Computer monitoring of fetal heart rate and uterine pressure. With the introduction of continuous recording cardiotocographs in the labor room the large quantity of numerical data produced suggested the computer would be of use. In this preliminary study two computers were used: one initially to collect data and later to give comment and advice as the data was collected and the other for in-depth anaylsis of the previously collected data. On the basis of this new information a new way of analyzing and categorizing labor is suggested and some of the clinical impact so far achieved is described.


The placental pathology of small-for-gestational age infants. There is a lack of placental studies of newborn infants who are small for gestational age (SGA). In a gross and light micorscopy evaluation of 63 referred placentas associated with singleton SGA infants, abnormalities were found in 58. In many instances these were considered of causal significance. Abnormalities included ischemic lesions (43 per cent), often related to a history of pre-eclampsia. In this group of specimens, severe X-cell proliferation was present, possibly related to a mechanism of delay of the onset of lavor. Approximately 25 per cent of the placentas showed villitis of unknown etiology. This is presumed to be of infectious etiology, probably viral. Sixteen per cent of the infants died.


Possible role of the fetal adrenal glands in the etiology of postmaturity. Plasma cortisol levels were studied in the cord blood and neonatal blood of the following vaginally delivered groups: (A) postmature; (B) postterm (but not postmature); and (C) term neonates. Significantly lower levels of 8 A.M. neonatal plama cortisol were found in postmature neonates when compared with term neonates (P LESS THAN 0.02) or merely postterm neonates (P LESS THAN 0.02). No difference was found in the cord blood cortisol levels in all three groups. Contrary to the traditional belief that postmaturity results from placental aging, our findings appear to indicate that postmaturity represents a specific fetal disorder. Fetal adrenal insufficiency may be a characteristic of this disorder. Prolonged pregnancy in these cases may be reflected inability of the affected fetus to initiate labor.


Correlation between urinary testosterone or estrogen excretion levels and interstitial cell-stimulating hormone concentrations in normal postmenopausal women. The purpose of the present study was to find out whether there is a correlation between the urinary levels of testosterone or of estrogens (estrone and estradiol) and ICSH urinary concentration in normal postmenopausal women. Examination of 35 normal subjects at different postmenopausal ages (from one year to over 10 years after menopause) showed a highly significant inverse correlation between ICSH and testosterone urinary excretion levels (coefficient of correlation "r" equals minus 0.548), but none between the urinary estrogen excretion levels and ICSH urinary concentrations.


Inhibition of cyclic gonadotropin secretion by endogenous human prolactin. The resumption of cyclic uterine bleeding reportedly accompanies the use of human prolactin (HPRL)-suppressing agents in postpill galactorrhea-amenorrhea. In this laboratory, HPRL suppression with L-dopa was variable and short lived. Basal plasma HPRL levels were elevated before and after as much as five months of therapy. Galactorrhea persisted and mean gonadotropin concentrations were subnormal. An immediate and sustained attenuation of HPRL secretion ( less than 200 per cent) followed the use of 2-Br-alpha-ergocryptine (CB-154). Cyclic gonadotropin secretion resumed and was accompanied by ovulation and, in one instance, pregnancy. The cessation of galactorrhea was positively correlated with the rise in the daily concentration of 17 beta-estradiol. Cyclic postovulatory menstruation continued after the cessation of CB-154 treatment. HPRL levels remained normal. The daily patterns of human follicle-stimulating hormone (HFSH) and human tuteinizing hormone (HLH) secretion created by the suppression of HPRL displayed an inherent rhythmicity identical to that observed at the time of menarche. The inhibitory effects of HPRL appeared directed at cyclic rather than tonic gonadotropin secretion. At the same time, diminished ovarian estrogen production seemed to increase mammary gland sensitivity to HPRL, leading to lactation. One may postulate, therefore, that the ingestion of sex steroids is associated with an over-all suppression of endogenous cyclic and, to a lesser extent, tonic gonadotropin secretion secondary to which ovarian function is attenuated. Without physiologic concentration of circulating estrogen, HPRL induces mammary alveolar function with the production of a milklike secretion.


Significance of timing for the postcoital evaluation of cervical mucus. This investigation was designed to determine the role of cervical mucus in the dynamic in vivo distirbution of transported spermatozia in the human reproductive tract. Forty-two normal subjects had midcycle cervical mucus collection at various times after insemination. Sperm were identified in the cervical mucus at the level of the internal as shortly after insemination. The numbers of sperm in cervical mucus were directly related to the numbers of sperm in the inseminate and were related to time from insemenation. In order to obtain optimal information, the postcoital examination for the presence of sperm should be performed within two and one-half hours after semen exposure. It was also determined that cervical mucus does serve as a reservoir for those sperm which are transported to the Fallopian tubes.


Prophylactic internal iliac artery ligation at cesarean hysterectomy. One hundred and eight preplanned cesarean hysterectomies have been evaluated in an effort to determine that advisability of prophylactic bilateral hypogastric artery ligation when there is anticipated heavy bleeding  associated with surgery. The data indicates that prophylactic bilateral internal iliac artery ligation is of questionable value in reducing operative bleeding, which can be controlled by more conventional means. However, when used therapeutically, it may be a lifesaving operation. Familiarity with the procedure is necessary for all those performing operative obstetrics and gynecology.


Hormone-releasing silicone-rubber intrauterine contraceptive devices. Effect of incorporation of various compounds on intrauterine contraceptive devices in rats. Intrauterine devices (IUD's) containing 0, 5, or 10 per cent by weight of progesterone, melengestrol acetate (MGA), norethindrone, norgestrel, medroxyprogesterone acetate, isoxsuprine, or R2323 or wound with fine copper wire were placed in one or both horns of cycling female rats. All the progestins improved retention of the silicone-rubber IUD's to some degree. The effects of these compounds on the estrous cycle, mating, ovulation, fertilization, tubal transport, and implantation varied among the compounds. Effects were local or systemic, depending upon the amount and the drug. Uterine motility studies showed clearly that 5 per cent MGA decreased uterine motility; however, no consistent results could be obtained using the other compounds in the same in vivo system.


Complications of pregnancy with an intrauterine contraceptive device in situ. Thirty-one consecutive pregnant women with intrauterine contraceptive devices in situ were studied. The devices consisted of the coil, loop, or bow. The pregnancies showed a high incidence of abortion, ectopic pregnancy, premature labor, premature rupture of the membranes, sepsis, and hemorrhage. Associated with these maternal complications was a high incidnece of fetal wastage. A recommendation is made for early interruption of the pregnancy.


Congenital absence of the uterine cervix. Surgical correction of congenital atresia of the uterine cervix by creation of a fistulous communication between the functioning endometrial cavity and the vagina with the use of the atretic cervix as a conduit has been performed in two patients. This technique, which permits egress of menstrual blood and the retention of the capacity to reproduce, should replace hysterectomy as the treatment of choice for this extremely unusual and formerly hopeless Müllerian duct anomaly.


Effect of thirty-two per cent dextran 70 on peritoneal adhesion formation. Twenty-one female rabbits underwent laparotomy and a standardized injury was produced on the right uterine horn and Fallopian tube. Following the injury eight animals were used as controls and thirteen were injected intrapertoneally with 50 ml. of 32 per cent dextran 70. Six weeks later the animals were killed and the adhesions graded. All control animals had dense adhersions of the injured areas to bowel or peritoneum. The dextran animals showed marked reduction in the extent and degree of adhesions. Possible mechanisms for these findings are discussed and the problems raised, by adhesion formation, to the gynecologist are reviewed.


Endometriosis of the appendix. Report of twelve cases and review of the literature. Twelve cases of endometriosis of the vermiform appendix are discribed and reviewed. The incidence of 0.80 per cent is higher than has been previously reported. None of the patients displayed symptoms of acute appendicitis, however, five (42 per cent) patients had symptoms suggestive of chronic or cyclic appendicitis. Laboratory tests were nondiagnostic of this lesion. There did not appear to be a correlation between the histologic location of the endometriosis and the symptoms of chronic or cyclic appendicitis. All cases of endometriosis of the appendix were discovered as a result of incidental appendectomy.


The efficacy of intramuscular 15 methyl prostaglandin E2 in second-trimester abortion. Coagulation and hormonal aspects. Termination of pregnancy in the second trimester is sometimes associated with serious complications. This led to clinical investigation seeking methods superior to the traditional technique utilizing hypertonic saline. Intra-amniotic administration of naturally occurring prostaglandin F2-alpha has been developed and appears to be advantageous--especially in the area of coagulation stability. This study describes a technique for intramuscular administration of a prostaglandin analogue--15 methyl prostaglandin E2. This analogue is much more potent than the natural compound. Administration to 32 patients resulted in abortion in 28. The coagulation milieu remained completely intact and all other parameters were similar to previous published data for prostaglandin administration. There were no infections in this group of patients.


The relaxing effect of terbutaline on the human uterus during term labor. The uterine and cardiovascular responses to the adrenergic beta2-receptor stimulator terbutaline (TRB) were investigated in 14 patients in normal term labor. TRB, administered intravenously at a rate of 10 to 20 mug per minute, effectively inhibited uterine activity in advanced labor and also expulsion. Intravenous injection of TRB, 250 mug, diminished oxytocin-induced uterine hyperactivity. No serious side effects of the drug were observed; the circulatory effects were minimal, except for a tolerable maternal tachycardia. The mode of action and clinical application of TRB for inhibition of unwanted uterine activity are discussed.


Methadone assays in pregnant women and progeny. Data on the concentration of methadone in maternal plasma and urine of pregnant women on methadone in relationship to levels of amniotic fluid, cord blood, fetal urines, and breast milk are presented. These findings do not demonstrate a simple relationship between methadone levels in the neonate and the intensity of the withdrawal syndrome. The effects of multiple drug abuse and other as yet unknown factors may influence the severity of withdrawal signs in the neonate.


Immunoreactive calcitonin in the mother, neonate, child and adult. Immunoreactive calcitonin (iCT) was measured in umbilical arterial and venous blood and in maternal peripheral blood in 32 normal deliveries. The results were compared with values found in nonpregnant adult females. The umbilical arterial blood contained significantly higher concentrations of iCT than umbilical venous blood (p less than 0.001). The serum iCT in maternal peripheral blood was significantly higher than in normal nonpregnant subjects (p less than 0.001). Serum iCT was also measured in 342 male and female subjects ranging in age from 1 hour to 60 years. Serum iCT was found to be high early in life and to diminish with age. Our data suggest that calcitonin may be of physiologic significance in bone formation during intrauterine life and childhood. High serum iCT may also be responsible for the hypocalcemia seen in the neonatal period.


