The primary empty sella syndrome: analysis of the clinical characteristics, radiographic features, pituitary function and cerebrospinal fluid adenohypophysial hormone concentrations. Twelve cases of the primary empty sella syndrome were analyzed in regard to clinical findings, roentgenographic features, pituitary function and cerebrospinal fluid adenohypophysial hormone concentration. The findings were compared with those in 247 cases of the primary empty sella syndrome reviewed from the literature in order to determine the major characteristics of this disorder. The majority of patients are obese, multiparous women with normal pituitary reserve, normal visual fields and undetectable adenohypophysiol hormone concentrations in cerebrospinal fluid. In addition occasional patients witll have hypertension, pseudotumor cerebri and cerebrospinal fluid rhinorrhea. Patients who present with the typical features of the primary empty sella syndrome should be evaluated periodically with pituitary function testing, visual field examinations and cerebrospinal fluid adenohypophysial hormone determinations. If these parameters remain normal during careful follow-up studies, the patient is likely to have an empty sella, and pneumoencephalographic and angiographic studies can be avoided.


Management of carcinoma in situ of the vulva. Concern about multicentricity and occult invasion has led authorities to recommend total vulvectomy in the management of carcinoma in situ of the vulva (VCIS). Of these considerations, only occult invasion has sufficient import to contraindicate a more conservative therapeutic approach. VCIS is being diagnosed with increasing frequency in young women for whom the deforming and sexually crippling effects of vulvectomy are especially repugnant. Because of its distinctive success in localizing preinvasive and early invasive squamous neoplasia of the cervix, colposcopy and directed biopsy were employed in evaluating all patients seen in our vulva clinic since 1971. Of 27 consecutive patients considered to have VCIS, 24 were treated either by local excision, skinning vulvectomy, topical 5-fluorouracil (5-FU), or cryosurgery. In no instance was occult invasion missed on pretreatment evaluation, and only one patient has developed a new in-situ lesion following conservative surgical therapy. Topical 5-FU therapy was unsuccessful in six of six cases. These results demonstrate that total vulvectomy for VCIS can be replaced successfully with more conservative operations.


Unilateral tuboovarian abscess: a distinct entity. In a 30 month interval at the Los Angeles County-University of Southern California Medical Center, 85 patients had tuboovarian abscesses removed that were unrelated to complications of pregnancy. Thirty-seven patients (44 per cent) of the 85 had unilateral abscesses. Twenty patients (54 per cent) of the 37 patients with a unilateral abscess were using an intrauterine contraceptive device (IUD). In 13 (65 per cent) of the 20 women using an IUD, the foreign body was a Dalkon Shield. Unilateral pelvic abscesses can occur with or without the presence of an IUD.


Electron microscopy of adrenergic, cholinergic, and "p-type" nerves in the myometrium and a special kind of synaptic contacts with smooth muscle cells. In the cat uterus, three types of axons have been indentified by electron microscopy on the basis of the appearance of the synaptic vesicles in the axon varicosities following treatment with 5-hydroxydopamine: (1) most axons were adrenergic, with numerous small osmiophilic vesicles of a diameter of approximately 50 nm. together with large (100 to 150 nm. in diameter) granules, (2) some axons contained only empty small granules together with the large granules; these are probably cholinergic, and (3) a small number of the axon varicosities had only large-sized vesicles with a moderately electron-dense content. They are interpreted as a polypeptide type of nerves ("p-terminals"). Close appositions at a distance of 25 nm. were sometimes found between the varicosities. A specialized neuromuscular connection was found: the muscle cells at "the end" of muscle bundles extended small stout processes, containing numerous myofilaments, onto a small nerve bundle, the distance being 20 to 25 nm.


Clinical, pathologic, and genetic findings in a case of 46,XY pure gonadal dysgenesis (Swyer's syndrome). Cytogenetic, pathologic, and clinical studies were conducted on a phenotypically female patient with primary amenorrhea and infertility. Analysis of blood cultures with routine and Giemsa-banded preparations indicated that the chromosomal complement of the patient was 46,XY. Buccal and peripheral blood smears prepared for fluorescent analyses confirmed the presence of a single F-body (Y chromosome). Pathologic examination of tissues removed at total hysterectomy and bilateral salpingo-oophorectomy revealed a gonadoblastoma of the right gonad, dysgerminoma of the left gonad, and an infantile hypoplastic uterus. The data were consistent with a diagnosis of 46,XY pure gonadal dysgenesis (Swyer's syndrome).


Clinical, pathologic, and genetic findings in a case of 46,XY pure gonadal dysgenesis (Swyer's syndrome). II. Presence of H-Y antigen. Evidence that expression of histocompatibility-Y (H-Y) antigen on human cells is determined by a Y-linked gene is provided by data demonstrating that male subjects with two Y chromosomes have higher antigen levels than male subjects with one Y chromosome. The widespread evolutionary conservation of H-Y antigen and its association with the Y chromosome suggest that the antigen has a specific, crucial function. We surmise that this function is the differentiation of the embryonic gonad into whichever mature gonad, testis or ovary, typifies the heterogametic sex of each species. Of particular interest are individuals whose gonadal sex does not correspond to their somatic genotype. In the present article, we report positive results in the first case of 46,XY pure gonadal dysgenesis (Swyer's syndrome) to be typed for H-Y antigen. This case suggests that the presence of H-Y antigen may not be sufficient to complete masculinization of the embryonic mammalian gonad. Alternatively, a mutant gene may govern expression of a cell surface component which cross reacts with H-Y antigen but which lacks the ability to function in the virilization of the gonad.


Effect of prenatal treatment with ethinyl estradiol on the mouse uterus and ovary. Oral ethinyl estradiol (0.01 or 0.02 mg. per kilogram) administered prenatally to ICR-JCL strain mice before the development of the uterine and ovarian blastemata induced cystic glandular hyperplasia with epidermization in the endometrium and excessive formation of degenerating follicles in the ovaries at 10 to 14 weeks of age. To the evidence for the production by estrogen of malignant uterine neoplasms in rodents and the clinical data showing that cystic glandular hyperplasia develops after prolonged estrogen administration in postmenopausal women and adenocarcinoma in premenopausal or menopausal women using oral contraceptives including ethinyl estradiol, we add the present results which suggest that ethinyl estradiol administered transplacentally can cause malignant transformation of the uterine endometrium in mice.


Inhibition of premature labor: a multicenter comparison of ritodrine and ethanol. A randomized controlled  study was carried out at three medical centers to compare the efficacy and side effects of ethanol and ritodrine in the treatment of threatened premature labor. One hundred and thirty-five patients judged to be between the twentieth and thirty-sixth week of gestation and presenting with clinical symptoms of premature labor were included. Sixty-seven patients were treated with intravenous infusion of 10 per cent ethanol. Sixty-eight patients were treated with intravenous infusion of ritodrine for 12 hours followed by oral ritodrine. If labor recurred prematurely, up to two additional courses of ethanol or ritodrine were given. Delivery was postponed for more than 72 hours in 49 of 67 patients (73 per cent) with ethanol and in 61 of 68 patients (90 per cent) with ritodrine; this difference was significant. Patients in the ethanol group gained a mean of 27.6 days while patients in the ritodrine group gained a mean of 44.0 days. Fifty-four per cent of the ethanol group and 72 per cent of the ritodrine group carried their infants to 36 weeks of gestation. Five infants in the ethanol group and one infant in the ritodrine group died from respiratory distress syndrome. The most frequent side effect of ethanol were nausea and vomiting. The most frequent side effects of ritodrine were tachycardia and blood pressure changes which were easily controlled by lowering the infusion rate. Ethanol and ritodrine were both found to be effective inhibitors of premature labor with ritodrine giving the most favorable results.


Surface IgM on lymphocytes from pregnant women. Surface IgM on peripheral lymphocytes from pregnant women were passively acquired from autologous serum. These cytophilic IgM antibodies occurred as relatively large molecules, suggesting that they were in the form of complexes or aggregates. The lymphocytes involved were mainly B cells. It was postulated that the present findings could be a mechanism for the modulation of lymphocyte surface receptors by serum factors during pregnancy.


Dilatation and curettage for second-trimester abortions. This study reports the outcome of 2,500 consecutive second-trimester abortions performed with the dilatation and curettage methods. Of the abortions, 99.2 per cent were for gestations between the fifteenth and eighteenth menstrual weeks of pregnancy. We determined that this procedure is both safer and less traumatic than intrauterine saline or prostaglandin instillation. The low incidence of uterine perforation (0.08 per cent) and over-all morbidity (2.8 per cent) and the short duration of hospitalization (average 1.1 days per patient per procedure), as well aa the absence of any death in our series, substantiate this premise.


Coagulation and fibrinolysis in molar pregnancy. Coagulation and fibrinolysis tests were performed in 14 patients with hydatidiform mole before any significant therapy was given and again, after evacuation of the mole, in eight instances. The results were compared with those found in a group of ten volunteers with normal pregnancies. The most frequent abnormalities in the problem cases were a shortening of the partial thromboplastin time and a prolongation of the thrombin time. From a total of seven cases with complete hematologic profiles before and shortly after evacuation of the mole, first showed important drops in platelets and fibrinogen. The most altered profiles occurred after expulsion of the mole in cases with important previous uterine activity. The findings suggested a latent state of hypercoagulability with higher turn over rate of fibrinogen and increased levels of fibrinogen-fibrin degradation products, that may exist even before the mechanism of expulsion begins. It was concluded that the alterations in coagulation and fibrinolysis seen in molar pregnancies most likely have a multifactorial pathogenesis, but the initiating causes must depend on several events taking place in the trophoblast itself and their consequences upon a very distorted intervillous blood circulation.


A simple method of fetal and neonatal heart rate beat-to-beat variability quantitation: preliminary report. Good base-line fetal and neonatal heart rate beat-to-beat variability appears to be a reassuring sign of well-being. Conversely, decreased base-line heart rate beat-to-beat variability during the latter part of the intrapartum period is often associated with neonatal acidosis and/or depression. A simple method of quantitation of the beat-to-beat neonatal heart rate is reported here. This method of variability quantitation (VQ) consists of a continuous integration and display of the baseline heart rate beat-to-beat variability on a scale of zero to four, expressed in beats per minute averaged over a one-minute period. Serial variability quantitation in 35 neonates with different clinical conditions appeared to demonstrate a good correlation between the variability quantitation and the outcome of the neonates. Further studies are planned for evaluating the method in the intrapartum period.


