Impotence in diabetes mellitus.

Impotence in diabetes mellitus. Long-standing psychogenic factors underlying impotence in diabetic males may, in many cases, play a more significant role than does prematurely presumed organic disease. With an explicit sexual history, a committed couple, an explanation of the sexual responses, and specific exchange at home, the physician may comfortably and competently intervene to provide enlightened sex therapy.


Diabetes mellitus and left ventricular function. Chronic diabetes mellitus can alter left ventricular function independent of vascular effects. On the basis of available morphologic data in human and canine diabetics, alterations of myocardial interstitium may be the basis for this preclinical abnormality. The abnormal function is independent of apparent duration and treatment by diet, insulin, or hypoglycemic agents. It occurs in both sexes and is independent of age. Whether the observed functional abnormality progresses to clinical heart failure may depend on intensification of the underlying pathophysiology of the myocardium or superimposition of complications such as hypertension, obesity, and obstructive disease of the coronary vessels.


Permanent pervenous atrial pacing.

Permanent pervenous atrial pacing. A new J-lead has now been designed and manufactured for both animal and clinical studies. This lead has silastic tines proximal to the electrode, arranged so that they become entangled in the trabeculae of the appendage and hold the lead in place. Studies in ten dogs have shown excellent tissue fixation at the site of the tines, and only minimal scarring occurs at the site of the terminal electrode, with preservation of good P-wave amplitude and good stimulating thresholds for a period of four to five months (Figure 8, see next page). The lead designed for humans has been used successfully in 12 patients. Follow-up now extends to 19 months, with stable P-wave-triggered atrial pacing in eight patients, fixed rate atrial pacing in one, and A-V synchronized pacing in three. No lead dislodgement has occurred.


Chromosome anomalies in Canadian Guernsey bulls. The performance records of a group of Guernsey bulls used for artificial insemination revealed lower 60 to 90 day non-return rates as compared to that for bulls of the Holstein breed, and nine out of the 19 Guernsey bulls in this group exhibited fertility level below the average for this group. A cytogenetic survey to test whether or not the reduced fertility of these bulls was due to chromosome anomalies revealed a relatively high frequency of chromatid breaks and achromatic gaps in three out of 19 bulls while two carried 59 chromosomes each including a translocation chromosome. The 1/29 translocation heterozygote and the bulls showing achromatic gaps and chromatid breaks were among the five bulls which were consistently below the breed average in fertility as evidenced by the t test (P less than 0.01), whereas the bull with translocation 27/29 (G3) exhibited a non-return rate slightly higher than the breed average (P less than 0.01). It is possible that the chromosomally abnormal bulls contribute to increased returns to service not only because of the defective gametes they themselves might produce but also through their influence on the performance of their daughters.


Experimentally induced lead poisoning in goats: clinical observations and pathologic changes. The effects of orally administered lead acetate were investigated in 9 adult and 3 kid goats by clinical and necropsy studies. One kid and 6 adults died after having received from 100 to 1392.5 Gm each, given over periods of from 10 to 52 days. Anorexia, diarrhea and body weight loss occurred in all lead treated goats in the study. Basophilic strippling of red blood cells was found in 6 of 8 animals on which weekly hemograms were performed. The pathologic changes were essentially the same as those that have been recorded for other ruminant species with lead poisoning. Intranuclar acid-fast inclusions in the cells of the proximal convulted tubules of the kidney were demonstrated in 9 of 12 lead treated goats and in the liver parenchymal cells of 2 of these animals.


Feline calicivirus: purification of virus and extraction and characterisation of its ribonucleic acid. Purification of feline calicivirus was achieved by cycles of differential centrifugation and two cycles of sucrose gradient centrifugation. Feline calicivirus grown in the presence of Actinomycin D and 3H-uridine-5, sediments in 15% to 45% sucrose gradients and forms a peak of radioactivity which corresponds with the peak of infectivity. Ribonucleic acid (RNA) extracted from the peak radioactive fractions taken from the sucrose gradient sedimented as a single peak ahead of the 28S peak of cellular RNA. It was sensitive to ribonuclease and was presumed to be single stranded feline calicivirus RNA with sedimentation of 32S-35S. A single peak of radioactivity at 35S was extracted from purified virus by heating at 60 degrees for two minutes in 1% sodium dodecyl sulphate (SDS), or by heating at 37 degrees for 5 minutes at 1% SDS. Virus extracted at 37 degrees for 10 minutes in 1% SDS showed also a small peak at 16S and by 15 minutes at 37 degrees only a broad peak at 16S occurred. All peaks were susceptible to ribonuclease. A component sedimenting at 18S which was resistent to degradation by ribonuclease under the conditions outlined by Baltimore (4) and presumed to be double-stranded RNA was present in kitten kidney cells infected with feline calicivirus.


