrin dose added with OP-CCK, shifted the OP-CCK dose-response curve to the left and significantly reduced the D50, but the calculated maximal response (CMR) did not change. Also, submaximal OP-CCK plus gastrin shifted the gastrin dose-response curve to the left and significantly lowered the D50 with no change in CMR. Secretin decreased CMR but did not change the D50 for gastrin. Responses obtained to gastrin and OP-CCK tested alone were not affected by tetrodotoxin (1 x 10(-5) M), hexamethonium bromide (4 x 10(-5) M), or atropine (1 x 10(-7) M). Larger doses of atropine (5 x 10(-6) M) reduced peptide responses an average 30%. The results indicate that OP-CCK, CCK, and gastrin share a common noncholinergic receptor site. Secretin acts at a different receptor site.


Drug uptake into everted intestinal sacs. I. Enhancement by hypertonicity. The transfer of the cationic drugs, pralidoxime (PAM) and tetraethylammonium, and anionic ampicillin from the mucosal-to-serosal sides of everted rat jejunal sacs is enhanced by mucosal hypertonicity. PAM uptake, which is proportional to initial mucosal concentrations up to 2.3 mM, is enhanced by mucosal hypertonicity due to addition of sodium, potassium, lithium and choline chloride, sodium sulfate, and the nonionic solutes, urea, sucrose, and mannitol. Bicarbonate, Tris, or phosphate buffer and the presence of magnesium and calcium do not affect this hypertonicity-induced acceleration of PAM passage. Serosal osmolality has no effect on transfer and mucosal hypertonicity is equally effective in the presence and absence of a transmural osmotic gradient. This observation and minimal changes in the concentration of inulin placed in the sacs suggest that fluid shifts and solvent drag are not responsible for the enhanced mucosal-to-serosal transfer of PAM from hypertonic buffer. Mucosal hypertonicity at 450 mosmol/kg causes reversible enhancement of PAM transfer, whereas the effect of 600 mosmol/kg cannot be reversed by replacing the tissue in isotonic buffer. The effect of osmotic manipulation on PAM transfer across the intestine thus differs from its effect on the passage of other ionized species and drugs across other epithelia.


Determination of human pancreatic cationic trypsinogen in serum by radioimmunoassay. A specific radioimmunoassay has been developed for human pancreatic cationic trypsin. The assay has been employed for the determination of immunoreactive forms of pancreatic cationic trypsin in blood. The trypsin employed as radioiodinated tracer in the assay was inactivated with tosyl-L-lysine chloromethyl ketone (TLCK) to prevent binding of the tracer to the serum inhibitors while maintaining its immunoreactivity. The average normal serum level determined was 26 ng/ml, with a range of 12--41 ng/ml. Eight of nine patients with acute pancreatic inflammation had at least a 15-fold elevation of total serum immunoreactive cationic trypsin. Cationic trypsinogen and cationic trypsin bound to alpha1-antitrypsin cross-react strongly in the radioimmunoassay. Thus it is possible to measure these potential molecular forms of cationic trypsin in serum. When normal human serum was fractionated on Sephadex G-200, all of the immunoreactive material eluted as a single peak of approximately 23,000 mol wt. No cationic trypsin could be detected in association with alpha1-antitrypsin or alpha2-macroglobulin. The 23,000-mol-wt peak was definitively shown to contain trypsinogen by affinity chromatography and by activation with human enteropeptidase. The identification of cationic trypsinogen in blood implies that the zymogen is secreted into the circulation by the pancreas rather than entering the bloodstream via absorption from the intestine.


Effects of AVP and DDAVP on plasma renin activity and electrolyte excretion in conscious dogs. Uninephrectomized adult female dogs with chronic indwelling catheters were maintained on a low sodium diet and studied without anesthesia. Following hydration with 3% dextrose, an intravenous infusion of either arginine vasopressin (AVP) or of 1-desamino-8-D-arginine vasopressin (DDAVP) was begun. The dose was calculated to achieve a near maximal physiological plasma concentration of AVP, or an equimolar concentration of DDAVP. Both AVP and DDAVP increased urinary osmolality from less than 60 to over 800 mosmol/kg H2O within 1 h. AVP infusion increased mean arterial pressure and renal electrolyte excretion and decreased heart rate and plasma renin activity (PRA), while DDAVP was without effect on these parameters. AVP infused into the renal artery at doses which did not alter systemic pressure and heart rate caused kaliuresis and reduced PRA. We conclude that the AVP-induced inhibition of renin secretion and increase in renal electrolyte excretion are not secondary to increased tubular permeability to water, but must represent a more specific action of AVP which is not shared by DDAVP.