Fetal growth after premature rupture of membranes. Four patients with preterm rupture of the membranes were treated conservatively. During the period of observation (five to nine weeks), each fetus displayed a normal rate of growth as measured by serial biperietal diameter determinations.


Effect of antepartum betamethasone treatment on cortisol levels in cord plasma, amniotic fluid, and the neonate. Antepartum betamethasone treatment in pregnancies which terminated at less than 37 weeks of gestation resulted in a rapid and significant decrease in cord plasma cortisol levels. Mean values +/- S.E. were 5.17 +/- 0.39 microng per 100 ml. in 90 untreated cases, 2.17 +/- 0.32 microng per 100 ml. in 29 cases treated at least 24 hours prior to delivery, and 2.27 +/- 0.38 microng per 100 ml. in 18 cases in which treatment was begun within 24 hours of delivery. The mean cortisol concentration in five amniotic fluid samples obtained after betamethasone administration (0.93 +/- 0.19 microng per 100 ml.) was significantly less than in seven control samples (1.85 +/- 0.21 microng per 100 ml.) These results suggest that betamethasone suppressed endogenous cortisol production by maternal and/or fetal adrenals. However, blood cortisol levels during the first days of life of treated neonates were considerably increased in comparison to those in cord plasma, suggesting that there was rapid recovery of their adrenal function.


Neonatal scalp abscess following intrapartum fetal monitoring: prospective comparison of two spiral electrodes. During a six-month period, 929 newborn infants had continuous, direct fetal heart rate monitoring during labor. Of these, 481 were monitored with the Berkeley Bio-Electronics spiral electrode and 448 were monitored with the Corometrics spiral electrode. The over-all incidence of scalp abscess complicating fetal monitoring was 4.5 per cent. In the group monitored with the Berkeley electrode, 25 newborn infants (5.2 per cent) developed a scalp abscess; in the group with the Corometrics electrode, 17 newborn infants (3.8 per cent) developed scalp abscess. The incidence of scalp abscess was not significantly different in the two groups.


Adenoepidermoid and adenosquamous carcinoma of the uterus. A clinicopathologic study of 118 cases. A series of 118 cases of adenoepidermoid carcinoma and adenosquamous tumors of the uterus is presented. The results indicate that cervical tumors are frequently occult and are often not diagnosed until late in the course of the disease. Stage for stage, the five-year survival rate is poorer than the usual results for cervical malignancy. Endometrial tumors also had a poor five-year survival rate, with a high incidence of myometrial extension. The incidence of myometrial invasion and survival figures were similar to those for poorly differentiated endometrial cancer.


Fetal malnutrition: an appraisal of correlated factors. Fetal malnutrition has emerged as a significant health problem over the past decade. Present evidence suggests that maternal environment plays the major etiologic role in fetal malnutrition. The association of fetal malnutrition in mothers with chronic hypertension is well known, but fetal malnutrition is associated with maternal hypertension in less than 25 per cent of cases. Among a group of 182 pregnant women studied at midpregnancy for blood levels of vitamins, trace metals, proteins, amino acids, and parameters of maternal leukocyte energy metabolism, it was found that the concentration of 10 amino acids, alpha-1-globulin, zinc, and total carotenes had a statistically significant relationship to fetal growth. Similarly significant correlations were found for maternal leukocyte adenosine disphosphate, phosphofructokinase activity, ribonucleic acid (RNA) synthesis, and cell size. Maternal cigarette smoking was correlated with reduced fetal growth. Analysis showed that there was a significant reduction in leukocyte RNA synthesis and phosphokinase activity and in the plasma levels of 14 amino acids, and carotene in smoking mothers. This information lends support to the hypothesis that factors which affect the growth of fetal cells also will affect maternal leukocytes in a definable way.


Age-incidence and risk of diethylstilbestrol-related clear cell adenocarcinoma of the vagina and cervix. This study was based on cases accessioned in the Registry of Clear Cell Adenocarcinoma of the Genital Tract in Young Females to ascertain the incidence of diethylstilbestrol (DES)-related cancers by age and year of birth. For accuracy in estimating the size of the reference population for the incidence rates, calculations were restricted to 127 white residents of the United States who were exposed prenatally to DES or other nonsteroidal synthetic estrogens. The disease is exceedingly rare prior to age 14 when the incidence rate begins to rise rapidly. The incidence peaks at age 19 (median 19.2 years) and then drops precipitately. Thus, DES-related clear cell adenocarcinoma is unusual in that nearly all cancers have been diagnosed in a narrow age range of 10 years (14 to 23 years). Women born in 1951 to 1953 have higher incidence rates than those born in the previous or subsequent three-year period. This suggests that the prevalence of pregnancy-related use of DES was at a peak in the early 1950's. The cumulative risk of this type of genital cancer, through age 24, for DES-exposed female subjects is estimated to be in the range of 0.14 to 1.4 per thousand. The wide limits are due to the fact that the number of young women exposed is not known precisly. The low risk of disease and the narrow age range of the cases, relative to the long latency period, suggest that DES is an incomplete carcinogen. Other factors, possibly related to puberty, may be involved in the causation of this disease.


Upper genital tract changes associated with exposure in utero to diethylstilbestrol. Hysterosalpingograms of 60 young women exposed in utero to diethystilbestrol were obtained. In 46 instances, documentation of this exposure was obtained from the mother's chart review or confirmed by the attending physician. In 14 instances, the patients' mothers were sure they had received stilbestrol, but documentation could not be specifically confirmed. Hysterosalpingograms of 23 women being investigated for infertility during the same period that the current study was conducted were also reviewed. In 40 women exposed to stilbestrol, changes in the uterus which differed significantly from those seen in the past in nonexposed individuals were noted. These changes consisted of a 'T-shaped appearance of the uterus,' constricting bands in the uterine cavity, a hypoplastic uterus, and less frequently, intrauterine polypoid defects, synechiae, and in one instance a unicornuate uterus. In 36 of the 40 women gross defects were also noted in the cervix. By comparison, in none of the control subjects were defects noted which could be considered comparable with those seen in the DES-exposed patient.


The incidence and significance of polynuclear follicles. In the treatment of pelvic disorders, ovarian tissue was surgically removed from 165 patients (divided into four age groups) and examined microscopically. This article presents the incidence of polynuclear follicles and discusses potential signficance of these structures in the histogenesis of the ovarian teratoma.


Carcinoma of the endometrium: radiation followed immediately by operation. A prospective study was established in August, 1967, to treat all adenocarcinomas of the endometrium by protocols of preoperative radiation followed immediately by operation. Two hundred and ninety-five women have been treated, 220 of whom had Stage I disease. In these cases, factors known to be associated with survival were studied, and their influence upon survival was noted. Preoperative radium followed immediately by operation was the primary method of therapy. Life tables demonstrated a five-year survival rate of 91 per cent with a low complication rate in patients with Stage I disease. Cell type, degree of differentiation, and depth of myomentrial invasion were the primary factors influencing survival.


A lung model of schistosome immunity in mice. When mice are challenged intravenously with schistosomula of Schistosoma mansoni, host cell reaction and parasite attrition proceed entirely in the lung, where these events can be followed by quantitative histology and worm recovery. In nonimmune animals the destruction of schistosomula in the lungs proceeds gradually, resulting in the elimination of about 80% of the challenge organisms after 6 days. Cell reaction begins promptly, as evidenced by the appearance of neutrophilic foci around many of the lung schistosomula within 30 minutes after injection, and results in increasing numbers of damaged organisms and residual inflammatory foci 24 hours and 6 days later, respectively. In contrast, when schistosomula are injected into mice immune by virtue of an established S. mansoni infection, parasite destruction is augmented and accelerated, a process already evident by 24 hours. By the sixth day, 98% of the challenge organisms have been eliminated, a substantially greater reduction in parasite survival than that occurring in the normal host. This increased attrition of schistosomula is also reflected in the decreased numbers of parasites recovered from minced lung tissue of immune mice 6 days after challenge. Immune cellular inflammatory reactions to schistosomula are, likewise, greatly intensified and can be readily distinguished from those of normal mice by the proportions of parasites involved and by the large numbers of eosinophils surrounding them. In some instances, degranulation of eosinophils onto the parasite tegument is observed. Schistosomula cultured for 24 or 44 hours in a medium containing mouse red blood cells elicit significantly less cellular reaction and show greater survival in the lungs of immune animals than do freshly derived schistosomula. It would therefore appear that the susceptibility of maturing schistosomes to immune cellular attack is limited to the first day or two after their metamorphosis from cercariae. These observations form the framework of a new in vivo model for analyzing the dynamics of the cellular and humoral processes involved in the immune destruction of a metazoan parasite. The model also lends itself to studies of the immunologic interrelationships between innate and acquired resistance to infection with schistosomes, as well as the mechanisms by which these parasites evade the host immune response.


Embolic pneumopathy induced by oleic acid. A systematic morphologic study. This paper presents a systematic study of acute and chronic pulmonary lesions resulting from a single intravenous injection of oleic acid and a new fibrosis lung model is proposed: pulmonary interstitial fibrosis is obtained by means of a number of oleic acid intravenous injections. Nineteen adult dogs received 0.045 g/kg or 0.09 g/kg of oleic acid. A systematic morphologic study was carried out after 1, 2, 3, 4, 6, 12, 24, and 48 hours and 1, 2 and 4 weeks. Eleven other adult dogs received weekly one injection of 0.09 g/kg of pure oleic acid over a period of 1 to 3 months. Examination of the lung was carried out by means of light and electron microscopy and morphometry. An early stage characterized by the formation of thrombosis and cellular necrosis was followed by a repair stage with the proliferation of Type 2 cells and fibrotic foci in the subpleural areas. Lipid staining with Sudan IV allowed the onset and disappearance of lipid-laden macrophages to be ascertained. The late stage showed pulmonary fibrosis. The extent of the lesions is related to the number of oleic acid injections. Since interstitial pulmonary fibrosis invariably appeared, and only 2 dogs out of 11 died, the model is satisfactory for pathologist and physiologist.


The induction of human myospherulosis in experimental animals. Tissue lesions similar to those in human myospherulosis were reproduced in experimental animals and studied by light and electron microscopy. The lesions were produced by the use of petrolatum-based antibiotic ointments. These ointments, which are marketed as nonsterile products, are similar to those used for hemostatic packing in otolaryngologic surgery. To date, use of these ointments has been reported to precede the finding of human paranasal sinus myospherulosis. The exact nature of the structures of myospherulosis remains unknown. The experimental evidence strongly suggests that they can be iatrogenically produced by the use of these nonsterile ointments.


