Human hexosaminidase isozymes. IV. Effects of oral contraceptive steroids on serum hexosaminidase activity.

Data from a mass screening program for identification of persons who are heterozygous for Tay-Sachs disease have been analyzed for the effects of oral contraceptive steroids on the activity in serum of hexosaminidase (hex) and the various hex isozymes. Women using oral contraceptives show a significantly higher total serum hex activity, reflecting mainly an increase in the heat-stable hex isozyme (hex I), and a smaller increase in the heat-labile hex A than do women using no medications. The changes in women using oral contraceptives are qualitatively similar to those observed during pregnancy. The distribution of responses to oral contraceptives is unimodal, and some of the variations may be related to differences in amount of steroid ingested. In addition, underlying genetic variation may contribute to the observed differences in enzyme activities.


Hypothalamic-pituitary responses to high concentrations of gonadal steroids in a three-month-old infant with a feminizing gonadal stromal tumor.

A 3-month-old female infant feminized by an ovarian stromal tumor is presented. Clinicopathologic aspects of such tumors occurring in infancy are discussed. In addition, the evaluation of hypothalamic-pituitary function preoperatively and postoperatively are presented. In the preoperative, high-steroid environment, both basal and stimulated secretion of follicle-stimulating hormone (FSH) was suppressed. Secretion of luteinizing hormone (LH) was normal. Following surgical castration, stimulated secretion of both gonadotropins clearly increased. These findings suggest an active but less sensitive negative feedback mechanism for FSH than for LH during infancy, i.e., high concentrations of gonadal steroids are necessary to maximally suppress FSH secretion while normal steroid concentrations appear to maximally suppress LH secretion. Developmental changes in hypothalamic-pituitary sensitivity to negative feedback controls are discussed in light of these findings.


Parenteral prophylaxis against enterococcal endocarditis.

Three commonly used antibiotic regimens for the prevention of enterococcal endocarditis were administered parenterally to six healthy men in a crossover manner. The regimens included 1 gm of streptomycin intramuscularly (IM) in combination with (1) procaine penicillin 600,000 units plus aqueous penicillin G 200,000 units IM; or (2) ampicillin 25 mg/kg intravenously (IV); or (3) ampicillin 1 gm IM. The combinations containing ampicillin IM or IV with  streptomycin produced bactericidal activity at dilutions of 1:2 or greater for the majority of the strains, whereas the penicillin-streptomycin regimen did not. All regimens were poorly bactericidal against three strains of enterococci which were highly resistant to streptomycin. These data suggest that ampicillin plus streptomycin is the preferred regimen for prophylaxis.


Premature rupture of the membranes: a conservative approach.

A conservative approach was followed in 188 patients with premature rupture of the membranes (PROM) over a 2 year period. There were no neonatal deaths from sepsis, and only one infant showed a positive central bacteriologic culture. Fifty-seven percent of all patients less than 37 weeks' gestation had a latent period of 24 hours and 19% went beyond 7 days before labor began. Patients less than 34 weeks' gestation who received antepartum steroids for lung maturation showed no increased infectious morbidity or mortality. A conservative approach to patients with PROM seems reasonable when either prematurity and/or a cervix unfavorable for induction further complicates the pregnancy.


Thalassemia and pregnancy: results of an antenatal screening program.

A thalassemia screening program was implemented at our institution using the finding of a mean corpuscular volume less than 80 fl as the index of abnormality. Further evaluation using hemoglobin (Hb) electrophoresis and serum iron studies was carried out according to the scheme detailed below. A diagnosis of thalassemia was made in 33 women (42 pregnancies). Eight patients had alpha-thalassemia trait, 23 beta-thalassemia trait, and two Hb H disease. Thalassemia trait did not have any adverse effect on pregnancy outcome. In two couples the fetuses were at risk for homozygous disease and in one couple the fetus was at risk for sickle cell beta-thalassemia. The screening program described is an effective and inexpensive means of detecting thalassemia in an antenatal population and is applicable to most every clinic or office setting.


Maternal and amniotic fluid steroids throughout human pregnancy.

Concentrations of testosterone, dihydrotestosterone, androstenedione, progesterone, 17 alpha-hydroxyprogesterone, and estradiol were measured by radioimmunoassay in the amniotic fluid and maternal peripheral blood obtained from normal pregnancies between 14 and 40 weeks of gestation. There was a sex difference in the levels of all the androgenic steroids in the amniotic fluid before 20 weeks with higher levels in pregnancies with male fetuses. Amniotic fluid 17 alpha-hydroxyprogesterone levels were significantly elevated in a pregnancy with the fetus affected with congenital adrenal hyperplasia. The levels of all the steroids in the amniotic fluid were significantly elevated in the pregnancy with molar degeneration of the placenta. There was a sex difference in the levels of dihydrotestosterone in the maternal peripheral blood before 20 weeks with higher levels in pregnancies with male fetuses. There was no correlation between the steroid levels in the maternal serum and amniotic fluid even though most of the samples of maternal serum were drawn at the same time as amniocentesis.


Effect of stress during labor on the concentration of cortisol and estriol in maternal plasma.

The effect of stress during labor on the plasma concentration of cortisol, unconjugated estriol, and human chorionic somatomammotropin was studied in 15 healthy primiparous women. According to the method of pain relief the parturients were divided into two groups. One group was given continuous epidural analgesia and the other group received pethidine, diazepam, and nitrous oxide/oxygen in response to pain. In the most stressed nonepidural group there was a significant rise in the cortisol level during labor and the estriol concentration fell significantly. In the epidural group no significant changes were observed with respect to the concentration of either cortisol or estriol. These results give further support to the hypothesis that severe maternal stress may lead to a reduced concentration of estriol in maternal plasma.


Short-term cycles in human fetal activity. I. Normal pregnancies.

Recordings of fetal motor activity in utero were carried out on 17 women with normal pregnancies at 23 to 37 weeks' gestation. Fetal motility was monitored by a method based on integrative EMG recordings derived through electrodes attached to maternal abdominal surface. Orthogonal spectral analysis revealed 40 minute and 80 minute cycles in fetal motility in 59% of the fetuses. The correlation between objective and subjective (maternal self-assessment) scores of fetal activity was generally confirmed. Methods of monitoring fetal activity, based on short-term recordings, are criticized in the light of the present results.


Collection and use of autologous fetal blood.

A prospective study was completed to evaluate the feasibility of autologous fetal blood collection. Following puncture on the umbilical vein, fetal blood was drawn into sterile heparinized plastic syringes and aliquots were subjected to coagulation and culture studies. None of the blood samples exhibited significant growth of bacterial pathogens and all patients had normal coagulation studies at 24 hours of age. These data demonstrate that fetal blood can be safely collected and given to infants subjected to shock or iatrogenic blood loss.


Human chorionic gonadotropin--like material: presence in normal human tissues.

With the use of radioreceptor assay for gonadotropin and a beta-chain radioimmunoassay for human chorionic gonadotropin (hCG), we have been able to demonstrate the presence of hCG-like material in all normal human tissues tested. This activity was completely absorbed by a hCHG-antibody affinity column and was demonstrated to have altered carbohydrate content by studies showing this material did not bind to concanavalin A (con A)-Sepharose affinity columns. In identical studies greater than 90% of placental hCG was bound to con A. However, if placental hCG is rendered carbohydrate free it also does not bind to con A. It is known that carbohydrate-free hCG is cleared rapidly from the circulation and thus possesses little or no biological potency in vivo. Accordingly, we hypothesize: (1) that this hCG-like material in normal tissues has the protein structure of hCG but does not possess the carbohydrate moieties of placental hCG and probably has little or no bioactivity in vivo and (2) that the trophoblastic cell is not unique in its ability to synthesize hCG but has developed the ability to glycosylate hCG, transforming a ubiquitous cellular protein into a hormone, hCG might better be called human cellular gonadotropin.


Platelet life span in pregnancies resulting in small-for-gestational age infants.

Platelet number and life span were determined in the last trimester of pregnancy in 22 women who were delivered of small-for-gestational age (SGA) infants and in 21 women with infants having normal birth weights. Platelet life span was determined by means of a nonradioisotopic method involving the use of acetylsalicylic acid. Mean platelet life span was 7.2 days in women with SGA infants, which is significantly shorter than the 9.2 days found in the control group. The mean platelet count in the SGA group was 235 x 10(9)/L, whereas in the control group it was 208 x 10(9)/L. These data indicate the existence of a compensated thrombocytolytic state in pregnancies with insufficient fetal growth. This could be explained by an increased platelet consumption in the uteroplacental arterial bed.


Evaluation of abnormal cervical cytology during pregnancy with colposcopy.

During a 6 1/2 year study period the authors used colposcopy to evaluate 174 pregnant patients with abnormal cervical cytology. The technique of colposcopy proved safe, accurate, and effective in determining the presence or absence of cervical cancer in the present patient's cervix. Colposcopy is mandatory for the evaluation of abnormal cervical cytology during pregancy.


The effect of pregnancy on the cervical squamocolumnar junction in patients with abnormal cervical cytology.

During a 6 1/2 year study period the author used colposcopy to evaluate 174 pregnant patients with abnormal cervical cytology. Of these patients, 42% had an exocervical squamocolumnar junction. In those patients beyond the age of 25, or with a parity greater than 1, 80% had endocervical junctions. The predominant effect of pregnancy is to stimulate endocervical migration of this junction.


The role of glucocorticoids, unstressful labor, and atraumatic delivery in the prevention of respiratory distress syndrome.

A 37 month review of the effects of glucocorticoids and uncompromised labor with atraumatic delivery on the incidence of respiratory distress syndrome (RDS) is presented. The incidence of RDS in the control and study population is not significantly different; however, the incidence of RDS in the control and study groups is markedly lower than the published figures for the same age and weight range. The low incidence of RDS in the control population is attributed to the avoidance of intrapartum hypoxia and stress during an uncompromised labor and atraumatic delivery.


Estriol determinations in diabetic pregnancies complicated by nephropathy.

In order to study the effect of renal disease on urinary estriol clearance rate, we have measured the concentrations of plasma and urinary estriol (E3) in pregnancies of 69 diabetic patients, 25 of whom had nephropathy. No correlation was found between endogenous creatinine clearance (CCr) and estriol clearance (CE3) rates (r = 0.07), and mean CE3 of diabetic patients with diminished CCr (less than 100 ml/min) was not significantly different from that of patients with normal CCr (greater than or equal to 100 ml/min). The ratios between total, unconjugated estriol and urinary estriol concentrations in patients with diminished CCr were not different from those patients with normal CCr. Cases where high plasma estriol and low urinary estriol concentrations coexisted were not found. It is concluded that in this group of diabetic patients, diminished CCr had no discernible effect on urinary CE3 possibly because renal tubular function remained intact. In patients with diabetic nephropathy either urinary or plasma E3 could be used to assess fetoplacental function.