Neural mechanism underlying tachycardia induced by nonhypotensive a-v shunt. The mechanism underlying tachycardia resulting from nonhypotensive arteriovenous shunt (shunt open plus infusion of blood to compensate for the fall in mean arterial pressure resulting from opening of a shunt) was investigated in anesthetized, artificially ventilated dogs. In dogs with intact autonomic innervation, dogs with beta-adrenergic blockage (BB), and dogs with BB plus spinal section at C7 (BBSS), opening of the shunt resulted in tachycardia (P less than 0.01 for all comparisons), which was, however, not significantly different on comparison among groups (P greater than 0.40 for all comparisons). This shows that afferent and efferent sympathetic-mediated reflexes do not play a significant role in this tachycardia response. Additionally, the tachycardia response was significant in dogs with BBSS plus right or left vagotomy, but it was completely abolished in dogs with BBSS plus bilateral vagotomy. This suggests that in dogs with blockade of sympathetic afferent and efferent pathways, tachycardia resulting from nonhypotensive arteriovenous shunt may be due to a cardioacceleratory reflex with its ascending and its descending pathways in each vagus nerve.


Bone blood flow measured by 85 Sr microspheres and bone seeker clearances in the rat. This paper investigates further the relationship between the initial bone clearance of a bone-seeking radioisotope or labeled substance and the bone blood flow. The bone blood flow of rats was modified over the widest possible range of physiological values by heating and cooling their hindlimbs. Osseous blood flow was measured by the arteriolar trapping of labeled microspheres of 15 micrometer diameter injected into the left ventricle. The plasma clearances of 45Ca and 99 m Tc by bone were measured 10 min after the intravenous injection of radiocalcium and of 99 m technetium pyrophosphate. The extraction ratio for 45Ca over the 10-min interval (45Ca clearance/bone plasma flow) was 0.60 for low blood flows, 0.40 for blood flows at rest, and 0.25 for high values of flow. The data for 99 m Tc were, respectively, 0.68, 0.34, and 0.22. Initial bone clearances of either substance should not be used to measure the increases in bone blood flow over the values at rest.


Effects of hypertonic mannitol on cardiac lymph in nonischemic myocardium. This investigation was designed to elucidate the effects of hypertonic mannitol on the nonischemic myocardium. In anesthetized open-chest dogs, we collected cardiac lymph for 2 h before and for 4 h during the infusion of hypertonic mannitol or normal saline. We studied the changes in the volume of lymph flow and the release of lysosomal enzyme acid phosphatase and protein into the cardiac lymph. In group 1 (n = 7) and group 3 (n = 8), the effects of 1-h and 4-h infusions of mannitol were studied, respectively. In these dogs, mannitol caused significant rises in lymph flow and release of total acid phosphatase into the cardiac lymph. In group 3, protein efflux increased significantly. In group 2 (n = 5) and group 4 (n = 4), infusion of normal saline for 1 and 4 h did not significantly change the release of total acid phosphatase and proteins into the cardiac lymph. Thus, infusion of hypertonic mannitol for 1--4 h in the nonischemic myocardium may have some deleterious effects because of its apparent ability to impair lysosomal membranes and to increase capillary permeability.


Contribution of myocardial contractility to myocardial perfusion. Myocardial contractility in open-chest anesthetized (sodium pentobarbital) dogs was varied while ventricular pressure, coronary perfusion pressure, and coronary tone were held constant. Under those conditions, changes in regional blood flow should reflect changes only in intramyocardial compression related to the altered inotropic state. Increasing contractility with isoproterenol caused flow to decrease in the outer myocardial layers without change at the subendocardium. When contractility was decreased with pentobarbital, flow at the subendocardium was increased with little change in the outer layers. By manipulating perfusion pressure in the latter experiments it was demonstrated that subendocardial compression was falling from a starting value that was somewhat above peak ventricular pressure.


Central interaction between the baroreceptor reflexes from the carotid sinus and aortic arch. The cardiovascular response to combined stimulation of the aortic nerve (AN) and carotid sinus nerve (CSN) with trains of electrical stimuli was studied in dogs under morphine-chloralose anesthesia. Combined stimulation of both nerves ipsilaterally resulted in systemic arterial depressor responses and cardiac slowing that were 59% and 77% greater (P less than 0.05) than the respective sum of the responses to separate stimulation of these nerves. The depressor response to combined stimulation of these nerves contralaterally was not different (P greater than 0.05) from the sum of the separate responses. However, cardiac slowing to contralateral stimulation of the nerves remained 43% greater (P less than 0.05) than the sum of the individual responses. The results suggest that an interaction between the aortic and carotid baroreceptor reflexes occurs centrally, which causes a greater than additive effect on the autonomic output. The degree of interaction between the reflexes did not change as the delay between the stimulus trains was varied over an interval of 0 and 100 ms. At intervals greater than 100 ms the reflex responses were additive.