Ultrastructural changes in the ischemic zone bordering experimental infarcts in rat left ventricles. Ultrastructural changes in myocardial cells from the ischemic border of infarcts (produced in rat left ventricles by ligating the anterior coronary artery in vivo) were examined 1 to 24 hours after ligation. Twenty-four hours after ligation, irreversibly injured cells showed a selective spreading of Z-band material over the I band; disappearance of M bands, prominent N bands, and disassembly of A bands were also noteworthy. Sixty minutes after ligation the cells of the ischemic border were ultrastructurally normal except for paradoxically relaxed sarcomeres, indicative of an inability to contract in response to the calcium influx produced by osmium tetroxide; progressive vacuolization of this zone was evident after 4 to 12 hours. Paradoxical relaxation may be an ultrastructural correlate of acute ischemic "pump failure".


Attachment and ingestion of mycoplasmas by mouse macrophages. I. Kinetics of the interaction and effects on phagocyte glucose metabolism. Rates of attachment and ingestion of Mycoplasma pulmonis by mouse peritoneal macrophages and the effect of the organism on phagocyte glucose metabolism were studied in vitro. Antimycoplasma antibody, but not complement, enhances attachment of mycoplasma to macrophages. Antibody-mediated attachment is not affected by the length of time the cell is maintained in culture or its adherence to a glass surface. Adherence of mycoplasma by nonimmunologic means to cell spread on glass is significantly greater than attachment to macrophages in suspension. Mycoplasmas attached to macrophage membrane do not increase glucose metabolism via the hexose monophosphate shunt. Because of this, the rate of glucose metabolism by macrophages is an accurate quantitative correlate of the recognition and ingestion stage of phagocytosis of mycoplasmas. Antibody induces a more rapid rate of particle ingestion than does altering the mycoplasma by proteolysis. Complement does not augment the rate of ingestion induced by antimycoplasma antibody. By analogy with enzyme and absorption kinetics, it appears likely that differences observed between phagocytosis induced by antibody and that induced by trypsin are due to different rates of recognition between particles rather than different ingestion mechanisms.


Transmission and scanning electron microscopy of host cell entry by Toxoplasma gondii. Entry by tachyzoites of Toxoplasma gondii, the causative agent of toxoplasmosis, into peritoneal cells was investigated with transmission and scanning electron microscopy. The process of entry is initiated by the parasite contacting the host cell with its anterior end, creating a small depression in the plasmalemma of the host cell. Occasionally, a small portion of the host cell cytoplasm protrudes and contaccts the anterior end of the parasite. A cylindrical structure (35 nm in diameter) extends from the pellicle of the parasite to the host cell. Such structures appear to assist host cell entry by T. gondii. As the entry process progresses, pseudopods of the host cell surround theparasite and finally T gondii becomes intracellular, being located in a vacuole separated from the host cell cytoplasm by a unit membrane. (Am J. Pathol 87:285-296, 1977).


The ultrastructural effect of estrogens on bone cells in thyroparathyroidectomized rats. To determine the direct effect of estrogen on bone cells, female rats were thyroparathyroidectomized and given either 200 microng of estradiol cypionate or placebo treatment for 4 to 30 days. After 8 days, an osteosclerosis of the tibial metaphysis developed in rats treated with estrogens. Osteoblasts in estrogen-treated rats were interpreted ultrastructurally to be less active in bone formation than controls. Osteocytes in estrogen-treated rats were inactive compared to osteocytes in control rats which were continuing the process of bone formation. Osteoclasts were decreased in numbers in rats treated with estrogen; however, the electron microscopic characteristics of osteoclasts did not differ from controls. These cellular changes were associated with a severe hypocalcemia in both estrogen-treated and control rats. Serum phosphorus and urinary hydroxyproline were lowered significantly by the administration of estrogen. It is concluded that metaphyseal osteosclerosis develops in estrogen-treated rats independent of parathyroid hormone and calcitonin. The osteoclerosis is due to an effect of estrogens to reduce osteoclast-numbers and a lesser inhibitory effect on the bone-forming activity of osteoblasts and osteocytes. (Am J Pathol 87:311-322, 1977).


Morphologic demonstration of tubular obstruction in acute renal failure. We used the qualitative Hanssen technique in albino rats to seek morphologic demonstration of tubular obstruction in two types of acute renal failure: one induced by folic acid and another by methemoglobin. Immediately after the intravenous injection of folic acid, 250 mg/kg body weight, the animals became almost anuric. Two to three hours after the injection, sodium ferrocyanide remained within the proximal convoluted tubules. After the intravenous injection of methemoglobin, 0.5 to 1.0 g/kg body weight, the animals became oliguric but not anuric. Sodium ferrocyanide injected with methemoglobin was seen mainly in distal tubules and collecting ducts 2 to 3 hours after the injection. The degree of tubular dilatation was more marked in the former model than in the latter, in agreement with the degree of oliguria. These morphologic findings were taken to indicate that the above two types of acute renal failure were caused by tubular obstruction rather than by intrarenal vasoconstriction and subsequent cessation of glomerular filtration. (Am J Pathol 87:323-330, 1977).


Attachment and ingestion of mycoplasmas by mouse macrophages. II. Scanning electron microscopic observations. Mycoplasmas adhere closely to the central region of the surface of mouse peritoneal macrophages in vitro. They do not appear connected to each other or the macrophage membrane, and they induce no change in the surface of the cell. After addition of antimycoplasma antibody, mycoplasmas show interconnections and the cell shows an increase occurrence of ruffled membrane and folding over the mycoplasmas. Large and small lacunae appear in the membrane at sites other than those taking in organisms, and the cell develops a diffusely granular appearance. These changes are associated with an increase in pinocytosis of horseradish peroxidase that is 85% above controls. Five minutes after addition of antibody, the macrophage appears contracted and engorged and has persistent membrane changes consisting of pits, openings, and membrane folds. Trypsin causes slow ingestion of surface mycoplasmas without the obvious membrane folding over organisms but with evidence of a predominantly invaginating process of phagocytosis. The macrophage surface has numerous microprojections, but is does not have the granular appearance seen after addition of antibody. Trypsin and Mycoplasma pulmonis antigen do not enhance macrophage pinocytic rates. (Am J Pathol 87:347-358, 1977).


Reduction of ischemic myocardial damage in the dog by lidocaine infusion. The effects of lidocaine infusion on the ultrastructural damage induced in cardiac muscle by normothermic cardiopulmonary bypass were assessed in 15 dogs. Six dogs received no medication other than sodium pentobarbital (25 mg/kg, intravenously) while 9 dogs were treated with lidocaine after anesthesia. Lidocaine was given as a 2-mg/kg loading dose 10 minutes prior to ischemic arrest and a 2-mg/min continuous infusion during the entire experimental period. Biopsy samples of the left ventricular apex were taken 15 and 45 minutes after the start of ischemic arrest and 5 minutes after resumption of coronary blood flow. Biopsy samples were also obtained from 4 animals after thoracotomy to serve as controls for experimental procedures. Myocardial ultrastructure in the 4 control animals was comparable to that reported by other investigators. Five of 6 of the nontreated dogs and 8 of 9 lidocaine-treated dogs survived the entire period of ischemia and 5 minutes of coronary reperfusion. However, the extent of ultrastructural damage varied considerably between the two groups. In the experimental dogs receiving no lidocaine, mitochondria were swollen, cristae were absent, the mitochondrial matrix was cleared, and sarcomeres were disrupted. Myelin figures and contraction bands were also observed. None of the surviving lidocaine-treated animals had ultrastructural changes comparable to the worst ones in nontreated dogs. Damage was limited to some swelling of mitochondria with focal clearing of matrix. Most cristae remained intact. There were no myelin figures and few contraction bands. The results suggest that lidocaine protects the integrity of ischemic myocardium. It is suggested that this protection resulted from stabilization of plasma and/or mitochondrial membranes. (Am J Pathol 87:399-414, 1977).


Device for synchronization of cinematographic and bioelectric data. The correlation of mechanical action and bioelectric activity during muscular movement necessitates accurate synchronization of photographic and bioelectric recordings. A device is described which in conjunction with a movie camera provides a pulse as the shutter opens, counts the number of the frame, displays the decimal count in the camera field, and provides a "decimal coded" output pulse for synchronizing other recordings.


Functional roles of the calf and vastus muscles in locomotion. Simultaneous and synchronized electromyography and cinematography were used to record the co-ordination of calf and vastus muscle activity with the angular motions of the segments and joints of the lower limb in two female and three male subjects, while each performed one complete series of tests in which they walked at 2.5, 3.2 and 4.2 mph on a treadmill, which was level, or held at upward tilts of 5 and 10 degrees. The raw EMG recordings were also integrated into uniform pulses, which were electronically counted in 5 second time blocks for each of the walking conditions tested. The objectives of this study were to: 1) quantitatively measure the relative increases of EMG activity in thses two groups of muscles under the various degrees of stress, which resulted from walking at increased speeds and degrees of upward tilt, and 2) correlate these gross quantitative relationships of activity with the patterns of co-ordination found between these two groups of muscles under the corresponding stressed conditions of walking. The results of this study indicate that although with increases of speed and upward tilt the absolute values of integrated EMG increased more for the calf than for the vastus muscles, the relative increases of EMG were consistently greater for the vasti, which reached their peak intensity of activity at moments during the walking stride, when their knee extending action stretched the gastrocnemius heads across the back of the knee joint, and thereby assisted the calf muscles lift the heel, and plantar flex the ankle joint--the most essential actions for producing the push-off and thrust in the normal walking stride.


Efficacy of EMG biofeedback in relaxation training: a controlled stury. Electrical activity in the right elbow flexors has been shown to have a high relationship with a general resting muscular tension factor. It was our purpose to evaluate the efficacy of EMG biofeedback in reducing electrical activity in this muscle group. It was found that EMG voltages were significantly reduced (P less than 0.001) due both to biofeedback treatment and to time of day (construed as a practice and/or restbreak effect). Replication of the experiment without biofeedback and designed to minimize the "restbreak" effect induced by repetitive testing produced no change in the EMG voltages. It was concluded that EMG biofeedback training is effective with the elbow flexor group, and the possibility for training subjects in overall deep relaxation through feedback from this one muscle group is suggested. The importance of the practice effect/restbreak is emphasized.