Continuous variability of fetal PO2 in the chronically catheterized fetal sheep.

A method of continuous monitoring of fetal intravascular PO2 at various sites in the circulation in the chronically catheterized fetal sheep for up to 41 days (mean 11.1 days) has been compared with values obtained in blood samples measured extracorporeally in a standard blood gas analyzer. A double-blind comparison of the two methods showed that there was no bias between the two methods and correlation was 0.94. The stability of the electrodes was superior to that of a conventional blood gas analyzer. In every animal there was continuous variability of fetal vascular PO2. In the period from 105 to 126 days' gestation we noted the presence of slow increases in basal uterine tone that we have called "contractures". The frequency of these contractures was very regular at approximately one per hour. The frequency of these contracutres was very regular at approximately one per hour. There is a statistically significant related fall in fetal vascular PO2 in relation to these contractures. Well-coordinated uterine contractions during labor also produced a fall in fetal vascular PO2 that was related to the uterine activity.


The relationship between prematurely ruptured membranes and fetal immunoglobulin production.

Cord blood and maternal sera were studied in a series of 227 cases of prematurely ruptured membranes (PRM) with respect to: (1) fetal immunoglobulin (lg) synthesis associated with PRM, (2) the interrelationship between different lg classes during infection, and (3) the relationship between lg values and the duration of PRM prior to the onset of labor. A preliminary report from this laboratory, which indicated that a humorla fetal immune response occurred in some but not all cases of PRM, and that significant increases in either IgA or IgM could be found, was confirmed. There was both clinical and immunologic evidence of one peak of infection one to 12 hours after onset of PRM and another after 72 hours after onset of PRM, suggesting that some patients were infected before the clinical onset of PRM symptomatology. Increased IgA and/or IgM was found in 16.3% of infants with clinical evidence of infection. This was comparable to the 18.5% of patients with PRM who had elevated IgA and/or IgM without clinical evidence of infection. Further, there was no correlation between the severity of infection and the presence of lg elevation. Based on the data in the present series, lg determination in cord blood cannot be used to distinguish cases of PRM with and without fetal infection.


Ovarian carcinoma: improved survival following abdominopelvic irradiation in patients with a completed pelvic operation.

A prospective, stratified, randomized study of 190 postoperative ovarian patients with Stages IB, II, and III (asymptomatic) presentations is reported. The median time of follow-up was 52 months. Patients in whom bilateral salpingo-oophorectomy and hysterectomy (BSOH) could not be completed because of extensive pelvic tumor had a poor prognosis which did not differ for any of the therapied tested. When BSOH was completed, pelvic plus abdominopelvic irradiation (P + AB) with no diaphragmatic shielding significnatly improved patient survival rate and long-term control of occult upper abdominal disease in approximately 25% more patients than pelvic irradiation alone or followed by adjuvant daily chlorambucil therapy. The effectiveness of P + AB in BSOH-completed patients was independent of stage or tumor grade and was most clearly appreciated in patients with all gross tumor removed. Chlorambucil added to pelvic irradiation delayed the time to treatment failure without reducing the number of treatment failures.


Induction of preterm labor in the rat by antiprogesterone.

The validity of a new concept, predicting that preterm labor can be induced without oxytocic stimulation by a regulatory imbalance, generated by antiprogesterone (A-P)-provoked P withdrawal (Pw), has been examined in the rat model. At day 19 of pregnancy a single oral dose of the steroidal A-O isoxazol, which inhibits P synthesis, significantly reduced uterine P levels, increased uterine estradiol and prostaglandin F levels, and induced preterm labor. This precocious regulatory imbalance and preterm labor were prevented, by blocking the A-P-induced Pw with P treatment. The regulatory imbalance which triggered the onset of spontaneous labor in the control animals was similar, but it occurred at term rather than before term. The potential of this method in improving the management of medically indicated induction of preterm labor is discussed.


Six years' experience with screening of a diethylstilbestrol-exposed population.

The physician population delivering obstetric care in Philadelphia between 1950 and 1970 was contacted to ascertain their use of diethylstilbesterol (DES) during pregnancy. Of the 31.8% of the physicians who responded to the questionnaire, 71.8% used DES during pregnancy and 12.7% desired assistance in review of their records. During the 6 years from the initial survey, 830 young women exposed to DES in utero were periodically screened for cervicovaginal abnormalities and clear cell adenocarcinoma. Of these 830 patients 61.7% were found to have cervicovaginal abnormalities, and 65.9% of the patients showed either adenosis or evidence of the prior existence of vaginal adenosis. Eight patients were treated for clear cell adenocarcinoma. Two cases were detected while asymptomatic. Seven of the patients are living with no evidence of cancer, and two of these have survived over 5 years.


Quality of life for the gynecologic oncology patient.

An attempt is made to define the quality of life in terms of the patient with gynecologic cancer. The effect of the diagnosis of cancer and its recurrence or its terminal state on the quality of life is considered. Possible methods of assessing the patient's individual feelings about the quality of her life are reviewed and suggestions made for incorporating these into plans of management at all stages of the disease.


Ectopic pregnancy: current clinical trends.

During the 16 year period ending in November, 1978, 191 cases of ectopic pregnancy were managed at the University of Virginia Hospital. The overall incidence was 1/126 deliveries but during the last 3 years of the study the incidence was 1/60 deliveries. Only 56 patients have had a subsequent conception. Thirteen have had a recurrent ectopic implantation. Only 36 women (23.7% of those available for follow-up) have had subsequent term pregnancies. Ectopic pregnancy continues to be a major gynecologic problem and the potential for subsequent fertility is poor.


Bicornuate uterus and partial atresia of the fallopian tube.

Partial atresia of the fallopian tube was discovered in two patients with double uteri of the bicornuate variety. The abnormal tube in each case was ipsilateral to a noncommunicating, nonfunctioning, rudimentary uterine horn. A normal fimbriated end led to a short, patent ampullary portion that ended blindly in the mesosalpinx. Realization of the potential for the coexistence of congenital malformation of the fallopian tubes with various uterine malformations suggests that extreme caution be exercised during adnexal surgery in patients with anomalous development of the müllerian ducts.


Tubal ligation by colpotomy incision.

A five-year review of colpotomy tubal ligation performed on 585 patients within a private-practice setting in Columbus, Georgia, is analyzed. Operative time averaged under 30 minutes, and average hospital stay was less than 3 days. The major postoperative complication rate was less than 2%. The patient population is reviewed as to age, parity, previous contraception, and medical indications for sterilization. Surgical technique is discussed, and several suggestions are made, A follow-up of subsequent gynecologic procedures and the interval following colpotomy is then presented.


Radical hysterectomy: a critical review of twenty-two years' experience.

One hundred seventy-eight patients who had radical hysterectomy performed for management of invasive carcinoma of the cervix over 22 year period at the Medical University of South Carolina were critically analyzed. The degree of differentiation of the malignancy appeared to be of more significance than tumor size in Stage 1 lesions. With proper patient selection and excellent operative technique, survival rates well over 90% with minimal complications can be obtained. The radical hysterectomy should never be used in association with irradiation.


Maternal transport: behind the drama.

Despite a lack of proof that overall perinatal outcome is improved, physicians and patients participate in a growing regional maternal transport program in a community hospital setting. Over the course of 3 1/2 years, 129 patients were transferred from 23 institutions. Maternal transport and the changes which result in the interactions of the physicians are compared to traditional referral systems. Obstacles and guidelines for minimizing them are discussed.


Hypothalamic-pituitary function and radiographic evaluation of women with hyperprolactinemia and an "empty" sella turcica.

A primary "empty" sella may be associated with significant hypothalamic-pituitary dysfunction. This report characterizes the endocrinologic and radiographic findings in six patients with hyperprolactinemia (range 34.3 to 1,170 ng/ml) ultimately found to have an enlarged empty sella. Lateral skull x-ray films and thin-section tomograms were suggestive of pituitary tumors in all patients. Four patients underwent transphenoidal sellar exploration after pneumoencephalography (PEG) failed to demonstrate air within the sella. The inability of PEG to demonstrate an empty sella in two patients was explainable on the basis of an intact diaphragma sellae with previous transient intrasellar pathology responsible for the sellar enlargement. Dynamic hypothalamic-pituitary testing yielded no consistent pattern of response. These studies suggest that an empty sella: (1) may be associated with hyperprolactinemia, regardless of etiology, (2) is not diagnosable by dynamic hormonal testing, and (3) may be indistinguishable from a pituitary tumor by current radiographic techniques.


Identification of differing etiologies of clinically diagnosed premature menopause.

Investigations were performed in eight young women to determine if the findings of secondary amenorrhea and high follicle-stimulating hormone levels were due to primary ovarian follicular atresia or to other causes. Karyotypes were determined from both peripheral leukocytes and ovarian tissue; one woman had XXX/XX/XO mosaicism. Another woman had normal ovarian histology and probably had the "gonadotropin-resistant ovary syndrome." No autoimmune antibodies were detected, but one woman with myasthenia gravis also had ovarian histology that demonstrated primary ova and a developing follicle. Only five of eight women had primary ovarian follicular atresia, and two of the other three women had conditions theoretically compatible with subsequent pregnancy.


Long-term course of chloroquine retinopathy after cessation of medication.

Seven patients with chloroquine retinopathy were examined ten years after their therapy with chloroquine or hydroxychloroquine, or both, had been discontinued and an additional five patients with chloroquine retinopathy were similarly examined from two to eight years after their therapy had been discontinued. Visual acuity, visual fields, and ophthalmoscopic examinations were compared to those performed at the time therapy was discontinued. These long-term observations confirmed the previously published observations based on short-term studies that chloroquine retinopathy tends to remain stable after therapy is discontinued, although a few patients in the early stages of retinopathy may show regression and occasionally a patient with a more advanced stage of the disease may show progression.


Aciclovir and corneal wound healing.