Stimulation of arteriolar number by salbutamol in spontaneously hypertensive rats. Experiments were performed to study beta2-adrenergic involvement in arteriolar development in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. Newly weaned 20-day WKY and SHR rats were injected with salbutamol, a selective beta2-agonist (50 microgram/day sc, plus 5 mg/100 ml in drinking water), for 20 days. At 40 days, under 2% chloralose-7.5% urethan anesthesia (6 ml/kg), either the cremaster muscle was prepared for in vivo microscopy to estimate the number and diameter of open arterioles or the arterioles were injected with latex to determine the total number of arterioles and their maximal diameters. Control SHRs had 62% (P less than 0.01) fewer open arterioles and a 32% (P less than 0.001) reduction in the total number of arterioles compared to WKY controls. Salbutamol stimulated 67% (P less than 0.001) and 22% (P less than 0.05) increases in total number of the smallest arterioles in the SHR and the WKY, respectively. Salbutamol also significantly reduced the maximum diameter of latex-injected arterioles. These results suggest that the decreased arteriolar density in the cremaster muscle of SHR rats may result from differences in the beta-adrenergic mechanism.


Oxygen consumption of pial arteries.

Oxygen consumption of pial arteries. Pial arterioles and arteries, normally responsive to alterations in PaCO2, were obtained by microdissection from the parietal cortex of 53 anesthetized cats. The oxygen consumption of these vessels, determined with the Cartesian diver microrespirometer, was found to be size dependent. It increased progressively from vessels 60 mum in diameter to vessels 250 mum in diameter. In vessels 250--375 mum in diameter there was a progressive decrease in oxygen consumption with increasing vessel size. The oxygen consumption was not altered by increasing the oxygen concentration in the diver from 20% to 95%, or that of glucose from 1.1 to 2.0 mM. Planimetry of histological sections showed that the percentage of endothelium and smooth muscle increased as vessel diameter increased from 60 to 200 mum, and thereafter decreased with increasing vessel size. When these differences in the composition of the vessel wall were taken into account, there was still residual dependence of the oxygen consumption on vessel diameter. This may represent intrinsic differences in the metabolic rate of vascular smooth muscle in vessels of different size.


Arteriolar closure mediated by hyperresponsiveness to norepinephrine in hypertensive rats. This study was designed to determine if a mechanism exists to cause abnormally large number of arterioles to be closed to blood flow in spontaneously hypertensive rats (SHR). The contributions to vessel closure by neural control and constrictor response to norepinephrine were investigated. Normal rats (WKY) and SHR were studied at age 18--20 wk. Their respective mean arterial blood pressures were 100 +/- 4 (SE) and 154 +/- 7 mmHg when anesthetized with 10% urethan and 2% alpha-chloralose (0.6 mg/100 g ip). The number of arterioles open to blood flow was counted in a large portion of the cremasteric muscle before and after denervation. The percent change in control diameter of denervated arterioles was measured during iontophoretic application (2 min) of norepinephrine at dose currents of 10--300 nA. Following denervation, a 22.2 +/- 6.3% (SE) and 61.8 +/- 12 increase in the number of third-order arterioles open to flow occurred in WKY and SHR. The diameters, wall thicknesses, and cross-sectional areas of vessel walls were not significantly (P less than 0.05) different for comparable types of denervated arterioles in WKY and SHR. The percent changes in diameters of arterioles in SHR were 3--5 times greater at all dose currents than for vessels of WKY. These data indicate arteriolar closure occurs with higher incidence in SHR than WKY and is mediated by hyperresponsiveness of arterioles to norepinephrine.


Role of receptor elements in baroceptor resetting. Spontaneously hypertensive rats (SHR), 4 wk of age, were treated with antihypertensive agents for 40 wk. The treatment was withdrawn for 2 wk so that the animals experienced hypertension for about 1 wk. The aortic arch was then perfused and aortic nerve activity was recorded. The threshold pressure was 140 mmHg in these SHR. This threshold pressure was less than that observed in age-matched untreated SHR (160--180 mmHg) but greater than that observed in age-matched Kyoto-Wistar rats (80--120 mmHg), indicating partial baroceptor resetting. No significant changes were observed in the vascular wall in these SHR, and partial baroceptor resetting was completely reversed when short duration of hypertension was reversed. On the other hand, baroceptor resetting in untreated SHR was always accompanied by significant changes in vascular wall, and reversal of baroceptor resetting was contingent upon regression of vascular wall hypertrophy. Partial baroceptor resetting in absence of significant changes in vascular wall may be explained by adaptation of baroceptors to persistent high blood pressure.