Hypnotic susceptibility and the Lamaze childbirth experience. This study explored the relationship between childbirth training and hypnotic susceptibility. A multiple linear regression analysis was performed on the various medical and attitudinal variables related to the subjects' Lamaze childbirth experience and these were tested against hypnotic susceptibility. The results of the analysis indicate that hypnotic susceptibility is not significantly related to Lamaze training, nor is it significantly related to the type of childbirth experience that a Lamaze-trained woman has.


Pulmonary insufficiency associated with pregnancy. Six obstetric patients with severe pulmonary insufficiency are presented. The volume respirator and quality intensive care remain the basis of treatment. Experience with extracorporeal oxygenation is discussed. The patients demonstrated the typical progression seen in lung disease. An acute, severe insult is followed by hypoxia and pulmonary insufficiency with ensuing pulmonary fibrosis. Serious infection, coagulopathies, and mechanical problems of ventilation add to the difficulty of treatment and the high mortality rate in what may be referred to as an adult respiratory distress syndrome. It is important for the clinician to take an aggressive approach in the management of severe respiratory insufficiency.


Hemolytic disease of the neonate secondary to anti-Fya. A case of hemolytic disease secondary to anti-Fya in a neonate requiring exchange transfusion is presented. A review of the literature reveals 18 previous cases, with 32 per cent requiring exchange transfusion and a 16 per Fya-b- or Fya-b+ blood can be obtained for exchange transfusion if indicated.


Amniotic fluid phospholipids and fatty acids in normal pregnancies. Relation to gestational age and neonatal condition. The plamitic acid/stearic acid ratio (P/S) follows such a rise during weeks 35 and 36 that it can be considered as a valuable index of gestational age.


Enzymes of normal and malignant trophoblast: phosphoglucose isomerase, phosphoglucomutase, hexokinase, lactate dehydrogenase, and alkaline phosphatase. In this study we compare the specific activities and isoenzyme patterns of five enzymes--phosphoglucose isomerase, phosphoglucomutase, hexokinase, lactate dehydrogenase, and alkaline phosphatase--in term placenta with the analogous enzymes in a clone of choriocarcinoma cells grown in culture. Phosphoglucose isomerase, phosphoglucomutase, and lactate dehydrogenase specific activities of the choriocarcinoma did not differ by more than two or three times from the mean activities of the comparable enzymes in placenta; the specific activity of hexokinase in the choriocarcinoma amounted to 14 per cent of the mean value for placenta. In contrast, the mean specific activity of heat-stable alkaline phosphatase in the choriocarcinoma amounted to only 1 per cent of the mean value for placenta. By growing the cells in 5-bromodeoxyuridine, 20 mug per milliliter, we were able to increase alkaline phosphatase activity to 68 per cent of the mean value for placenta. For both extracts, phosphoglucose isomerase zymograms were similar and phosphoglucomutase zymograms were similar. The hexokinase zymogram of term placenta showed two isoenzymes which stained more intensely with 0.5 mM. glucose than with 0.1M glucose. A hexokinase isoenzyme was observed in zymograms of both extracts which stained more intensely with 0.1M glucose than with 0.5 mM glucose. Lactate dehydrogenase exhibited an extra isoenzyme in the choriocarcinoma extract. When the cells were cultivated in medium containing 5 mug per milliliter of 5-bromodeoxyuridine, the induced phosphatase in the cell line was electrophoretically similar to placental phosphatase. At higher concentrations of 5-bromodeoxyuridine, the most anodal isoenzyme was 0.5 cm. slower in mobility than the comparable placental isoenzyme.


Log normal distribution of gonadotropins and ovarian steroid values in the normal menstrual cycle. In the statistical analysis of the values of luteinizing hormone, follicle-stimulating hormone, estradiol, and progesterone obtained from normal menstrual cycles, a depature from normality was noted. Chi square, W test, and linear transformation were used to check the normality of the distributions. The results of this investigation showed that the distributions were not normal (Gaussian) but log-normal. By plotting the probit of the percentages of cumulative frequency on a log scale (probit-log), linearity of the data was obtained. This resulted in direct graphical estimations of values with a useful clinical range, which included the mean and the 95 per cent confidence interval.


Clinical categorization of patients with secondary amenorrhea using progesterone-induced uterine bleeding and measurement of serum gonadotropin levels. A group of ninety unselected women with secondary amenorrhea of at least six months' duration were studied retrospectively. By the use of intramuscular progesterone in oil, it was possible to categorize these patients according to their positive or negative uterine bleeding response. LH, FSH, and estradiol values in the 63 patients of the positive category had a log-normal distribution. LH values were found to be composed of two different populations; FSH and estradiol values were composed of only one population. Based on these LH determinations the entire positive category was then divided into two groups. Patients with high levels of LH (Group I) were clinically diagnosed to have polycystic ovarian disease. Patients with normal levels of LH (Group II) were diagnosed to have hypothalamic-pituitary dysfunction. The 27 patients who failed to have withdrawal uterine bleeding were placed in the negative category. These patients also were shown to have a log-normal distribution for LH, FSH, and estradiol. In contrast to the patients in the positive category, FSH values in these patients were made up of two different populations whereas LH and estradiol values showed only one population. Based on the FSH values these patients were divided into two groups, one with low and normal levels of FSH (Group III) and the second population with high levels of FSH designated as Group IV. Group III represented those patients with hypothalamic-pituitary failure and patients in Group IV were those with ovarian failure. Serial determinations of LH, FSH, and estradiol done prospectively on five consecutive days in 19 of the 90 patients did not give any further information in differentiating among the four groups.


Clinical study of a progesterone-releasing intrauterine contraceptive device. A double-blind clinical study was performed to determine whether the release of progesterone from an intrauterine contraceptive device (IUD) had any effect on IUD event rates. A total of 101 women received intrauterine contraceptive devices containing progesterone, resulting in the accumulation of 877 women-months experience; 100 women received IUD's without steroid, resulting in the accumulation of 780 women-months. The only significant difference was a higher incidence of pregnancy in those patients using devices which did not contain progesterone.


Teaching pelvic examination to second-year medical students using programmed patients. A great deal of interest has been expressed in the use of the "programmed" patient during the past several years. This pilot study used programmed patients to teach medical students the techniques of pelvic examination. From the study, it was concluded that the experience with the programmed patient adds significantly to an undergraduate learning program, that this technique is well accepted by students and faculty, and that it adds realism to the study of obstetrics and gynecology early in a medical school curriculum.


Investigations into the spontaneous contractile activity of isolated human uterine arteries in vitro. Uterine artery strips and myometrium from the same uterus were placed in the same water bath and their rates of contractile activity were registered simultaneously. Isolated strips of uterine arteries showed spontaneous contractile activity--a phenomenon especially marked in the secretory phase of the cycle. In the proliferative phase spontaneous contractions of blood vessels, characterized by low intensity and a frequency of three contractions in 10 minutes, were seen. In the secretory phase the contractions were of lesser intensity and higher frequency. The rhythm of contractions of the myometrial vessels was markedly different from the spontaneous activity of the myometrial strips. In discussion of the results, special attention has been paid to the role of spontaneous contractility of myometrial vessels in the contractile activity of the whole uterus.


Estrogen and the metabolism of progesterone in vivo. The effect of estrogen administration on the metabolism of progesterone was studied in ovariectomized, hysterectomized women. Estrogen was withheld from each subject for at least 4 weeks, then 200 mug of ethinyl estradiol were administered orally each day for 3 weeks and then no estrogen was given for 3 weeks. The subjects were studied before estrogen was started, on the third day of estrogen, after 3 weeks of daily estrogen and after the estrogen was withdrawn for 3 weeks. In 5 women plasma transcortin concentrations, measured by equilibrium dialysis, were 0.82 plus or minus 0.06, 1.5 plus or minus 0.16, 2.1 plus or minus 0.13, and 0.90 plus or minus 0.09 (S. E.) muM before starting estrogen (control), on the third day of estrogen treatment, after 3 weeks of estrogen, and after having stopped estrogen for 3 weeks, respectively. Corresponding values for the metabolic clearance rates (MCR) of cortisol (by the continuous infusion method) were 306 plus or minus 33, 172 plus or minus 18, 136 plus or minus 14, and 258 plus or minus 23 (S. E.) L. per day. Although estrogen administration caused a significant elevation of the plasma transcortin concentrations and a significant decrease in the MCR of cortisol, it had no significant effect on the MCR of progesterone or of cortisone. The estrogen administration did cause a decrease in the peripheral conversion of progesterone to 20alpha-hydroxy-pregn-4-en-3-one (20alpha-OHP) and of cortisol to cortisone but an increase in the conversion of 20alpha-OHP to progesterone and of cortisone to cortisol.


Levels of prostaglandins F-2alpha and E-2 in human endometrium during the menstrual cycle. A comparison between the prostaglandins found in proliferative and secretory endometrium in normal and tumor-bearing tissues is reported. The content of prostaglandins F-2alpha and E-2 is related to the three phases of the menstrual cycle and correlates with cyclic ovarian hormone variations. The menstrual phase is characterized by a high content of PGF-2alpha. High prostaglandin levels are found in tissues from patients with pathologic diseases such as adenocarcinoma of the endometrium when compared to normal tissues.


Further experience with suprapubic drainage by trocar catheter. In 1972 a preliminary report described the use of a large-bore (Nos. 12 and 16 Fr.) vinyl catheter, which contained a steel trocar within its lumen, in repair of cystourethrocele in 86 patients. Further experience in an additional 158 patients undergoing cystourethrocele repair, and a variety of other gynecologic procedures, is now evaluated. The prototype of a sharp, beveled, cutting-edge trocar tip proved to increase substantially the ease of insertion. Problems of design and production of the catheter were encountered and corrected. Two points of technique, (1) insertion of the catheter prior to the surigcal procedure and (2) use of the two-hand method, are advocated. The trocar catheter was found to be a simple, practical, and safe instrument for suprapubic bladder drainage.