Masked controlled rabbit studies were done to determine the toxic effects on corneal wound healing of the antiviral drugs 3% aciclovir and 0.5% idoxuridine ointment in therapeutically effective concentrations. Aciclovir had no significant detrimental effect in comparison to controls on the quality of regenerating epithelium or the re-epithelialization of epithelial wounds. Idoxuridine treatment caused significant toxic changes in the regenerating epithelium clinically and histologically with a significant delay in epithelial wound healing in comparison to control or aciclovir treated eyes. Aciclovir had no significant effect on the collagen content of stromal wounds as measured by hydroxyproline levels. Idoxuridine caused a reduction in collagen content not significantly different from controls but significantly lower than aciclovir.


Apneic spells associated with timolol therapy in a neonate.

A 2-week-old premature child with congenital glaucoma secondary to anterior cleavage syndrome was treated with timolol maleate and cyclocryotherapy. The patient had apneic spells of up to 30 seconds that stopped soon after timolol maleate therapy was discontinued. No apnea was seen before timolol maleate administration, and no further spells were noted after subsequent cyclocryotherapy without timolol maleate treatment. Possible central nervous system toxicity of timol maleate or its metabolic by-products in neonates with immature blood-brain barriers was noted.


Massive subretinal exudate after retinal detachment surgery.

A 70-year-old woman developed massive subretinal exudation after surgical repair of a rhegmatogenous retinal detachment. Postoperative choroidal detachment suggested a choroidal source of the subretinal exudate. We believe the cause of the choroidal detachment and exudation was vortex ampulla obstruction resulting from the encircling band. The subretinal exudate underwent gradual resolution and did not influence the anatomic result of retinal reattachment.


A wireform surgical drape-retractor.

I devised a malleable plastic-coated wireform drape-retractor that increases patient comfort during surgery by keeping drapes off the nose and mouth. It is small and does not interfere with the surgeon's hand movements.


A retention modification for the limbal ring method of foreign body localization.

For intraocular foreign body localization, we used a modification of the limbal ring method with surgical adhesive instead of limbal sutures. After taking x-ray films of the eyeball, we removed the ring and the adherent glue with toothless forceps.


Traumatic retinal pigment epithelial edema.

A 17-year-old girl was struct in the right eye by a mortarboard tossed into the air during high school graduation exercises. She suffered commotio retinae with damage to the retinal pigment epithelium and macular hole formation. Fluorescein angiography in the acute stages revealed diffuse staining at the level of the pigment epithelium. Five months later, the areas of abnormal staining had undergone depigmentation and dye no longer accumulated in the pigment epithelial layer. The fluorescein findings in traumatic retinal pigment epithelial edema are unusual.


Cystoid macular edema as the primary sign of neurosyphilis.

A 34-year-old man had a six-month history of bilateral visual loss that was secondary to cystoid macular edema, which was assumed to be secondary to neurosyphilis on the basis of cerebrospinal fluid serology, cell count, and protein. Good visual acuity was recovered with systemic corticosteroids only after they were used in combination with antitreponemal therapy. This is the first report, to the best of our knowledge, of cystoid macular edema as the primary sign of neurosyphilis documented by fluorescein angiography.


Retinal astrocytoma.

A 41-year-old man had a 6 x 6 x 5-disk diameter amelanotic tumor in the posterior fundus. The clinical and fluorescein angiographic appearance suggested a benign retinal vascular tumor, although amelanotic choroidal melanoma and retinoblastoma were diagnostic possibilities. An incisional 48-hour radioactive phosphorus (32P) uptake test was performed and the result showed an increased uptake over the tumor mass of 100% as compared to the control quadrants. The globe was enucleated and the pathologic diagnosis was isolated astrocytic glioma of the retina with minimal, if any, malignant potential. The highly developed vascular system of the tumor probably contributed to the false-positive test result.


Adenoma of the pigment epithelium of the ciliary body simulating a malignant melanoma.

A benign adenoma of the pigment epithelium of the ciliary body in a 27-year-old woman simulated a malignant melanoma clinically and resulted in enucleation. The correct diagnosis was not made clinically despite the use of A- and B- scan ultrasonography and the radioactive phosphorus (32P) uptake test, procedures which are usually reliable in differentiating between melanoma and pseudomelanoma. We emphasize the shortcomings of these ancillary tests in differentiating pigment epithelial tumors from malignant melanoma.


Cystoid macular edema in aphakic and pseudophakic eyes.

A prospective fluorescein angiographic study, comparing the incidence of cystoid macular edema in patients 67 years or older after intracapsular cataract extraction with a Binkhorst 4-loop implant, extracapsular cataract extraction with a Binkhorst 2-loop or 4-loop implant, and intracapsular cataract extraction with no implant (controls) was begun at the Bascom Palmer Eye Institute of the University of Miami School of Medicine on May 14, 1974. Excluded from these groups were all patients whom we did not consider to be suitable candidates for lens implant surgery. Fundus fluorescein angiograms were taken four, eight, and 16 to 24 months postoperatively. The surgery was performed by one group of surgeons and the angiograms were read by a group of retinal specialists. The intracapsular cataract extraction-implant and intracapsular-no implant groups had a comparable incidence of cystoid macular edema four, eight, and 16 to 24 months postoperatively. The extra capsular cataract extraction-implant and an intact posterior capsule group had a significantly lower incidence of cystoid macular edema than the intracapsular cataract extraction-implant group 16 to 24 months postoperatively. The differences were less significant at four and eight months. Visual function as measured by visual acuity was 6/12 (20/40) or better in approximately 80% of eyes with angiographic-proven cystoid macular edema.


Retinal detachment in pseudophakia.

In a series of cataract patients excluding myopic individuals, under age 60 years, and cases in which vitreous loss occurred, retinal detachment was no less frequent after intracapsular cataract extraction and Sputnik iris supported lenses than in controls. Both groups were followed up for a minimum of two years. The detachments predominantly occurred from retinal breaks in areas of the retina that looked normal preoperatively.


Time analysis of corneal endothelial cell density after cataract extraction.

Serial endothelial photographs were taken preoperatively and postoperatively in 200 eyes; 111 eyes contained a Rayner iris clip lens, 54 eyes contained a Fyodorov Sputnik lens, and 35 eyes had no lens. Central endothelial cell density was changed in all instances, with counts in implanted eyes declining 25 to 30%, and in nonimplanted eyes 10 to 15%. In both instances, the decline essentially ceased at about three months. The cause of the greater decline in implanted eyes appeared to be mechanical and subsequent cell loss after the 90-day period was virtually equal for the two groups. Methods that may be used to alter the difference in cell density occurring with implantation are best analyzed by using the 90-day period data for comparison.


Culture of human glomerular cells.

Human glomeruli were routinely cultured in Waymouth's medium supplemented with insulin and conditioned medium. Three cell types were seen in the culture of both adult and infant kidneys, but the morphology of the glomerular cellular outgrowths depended on the age of the patient from which the kidney was obtained. Cultures of glomeruli from older individuals resulted in more "differentiated" cells, but both adult and infant glomerular cells rapidly became "dedifferentiated" as the length of time in culture increased. Outgrowths of cultured glomeruli did not contain fibroblasts or tubular cells. Finally, synthesis of basement membrane material by these cultured glomerular cells was demonstrated.


Correlation of estrogen and progesterone receptors with histologic differentiation in endometrial adenocarcinoma.

Endometrial carcinomas from 58 patients were graded histologically, and the histologic grade was compared with the estrogen and progesterone receptor content of the tumor tissues. Receptor content was determined by multiple concentration saturation analysis and sucrose density gradient analysis. A positive correlation was found between the presence of estrogen and progesterone receptors and the degree of tumor differentiation. The majority (85%) of well-differentiated lesions contained significant amounts of both steroid receptor proteins. In contrast, only 13% of the poorly differentiated lesions were characterized by the presence of detectable levels of both estrogen and progesterone receptor proteins. The relationship of receptor content and degree of differentiation to prognosis and potential for response to hormonal therapy is discussed.


Gene complex controlling growth and fertility linked to the major histocompatibility complex in the rat.

The B1 strain of rats carries a unique mutation which causes defects in growth and reproduction: the males and females are small, the testes are hypoplastic and aspermatic, and the females have a reduced reproductive capacity. The loci controlling these defects are linked to the major histocompatibility complex (MHC) as determined by segregation studies in backcross and F2 hybrid populations. The levels of pituitary hormones and somatomedin C in the B1 strain are elevated or normal, and the testosterone level is elevated relative to the size of the testes. These findings suggest that hormone deficiencies are not the cause of these defects. The genes governing these defects have been designated the growth and reproduction complex (Grc). The recessive gene regulating small body size has been designated dw-3 (dwarf-3), and the recessive gene influencing reproductive capacity has been designated f. The Grc and MHC are separable by recombination, and the dw-3 and f genes are also separable by recombination. Studies in the (B1 X DA)F2 hybrid indicate that the map distance between the Grc and the MHC is 0.6 cM. Segregation distortion due to a deficiency of RT11 homozygotes is seen in some F2 hybrid populations derived from the B1 strain. Litter size data suggest that the loss of the RT11 homozygotes is due to intrauterine death. There is no apparent sex influence on the inheritance of the Grc, at least as it is presently understood, since it can be transmitted by either females or males. The growth and reproduction complex in the rat may be the analog of the T/t complex in the mouse, and the importance of the region of the chromosome adjacent to the major histocompatibility complex in the control of developmental processes may be a general phenomenon in mammals.


The structure of tight junctions in human thyroid tumors. A systematic freeze-fracture study.

Tight junctions of normal human epithelium comprise 6--8 intramembranous ridges. Tight junctions of adenomas and one case of follicular carcinoma were morphologically identical with normal controls. Another follicular carcinoma (clinically less malignant than the case mentioned above), however, showed loss of junctional polarity with spreading of ridges on lateral cell membranes. One case of papillary carcinoma (clinically low malignancy) displayed only focal attenuations of the tight junction belt. Another more malignant tumor of the same histologic type showed breaks of ridges and focal interruptions of the tight junction meshwork. Cell membranes of two anaplastic carcinomas of high malignancy were completely devoid of tight junction ridges. We conclude that tight junction alterations are not necessarily implicated in malignant transformation and that they correspond with tumor differentiation rather than directly with a single parameter of thyroid tumor malignancy.


Studies of the Pelger-Huët anomaly in foxhounds.

