Influence factors affecting career choice of preclinical medical technology students. Over a seven-year period, data were gathered on 249 declared medical technology majors enrolled in an Introduction to Medical Technology course at the University of Iowa. The Kendall Tau C test for significance (p = less than .05) was utilized in determining the influence of several variables or factors in the students' choice of medical technology as a career. Such factors as the type of work, demand for medical technologists, and desire to help people were found to be highly motivating factors in choice. It appeared the motivation was primarily internalized with assistance sought from various sources. The decision of medical technology as a career was predominantly made in the junior/senior year in high school or freshman/sophomore year in college.


A dynamic computer system for the clinical laboratory. The Clinical Laboratory Computer System currently in use at the Medical University of South Carolina is described. Not only is the existing hardware listed and shown in some detail, but also the workload, laboratory data center personnel, typical procedures, and examples of selected input and output documents are included. Particular emphasis is placed on the dynamic nature of the system, which allows the user to proceed easily in developing new programs as the requirements of the laboratory continue to change and grow. To illustrate this point, programs written by the user are described in general terms.


A study of antimicrobial misuse in a university hospital. We undertook a prospective study to determine patterns and sequelae of antimicrobial misuse and factors associated with inappropriate antimicrobial therapy in a teaching hospital. Over an eight-week period, 144 (26.2%) of 549 hospitalized medical and surgical patients received one or more courses of antimicrobial therapy. An average course comprised 1.4 drugs. Presumptive infection was the reason for 70% of courses and prophylaxis, 30%. Therapy was judged appropriate in 59% of courses overall. Unnecessary therapy, poor drug choice (bacteriologically, pharmacologically, or both), or misguided prophylaxis most frequently underlay inappropriate therapy. Adverse reactions (17% overall) were twice as frequent and the cost of therapy was 55% greater in inappropriate courses. Performance of pretherapy cultures (p less than 0.05), obtaining gram-stained smears of sputum in presumed respiratory tract infections (p 0.001), and notation in the record that antimicrobial therapy had been instituted (p less than 0.001) were strongly associated with appropriate therapy. This study underscores the need for more effective programs of postgraduate education which stress basic principals of infectious disease and antimicrobial pharmacology and guidelines for prophylaxis. Antimicrobial utilization review should figure heavily in hospital programs of medical self-evaluation. Additional measures to upgrade the use of antibiotics are discussed.


Coccidioidomycosis in potentially compromised hosts: the effect of immunosuppressive therapy in dissemination. Charts of 126 patients with coccidioidomycosis were reviewed. Sixteen of these were patients who had malignancies, uremia, or a collagen-vascular disease and/or had received recent immunosuppressive drug therapy. The rate of disseminated infection was 50% in this group. (The dissemination rate was 14% in 110 control patients.) No case of dissemination occurred in patients who only had the above underlying diseases; all cases of dissemination were among those who had received immunosuppressive therapy. The dissemination rate in control patients was higher for patients age 40 or over than for younger patients. The dissemination rate showed no age-related difference, however, in patients treated with immunosuppressive drugs. The dissemination rate was similar in control patients of both sexes and uniformly higher for both immunosuppressively treated males and females. The dissemination rate did not appear to be influenced by the number of circulating lymphocytes if the patient had received immunosuppressive drugs. Patients with disseminated disease who had received immunosuppressive drugs were capable of producing a serological response to the coccidoiidal organism in high titer but none had positive skin test reactivity. Disseminated coccidioidomycosis is not uniformly fatal in the immunosuppressed host: half of our patients are alive an average of 33 months after diagnosis.


Hairy cell leukemia: diagnosis and management. Long-term follow-up of 18 patients with hairy cell leukemia seen at a single institution is reported: diagnostic and therapeutic modalities are described. Although the clinical features of this disease are homogeneous, it is frequently misdiagnosed initially. Bone marrow biopsy was diagnostic in all 17 patients studied prior to splenectomy. The presence of circulating "hairy" cells is greatly variable. The cause of pancytopenia is unclear: splenic sequestration was not demonstrated by 51Cr red cell studies in three of four patients. In most patients, splenectomy resulted in amelioration of pancytopenia. No clinical features prior to splenectomy could predict response to surgery. The results of chemotherapy and splenic irradiation were variable and unpredictable. Although bone marrow infiltration persists following splenectomy, this remains the only established therapy in hairy cell leukemia and is usually followed by long, uncomplicated survival.


Problems encountered in the treatment of pregnancy-induced hypertension. A point of view. This point of view encountered in the treatment of pregnancy-induced hypertension enumerates the most common problems encountered when treating the disease. These problems include: terminology, etiology and pathogenesis, known facts, failure to identify the patient, loss of life for mother and baby, complications, recognition of early disease, and treatment not uniform or individualized. The severe forms of the disease are preventable and should never occur, but once present they should yield a zero maternal mortality rate and a fetal salvage of greater than 90%. Proper therapy of severe disease is primarily the use of pharmacologic doses of magnesium sulfate given intravenously and the prevention of a cerebral vascular accident in the mother. Induction of labor and removal of the products of conception will cure the disease.


The emotional and psychosexual aspects of hysterectomy. The emotional sequelae of hysterectomy have long been suggested as a concern of the gynecologist. A review of the literature reveals that there are surely concrete changes in the functioning, attitudes, and behavior of patients who undergo this procedure. Since the gynecologist acts as the "uterus remover," it is our specialty that should be dealing with these women patients to carry them through the possible effects of such surgery. In addition, it would be wise for all of us to examine our own indications for this procedure in order to be confident when faced with criticisms that our specialty considers the uterus less valuable than other organs, rendering it more vulnerable to the unthinking surgeon.


Remission of pure red cell aplasia following oxymetholone therapy. A 53-year-old male with a long-standing idiopathic pure red cell aplasia, refractory to testosterone cypionate, fluoxymesterone, and corticosteroid, was successfully treated with oxymetholone. Blood count, bone marrow, reticuloendothelial bone marrow scan, and ferrokinetic studies showed a marked increase of erythropoiesis in response to oxymetholone. The patient became hematologically normal within 12 weeks and has required no further transfusions. This observation suggests possible difference of mechanisms in the action of various androgenic drugs. It also suggests that failure of response to one androgenic agent does not necessarily mean the other androgenic agents will not be effective in cases of refractory idiopathic pure red cell aplasia.


Essential hypernatremia.

Essential hypernatremia. Described is a patient who presented with hypernatremia in the absence of dehydration. Further investigation revealed a tumor in the hypothalamic area, and evidence of anterior pituitary hypofunction. Water loading did not correct hypernatremia, and the results of the water-loading test suggested that hypernatremia had resulted from an elevated "osmotic set point" for the release of antidiuretic hormone, ie, "essential hypernatremia."


Steroids in human myometrium and peripheral blood during the menstrual cycle. Blood samples were collected prior to vaginal hysterectomy from nine women in the proliferative phase of the cycle and from 15 women in the secretory phase, and from each uterus five grams of the fundus were obtained. The concentrations of progesterone (P), 20alpha-dihydroprogesterone (20alpha-DHP), estradiol-17beta (E2), and estriol (E3) were determined in serum and in the tissue with the use of specific radioimmunoassays. The concentrations of P and 20alpha-DHP in serum and myometrium were significantly higher in the secretory than in the proliferative phase. Furthermore, the concentration of P in myometrium was significantly higher than in serum in the secretory phase, indicating a specific uptake of P by the myometrium. The concentration of E2 was about 10 times higher in the myometrium than in the serum during both phases of the cycle and appeared to be independent of the serum levels. This indicates a specific but limited uptake of E2 by the myometrium. The E3 levels in the tissue showed no significant differences during the menstrual cycle, whereas in the serum the E3 concentrations were higher in the secretory than in the proliferative phase of the cycle.


Vaginismus.

Vaginismus. Eighty patients with vaginismus were seen in the Human Sexuality Clinic, McMaster University Medical Center, between 1972 and 1976. The diagnosis was made based on history and physical demonstration of perineal muscular spasm. The patients were classified according to the presenting complaint as well as to the degree of muscle spasm experienced at the time of physical examination. In the management of these patients, relaxation, self and mutual pleasuring exercises, Kegel exercises, and physical examination played an important role in successful treatment. Certain male problems were identified during treatment, including situational impotence and premature ejaculation. In our series the women who chose to be treated without an involved partner had comparable success rates to those choosing conjoint therapy. With the use of the combination of available techniques with special emphasis on the pelvic assessment as an educational experience for the patient, good success can be obtained in treating vaginismus with the conjoint approach or office management of the woman alone.


Extreme hyperbilirubinemia in a patient with hereditary spherocytosis, Gilbert's syndrome, and obstructive jaundice. Hyperbilirubinemia may be of several etiologies in the individual patient. An 18-year-old man presented with extreme hyperbilirubinemia (direct bilirubin 23.0 mg/dl, total bilirubin 60.0 mg/dl), hepatosplenomegaly, and anemia. Hematologic studies prelaparotomy documented the presence of hereditary spherocytosis. Intraoperative liver biopsy revealed moderately reduced levels of glucuronyl transferase activity (Gilbert's syndrome). Common bile duct obstruction secondary to choledocholithiasis was found, and a cholecystectomy and splenectomy were performed. This case stresses the potential confusion among several diseases which may present with hyperbilirubinemia.


The influence of lung volume on expiratory flow rates in diffuse interstitial lung disease. This study evaluated maximum expiratory flow rates with respect to lung volume and maximum recoil pressure in selected patients with diffuse interstitial lung disease who had normal large airway function by standard technique. Coefficient of retraction was normal or greater than normal in all. Peak flow varied directly with lung volume as in normals. At 50% vital capacity (VC) and 25% VC, the absolute flow rates varied from higher to lower than normal. However, when flow was adjusted to volume, the flow/volume ratio was normal or high in all. Flow/volume ratio at mid-lung volume appeared to increase with increase in coefficient of retraction. Patients with frequency dependence of compliance had lower flow/volume ratios at 25% VC than those without, although still within normal range. Thus, despite recognized wide variations in normals, the flow/volume ratio is pertinent to the evaluation of reduced air flow rates in in interstitial lung disease to distinguish abnormal upstream airway resistance from volume-dependent reduction of flow rate. An effort-independent flow rate that yields a supernormal flow/volume ratio suggests increased recoil properties of the respiratory system.