An automatic cardiac action potential duration meter. The duration of a cardiac action potential (AP) is measured from the beginning of its upstroke to the end of its asymptotic repolarization phase: the end being given by a point in proportion to the AP amplitude. If the resting potential, AP amplitude, as well as the duration, alter simultaneously, frequent accurate measurements can be extremely tedious. A fully automatic AP duration meter has thus been constructed to cope with these difficulties while measuring within about 2% on a beat-to-beat basis. It is suitable either for brief sampling of AP durations when recording with microelectrodes, which may impale cells intermittently, or for continuous monitoring, as with suction electrodes on intact beating hearts in situ. For example, the device can faithfully track changes in duration during periods of regional myocardial ischemia in intact ventricles in situ while the AP alters its base line, upstroke velocity, amplitude, and duration.


Measurement of myocardial PCO2 with a microelectrode: its relation to coronary sinus PCO2. A micro-PCO2 electrode, with dimensions of 1 x 10 mm, and a 63% response time of 14 s was inserted into the left ventricular myocardium of the pentobarbital-anesthetized dog. Continuous recordings were made of myocardial PCO2 (PmCO2), arterial PCO2 (PaCO2), and coronary sinus PCO2 (CSPCO2) during variation of respiratory rate. PmCO2 and CSPCO2 were compared at varying coronary flow. PmCO2 was similar to and closely followed changes in CSPCO2. The difference between PmCO2 and CSPCO2 was -0.52 +/- 3.63 (SD) mmHg, and PmCO2 exceeded PaCO2 by 20.69 +/- 5.12 mmHg. After coronary occlusion, PmCO2, rose promptly, but CSPCO2 was only slightly elevated until the occlusion was released, when a CO2 efflux into the coronary sinus occurred. It is concluded that the electrode measures extracellular PCO2 and that extracellular and myocardial PCO2 are essentially equal. PmCO2 rises rapidly following coronary occlusion.


Effect of central venous pressure on arterial baroreflex control of heart rate. There is considerable evidence that the level of afferent cardiopulmonary receptor activity modulates sinus node responses to arterial baroreflex stimulation in experimental animals. We tested the hypothesis that this reflex interaction occurs also in man by measuring sinus node responses to arterial baroreceptor stimulation with phenylephrine injection or neck suction, before and during changes of central venous pressure provoked by lower body negative pressure or leg and lower trunk elevation. Variations of central venous pressure between 1.1 and 9.0 mmHg did not influence arterial baroreflex mediated bradycardia. Baroreflex sinus node responses were augmented by intravenous propranolol, but the level of responses after propranolol was comparable during the control state, lower body negative pressure, and leg and trunk elevation. Sinus node responses to very brief baroreceptor stimuli applied during the transitions of central venous pressure also were comparable in the three states. We conclude that physiological variations of central venous pressure do not influence sinus node responses to arterial baroreceptor stimulation in man.


Prevention of salt-induced hypertension in the Dahl strain by 6-hydroxydopamine. Salt-induced hypertension in Dahl's genetically hypertensive rat has been attributed to humoral or renal factors. However, a recent study from our laboratory suggested that neurogenic mechanisms contribute to salt-induced increased in hindquarters vascular resistance in Dahl salt-sensitive (S) rats. In the present study, we examined the hypothesis that "chemical sympathectomy" with 6-hydroxydopamine (6-OHDA) prevents salt-induced hypertension and increased vascular resistance in S rats. Hypertension did not develop during high-salt diet (8% NaCl) in S rats treated with 6-OHDA, (75--100 mg/kg ip), whereas in rats treated with vehicle, hypertension developed after 4 wk of high salt diet. Chow consumption, sodium excretion, and weight gain were not altered by 6-OHDA. Hindquarters vascular resistance and neurogenic vasoconstrictor tone were significantly lower in S rats treated with 6-OHDA than in S rats treated with vehicle. 6-OHDA also significantly reduced responses to direct sympathetic nerve stimulation and tyramine. These results suggest that an intact sympathetic nervous system plays an essential role in the development of salt-induced increase in blood pressure in Dahl S rats.