An inbred family of foxhounds with four members expressing the Pelger-Huët (P-H) anomaly is described. The disease-free status of all P-H affected dogs suggests a benign disorder, although review of breeding records indicated a lower percentage of pups weaned (63%) by P-H females compared with the percentage of pups weaned (81%) by outcrossed females throughout the foxhound colony. Light-microscopic examination of blood films from affected dogs revealed 50--67% neutrophils with round, oval, or bean-shaped nuclei and rarely (0.5%) segmented nuclei. Neutrophils examined by electron microscopy showed the nuclei to have a fine nuclear cleft and condensed chromatin and the cytoplasm to have mature heterochromatic granulation. Local P-H neutrophil mobilization through a standard skin abrasion into a chamber containing autologous serum was impaired at all time periods evaluated (1, 4, 8, and 24 hours) compared with the neutrophil mobilization by normal dogs. Antibody response to sheep erythrocyte immunization was also impaired. In vitro reactivity of normal and P-H lymphocytes stimulated by pokeweed mitogen was depressed when lymphocytes were cultured in plasma from a P-H dog but not when cultured in plasma from a normal dog. Vigorous blastogenic responses to phytohemagglutinin by normal and P-H lymphocytes cultured in P-H or normal plasma suggest the presence of a factor(s) in the P-H plasma which interferes with B-lymphocyte reactivity.


Induction of IgE antibodies to antigen isolated from tobacco leaves and from cigarette smoke condensate.

Neonatal California White rabbits were sensitized with a glycoprotein purified from cured Virginia Bright tobacco leaves. Their serums, but not serums from normal rabbits, were demonstrated by passive cutaneous anaphylaxis technique to contain heat-labile, homocytophilic antibodies to this antigen and to similar material purified from cigarette smoke condensate. Serums containing IgE antibodies to tobacco antigen would not be demonstrated to contain hemagglutinating antibodies to this antigen. These experiments demonstrate that antigen capable of triggering specific IgE-mediated release of inflammatory mediators is present in cigarette smoke. It can be hypothesized that IgE-mediated responses to antigen in cigarette smoke are causally related to the development of vascular injury and of myocardial arrhythmia in hypersensitive smokers.


A phenomenologic description of clot lysis in dilute human plasma correlating structure and function of platelets.

Platelets in a dilute platelet-rich plasma clot formed by the addition of thrombin at 4 C do not lose their alpha-granules or develop platelet-fibrin interconnections. These clots do not retract or lyse. If after clot formation for 30 minutes the clots are transferred to 37 C, the alpha-granules then disappear from the platelet, extensive platelet-fibrin interconnections develop, and the clots retract and lyse. When the dilute plasma clots, however, are formed at 37 C, alpha-granules are quickly lost, few platelet-fibrin interconnections develop, and the clots do not retract or lyse. Deoxyglucose and antimycin, when added before thrombin at 4 C, prevent the loss of alpha-granules and development of platelet-fibrin interconnections after transfer of the clot to 37 C. These inhibited platelets did not retract or lyse. From the results reported here we conclude that the development of platelet-fibrin interconnections as well as the retraction and lysis of the clot occur in conjunction with the release of alpha-granules from the platelet. It may be necessary for this release to occur after the fibrin network is completed, since release of the alpha-granules in the 37 C clot before clot formation did not result in formation of many platelet-fibrin interconnections or in clot retraction or lysis.


Hypoxia and incorporation of 3H-thymidine by cells of the rat pulmonary arteries and alveolar wall.

In the pulmonary arterial circulation hypoxia produces increase in thickness of the medial muscle coat as well as of the adventitia; in addition muscle appears in smaller arteries than is normal and the number of small arteries that fill on Micropaque-gelatin injection is reduced. To assess the role of hyperplasia in these changes, the uptake of 3H-thymidine by the cells of the pulmonary arterial wall has been studied in rats exposed to hypobaric hypoxia (exposure to 380 torr) after 1, 3, 5, 7, 10, and 14 days. Using autoradiographs of 1-micron sections, the glutaraldehyde-distended intrapulmonary hilar muscular artery, the peripheral, intraacinar arteries less than 100 micron in external diameter, and the alveolar wall had different patterns of uptake. In the hilar pulmonary artery, after 24 hours of exposure, the labeling index for adventitial fibroblasts is increased eightfold over the control value, and for endothelial cells, threefold, while for medial smooth muscle cells, there is a gradual and small increase to Day 14. Newly muscularized intraacinar arteries are first apparent at Day 3, when they comprise 40% of the intraacinar arteries, increasing to 80% at Day 7. No decrease in density of arteries is found. Uptake of 3H-thymidine by new muscle cells is not apparent until Day 5 when labeling is maximum. The endothelial cells of the newly muscularized arteries show an increased labeling index only at Days 7 and 10. The veins and normally muscular arteries do not show these changes. In the alveolar walls, the concentration of labeled cells is significantly above the control value at Days 3, 5, and 7 and significantly below, at Day 14. At this level, the interstitial, epithelial, and endothelial cells contribute to the increase.


Acute inflammatory pulmonary reactions induced by chemotactic factors.

Acute inflammatory reactions have been produced in hamster lungs by the intrapulmonary instillation of preformed chemotactic mediators (C5fr and F-Met-Leu-Phe). By the use of 111Indium and 125Iodine labeling of homologous neutrophils (PMNs) and homologous albumin, respectively, it has been possible to obtain highly reproducible and quantitative parameters of the acute inflammatory response. The lung responds in a dose-dependent and time-dependent manner to the instillation of preformed chemotactic mediators. The quantitative parameters indicative of PMN influx were more prominent than changes in vascular permeability. The data obtained by the use of radiolabeled PMNs were confirmed by observation with light microscopy. Nonchemotactic substances such as human IgG, serum albumin, and C4 failed to induce inflammatory responses in lung. Interestingly, intact C5 instilled into lung was extremely phlogistic, apparently due to hydrolysis once within the lung. These studies provide an approach to reliable quantitative parameters of inflammatory reactions in the lung and emphasize the in vivo biologic effects of chemotactic mediators.


Ultrastructural radioautography and cytochemistry of lead absorption.

Lead is a universal environmental contaminant absorbed largely through the gastrointestinal tract by unknown mechanisms. Because lead absorption is influenced by iron content in the body and diet, we used ultrastructural radioautography and cytochemistry to study absorption of physiologic lead doses in the rat duodenal epithelial cell and compared these findings to those previously reported for iron absorption. Rat duodenal loops exposed in vivo to 210Pb for 1 minute demonstrated the majority of labels on the microvilli, terminal web, and apical cytoplasm. Specimens exposed to radiolead for 10 minutes demonstrated more abundant labeling with a relative increase in labeling of epithelial cell mitochondria, nuclei and basal cytoplasm, as well as phagocytic cells, endothelial cells, and circulating erythrocytes of the lamina propria. Timm's sulfide-silver method localized trace metals in epithelial cells. After administration of lead, a significant increase in staining was observed in microvilli, mitochondria, non-membrane-bound cytoplasm, and nuclear chromatin. The rapid appearance of absorbed lead in epithelial cell mitochondria and nuclei, as well as phagocytic cells in the lamina propria, was distinctly different from that reported for absorbed iron and suggests different mechanisms for the subcellular transport of these cations. The combination of radioautography and Timm's sulfide-silver staining provides the specificity and resolution needed for ultrastructural evaluation of lead absorption and should be useful in further studies of lead metabolism.


Treatment with a position feedback-controlled head stabilizer.

A position feedback-controlled head stabilizer has been developed to provide cerebral palsied individuals with resistive exercise to strengthen the neck musculature. This apparatus detects "involuntary" head motion and stabilizes the head by applying opposing forces; it also can be used to facilitate muscular contraction by resisting the subject's voluntary movements. The purpose of the present study was to determine whether voluntary head control in cerebral palsied individuals can be improved through systematic exercise using the stabilizer to strengthen the muscles of the neck and improve their balance of action. The findings support the author's contention that this is possible. The apparatus consists of a helmet and shoulder pads, interconnected so that the head is supported in the helmet by a manipulator arm. At its lower end, the manipulator arm is attached to the shoulder pad mounting frame via a gimbal assembly which allows head movement in two planes of tilt (pitch, or forward-and back, and roll, or side-to-side). Feedback control circuitry is so arranged that any deviation of the head from the desired position leads to actuation of pneumatic cylinders, which apply torques to the manipulator gimbal axes so as to oppose or conteract the incipient head movement. It is particularly significant that none of these patients participating in these experiments were at all apprehensive about or resisted being placed in the apparatus. (Even the youngest subject to use the apparatus--five year old-- did not mind being restrained by the shoulder pads or having his head gripped by helment.) While JG utilized the safety release valve quite often during the first few head control training sessions, he soon became confident enough in the action of the stabilizer that he did not even bother to grip the handle of the release valve. While DA had the action of safety valve explained and demonstrated for her, she never bothered to use it even from the outset of her experience with the stabilizer. Thus, it seems that the football shoulder pads use to stabilize the shoulders and the hockey helmet used to grip and manipulate the head actually make the apparatus attractive to younger patients, while the padding thereby provided makes it comfortable enough to be tolerated well by older individuals. And, the subject's knowing that he has an override control by means of which he can assert command over the entire system appears to be of psychological benefit in establishing confidence in both the apparatus and the investigator.


Efficacy of myofeedback therapy in regaining control of lower extremity musculature following stroke.

The short-term efficacy (three months or less) of electromyographic biofeedback on the control and strength of six lower extremity muscles in twenty-two hemiplegic patients was investigated. The analysis of the data shows that patients receiving myofeedback therapy achieve a much larger increase in the control of muscle activity whereas there is no significant difference in the increase in strength.


The C3 component of complement; gene frequency variation in Iraq.

Heterogeneity of gene frequencies in the polymorphism of the third component of complement among local samples in Iraq is analysed. It appears to derive essentially from population and not from regional differences.


Telemetered electromyography of flexor digitorum profundus and flexor digitorum superficialis in Pan troglodytes and implications for interpretation of the O. H. 7 hand.

The importance of knuckle-walking in the locomotor repertoire of African apes raises the possibility that the long digital flexors may be specially adapted more to meet the demands of ground quadrupedalism than those of suspension. To investigate this possibiltiy, the activities of the flexor digitorum superficialis and flexor digitorum profundus were studied by means of telemetered electromyography in three chimpanzees. Results clearly indicate that the fasciculi of the muscles to digits bearing weight in knuckle-walking are not called upon to contract in quadrupedal postures or in slow and moderately fast quadrupedal locomotion except to help clear the fingers from the ground as the forelimb begins its recovery stroke. At the most rapid speeds, a slight to moderate level of activity sometimes occurs in the latter half of stance phase. The long digital flexors display maximum and sustained activity during suspension. It is concluded that any role for these muscles in maintenance of stability at the metacarpophalangeal joints during knuckle-walking must be predominantly passive. Prominent markings for insertions of these muscles in a fossil hand (such as O.H. 7) suggest use of the forelimb in suspensory climbing behaviors.