Diagnosis of intrauterine growth retardation by a simple clinical method: measurement of uterine height. Generally there is a tendency to underrate the value of uterine height in the diagnosis of intrauterine growth retardation (IUGR). This fact is probably due to the lack of standard normal values for this measurement. In a group of 298 healthy pregnant women, the 10th, 50th, and 90th percentile were calculated by week of amenorrhea. Uterine height was measured with a nonelastic measuring tape, from the symphysis pubis to the fundus uteri. With the use of these standard values the predictive value of the method was established. Of 44 neonates with low birth weight for gestational age, 38 had a uterine height below the 10th percentile (sensitivity 86%). Six cases of IUGR were not diagnosed by this method. Of 95 neonates with adequate birth weight, 85 had uterine values above the 10th percentile (specificity 90%). Ten (10%) of these were predicted as low birth weight but were born with adequate weight. The uterine height measurement is shown to be a very good method for detecting IUGR. It can be used as a screening test to detect impairment in fetal growth and to make early referral of those pregnancies.


Pasteurella multocida infectious arthritis. Pasteurella multocida, a small gram-negative rod, is a domestic animal saprophyte that occasionally causes disease in humans. Infectious arthritis may develop from a superficial animal bite or scratch. Nine previous cases of infectious arthritis due to this organism have been documented in the literature, and a tenth case is reported here. Most patients had recent animal exposure, and half the patients had underlying chronic rheumatoid arthritis. Clinical signs of inflammation were consistently present; however, systemic infection was infrequent. The lack of positive synovial fluid gram-stain smears may make differentiation from other forms of infectious arthritis difficult. Penicillin in moderate doses is effective therapy, with osteomyelitis developing in only two patients. The tendency for this syndrome to affect patients with rheumatoid arthritis may reflect deficient local defense mechanisms, chronic steroid therapy, or increased ownership of pets. The mechanism of spread of infection to the joint space appears to be through contiguous spread from a skin site rather than by the hematogenous route in most cases.


Use of supine pressor test to prevent gestational hypertension in primigravid women. The supine pressor (roll-over) test was performed on 62 nulliparous patients under 20 years of age at conception. The 28 patients (45%) with positive tests were treated to prevent the development of gestational hypertension. Four of those with a positive test and two of those with a negative test developed gestational hypertension. Compared with a composite of other reported studies of this test in which the patients were not treated, our results indicated a statistically significant reduction in the incidence of gestational hypertension. The supine pressor test appears to be useful clinically in young nulliparous women.


The syndromes of hydatidiform mole. I. Cytogenetic and morphologic correlations. Cytogenetic and morphologic analysis of 23 hydatidiform moles allowed the division into at least two syndromes: (1) the syndrome of complete (classical) mole is without an ascertainable embryo/fetus, gives a diploid karyotype, and manifests a progressive fluid engorgement of the villi as well as a gross, haphazardly distributed trophoblastic hyperplasia; (2) the syndrome of partial (incomplete) mole has an ascertainable fetus (alive or dead), gives a triploid karyotype, and exhibits a slowly progressing hydatidiform swelling in the presence of functioning villous capillaries that spares many villi; trophoblastic immaturity is constant and focal hyperplasia is inconspicuous but present. A single case of diploid mole with unusual morphologic features, complete with a fetus, may herald yet another syndrome. Human chorionic gonadotropin levels were initially high in practically all cases. There was no malignant trophoblastic disease in this small series, but a plea is made that partial moles be followed carefully in order to establish their relation to choriocarcinoma.


Effects of dexamethasone on leukocyte counts in pregnant sheep and fetal lambs. In adult nonpregnant animals and human beings, glucocorticosteroids increase circulating leukocytes (predominantly neutrophils) and decrease lymphocytes, monocytes, and eosinophils. We were interested in studying effects of glucocorticoids on leukocyte counts during pregnancy to determine any differences between responses in the nonpregnant and pregnant states. After general anesthesia was administered, we placed catheters in a carotid artery and a jugular vein in pregnant sheep and in fetal lambs. Six  days after surgery, we administered dexamethasone intravenously to the mother (0.2 mg. per kilogram) or to the fetus (0.06 mg. per kilogram) and obtained maternal and fetal jugular venous blood samples immediately before (control) and 3, 6, 12, 24, 48, and 72 hours after steroid injection. Administration of dexamethasone to the mother significantly increased total leukocyte and neutrophil counts (leukocytes per cubic millimeter blood) and decreased lymphocyte and eosinophil counts, but it did not change monocyte counts. Leukocyte counts returned to control values within 48 hours. Administration of dexamsthasone to the fetus rapidly increased total leukocyte and neutrophil counts, decreased monocyte and eosinophil counts, and had not effect on lymphocyte counts. Fetal leukocyte counts returned to control values by 24 hours after dexamethasone injection. Our results suggest that maternal and fetal leukocytes can respond to glucocorticoids as they do in the adult nonpregnant state.


SQ 20,881: effect on eclamptic--pre-eclamptic women with postpartum hypertension. The renin-angiotensin system has been implicated in the genesis of pre-eclampsia. To avoid fetal toxicity, five women were studied who developed hypertension, proteinuria, and edema in the last trimester of pregnancy and whose BP elevation persisted immediately postpartum. At about 6 hours after delivery the CE enzyme inhibitor (SQ 20,881) was given in incremental doses ranging from 0.25 to 3.0 mg. per kilogram intravenously, before and after diuresis with furosemide, 40 mg. intravenously. BP was measure every 2 minutes and PRA and angiotensin II concentration before treatment, 30 minutes after 0.25 to 0.30 mg. per kilogram, and 30 minutes after 2.0 to 3.0 mg. per kilogram. Echocardiographic assessment of CI and PVR was performed before treatment and after a maximum dose in three patients. Before diuresis, CE blockade had no effect on heart rate, BP, CI, PVR, or PRA, regardless of whether the patient was in positive or negative fluid balance or was sodium loaded or restricted over the preceding 24 hours. Angiotensin II fell by 77 and 10 per cent, respectively, after 0.25 mg. per kilogram was given to two patients, but rose slightly in the other three patients, then fell an average of 46 per cent after 1.0 to 3.0 mg. per kilogram were given. After diuresis, 1.0 mg. per kilogram resulted in a 24 per cent fall in BP which persisted for 3 hours in two patients and a 14 per cent fall which lasted for 30 minutes after 1.0 or 3.0 mg. per kilogram in a third patient. It is concluded that the BP elevation which persists after delivery in certain patients with pre-eclampsia is not angiotensin II dependent.


Uterine and cardiovascular effects of aminophylline. Aminophylline (250 mg., over five minutes) was infused intravenously to 10 patients with oxytocin-induced contractions. The uterine activity decreased to 87 per cent because of the effect on contraction intensity; contraction frequency was unaffected. The maximum maternal pulse rate increased to 33 beats per minute. Blood pressure was unaffected. The fetal heart rate and beat-to-beat variability increased. An increased dosage of aminophylline produced unacceptably high maternal tachycardia. Comparing the results to those produced by the beta-sympathomimetic drugs in the same experimental model, it is concluded that aminophylline exhibits poor uterine selectivity with an unfavorable cardiovascular/tocolytic ratio.


Amniotic fluid phosphatidylglycerol in diabetic pregnancies. Despite L/S ratios indicating fetal lung maturity, respiratory distress continues to occur more frequently in infants of diabetic mothers. Amniotic fluid pulmonary phospholipids were studied in an attempt to understand the occurrence of false-positive L/S ratios in preterm diabetic pregnancies. Qualitative chromatography assays of surfactant phosphatides revealed reduced or absent phosphatidylglycerol in diabetic amniotic fluid specimens between 34 and 37 weeks' gestation. Mean phosphatidylglycerol in 15 nondiabetic and 29 diabetic specimens was 16 and 4 per cent of total extracted pulmonary phospholipids (P less than 0.001). Non-insulin-dependent diabetic pregnancies had lowest mean per cent phosphatidylglycerol. Respiratory distress occurred in six infants of diabetic mothers delivered preterm with L/S ratios of 2:1 or greater; phosphatidylglycerol was absent in five. The inclusion of phosphatidylglycerol in amniotic fluid phospholipid assessment may be an adjunctive index for fetal lung maturation in diabetic pregnancies.


Prolongation of rat gestation time by unsaturated fatty acids. Arachidonic, linoleic, linolenic, and oleic acids, administered to Sprague-Dawley rats on Days 20 and 21 of gestation prolonged the gestation time; neither the duration parturition, parturitional bleeding, nor the perinatal mortality rate was affected. Since arachidonic acid is the obligatory precursor of prostaglandins E2 and F2 alpha, currently believed to be associated with the initiation of labor, and polyunsaturated fatty acids inhibit the cell-mediated immune response in vivo, the precise role of prostaglandins and their precursors in the initiation of parturition must be critically examined.


Bacteriuria in the puerperium: an evaluation of methods for collecting urine specimens. Five hundred and eighteen puerperal patients were screened for bacteriuria by examination of clean-catch, midstream urine specimens using the dip-slide cultivation technique. Bladder urine from 105 patients showing 10(4) or more bacteria per milliliter of midstrean urine was obtained by suprapubic bladder aspiration and cultivated, along with two consecutive midstream specimens. The bacteriologic results in these specimen categories are compared. Of 23 patients showing growth in the midstream samples compatible with a true bacteriuria, 18 had sterile puncture urine specimens. Consecutive contaminated midstream specimens from the same patient usually yielded growth of the same bacterial species. It is concluded that a diagnosis of bacteriuria in the puerperium cannot be based upon cultural results of midstream specimens alone. In several of the bladder urine specimens, microogranisms being nonpathogenic in the urinary tract and residing normally in the vaginal flora were found, probably due to the traumatic effect of partus. In Oslo the frequency of bacteriuria among women post partum is estimated at a maximum of 1 per cent.


One-year follow-up of infants exposed to ultrasound in utero. Neonatal and infant follow-up data from the Amniocentesis Registry of the National Institute of Child Health and Human Development were analyzed for possible effects of diagnostic ultrasound exposure in the second trimester of pregnancy. A total of 297 infants of mothers receiving both amniocentesis and diagnostic ultrasound were compared with a similar group of 661 infants of mothers who had amniocentesis but not ultrasound and with 949 infants exposed to neither amniocentesis nor ultrasound. Results of newborn and 1 year examinations were similar for the amniocentesis with ultrasound group when compared to the other two groups. However, in view of the small sample size and other limitations of these data, larger and more detailed studies are needed to adequately assess possible effects of ultrasound in pregnancy.