Element and chlorinated hydrocarbon content of commercial pet foods. An analytical survey has been conducted of 42 elements, p,p'-DDE, dieldrin andpolychlorinated biphenyls in 31 commercial canned pet foods. Neutron activation analysis, graphite furnace atomic absorption, anodic stripping voltammetry, electron affinity gas chromatography and other methods were used. Arsenic, bromine, cadmium, chromium, mercury, selenium and DDE were highest in fish-containing cat foods. Lead was most consistently high in those products containing chicken. Barium, nickel and tin also appeared high in certain of the samples.


Hypercholeresis in turkeys following the ingestion of Crotalaria spectabilis seeds. Young female turkeys received diets containing Crotalaria spectabilis seeds for 18 weeks. Mean values for total bile flow, biliary bile acid excretion, bile acid-dependent flow and bile acid-independent flow were significantly higher in crotalaria-fed turkeys than in controls. The hypercholeresis observed in crotalaria-fed birds involved both bile acid-dependent and bile acid-independent components of bile. Crotalaria-fed turkeys developed biliary hyperplasia. Liver weights were similar in the two groups. Since increases in 14C-erythritol clearances paralleled increases in total bile flow in crotalaria-fed turkeys (14C-erythritol bile to plasma ratios were similar in both groups), it was evident that the hypercholeresis in crotalaria-fed turkeys did not involve the ductal/ductular component of bile. Little or no ductal/ductular bile flow occurred in either group since total bile flow was equal to erythritol clearance and extrapolation to zero erythritol clearance yielded zero bile flow rates in both groups. Crotalaria-fed turkeys exhibited significantly higher biliary concentrations of chlorides (associated with lower sodium , potassium and bicarbonate concentrations) than did control birds. Validation of the use of 14C-erythritol clearance for the estimation of canalicular bile flow in turkeys was provided both by substantial decreases in bile to plasma 14C-erythritol concentration ratios following the injection of avian vaso-active intestinal peptide and the failure to demonstrate chromatographically the presence of radioactive metabolites of 14C-erythritol in plasma.


Recurrent esophageal obstruction due to squamous cell carcinoma in a horse. Squamous cell carcinoma involving the pars esophagea of the stomach caused recurrent esophageal obstruction in an 11 year old Pinto gelding. The tumor encircled the esophagus and was attached to the diaphragm, spleen, aorta, left adrenal gland and kidney. Definitive diagnosis was provided by biopsy of the mass via standing left flank laparotomy.


The effect of changes in blood glucose on the motility of the duodenum in sheep. Experiments have been carried out on four adult ewes to determine the effects on duodenal motility of intravenous or intraduodenal infusion of glucose solution and intravenous injection of insulin. At blood glucose levels below 80 mg%, the mean frequency of duodenal contractions was 1.6/min, but following the establishment of hyperglycemia by either intraduodenal or intravenous glucose infusion, contraction frequency fell to 0.9/min. The strength of contraction was unaffected.


Expired gas monitoring by mass spectrometry in a respiratory intensive care unit. The application of a medical mass spectrometer for the monitoring of respired gases in the respiratory intensive care unit of a community hospital is reviewed. This monitoring system is routinely used with intubated patients for periodic monitoring of end-tidal CO2 tensions (PETCO2), FIO2, and PETO2 dead space to tidal volume ratios, and the determination of AaDO2; the value of these measurements is discussed. It is especially useful for continuous monitoring at critical points in the patient's course such as weaning from the ventilator, determining optimal ventilator settings, monitoring, unstable nonintubated patients, and in better defining the pathophysiological disturbances impeding patient progress, examples of which are presented. Preliminary observations suggest it may also provide a simple technique for determining optimal expiratory retard settings. The initial cost of such a system is justified by the benefit to the patient, i.e., reduction in the frequency of nonessential arterial blood gas determinations, shortened weaning period, and early detection of potentially dangerous trends. Technical problems encountered with this system and potential future uses are also discussed.