Placental alkaline phosphatase: population studies in Sardinia and data on the anthropological value of this genetic marker.

The analysis of human placental alkaline phosphatase polymorphism in Sardinia has shown a further difference in the genetic structure of this population in comparison with the populations of Continental Italy and Western Europe. Ethnic and geographic variations in world distribution of placental alkaline phosphatase gene frequencies suggest the considerable anthropological value of this genetic marker.


The statistical treatment of correlated bilateral traits in the analysis of cranial material.

At present there is no standardized method to derive frequencies from bilateral non-metric traits. In this paper the commonly used methods are evaluated in light of statistical considerations and degree of sample preservation. In particular, we explore the question of dependence between sides for the bilateral traits. Several workers have tested for bilateral trait correlation in incorrect ways, confusing tests for differences in side frequencies with tests for independence. An easy method to test for independence, using the chi-squared test, is recommended. This test is used on 16 bilateral traits in a large sample of prehistoric carnia from Central California and significant dependence is found for all 16 of these traits. We suggest the traditional method of deriving frequencies be used. Both sides of the cranium should be considered, dividing the number of times the trait occurs by the number of sides available for observation. This method can be used even in poorly preserved samples. Side to side correlation may be compensated for by modifying the constants subtracted in the mean measure of divergence and in the expression for the approximate variance of the mean measure of divergence when the samples are drawn from identical populations.


Sex assessment of the femur: a test of a new method.

Simple and multiple discriminant functions using mid-shaft femoral circumference for the determination of sex were used to test a sexing method recently proposed by Black. The method was able to correctly assign sex for 82% of the sample, which consisted of 115 North American White femora of verified age and sex. Circumference proved as accurate as any other criteria that have been used in sexing the femur. This suggests a usefulness beyond the limited archaelogical scope originally proposed by Black.


Active and passive Ca movements in dog red blood cells and resealed ghosts.

Dog red blood cells accumulate Ca rapidly when deprived of substrate or cooled to 5 degrees C. The latter effect is reversible as the cells are rewarmed to body temperature. Resealed ghosts extrude Ca, provided ATP is incorporated in them. Passive fluxes of Ca are stimulated by Na on the opposite side of the membrane, consistent with a model for Ca-Na countertransport. Quinidine, cell shrinkage, and low pH--all known to suppress net Ca influx--have no accelerating effect on Ca efflux, thus validating earlier conclusions about the variability of the coupling ratio for Ca-Na exchange. The significance of these findings for cell volume regulation is discussed.


Lithium fluxes in human erythrocytes.

The contribution of four transport pathways to Li+ influx and efflux in human erythrocytes was determined quantitatively, using Li+ concentrations comparable to those found in vivo when Li+ is used as treatment for manic-depressive illness. All pathways were measured simultaneously on each subject's blood sample to avoid possible temporal variations in transport parameters. We found that Li+ efflux is 75% via countertransport and 25% via a leak. The bicarbonate-sensitive pathway accounts for 30% of influx while the remaining 70% is via a leak. The Na+-K+ pump makes no significant contribution to Li+ influx or efflux under physiological conditions. Li+ efflux for a given [Li+]i is 3-5 times the Li+ influx for the same [Li+]o. However, due to interindividual variations in Na+-Li+ counter-transport, Li+ efflux but not influx varies considerably among individuals.


Maintenance of ion concentration gradients in the cold in aorta from rat and ground squirrel.

Cell water and ionic content were measured in aortic smooth muscle from rats and ground squirrels during 48 h of incubation in oxygenated Krebs solution held at low temperatures. Cells from the ground squirrel, a hibernator, maintained sodium and potassium contents near normal levels during incubation at 7 degrees C. In sharp contrast, cells from the rat lost potassium and gained sodium with half times of 14 and 11 h, respectively. The [K] in cell water for the rat decreased 138 mM while [Na] in cell water increased about 148 mM. Cells from the hibernator tended to lose 10 mM K and gain 13 mM Na. Vascular smooth muscle of both the rat and squirrel was able to maintain K content at 17 degrees C. Tissue content of the divalent cations Ca and Mg did not change in vessels from either animal. The present findings suggest that aortic smooth muscle cells from a hibernator have adapted in such a way as to maintain ionic gradients upon prolonged exposure to low temperatures.


Length-dependent activation of in situ canine skeletal muscle.

This study was designed to assess the contribution of length-dependent activation to the peak isometric twitch tension developed and the maximal rate of tension development (dP/dt) of in situ canine skeletal muscle. Length-developed tension and length-dP/dt relationships were generated for the dog gastrocnemius-plantaris muscle group at three different levels of inotropic state as determined by stimulation frequency. These relationships were then normalized with respect to maximal developed tension and maximal dP/dt and the normalized curves were superimposed for comparison. At progressively shorter muscle lengths the augmentation of tension production by a given increment in inotropic state was greater as measured by either developed tension or dP/dt. Thus, a given change in muscle length produced a greater change in performance in less potentiated muscles. These findings are similar to those from studies of isolated cardiac muscle and illustrate the lack of independence between activational state and muscle length for in situ skeletal muscle.


Effect of chemotactic factors on calcium levels of rabbit neutrophils.

Studies were undertaken to provide a systematic investigation of the effect of the chemotactic factor, formyl-methionyl-leucyl-phenylalanine (F-Met-Leu-Phe), on the levels of total and exchangeable calcium in rabbit neutrophils. The 45Ca2+ specific activity of the cells was thus determined before and after stimulation by chemotactic factors. Total cell calcium was found to be constant in neutrophils equilibrated with 50-1,000 microM extracellular calcium but decreased by 30% at an extracellular calcium concentration of 5 microM. F-Met-Leu-Phe had little, if any, statistically significant effect on the level of total cell calcium. In contrast, F-Met-Leu-Phe affects greatly the steady-state levels of radioactive calcium in the neutrophils. The primary effect is an initial loss followed by an increase of cell-associated radiolabeled calcium. The extent and even the direction of the effect depends on the level of extracellular calcium as well as the concentration of the chemotactic factor and the duration of its interaction with the cell. The results are discussed in terms of the hypothesis that the binding of the chemotactic factor to its receptor leads to, among other things, a graded displacement of previously bound Ca2+.


Energetics of sugar transport by isolated intestinal epithelial cells: effects of cytochalasin B.

The capability of isolated intestinal epithelial cells to establish concentration gradients of 3-O-methylglucose (3-OMG) by a Na+-dependent transport system is limited by concomitant function of a Na+-independent, facilitated diffusion transport system. Monosaccharides accumulated by the active system are continuously lost via the passive system, which acts to lower steady-state sugar gradients maintained by the cell. Cytochalasin B is a potent inhibitor of the passive system and allows the cells to establish a sugar gradient that is much higher than normal. When extracellular [3-OMG] is 1 mM, cytochalasin induces sugar accumulation ratios of 30-fold (+/- phlorizin) in contrast to control ratios of approximately 10-fold. When [3-OMG] is 0.1 mM, cytochalasin (0.1 mM) induces 40-fold accumulation ratios. When changes in extracellular sugar concentration are considered, steady-state concentration gradients observed are 70-fold. For a Na:sugar coupling stoichiometry of 1:1, gradients of this magnitude represent the approximate theoretical maximum for a transport system driven exclusively by the transmembrane electrochemical potential for Na+.


Electrical activity of rat myocardial cells in culture: La3+-induced alterations.

Intracellular analysis of neonatal rat (1-2 day old) ventricular cells in culture shows that contracting myocardial cells exhibit an array of different patterns of spontaneous electrical activity. Resting membrane potentials varied between -40 mV and -98 mV. Our results indicate that some cultured cells show resting membrane potentials, overshoot, and total spike amplitude values comparable to those normally found in neonatal and adult rat heart. A low ratio of pacemaker (40%) to nonpacemaker cells (60%) and low incidence of hyperpolarizing after-potentials (35%) were found. La3+ application (0.1-4.0 mM) induced progressive cell depolarization, concomitant diminution in discharge frequency, and marked alteration of action potential configuration. A parallel decline in frequency and strength of rhythmic contractions was observed. Abolition of contractility occurred only in association with depolarization and complete disappearance of action potentials. Recovery of electrical and contractile activity followed medium replacement. Our results indicate that La3+ does not act as a specific excitation-contraction (E-C) uncoupler in the cultured cells but has multiple effects upon their normal electrical characteristics.


Calcium transport in human red blood cells under hypertonic conditions.

Calcium accumulation in intact human erythrocytes is enhanced by incubation in hypertonic solutions. Hypertonicity produces an increased permeability of the membrane to calcium that is time-dependent and occurs in the presence or absence of calcium. When hypertonically treated cells are incubated for more than 30 min in 300 mosmol/kg solutions the permeability of the membrane to calcium returns to basal values. Oligomycin inhibits the effect of hypertonicity on calcium uptake. The inhibitory action of oligomycin diminishes as the external sodium increases and can only be observed when the external concentration of potassium is at or below 3 mM. Low intracellular sodium and high intracellular potassium concentrations increase the uptake of calcium. It is concluded for human erythrocytes that 1) the increased permeability of the membrane to calcium produced by hypertonicity is a time-dependent, reversible phenomenon and is independent of calcium, 2) the increase in intracellular potassium concentration associated with hypertonic exposure is an important factor contributing to this response, and 3) interactions between calcium and components of the sodium-potassium transport system may account for the enhanced uptake of calcium produced by hypertonicity.


Evidence that dog kidney is an endogenous source of histidine.