Modification of ovine fetal respiratory-like activity by chronic diazepam administration. Chronic maternal administration of diazepam resulted in a modification of fetal respiratory-like activity (FRLA) in the sheep. An over-all increase in this activity occurred. This increase was probably due to a rebound effect following periods of acute suppression with each administration of diazepam. Loss of central control in the regulation of FRLA was implied. A complete reversal of a circadian rhythm of FRLA was observed in animals receiving diazepam. These changes have implications with respect to the antenatal monitoring of the fetus and sequelae in the newborn infant.


Hemolytic disease of the newborn due to anti-Jsb. A case of hemolytic disease of the newborn due to anti-Jsb is described. The immunohematologic status of the mother and her offspring is presented.


Reactivities of the nongravid uterine vasculatures: effects of norepinephrine. Responses of the component tissues of the nonpregnant ovine uterus to intravenous administration of norepinephrine were determined with radioactively labeled microspheres under flowmeter guidance. During a mean decrease in uterine conductance to 42 per cent of control, no significant differences in the distribution of uterine blood flow to caruncles, endometrium, myometrium, or cervix occurred. These observations differ from those during the last half of gestation, when placental vascular reactivity to norepinephrine is muted. They support the concept that fundamental changes in placental vascular responses occur during placentation.


The development of a double-antibody radioimmunoassay for detecting ovarian tumor-associated antigen fraction OCA in plasma. Ovarian tumor-associated antigen isolated from human tumor tissue was shown to have a different mobility from that of carcinoembryonic antigen (CEA) in both acrylamide gel electrophoresis and immunoelectrophoresis in agarose. The ovarian tumor antigen is composed of six species with different electrophoretic mobility in acrylamide gel electrophoresis. Three of these species were detected in Sephadex G-100 ovarian fraction OCA (from the void volume peak) and the other three species of lower apparent molecular weight were detected in fraction OCD (from the second peak). Fractions OCA and OCD did not share common antigenic determinations as determined by immunodiffusion. CEA was shown to share antigenic determinants with both OCA and OCD. A double-antibody radioimmunoassay capable of detecting nanogram quantities of plasma OCA was developed. In a preliminary study of ovarian cancer patients, OCA appeared to be a more sensitive marker for ovarian cancer than CEA. There was vitually no correlation (r2 - 0.1) between OCA and CEA levels in these patients, as determined by radioimmunoassay.


Preoperative localization of virilizing tumors by selective venous sampling. Two postmenopausal patients with virilization had preoperative localization of ovarian tumors by selective blood sampling from both ovarian and adrenal veins and assay of hormone levels. In the first patient, the peripheral concentrations of testosterone (T), androstenedione, and estrone were 936, 1,508 and 73 pg. per milliliter, respectively, levels which are above the ranges found in normal postmenopausal women. The catheterization study showed an increase in the left ovarian vein of all hormones except cortisol. It was predicted that a tumor was present in the left ovary. At operation a 7 by 4 mm. lipid cell tumour was found. In the peripheral blood of the second patient, the T level (4,518 pg. per milliliter) was markedly elevated and the estradiol concentration (73 pg. per milliliter) was increased. At retrograde catheterization the concentration of T in the right ovarian vein was markedly elevated at 120,400 pg. per milliliter. At operation a hilus cell tumor of the right ovary was found. These two cases represent the third and fourth consecutive androgen-secreting tumors from this institution that have been localized by selective ovarian and adrenal vein catheterization and sampling.


Treatment of cervical intraepithelial neoplasia with the carbon dioxide laser beam. A preliminary report. Forty-five patients with histologically proved cervical dysplasia or carcinoma in situ were treated by the carbon dioxide-laser method. The carbon dioxide laser induces cell vaporization by causing intracellular steam combustion stimulated by the emission of a mixture of carbon dioxide, nitrogen, and helium. This method of treatment is easily performed in the outpatient clinic without anesthesia, is inexpensive, and is effective in the treatment of cervical intraepithelial neoplasia. The treatment allows preservation of the transformation zone, thus permitting future colposcopic visualization.


Ovarian hemorrhage due to anticoagulants. Six cases of ovarian hemorrhage secondary to anticoagulant therapy are described. Cardiac valvular prostheses required the use of oral anticoagulants in four patients in this series; the other two suffered a pulmonary infarction secondary to thromboembolism and required sustained anticoagulant therapy. Pertinent data from 28 other case reports are reviewed. Awareness of this syndrome during child-bearing years, early recognition, and aggressive management should prevent a fatal outcome.


Malignant teratoma of the ovary: prognostic factors and treatment. A series of 25 patients with malignant teratoma of the ovary is presented. In 56%, diagnosis was made before the age of 20; none had bilateral tumors, and 52% were in Stage I at the time of the original diagnosis. Treatment with operation followed by irradiation or single-agent chemotherapy was ineffective; there were no survivors in eight patients treated with either of these regimens. However, combination chemotherapy with vincristine, actinomycin D, and cyclophosphamide used postoperatively appears to be more effective since 10 to 12 patients who were treated with this method are surviving. Histologic grade appears to have questionable prognostic significance.


Anaerobic microflora of the vagina in children. Vaginal cultures from 25 healthy girls from two months to 15 years of age were examined for aerobic, facultatively anaerobic, and obligately anaerobic bacteria. An average of 8.7 species (3.7 aerobic and facultatively anaerobic species; 5.3 obligately anaerobic species) were isolated from these cultures. Staphylococcus epidermidis (21), diphtheroids (20), bacteroides (19), peptococci (19), peptostreptococci (14), and Bacteroides melaninogenicus (14) were most prevalent organisms.


Ultrasonic assessment of fetal head and body sizes in relation to normal and retarded fetal growth. Data on consecutive ultrasonic measurements of fetal biparietal diameter (B.P.D.) and fetal chest area in 303 normal and 84 small-for-dates fetuses are presented. Duration of pregnancy varied from 24 to 41 weeks. A normal curve of the fetal B.P.D., chest area, and head-to-chest ratio was constructed. At 24 weeks mean fetal B.P.D. was 6.29 cm., mean fetal chest area was 24.9 sq. cm., and mean head-to-chest ratio was 1.59. At 41 weeks the mean values were 9.81 cm., 92.4 sq. cm., and 1.05, respectively. In the group of small-for-dates fetuses, a normal head-to-chest ratio was almost always associated with early onset of fetal growth retardation whereas in the majority of fetuses with increased head-to-chest ratios, growth retardation appeared to have started only in the third trimester of pregnancy.


The use of continuous insulin infusion for the peripartum management of pregnant diabetic women. Sixteen pregnant diabetic patients near term were maintained on a regimen of continuous insulin infusion during the peripartum period. Blood glucose remained in the range of 75 to 150 mg. per deciliter, with insulin infusion rates between 0.25 and 2.00 U. per hour. Following delivery the infusion was continued through the first postpartum day or until oral intake was tolerated and subcutaneous long-acting insulin could be given. Sliding scale regimens were unnecessary; insulin dosage for discharge was easily determined; and the metabolic care of these patients was greatly simplified. Neonatal hypoglycemia in the 17 infants delivered of these diabetic patients was not entirely eliminated despite euglycemia in the mothers.


Effects of tricyclic antidepressants on cardiovascular responses to norepinephrine and phenylephrine during pregnancy. The effects of imipramine and amitriptyline on the responses of the uteroplacental vasculature to norepinephrine and phenylephrine were investigated in the pregnant ewe. Experiments were performed on conscious animals in which electromagnetic flow transducers were chronically implanted on the uterine arteries. Administered alone, the tricyclic antidepressants had no effect on mean arterial pressure (MAP) or estimated uteroplacental vascular conductance (UPVCe). Following intravenous infusion of either imipramine (1 mg. per kilogram) or amitriptyline (2.5 mg. per kilogram), the pressor response to norepinephrine (1 microgram per kilogram) and the duration of that response were significantly increased (p less than 0.05). In addition, both the duration of the norepinephrine-produced decrease in uteroplacental blood flow (UPBF) and the amplitude of the decrease in UPVCe were enhanced. In contrast, responses to phenylephrine (2.5 microgram per kilogram) were unaffected by prior administration of either imipramine or amitriptyline. Of additional interest were findings suggesting differential sensitivities to alpha-agonists of the uteroplacental compared with other vascular beds. These observations bring attention to the possibility of interactions between endogenous or exogenous norepinephrine and the tricyclic antidepressants and suggest that the possibly unique sensitivities of the uteroplacental bed should be considered when prescribing drugs during pregnancy.


Microanatomy of the human amniotic membranes. A light microscopic, transmission, and scanning electron microscopic study. The human amnion was examined by means of light microscopy and scanning and transmission electron microscopy. The surface shows apart from microvilli a particular structure, called "blebs"; the intercellular junction is formed by desmosomes and a labyrinthine channel system, and at the base pedicels extend into the basement membrane. Cell shedding uncovers the basement membrane which seems to play a primordial role in preserving the intact amniotic cavity. These data underline the complex structure and the multiple role the amnion performs during gestation.


Tissue concentrations of free amino acids in term human placentas. Five human term placentas were analyzed for total free amino acid concentrations. Calculation of tissue fluid distribution via 14C-inulin space enabled an estimation of placental intracellular amino acid concentrations based upon cord and maternal plasma concentrations. Maximum and minimum estimates for amino acid concentration in intracellular water are given. Data are compared to concentrations in organs of various species. Taurine was present in the highest concentration (3.529 +/- 1.120 mumoles per gram wet weight). Glutamic and aspartic acids, alanine, glycine, and glutamine were all present in concentrations greater than 0.5 mumoles per gram wet weight.


How does maternal smoking affect birth weight and maternal weight gain? Evidence from the Ontario Perinatal Mortality Study. A large data set was used to examine the possibility that maternal smoking during pregnancy causes low birth weights by reducing maternal appetite, eating, and weight gain. As always, birth weight distributions shifted downward as maternal smoking level increased. Maternal weight gain distributions, on the other hand, were the same for smokers and nonsmokers. Within each level of maternal weight gain, from less than five pounds to over 40 pounds, the more the mothers smoked the greater was the percentage of neonates weighing less than 2,500 grams. This evidence supports a direct effect of maternal smoking on birth weight, possibly due to the hypoxic effects of carbon monoxide, rather than one mediated through eating. Efforts to prevent or reduce smoking should have greater benefits for mother and child than would efforts to increase food intake among pregnant women who smoke.