Mass spectrometry for innovative techniques of respirator care, ventilator weaning and differential ventilation in an intensive care unit. The medical mass spectrometry as a monitoring instrument in a respiratory intensive care unit (RICU) is described. Its uses, both routine and as a tool for innovative techniques in respiratory care, are many. As an adjunct to traditional and intermittent mandatory ventilation (IMV) weaning techniques, monitoring of expired respiratory gases can hasten the safe removal of patients from mechanical ventilators. A specialized technique of dealing with ventilating the lungs differentially when their mechanical properties differ is described to illustrate the versatility of the instrument. In critical care areas, monitoring of patients with respiratory problems should include continuous monitoring of end-tidal or expired CO2.


Mass spectrometry: application in the exercise sciences. This paper outlines a computerized system for monitoring physiological functions during exercise, using a mass spectrometer for analyzing the concentration of the mixed expired air. Examples are provided illustrating the operation of this system in both research and clinical situations. The most remarkable aspect of the system is its versatility, coupled with its accuracy. While the applications reviewed in this paper are rather narrow, work has been initiated using the mass spectrometer to measure residual lung volumes by the oxygen dilution technique, cardiac output by the CO2 rebreathing technique, and total body density by the helium dilution technique. The application of the mass spectrometer into other areas most certainty will occur in the near future.


Factors influencing successful discontinuance of mechanical ventilation after open heart surgery: a clinical study of 41 patients. Circulatory, respiratory, and metabolic variables were measured with a mobile clinical bedside unit in 41 patients during the first 48 hours after open heart surgery. Calculations were carried out off-line by a computer program. The variables were measured during controlled mechanical ventilation and compared with those obtained during spontaneous breathing and after resumption of mechanical ventilation; attempts at spontaneous breathing were categorized as successful or unsuccessful. The variables were compared before, during, and after the successful and the unsuccessful attempts at spontaneous breathing. In the series as a whole, the onset of spontaneous breathing was characterized by increases in cardiac output, radial arterial and pulmonary arterial pressures, and mixed venous oxygen tension (PVO2) and content (CVO2), as well as diminished arterial and mixed venous oxygen content differences (avDO2); no significant changes in oxygen consumption (VO2) were seen. Unsuccessful attempts disturbed the patient's physiological equilibrium by reducing oxygen delivery and not increasing VO2, while increasing ventilatory work. In general, resumption of controlled ventilation restored the physiological variables to their control conditions. Successful attempts at spontaneous breathing did not greatly affect the physiological variables. The indication for resumption of controlled ventilation after periods of spontaneous breathing is the combination of increased ventilatory work with diminished circulatory and respiratory functions.


The measurement of myocardial tissue gas tensions by mass spectrometry. The mass spectrometer is a well established tool for the measurement of the partial pressures of gases in respiratory gas mixtures and in flowing blood. Only recently has mass spectrometry been applied to the measurement of gas tensions in tissue. Both blood and tissue gas tension measurements by mass spectrometry were made possible by the development of a special sampling catheter surrounded at its tip by a gas--but not liquid--permeable membrane. The partial pressure of each gas at the external surface of the membrane determines the flow of that gas across the membrane which, in turn, is measured by the mass spectrometer. The use of a Teflon membrane permits tissue measurements because its low permeability to gases reduces the sampling rate of gas molecules with the result that the depletion of gas molecules in the tissue surrounding the membrane is minimal. Mass spectrometry is the only technique whereby it is possible to measure regional tissue pO2 and pCO2 and other gas tensions simultaneously and continuously. One application of mass spectrometric tissue gas tension measurements is the monitoring of myocardial ischemia through measurements of myocardial tissue pO2 and pCO2. We have reviewed the work of others and ourselves in this field.


Imipramine (Tofranil) intoxication: a case report and review of management. A fatal case of imipramine intoxication is reported. The patient presented with the typical findings of imipramine poisoning: coma, fixed dilated pupils, cardiac disturbances, and hyperpyrexia which, at first, were attributed to head trauma. The importance of prompt recognition of such poisoning is emphasized, and a general scheme of treatment is outlined.