The effect of intrauterine hypoxia on the child surviving to 4 years. Intrauterine hypoxia/asphyxia is an unchallenged cause of perinatal death, but whether sublethal degrees of hypoxia result frequently in brain damage in surviving infants is less certain. To test this hypothesis, obstetric patients with abruptio placentae, placenta previa, and prolapse of the umbilical cord were computer matched on several factors with normal control patients to determine the degree of risk of lower 4 year Stanford-Binet I. Q. scores or abnormalities on the 4 year fine motor and gross motor testings. The mean I. Q. score of babies born of mothers with one of these complications was no different from that of the normal controls. Similarly negative results were recorded on the 4 year fine motor and gross motor testings. Children of low birth weight in either group experienced lower I. Q. scores and higher risk of abnormal findings on the motor tests at 4 years than the babies of mature birth weight. Intrauterine hypoxia/asphyxia apparently is not a major cause of neurologic dysfunction in the surviving child.


Exenterative operations: experience with 198 patients. In a series of 198 exenterative operations performed at the Mayo Clinic for various pelvic malignant lesions, a 5 year survival rate of 33 per cent was obtained. This rate is commendable, since almost 80 per cent of the operations were accomplished for recurrent malignancy. The diminished over-all operative mortality rate of 8.1 per cent, a reduction from 13.5 per cent (1950 through 1962) to 3 per cent (1963 through 1971), is attributed to better methods of urinary diversion and to better management of fluid replacement and of infectious complications. Major complications, excepting bowel fistula and obstruction, now can be controlled reasonably well. When more conservative and equally curative methods of therapy have been exhausted, all patients with pelvic malignancy (whether primary in cervix, vagina, bladder, urethra, rectum, or vulva) should be considered potential candidates for exenteration.


Renal hypertension and pregnancy in the sheep. I. behavior of uteroplacental vasomotor tone during mild hypertension. The progressive changes in arterial pressure and uteroplacental hemodynamics were studied in 13 pregnant sheep from about the eightieth gestational day. All animals were followed to term. The results revealed a progressive increase in uteroplacental blood flow as the pregnancy progressed in the seven control animals. In six of the animals, mild hypertension was induced by unilateral renal artery constriction at about the one hundred fifteenth day. Following the induction of mild hypertension, there was a transient increase in uteroplacental vascular resistance and a reduction in uteroplacental blood flow. The arterial pressure remained significantly increased throughout the remainder of the gestation.


Maternal-fetal plasma glucose relationships in late monkey pregnancy. Maternal hyperglycemia was induced in six late gestation monkey pregnancies with intravenous glucose injection plus infusion. The maximum measured plasma glucose levels of the mother varied from 380 to 1,020 Gm. per cent. A significant linear relationship evolved between maternal and fetal plasma glucose peak concentrations. A saturation limit to placental transfer of glucose across the placenta is not apparent from these data.


Oxytocin administration, instillation-to-abortion time, and morbidity associated with saline instillation. Among 4,069 healthy gravidas undergoing saline abortion, patients administered intravenous oxytocin had a significantly shorter instillation-to-abortion time (median, 25.5 hours) than did patients not administered oxytocin (median 33.3 hours). The instillation-to-abortion time was independent of the rate of oxytocin administration, which ranged from 1 to 4 U. per hour (17 to 67 mU. per minute), but was associated with the time at which oxytocin infusion was begun. When oxytocin infusion was started within eight hours after instillation, a shortened time from instillation to abortion was observed. Although oxytocin augmentation may result in a lower proportion of patients being exposed to the risk of infection associated with prolonged intervals from instillation to abortion, this potential advantage appears counterbalanced by an increased incidence of clinical consumptive coagulopathy associated with instillation-to-abortion intervals of less than 24 hours.


The oxytocin challenge test in the management of high-risk pregnancies. Appearance of a repetitive late deceleration pattern following oxytocin-induced uterine contractions in the prepartum patient may indicate fetal compromise, while absence of this finding may reflect fetal well-being. In this study, 72 patients at risk for intrauterine asphyxia underwent 81 satisfactory oxytocin challenge tests. Eight tests in seven patients were interpreted as positive; 72, as negative; and one, as suspicious. In 64 patients with negative tests, no fetal deaths or neonatal asphyxial depressions were observed. One patient developed intrapartum fetal distress with late decelerations 8 days after a negative test and was delivered by cesarean section. The positive test appears to correlate meaningfully with other clinical parameters reflecting intrauterine compromise.


Minimal deviation adenocarcinoma ("adenoma malignum") of the cervix: a reappraisal. Five cases of so-called "adenoma malignum" of the cervix are presented. This term has been used to describe an extremely well-differentiated adenocarcinoma characterized histologically be distorted and architecturally irregular endocervical glands which penetrate deeply into the wall of the cervix, but without more than minimal and focal evidence of gland cell stratification, anaplasia, or mitotic activity. Despite this innocuour histologic appearance, these tumors have classically been thought to be clinically highly malignant, with an almost invariably rapid lethal outcome. This discrepancy between the histology and behavior has been presented as justification for the otherwise paradoxical name, "adenoma malignum". In the present series, all patients were treated with modern radiotherapeutic techniques, and four of the five are long-term survivors. Of the patients in the literature who died after rapid dissemination, none received treatment with acceptable radiotherapeutic techniques. Thus, we believe that with proper therapy this tumor is no more malignant than one would expect for a highly differentiated adenocarcinoma, and we suggest that the name, "adenoma malignum," be replaced by "minimal deviation adenocarcinoma of the cervix."


Chromosome breakage studies in lymphocytes from normal women, pregnant women, and women taking oral contraceptives. Cytogenetic studies of 977 lymphocyte cultures from ten normal men and 54 normal women have shown: (1) variations in the frequencies of chromosome breakages among consecutive cultures from the same person and among cultures from different people, indicating that many extraneous factors may affect lymphocyte chromosomes, and (2) significantly higher average breakages in cultures from nulligravidas taking oral contraceptives (OC) and in pregnant women who had had previous pregnancies than in nulligravidas who had never taken the pill. The increase in breakages in cultures from the OC users was not observed in all cultures and could not be correlated with length of time on pill or stage of the pill cycle, suggesting that synthetic hormones do not directly damage lymphocyte chromosomes. Since estrogens and progestogens are known to affect many metabolic and biochemical systems, it is possible that these substances may induce in OC users and pregnant women a slightly altered in vivo condition in which increased chromosome breakages may be expressed.


Effect of intrauterine copper on the nucleic acids, polysome pattern, and glycoprotein composition of the human endometrium. The modifications induced by the intrauterine release of copper in the macromolecular and glycoprotein composition of the proliferative and secretory human endometrium were studied. In addition, the endometrial changes produced in women users of copper-T intrauterine devices in the polysome pattern and in the content of ribonucleoprotein particles were determined during the secretory phase. A group of ten untreated normal women (control group) and 15 users of 200 mm.-2 copper-T intrauterine device were selected for this study from the outpatient clinic of the Hospital de Ginecologia y Obstetricia No. 2 del Instituto Mexicano del Seguro Social. The main changes observed in the copper-T users were: a significant decrease in the endometrial content of RNA in both phases of the menstrual cycle, a significant decrease in protein in the secretory phase, and drastic changes in the fucose-sialic acid ratios, which decreased during the proliferative and increased during the secretory phases. Normal human secretory endometrium contained 4.89 plus os minus 0.28 (mean plus or minus standard error (S. E.) mg. ribonucleoprotein particle per gram wet weight, while the endometrium of the Cu-T users showed a significant decrease to 2.52 plus or minus 0.17 (mean plus or minus S. E.). In addition, the Cu-T induced a decrease in the heavy components of the polysome pattern with a concomitant increase in the lighter components.


Serum prolactin levels during puberty.

Serum prolactin levels during puberty. Serum prolactin (PRL) concentrations and total estrogen levels were determined in groups of boys and girls from ages eight through 15. There was no significant change in PRL concentration with advancing age in boys, and levels were comparable to adult men. In girls, mean serum PRL and estrogen levels were not significantly different from ages eight through 13 and were comparable to those found in boys of the same age groups. At age 14 and 15, an increase in PRL and estrogen levels was found in girls.


Late seroconversion following HPV-77, DE5 rubella virus vaccine. The HAI antibody responses to HPV-77, DE5 rubella virus vaccine were evaluated with respect to time in 258 rubella-susceptible children. Seroconversion after 28 days post inoculation with this vaccine was not uncommon. These findings indicate a greater degree of modification of the HPV-77, DE5 rubella virus vaccine since most vaccines have been shown to seroconvert by 28 or 30 days post inoculation with the HPV-77 and other HPV-77 derived rubella vaccines. With respect to the routine of inoculating rubella-susceptible women in the childbearing age, late seroconversion could be of importance because of this uncertainty of the time of viremia and the increased chane of pregnancy with increasing time following immunization. Comparative information is needed for the Cendehill and candidate RA 27/3 rubella virus vaccines. That vaccine showing an early and predictable higher conversion ratio would be the most desirable for use in the above population.


Congenital hypertrophy of the retinal pigment epithelium. The flat, circumscribed, and hyperpigmented lesion of the retinal pigment epithelium (RPE) without clinically apparent involvement of the overlying retina, designated as congenital hypertrophy, was found to be associated with corresponding scotomas in the visual field. The depth of the scotoma increased with the age of the patient. These lesions did not grow. They could be readily differentiated from other pigmented fundus lesions on the basis of their typical clinical appearance. Histopathology revealed a single layer of hypertrophied cells, containing numerous large pigment granules, and degeneration of photoreceptor cells overlying the area of abnormal RPE. The clinical as well as the histologic findings suggested that the retinal abnormality overlying the hypertrophied RPE was due to secondary degeneration rather than primary maldevelopment of photoreceptor cells.


Pigmentation and retinal breaks.

Pigmentation and retinal breaks. Of 260 patients with primary, nontraumatic, rhegmatogenous retinal separation analyzed for the presence of retinal or subretinal pigmentation associated with the retinal breaks, some 48.5% of all patients had significant pigmentary changes, especially occurring with lattice degeneration and nonlattice horseshoe tears. Critical analysis of the age of the patient, type of retinal break, vitreoretinal degeneration, and type and extent of pigmentation is essential before ascribing a protective effect of the pigment in the prevention of subsequent retinal separation.