Intermittent breathing before death in fetal lambs. The presence of fetal breathing, even if episodic in character, may not indicate fetal well being. In a study of fetal lambs with long-term implantation of catheters and electrodes, five of six lambs which died before the onset of labor had terminal episodes of continuous breathing, preceded by 4 1/4 to 45 1/2 hours of abnormal intermittent breathing. Intermittent bursts of slow gasping or rapid breathing at exceptionally regular rates and depths were observed. The rapid pattern was associated with epileptiform seizures in two of three lambs. In all lambs, the abnormal intermittent breathing was preceded by prolonged apnea.


Ovarian pregnancy associated with intrauterine contraceptive devices. Four cases of ovarian pregnancy, occurring over a two-year period in the same hospital, are presented. Each case fulfills Spiegelberg's criteria. Each patient conceived with Cu-7 intrauterine contraceptive device (IUD) in situ. Review of the literature reveals an apparent increase in the frequency of ovarian pregnancy associated with IUD's. This aspect of the problem, as well as the management of this unusual type of ectopic pregnancy, is discussed. The data available do not justify a conclusion that ovarian pregnancies are caused by IUD's. Unless future studies demonstrate a cause-and-effect relationship, this may be merely an interesting coincidence. However, it seems that more than just coincidence is involved, even though the mechanism is unclear.


Maternal deaths from ectopic pregnancy in the South Atlantic region, 1960 through 1976. The authors have calculated the maternal mortality rates from ectopic pregnancy in the Southeastern United States. Between 1960 and 1975 81 per cent of 207 ectopic deaths occurred in nonwhite women. A more detailed study of 24 deaths from ectopic pregnancy in North Carolina shows that from 1961 to 1976 4.2 per cent of all direct obstetric deaths and 15.9 per cent of deaths from hemorrhage were due to reptured ectopic gestation. The most striking observation was the dramatic reduction in deaths from ectopic pregnancy among nonwhite women. Maternal mortality rates for ectopic pregnancy should properly be based on the conception rate, consisting of live births plus abortions rather than live births alone. Missed diagnosis of ectopic pregnancy as a factor in maternal mortality rate requires more intensive educational efforts directed toward primary-care physicians.


Adnexal malignancy detected by cervical cytology. These case presentations are submitted to focus attention on positive (Class V) cervicovaginal cytologic results compatible with adenocarcinoma in the face of benign endocervical and endometrial tissue and in the absence of clinically detectable adnexal disease. Two patients were found to have primary ovarian malignancy, and one patient had adenocarcinoma of the distal end of the right Fallopian tube. Provided that there is confidence in the cytologic diagnosis and that primary disease has been ruled out elsewhere, the clinician is encouraged to utilize additional diagnostic methods, such as laparoscopic visualization of the pelvis and peritoneal fluid studies, in an attempt to facilitate early diagnosis of nonpalpable adnexal disease.


Effects of steroids on serum lipids and serum cholesterol binding reserve. Serum cholesterol binding reserve (SCBR) denotes the capacity of serum to solubilize additional cholesterol. It as been shown previously that a decrease of the SCBR in the presence of elevated cholesterol and/or triglyceride levels is associated with the development of coronary artery disease in man. This is a preliminary report of the effect on serum lipids and SCBR by alteration of the sex steroid environment in women. The hormonal changes associated with pregnancy appear to elevate cholesterol, triglycerides, and SCBR, SCBR being elevated to the greatest extent. No differences were observed in SCBR and serum lipids in a short-term study of premenopausal women when values prior to castration are compared with values after castration during administration of conjugated equine estrogens. In women observed over a period of over 20 weeks, who were using a combination oral contraceptive pill with 1 mg. of norethindrone and 50 or 80 mcg. of mestranol, there was a significant elevation of triglycerides, some decrease of cholesterol, and no change in the SCBR. The possible significance of these findings in relation to the risk of coronary heart disease deserves further investigation.


Deaths caused by pulmonary thromboembolism after legally induced abortion. Pulmonary thromboembolism is an infrequent but serious complication of induced abortion. Of the 104 abortion-related deaths reported to the Center for Disease Control in 1972 through 1975, 10 (9.6 per cent) involved fatal pulmonary embolism; eight of these cases were proved at autopsy. All but one of the women had pre-existing risk factors for thromboembolic disease, including obesity, previous thrombophlebitis, use of oral contraceptives, or type A blood. All but one case occurred in women who had received general anesthesia. In addition, four of the eight women had undergone a concurrent sterilization procedure at the time of the abortion. Preventive efforts should focus on identifying women at high risk for thromboembolic events prior to the abortion procedure and then selecting the abortion procedure least likely to produce postoperative embolism.


Characteristics of patients with placenta previa and results of "expectant management". To determine the differences between pregnancies complicated by placenta previa and those without placenta previa, the characteristics of 31,070 consecutive deliveries at one institution were analyzed. The philosophy of "expectant management" of the premature fetus and frequent use of cesarean section was utilized in the 185 patients with placenta previa. A higher proportion of these patients were multiparous, were older, had had previous abortions, and were carrying a male fetus or twins. The fetal and placental weights in these patients were similar to those in other patients throughout pregnancy. Rates of prematurity, antepartum and intrapartum fetal death, neonatal death, congenital abnormality, and low Apgar scores were higher among patients with placenta previa. Data were compiled in a manner that allows the obstetrician to: (1) evaluate the fetal weight and expected fetal growth; (2) estimate the probability that his patient will deliver prematurely and will deliver within the next one-, two-, or four-week interval; (3) determine the relative risks to the fetus prior to labor, during labor, and in the neonatal period at each stage of gestation.


Asessment of fetal gestational age in high-risk pregnancies by amniotic fluid analyses and ultrasound mensuration. Maturity studies are reported on 204 women with high-risk pregnancies. Estimates of fetal maturity were made prenatally by the use of ultrasonic measurements, the lecithin/sphingomyelin (L/S) ratio, and a gestational index based on amniotic fluid creatinine, urea nitrogen, and cytology. These estimates were compared with the neonatal pediatric estimate of maturity. The gestational score agreed with pediatric maturity to within 14 days in 95 per cent of the cases. Estimates of L/S ratio distinguished between mature and immature infants in 86 per cent of the cases. Ultrasound could estimate gestational age only to within 14 days in 75 per cent of the cases, and the disagreements were greatest where either growth retardation or macrosomia was present. However, ultrasound is more useful in estimating fetal size and abnormalities of growth pattern. An estimate of gestational age by gestational score aids management, particularly where growth retardation is present, enabling a decision about delivery to be made even though the infant is very small and has an immature L/S ratio.


Preoperative radiation therapy in the management of squamous cell carcinoma of the vulva: preliminary report. Fourteen cases of squamous cell carcinoma of the vulva treated preoperatively by use of cobalt-60 irradiation directed to the vulva and inguinal areas are reviewed. Toral dose varied from 3,600 to 5,500 rads according to reaction and tolerance. No treatments had to be interrupted due to excessive radiation effects. Surgical procedures were performed six weeks after irradiation. Histologic investigation of the surgical specimen showed no sign of tumor in five cases, almost complete regression in three, and a substantial reduction of the lesion in the remainder of the cases. In situ lesions surrounding the invasive tumors were cleared in three cases. Lymph node involvement was found in only two patients, one of whom did not receive preoperative radiation to in inguinal areas. Only one local recurrence was encountered and this was in the abdominal skin outside of the irradiated area. The healing process does not seem to be impaired after radiation treatment in spite of the fact that in many patients a very extensive type of surgical procedure was carried out.


Legalized abortion: effect on national trends of maternal and abortion-related mortality (1940 through 1976). Both non-abortion-related maternal and abortion-related mortality declined prior to the Supreme Court decisions of 1973. In order to determine the effect of legalized abortion on maternal mortality, we have analyzed the secular trends in national abortion mortality ratios for 1940 through 1976, compared the trends to those maternal mortality ratios, and hypothesized reasons for differences between these trends. Between 1940 and 1950 and after 1965, deaths from abortion declined more rapidly than deaths from other causes associated with childbirth. However, between 1951 and 1965, maternal mortality related to pregnancy of childbirth declined more rapidly than abortion-related mortality. Five possible explanations exist for the more rapid decline in abortion deaths since 1965--selected underreporting, changes in coding practices, improved safety of illegal abortion, introduction of more effective contraception, and increased availability of legal abortion. We consider the last two explanations as the most likely reasons for the accelerated decline in abortion-related deaths.


The relationship between fixation disparity and heterophoria. Twenty-five asymptomatic subjects with normal binocular vision underwent determination of the magnitude and direction of their heterophoria and their fixation disparity. Fixation disparity was measured at a 2-m fixation distance with the phase-difference haploscope under conditions simulating those of casual seeing. When combined with careful attention to symmetrical control of accommodation, this method eliminates several known technical artifacts. Examples of the normal fluctuation of the magnitude and direction of fixation disparity for individual subjects were demonstrated. Whereas only a slight preponderance of subjects were esophoric, many subjects had convergent fixation disparity (esodisparity). Linear regression analysis of the data revealed a coefficient of correlation between fixation disparity and heterophoria at 6 m of 0.61, and at 33 cm of 0.50. The results suggest that normal, small magnitude heterophoria does not necessarily produce fixation disparity and that fixation disparity does not necessarily sustain heterophoria.


Retinal vascular changes in retrograde optic atrophy. Five patients with unilateral optic atrophy of extraocular origin had a normal retinal vasculature. Clinical examination of the patients included color fundus photographs and fluorescein angiography. After comparing the blood vessels in the blind eye with those in the normal fellow eye, we concluded that vascular attenuation is neither invariably associated with optic atrophy, nor solely caused by decreased local oxygen demand in the retina.


Unilateral congenital iris pigment epithelial hyperplasia associated with late-onset glaucoma. We observed a 41-year-old man with congenital unilateral iris pigment epithelial hyperplasia associated with unilateral glaucoma, and considered the possible pathogenesis of this unique lesion and its relationship to the patient's glaucoma.