Hydraulic conductivity of the endothelial and outer layers of the rabbit aorta. Pressure-driven fluid flow across the arterial wall was measured to determine wall hydraulic conductivity (Lp) before and after removal of the endothelium. The thoracic aortas of rabbits, anesthetized with Nembutal, were cannulated, perfused with oxygenated Ringer solution, and removed. With one cannula connected to a capillary manometer and the other closed, the manometer meniscus shift could be used as an indication of fluid loss through the wall plus vessel volume increase (creep). The latter effect, when measured, accounted for about one-fourth of the total volume displacement. The Lp given in cm/(s.cmH2O) +/- SD, was 3.30 +/- 0.96 x 10(-8). Another method employed continuous weighing of a closed aortic segment to obtain fluid loss, and yielded an Lp of 4.07 +/- 1.3 x 10(-8), and after mechanically removing the endothelium, the Lp became 7.73 +/- 2.8 x 10(-8). Using the above data, an Lp could be calculated for aortic endothelium of 8.6 x 10(-8). This suggests that about half the total transmural pressure drop occurs across the endothelium. Scanning electronmicrographs were used to check the condition of the endothelium.


Ovine placental vascular responses to indomethacin. The administration of 10 mg/kg indomethacin to chronically catheterized near-term sheep resulted in a change in cotyledonary vascular resistance from 0.133 +/- 0.016 to 0.180 +/- 0.022 (mmHg . min)/ml (P less than 0.001). The noncotyledonary uterine vascular resistance increased to 191% of the original value (P less than 0.001) and the renal vascular resistance increased to 147% of the control value (P less than 0.001). The maternal blood pressure increased from 96 +/- 3.4 to 108 +/- 3.4 mmHg (P less than 0.001). Indomethacin (12 mg/kg) was given to nine fetuses, and observations were made in the control condition and at 15, 120, and 240 min. Cotyledonary vascular resistances were 144%, 152%, and 213% of the control values at those times. All changes were significant (P less than 0.03). The umbilical vascular resistance rose slowly throughout the study even though the concentration of indomethacin was falling during that time. These data suggest that this response may be an indirect effect. In the maternal circulation the rapid increase in the cotyledonary vascular resistance seen after indomethacin was probably due to a decreased level of endogenous prostaglandin synthesis.


Shunting of microspheres across the canine coronary circulation. Coronary shunting of 9 +/-1 micrometer and 25 +/- 5 micrometer radiolabeled microspheres was examined in anesthetized, open-chest dogs, whose left common coronary arteries were perfused at controlled pressures. Shunting was estimated from the difference in radioactivity between perfusion line and coronary sinus blood samples during selective elevations of coronary perfusion pressure (CPP), left ventricular afterload, and inspired oxygen. A linear relationship was found between coronary shunting of 9-micrometer microspheres and CPP over the range 100-200 mmHg. According to regression analysis, percent shunt flow was 4.0% at control CPP (100 mmHg) and 10.0% at CPP of 200 mmHg. No shunting of 25-micrometer microspheres occurred at any CPP. Raising afterload did not affect shunting at control CPP but attenuated the increase in shunting at elevated CPP. Changing inspired gas from room air to 100% oxygen did not influence shunting at control or elevated CPP. Raising CPP to 150 and 200 mmHg also released 2.5% and 5.9% of pretrapped 9-micrometer microspheres, respectively. This study demonstrates that vessels permitting passage of microspheres across coronary circulation are sensitive to elevated perfusion pressure.


Plasma volumes and hematocrits in rats with chronic sinoaortic denervation hypertension. Plasma volume changes were assessed in female Wistar rats with neurogenic hypertension induced by sinoaortic denervation, SAD. Tail veins of conscious, restrained rats were used for injection of Evans blue dye and for sampling into microhematocrit tubes. Only at 3 days did total plasma volume of SAD rats show a modest reduction of about 16% (P less than 0.05 vs. sham-operated plus unoperated controls). At 3, 6, and 13 wk, SAD mean body weight, plasma volume, and sodium concentration were similar to sham values. SAD hematocrits, however, like arterial pressures, were elevated at all postoperative times studied. In anesthetized SAD and sham rats, red blood cell (51Cr method) and plasma volumes were the same and so were hematocrits. The latter was unlike the finding in unanesthetized groups. Hematocrits from the same SAD rats were lower after induction of anesthesia than before (P less than 0.025). Thus, elevated hematocrits apparently resulted from the release of sequestered red blood cells into the circulation by unanesthetized SAD rats. In conclusion, plasma volume is within the normal range in SAD rats except for the first few postoperative days. Factors affecting volume regulation at that time are discussed.


Plasma and lymph dopamine-beta-hydroxylase and norepinephrine during carotid occlusion. Dopamine-beta-hydroxylase (DBH) and norepinephrine (NE) levels in superior mesenteric venous (SMV) and arterial blood and in intestinal lymph were determined sequentially before and during carotid artery occlusion (CAO) in anesthetized rabbits. During the first 15 min of CAO, SMV plasma NE increased 77% but SMV plasma DBH increased only 11%. During the second 15 min of CAO, SMV NE declined to 36% above control but SMV DBH rose further and peaked to 29% above control after CAO was released; arterial DBH and NE showed small insignificant changes. Lymph DBH and NE increased simultaneously throughout the period of CAO. Increases in mean arterial pressure during CAO correlated with superior mesenteric venous NE (r = 0.58, P less than 0.01). In additional experiments, hepatic vein plasma NE was 74% lower than portal vein NE. Thus, during acute sympathetic activation, DBH and NE increase in mesenteric venous plasma and intestinal lymph but the peak response of plasma DBH lags behind that of NE. The degree of NE change in the general circulation is minimized due to hepatic clearance of NE.