Equatorial lens pigmentation, myopia, and retinal detachment. Five myopic male retinal detachment patients had pigmentation of the lens equator that mildly obscured the view of the ora serrata. It may be related to a prepigmentary glaucoma state or to development of the ciliary ring predisposing to retinal detachment, or both.


Prophylaxis of retinal detachment.

Prophylaxis of retinal detachment. The incidence of retinal detachment after prophylactic treatment is between 1 and 14%. In a series of 701 eyes treated prophylactically with photocoagulation or cryopexy (with and without scleral buckling), incidence of retinal detachment was 4.7%. The incidence of new break formation was 8.0%; in 26 eyes, new breaks were responsible for the subsequent formation of retinal detachment; in seven eyes, retinal detachment resulted from inadequate reaction around the treated retinal break. Twenty eyes suffered a deterioration of visual acuity of two or more lines after treatment. The incidence of complications after photocoagulation was higher than after cryopexy, although there was no significant difference in the efficacy between the two methods.


Thermokeratoplasty in the treatment of keratoconus. Of 59 keratoconus eyes treated with the thermokeratoplasty procedure and followed for as long as two years visual acuity improved to better than 20/30 in most. Despite the varied procedures, temperatures, sites and duration of application, sizes and shapes of the probe, as well as follow-up periods, the results were satisfactory and compared favorably with the results of penetrating keratoplasty. Thermokeratoplasty did not preclude later penetrating keratoplasty. The disadvantages of the thermokeratoplasty procedure were: (1) a transitory corneal haziness; (2) production of corneal scarring if not properly done; and (3) the fact that further studies are necessary for better standardization of the technique. Despite these disadvantages, less than 5% of the patients who underwent thermokeratoplasty required further penetrating keratoplasty.


Retrocorneal fibrous membrane in the vitreous touch syndrome. The retrocorneal fibrous membrane in eight cases of the vitreous touch syndrome was characterized by homogeneous granular material, fine filaments arranged either singly or in bundles, multiple lamellae of basement membrane-like material, and banded figures of similar to 110 nm periodicity. Seven cases demonstrated an intact endothelial monolayer while only one showed cells in a markedly thickened fibrous layer. These findings support the pathogenic mechanism of endothelial fibrous metaplasia and secretory activity as the origin of the retrocorneal fibrous membrane in the vitreous touch syndrome.


Disinserted extraocular muscles.

Disinserted extraocular muscles. In two patients, a muscle that slipped from the globe posteriorly created the clinical pattern of reduced rotation amplitude, reduced saccadic velocity, reduced active force, and increasing exophthalmos with gaze into the field of action of the muscle. The muscle was surgically identified by an electronic stimulator that caused the muscle to contract, thus allowing the surgeon to fell it pull on the forceps or see its traction on adjacent tissues.


Retinal detachment after strabismus surgery. Four nonmyopic eyes in three patients developed retinal detachment after strabismus surgery. Certain features common in all four eyes included the presence of a chorioretinal scar corresponding in location to the muscle operated on, proliferating fibrous tissue adjacent to the scar, and varying degrees of vitreous hemorrhage. These findings were similar to those in retinal detachments after perforation of the eye by foreign bodies. Penetration of the globe by the needle during muscle surgery was considered the etiologic factor. The use of spatula needles to prevent piercing of the globe is suggested, and in case such accident is suspected, diathermy or cryoapplication over the perforation site is advised.


Deep orbital dermoid with draining sinus. A dermoid cyst in a 6-year-old girl, deep within the orbit, extended from the apex, through the lateral wall, via a fistulous tract to the skin, forming a draining sinus. Both the deep location and the cutaneous drainage of the cyst are rare presentations of this tumor. We used a Krönlein orbitotomy to successfully remove the tumor without loss of vision.


Familial bilateral optic nerve hypoplasia. Bilateral optic nerve hypoplasia affected five individuals corresponding to four generations of a family. Two decreased men were also apparently affected. The three patients studied, two women and a girl, presented the same clinical picture: poor visual acuity; small, pale and malformed papilla; two concentric peripapillary halos; and wandering movements of the eyes. Fluorescein angiography performed in the propositus mother showed a faint papillary fluorescence. At variance with the two familial cases reported, the pedigree clearly suggest an autosomal dominant type of inheritance. Similar clinical features found in other patients suggest a stationary nature of the defect.


Electron microscopic diagnosis of medulloepithelioma. A 20-month-old boy with a ciliary body tumor presented with two white flocculi floating in the anterior chamber of his left eye. This material was examined by electron microscopy. Both the clinical appearance of the tumor and the ultrastructural findings suggested the diagnosis of medulloepithelioma. The flocculi contained tumor cells forming lumina and displaying neuronal-type cilia, neurotubules, and a complex band of apical desmonosomal junctions. Since the last finding is not present in retinoblastoma rosettes in the absence of fleurette differentiation, it distinguishes medulloepithelioma from retinoblastoma. The electron microscopic diagnosis has permitted a trial period of conservative cryotherapy directed at the tumor and the associated glaucoma. The electron microscopic characteristics of the tumor favor the neuroepitheliomatous and neuroblastic differentiation of medulloepithelioma rather than ependymal differentiation.


New extraocular muscle clamp.

New extraocular muscle clamp. A small vascular clamp with the serrated edges at a 45 degree angle holds extraocular muscles firmly without crushing.


Orbital floor elevator.

Orbital floor elevator. A 15-cm  orbital floor elevator was used to lift orbital contents, and to reposition and remove bony fragments during orbital floor repair procedure.


Creative technological aids for the learning-disabled child: an interdisciplinary project. An interdisciplinary team of engineering students and occupational therapists have developed prototype electromechanical toys to enhance adaptive learning performance of developmentally disabled children. This paper describes the Creative Technological Aids (CTA) project undertaken under the joint auspices of the Undergraduate Research Opportunities Program (UROP) of the Massachusetts Institute of Technology and the Kennedy Memorial Hospital occupational therapy department. Four prototype CTA devices were evaluated in clinical and community settings and preliminary results show that these devices are highly motivational in teaching eye-hand coordination and perceptual-motor skills.


A performance rating scale for evaluating clinical competence of occupational therapy students. This study was conducted to assess the effectiveness of a 53-item rating scale, the Field Work Performance Report (FWPR), developed to evaluate the performance of occupational therapy students during field work. University faculty and field work supervisors from five different geographic regions in the United States participated in instrument construction. The FWPR was field-tested on a standardization group of 934 student affiliates. An item-analysis and cross-validation design was used to investigate instrument reliability and validity. When FWPR ratings were correlated with other supervisor ratings of student performance, validity coefficients for this scale ranged from .62 to .83. The tests of reliability yielded an inter-rater correlation coefficient of .75, where the consistency coefficient was .97. The FWPR has now been adopted as the official instrument of the AOTA for evaluation of field work performance.


Teaching dressing skills to a severely retarded child. An eight-year-old, severely retarded boy was taught to remove his polo shirt independently in sixteen training sessions using operant techniques. Reinforcement was dispensed contingent upon successful independent performance on each of five undressing subtasks.


Neurodevelopment and sensory integration. This is the report of a nine-month study of three profoundly retarded, multiply handicapped subjects less than five years of age, who received mother-administered, clinic-supervised treatment for neurodevelopmental sensory integration. The emergence of more advanced postural reactions, changes in affect, and responses to objects were recorded. Trends toward early cognitive emergence are discussed in terms of the development of interest and affect, as related to the concept of "fixation attention" of normal nine-month-old thinking infants.


Changes in beliefs held by occupational therapy students before and after the first field experience. Occupational therapy programs seek to integrate classroom theory and clinical reality. Early introduction of clinical contacts, concurrency of theory and practice, and coordinated program planning is directed to orderly growth and change in the occupational therapy student. It was hypothesized that, with complete integration of theory and practice, no sharp belief changes would occur during the first full-time field experience. Data from responses to social psychological instruments by one group of 28 occupational therapy seniors supported the hypothesis. There were no statistically significant changes in authoritarianism, dogmatism, or Machiavellianism during the first full-time field experience.


Influencing students' observations.

Influencing students' observations. This article presents a study concerned with the influence of a descriptive introduction on occupational therapy students' perception of a child's behavior. Seventy-two students were divided into four groups. Each group received different information or set before seeing the same seven-minute videotape of a four-year-old boy doing a series of developmental tasks. This study measures the effect of prior information on the students' choice of descriptive words and on a narrative paragraph they wrote after seeing the videotape. Word choice results were significant at the .05 level for two of the four groups.


The teenage job hunter.

The teenage job hunter. Job hunting is a significant aspect of occupational behavior and a task that recurs at intervals during the lifespan. Adolescents constitute a vulnerable population-at-risk in their efforts to enter the labor market. Their self-esteem, mastery, and sense of competency are at stake. This paper describes an adaptation of a method currently being used by business management firms that counsel executive clients in the job-hunting process. The method described is tailored to the needs of teenagers and is presented so that occupational therapists can use or modify the method for clients who lack confidence or experience in job hunting.


Communication and the nonverbal, multihandicapped child. A pupil at the Kennedy Memorial Hospital Day School, Boston, was trained by an occupational therapist to use the Auto-Com, a device that enables those with severe motor impairment, such as cerebral palsy, to communicate effectively with others. The device was developed by the Cerebral Palsy Communication Group of the University of Wisconsin, Madison. The child continues to use the device and has become a more involved member of the class.


Particle-free and glycogen-bearing double membrane arrays in extraocular muscle of rabbit. Smooth double membrane arrays were observed in apparently normal extraocular muscle. These were fully or partially glycogen bearing, or completely particle free. The respective structures were often closely associated. Comparable arrays have been reported in normal and pathologic muscle; in liver cells, particle-free and glycogen-bearing double membrane arrays are frequently seen under an assortment of abnormal conditions. The significance of such structures is not clear. The present observations suggest that particle-free arrays are related to those bearing glycogen and may thus be associated with anabolic functions.