Net production or utilization (Qmet) of histidine by the kidney was evaluation or utilization (Qmet) of histidine by the kidney was evaluated in 11 normal and 8 chronically uremic female dogs during intravenous infusion, first of half-normal saline and then an amino acid solution containing L-histidine. Also, Qmet for histidine, alanine, beta-alanine, and carnosine (beta-alanyl-L-histidine) was determined during infusion of half-normal saline and then carnosine into the renal artery in seven normal dogs. During infusion of half-normal saline, Qmet histidine, calculated from the plasma data, was significantly positive in normal but not uremic dogs. Qmet histidine correlated with creatinine clearance. In uremic dogs, plasma histidine was decreased possibly due to decreased renal production and increased urinary excretion. Qmet histidine, calculated from the whole blood data during infusion of half-normal saline, was positive but not significantly so. During carnosine infusion, there was significant utilization of carnosine, and histidine production increased. Thus during fasting, the dog kidney appears to produce histidine, and histidine production increases with carnosine infusion. Hydrolysis of carnosine, possibly by carnosinase, may be a source of histidine released by the dog kidney.


Acrosin of mouse spermatozoa.

Mouse spermatozoa possess a neutral proteinase, acrosin, that is to a large extent (70-80%) present in the zymogen (proacrosin) form. Acid extraction yields higher amounts of acrosin than detergent extraction. Synthetic inhibitor studies indicate that mouse acrosin has a serine and histidine at its active site and hydrolyzes the peptide bonds of lysine and arginine but of not phenylalanine. An inhibitor of acrosin is associated with mouse spermatozoa, capable of preventing the activity of at least 60% of all available acrosin. Acrosin activity is essential for fertilization because natural and synthetic inhibitors of mouse acrosin prevent the union of the gametes. Also, the relative inhibitory activity of synthetic agents toward acrosin runs approximately parallel to their antifertility activity. The percent of acrosin in the proacrosin form does not change after capacitating mouse spermatozoa in vitro.


Glucose-induced insulin release during acute and chronic hypoxia.

Glucose-induced insulin release was studied in young dogs during acute and chronic hypoxia, alone and in combination. Six experimental animals were rendered chronically hypoxic (PaO2, 43.4 +/- 0.5 torr) by creation of a right-to-left shunt at age 6-8 wk. Six control animals underwent sham procedures (PaO2, 85 +/- 2.2 torr) at the same age. During air breathing, glucose-induced plasma insulin increases were similar in chronically hypoxic and control animals. When severe hypoxia was acutely produced by ventilation with low-oxygen mixtures in experimental (PaO2, 23.7 +/- 1.7 torr) and control animals (PaO2, 26.3 +/- 1.0 torr), plasma insulin responses were markedly inhibited in both. On the other hand, acutely lowering oxygen tensions of control animals (PaO2, 37.5 +/- 1.4 torr) to levels close to those of air-breathing chronically hypoxic animals did not affect the insulin responses. These observations suggest that glucose-induced insulin release is inhibited by acute severe hypoxia despite previous chronic oxygen deficiency. In contrast, moderate hypoxia, acute or chronic, does not appear to affect the insulin response to a glucose load.


Effect of angiotensin II on parotid saliva secretion in conscious sheep.

Intravenous infusion of angiotensin II over the dose range 3-20 microgram/h for 15 min caused a dose-dependent reduction in parotid saliva secretion and increase in arterial blood pressure in conscious sheep. The blood levels of angiotensin II contrived by these infusions were probably within the physiological range for sheep. Infusion of angiotensin II (3 microgram/h) into the carotid artery ipsilateral to the parotid gland under study caused greater reduction in saliva secretion rate than an equivalent infusion of angiotensin II into the contralateral carotid artery. This result suggests a direct effect of angiotensin II at the parotid, possibly by a constrictor action on its vasculature or by altering water and electrolyte transport by the gland. In sodium-deplete sheep, intravenous infusion of the angiotensin antagonist saralasin (1 mg/h for 1 h) caused transient increase of saliva flow for 20-30 min. It is suggested that angiotensin II may have a physiological role in regulating parotid saliva secretion during sodium depletion.


Perinatal development of intestinal myoelectrical activity in dogs and sheep.

Both slow waves and bursts of spike potentials were recorded prior to birth in dogs and sheep. At 0l7-0.8 of term the slow-wave frequency of the jejunum did not exceed 12/min. It increased in a similar way during the last stage of fetal life in sheep and after birth in dogs. Adult values were attained 10-15 days after birth in the lamb but only by 40 days of age in the puppy. In both species, three stages of development of the spiking activity were identified. Stage 1, termed unorganized spiking activity, was converted in the fetal lamb at 0.8 of term to a fetal pattern (stage 2) characterized by cyclic 3- to 4-min periods of regular spiking occurring at 10- to 20-min intervals and propagated along a short intestinal segment. Stage 3, which corresponds to myoelectric complexes, occurred during the last 10 days of fetal life. In dogs, the fetal pattern (stage 2) was recorded from 5 days before to 15 days after birth. Stage 3 was seen in the 15-day-old neonate. The results suggest that the patterns of electrical activity seen in the last third of fetal life can be related to their function of mixing and absorbing but not expelling intestinal contents. They indicate that the electrical phenomena of the gastrointestinal tract are in accord with the overall greater maturity and independence of the newborn sheep compared to the dog.


Nerve pathways in celiac plexus of the guinea pig.

In vitro preparations consisted of the right and left celiac, superior mesenteric and inferior mesenteric ganglia with attached extrinsic nerves, vasculature, mesentery, and colon. There were no systematic differences in membrane electrical properties (recorded intracellularly) between neurons in the different ganglia. Stimulation of associated nerve trunks produced graded synaptic responses in plexus neurons. Presynaptic fibers were found in splanchnic and mesenteric nerves. Input from celiac nerves dominated in the celiac galglia; input from the intermesenteric fibers dominated in the superior mesenteric ganglion. When the ganglia were attached to the entire colon, 33% of the neurons in the celiac and 54% in the superior mesenteric ganglion received a continuous excitatory synaptic input that was increased by distending the colon. This input was interrupted irreversibly by transsection of the mesenteric nerves. These results show that both the afferent and efferent pathways of a peripheral reflex arc are located in the mesenteric nerves and may mediate visceral reflexes between mechanoreceptors and sympathetic neurons in the colon.


Changes in gastrin levels, food intake, and duodenal mucosal growth during lactation.

Gastrointestinal epithelial cell proliferation is stimulated during lactation in the rat. Serum gastrin levels and food intake are also increased during lactation. We investigated the role of gastrin and food intake as possible mediators of duodenal mucosal growth during the first 15 days of lactation. As the lactation period progressed, significant increases in the following crypt properties were noted: 1) crypt length; 2) cells/crypt; 3) labeling index; and 4) dimensions of the proliferative zone. Maternal serum gastrin levels rose abruptly by the first day of birth and remained elevated throughout lactation. The increases in crypt cell proliferation significantly correlated with food intake but not with serum gastrin levels during lactation. Mucosal mass and villus-crypt dimensions were also significantly increased above virgin levels in lactating antrectomized rats. These results suggest that the increase in duodenal growth during lactation most probably is not mediated by postpartum hypergastrinemia and that the increase in cell proliferation may be a direct response to an enhancement in food intake.


Renal tubular reabsorption in spontaneously hypertensive rats.

We characterized renal tubular reabsorption before and during acute expansion in anesthetized 12-wk-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Although mean arterial pressure was higher in euvolemic, nondiuretic SHR than in WKY, 158 vs. 114 mmHg, kidney and nephron glomerular filtration rate (GFR) as well as fluid reabsorption by the proximal convoluted tubule, loop of Henle, and distal convoluted tubule-collecting duct were similar. In euvolemic SHR with aortic constriction (SHR-AC), an acute decrease in renal perfusion pressure to 114 mmHg reduced sodium and water excretion. Kidney and nephron GFR and fluid reabsorption by segments along the nephron resembled values for SHR and WKY. Infusion of isotonic saline (3 ml.100 g body wt-1.h-1) produced similar increases in fractional sodium and water excretion by SHR and WKY, whereas SHR-AC exhibited a blunted natriuresis and diuresis. During expansion, fluid reabsorption by the nephron segments did not differ appreciably among the three groups. The effect(s) of perfusion pressure on reabsorption by superficial nephrons may be covert and was not unmasked, or may be manifested preferentially by deeper nephrons. We conclude that kidneys of SHR require a higher arterial pressure than kidneys of WKY to excrete a given amount of salt and water.


Phosphate transport along the inner medullary collecting duct of the rat.

The question of phosphate transport along the collecting duct remains controversial inasmuch as no data from direct in vivo evaluation of this nephron segment have been reported. We measured net phosphate transport along the inner medullary collecting duct (IMCD) using the collecting duct microcatheterization technique in five groups of rats. In control rats no net phosphate transport was found and 9.4% of the fraction of filtered phosphate (FFP) entered the IMCD and was excreted. After acute thyroparathyroidectomy (TPTX) there was a striking reduction in the FFP entering the IMCD, 1.8%, and significant reabsorption occurred, 0.5% being excreted. With acute TPTX and parathormone infusion, delivery increased to 33% without significant change along the IMCD. With acute TPTX and phosphate infusion, delivery was increased to control levels but no change was found in net phosphate transport. In rats studied 5-7 days after uninephrectomy alone, phosphate delivery was greater than in control, 25%, and no net phosphate transport was found. These studies demonstrate that phosphate absorption occurs along the IMCD in acutely TPTX rats when the delivery of phosphate to the IMCD is markedly reduced. The increase in phosphaturia which occurs after a reduction in renal mass cannot be accounted for by changes in net phosphate transport along the IMCD.


Feedback mediation of SNGFR autoregulation in hydropenic and DOCA- and salt-loaded rats.

Tubuloglomerular feedback (TGF) mediation of autoregulation was investigated by measuring the response of single nephron glomerular filtration rate (SNGFR) to changes in arterial pressure (AP) following acute or chronic TGF inhibition. In hydropenic rats with intact TGF, distal SNGFR was 25.0 +/- 1.2 (SE) and 23.9 +/- 1.4 nl/min at AP of 111 and 135 mmHg, respectively. In the same 20 nephrons during proximal tubular microinfusion of furosemide, distal SNGFR was 23.6 +/- 1.4 (n = 16) and 29.7 +/- 1.4 nl/min (n = 20) (P less than 0.001, n = 16) at 112 and 133 mmHg. When determined proximally, SNGFR was 25.6 +/- 1.0 and 29.5 +/- 0.9 nl/min (P less than 0.001, n = 31) at 112 and 157 mmHg; kidney GFR increased similarly. These data and the predictions of a GFR model were then used to estimate autoregulatory efficiency. This analysis indicated that partial autoregulation occurred during TGF inhibition. Therefore, TGF is an essential, but probably not the only, mechanism mediating SNGFR autoregulation.