Acquired color vision defects in retrobulbar neuritis. We used the Farnsworth-Munsell 100 Hue Test to study the incidence of acquired color vision defects in 16 patients with unilateral and and seven patients with bilateral retrobulbar optic neuritis whose visual acuity had recovered to 6/12 (20/40) or better. We recorded the visual-evoked response to a pattern stimulus on the same day. All 30 affected eyes showed an excessive number of errors on Farnsworth-Munsell 100 Hue testing. The number of errors increased with greater residual optic nerve damage. One false-positive and two false-negative visual-evoked responses were found.


Embolic ischemic optic neuropathy.

Embolic ischemic optic neuropathy. On examining the postmortem enucleated eyes of a 68-year-old man, we found the left eye had focal infarction 3 mm behind the lamina cribrosa caused by thromboembolic compromise of three discrete pial and pial-derived arterioles. The optic nerve had been destroyed focally, whereas the retinal and choroidal tissue supplied by a similarly occluded vessel had been preserved. We diagnosed nonarteritis ischemic optic neuropathy.


Chronic unilateral blepharoconjunctivitis caused by sebaceous carcinoma. A patient with chronic unilateral conjunctivitis of six years' duration was discovered to have sebaceous carcinoma of the eyelid. This case is in many respects typical of the delay between onset and diagnosis frequently seen in this disease. Our case is unique, however, because it demonstrates that if not specifically alerted to the possibility of malignancy, even the experienced ophthalmic pathologist may misdiagnose. The factors necessary for early diagnosis of this disease are: (1) suspicion on the part of the clinician, (2) adequate surgical biopsies, and (3) examination of the biopsy specimen by an experienced pathologist who has been alerted to look for malignant changes.


Anterior uveitis in geographic or serpiginous choroiditis. A 51-year-old man and a 45-year-old man had geographic or serpiginous choroiditis and anterior uveitis as shown by ophthalmoscopy and fluorescein angiography. Anterior uveitis, a previously undescribed feature of this disease, was found in both patients. Despite clear-cut evidence of inflammatory disease, corticosteroid therapy generally proved to be ineffective.


Comparative ultrasonographic study of the effect of pilocarpine 2% and Ocusert P 20 on the eye components. The ultrasonographic examination of pilocarpine 2%- and Ocusert P 20-treated eyes clearly demonstrated that the side effects, such as accommodative myopia and changes of the anterior chamber depth and of the lens thickness, were less pronounced in the Ocusert-treated group.


Subretinal pigment cells in malignant melanoma of the choroid. On examining 54 globes that harbored choroidal malignant melanomas, we found 28 tumors to be composed of spindle cells; 24, of mixed cells; and two, of epitheloid cells. In 80% of the tumors studied, pigment-laden cells had accumulated away from the tumor region and at the periphery of the subretinal space. The number of cells increased in proportion to the extent of retinal detachment, a finding that related directly to the size of the tumor.


Number of inflammatory cells in the normal conjunctiva. We counted inflammatory cells per cubic millimeter in both the epithelium and the substantia propria of samples from upper tarsal conjunctiva of 15 normal subjects and from lower forniceal conjunctiva of ten normal subjects. The upper limit of normal for number of cells was nearly 500,000/mm3. Lymphocytes accounted for about 70% of the inflammatory cells. Neutrophils and lymphocytes were almost always present in both the epithelium and the substantia propria. Plasma cells and mast cells were present in the substantia propria of all subjects, but never in the epithelium. Neither eosinophils nor basophils were found in any specimen. We concluded that conjunctiva of the white and quiet eye usually contains heavy infiltrates of inflammatory cells.


Therapy of scleritis with cytotoxic agents. Four patients with severe anterior scleritis that had not responded to conventional therapy were treated with cytotoxic immunosuppressive alkylating agents alone (one case) or in combination with prednisone (three cases). Two of the patients had Wegener's granulomatosis, one pyoderma gangrenosum, and one rheumatoid vasculitis. All patients responded well to this therapy with a decrease in inflammation and a healing of the sclera. Other systemic manifestations of the underlying diseases often responded well also.


High magnification direct ophthalmoscopy. The combination of a high minus setting of the ophthalmoscope and an extra positive lens in front of the patient's eye forms a Galilean telescope that increases magnification in direct ophthalmoscopy. The telescope magnification equals the ratio between objective and ocular focal lengths.


A technique for improving corneal clarity during retinal surgery. To maintain corneal clarity during scleral buckling operations, the surgeon firmly rolls a dry cotton applicator across the edematous corneal surface, and the epithelial edema fluid is pressed out and absorbed by the applicator. This technique, which may be repeated a number of times, reduces the number of cases that require removal of the epithelium.


Line copy presentation slides with Kodalith. Line copy presentation slides with white letters on a blue background can be produced with a two-step process. The slides are more permanent than diazo slides, and the process is faster and less expensive.


Cycloplegics for refraction.

Cycloplegics for refraction. The actions and indications of cypcloplegics are presented along with recommended dosages and uses for clinical measures of refractive error.


Administration of and adverse reactions to cycloplegic agents. A minimum clinical history and examination preceding drug instillation is described. Clinically effective doses of topically applied cycloplegic agents are summarized. A presentation of the causes and incidence of adverse drug reactions, both systemic and ocular, is followed by a discussion of general guidelines for their prevention or management.


Corneal effects of high plus hydrogel lenses. Five aphakic patients and five phakic patients were fitted with high plus Bausch & Lomb Soflenses. We evaluated corneal edema, staining, vertical striae, and corneal thickness before and after a 5-hr wearing period. The high plus lenses produced average corneal-thickness changes of 9.6% and 7.1% for the phakic and aphakic groups, respectively. Biomicroscope examination showed moderate amounts of vertical striae, epithelial staining, and corneal edema for both groups. The amounts of edema, staining, and striae were higher than when regular and thin minus lenses were worn. It is likely that the thickness of the high plus lenses reduces the oxygen supply to the corneal epithelium, causing relatively marked edema.


Choosing the base curve for an ophthalmic lens. Although optometrists can be expected to be responsible for the base curve, which determines the form of the lens they prescribe, they seldom specify the base curve to the optical laboratory. They may ask for a corrected-curve lens without specifying the kind of corrected-curve lens. If optometrists were to specify what they want in terms of a convex spherical base curve and allow the laboratory a leeway of p1.00 D, the laboratory could probably fill the order with an uncut lens from stock. With a series of semifinished lenses with convex spherical base curves spaced 2.00 D apart, the laboratory can supply a finished lens that will meet almost any need. For glasses to be used for distant objects, first consideration is usually given to minimizing the unwanted sphere and cylinder in the periphery of the lenses. For those who want to aim at this objective, I have worked out a series of convex spherical base curves that can be used for various combinations of spheres and cylinders.


A subjective method of monitoring corneal scattering. Border-enhancement spread is a new criterion for assessing the quality of the retinal image. In one study, it was found that the width of the enhanced region increases with the steepness of a contact lens fit, and this increase was attributed to scattering accompanying corneal edema arising from tight-fitting lenses. The present study tested this hypothesis. Corneal thickness and border-enhancement spread were measured concurrently at regular intervals during and after contact lens wear. It was found that border-enhancement spread generally follows changes in corneal thickness. Since scattering increases with corneal swelling, the findings generally support the hypothesis. However, it was also found that variables not originating in the cornea sometimes modify the retinal-image quality and thus mask the scattering effects. Future applications of the methods are discussed.


Optometric education in Nigeria.

Optometric education in Nigeria. A 3-year optometry program was established at the University of Benin, Nigeria in 1973. The program is considered from the standpoint of curriculum, faculty, clinical instruction, and grading. Some background is given about Nigeria itself. Present eye care facilities are reviewed as well as the increasing requirements of a developing nation. The need of strong support from established optometry schools is indicated.


Influence of methylprednisolone on ultrastructural and cytochemical changes during myocardial ischemia. Selective effects on various cell inclusions and organelles including lysosomes. Occlusion of the circumflex branch of the coronary artery of rabbit hearts for 45 minutes elicits structural and cytochemical changes in myocytes similar to those observed in ischemic dog myocardium, which are indicative of irreversible cell injury. When methylprednisolone is administered prior to occluding the artery, myocytes are transiently protected and many of the electron microscopic signs of irreversible damage are delayed for 15 minutes or more. During this period, the steroid preferentially protects mitochondria, lysosomes, and sarcolemma from the ischemic changes that normally develop. However, some other events, including depletion of glycogen and margination of nuclear chromatin, are only minimally influenced by the therapy, if at all. In all hearts, treated and untreated, the development of severe cell damage, whenever it occurs, is closely associated with cell swelling, mitochondrial dilation with concomitant appearance of amorphous osmiophilic densities, and abnormalities in and, ultimately disappearance of lysosomes, suggesting that damage to cell membranes is a central event in the progression of reversible injury to irreversible infarction and that protection of membrane integrity should be a reasonable aim in efforts to ameliorate or delay ischemic injury.


The histologic border zone of acute myocardial infarction--islands or peninsulas? Observation of isolated islands of apparently surviving myocardium within areas of necrotic tissue at the edge of myocardial infarctions has been interpreted by some as histologic evidence of a unique "border zone" region. Serial section reconstruction of transmural canine myocardial infarctions was performed in this study to establish whether these islands were truly isolated or were continuous peninsulas of tissue separated by the plane of section. Three-dimensional analysis of the infarcts revealed no true islands but instead demonstrated a region composed of highly complex interdigitating peninsulas. We conclude that there is an extremely irregular but sharp boundary demarcating normal and infarcted myocardium with no intermediate zone. This observation is discussed in relation to recent data, based on coronary blood flow and creatine phosphokinase analysis, which also demonstrates a sharp boundary between the normal and infarct zones.


Human glomerular cells in culture. Three subcultured cell types bearing glomerular antigens. In this paper, we describe three cell types from the explanted human glomerulus: the circular glomerular cell (CGC), the rhomboid glomerular cell (RGC), and the small ovoid glomerular cell (SOGC). These cells were compared with subcultured human umbilical vein endothelial and smooth muscle cells, uterine smooth muscle cells, and skin fibroblasts. Immunochemical comparisons utilized antiserums to antigens in the human glomerulus: antiglomerular basement membrane, antifibroblast surface antigen (FSA) (reactive extensively with the mesangium), antiactomyosin (AMY) localizing more restrictively in the mesangium, and antihemophilic factor (AHF) localizing to the endothelium. No cultured glomerular cells bore the AHF marker of endothelial cells. The epithelioid CGC excrete most GBM antigen as an orderly  palisade of granules from the cell surface. FSA is rapidly lost from the cell surface. RGC have a typical multilayered smooth muscle morphology and have a most prominent complex AMY pattern of periodic aggregates and fibrils. FSA adheres to the cell surface. SOGC form an initial nonoverlapped monolayer resembling endothelial cells but elongate and form multilayers after confluency. The AMY fibril pattern of SOGC is distinctively multidirectional. The translation of in vitro characteristics into in vivo identification must be interpreted cautiously: CGC may derive from glomerular epithelial cells; RGC may derive from mesangial cells; and SOGC may represent a more rapidly proliferating, less differentiated form of the epithelial cell or another, unidentified, glomerular cell type.