Spontaneous aortic aneurysms in blotchy mice. The pathogenesis of aneurysm formation was studied in Blotchy (Blo) mice which have a hereditary defect in collagen and elastin cross-linking. Elastin breakdown began at an early age and progressed rapidly. Changes observed included replacement of elastica by fibroblasts and ground substance. More advanced lesions were characterized by infiltrates of inflammatory cells, hemorrhages, and eventual ruptures of the aortic wall. Accumulations of lipids, Schiff-positive mucopolysaccharides, iron or calcium were not found. The lesions occurred primarily at points of greatest stress and were confined to the thoracic aorta. Androgen-insensitive mice (Tfm/Y) with the Blo gene died at a significantly earlier age than did normal Blo males or Blo/plus females. The Blo mouse is compared with other animal models of spontaneous and experimentally produced aneurysms.


Regulation of spleen growth and portal pressure in hepatic shcistosomiasis. Growth rate and histology of splenic autotransplants in subcutaneous pockets were compared with those of autotransplants in the extrahepatic portal bed in splenectomized mice infected with cercariae of Schistosoma mansoni and in splenectomized uninfected controls. By the fifteenth week after transplantation (and tenth week after injection of cercariae) subcutaneous transplants gained 6.5 times and omental transplants 8.2 times more weight in infected animals than corresponding transplants in uninfected animals. Portal pressures averaged 11 to 13 cm of water in infected animals with transplants and 17 cm in those with intact spleens (compared to that of 6 to 7 cm in controls). Hyperplasia of white pulp with increase in germinal center activity characterized transplants as well as intact spleens of infected animals. The results suggest that a) During the first 10 weeks of experimentally induced infection, portal congestion is not the predominant mechanism regulating increased spleen growth; and b) An intact enlarged spleen appears to contribute to elevated portal pressure.


Atheromatous emboli in renal biopsies. An ultrastructural study. In a series of 755 renal biopsies atheromatous emboli were found in biopsies of 8 men from 49 to 72 years of age. Unexplained recent deterioration of renal function was present in each. This previously unreported incidence of 8/755 biopsies is ascribed to the selection for biopsy of patients with unexplained decrease in renal function. Hypertension was a major feature in 6, hyperlipidemia in 2, a leaking aortic aneurysm in 1, carcinoma of the pancreas in 1, and chronic glomerulonephritis in 1 patient. Toluidine-blue-stained epoxy sections proved to be more effective in recognizing small emboli than paraffin sections. Ultrastructural observation concerned a) early lesions (eg, fresh emboli with endothelial distortion or injury), b) intermediate lesions (eg, histiocytic or giant cell reaction and intimal proliferation), and c) later lesions (eg, extraluminalization of the crystals eventually resulting in inert location in intimal stroma). Osmiophilic deposits on the crystal surfaces were myelin-form in structure and were felt to result from lysosomal action.


Acceleration of amyloidosis by syngeneic spleen cells from normal donors. Intravenous administration of syngeneic spleen cells from normal donors was found to markedly shorten the induction time for casein-associated splenic amyloid diposition in the mouse. The effect of intravenous donor cells seemed purely one of acceleration; it did not provoke amyloid deposition either by itself or in combination with independently ineffective heterologous proteins. The accelerator effect did not depend on the viability of the cell suspension, and after physical disruption of the cells all the accelerator activity seemed localized to the sedimentable fraction of damaged cells, nuclei and coarse debris. It is suggested that the accelerator acts through affecting the function of perifollicular splenic macrophages.


The skeletal correlates of behavioral modification in the laboratory mouse (Mus musculus). The effects of behavioral modification on the skeletal morphology of the laboratory mouse (Mus musculus) are investigated. Climbing, with increased prehensile use of the foot, is found to bring about significant changes in metatarsal and long bone morphology. Differences in metatarsal robusticity related to weight-bearing differences associated with different locomotor patterns are reported for a natural history setting for Peromyscus.


Eruption of permanent teeth in Brazilian Whites and Blacks. A total of 302 White and 904 Black children six, nine and 12 years of age were studied for the eruption of their permanent teeth. Differences between the two ethnic groups were not large, but the Black subjects were generally more precocious at the beginning of the process (especially the girls, both in the upper and lower incisors). At nine and 12 years of age, however, these dissimilarities disappear. The latter do not seem to be related to distinct rates of extraction or agenesis of deciduous teeth. No significant differences were observed in the degree of asymmetry present in the permanent dentition of the White and Black individuals studied.


Manibular growth in the rhesus monkey (Macaca mulatta). Mandibular growth of 42  /1 735) (Macaca mulatta) was analyzed quantitatively and qualitatively. Four groups of animals were defined according to dentitional age (i.e., infant, juvenile, adolescent, young adult). At each age growth was observed fopment, 57 periods of growth were studied. The growth incremental data were collected by superimposing serial cephalograms on mandibular implants. Growth and remodeling of both the skeletal and dento-alveolar components of the rhesus mandible were greatest in the infant monkeys and were less in successive age groups. Posterior relocation of the ramus was noted in all age groups while bone deposition on the anterior and inferior borders of the mandibular body was greatest in the younger animals. The most pronounced dental changes also occurred in the younger animals while the dentitions of the adolescent and adult animals were generally more stable. This study demonstrates that the rate and direction of normal mandibular growth varies with the age of the animal. Furthermore, mandibular growth is quantified at four defined maturational levels to provide a set of values illustrating normal mandibular growth. These values can also be used as control data for experimental studies.


The skin primates. XLIV. Numerical taxonomy of primate skin. Data on 84 characteristics of the skin of 36 species of primates were extracted from a series of articles describing the histological and histochemical properties of the skin of primates. The data were subjected to a cluster analysis. The results were in reasonably good agreement with orthodox primate taxonomies although some exceptions were apparent. The species clustered into four main groups approximately comparable to Prosimii, Cercopithecoidea, pithecoidea, and Hominoidea are commensurate with standard taxonomic practice. Within the Ceboidea, however, the Atelinae and Alouattinae tend to group with the Hominoidea, Aotus and Saimiri show variable placements, and Callimico groups with the Callithricidae.


The genetic structure of a tribal population, the Yanomama Indians. XII. Biodemographic studies. The Yyanomama Indians of Southern Venezuela and Northern Brazil are one of the largest, relatively unacculturated tribes of the tropical rain forest. Over a period of eight years data have been collected from a considerable portion of their territory on estimated age, sex ratio, fertility rates (as determined by physical examination and urine tests), and infant death rates. Although it has been impossible to collect direct data on infanticide, this subject can be approached indirectly through distortions of the sex ratio and anecdotal information. Some historical data are also available as a basis for estimating tribal expansion in the past 100 years. With this material it has been possible to construct Life Tables for the anomama,, and to explore the results of various perturbations of the input parameters. Data are also presented on patterns of mating and reproduction: number of spouses, mean and variance in number of surviving children, frequency of "extra-marital conceptions" based on the results of extensive blood group typings, and consanguinity rates as determined by observation and computer simulation. Although we do not present the Yanomama as typical, these data are seen as providing a basis for more realistic population models than have existed in the past. In addition, the data provide a basis for relatively precise estimates of such demographic measures as Fisher's Reproductive Value, Crow's Index of Total Selection, and Weiss' Index of Growth Regulation.


Septal apertures in the humerus of normal and experimental rats. Septal apertures of the humerus are rare in wild and domesticated rats but their occurrence is more frequent in females than in males and on the left than on the right side. Septal apertures can be produced experimentally by hypophysectomy due to an extreme reduction of the thickness of the septal wall. Other endocrine ablations, starvation and unilateral front leg paralysis do not produce a sufficient reduction of septal wall thickness to cause septal apertures. Their occurrence is also not correlated with total humeral robusticity. Thus, the manifestations of septal apertures in a non-specialized mammal such as the rat do not differ from those in higher primates.


Papago Indian admixture and mating patterns in a mining town: a genetic cauldron. Problems of delineation of population units and sub-units and the poor fit of genetic models make populations with high mobility and low stability difficult to analyze by present means. Examination of three processes  īn-migration, admixture, and dispersal  as well as the mate selection factors involved in out-mating and changing population boundaries are suggested as alternate procedures in these cases. The Papago Indian community of Ajo, Arizona, is characterized by historical instability, an in-migration rate of 72.3%, a dispersal rate of 20.6%, and an admixture rate of 36.7%. In-migrant parents continue to come from all parts of the reservation, reservation ties are strong, and families often fragmented between reservation and Ajo homes. For these and other reasons the community cannot be delineated as a population unit nor incorporated into models of subdivided populations. Ajo's function as a cauldron in which genes are mixed and from which they are scattered is evident in sharp increases in the percentage of mixed Papagos among residents and out-migrants. Among the latter more than twice as many mixed Papago leave Ajo as entered in the parental generation. Mate selection factors possibly involved in admixture are considered.


Magnitude of sex differences in dichotomous ossification sequences of the hand and wrist. Among the dichotomous (present/absent:absent/present) ossification sequences individually ascertained in 3059 boys and girls with at least one but not more than 27 ossification centers of the hand and wrist, 54 such sequences exhibit statistically-significant sex differences in frequency, 32 of them at the 1% confidence level or better. Analyzed by regions (rows and rays, epiphyses and round bones), ten centers, primarily distals and those of the first digit, account for the majority of the significant sex differences.


A factor analysis of morphogenetic fields in the human dentition. The traditional morphogenetic fields of the human dentition were evaluated by means of factor analysis of dental dimensions taken from a series of human crania. When crown length, crown width and crown index were considered separately, factors emerged which could be identified with the tooth group fields. But a combined crown length-crown width analysis generated factors which extended beyond the regional tooth groups. Crown width itself was revealed to be an important axis of morphologic intergration. It was concluded that univariate methods are not adequate for identifying morphogenetic fields; the teeth must be treated as multidimensional units where the correlation among dimensions is accounted for.


Adaptive tolerance of fish myocardium to hypercapnic acidosis. Isometric, electrically paced strips of cardiac ventricle from two species of fish (plaice, Pleuronectes platessa; cod, Gadus morrhua) with different tolerance to hypoxia were compared with respect to effects of hypercapnic acidosis. Acidosis was induced by altering the equilibrating gas mixture for the muscle strip chamber from 3% CO2 in 97% 02 to 15% CO2 in 85% O2. The pH was varied further by changing the NaHCO3 content of the Cortland-Ringer solution used in the muscle chamber. After onset of acidosis with the highest buffer value of the Cortland-Ringer solution (35.7 mM NaHCO3), the force decay was similar for the initial 10 min of exposure to high Pco2. Subsequently the cod heart continued to lose force at the same rate, whereas the plaice heart regained a cardiac contractile force that after 40 min even exceeded prehypercapnic values. When buffer values were varied by changing the bicarbonate content of the Cortland-Ringer solution in steps from 0.0 to 35.7 mM NaHCO3, the cod heart showed steep force decays at all buffer values during hypercapnic acidosis. The plaice heart showed a similar decline at low buffer values but at a bicarbonate concentration above 23.8 mM NaHCO3, the initial force decline was reversed and prehypercapnic force restored.