Effect of hematocrit on electrocardiographic potentials and dipole moment of the pig. The Brody hypothesis posits that blood in the heart chambers enhances body surface potentials due to radially oriented excitation and diminishes those due to tangentially oriented excitation. Evidence supporting the hypothesis has been found in models and in dogs. The current study was performed in pigs (Sus scrofa), anesthetized with sodium pentobarbital, to determine whether the phenomenon could also be demonstrated in a species having a ventricular activation pattern distinctly different from that of dogs. Hematocrit was varied from normal 35.3 +/- 1.1% to as low as 19.8% by hemodilution and to as high as 68.0% by hemoconcentration. Surface potentials early in QRS increased and those late in QRS decreased in hemodilution experiments, while the reverse was true in hemoconcentration experiments. Total QRS duration was 38.0 +/- 0.8 ms. The first peak in resultant dipole moment magnitude, at 5.4 +/- 0.2 ms, was inversely related to blood resistivity with a linear regression correlation coefficient r = -0.76; the second peak, at 10.9 +/- 0.1 ms, was directly related, r = 0.52; and the third peak, at 17.5 +/- 0.2 ms, was directly related, r = 0.89. When interpreted in accordance with the Brody hypothesis, changes in body surface potentials and in resultant dipole moment were consistent with radial excitation of the apical septum, ill-defined orientation of free ventricular wall excitation, and tangential excitation of basal left ventricle and septum.


Pulmonary fatty acid synthesis. I. Mitochondrial acetyl transfer by rat lung in vitro. Incorporation of tritiated water into fatty acids by rat adipose tissue and lung tissue slices incubated with 5 mM glucose indicated a level of fatty acid synthesis in rat lung approximately 15% that observed in adipose tissue in vitro. (-)-Hydroxycitrate, and inhibitor of ATP citrate lyase, markedly reduced tritiated water incorporation into fatty acids by lung tissue slices. The effects of (-)-hydroxycitrate and n-butymalonate on the incorporation of 14C-labeled glucose, pyruvate, acetate, and citrate suggested that citrate is a major acetyl carrier for de novo fatty acid synthesis in lung tissue. Alternative mechanisms to citrate as an acetyl carrier were also considered. Lung mitochondrial preparations formed significant levels of acetylcarnitine in the presence of pyruvate and carnitine. However, the effect of carnitine on the incorporation of 14C-labeled glucose, pyruvate, acetate, and citrate into fatty acids by lung tissue slices indicated that acetylcarnitine may not be a significant acetyl carrier for fatty acid synthesis but may serve as an acetyl "buffer" in the control of mitochondrial acetyl-CoA levels. Additionally, it appears unlikely that either acetylaspartate or acetoacetate are of major importance in acetyl transfer in lung tissue.


Pulmonary fatty acid synthesis. II. Amino acids as fatty acid precursors in rat lung. The incorporation of various 14C-labeled amino acids into CO2 and lipids by rat lung slices was examined. Alanine, valine, leucine, isoleucine, aspartate, and glutamate were oxidized by lung tissue, whereas glycine and phenylalanine were not oxidized. Carbon originating from alanine, leucine, and glutamate was incorporated into pulmonary fatty acids by a mechanism indicative of de novo synthesis. Experiments with specifically labeled [14C]aspartate and [14C]glutamate revealed that the complete citrate-malate cycle described by Patel et al. (25) is of minor importance in pulmonary lipogenesis due to the extremely low activity of NADP-malate dehydrogenase. Glucose and pyruvate were also actively incorporated into fatty acids, and it is suggested that citrate in pulmonary tissue, as in other tissues, plays an important role in the transport of acetyl units from the mitochondria to the cell cytosol during lipogenesis from various carbohydrate and amino acid substrates.


Regulatory mechanisms of hepatic phosphorylase in fetal and neonatal livers of rats. Active phosphorylase was determined in rat livers during the end of the fetal period and the first days of life. This enzyme increases between the 16th day of gestation and birth. After birth, another increase in observed that takes place with 6 h. In the neonatal liver, the rapid increase in active phosphorylase, is inhibited by high levels of blood glucose, but is unaffected by actinomycin D. In fetal liver glucagon administration is followed after 5 h by an increase in total phosphorylase with only a small increase in active phosphorylase; this effect is blocked by actinomycin D. The fetal changes are interpreted as de novo synthesis, whereas the neonatal increase is due to an activation of inactive phosphorylase. Both enzymatic changes appear to be regulated by glycogen. The role of phosphorylase in the regulation of glycogen metabolism in neonatal liver is discussed.


Circadian rhythms of enzyme and running activity under ultradian lighting schedule. Serotonin N-acetyltransferase activity in the pineal gland and running acitvity of rats were measured under an ultradian lighting schedule (light/dark 6:6). When rats were moved from a diurnal lighting condition to the ultradian conditions, N-acetyltransferase activity showed a circadian rhythm, increasing once a day. N-acetyltransferase activity in the pups born and raised under the ultradian lighting conditions also exhibited a circadian change, the phase of which coincided with that of their mothers. When pups were raised by a foster mother with an inverted rhythmic phase from that of the original mother, the phase of the rhythm in N-acetyltransferase activity of the pups synchronized with that of the foster mother. When pups were separated from their mothers for 12 h/day, the circadian increase of N-acetyltransferase activity appeared during the dark period when they were separated from their mothers. The circadian rhythms of running acitvity were in phase with those of N-acetyltransferase activity in the pineal gland.


Dependence of pulmonary prostaglandin metabolism on carrier-mediated transport processes. Inhibitors of prostaglandin (PG) transport (probenecid, indomethacin, or bromcresol green) were found to eliminate the difference between the pulmonary transit time of 3H and 14C when [3H]PGF2alpha and E114C]sucrose were injected as a single intra-arterial bolus into the isolated perfused rat lung. Similar results were obtained with PGE1. The transit time of [3H]PGA1 was not significantly different from that of [14C]sucrose even in the absence of an inhibitor. These inhibitors increased the amount of [3H]PGF2alpha or [3H]PGE1 and decreased the amount of [3H]PG metabolites found in the venous effluent: these agents also inhibited the pulmonary metabolism of continously infused, nonradioactive PGF2alpha. One of the three inhibitors, bromcresol green, was shown not to be an effective inhibitor of PG metabolism in cell-free preparations of rat lung homogenates. These results indicated that under normal conditions, PG's are rapidly transported into intracellular compartment(s) where they are metabolized. Inhibition of this transport process prevents rapid access of PG's to the cytoplasmic enzymes and therefore inhibits pulmonary PG metabolism. This implies that inhibitors of PG transport, including anti-inflammatory organic acids, and some PG antagonists, metabolites, and analogues, can be expected to inhibit the pulmonary metabolism of PG's and thus could potentiate the systemic effects endogenous or exogenous PG's.


Epithelial cell extrusion during fluid transport in canine small intestine. Epithelial cell extrusion during fluid transport was studied under both in vitro and in vivo conditions. The rate of cell extrusion from the villus tips in vitro increased by about onefold in the villi with obstruction of lymph flow associated with the increase of lymph and tissue fluid pressure. When lymph pressure in the jejunal and ileal villi was increased to 6.4 +/- .2 and 12.3 +/- .5 mmHg, respectively, by injection of Ringer solution into the central lacteals, fluid leaked out of the villi and a shedding of epithelium occurred. Vigorous villus spasmodic contraction induced by cocaine or atropine also caused a shedding of epithelium. Cells always appeared in the lumen of intestine in vivo either during fluid absorption or secretion. A copious secretion of fluid, increase of cell loss, and congestion of blood in the villi occurred by the action of cholera toxin, MgSO4, and choline chloride. The rate of cell loss was highest during fluid secretion induced by an elevation of tissue fluid pressure such as at high venous pressure or during intra-arterial histamine infusion. It is thus concluded that elevated tissue fluid pressure is involved in epithelial cell extrusion during fluid transport.


Body elemental composition: comparison between black and white adults. The age-related changes in body chemical composition were measured in a normal black population ranging in age from 30 to 80 yr. The levels of total-body calcium, phosphorus, sodium, and chlorine were measured by in vivo neutron activation. In addition, the lean body mass (total-body potassium) was measured by whole-body counting of 40K. These data were compared with the same data obtained on a normal white population in a previous study. Although there were no significant differences in the height of the two groups, black men and women had significantly higher total-body calcium, phosphorus, sodium, chlorine, and potassium than the sex-and age-matched white population. The increased levels of total-body calcium and potassium when normalized for the weight and height of the subjects were reduced but still remained significantly higher than those of the white population. Clearly specific reference standards for skeletal and muscle mass as well as for sodium and chlorine need to be established for black populations.


Temperature dependence of responses of esophageal smooth muscle to electrical field stimulation. Strips of smooth muscle, cut transversely from the smooth-muscle segment of opossum esophagus, were superfused with oxygenated Krebs-Ringer solution at 37 degrees C in a system that allowed electrical field stimulation of the intrinsic nerves. Three-to-five-second trains of rectangular pulses (0.5 ms long at 10 Hz) were delivered at 30-s intervals at supramaximal maximal current strength. In strips from the esophageal body, each train resulted in a twitch which followed after the end of train with a particular latency, the off-response. Strips from the esophagogastric sphincter relaxed during the train. Temperature was varied above and below 37 degrees C to observe the temperature dependence of the responses. Latency of the off-response varied exponentially with temperature. Amplitude of the off-response showed a linear decline with changes in temperature, both above and below 35 degrees C, the zero-intercepts being 19.6 and 42.3 degrees C, respectively. Amplitude of relaxation of strips from the junction varied little between 20 and 37 degree C but declined sharply beyond those limits, the zero-intercepts being 14.2 and 42 degrees C, respectively.


Stimulation of renal sodium reabsorption by angiotensin II. Various parameters of renal function were studied before, during, and after the infusion of physiological increments of angiotensin II directly into one renal artery of anesthetized dogs. During water diuresis and during antidiuresis induced with exogenous antidiuretic hormone (ADH), angiotensin II consistently reduced UNaV, UKV, and CPAH, and increased the filtration fraction in the infused kidney. Urinary osmolality was increased only in the presence of ADH, while during water diuresis angiotensin II had no apparent effect on urinary osmolality or flow rate. During saline diuresis, a mean increment of angiotensin II concentration of 14 pg/ml was sufficient to significantly reduce UNaV and urinary flow rate. Changes in CCr, CPAH, and filtration fraction did not correlate with changes in sodium excretion, and intracortical distribution of blood flow remained unaltered. These data support the hypothesis that normal circulating levels of angiogensin II play a direct renal role in the control of sodium, potassium, and water homeostasis, and that angiotensin II exerts a direct, stimulatory effect on tubular sodium reabsorption independent of changes in GFR, RPF, filtration fraction, or intracortical distribution of blood flow.