C3b receptors on human glomeruli in vitro. Loss in culture. C3b receptors, easily demonstrated on isolated human infant glomeruli, are lost as cells grow in culture. This suggests that epithelial cells are dedifferentiated or that the C3b receptor is not intrinsic to the epithelial cell.


Relation between high energy phosphate and lethal injury in myocardial ischemia in the dog. The relationship between progressive depletion of high energy phosphate and the onset of lethal cell injury in ischemic myocardium following coronary occlusion has been evaluated. Myocardial ischemia was induced by proximal occlusion of the circumflex coronary artery for 15, 30, 40, or 60 minutes. Cell injury in the severely ischemic posterior papillary muscle (PP) was evaluated by electron microscopy and by measuring the capacity of slices of the injured PP to maintain electrolytes, resynthesize high energy phosphate, and exclude inulin during in vitro incubation. ATP content in the ischemic myocardium decreased to 35%, 9%, 7%, and 5% of control values after 15, 30, 40, and 60 minutes of ischemia, respectively, and was associated with a corresponding depletion of total adenine nucleotides. The loss of 65% of the ATP after 15 minutes of ischemia (reversible injury) was associated with only minimal ultrastructural changes and no significant defects of electrolytes in incubated slices. However, the depletion of over 90% of the ATP after 40 minutes of ischemia (irreversible injury) was associated with significant fine structural changes and markedly altered cell volume regulation. The results suggest a close relationship between the marked depletion of high energy phsophates and the development of lethal injury in acutely ischemic myocardium.


The cyclic hematopoietic dog: a model for spontaneous secondary amyloidosis. A morphologic study. Spontaneous amyloidosis was found in dogs affected with hereditary cyclic hematopoiesis (CH dogs). Early perifollicular deposits of amyloid were observed in the spleens of 15-week-old CH dogs. By the 24th week, amyloid deposits were also found in the liver, kidneys, pancreas, adrenals, and small intestine; the incidence of the condition rose to more than 90%. The visceral involvement and the histologic characteristics of amyloid deposition closely resemble those of the secondary form in humans. A transient lymphoid hypoplasia was noted in the spleens of neonates and pups. This abnormality did not appear to be related to exogenous conditions. In young adult dogs, the initial hypoplastic characteristics were replaced by enlarged marginal zones in the follicles of the spleen, composed  of pyroninophilic cells and, in a later stage, of PAS-positive cells. These cellular changes preceded the amyloid deposition. Due to the characteristic cyclic neutropenia of the hereditarily transmitted hematologic syndrome, most CH dogs experience episodes of infectious diseases, although the episodes of infection may be separated by long periods of relatively good health. This may provide the underlying antigenic stimulation which triggers the process of amyloid deposition. However, the lag period for the onset of amyloidosis is extremely short and the type of infections is not considered a predisposing factor for amyloid deposition. It is possible that a peculiar sensitivity of the lymphoid system in the CH dog would facilitate the development of widespread amyloidosis. Since the sequence of splenic lymphoid hypoplasia, follicular activation, and amyloid deposition associated with age are consistently repeated, the CH dog may be a suitable animal model for the study of the pathogenesis of secondary form of amyloidosis in humans.


The origin of subdural neomembranes. I. Fine structure of the dura-arachnoid interface in man. A method for the in situ fixation of human meninges for electron microscopic examination is described. It was found that the cranial meninges of humans do not include a subdural space. Instead there is a complex, tight layer of cells, the interface layer, composed in the innermost portion of the dura mater (the dural border cells) and the outermost portion of the arachnoid (the arachnoid barrier layer). The fusion of these components within the interface layer is much more intimate than is either the attachment of the dural border cells to the dura proper or that of the arachnoid barrier layer to the rest of the arachnoid. The fine structural characteristics of these layers are defined. The erroneous macroscopic impression of a subdural space results from an extraordinary lack of cohesion within the dura-arachnoid interface layer conditioned by a) a complete absence of a collagenous reinforcement within this zone, b) the presence of large extracellular cisterns between the dural border cells, and c) a paucity of intercellular contacts within that latter layer. An understanding of the fine structural organization of the interface layer is essential to any consideration of the pathogenesis of subdural lesions: these form within a sheet of torn dural border cells and not within a preexistent tissue compartment.


The origin ofsubdural neomembranes. II. Fine structural of neomembranes. A comparison of the fine structure of subdural neomembranes with the fine structural organization of the normal human dura-arachnoid interface discloses that neomembranes are not de novo proliferations of tissue from a smooth inner dural surface. Rather, a neomembrane is the result of proliferation and excessive thickening of the normal layer of dural border cells. On proliferation, the dural border cells form multilayered tiers and clusters of cells, transfixed by capillaries, with collagen fibrils and elastic fibers between them. Capillaries and collagen fibrils are absent from the normal interface layer. Pathogenetic concepts of chronic subdural hematoma need to be revised. Any pathologic condition inducing cleavage of tissue within the dural border layer at dura-arachnoid interface will be followed by proliferation of fural border cells with production of a neomembrane. There is no compelling reason to postulate that proliferation of the border cell layer is always secondary to traumatic hemorrhage.


Relationship between glomerular mesangial cell proliferation and amyloid deposition as seen by ultrastructural and morphometric analysis in experimental kala-azar of the hamster. Light and electron microscopic studies combined with a morphometric analysis of the hamster glomerulus in experimental kala-azar showed progressive hyperplasia of mesangial cells beginning on the 10th day and reaching a peak on the 20th day after infection. Afterward, the number of mesangial cells declined and a progressive rise of amyloid deposits over the mesangial matrix was observed. This system for amyloid production is unique if we consider that probably one cell, the mesangial cell, is involved in glomerular amyloid deposition. Our data support a slight modification in the sequence of events of the biphasic theory of amyloid formation. We observed that the number of mesangial cells declines when amyloid deposition increases and that mesangial cell morphology in this stage is not that of an actively secreting cell. It is therefore hypothesized that amyloid precursor material is secreted into the matrix during the proliferative phase. In the second phase, amyloid deposits occur in the extracellular media close to functionally impaired mesangial cells.


The effect of steroids on peripheral blood lymphocytes containing parallel tubular arrays. The response of lymphocytes containing cytoplasmic inclusions called parallel tubular arrays (PTA) was determined after the administration of the glucocorticoid dexamethasone to 10 healthy volunteers. The percentage of these lymphocytes was found to increase during the lymphopenia induced by steroid administration. The size and number of parallel tubular arrays per cell showed no differences before and after steroid administration, indicating that the increase was a result of a change in the proportion of whole cells. This indicates, for the first time, that a morphologically defined population of lymphocytes from the normal peripheral circulation has been linked to a specific response, ie, steroid resistance. The possible mechanism of steroid resistance is discussed.


Focal glomerular sclerosis in the fawn-hooded rat. We have examined the nature of focal glomerular sclerosis (FGS) in fawn-hooded (FH) rats. The fawn-hooded rat develops pathologic features similar to those observed in steroid-resistant focal glomerular sclerosis, ie, by light microscopy some of the glomeruli appear normal but others show areas of solidification confined to one or two lobules of the tuft. The pathogenesis of this disease is not well known and there is a great need for an animal model. In the FH animal, a marked difference in the development of the lesion was noted between male and female rats. Fifty percent of 4-month-old males had proteinuria in excess of 10 mg/day (none of the females had significant proteinuria), while all 12-month-old males had proteinuria in excess of 45 mg/day (female 12-month-old FH rats had mean proteinuria of 7 mg/day). At 6 months of age continuing through 12 months of age, male FH rats had mesangial deposits of IgG, IgM, and, occasionally, C3, demonstrable by immunofluorescence, whether or not FGS was present. Subepithelial electron-dense deposits were never seen by electron microscopy either at 6 of 12 months. Six-month-old animals frequently did not exhibit FGS. Instead, the glomerular epithelial cells, exhibited fusion of foot processes, vacuolization, and, in some areas, focal loss of the epithelial covering on the glomerular basement membrane (GBM). Six-month-old males with proteinuria exhibited focal loss of negative charge from all layers of the filtration barrier. The GBM from sclerotic glomeruli of 12-month-old rats was commonly denuded of epithelium. None of the animals in this study was uremic. FH rats demonstrated FGS associated with progressive glomerular epithelial cell injury.


Functioning oxyphil adenoma of parathyroid gland. An ultrastructural and biochemical study. Oxyphil cells and oxyphil cell adenomas of parathyroid glands are, in most instances, regarded to be nonfunctioning. Although 21 cases of hyperparathyroidism associated with parathyroid oxyphil cell adenoma have been reported, secretion of hormone by these tumors has not been conclusively demonstrated. A parathyroid adenoma, diagnosed by light microscopy as oxyphil type, together with the results from ultrastructural and biochemical studies of the patient's adenomatous tissue, are reported here. The patient, a 64-year-old male, was found to have elevated serum calcium, low serum phosphorus, and elevated serum immunoreactive parathormone: findings consistent with hyperparathyroidism. After excision of two small normal-appearing glands and one greatly enlarged (1.9 g) parathyroid gland, those laboratory values returned to normal. Light microscopy of the enlarged parathyroid indicated that it consisted almost entirely of an oxyphil adenoma. Electron microscopy revealed that the adenoma was composed mainly of mitochondria-rich oxyphil cells but also of interspersed transitional oxyphil cells and rare scattered chief cells. Golgi zones, rough endoplasmic reticulum, and prosecretory and secretory-like granules were observed in some oxyphil cells, in most transitional oxyphil cells, and in the infrequent chief cells. Thus, many of these cells appear to contribute to the production and secretion of parathormone. Biochemical studies performed directly on the adenomatous tissue demonstrated that it was able to synthesize proparathormone and parathormone, although the proportion of hormonal peptide synthesis relative to that of the total protein synthesis in this tissue was much smaller (0.9%) than that found in normal parathyroid tissue (5.7%). There was a small increase in immunoreactive parathormone when the adenoma tissue was incubated in a low-calcium medium. These findings indicate that this oxyphil adenoma of the parathyroid gland synthesized and secreted parathormone, apparently to some extent autonomously, but suggest that its capacity to do so was largely dependent on its component of cells other than fully developed oxyphil cells, such as transitional oxyphil cells.