Acyl-CoA inhibition of adenine nucleotide translocation in ischemic myocardium. The translocation of adenine nucleotides across the inner mitochondrial membrane and the tissue concentration of long-chain acyl-CoA esters were studied in dog heart after experimental myocardial ischemia. Ligation of the anterior coronary artery initiated events leading to an early decrease in adenine nucleotide translocase activity. A reciprocal increase in the concentration of heart tissue long-chain acyl-CoA esters was also observed. Adjacent nonischemic tissue showed changes intermediate between that of ischemic and normal heart tissue. It is postulated that a decrease in fatty acid oxidation after myocardial ischemia would lead to an accumulation of long-chain acyl-CoA esters, which in turn would inhibit adenine nucleotide translocation. The net result would be a lowering of the energy charge of the cell, adversely affecting muscle contraction and electrical conduction.


Renal glutaminase adaptation and ammonia excretion in infant rats. The purpose of this investigation was to determine the role of enzyme adaptation in the response of ammonia excretion to acidosis in developing rats. The response of renal ammonia excretion was low in infant rats (7-12 days old) following administration of a single dose of acidifying salt (5 mmol NH4CL/kg). However, repeated administration (2 times daily) of the salt increased ammonia excretion two- to threefold within 2 days. This adaptive response was associated with a concomitant rise in renal phosphate-dependent glutaminase (PDG) activity; PDG activity increased from approximately 36% adult level in untreated infants to 79% adult level in infants given NH4Cl for 2 days. Ammonia excretion and PDG activity decreased in parallel following cessation of NH4Cl treatment. Administration of the antibiotic, actinomycin D (100 mug/kg, ip, 2 times daily for 2 days) completely inhibited the response of PDG to repeated NH4Cl administration. In contrast to the situation previously observed in adult rats, actinomycin D treatment prevented the acid-induced rise in renal ammonia excretion. These results suggest that the level of renal PDG plays a more direct role in the adaptation of ammonia excretion to acidosis in infant rats than in adults.


Potassium-sparing effect of enhanced renal ammonia production. The effect of a primary alteration in renal ammonia production on potassium excretion was explored in normal men utilizing ingestion of glutamine to increase ammonia production independent of concomitant acid-base manipulations. After ingesting a constant-formula diet of normal electrolyte content for 3 days, normal men underwent on separate occasions in a rigidly paired fashion an acute study with ingestion of glutamine (4.3 mmol/kg) or only water. Glutamine ingestion under conditions of normal acidification or concomitant with an acute acidifying stimulus resulted in an increase in ammonium and concomitant decrease in potassium excretion. The potassium conservation could not be accounted for by changes in urinary sodium excretion or in plasma potassium or acid-base parameters. Furthermore, when NaHCO3 was ingested for 3 days preceding both the water and glutamine studies, the influence of glutamine on both ammonium and potassium excretion was reduced significantly. These studies suggest that altered ammonia production can affect potassium excretion, providing further evidence in support of a renal potassium-ammonia homeostatic mechanism.


An effect of hyposmolarity on insulin release in vitro. An abrupt reduction of medium osmolarity by as little as 20 mosM evoked a discrete short-lived insulin secretory response from perifused chopped pancreas or isolated islets. The insulin response occurred earlier than that induced by either glucose or tolbutamide. None of the usual modifiers of insulin secretion significantly altered this secretory response. Glycolytic inhibitors, adrenergic agonists and blocking agents, cholinergic blocking agents, mitotic spindle inhibitors, and agents influencing sodium pump activity failed to alter hyposmolar-induced insulin secretion. Manipulation of the perifusion medium calcium concentration was the only procedure tested that influenced the secretory response. Perturbations of medium calcium concentration that increased the tissue-to-medium calcium gradient augmented the hyposmolar-induced insulin response and those that decreased tissue-to-medium calcium gradient greatly inhibited the response. The precise cause of the insulin response to a decrease in bathing fluid osmolarity remains undefined; however, the stimulus is not specific for insulin because increases in glucagon and amylase were also elicited by the hyposmolar stimulus.


Regulation of body mass in rats exposed to chronic acceleration. Female rats approximately 6 mo old were chronically centrifuged for up to 30 days at 2.76 G or 3.18 G and sacrificed at intervals for body-composition study. Both fat and the fat-free body mass (FFBM) were reduced during the 1st wk of centrifugation, with the fat showing considerably more variation both within and between groups. The FFBM was reduced below control level to the same extent in rats fed commercial chow, a high-fat diet, or a high-protein diet or in rats prefasted to produce a body-mass deficit at the start of centrifugation. There were no centrifugation-associated changes in body water content. It was concluded that body fat showed no evidence of regulation, FFBM is regulated at any constant level of acceleration between 1 and 4.15 G, and the change in FFBM induced by a change in acceleration is probably not regulated.


Plasma and hepatic binding of indocyanine green in guinea pigs of different ages. Binding of indocyanine green (ICG) to the proteins in plasma and bile of guinea pigs ranging in age from 1 day old to adult was studied. The ICG in plasma was almost totally bound to the protein and there was no significant difference in the binding between newborn and adult animals. Binding of ICG to biliary protein was similar in all age groups. Particulate fractions of liver from adult guinea pigs had a higher ICG binding capacity than that from the newborn at all concentrations tested. The uptake of ICG by liver slices involved mostly active processes. The slice-to-medium (S/M) ratio of ICG was lowest in liver preparations from the newborn; however, the S/M ratio for adult animals was lower than that for 10-day-old animals. Liver slices from adult guinea pig showed the fastest ICG efflux rate, and the efflux rate with liver slices from the newborn was the slowest. Processes of hepatic uptake and release of ICG were incompletely developed in the newborn guinea pig.


Cardiac output and its distribution during diving in the rat. The diving response was produced by submerging the head of the unanesthetized rat for 60 s, while it was confined in a mesh-wired cone. Heart rate and cardiac output decreased by 73% and 74% from the predive values, respectively, indicating insignificant change in stroke volume. Central systemic arterial blood pressure rose by 22% during diving and a fourfold increase in total peripheral resistance was observed. Blood flow to the coronary, cerebral, and bronchial circulations remained unchanged while a 95% reduction in the intestine and the spleen, a 97% reduction in the kidney, and greater than 99% reduction in the tail and skin were observed during diving. The blood flow reduction from predive values ranged from 50% for liver and skeletal muscle to 75% for the adrenals and 65% for the diaphragm. The redistribution of the drastically reduced cardiac output during head immersion in the rat is similar to that reported for diving mammals. It is suggested that the rat may serve as a useful cardiovascular model for further studies of the diving response in mammals.


Increased uptake and utilization of glucose by diaphragms of rats exposed to chronic centrifugation. Weaning female Sprague-Dawley rats were exposed to 2.76 or 4.15 G for periods ranging from 2 to 20 wk. The isolated diaphragm tissues from these rats were studied in vitro to determine the uptake of glucose and its utilization to CO2 and glycogen. The diaphragm muscle tissues obtained from centrifuged rats showed higher rates of glucose uptake and 14CO2 production from [U-14C]glucose than those obtained from noncentrifuged controls, but no significant differences in the rate of incorporation of [U-14C]glucose into glycogen were observed. Rats centrifuged for 12 wk at 4.15 G continued to show an increase in diaphragm tissue glucose uptake for periods up to 2 wk after return to normal gravity. The stimulating effect of insulin on the uptake of glucose and its incorporation into glycogen was much higher in the diaphragms of centrifuged rats. From the results of this study, it is concluded that one of the adaptive responses of rats to chronic centrifugation is an increase in glucose metabolism of their muscle tissues.


Adrenergic responses in canine cutaneous vasculature during acute hemorrhagic hypotension. The purpose of this study was to determine the effect of acute hemorrhage on vascular responses to sympathetic nerve stimulation and norepinephrine. The experiments were carried out with sodium pentobarbital anesthesia. The preparation employed was the dog's hindpaw perfused at constant blood flow. Changes in vascular resistance in the paw were indicated by changes in perfusion pressure. Changes in perfusion pressure elicited by sympathetic nerve stimulation and intra-arterially administered norepinephrine were determined before and after hemorrhage of 15 ml/kg in normal and acutely nephrectomized animals. The response to sympathetic stimulation was increased by about 50% in normal but not in nephrectomized dogs, whereas the response to a low dose of norepinephrine (0.5-1 mug) was not significantly changed in either group of animals. In additional experiments in which the plasma renin level was measured, the potentiation of responses to sympathetic stimulation and a high dose of norepinephrine (2 mug) occurred at the time that the renin level was increased by hemorrhage. These results indicate that the level of circulating angiotensin attained after hemorrhage may facilitate vasoconstrictor responses to adrenergic stimuli.


Nonsustained pulmonary vasoconstriction during acute hypoxia in anesthetized dogs. The objectives of this study were to describe in greater detail the initial rise and spontaneous decline in acute hypoxic pulmonary vasoconstriction and to investigate a number of mechanisms that could have caused this secondary vasodilation. With the onset of isocapnic hypoxia (Pao2 of 28, 44, or 56 mmHg), pulmonary vascular resistances increased to maximum values at 3 min and then spontaneously declined toward control values. Pulmonary perfusion pressures rose to maxima at approximately 4 min and then also declined. During severe hypoxic exposures (Pao2 of 30-37 mmHg) this secondary vasodilation was found not to be due to beta-adrenergic-induced vasodilation, withdrawal of alpha-adrenergic-induced vasoconstriction, vasodilation caused by a sustained increase in pulmonary blood flow, fatigue of the vascular smooth muscle contractile mechanism, or release of vasodilatory prostaglandins. It is suggested that the decline in hypoxic pulmonary vasoconstriction may be due to an exhaustion of a chemical mediator, release of a pulmonary vasodilator agent, or myogenic stress relaxation.