A micropuncture study of salt and water retention in chronic experimental cirrhosis. The object of this study was to localize increased sodium resorption in rats with chronic hepatic cirrhosis. Cirrhosis was induced by the administration of phenobarbital and carbon tetrachloride. The animals retained salt and water after loading and showed edema and ascites. Salt and water balance, clearance, and micropuncture tests were performed. Five or six weeks after the start of procedures to induce injury, the rats were unable to excrete salt and water loads promptly. Urine flow and sodium concentration were significantly less in cirrhotic rats with edema and ascites than in the normal controls. The glomerular filtration rate was slightly lower in the right, nonmicropunctured kidney but was the same in the left. The nephron glomerular filtration rates of surface nephrons were equal in both the experimental and control rats. The fractional proximal resorption rate was notably greater in cirrhotic rats, as was the total proximal nephron resorption rate. That increased proximal resorption alone might account for diminished sodium and water excretion cannot be demonstrated from this study, although we believe that major evidence is provided of the importance of proximal resorption in this phenomenon.


Handling of angiotensin II and oxytocin by renal tubular segments perfused in vitro. In order to study renal tubular handling of two small peptide hormones, [14c]angiotensin II ([14C]AII) and [3H]oxytocin ([3H]OT) were microperfused through rabbit kidney tubule segments in vitro. The reabsorption and tubular sequestration of radioactive label were determined, and the collection fluid was electrophoretically analyzed. The data suggest that [14C]AII is extensively hydrolyzed in the pars recta of the nephron and is rapidly reabsorbed across the tubular epithelium. Under similar experimental conditions, hydrolysis of [3H]OT was not observed in either the proximal straight or cortical collecting tubule segment, and the rate of reabsorption was low. Thus, tubular handling of OT appears to differ from that of AII, probably because of differences in molecular structure.


Regulation of filtration rate in sodium-depleted and -expanded dogs. Sodium balance may affect the response of single-nephron filtration rate (SNFR) to changes in renal arterial pressure (deltaRAP) when the SNFR is measured in the absence of orthograde fluid delivery from the proximal tubule. This thesis was tested in sodium-depleted and -expanded dogs given furosemide, Doca, and low- or high-salt diets, respectively. After 7 days of treatment, renal renin content was significantly greater in the sodium-depleted group (delta = 23.5 +/- 7.4 DU [dog units]/g kidney). Glomerular filtration rate and renal plasma flow were similar in both groups following changes in RAP of 29 +/- 4 and 29 +/- 3 mmHg in the sodium-depleted and -expanded groups, respectively. SNFR at high RAP was not different from SNFR at low RAP in the sodium-depleted group (delta = -0.2 +/- 4.9 nl/min) and slightly, but significantly, greater in the sodium-expanded group (delta = 7.6 +/- 2;1 nl/min). However, the response of SNFR was similar to that of whole-kidney filtration rate. Furthermore, the autoregulatory response (deltaSNFR/deltaRAP) was not significantly different between the groups but was significantly greater than the response calculated for RAP below the range studied. It is concluded that an autoregulatory response of SNFR, in the absence of orthograde fluid delivery from the proximal tubule, is observed in both sodium-depleted and -expanded dogs.


Nephron filtration rate in conscious rats recovering from anesthesia. Single-nephron glomerular filtration rate (SNGFR) of superficial (S) and juxtamedullary (JM) nephrons was measured in conscious rats with a [14C]ferrocyanide infusion technique. Experiments were carried out in nondiuretic (ND), salt-loaded (SL), and hemorrhagic hypotensive (HH) rats. Mean SNGFR values of S and JM nephrons were 48.7 +/- 4.5 SE and 61.7 +/- 4.2 in ND, 73.6 +/- 8.7 and 87.5 +/- 10.8 in SL, and 29.9 +/- 5.9 and 36.4 +/- 7.1 in HH rats. These values are higher than the values reported in anesthetized rats. The S-to-JM SNGFR ratio was not significantly different in the three experimental conditions (ND, 0.788 +/- 0.032; SL, 0.843 +/- 0.018; and HH, 0.824 +/- 0.030), and did not differ from the values reported in anesthetized rats in similar experimental conditions. It is concluded that anesthesia exerts a depressive effect on GFR, but does not modify intrarenal SNGFR distribution. Neither saline loading nor hemorrhagic hypotension induces SNGFR intrarenal redistribution in conscious rats.


Renal vasopressin clearance with reductions in renal blood flow in the dog. These! experiments were designed to evaluate directly the effects of a reduction in renal blood flow on the renal metabolism of vasopressin (ADH) in the anesthetized dog...


Origin of electrical PD's in hamster thin ascending limbs of Henle's loop. Microelectrodes with 2-micronm-tip diameters arranged to record differentially between this ascending limbs (ALH) and ascending vasa recta (AVR), gave values of 1.95 +/- 0.17 mV, ALH positive, in hydropenia with mineral oil bathing the kidney. Average values remained in the range of 1-2 mV when the ALH and AVR values were obtained sequentially, when the kidney was bathed in Ringer solution, when 5-8 Momega Ling-Gerard microelectrodes were used in the ALH, or when the hamsters were in saline diuresis. These results contradict reports of earlier studies with high impedance Ling-Gerard electrodes that the PD was -9 mV, ALH negative. Perfusion of ALH in saline diuresis with solutions of various compositions provided estimates of ionic transport numbers: tNa+ = 0.33 +/- 0.01, tK+ = 0.00 +/- 0.02, tC1- = 0.67 +/- 0.02. When the perfusion solution was designed to have the same Na+, K+, and C1- concentrations as AVR plasma, the PD was 1.36 +/- .20 mV; when ouabain or furosemide were included (10(-5) M), the PD declined 1.35 +/- 0.21 mV and 1.41 +/- 0.28 mV, respectively. The results suggest that active C1- transport is mainly responsible for the PD, but that diffusion potentials can contribute.


Autoradiography of the water compartments in developing teeth of young mice. The distribution of [14C-a1acetyl-4-aminoantipyrine ([14C]NAAP), as indicators of total tissue water, and [carboxy-14C]inulin ([14C]inulin), as an indicator of extracellular water, were studied by autography in mice 4-16 days old. An autographic technique was used that does not translocate or remove the radioactive material. Photometric densities of the autoradiographs revealed wide variations in radioactivity among the various areas of the teeth. Evidence for binding of [14C]urea to bone limits the usefulness of this compound as an indicator. Although [14C]inulin appeared to be a reliable indicator, it is difficult to correlate its distribution with the progress of mineralization determined by electron microprobe analysis. [14C]NAAP was considered to be the most reliable indicator; it revealed that the water content of various areas of the teeth ranged from 7 to 100% of that in blood.


Stimulation of renin release in perfused kidney by low calcium and high magnesium. These experiments were designed to test whether changing perfusate calcium or magnesium concentrations affected renin release in the isolated perfused rat kidney, and whether kidneys removed from sodium-loaded or sodium-deprived rats released the same amount of renin in response to identical stimuli. Kidneys were perfused with Kreb-Henseleit solution containing albumin. Renin release was inversely related to perfusate calcium concentration, whereas renin release was directly related to perfusate magnesium. Although a low calcium medium or low perfusion pressure (50 mmHg) stimulated renin release, the release was substantially greater in the sodium-deprived rats. Increasing the perfusate sodium concentration from 85 to 206 mM increased excretion, but did not alter renin release. It is concluded that a) low perfusate calcium and high magnesium concentrations stimulate renin release, b) kidneys removed from sodium-deprived rats released substantially more renin thatn those from sodium-loaded rats, and c) changing perfusate sodium concentration alters sodium excretion, but does not affect renin release.


Influence of prostaglandins on sodium transport of isolated medullary nephron segments. The possibility that prostaglandins (PG) located in the renal medulla may influence renal excretion of sodium by a direct tubular action was examined by the addition of prostaglandins PGE2, PGF2alpha, and PGA2 to the peritubular and luminal surfaces of isolated perfused medullary thick ascending lumbs and collecting tubules from rabbit kidneys. The prostaglandins at both high (2.5 x 10(-4) M) and low (10 (-10) M, 10 (-7) M) concentrations had no effect on transepithelial potential difference and net sodium flux across these segments. Pretreatment of the animals with indomethacin did not influence the results. In vivo, both PGE2 and PGF2alpha, caused a natriuresis when infused directly into one renal artery, whereas PGA2 had no effect on sodium excretion. The prostaglandin inhibitors indomethacin, meclofenamate, and RO 20-5720 similarly had no direct effect on sodium transport in the nephron segments studied. It is concluded that the previously observed influence of prostaglandins and prostaglandin inhibitors on renal excretion of sodium in vivo are not mediated by a direct tubular action.


Inhibition of endo- and epicardial glycogenolysis by propranolol in ischemic hearts. The effect of coronary artery ligation on myocardial glyocogenolysis was studied in the endo- and epicardial layers of the left ventricle in dogs pretreated with saline or 1 mg/kg of propranolol. Coronary artery ligation was performed by ligating one of the small branches of the left anterior descending coronary artery. Even after coronary artery ligation, neither increase in phosphorylase activity nor breakdown of glycogen was observed in both layers of ischemic region of myocardium in propranolol-pretreated dogs. These results indicate that pretreatment with propranolol inhibits the increase in glycogenolysis being caused by coronary artery ligation. Propranolol howefer, did not inhibit completely the coronary artery ligation-induced increase in glucose 6-phosphate and lactate and decrease in phosphocreatine in the myocardium, especially in the endocardial layers.


Capillary filtration measurement by strain gauge. I. Analysis of methods. The strain-gauge method for measuring changes in limb size, introduced by Whitney in 1953 has not received wide usage for measurement of capillary filtration coefficient (CFC). This method was compared for the dog hindlimb to simultaneous measurements by the classic gfavimetric technique and was found to give comparable results. The larger question of whether either method gives useful information about the true CFC of the limb was addressed by a mathematical analysis of the technique combined with analysis of data concerning methodologically induced alterations in the Starling forces in and around the capillaries. It was concluded that systematic error due to the method is probably less than -1% with an outside error of -14.6%. These findings demonstrate the strain gauge to be a useful tool in determining CFC.