Irreversible ischemic cell injury. Prevention by chlorpromazine of the aggregation of the intramembranous particles of rat liver plasma membranes. Ischemic rat liver tissue has been shown previously to exhibit a markedly accelerated rate of phospholipid degradation, producing a loss of almost one half the total cellular phospholipid with 3 hours of ischemia. Pretreatment of the rats with chlorpromazine completely prevented the disturbed phospholipid metabolism at the same time that it prevented the cell death associated with as much as 3 hours of ischemia. Lipid-depleted microsomal membranes were shown previously to manifest alterations in their structure and function. The present report documents that similar structural alterations are evident in ischemic liver cell plasma membranes. The technique of freeze-fracture electron microscopy was used to examine the morphology of ischemic liver cell plasma membranes. Freeze-fracture replicas of whole tissue fragments exhibited a diffuse aggregation of the intramembranous particles in the P face of the plasma membranes. The incidence of this change correlated with the duration of ischemia. Pretreatment of the rats with chlorpromazine (20 mg/kg) for 30 minutes before inducing ischemia prevented the aggregation of the membrane-associated particles. These findings establish the existence of plasma membrane alterations in ischemic liver cells. The time course of these changes, their prevention by chlorpromazine, and their similarity to the previously described structural alterations in the microsomal membranes suggest that they are related to the loss of liver cell phospholipid. The data in the present report support the hypothesis that an accelerated phospholipid degradation and its resultant membrane dysfunction are the critical alterations that produce irreversible liver cell injury and, ultimately, cell death in ischemia.


Experimental Acanthamoeba infections in mice pretreated with methylprednisolone or tetracycline. Human infections due to free-living amebas of the genus Acathamoeba have been reported sporadically, occasionally in individuals with underlying diseases. To determine if such infections may be considered opportunistic, groups of laboratory mice were pretreated with either methylprednisolone or tetracycline and inoculated intranasally with 1.075 times 10(4) Acanthamoeba castellanii isolated from a natural fresh water well. Results were compared with controls receiving either drug or amebas alone and with controls receiving saline injections with and without amebas. The mortality rate for those animals receiving methylprednisolone and amebas (50%) was found to be greater than the mortality in ameba controls (10%) (P equal 0.074). Similarly, the mortality rate for animals receiving tetracycline and amebas (60%) was higher than the mortality in the ameba controls (10%) (P equal 0.0286). Precise mechanisms for the increased mortality were unknown but were suspected to be due to the capacity of either corticosteroids or tetracycline to suppress host defenses, particularly those depending on neutrophils. The findings suggest a potentially pathogenic role for naturally occurring Acanthamoeba sp in humans with depressed host immunity.


The Chédiak-Higashi syndrome. Evidence that defective leukotaxis is primarily due to an impediment by giant granules. The primary defect of the Chédiak-Higashi syndrome (CHS) which links the several known neutrophil abnormalities in this disorder remains enigmatic. In an attempt to clarify the mechanism of one of the abnormalities of CHS neutrophils, ie, chemotactic migration, the effect of filter pore size was examined in the standard Boyden chamber assay. The response of normal neutrophils to a gradient of zymosan-activated serum was not influenced by increasing the filter pore size from 5 to 8 microgram. However, while CHS neutrophils showed a significant reduction in migratory response from the controls with 5-mu filters, the difference was eliminated when 8-mu filters were employed. Again, when an arachidonic acid gradient was used as the stimulus, migration of CHS neutrophils through 8-mu filters equalled that of controls. These findings indicate the intact nature of the surface receptor and motility systems of the CHS neutrophils and further suggest that the previously defined chemotactic defect in these cells can be explained in terms of the mechanical impediment provided by the CHS giant cytoplasmic granules.


Turnover of kidney beta-glucuronidase in normal and Chédiak-Higashi (beige) mice. Kidney beta-glucuronidase turnover has been examined by specific antibody methods in normal C57BL/6J mice and in coisogenic C57BL/6J beige mice, an animal model for the human Chédiak-Higashi syndrome. No effect of the beige gene on the rate of glucuronidase synthesis was detected in either untreated or testosterone-treated mice. Moreover, glucuronidase of beige mice decayed relatively slowly in pulse labeling and in hormone withdrawal experiments. Direct measurements of secretion confirmed that both in the presence of testosterone and following its withdrawal, there was a threefold lower rate of secretion of kidney glucuronidase in beige mice. Following hormone withdrawal, the loss of glucuronidase activity in beige mice was biphasic, with the second more slowly turning over component apparently lost by a nonsecretory mechanism. This persistent nonsecreted glucuronidase activity was specifically associated with giant lysosomes in kidney proximal tubule cells near the corticomedullary border. Thus, there are two major populations of lysosomes in proximal tubule cells of beige mice. Cells of the outer cortex contain mainly morphologically normal lysosomes, and their lysosomal enzymes are secreted at near normal rates. However, lysosomal enzymes derived from the giant lysosomes of cells near the corticomedullary border are secreted either very slowly or not at all. The altered secretion of lysosomal enzymes from specific kidney cells of beige mice may serve as a model system for study of defective fusion of lysosomes with phagocytosed bacteria in cells of Chédiak-Higashi patients.


Effect of starvation on initiation of protein synthesis in skeletal muscle and heart. Psoas muscle of rats starved for 2 or 4 days contained increased levels of ribosomal subunits and exhibited reduced rates of protein synthesis in vitro, demonstrating a starvation-induced inhibition of peptide-chain initiation. The activity of an eIF-2-like initiation factor, assayed in postribosomal supernatants, decreased in psoas during starvation, parallel to a 25% reduction in the RNA level. Reduced eIF-2 activity did not result from nucleotide depletion or increased deacylation of initiator tRNA, nor was it abolished by extensive dialysis. Perfusion of psoas muscle in the presence of insulin reversed the starvation-induced block in peptide-chain initiation, but did not alter the activity of eIF-2 or level of RNA. Furthermore, heart muscle did not manifest a starvation-induced block in peptide-chain initiation even though the activity of eIF-2 and the level of RNA decreased as a result of food deprivation. Thus loss of eIF 2 activity in psoas and heart did not parallel changes in peptide-chain initiation but was associated with a reduction in tissue RNA. These results indicate that the level of eIF-2 is not rate-limiting for peptide-chain initiation under the conditions tested in this study.


Protein turnover in man measured with 15N: comparison of end products and dose regimes. Whole-body protein synthesis was measured with [15N]glycine in malnourished and recovered infants and in obese patients. Comparisons were made: 1) between results obtained with single (S) and repeated (R) oral dosage of tracer; and 2) between urea and ammonia as end products. In the infants S and R gave similar values for the synthesis rate. With both methods of dosage, the values obtained with NH3 as end product were about two-thirds of those with urea. It is suggested that the cause of this result is that glycine contributes preferentially to the formation of urinary NH3. With NH3 as end product, a collection period of 12 h has been found to be suitable. With urea it is not possible to define an appropriate collection period. The combination of single dose of [15N]glycine with urinary NH3 as end product provides a simple method for measuring whole-body protein synthesis under clinical and field conditions. It can be repeated at short intervals and can give useful comparative information provided that conditions are carefully standardized. The reproducibility so far is +/- 13%.


Chylomicron composition during duodenal triglyceride and lecithin infusion. In lymph fistula rats infused intraduodenally with trioleoylglycerol emulsions, the secretion of triglyceride was enhanced and that of total and esterified cholesterol in chylomicrons was strikingly reduced when lecithin was added at 4-5 times the biliary lecithin secretion rate. During continued triglyceride secretion in the presence of lecithin, the phospholipid: unesterified cholesterol ratio of the chylomicrons increased significantly in contrast to lecithin-free emulsions. Bile-diverted lymph fistula rats secreted significantly less esterified and total cholesterol in lymph chylomicrons than controls, and the difference was magnified by lecithin administration. Cholesterol appears to become relatively unavailable for incorportion into chylomicrons when lecithin is administered at high rates.


Plasma ammonia and liver ornithine transcarbamoylase activity in zinc-deficient rats. The effects of zinc deficiency on the activity of hepatic ornithine carbamoyltransferase (OCT) and plasma ammonia were studied in rats. One group received (ad libitum) zinc-deficient diet containing 2 ppm zinc and the other group received a diet containing 110 ppm zinc (group pair-fed control) equal to the amount consumed by zinc-deficient rats during the previous 24 h. Rats were killed at weekly intervals. Blood urea nitrogen (BUN), plasma ammonia, and hepatic OCT activity were determined. By end of the 1st wk on zinc-deficient diet, the plasma ammonia levels became significantly higher than those of the controls and remained elevated thoughout the study period. BUN increased initially for 2 wk in the deficient rats, but by the end of 4 wk the levels were lower than in the controls. The hepatic OCT activity in deficient animals was significantly lowered as compared to the controls by the 3rd wk. It is concluded that an increase in plasma ammonia may occur as a result of deficiency of zinc.


Galactosyltransferase in fetal, neonatal, and adult colon: relationship to differentiation. Microsomal galactosyltransferase activity of fetal rat colon increased fourfold between 18 and 22 days of gestation and then more slowly during neonatal life reaching adult levels after 14 days. The Km for uridinediphosphate- (UDP) galactose, pH optimum, cation, and detergent requirements were identical in fetal and adult galactosyltransferase. Cytidine 5'-diphosphate-choline stimulated the adult but not fetal colonic galactosyltrasferase activity by inhibition of UDP-galactose pyrophosphatase. The increase in colonic galactosyltransferase in late fetal development is correlated with our previous observation that incorporation of [3H]galactose is markedly increased during differentiation of the fetal colon.