Spinal cord, hypothalamic, and air temperature: interaction with arousal states in the marmot. Yellow-bellied marmots, Marmota flaviventris, prepared with U-shaped thermodes in the epidural space of the thoracic vertebral canal, a thermode in the preoptic hypothalamus, and cortical surface and hippocampal electrodes, were used to investigate the interaction of arousal states with temperature regulation. It was found that arousal state of the animal influences the thermoregulatory responses initiated in either the spinal cord or hypothalamus. Further, changes in ambient temperature affected both the gain and the threshold of these responses. The interaction of the hypothalamus and spinal cord was not an additive function, however the threshold for shivering of each could be altered by temperature manipulation of the other. Future studies in modeling of temperature regulation should consider the contributions of temperature receptors of the spinal cord and the arousal state of the animal during the stimulation period.


Inhibition of osmotic thirst by electric stimulation of the basal forebrain in dogs. The effect of electrical brain stimulation (ESB; 50 Hz, 50-150 microA sine wave, 5 s on/5 s off) on osmotic thirst was examined in 10 conscious dogs chronically implanted with electrodes aimed at the anteromedial part of the basal forebrain. Suppression of osmotic thirst (SOT) was observed during stimulation through 18 of 41 electrodes located in the olfactory tubercle, the nucleus accumbens, the caudate nucleus, the medial septum, and the lateral preoptic-anterolateral hypothalamic area (PrA/ALH). Mean increment in plasma osmolality necessary to cause drinking rose from 9.0 +/- 1.5 mosmol (X +/- SE; n = 15) under control conditions to 15.8 +/- 2.6 mosmol (n = 18) during ESB in SOT placements. Threshold cellular dehydration eliciting drinking increased from 2.70 +/- 0.50% of intracellular water (ICW;n = 16) to 4.77 +/- 0.68% of ICW (n = 18), respectively. The strongest SOT was found during ESB in the nucleus accumbens, and the PrA/ALH. The same stimulation failed to inhibit feeding, support self-stimulation or produce appreciable changes of dog's gross behavior. The results give evidence for the existence in the basal forebrain of the dog a widely distributed neural system suppressing osmotic thirst. The nucleus accumbens and the PrA/ALH seem to play an important role in this system.


A chronic cannula for obtaining CSF from the cisterna magna of awake dogs. We have designed a cannula system that can be chronically implanted to end above the dura of the cisterna magna of the dog. During experiments in the awake dog, a screw cap with stylet is removed from the cannula and a spinal needle inserted for the withdrawal of samples of cisternal cerebrospinal fluid (CSF) or for making continuous measurements of pressure. The system can be used for repeated experiments extending over several weeks.


Metabolism of the acutely ischemic dog heart. II. Interpretation of a model. The glycolytic oscillations occurring in an acutely ischemic dog heart are analyzed with a computer model. The major regulations of the glycolytic pathway flux occur at phosphohexose isomerase, which is inhibited by accumulated pentose shunt intermediates; at phosphorylase, which shapes the first cycle of the oscillation; and at aldolase, which shapes the last two cycles. Aldolase is not under normal substrate control. Its activity, and that of some subsequent glycolytic enzymes, appears to be regulated by known interactions with the muscle proteins. The mitochondria become reduced as a result of anoxia, and their metabolism reorganizes to export rather than import reducing equivalents. It is in general feasible to account for the behavior of this preparation in terms of the known metabolism of less severely perturbed hearts, especially (but not completely) in terms of effects of anoxia. The reasons for the inapplicability of the crossover theorem previously used to analyze this preparation are described.


Essential role of mean circulatory filling pressure in salt-induced hypertension. Experimental hypertension was produced in nine dogs by continuously infusing isotonic saline after renal mass had been surgically reduced to approximately 30% normal. Data were collected during 8 days of base-line measurements and 13 days of saline infusion to determine the cause of the initial increase in cardiac output observed in this type of hypertension and to measure other variables possibly important in the pathogenesis of hypertension. During the infusion period, these dogs demonstrated an increase in arterial pressure to hypertensive levels, transient increases in blood volume, sodium space, and cardiac output, initially depressed then subsequently elevated total peripheral resistance, and decreases in plasma renin activity and plasma aldosterone concentration. The mean circulatory filling pressure increased 4.7 Torr by day 3 and was still elevated 2 Torr at the end of the 2nd wk of infusion. We conclude that the initial increase in cardiac output in salt-loading hypertension is due to elevated fluid volumes and the associated increase in mean circulatory filling pressure.