Capillary filtration measurement by strain gauge. II. Effects of mannitol infusion. Maintenance of normal partition of extracellular fluid into vascular and interstitial compartments is a tightly controlled system. One means of studying control of this system is to induce filtration by fluid loading, and to measure associated changes capillary filtration coefficients (CFC) and Starling pressures in a particular vascular bed. We therefore measured responses of the dog hindlimb to isotonic mannitol infusions. Using strain-gauge plethysmography to measure CFC, the Johnson zero-flow technique to measure isogravimetric capillary hydrostatic pressure, and chronically implanted capsules to measure muscular interstitial hydrostatic pressure, we infused isotonic mannitol into anesthetized dogs for 30 min at 20 ml/min and 30 ml/min. There was a sustained 75% increase in CFC in intact hindlimbs, no change in hydrostatic capillary or interstitial pressure, and a 4-5 mmHg rise in filtration pressure due to dilution of serum protein. The most likely mechanism for increased CFC is capillary recruitment, since distension of capillaries requires large increases in hydrostatic pressure. Interstitial fluid compliance appears high. These studies indicate capillary intermittency may be an important mechanism in the disposition of fluid loads.


Cerebral blood flow during hemorrhagic hypotension in the unanesthetized goat. Changes in cerebral blood flow (CBF), arterial blood pressure (AP), and cardiac output (CO) were studied during stepwise blood losses in 12 unanesthetized goats. Bleeding was followed by a drop in CBF, AP and CO in a nearly parallel fashion. Control values (means +/- SE) for CBF, AP, and CO were 117 +/- 5.6 ml/min per 100 g, 105 +/- 3.1 mmHg, and 2,825 +/- 124 ml/min, respectively; and after bleeding, 66 +/- 3.9 ml/min per 100 g, 57 mmHg, and 1, 383 ml/min. Arterial blood samples obtained before bleeding, during the hypotensive state, and after reinfusion did not show any significant differences in pH, PCO2, and PO2 values. In phentolamine-treated animals, bleeding produced a drop in AP and CO similar to that observed in the nontreated animals; however, the decrease in CBF was less marked. These findings show that CBF follows pari passu the fall in AP, and they indicate that the alpha-adrenergic receptors of the cerebral vessels are involved in the cerebral blood flow changes in hemorrhage.


Increased dynamic stiffness of trabeculae carneae from senescent rats. Dynamic stiffness was measured in both adult and senescent Wistar rats using sinusoidal length perturbations from 17 to 40 Hz, superimposed on isometric contractions at low and below Lmax. The slope of the stiffness-tension relationship was found to be increased in senescent muscles of both sexes and at two different temperatures. The age dependence of the slope was independent of resting muscle length. The slope also exhibited frequency dependence and hysteresis that indicates the presence of viscoelasticity during activation. No age dependence was seen in peak active tension, peak dT/dt, or resting stiffness. The findings of this study, taken together with other studies that have shown a decreased shortening ability in the senescent muscle, explain in part the maintenance of active tension development in the face of decreased shortening ability associated with the senescent muscle.


Androgen-mediated sensitivity in platelet aggregation. Platelet responsiveness to an aggregating stimulus (ADP) was greater (X10) in male than in female rats. Castration reduced aggregability in males (X4) and increased it in females (X3). Pretreatment with testosterone (1 mg/kg, sc) enhanced platelet aggregability in both sexes and restored the diminished responsivity observed in castrated males. Incubation of platelets with testosterone (1-10 ng/ml) potentiated rat (18.0 +/- 1.5%) and guinea pig (40.0 +/- 5.0%) aggregability when compared with vehicle-treated platelets. Estradiol (1 mg/kg, sc) in vivo or estradiol, progesterone, and deoxycorticosterone (1 microng/ml) in vitro had the opposite effect and decreased aggregability. The rank order of effectiveness of androgens in vitro was dihydrotestosterone, testosterone, methyltestosterone, androstendione, and androsterone, which correlates with their androgenicity. The effect of androgens was antagonized in vitro by the antiandrogen (Flutamide) and by estradiol. These data suggest that gonadal steroids may play a role in regulating platelet function in the rat and guinea pig.


Relationship between microvascular blood velocity and pressure distribution. Red blood cell velocity and diameter were measured in vessels of the wing of the unanesthetized bat (Myotis lucifugus) from the supplying artery to the capillaries. These data were used to determine the manner in which velocity, shear rate, volume flow, and blood pressure depend on the vessel's hierarchical position within the vascular network. The results show that velocity decreases in an almost linear fashion as the capillary is approached but that the shear rate increases as one progresses distally from the supplying artery. Blood volume flow was found to decrease as an exponential function of the branching order. Comparison with available date in some animal species, including man, indicates some agreement in capillary velocity, although significantly lower values have been reported in some preparations. Using a method whereby blood pressure distribution could be obtained from anatomical data and center-line blood velocity, the rheologic alterations accompanying consecutive vessel branching were deduced and found to be in good agreement with data available in the literature.


Reactive hyperemia in capillaries of red and white skeletal muscle. Reactive hyperemia was examined in individual capillaries of the red anterior (ALD) and white posterior (PLD) latissimus dorsi muscles of the anesthetized chicken following total blood flow occlusion of 3.5-180 s in length. Capillary red cell velocities were measured by the dual-slit photometric technique. The control capillary velocities in the ALD and PLD were 0.56 +/- .03 (SE) and 0.34 +/- .03 mm/s, respectively. With increasing occlusion lengths, the reactive hyperemia peak velocity, hyperemia duration, and excess flow were found to increase progressively in both muscles suggesting a metabolic origin for the response. The ALD showed a greater peak reactive hyperemia flow than the PLD following occlusion lengths of 7-60 s and a greater excess flow following occlusion lengths of 15 s and longer. However, when these data were normalized to control velocities by calculating the peak-to-control velocity ratio and percent flow debt repayment, no significant differences were found between the two muscles. Furthermore, the reactive hyperemia durations were similar in the two muscles at each occlusion length. These data demonstrate that reactive hyperemia is similar in two muscle types which are known to differ considerably in resting metabolism and anaerobic capacity.


Central angiotensin II-induced responses in spontaneously hypertensive rats. The brain isorenin angiotensin system has been implicated in the development of spontaneous hypertension by several investigators. The experiments reported here were designed to test the responsiveness of unanesthetized spontaneous hypertensive (SH) rats to intracerebroventricular angiotensin II injections compared to Wistar-Kyoto (WK) normotensive controls. The results indicate that there is no difference between SH and WK animals in drinking responses or antidiuretic hormone release to central angiotensin II injections; however, an increased pressor responsiveness to intraventricular angiotensin II in SH as compared to WK was observed. The results of intravenous infusions of pressor substances in these experiments and reports by other investigators suggest that the increased blood pressure effects to central angiotensin are due to three possible factors: 1) increased vascular responsiveness of SH to vasoconstrictor substances in general, 2) increased vascular sensitivity of SH rats to sympathetic outflow, and 3) decreased baroreceptor reflexes to acute increases in blood pressure. We suggest that the brain isorenin-angiotensin system may be involved in spontaneous hypertension by increased production of angiotensin II or by activation of a potentiated sympathetic system, but not by a generalized increased sensitivity of brain receptors to central angiotensin.


A new method for internal calibration of left ventricular cineangiography. Previous methods of internal calibration for cineangiography have made use of reference objects such as catheters or wires of known length or diameter. Such devices have either insufficient X-ray resolution, or require a specific orientation within the ventricle which is difficult to confirm. External calibration methods, while eliminating these errors, can only estimate actual position of the left ventricle. The use of a Swan-Ganz balloon catheter as a calibration object diminishes these problems. When positioned within the left ventrical and filled with a radiopaque medium, the balloon is of sufficient size and density to avoid errors induced by previously employed objects. The inflated balloon geometry is simple and reproducible. The use of this internal calibration catheter markedly diminishes major sources of errors in the determination of ventriculograms for both dogs and humans.


A solid-state arteriovenous oxygen difference analyzer for flowing whole blood. This communication describes a spectrophotometric device which determines the arteriovenous oxygen difference (a-v O2) on whole blood flowing through optical cuvettes. The instrument consists entirely of commercially available solid-state components, including the light sources, light-emitting diodes. When calibrated against conventional determinations of blood oxygen content, the output of the a-v O2 analyzer was shown to be highly linear and to be independent of total hemoglobin concentration. The electronic circuit, the theory of the measurement, and sources of error are described in detail.


An electron-dense extracellular material in the nervous system of Aplysia. An electron dense material is found in the extracellular space of the nervous system of Aplysia, a marine mollusc whose ganglia are widely studied by neurobiologists. This material appears to consist of irregular electron-dense granules, with diameters of approximately 600 A. This material is found between the glial cells that surround the neuronal perikarya. It is not found in other regions of the nervous system. Because it is found in the ganglion cell layer of the nervous system and because the neurons contain what may be the precursor of this substance, the electron-dense material is regarded as most probably being a neuronal product. The importance of this material is that it is one of the few examples of visible structure in the extracellular space of the nervous system.


The early stages of Wallerian degeneration in the severed optic nerve of the newt (Triturus viridescens). The initiation of Wallerian degeneration in the severed optic nerve of the newt (Triturus viridescens) was very rapid and intense. Significant degeneration of nonmyelinated axons was observed as early as six hours after lesion (h.a.l.) and was almost complete by 48 h.a.l. Initial degeneration of non-myelinated axons began in "extracellular digestion chambers" formed between burgeoning ependymoglial processes. The remaining fragments and debris were later phagocytized by surrounding ependymoglial processes. Many axons of myelinated fibers have degenerated as early as 6 h.a.l. However, the overall population of myelinated axons degenerates at a much slower rate than nonmyelinated ones, for many of them appear intact as late as 48 h.a.l. Some myelin sheaths show significant signs of degeneration by 6 h.a.l. Indeed, by this time a number of myelinated fibers have completely degenerated leaving only large vacuolated spaces in the nerve parenchyma. Swelling and vacuolization of the sheath are among the earliest signs of myelin degeneration. The ependymoglial cell response to optic nerve lesion is manyfold and dramatic. By 6 h.a.l. there are signs of burgeoning ependymoglial processes which begin to resemble scar formation (gliosis) by 48 h.a.l. The morphological evidence is consistent with the concept of an important phagocytic role of ependymoglial cells during the early stages of optic nerve degeneration.