Effects of thyroxine on protein turnover in rat skeletal muscle. The effects of thyroxine (T4) on protein turnover in skeletal muscle were studied using normal, thyroidectomized (thyrex), and hypophysectomized (hypox) rats. Thyrex rats had a depressed growth rate that was accompanied by 50% reductions in the level of RNA and the rate of protein synthesis in gastrocnemius muscle, as determined in the perfused hemicorpus. Protein synthetic efficiency (protein synthesis per unit RNA) was decreased by 18%. Daily treatment of thyrex rats with T4 at different dose levels for up to 16 days led to improved growth rates, elevated RNA concentrations, and increased protein synthesis rates. The primary effect of T4 was to increase the protein synthetic capacity of muscle. Protein degradation, determined in the perfused hemicorpus, and activity of a lysosomal protease, determined in unperfused muscle, were reduced in the thyrex condition. Treatment of thyrex rats with T4 increased protein degradative rates, but not protease activity. Hypox rats, which also exhibited depressed skeletal muscle protein synthesis, responded to T4 and combined T4 and growth hormone with marked improvements in protein synthesis.


Simultaneous analysis of families of sigmoidal curves: application to bioassay, radioligand assay, and physiological dose-response curves. Physiological and pharmacological studies of hormones, drugs, and neurotransmitters often generate families of sigmoidal dose-response curves. Optimally efficient data analysis should involve simultaneous description of all curves, rather than fitting each one individually. We have developed a general computerized method to describe the dose-response curves in terms of basal and maximal responses, ED50, and curve shape or steepness. This facile method permits rigorous statistical analysis, provides a basis for pooling of information from separate experiments, and allows one to test which characteristics are shared by various curves.


Effects of renal fuels on uptake of PAH and uric acid by separated renal tubules of the rabbit. A rapid-filtration procedure was used to examine the effects of a wide variety of renal fuels on the uptake of p-aminohippuric acid (PAH) and uric acid (UA) by separated rabbit renal tubules. PAH and UA uptakes in 15 min over a range of substrate concentrations of 0.01-10.2 mM were determined. All tricarboxylic acid cycle intermediates and pyruvate showed biphasic stimulation of PAH and UA uptake. alpha-Ketoglutarate produced a 320 +/- 54% increase in PAH uptake and a 192 +/- 60% increase in UA uptake at 0.16 mM, the concentration at which uptake was maximal, while causing 20 +/- 3 (PAH) and 35 +/- 7% (UA) inhibition at 10.2 mM. Citrate produced a 373 +/- 19% increase in PAH uptake and a 246 +/- 41% increase in UA uptake at 0.64 mM. PAH and UA uptake were also stimulated by acetate, glucose frutose, phosphoenolypyruvate and L-glutamic acid. The data indicate a direct relationship between stimulation of PAH and uric acid transport and stimulation of renal cortical oxidative metabolism.


Determinants of proximal tubular reabsorption as mechanisms of glomerulotubular balance. The determinants of absolute proximal reabsorption (APR) were studied in four groups of rats during hydropenia, partial renal vein occlusion (RVO), saline expansion, and RVO after saline expansion. Nephron filtration rate (SNGFR), nephron plasma flow (RPF), APR, and proximal tubule (Pt) peritubular capillary (HPc), and interstitial (HPi) hydrostatic pressures were measured by micropuncture techniques. Subcapsular space (pii) and star peritubular capillary (piE) oncotic pressures were also determined. The peritubular capillary permeability coefficiency (LpAR) and the corresponding effective reabsorptive pressure (ERP) were computed, where APR = LpAR . ERP, and ERP = net reabsorptive pressure across the peritubular capillary. The results indicate that APR correlates best with SNGFR (P less than 0.05), but not with (pii - HPi), RPF, or LpAR. There was a significant relationship between piE and LpAR, where LpAR fell with increases in piE (P less than 0.01). In conclusion, 1) changes in absolute proximal reabsorption correlate best with changes in nephron filtration rate but not with (pii - HPi) across this range of values, 2) changes in efferent oncotic pressure (piiE) correlated inversely with LpAR, and 3) glomerulotubular balance in the proximal tubule can be partially attributed to intraluminal factors.


Further studies on ion permeation in proximal tubule of necturus kidney. In the perfused Necturus kidney, the ratio of transepithelial sodium-to-chloride permeabilities (PNa/PCl) was estimated from dilution potentials at 1:7. The ratio of transepithelial permeabilities PHCO3/cl was estimated from bi-ionic potentials at 1:4 and that of Plact/PCl at 1:12. The permeability sequence, therefore, is PCl greater than PHCO3 greater than than PNa or PnaCl greater than PNaHCO3. The latter is similar to the situation in the rat. However, because of the low Na permeability, passive NaCl absorption by solvent drag is probably less important in Necturus than in the rat. The measurement of transepithelial input conductance during replacement of extracellular chloride by either bicarbonate or lactate shows that the former reduces the transmural conductance to 31% of control values as compared with 40% for the latter. Such discrepancies between permeability and conductance sequences are consistent either with an interference of the test anion with chloride permeation or with the presence of positive fixed changes within the shunt pathway.


Increased in blood flow to ischemic myocardium caused by a new dopamine analog. In the anesthetized, open-chest dog, intravenous infusion 8-13 microgram . kg-1. min-1) of a new dopamine analog 5,6-dihydroxy-2-methylaminotetralin hydrobromide (M-8) demonstrated potent coronary vasodilator properties. Blood flow to normal myocardium was increased an average of 53% above control flow values and this was associated with a decrease in coronary vascular resistance of 50%. The increase in blood flow was distributed uniformly to all portions of the myocardium (left ventricular free wall, right ventricular free wall, and septum). Subendocardial/subepicardial (endo/epi) flow ratios of the left ventricle, right ventricle, and septum were not significantly changed from control. In dog hearts subjected to acute, sudden occlusion of portions of the left anterior branch of the left coronary artery, M-8 produced a 93% increase in flow to the whole heart over postocclusion flow values. Flow to tissues of the heart made ischemic by the occlusive procedure in creased by an average of 94% during M-8 administration despite the fact that the occlusive ligatures remained in place. The vasodilation produced by M-8 was accompanied by a 22-24% increase in myocardial capillary surface area available for exchange of lipid-insoluble substances, fructose and sucrose. Hemodynamic changes associated with M-8 include a transient decrease in aortic pressure, but no change in heart rate, left ventricular (dP/dt)/P, or central venous pressure. Propranolol blocked the vasodilator activity of M-8. It was concluded that M-8 is a beta2-adrenergic receptor agonist having potent coronary vasodilator properties which also has the ability to open preexisting collateral blood flow channels and provide nutritive flow to ischemic, marginally ischemic, and normal myocardium. The cardiovascular actions of M-8 increase blood flow and oxygen delivery to the myocardium while decreasing the work and oxygen utilization by the heart, suggesting that it may have important antianginal characteristics.


Effect of arterial pulse pressure and hypoxia on myogenic responses in the gut. In intestine, raising venous pressure (PV) elicits a precapillary vasconstriction that has been ascribed to a myogenic mechanism through which passive stretch elicits active contraction of vascular smooth muscle. A previous report from this laboratory indicated that myogenic responses in the gut were largely dependent on control conditions. The purpose of the present study was to determine whether control blood flow rates or the arterial pulse pressure affects the magnitude of myogenic responses. In isolated perfused canine small bowel arterial hypoxia was used to increase blood flow. Myogenic responses to elevated PV were not significantly different in the normoxic and hypoxic periods, indicating that blood flow per se does not greatly alter myogenic responses. When gut loops were perfused with pulsatile arterial pressure, myogenic responses occurred more than twice as frequently as during nonpulsatile pefusion and they had a greater magnitude. The results are consistent with the observation that vascular smooth muscle is stimulated not only by steady stretch but also by the rate of stretch. The results also suggest that the arterial pressure pulse should be considered in the design and interpretation of future studies of local circulatory control.


Regulation of cerebral blood flow in the ovine fetus. The effects on fetal cerebral blood flow (Qc) of changes in the carotid arterial and sagittal sinus venous PO2, PCO2, and oxygen content were studied in the chronically catheterized ovine fetus in utero at 130-140 days of gestation. Forty-seven measurements of Qc were made in 20 fetuses with radioactive microspheres. In 11 of these animals, 84 measurements of cerebral arteriovenous differences of oxygen content were performed, permitting an indirect measurement of cerebral blood flow (Qc*), assuming a constant cerebral metabolic rate. Arterial and, in 11 animals, sagittal sinus blood was withdrawn for analysis of PO2, PCO2, oxygen content, and pH at the time of the flow measurements. Preliminary analysis showed the best predictor of Qc and Qc* to be the reciprocal of the arterial oxygen content (1/CaO2). Multiple linear regression analysis combining the effects of 1/CaO2 with arterial PCO2 (PaCO2) gave the following equations: Qc = 458.8 (1/CaO2) + 2.68 PaCO2 - 107.93 (R2 = 0.68); Qc* = 435.54 (1CaO2) + 2.20 PaCO2 - 75.03 (R2 = 0.86). As a result of the hyperbolic relationship between Qc (and Qc*) and CaO2, changes in CaO2 at the low levels found during intrauterine life exert an important influence on the fetal cerebral circulation.


Effect of tris(hydroxymethyl)aminomethane on ischemic myocardium. Intracellular acidosis may depress myocardial function and metabolism during ischemia. In the present study, the function and metabolism of a globally ischemic, isovolumic cat left ventricle preparation, perfused with oxygenated Krebs-Ringer biocarbonate solution, was examined. Addition of tris(hydroxymethyl)-aminomethane (Tris) (15 mM) to the perfusate at physiologic pH and PCO2 increased performance during ischemia to a greater extent and for a longer period than low PCO2 )15 mmHg), alkalotic (pH, 7.8) perfusate and a control sucrose perfusate. Under nonischemic conditions the inotropic effect of Tris was only briefly greater than sucrose perfusate. The inotropic effect of Tris during ischemia did not appear to depend on changes in coronary flow, oxygen consumption, sodium concentration, perfusate osmolality, or catecholamine release. During ischemia, lactate production was unchanged with Tris, but increased with low PCO2-alkalosis. Tissue levels of ATP and creatine phosphate for control ischemic hearts did not differ from Tris-perfused or low PCO2-alkalosis hearts. Thus, Tris appears to exert an inotropic effect that is more prominent in ischemic than nonischemic myocardium. The results are consistent with the possibility that Tris acts as an intracellular buffer to increase the efficiency of energy production and/or utilization during ischemia.