Analysis of a periodic breathing pattern associated with Mayer waves. Cats subjected to common carotid artery occlusion and hemorrhage developed a waxing and waning of respiratory amplitude recurring with a period of 24 s (range 10-60). Occasionally the waning phase terminated with apnea. This respiratory pattern, reminiscent of "periodic" breathing, was usually associated with an oscillation of sympathetic neural activity, and of systemic arterial pressure, of the same period. A similar pattern of modulation of phrenic nerve activity was observed during neuromuscular block and artificial ventilation and when, at the same time, the associated systemic arterial pressure oscillation was eliminated. These findings suggest that this breathing pattern is not the result of an analogous pattern in the discharge of gas tension-sensitive and/or blood flow- and pressure-sensitive receptors that is fed back to the central nervous system (CNS). Hence the pattern must be generated within the CNS with no need of rhythmic sensory information. The pattern can be accounted for by the assumption that the central respiratory drive potentials are riding on top of a slow oscillation of phrenic motoneuron membrane potential with a 24-s period.


Influence of cardiac neural inputs on rhythmic variations of heart period in the cat. Spectral analysis was used to investigate variations of heart period in 13 decerebrate cats under different conditions of neural input to the heart. Spectral density plots in intact animals showed three well-defined peaks: P1 (1.5-2.5 cycles/min), P2 (6-10 cycles/min), and P2 (respiratory frequency). In the presence of sympathetic input only the amplitudes of all peaks were decreased; when only vagal input was present the amplitudes of P1 and P2 were increased and there was no change in P3; when neither sympathetic nor vagal input was present the amplitudes of all peaks were decreased. In addition, the amplitudes of P1 and P2 were increased and there was no change in P3; when neither sympathetic nor vagal input was present the amplitudes of all peaks were decreased. In addition, the amplitudes of P1 and P2 were found to be significantly correlated with the mean heart period under the condition of vagal control only. It is concluded that P3 is related to sinus arrhythmia and that P1 and P2 may be related to spontaneous rhythms that are an intrinsic feature of the dynamic regulation of heart period by the vagus system. Sympathetic activity plays no role in the genesis of these rhythms.


Microvascular pressure distribution in skeletal muscle and the effect of vasodilation. In cats anesthetized with pentobarbital, 188 direct microvascular pressure and diameter measurements were made of the tenuissimus muscle. The microvascular pressure in arterioles of 70 mum in diameter or larger was proportional to the systemic arterial pressure (PA). The arterioles with diameter-s ranging from 35 to 20 mum have been shown to be the principa-l source of arteriolar resistance regulating micropressures downstream. Across the capillary bed proper, the drop in pressures was about 15% of PA. Micropressures in the smallest venules (8-15 mum) averaged 24 mmHg and reflect closely capillary blood pressure. With a background of basic microvascular data, the vasodilatory mechanism of papaverine (P) and isoproterenol (IPR) in the skeletal muscle was analyzed. Administration of IPR decreases both arteriolar and venular pressure, while P infusion decreased the pressure in arterioles wider than 20 mum in diameter; however, in smaller arterioles there was a substantial elevation in micropressure. The data establish two basically different vasodilatory effects on the terminal vasculature: one with increased capillary pressure and fluid filtration (P), a second with a decrease in capillary pressure enhancing absorption (IPR).


Reflection coefficients of dog lung endothelium to small hydrophilic solutes. Step additions of small hydrophilic solutes to the perfusate of isolated dog lungs produce weight changes (Vargas-Johnson). The product: (observed reflection coefficient) times (observed filtration coefficient) for the lung endothelial barrier is obtained from the initial weight slope per unit osmolality change. The observed filtration coefficient determined from the sustained constant weight slope per increment of pulmonary outflow pressure was 0.038 plus or minus 0.011 cm/s (assumed exchange area 500 cm2/g lung). Correction to average transcapillary pressure (32% upward) and for osmotic buffering by resident solute (25% upward) gave 0.063 plus or minus 0.018 cm/s. The observed reflection coefficients were (mean plus or minus 2 SE): sodium chloride, 0.30 plus or minus 0.11; urea, 0.30 plus or minus 0.12; glucose, 0.48 plus or minus 0.26; sucrose, 0.39 plus or minus 0.17; raffinose, 0.35 plus or minus 0.16; hypotonic response: interstitial solute, 0.26 plus or minus 0.10. The observed reflection coefficient of sodium chloride, corrected for the preceding filtration coefficient effects (65% downward) and for combined flow limitation and osmotic buffering effects (50% upward) was 0.27. Transcapillary gradients of small hydrophilic solutes produce substantial osmotic effects for short times (seconds). Passive exchanges and net fluxes across the endothelium of the lung capillaries have parameters similar to those of the endothelium of skeletal muscle.


Rabbit testicular contractions: bimodal interaction of prostaglandin E1 with other agonists. Contractions of rabbit testicular capsules in vitro and in vivo in response to prostaglandin F2a, epinephrine, and acetylcholine were measured in the presence of prostaglandin E1 (PGE1). Contractions induced by these agents were markedly inhibited at 10-7 M concentrations of PGE1 in both preparations. Even so, lower levels of PGE1 (10-8 or 10-9 M) potentiated epinephrine- or acetylcholine-induced stimulation of increased tonus in vovo. Epinephrine, PGE1, and PGF2a caused increased tonus and contractions in vitro and in vovo; however, acetylcholine stimulated the testicular capsule much more in vivo than in vitro. The control log dose-response curve for epinephrine stimulation showed a slight decrease in the upper concentration range. Propranolol, a beta-adrenergic blocking agent, more than overcame this decrease and also prevented a theophylline inhibition of epinephrine-induced contraction. Prostaglandin E1's bimodal effect gives it the ability to modulate testicular contractions by increasing stimulation by other agonists in vovo at low concentrations of PGE1 but inhibiting it at higher concentrations. Thus PGE1 is a potential regulator of testicular capsular motility and possibly sperm transport and hemodynamics.


Restitution of blood volume after hemorrhage: mathematical description. An analytical model was developed to simulate the restitution of blood volume after hemorrhage. This model was used to test two previously proposed hypotheses for the restoration of plasma oncotic pressure required for full restitution of blood volume: increased lymphatic flow or decreased trans-capillary leakage of albumin. Neither hypothesis could account for the temporal and quantitative features of experimentally observed restitution of blood volume. An alternate hypothesis, that restitution of blood volume results from a fluid shift from intracellular-extracellular fluid shift occurs in dogs treated with high doses of cortisol analog. Thus the results of the simulation support the hypothesis that full restitution of blood volume requires an intracellular-extracellular fluid shift. This fluid shift may be mediated by high circulating levels of cortisol secondary to hemorrhage.


Citric, orotic, and other organic acids in rats injected with active or inactive urease. Male rats were fed laboratory chow or a purified L-amino acid diet containing 11.2 or 5.6 g arginine/kg. Hyperammonemia was produced by injection of crystalline jackbean urease. Control animals were injected with saline or inactivated urease. Rats injected with 55 U urease activity/kg body wt (an LD50 dose) exhibited acute signs of hyperammonemia and elevated orotate and citrate in their urine. Plasma glucose, lactate, citrate, and alpha-ketoglutarate concentrations were also markedly elevated. Three injections of active urease (10 U/kg body wt) given at intervals of about 10 h produced hyperammonemia, which persisted for 25 h after the first injection. Blood glucose and ammonia concentrations were increased 2.6- and 22-fold, respectively, when compared with controls. Total urinary citrate excretion for 25 h was 371 mueq for active urease-injected rats compared with 62 mueq for rats injected with inactivated urease. Rats fed a purified amino acid diet containing 5.6 g arginine/kg excreted greater quantities of urea, citrate, and orotic acid than rats fed 11.2 g arginine/kg of diet. Injection of active urease increased citrate excretion by rats fed either concentration of dietary arginine. Changes produced with active urease were not observed if inactivated urease was injected.


Cold resistance of the brain during hibernation. III. Evidence of a lipid adaptation. The composition of membrane-bound lipids of brain from both warm-adapted and hibernating hamsters were different in the complex lipid fraction as well as their fatty acyl chains. During hibernation the content of cholesterol was less, but there were greater amounts of both the phosphatidylcholines and phosphatidylethanolamines. There were small but significant increases in monounsaturated fatty acids as well as arachidonic acid in all the glycerophosphatides of the hibernating hamster, whereas a decrease in isomyristic acid was o0served in the sphingomyelins. The most significant changes observed occurred in the fatty aldehyde composition of ethanolamine plasmalogen. A dramatic increase in oleyaldehyde was observed during hibernation. These changes in membrane-bound lipids may account for the cold-resistant properties of the brain during hibernation by retaining the fluid nature of the cell membrane.


Effects of unilateral sodium replacement on sugar transport across in vitro rabbit ileum. The effects of unilateral sodium replacement with either choline or mannitol on passive and active 3-O-methyl-D-glucose (3-MG) absorption by in vitro rabbit ileum were examined. The results indicate that the predominant factor influencing 3-MG absorption is the presence of sodium in the mucosal bathing solution. Replacement of sodium in the mucosal solution alone markedly inhibits passive and essentially abolishes active 3-MG absorption regardless of the presence or absence of sodium in the serosal bathing solution. The presence or absence of sodium in the serosal solution does not affect transmural 3-MG transport regardless of the sodium concentration in the mucosal solution. Further, when sodium is replaced in the mucosal solution alone, the bidirectional transmural fluxes of 3-MG do not differ markedly from those of D-mannitol, a solute whose transport is probably attributable to simple diffusion. The present findings together with those of previous studies (15, 16) are consistent with the notion that replacement of sodium in the mucosal solution alone essentially abolishes transcellular 3-MG transport and that the remaining transepithelial fluxes are largely due to diffusion through the paracellular or shunt pathway. The relation of these findings to in vivo and in vitro studies in which perfusion of a segment of small intestine with a Na-free solution disclosed little or no inhibition of sugar absorption is discussed.