Evaluation of in vivo brain site perfusion with the push-pull cannula. The effect of tissue site perfusion with push-pull cannulas on the integrity of brain tissue was evaluated during in vivo studies in conscious New Zealand rabbits. The mean rate of perfusion-induced tissue disruption was 1.09 microgram tissue wet wt/min as estimated from the perfusate levels of endogenous nervous system specific proteins (S-100 and 14-3-2). The level of intravenously injected 125I-labeled bovine serum albumin recovered in perfusate samples indicated that approximately 2.0 nl serum/min penetrated the vascular barrier into the perfused tissue site. The appearance of intraventricularly injected solutes in perfusate samples was subjected to regression analysis. It was demonstrated that nonspecific variations in the appearance of one substance in the perfusate could be controlled for by a regression on the levels of another concurrently recovered inert substance. The experiments demonstrate that tissue site perfusion can provide useful access to brain extracellular fluid when suitable controls are incorporated for recovery variation and blood-brain barrier seepage.


Effects of vagotomy with and without pyloroplasty on weight and food intake in rats. Bilateral truncal vagotomy performed in 13 rats reduced weight gain by 26% compared to controls, but also produced gastric distension. Addition of pyloroplasty was found to facilitate gastric drainage in vagotomized rats, and both procedures were then performed in 57 rats of both sexes and varying initial weights. When fed ad libitum, vagotomized animals maintained a weight 14-30% less than controls over periods of 30-300 days. When pair fed, normal rats and rats with vagotomy and pyloroplasty weighed the same. Various partial vagotomies had no effect on weight gain. It was concluded that vagotomy reduces weight gain in rats, that the reduction is the result of decreased food intake, and that the effect of vagotomy is probably not due to gastric distension.


Modes of thermal protection in polar bear cubs--at birth and on emergence from the den. At birth in late December the polar bear is small (700 g), uninsulated, and helpless. It probably has a modest capacity for metabolic heat production and depends on the female and a snow den in which it is born for thermal protection. The microclimate of an artificial polar bear den was investigated at Point Barrow, AK, and the temperature therein found to stay around 0 degrees C provided a heat source (200 W) equivalent to an adult polar bear was introduced. When the bears desert the den in early April the cub has grown to about 10 kg and has a well-developed fur insulation, but almost no subcutaneous fat. The cub has a high resting metabolic rate (4.6 W.kg-1), which is supported by the fat polar bear milk. Its lower critical temperature is about -30 degrees C, and an ambient temperature of -45 degrees C results in only a 33% increase in metabolism. The cub can tolerate a wind chill of 2.3 kW.m2 without apparent stress of drop in rectal temperature. If the cub is immersed in ice water rectal temperature drops 11 degrees C in 30 min. It is concluded that the cub can tolerate extremely low temperatures in air due to fur insulation and high metabolic heat production, but is unable to cope with the chill of ice water for any prolonged period of time.


Osmosensitivity of rat third ventricle and interactions with angiotensin. Injections of hyperosmotic solutions (1- to 5-microliter injections of NaCl or sucrose solutions ranging in osmolarity from 0.34 to 0.90 osmol/l) into the anteroventral third ventricle (AV3V) of rats resulted in short latency drinking antidiuretic, and pressor responses. AV3V injections or infusions of combined angiotensin-hyperosmotic NaCl solution did not result in drinking greater than the sum of drinking to angiotensin and hyperosmotic NaCl separately administered. Differences in water versus saline drinking fluid preferences provided a behavioral dissociation of angiotensin and hyperosmotic sensitive neural mechanisms. Comparison of AV3V and lateral preoptic injection sites provided an additional separation since angiotensin was equally effective at both sites whereas osmotic stimulation was more effective at the AV3V site. AV3V lesions have previously been reported to abolish drinking, antidiuretic, and pressor responses to angiotensin and hyperosmotic stimulation. The data reported here provide additional evidence that angiotensin and hyperosmotic stimuli may both act on tissue surrounding AV3V but suggest that the neural substrates for these stimuli are not identical.