Degeneration of germ cells in normal, hypophysectomized and hormone treated hypophysectomized rats. In normal adult rats some germ cells degenerate at several vulnerable steps of spermatogenesis. These are the type A spermatogonia, midpachytene spermatocytes, primary and secondary spermatocytes which degenerate during their respective maturation divisions and step 7 and 19 spermatitids. In the present study, these degenerating cells were examined under the electron microscope, and their frequency was determined in toluidine blue stained semithin sections of testes from normal, hypophysectomized (at 5.5 days after operation) and hypophysectomized rats injected with FSH and LH separately or in combination. With the exception of the step 19 spermatids, the degenerating germ cells underwent necrosis in vacuolated spaces delimited by Sertoli cells. In the case of the affected step 19 spermatids, an apical cytoplasmic process of the Sertoli cell initially ensheathed a long segment of their flagellum, and then each degeneration cell was drawn deep in the seminiferous epithelium where it was phagocytozed by the Sertoli cell. Soon after hypophysectomy the incidence of degenerating mid-pachytene spermatocytes, step 7 and 19 spermatids which are present in stages VII or VIII of the cycle of the seminiferous epithelium, increased significantly. In contrast the number of degenerating primary or secondary spermatocytes during the meiotic divisions seen in stage XIV of the cycle or of any other germinal cell was not significantly modified. While the injection of FSH alone had no influence on the number of degenerating cells in hypophysectomized rats, injections of LH at the two doses administered (0.7 microng or 20 microng) reduced significantly the number of degenerating cells seen in stages VII-VIII of the cycle; combined injections of FSH and LH (20 microng) reduced the number of these degenerating cells to the normal low values. Thus it appeared that the mid-pachytene spermatocytes and the step 7 and 19 spermatids, all present in the adluminal compartment of the seminiferous epithelium in stages VII or VIII of the cycle, were more sensitive to the presence of absence of gonadotropic hormones than the other germ cells present in the seminiferous epithelium.


Electron microscopic autoradiographic analysis of the uptake and intracellular transport of H3-leucine by the rat submandibular gland acinar cells in tissue slices. Uptake of H3-leucine into secretory product and its subsequent intracellular transport was analyzed by electron microscopic autoradiographic techniques in the rat submandibular gland acinar cells in vitro. The route and kinetic timetable of intracellular transport was established for the acinar cell secretory product by calculating the present of silver grains and relative grain density associated with the various organelles on a time sequence basis. Radioactivity was first associated with the rough endoplasmic reticulum; then the convex surface of the Golgi apparatus; the concave surface of the Golgi apparatus; and finetics of intracellular transport in the rat submandibular gland acinar cell with other established systems revealed only a difference in the exit of radioactivity from the concave surface of the Golgi apparatus.


Electron microscopic studies on the myotomes of larval lamprey, Lampetra japonica. Myotomes of the caudal one-third of the body of 26-day-old larval lampreys, Lampetra japonica, were studied by electron microscopy. Each myotome consists of horizontally stacked muscle lamellae. The myotomes are covered laterally by a single layer of flattened cells called here "lateral cells", and the other aspect is covered by an external lamina. The myotomes are midsegmentally innervated. Each muscle lamella usually contains two single cortical layers of myofibrils along the dorsal and ventral sarcolemma with a nucleus and mitochondria interposed between two layers. Numerous peripheral couplings are observed with relatively less developed triads. There are no membrane specializations to connect adjacent muscle lamellae within a myotome. Intermyotomal junctions are, however, noted between tips of cytoplasmic processes of muscle lamellae of adjoining myotomes. They resemble tight or gap junctions. No myofibrils are present in these cytoplasmic processes. Myotendinous junctions, with "terminal couplings" (Nakao, '75), are seen under development at the myoseptal ends of muscle lamellae. Lateral cells contain only ordinary organelles and no special structures such as myofibrils are found in the cytoplasm. They are connected to each other and to muscle lamellae by primitive desmosomes. They generally have no external lamina investment.


Alteration by halothane of glucose and glycogen metabolism in rat skeletal muscle. Exposure of resting rat diaphragm for one hour in vitro to halothane (1-1.5, 2-2.5 and 4-4.5 per cent in oxygen) produced significant alterations of intracellular glucose disposition. Glycolysis (as measured by lactate production) increased, while glycogen formation was inhibited in a dose-related fashion. Net glucose uptake was unaffected by the anesthetic except during exposure to 4-4.5 per cent halothane, when 14 per cent depression of uptake was found. Total glycogen content decreased, due mainly to the inhibition of glycogen synthesis and to some extent to a stimulation of glycogenolysis. The anesthetic did not interfere with the effect of insulin on glucose uptake or the intracellular disposition of glucose. Creatine phosphate concentrations decreased following exposure of diaphragm to 1-1.5, 2-2.5 and 4-4.5 per cent halothane, while the adenosine triphosphate concentration declined after exposure to 4-4.5 per cent only. Although the mechanism(s) whereby halothane alters glucose and glycogen metabolism are unknown, it is possible that the anesthetic acts primarily by affecting membranes containing enzymes involved in the metabolism of glycogen.


Mucociliary flow in the trachea during anesthesia with enflurane, ether, nitrous oxide, and morphine. Tracheal mucociliary flow rates in dogs were measured with a radioactive droplet technique during thiopental anesthesia, and subsequently during enflurane, either, and nitrous oxide-morphine anesthesia on different occasions. Enflurane, at 0.6, 1.2, 1.8 MAC, produced a dose-dependent, reversible depression of mucociliary flow equal to that previously reported for halothane. Nitrous oxide-halothane and nitrous oxide-morphine depressed mucociliary flow to the same extent as halothane at equivalent MAC levels. Ether did not depress mucociliary flow significantly from the thiopental control at any MAC level.


Pancuronium-induced neuromuscular blockade, and its antagonism by neostigmine, at 29, 37, and 41 c. To determine the effects of variations in temperature on the neuromuscular blockade produced by pancuronium, the drug was infused intravenously into 18 cats anesthetized with chloralose and urethane at a constant continuous rate to produce and maintain 90 per cent depression of twitch tension of the anterior tibial muscle following supramaximal stimulation of the peroneal nerve. The mean (+/-SE) infusion rates of pancuronium needed were 0.44 +/- 0.05, 0.99 +/- 0.11, and 1.05 +/- 0.09 microng/kg/min (r = 0.73) at 29, 37, and 41 C, respectively. In contrast, the doses of neostigmine necessary for 50 per cent antagonism of the pancuronium-induced depression of twitch tension were not significantly different at the three temperatures. The time required to achieve peak neostigmine effect was longer at the lowest temperature. The durations of neostigmine action were longer at 29 and 37 than at 41 C. It is concluded that hypothermia augments neuromuscular blockade produced by pancuronium and prolongs the time to peak effect, and possibly the duration of action, but not the dose of neostigmine needed to antagonize the blockade.


Pancuronium bromide enhances atrioventricular conduction in halothane-anesthetized dogs. The effect of pancuronium bromide on atrioventricular conduction was studied by His-bundle electrocardiography during atrial pacing at different heart rates in halothane-anesthetized dogs. Pancuronium bromide, 0.1 mg/kg, uniformly enhanced atrioventricular conduction, as evidenced by decreased A-H interval (the time from the onset of the first high-frequency component of atrial depolarization to His deflection). Wenckebach second-degree atrioventricular block appeared in five of 14 animals during atrial pacing with halothane anesthesia. This block was uniformly abolished by pancuronium. The enhancement of atrioventricular conduction may contribute to the development of tachyarrhythmias following administration of pancuronium in certain patients, particularly those who have atrial fibrillation or atrial flutter.


Circadian rhythms in the cutaneous reactivity to histamine and selected antigens, including phase relationship to urinary cortisol excretion. Data show that intradermal skin reactions to histamine, house dust and grass pollen extracts follow a prominent circadian pattern, the response elevated in the afternoon, peaking in the evening and with a morning trough. Urinary hydrocortisone excretion curves exhibit agreement in antiphase timing.


Physiology of steroid dependent and non-steroid dependent asthmatic youths. This study was designed to compare physical findings, pulmonary function and pituitary-adrenal function in steroid dependent (SD) and non-steroid dependent (NSD) children and adolescents in order to clarify similarities and differences between these groups. Study patients included 20 steroid dependent and 14 non-steroid dependent subjects. Abnormalities confined to the SD group included growth suppression, bone age retardation and cataracts. Pulmonary function abnormalities were severe in both groups. While the SD group also showed a degree of pituitary-adrenal abnormality. This suggests that chronic pulmonary disease may have physiologic consequences extending beyond the pulmonary tree.


The long-term use of beclomethasone dipropionate for the control of severe asthma in children. Thirty-nine children with severe asthma who had been treated with aerosol inhalations of beclomethasone dipropionate for 33 to 34 months were studied. Twenty-eight were still benefitting from the drug, thrush had occurred in three, and only six of the 20 originally steroid-dependent now required steroid orally. The authors feel that this is an efficacious, safe medication but stress that systemic steroid therapy should be promptly reinstituted during acute exacerbations in steroid-dependent patients.


Atopic skin test re-evaulated. IV. The use of compound 48/80 in routine skin testing. Analysis of skin-test results obtained with compound 48/80 has indicated that this substance deserves a place in the standard series of test fluids for routine skin testing. No influence of sex or season was detected but there were significant differences in response related to the age (strongest reactions in the 16-40 year age group) and to the diagnosis (strongest reactions in the atopic patients).


Response of the nasal mucosa to allergen challenge measured by two different methods of rhinomanometry. Nasal provocation tests with allergen (House Dust 5.0 mg/ml or Grass-Pollen 10000 Noon Units/ml) were performed on patients suffering from perennial rhinitis or pollinosis. The changes of the nasal passages before and after allergen challenge were measured by two different methods, (1) the rhinomanometry anterior (Balloon Method) and (2) the rhinomanometry posterior (V-P Method). No distinct differences were observed between results obtained by the two methods. Both are therefore considered suitable and applicable for nasal provocation tests. For a satisfactory result using both techniques, the measurements should be made within at least 30 minutes but preferably 60 minutes after the allergen challenge.


Atmospheric fungi in the desert town of Arad and in the coastal plain of Israel. A two years' volumetric survey of the airborne fungi in the arid town of Arad revealed markedly lower spore concentrations than in the coastal region of the country. Low incidence prevailed throughout the year except for high peaks in October-November, closely related to the distribution of Cladosporium spores. Air-spora composition, annual frequency and seasonal variation of fungal genera and species at the two sites were compared.