Operant conditioning of heart rate in curarized rats: hemodynamic changes. Three groups of curarized rats were subjected to operant heart rate conditioning with use of a shock-avoidance procedure while cardiac output, mean arterial pressure, and total peripheral resistance were measured. Heart rate changes in the control group remained constant during the entire 90-min experimental period, while cardiac output decreased significantly. Those rats that were reinforced for increasing their heart rate had a small but statistically significant increase in heart rate, but cardiac output decreased to approximately the same extent as in the control group. The group reinforced for decreasing their heart rate demonstrated a large, significant decrease in heart rate and an even larger drop in cardiac output, which was significantly greater than that of either of the other two groups. Operant conditioning of a single facet of the cardiovascular system resulted in significantly larger changes in other cardiovascular parameters, which may have been partly masked by the physiological effects of d-tubocurarine. Therefore, only when these other measures of cardiovascular function are taken into consideration can interpretation of operant heart rate conditioning become meaningful.


Distal permeability to urate and effects of benzofuran derivatives in the rat kidney. Effects of benziodarone and benzbromarone on renal tubular permeability to urate-14C were investigated in anesthetized rats by microinjection and clearance experiments. Urate-14C and inulin-3H were injected into proximal and distal convolutions and their recovery was measured in urine collected serially. In control rats, total and direct recoveries were significantly lower after early proximal (72 and 52%, respectively) than after late proximal injections (83 and 63%), whereas distal recoveries were higher (94 and 69%). Delayed excretion (ca. 25%) did not change with site of injection. Total distal recoveries were always less than 100% (P smaller than 0.001) but increased to 98% at high loads. After proximal injections in drug-pretreated rats, total and direct recoveries increased significantly (P smaller than 0.001). Recoveries after distal injections did not change in benzbromarone-treated rats, whereas direct and delayed excretion, respectively, increased (87%) and decreased (9%) significantly (P smaller than 0.001) following benziodarone infusion. These findings demonstrate inhibition of proximal urate reabsorption by benzofuran derivatives. The results also suggest distal reabsorption of urate, presumably along the collecting ducts.


Thermoregulation of myocardial protein synthesis. The effect of temperature on myocardial protein synthesis was evaluated using L-[14C]phenylalanine incorporation into total protein of isolated rabbit right ventricular papillary muscles. Muscles were incubated in oxygenated Krebs-Ringer buffer containing tracer amino acid at temperatures of 25-43 degrees C or incubated without tracer at varying temperatures up to 120 min and then incubated at 37 degrees C for an additional 2 h with the tracer present for the final hour of incubation. Higher as well as lower than physiological temperatures depressed tracer amino acid incorporation. Recovery of myocardial protein synthesis from thermal injury was incomplete when the experimental temperature deviated by 6 degrees C or more from the control and exposure exceeded 60 min. In addition, tracer amino acid incorporation on reoxygenation and return to 37 degrees C in muscles exposed to anoxia at 25 degrees C did not differ from that in muscles exposed to anoxia at 37 degrees C. Specific activity of the intracellular amino acid pool was directly measured in appropriate experiments and variation of this parameter could not account for the depressed tracer amino acid incorporation. Likewise methylprednisolone (10-5 M), chloroquine phosphate (10-5 M), and glucose (15 mM), if present during hyperthemia, did not ameliorate thermal damage. It is concluded that hyperthermia as well as hypothermia can cause irreversible alterations rather than reversible inhibition of myocardial protein synthesis.


Conduction in descending spinal pathways initiated by somatosympathetic reflexes. In anesthetized, paralyzed cats, the effects of stimulation at the dorsolateral sulcus (DLS) of the spinal cord at the C8 segment were recorded from the T2 white ramus. Stimulation of the DLS at the C8 segment produced evoked responses which had average conduction latencies of 13.3, 25.8, and 43.4 ms and were designated as the early, intermediate, and late response, respectively. Intermediate and late evoked responses were also recorded when the contralateral funiculus, the third or late evoked response was abolished or greatly attenuated, but the intermediate response was still observed although it was diminished in amplitude. The early evoked response was usually observed with stimulation at the ipsilateral C8 segment following placement of the lesion. These data suggest that afferent impulses, which ascend to supraspinal segments of the central nervous system, are transmitted to preganglionic neurons of the sympathetic nervous system through descending pathways in the dorsolateral funiculus of the spinal cord. Stimulation of afferent fibers on the ipsilateral or contralateral side of the spinal cord produces volleys which ascend unilaterally and descend bilaterally to preganglionic neurons. The pathways producing the intermediate evoked response, which was still observed after an ipsilateral lesion was made in the spinal cord, may include both the ascending pathway and other connections with the preganglionic neurons.


Acute effects of lithium on the renal concentrating mechanism in a primate. Although chronic lithium therapy has been associated with a defect in the urinary concentrating mechanism, short-term renal effects of lithium have received little attention in the intact animal. Solute-free water reabsorption (T-cH2O) and free water clearance (CH2O) were measured in primates of the genus Galago under control conditions and while animals were receiving either 0.5 mmol/kg-h or 1.0 mmol/kg-h lithium chloride (135 mM) intravenously. CH2O was unchanged by lithium infusion (P greater than 0.10), whereas T-cH2O was significantly depressed at all levels of osmolal clearance (P smaller than 0.01). Spontaneous recovery of near-normal T-cH2O was documented in two animals within 1 wk following acute lithium infusion. In addition it was observed that lithium-induced depression of T-cH2O could be partially prevented by pretreatment with intravenous amiloride. These results suggest that alterations in the renal concentrating mechanism can occur rapidly following the onset of lithium administration. They also imply that impairment of the renal concentrating mechanism by lithium is due at least in part to antagonism of the action of vasopressin on the collecting duct.


Relation between length, isometric force, and O2 consumption rate in vascular smooth muscle. The length-tension and length-oxygen consumption rate relationships were studied in bovine mesenteric vein at 37 degrees C. The absence of spontaneous mechanical activity permits straightforward interpretation in terms of active (smooth muscle) and passive components of the vein wall. Longitudinal loops, the predominant smooth muscle component being oriented in the longitudinal (axial) direction, were maximally stimulated using epinephrine (2-5 mug-ml-1). An optimum length for isometric tension development was exhibited at which the passive tension was 25% of the total tension. The population regression indicated that tension was developed at lengths which ranged from 0.33 to 1.41 times the length at which maximum tension was developed. Oxygen consumption was measured using a Clark-type polarographic electrode. Basal oxygen consumption was 0.432 plus or minus 0.014 (n equal to 121) mumol-min-1 (g dry wt)-1. The basal rate was found to be independent of the passive tension. Under conditions of maximal stimulation, the oxygen consumption rate at L-o, the resting length at which the tissue maintained 1 g-wt passive tension, was approximately twice the basal rate. The length dependence of the suprabasal oxygen consumption was parallel to that of the active isometric force. This parallel relation reflected a linear relation between active isometric force (deltaP-o) and suprabasal oxygen consumption rate (deltaJ-o2). The slope of the deltaJ-o2-deltaP-o linear regression was 0.142 plus or minus 0.013 nmol O2-MIN-1 (G-WT-CM)-1. DeltaJ-o2 at the minimum contracted length, at which no active force was developed, was 15-20% of the deltaJ-o2 measured when maximum isometric force was developed. This provides an upper bound to the rate of chemical energy utilization required for activation processes. The length dependence of active isometric force and chemical energy utilization is most simply interpreted in terms of a sliding-filament model.


Effect of posterior hypothalamic stimulation on ventricular fibrillation threshold. The effect of posterior hypothalamic stimulation on cardiac susceptibility to ventricular fibrillation (VF) was studied in 34 dogs. VF threshold was determined by inducing a sequence of early extrasystoles (R/T pulsing). Hypothalamic stimulation was associated with sinus tachycardia, systemic hypertension, and a 40% reduction in VF threshold. The effects of hypothalamic stimulation on the VF threshold persisted when heart rate acceleration and the pressor response were prevented. Cervical vagotomy and bilateral adrenalectomy were likewise without effect on fibrillation threshold changes. However, the decrease in threshold was abolished by beta-adrenergic blockade. It is concluded that the reduction in VF threshold associated with hypothalamic stimulation derives from the direct action of sympathetic nerves upon the myocardium, rather than from secondary hemodynamic effects.


Cardiovascular chemoreflexes from the perfused innervated ileum of the cat. The vascular supply of innervated segments of ileum in urethan-anesthetized cats was perfused by an electrolyte-glucose solution, containing heparinized cat blood. Addition of acetylcholine or nicotine to the perfusion inflow was followed by increases of systemic arterial pressure. Calculated mean concentrations of 32 mug/ml acetylcholine or 35 mug/ml nicotine in the perfusion fluid induced mean pressor responses of 19 and 23 mmHg. These responses began within 2-6 s, reached a maximum within 20 s, were unaffected by vagotomy, and were frequently accompanied by cardiac acceleration and increase in rate and depth of respiration. Evans blue in the perfusion fluid did not enter the general circulation. Systemic responses were abolished or markedly decreased after perfusion of 40-180 mg procaine through the innervated gut segments or by cooling the nerve fibers between the perfused ileum and the body of the animal. In itself, procaine injected into the isolated circulation or nerve cooling commonly induced decreases of arterial pressure. The vascular isolation of the perfused segments and the dependence of the systemic responses on the nervous connections indicate that the effects were reflex.


Synthesis of uric acid in isolated normothermic perfused mongrel and Dalmatian dog kidneys. Renal synthesis of uric acid (urate) in the dog was demonstrated by use of two isolated kidney preparations during pulsatile perfusion at 37 degrees C with artificial perfusate or with a plasma fraction. During perfusion of mongrel and Dalmatian dog kidneys with 0.5 mg of [14C]xanthine per 100 ml, a mean of 24.3 and 25.4 mug of [14C]urate per minute, respectively, entered either urine or perfusate after its synthesis in the isolated kidney. Approximately 6.2% of the combined extracellular radiolabeled urate formed in the isolated mongrel kidney was excreted in the urine and 15.7% in the urine of isolated Dalmatian dog kidneys. Recirculating the perfusate without the kidney did not convert any radioactively labeled xanthine to urate and therefore the radioactively labeled urate appearing in the urine and recycled perfusate must have been formed in the renal parenchyma. Renal synthesis of urate was blocked by the xanthine oxidase inhibitor allopurinol. In the presence of allopurinol, [14C]xanthine was excreted unchanged into the urine.