Effect of fluoroacetate on the inhibitory action of ketone bodies and fatty acids on renal ammoniagenesis.

Renal cortical slices from acidotic dogs (NH4CL) were incubated at pH 7.0 with L-glutamine (1 and 5 mM) or L-glutamate (5 mM) with or without DL-beta-hydroxyburyrate 1 mM, acetoacetate 0.5 mM, as well as oleate, palmitate, octanoate, and crotonate 0.5 mM and in the presence or absence of fluoroacetate 0.05 mM. Fluoroacetate alone increased glutamine or glutamate uptake and ammoniagenesis whereas gluconeogenesis rose only when glutamine 5 mM or glutamate were used. Alanine production also rose by 30% when glutamine but not glutamate was used as substrate in the presence of fluoroacetate. Efficient blocking of the Krebs cycle at the aconitase level by fluoroacetate was evidenced by the release of citrate in the incubation medium and by a slight but significant decrease in oxygen consumption (10-20%). The marked decrease in glutamine uptake, ammoniagenesis, and gluconeogenesis induced by ketone bodies and fatty acids was completely corrected by addition of fluoroacetate. The present studies demonstrate that ketone bodies and fatty acids inhibit renal ammoniagenesis and gluconeogenesis in vitro through their oxidation in the mitochondria. They also suggest that direct transamination of glutamine into alanine (glutaminase II pathway) may be significant when oxidation of pyruvate is inhibited by fluoroacetate.


Adenosine content of skeletal muscle during active hyperemia and ischemic contraction.

If newly formed adenosine is the mediator of active hyperemia in skeletal muscle, tissue adenosine must increase and remain elevated during sustained muscle contraction. We tested this prediction using isolated canine anterior calf muscles. Muscle samples were obtained before and during contraction by punch biopsy and adenosine was measured by spectrophotometric enzyme assay. Tissue adenosine content didnot increase significantly above the precontraction level during either the 2- or 6-Hz contraction. We estimated (by infusing adenosine) that the adenosine concentration required to cause a dilation equal to that observed during 6-Hz contractions was 3.7 X 10(-5) M. We would have detected an increase in tissue adenosine if this concentration were established in as little as 10% of the skeletal muscle interstitium during free flow. These results indicate that adenosine released into the whole interstitial space is not the cause of free-flow exercise hyperemia.


Catecholamines and cardiac rhythms in the unanesthetized dog with chronic AV block.

The effects of epinephrine, norepinephrine, and isoproterenol were studied in the nonanesthetized dog with chronic atrioventricular block before and after blockade of cholinergic receptors. Epinephrine and norepinephrine reduced the atrial rate in a reflex manner, whereas isoproterenol increased it. In contrast, all three substances increased idioventricular rate. After atropine, atrial and ventricular rate increases were observed after administration of the three catecholamines. Moreover, blockade of cholinergic receptors led to an increase in ventricular acceleration induced by epinephrine and norepinephrine, but did not significantly modify the acceleration induced by isoproterenol. These results appear to indicate the possibility of the involvement (intensified by a reflex mechanism) of ventricular cholinergic innervation.


Determinations of blood flow and shunting of 9- and 15-micrometer spheres in regional beds.

In 17 pentobarbitalized dogs, the shunting of 15-micrometer and 9-micrometer microspheres was studied in the brain, myocardium, kidney, intestine, and lung. The veins of these organs were catheterized for constant blood withdrawal for 2 min by direct venipuncture. The ratio of microsphere radioactivity in the venous blood to that in the arterial blood gave the shunting of microspheres by the venous sampling technique. The 15-micrometer microspheres showed 2% or less shunting for all organs studied, whereas the 9-micrometer microspheres had shunting ranging from 3% in the coronary sinus to 24% in the portal vein. The shunting of 9-micrometer microspheres was also calculated from direct tissue counting, where the 15-micrometer spheres were considered to be completely entrapped. The results of direct tissue counting indicate that the 2-min venous sampling underestimates microsphere shunting. CO2 administration increased significantly the shunting of 9-micrometer spheres, whereas the shunting of 15-micrometer spheres determined by venous sampling remained less than 2%. Consideration of shunting indicates that the 15-micrometer microspheres might be more appropriate for regional organ blood flow measurements, including the myocardium.


Depressed responsiveness of the carotid sinus reflex in conscious newborn animals.

The responsiveness of the carotid sinus reflex was evaluated by comparing the effects of bilateral carotid occlusion (BCO) in conscious adult dogs and puppies on measurements of arterial pressure, cardiac output, heart rate, and calculations of total peripheral resistance (TPR). In eight adult dogs, BCO increased mean arterial pressure by 57 +/- 6%, TPR by 48 +/- 5%, and heart rate by 45 +/- 15%. In puppies, BCO induced smaller increases (P less than 0.05) in mean arterial pressure (30 +/- 5%) and TPR (29 +/- 4%), while heart rate did not change. After elimination of opposing vagal and aortic baroreceptor reflexes, the differences in responses to BCO of mean arterial pressure and TPR between adults and newborns were even greater. Thus, the carotid baroreceptor reflex appears to be depressed in the newborn when compared with the fully developed reflex in the normal, conscious adult.


External assessment of myocardial metabolism with [11C]palmitate in rabbit hearts.

To determine whether the rate of fatty acid utilization, reflecting myocardial oxygen consumption under steady-state conditions, can be assessed noninvasively, we assayed positron emission from [11C]palmitate (100 muCi) in isolated rabbit hearts and after intra-atrial injection in vivo. In 11 isolated hearts, clearance of 11C-radioactivity during a monoexponential portion of residue detection curves correlated with tension-time index (TTI)(r = 0.86) and peak dP/dt (r = 0.89). Among 9 hearts prelabeled with [14C]palmitate, 14CO2 production from neutral lipid stores correlated with TTI (r = 0.83). In vivo the decline of 11C-radioactivity was 1st order and constant when physiological conditions were maintained constant (slope of the semilog plot = 0.099 +/- 0.002 (SE) in counts/min) (n = 2 animals, 7 injections). Decline of activity changed predictably when oxygen requirements were increased by administration of methoxamine. Thus, residue detection of [11C]palmitate 1) permits external assessment of global myocardial metabolism in vitro, and 2) reflects effects of interventions that alter the rate of substrate utilization in vivo, and should, therefore, permit comparison of rates of regional myocardial metabolism in patients with detection of radioactivity by positron-emission transaxial tomography.


Microvascular myogenic reaction in the wing of the intact unanesthetized bat.

Microvascular dimension and flow responses to stepwise changes in arterial and venous pressures, ranging from zero to +100 mmHg and zero to -75 mmHg have been recorded. Observations were made in arterioles, terminal arterioles, and precapillary sphincters in the wing web of intact, unanesthetized bats. The results show for all categories of vessels that with reduced transmural pressures there is a progressive increase in mean diameter and a decrease in rhythmic vasomotion rate. Flow changes are variable. For elevated transmural pressures there is a vasoconstriction with drastic flow reduction that is inconsistent with metabolic control. However, after prolonged elevation of pressure there is a progressive increase in flow, suggesting a "metabolic escape". Computed wall tension remains reasonably constant for a wide range of transmural pressures, suggesting that wall tension may be the controlled variable. These findings support the hypothesis of a myogenic reaction as a mechanism for maintenance of basal vascular tone in the intact unanesthetized bat.


Myocardial performance in the newborn lamb.

We compared myocardial performance in newborn lambs over the first 3 wk of life with that of ewes. Heart rate was higher in newborn lambs than in ewes. The ratio of left ventricular preejection period to left ventricular ejection time was similar for newborns (0.31 +/- 0.02) and ewes (0.31 +/- 0.01). Cardiac output in ml/min per kg body weight in the newborn was 397 +/- 55 at 1 wk, 314 +/- 30 at 2 wk, and 274 +/- 10 at 3 wk, compared to 125 +/- 8 in ewes. Stroke work was comparable in both age groups. Left ventricular dP/dtmax averaged 3,723 mmHg/s in lambs compared to a mean value of 2,257 in ewes. These studies establish that the myocardium of newborn sheep contracts vigorously in vivo and equals or exceeds the level of performance of the myocardium of adult sheep, as estimated by a variety of indices of myocardial function.


Postnatal regulation of oxygen delivery: hematologic parameters of postnatal dogs.

Hematologic parameters influencing tissue oxygen delivery in dogs during the first 4 mo of life have been investigated. The rapid growth and increase in body temperature during this period imply an increased metabolic rate and increased tissue oxygen demand. Hemoglobin concentration and hematocrit decrease during the 1st mo following birth. The total red cell mass does not decrease during this period. The observed hemodilution can be attributed to an increasing plasma volume in the growing animal. The blood oxygen affinity decreases during this same period, resulting in a more effective tissue oxygen delivery. Erythropoiesis, as estimated from the percent circulating reticulocytes, decreases following birth and does not increase until 1 mo of postnatal life. The increase of erythropoietic activity during the 2nd mo of postnatal life coincides with an increase in red cell mass, hematocrit, and hemoglobin concentration.


Postnatal changes in response of canine neonatal pulmonary arteries to histamine.

Postnatal development of histamine receptors in the canine pulmonary circulation was examined utilizing histamine cumulative dose-response curves of pulmonary arteries isolated from neonatal and adult dogs. The maximal contractile response to histamine was relatively low at birth (avg 0.069 g) and increased with postnatal age, reaching a maximum in the adult (avg 1.10 g). H2-receptor blockade with metiamide increased the contractile response to histamine during the first 2 wk of life (avg 0.38 g), suggesting H2-receptor dominance over H1-receptors in the newborn. Maximal developed tension, in response to KCl, gradually increased with postnatal age, suggesting progressive maturation of the smooth muscle response. In contrast to pulmonary arteries, isolated tracheal segments from puppies aged 1-5 days demonstrated large contractile responses (avg 5 g). Histamine (in microgram/g of wet wt of lung tissue) was absent in the lungs from 3rd trimester fetal dogs and rapidly increased over the first 2 wk of life, reaching a maximum in the adult. It is concluded that 1) the response of pulmonary arteries to histamine changes during the first 2 wk of life; 2) this change may reflect a decrease in H2-receptors and an increase in H1-receptors; 3) the contractile ability of pulmonary vascular smooth muscle increases with postnatal age; and 4) histamine is unavailable for physiological responses in the fetal dog pulmonary circulation.


Species differences in cardiac energetics.