Effects of autonomic drugs on the cardiovascular system: dogs with achalasia (under halothane anesthesia). The parasympathetic and sympathetic components of the autonomic systems as they relate to cardiovascular function were studied on dogs with achalasia of the esophagus. This was accomplished by administering the parasympathomimetic drugs methacholine (0.2 mg/kg, subcutaneously), 2 doexy-D-glucose (100 mg/kg, intravenously (IV), the parasympatholytic drug atropine (0.2 mg/kg, IV), the sympathomimetic agent epinephrine (2.5 microng/kg, IV), and the beta adrenergic blocker propranolol (0.5 mg/kg, IV); and then measuring cardiac output, stroke volume, heart rate, mean arterial pressure, pulse pressure, central venous pressure, total peripheral resistance, PaCO2, PaO2, pH, and base deficit. Cardiovascular responses to the administration of the parasympathomimetic drugs, methacholine and 2 deoxy-D-glucose, or the parasympatholytic drug, atropine, were similar to those observed in normal dogs. Cardiovascular responses to the administration of the sympathomimetic drug epinephrine and the sympatholytic drug propranolol or beta blocker were also consistent with those observed in normal dogs. It can be interpreted from this pharmacologic evidence that parasympathetic and sympathetic innervations to the cardiovascular system are present in dogs with achalasia of the esophagus. Fewer cardiovascular variables were significantly altered in dogs with achalasia than in normal dogs. Since this was true for both the sympathetic and the parasympathetic values, it is interpreted as reflecting their general health rather than a specific lesion.


Increased sensitivity of canine sarcoma cells to lysis with alloantiserum and complement after pretreatment of cells with doxorubicin HC1. The 51Cr release assay was used to detect lysis of canine sarcoma cells incubated in vitro with alloantiserum and complement. Preincubation of the target cells with the anti-cancer agent doxorubicin-HCl increased the sensitivity of the cells to antibody-mediated lysis. The effect was dependent upon drug dose and was not reproduced by treatment with methotrexate, cytarabine, or dactinomycin. The observation suggests a possible ancillary mode of action for doxorubicin-HCl on neoplastic cells.


Toxic effects of aflatoxin B1 in male Holstein calves with prior infection by flukes (Fasciola hepatica). This experiment was designed to compare 3 dose levels of aflatoxin B1 (0.0, 0.5, and 1.0 mg/kg of body weight) and 2 infection levels of Fasciola hepatica metacercariae (0 and 220) to determine whether an additive effect from aflatoxin B1 occurs when fascioliasis is present in dairy calves. Twenty-four male, Holstein calves, 4 weeks old, and averaging 45.8 kg each, were assigned at random to 6 treatment groups, 4 calves per group: group 1--negative control; group 2--0.5 mg of aflatoxin B1/kg; group 3--1.0 mg of aflatoxin B1/kg group 4--220 metacercariae; group 5--220 metacercariae plus 0.5 mg of aflatoxin B1/kg; and group 6-220 metacercariae plus 1.0 mg of aflatoxin B1/kg. The single oral dose of 220 metacercariae was given (groups 4, 5, and 6) at the start of the 10-week experiment, and 5 weeks later, the single oral dose of aflatoxin B1 was given (groups 2, 3, 5, 6). Results from the principals, as compared with that from the controls (group 1), included significant decreases of dry matter intake (P less than 0.006), body weight (P less than 0.024), and serum albumin (P less than 0.04), and in groups 4, 5, and 6 infected with 220 flukes, there were significantly increased values of prothrombin time (P less than 0.014), serum alkaline phosphatase (P less than 0.04), and serum sorbitol dehydrogenase (P less than 0.007). Significant differences in number of flukes recovered from liver were seen in groups 4 to 6 given 0, 0.5, and 1.0 mg of aflatoxin B1/kg (P less than 0.046). The single oral dose of 22* fluke metacercariae in groups 4, 5, and 6 resulted in significantly increased concentrations of serum total protein (P less than 0.003) and globulins (P less than 0.01). Results from the development of the flukes from metacercariae to the mature state with sizes, numbers, feeding habits, and pathologic lesions were described. Differences in numbers of flukes recovered from liver of groups 4 to 6 and the presence of pneumonia in calves of group 6 indicated aflatoxin B1 produced persisting, lowered resistance. In all animals necropsied, the liver was the organ most affected by aflatoxin B1 as well as with flukes. Periportal fibrosis, monocytic infiltration, fatty infiltration, and bile duct proliferation were the usual lesions induced by aflatoxin B1. Additive toxic effects were observed in the groups 5 and 6 dosed with flukes and aflatoxin B1, with significant variations of serum and plasma values, as well as increased severity of histopathologic changes.


Hemodynamics and myocardial function during acute hypoxia in the pony. Hemodynamics and myocardial contractility were evaluated in 6 unanesthetized ponies during hypocapnic and isocapnic hypoxia  and during hypocapnic hypoxia after beta adrenergic blockade with propranolol. Hypocapnic hypoxia, with a mean arterial oxygen pressure (PaO2) of 41.9 mm of Hg, produced a decrease in stroke index and an increase in heart rate, with no change of cardiac index. A moderate increase in left ventricular contractility occurred during hypocapnic hypoxia. Beta adrenergic blockade abolished changes in nearly all indices of left ventricular contractility during hypocapnic hypoxia, suggesting that the antonomic nervous system plays a definite role in the genesis of circulatory changes during acute hypoxia. Isocapnic hypoxia produced a more well-defined increase in left ventricular contractility. Changes in right ventricular contractility were not observed in any of the hypoxia periods when the concurrent effects of a significant increase in afterload was taken into consideration. The tension-time index, measured as a guide to myocardial oxygen consumption, increased during each hypoxia period in both the right and left ventricle, and was not affected by beta adrenergic blockade.


Effects of hypothermia on the visual-evoked brain potential in dogs. Visual-evoked potentials, as seen on a signal-averaged electroencephalogram, demonstrated clearly recognizable changes in 6 normal dogs undergoing deep hypothermia and rewarming. These changes were more clearly recognizable than changes in the unevoked electroencephalogram with or without signal averaging.


Anticoccidial activity of eight compounds in domestic mink. Eight compounds were tested for anticoccidial activity in 44 domestic mink (Mustela vision). A treatment group consisted of 4 mink exposed to 2 inoculumns of sporulated oocysts on day 0 and day 22 of the experiments. Each inoculum contained 2,000 Isospora laidlawi, 2,000 Eimeria vision, and 2,000 Eimeria sp. One compound was administered to each treatment group; a control of 4 juvenile mink and a control group of 4 adult mink were designated. All treatments were given each day for 30 days after the initial exposure, except lincomycin which was administered for 14 days. In juvenile mink (3 to 4 months old), amprolium at dose level of 0.012% and sulfaquinoxaline at dose level of 0.024% in the water inhibited almost all of the oocyst production when compared with that of the control group. Lincomycin injected at dose level of 5 mg/day/mink was ineffective in suppressing oocyst production. In adult mink (2 to 4 years) monensin sodium at dose level of 0.012% a commercial antiobiotic-sulfonamide mixture at dose level of 0.49%, and lasalocid solium at dose level of 0.01% in the feed inhibited almost 100% oocyst production. Lasalocid sodium at dose level of 0.10% in the feed was lethal to 3 to 4 mink. Sulfamethazine at dose level of 0.014% and sulfathiazole at 0.014% in the feed had limited anticoccidial activities.


Intoxication of cattle with sodium bromide-contaminated feed. Five concentrations of bromide ion, sodium bromide, were incorporated into a pelleted ration and fed to 5 groups of cattle for 49 days. Another group of cattle was fed volunteer oat hay cut from a field that had been fumigated with methyl bromide. On analysis, the hay contained between 6,800 and 8,400 parts per million of bromide ion. Groups fed the pelleted ration containing the highest concentration of bromide and those eating the contaminated hay developed signs of motor incoordination between the 10th and 12th days. The sign of incoordination correlated with serum bromide concentrations of 30 mEq/L or more. Serum bromide concentrations and associated neurologic signs subsided markedly 14 days after feeding of the toxic feeds was discontinued.


Antibody studies in ponies vaccinated with Venezuelan equine encephalomyelitis (strain TC-83) and other alphavirus vaccines. Serologic studies in 24 ponies indicated that prevaccination antibodies to Venezuelan equine encephalomyelitis (VEE) virus (strain TC-83) had no influence on hemagglutination-inhibition (HI) antibody stimulation by western equine encephalomyelitis (WEE) or eastern equine encephalomyelits (EEE)-WEE vaccines. However, studies of the effects of VEE neutralizing antibodies on neutralizing antibody stimulation by the heterologous alphavirus vaccines were inconclusive. The VEE, WEE, and EEE antibody responses were studied in 18 VEE-vaccinated (strain TC-83) animals (13 ponies and 5 horses) at 9 to 14 months after challenge of immunity with virulent VEE virus. The VEE HI, and neutralizing antibodies in combination were associated with greater suppression of VEE antibody stimulation than were VEE neutralizing antibodies alone. The VEE geometric mean antibody titers (GMT) increased 26- and 64-fold for HI antibodies and for neutralizing antibodies, respectively, in 5 animals that had prechallenge exposure titers of VEE neutralizing antibodies only. In contrast, the GMT increased only threefold and eightfold for VEE HI antibodies and for neutralizing antibodies, respectively, in 8 animals that had prechallenge exposure titers of both VEE HI and neutralizing antibodies. Five animals which were seronegative for prechallenge VEE antibodies and had survived challenge exposure gave primary VEE-immune response. Protection in these animals may have resulted from high-titer cross-reacting antibodies to WEE or EEE viruses, or both. Changes in the GMT for WEE HI, neutralizing, and complement-fixation antibodies after challenge exposure were statistically insignificant. However, a statistically significant increase in the EEE HI-GMT occurred in ponies that had low (or no) prechallenge exposure titers of VEE antibodies.


Pharmacology of procaine in the horse: evidence against the existence of a "procaine - penicillin" complex. It has recently been suggested that procaine penicillin existed in solution in vitro and in vivo as a "procaine - penicillin" complex rather than as dissociated ions. In vivo, this complexed procaine was considered unavailable for hydrolysis by plasma esterases or for interaction with pharmacologic receptors for procaine. When procaine penicillin was intramuscularly given to horses, about 90% of the procaine in blood drawn from these horses was split at the same rate as authentic procaine or procaine penicillin added to equine blood in vitro. In vitro, procaine and procaine penicillin partitioned similarly from aqueous medium at physiologic pH into several organic solvents and were split at the same rate by blood or plasma esterases. Experiments on the time course of the partitioning of procaine from procaine penicillin into benzene showed no evidence for the existence of a "procaine - penicillin" complex within seconds after procaine penicillin was added to aqueous medium. Thin layer chromatography in 2 dimensions also yielded no evidence for the existence of this postulated complex. These results show no evidence in support of the "procaine - penicillin" hypothesis and argue against the physical and pharmacologic and forensic implications of this hypothesis.