A model of potassium ion efflux during exercise of skeletal muscle. Potassium (K+) is a vasoactive agent and is released from muscle cells during exercise. A simple diffusion model does not predict the time course of K+ efflux during exercise, which decreases as the exercise progresses. We constructed a mathematical model using the concept of an active Na+-K+ ion pump to account for the decreased efflux during and uptake after exercise. Passive fluxes are calculated by the Nernst equation. Active fluxes are constrained to balance these passive fluxes at rest. The pump activity increases as either extracellular K+ or intracellular Na+ concentration increases. To test the model, the venous K+ efflux profile was simulated for direct stimulation (4/s) of the anterior calf mus cles of dogs. The model simulated the K+ release during the stimulation period and [K+] undershoot after the stimulation. The active Na+-K+ ATPase transport concept used in the model was further tested by observing K+ efflux after administration of ouabain. Ouabain infusion decreased K+ uptake during exercise slightly and abolished [K+] undershoot after the stimulation. These experimental data were matched by the model only if a discontinuous effect of ouabain is assumed. This suggests that ouabain may more completely block the sensitivity of the pump to intracellular [Na+] than to extracellular [K+].


Influence of thermal acclimation on membrane lipid composition of rainbow trout liver. Rainbow trout (Salmo gairdneri) acclimated to 5 degrees C possessed larger livers and less neutral lipid per gram of liver than 20 degrees C-acclimated animals; quantities of liver glycolipid, phospholipid, and cholesterol did not vary significantly with acclimation temperature. The relative proportions of phosphatidylethanolamine increased significantly following cold exposure, whereas the quantities of sphingomyelin and cardiolipin declined. For all phosphatides examined (phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine, phosphatidylinositol, lysolecithin, cardiolipin, sphingomyelin) cold acclimation resulted in 1) an increase in the quantity of polyunsaturated fatty acids, 2) a reduction in the level of saturated fatty acids, and 3) little change in the total content of monoenes and dienes. The increased content of polyunsaturated fatty acids in choline and ethanolamine phosphatides following cold acclimation was confined to the 2-position and occurred at the expense of monoenes and dienes. The relative proportions of n - 3 fatty acids, and less frequently n - 6 fatty acids, increased in phosphatides of cold-acclimated trout, whereas the relative proportions of n - 9 fatty acids declined. These data suggest a preferential incorporation of fatty acids belonging to the linolenic acid family at reduced temperatures. Temperature-induced changes in the chemical composition of trout liver phospholipids counteracted the effects of acute temperature change on nonelectrolyte permeability of isolated liposomes.


Intraventricular 2-deoxyglucose, glucose, insulin, and free fatty acid mobilization. The possibility of eliciting changes in the activity of lipomobilizing centers in the rat central nervous system was investigated by injecting glucose or substances that affect glucose metabolism directly into the cerebrospinal fluid of conscious, unrestrained rats. Intracerebroventricular administration of minute amounts of 2-deoxyglucose to fed rats induced a rapid increase in the concentration of plasma free fatty acids (FFA) without affecting plasma insulin levels. Furthermore, small amounts of either glucose or insulin injected intraventricularly reduced the increased plasma FFA levels of normal fasted rats without affecting the glycemia or plasma insulin levels in these animals. In diabetic rats, the increased levels of plasma FFA were not affected by intraventricular administration of glucose, but clearly decreased after intraventricular insulin. The results suggest that the lipomobilizing centers are insulin sensitive and that their activity is modulated by the rate of glucose uptake, rather than by external hexose concentration. The data are also consistent with our previous hypothesis of a direct control of the sympathetic tonus of adipose tissue by these centers.


Glucose intolerance following chronic metabolic acidosis in man. The effect of chronic metabolic acidosis (0.1 g/(kg . day) X 3 days) on carbohydrate metabolism was examined with the glucose-clamp technique in 16 healthy volunteers. Hyperglycemic clamp. Plasma glucose concentration is acutely raised and maintained 125 mg/dl above the basal level. Because the glucose concentration is held constant, the glucose infusion rate is an index of glucose metabolism (M). Following NH4Cl, M decreased from 8.95 +/- 1.12 to 7.35 +/- 0.76 (P less than 0.05) despite an increased plasma insulin concentration (I) 23 +/- 9%, P less than 0.05). Consequently the M/I ratio, an index of tissue sensitivity to insulin, decreased by 32 +/- 5% (P less than 0.005). Euglycemic clamp. Plasma insulin concentration is acutely raised and maintained 101 +/- 3 microU/ml above basal and plasma glucose is held constant at the fasting level by a variable glucose infusion (M). Following NH4Cl both M and M/I decreased by 15 +/- 4% (P = 0.005) and 15 +/- 5% (P = 0.01), respectively. Metabolic acidosis had no effect on basal [3-3H]glucose production or the percent of decline (91 +/- 4%) following hyperinsulinemia. Both hyperglycemic and euglycemic clamp studies indicate that impaired glucose metabolism following metabolic acidosis results from impaired tissue sensitivity to insulin.