The energy flux of rat, guinea pig, and cat papillary muscles was measured myothermically under resting, isometric, and isotonic conditions at 27 degrees C. Resting heat rate was highest in the smallest species and declined with body size. The slope of the isometric heat-stress relationship was constant across species, whereas the stress-independent heat component was least for rat muscles. The shape of the load enthalpy relationship was similar across species. Maximum mechanical efficiency, work-enthalpy, occurred with lighter loads than for skeletal muscle (approximately 0.2 Po). Rat muscle had the smallest enthalpy per beat and the highest active mechanical efficiency, but this advantage was nullified by the higher basal heat rate. The myothermic data are compared with cardiac oxygen consumption values in the literature and it is concluded, contrary to the deductions of common dimensional arguments, that cardiac energy expenditure across species is not directly proportional to heart rate. Reasons for this discrepancy are considered together with the likely contribution of cardiac metabolism (EH) to total body metabolism (EB). It seems likely that smaller species have lower EH/EB.


Resistance and volume changes caused by nitroprusside in the dog.

Changes in vascular volume caused by a pharmacologic agent are frequently inferred rather than directly measured. We investigated the effects of nitroprusside in 8 dogs divided into 2 groups: control and splenectomized. We anesthetized the dogs using pentobarbital, and surgically prepared a veno-right atrial bypass preparation whose controlled cardiac output and external reservoir allowed measurement of both changes in vascular resistance and changes in vascular volume. In both groups, blood pressure (mean +/- SD) decreased at each successive level of nitroprusside: 114 +/- 24 mmHg (base line), 101 +/- 19 mmHg (45 microgram/min), 90 +/- 16 mmHg (90 microgram/min), 81 +/- 17 mmHg (180 microgram/min), 68 +/- 18 mmHg (360 microgram/min). Nitroprusside caused a large and similar decrease in vascular resistance in both groups. In the control group, vascular volume increased above base line 5.5 +/- 2.7, 8.3 +/- 3.2, 11.6 +/- 2.9, and 14.7 +/- 3.5 ml/kg at each successive level of nitroprusside infusion, whereas in the splenectomized group vascular volume increased above base line 0.9 +/- 0.3, 2.5 +/- 1.0, 3.3 +/- 1.1, and 4.0 +/- 1.3 ml/kg at each successive level of nitroprusside infusion, but increased significantly less than the control group. We concluded that nitroprusside decreases vascular resistance and increases vascular volume and that the spleen is the major site of changes in vascular volume caused by nitroprusside.


Laryngeal reflex apnea in the chemodenervated newborn piglet.

Effects of peripheral arterial chemodernervation on laryngeal reflex-induced apnea were studied in 18 piglets of either sex varying in age from 4 to 63 days. The distal trachea was cannulated with a cuffed endotracheal tube to secure a free airway and permit ventilatory measurements with a pneumotachograph. The proximal trachea was used to introduce fluids into the larynx. Water elicited apnea, bradycardia, and arterial hypertension, whereas saline caused only transient disturbances. Electrical stimulation of the superior laryngeal nerves reproduced, and conduction anesthesia ablated, the effects of water in the larynx. Carotid body contribution to respiratory drive was assessed by the ventilatory responses to increased (100%) and decreased (10%) anbient oxygen concentration. These indicated significant peripheral chemoreceptor ventilatory activity from birth with little further change in the neonatal period. Ventilatory responses to oxygen were ablated by carotid chemodenervation, but there was no change in the duration of laryngeal reflex apnea. We conclude that attenuation of laryngeal-induced apnea during postnatal development is independent of peripheral chemoreceptor activity. Our findings may have relevance to the clinical problem of sudden infant death syndrome, in which carotid body abnormalities have recently been described.


Abolition of hypoxic vagal bradycardia by lateral mesencephalic lesions in spinal cats.

To examine central sites that integrate the vagal bradycardia induced by hypoxia, heart rates were recorded continuously in spinal, precollicular, decerebrated cats during transient hypoxia induced by ventilation with 100% nitrogen. Bilateral lesions in the lateral mesencephalic reticular formation either decreased the extent of bradycardia or caused a reversal to tachycardia; anesthesia induced the same change. In contrast, bilateral lesions in the medial mesencephalic reticular formation failed to alter the bradycardia. Hence, the lateral mesencephalic reticular formation is essential for the appearance of hypoxia-induced vagal bradycardia.


Aortic wavelength as a determinant of the relation between heart rate and body size in mammals.

Measurements of aortic input impedance in the rat, dog, and man suggest a new hypothesis to explain the inverse correlation between rate and body size: that pulse wavelength and arterial length are matched in a way that minimizes cardiac work. The optimal rate is fast enough to avoid the high impedances produced by reflections at relatively low frequencies, yet slow enough to permit orderly excitation and recovery of the myocardium.


Renin and aldosterone secretions during hypovolemia in rats: relation to NaCl intake.

Plasma renin activities (PRA) and aldosterone concentrations increased in parallel over a wide range of plasma volume deficits produced in unanesthetized rats by extravascular administration of polyethylene glycol (PEG) solution. When PEG-treated rats were given water to drink, their intakes were proportional to PRA; when given water and 0.5 M NaCl, PRA and the steroid concentrations diminished concurrently in association with sodium consumption. Aldosterone concentrations and NaCl intakes were markedly enhanced after PEG treatment in rats maintained on a sodium-deficient diet for 4 days. On the other hand, a clear relation between PRA and water intake, and between circulating aldosterone levels and sodium intake, was not suggested by other experiments in this series. For example, bilateral nephrectomy abolished the rise in PRA during hypovolemia yet rats drank water normally. Moreover, aldosterone concentrations were substantially elevated by PEG treatment in the nephrectomized rats yet sodium appetite was abolished. These and other findings suggest that neither angiotensin nor aldosterone plays a prominent role in stimulating water and saline intakes during hypovolemia.


O2 delivery to the pregnant uterus: its relationship to O2 consumption.

Normal sheep were studied at intervals of 3-5 days during the last weeks of pregnancy in order to evaluate variability in rate of O2 consumption (QO2) of the uterus in relation to several variables involved in delivery of O2 to the organ. Among-animal differences of uterine QO2 were statistically significant and directly related to birthweight of the lamb. Among-animal differences of uterine blood flow (UBF) and uterine arteriovenous O2 content difference [C(a-v)O2] also were statistically significant, though neither was related to birthweight, presumably since they tended to vary inversely with one another. In a given ewe relative magnitude of UBF and of C(a-v)O2 was related to maternal arterial O2 content (CaO2), day of pregnancy, and whether the animal carried singlets or twins. Variability in QO2 was most closely related to UBF, although its relations to C(a-v)O2 and CaO2 were significant also. These data suggest there are systematic relationships among variables involved in the delivery of O2 to the uterus of pregnant sheep.


Independence of brain and body temperatures in flying American kestrels, Falco sparverius.

Brain and body temperatures were measured via small thermocouples implanted in the anterior hypothalami and colons, respectively, of five adult American kestrels (F. sparverius, mean mass 119 g) during descending flights in a wind tunnel at angles of 4 and 6 degrees below horizontal, at 10 m.s-1 air speed, and at 23 degrees C air temperature. For comparison, temperatures were recorded from resting birds at 22.5-36.1 degrees C air temperatures. Colonic (Tc) and hypothalamic (Th) temperatures both increased after the onset of flight; steady-state levels were attained after 1 min in the hypothalamus and after 5 or more min in the colon. The steady-state difference (delta T = Tc - Th) averaged 1.2 degrees C, higher by 0.5 degrees C than delta T in resting kestrels. The establishment of delta T during flight may be correlated with increased respiratory and corneal evaporation. The response apparently confines most stored body heat to noncranial regions, thus protecting brain tissue from thermal extremes.


Effects of carotid occlusion and left atrial stretch on supraoptic neurosecretory cells.

Acute experiments were performed on pentobarbital-anesthetized cats to determine whether atrial and carotid baroreceptors affected the same neurosecretory neurons in the supraoptic nucleus (SON) of the hypothalamus. The osmosensitivity of these neurons was also determined. Eighty-two SON neurons were antidromically identified and 63 of these increased their firing rates during complete occlusion of the right carotid artery. Further testing of these 63 neurons demonstrated that 56 were inhibited by directly stretching the left atrium and 61 were excited by intracarotid injection of hypertonic saline. Left atrial stretch greatly reduced the neuronal response to carotid occlusion. These results show that the activity of the majority of the antidromically identified SON neurons is altered by left atrial and carotid artery receptors as well as changes in plasma osmolality. Results are consistent with the known influence of these receptors on plasma vasopressin.


Body weight and body composition of male rats following hypothalamic lesions.

Carcass analyses were performed on 160 male rats maintaining reduced, normal, or elevated levels of body weight following lateral hypothalamic (LH), sham (control), or ventromedial hypothalamic (VMH) lesions, respectively. Extracted body lipid (ranging from 26 to 738% of the control mean) correlated highly (r = +0.95) with the level of maintained body weight (which ranged from 67 to 191% of control). Neither the nonfat solids (which ranged from 60 to 123% of control) contributed significantly to the variance in body weight (r = +0.01 and +0.06, respectively). Fat thus accounted for approximately 90% of the overall variance in body weight among LH, control, and VMH animals. Consideration of only the LH data, however, revealed a breakdown of this close covariance of body fat and weight. Fat mass correlated significantly with body weight in LH rats maintaining weight 0-12% below normal; but, at maintained body weights below 88%, the correlation between weight and fat in LH rats was only +0.07. Variation in lean body mass then better accounted for differences in body weight. The implications of these observations for existing lipostatic theories of weight regulation are discussed.


Influence of dietary magnesium in experimental phosphate depletion: bone and soft tissue mineral changes.

We studied weanling rats fed 0.06% (group 1) and 0.10% (group II) magnesium (Mg) during phosphate depletion (PD) in order to evaluate the role of Mg in the bone, soft tissue, and serum changes of PD. The following results were obtained: 1) serum Mg remained stable in the face of a negative Mg balance; 2) the hypercalcemic and hypercalciuric response to PD was the same in both groups; 3) bone Mg content was decreased with PD in both groups and was associated with a significant decrease in bone calcium and phosphorus. We conclude that: 1) the hypomagnesemia of PD is dependent mainly on the dietary intake of Mg; 2) the hypercalcemia and hypercalciuria of PD are not caused by primary changes in Mg homeostasis; 3) low-dietary Mg during PD may cause a defect in soft tissue utilization of P in the growing rat.