Automated respiratory gas monitoring of critically injured patients. Since 1971, we have used a mass spectrometer system for automatic hourly sampling of airway gases on a 24-hour basis in our 12 bed Critical Care Unit. Used in conjunction with arterial and mixed-venous blood samples, the availability of end-tidal O2 and CO2 values allows early identification of increasing AaDO2 and aADCO2 gradients. The ability to monitor end-tidal CO2 allows the monitoring of the adequacy of alveolar ventilation both in patients on and following removal from mechanical ventilation. Continuous information of the end-tidal PCO2 is of particular value in the management of patients with severe head injury.


Complications of long tracheostomy tubes. Complications of long tracheostomy tubes are not generally appreciated. We report three cases which illustrate that long tracheostomy tubes may impinge on the carina or, less commonly, intubate the right main-stem bronchus, with resultant atelectasis of the left lung. Since larger diameter tracheostomy tubes are also longer, they are much more likely than narrow tracheostomy tubes to produce this complication. The tracheostomy tube position should be checked frequently, especially in patients who develop atelectasis and pneumonia of the left lung.


A pediatric flexible fiberoptic endoscope. Clinical experience with a flexible fiberoptic endoscope constructed for children is described. The endoscope fits through a 3.5 mm endotracheal tube without removing the tube adaptor. The endoscope was used on artificially ventilated newborns and infants for determining the position of the endotracheal tube, the integrity of the tracheal mucosal wall, and possible obstruction of the endotracheal tube. Visualization of the interior of the tube and the airways can be performed without moving the infant from the incubator. The instrument aids in the management of children requiring prolonged respiratory support. The most common lesion detected was trauma to the tracheal mucosal wall by the suction catheter.


Comparison of G-, Q-, and R-banding in 28 cases of chromosomal abnormalities. Twenty-eight cases of chromosomal abnormalities were ascertained using G-banding. Seventeen of these had structural abnormalities of a complex nature and are discussed in detail. An independent assessment of chromosome abnormalities was carried out using sequential Q- and R-banding. In no case was there a difference in the identification of the abnormal chromosome, but in two cases a more precise localization or definition of the abnormality was obtained from the R-banded cells. In one case the initial diagnosis of the terminal deletion was altered to interstitial deletion; in the second case a break point in one chromosome involved in a reciprocal translocation was found to be in a different band by R-banding. In several others better delineation of break points or confirmation of complex abnormalities was obtained from the R-banded cells. R-banding was especially helpful in the localization of break points because of the color differentiation obtained with acridine orange. Q-banding was not found to have added any additional information. It was concluded from this study that the use of both G-banding and R-banding in complex abnormalities proved worthwhile.


Giemsa-banding and the identification of the Y/autosome translocation in the african marsh mongoose, Atilax paludinosus (Carnivora, Viverridae). The diploid chromosome number of 35 in the male and 36 in the female African marsh mongoose, Atilax paludinosus, has been confirmed. C- and G-banding analyses have shown that the Y chromosome is probably translocated onto the proximal end of the acrocentric partner of a heteromorphic autosomal pair (C3). The other partner is a subtelocentric with a heterochromatic short arm. During the translocation process, this short arm was removed and presumably lost. The sex determining mechanism in Atilax could be written as XX in the female and XYA-A in the male.


Location of nucleolar organizing regions on the chromosomes of the Syrian hamster (Mesocricetus auratus) and the Djungarian hamster (Phodopus sungorus). Terminal chromosome associations ("satellite associations") in ASG-banded preparations have been used to determine the number and location of staellites in the Syrian hamster (Mesocricetus auratus) and the Djungarian hamster (Phodopus sungorus). Five pairs of satellites are found in the former and four in the latter. Nucleolar organizing regions (NORs) were visualized with the Ag-AS silver precipitation technique, and their number and position corresponded exactly with the number and position of satellites in Phodopus, where positive chromosome identification can be made in the absence of banding. Numerical agreement is exact in Mesocricetus as well, and the morphology of the silver-tagged NOR-bearing chromosomes strongly suggests that corrrespondence also occurs in this species.


Chiasmata, meiotic univalents, and age in relation to aneuploid imbalance in mice. Chiamata were counted and paired and unpaired configurations at first meiotic division and chromosome errors at second meiotic division were assessed at different ages in males and females of two strains of laboratory mice. In the females a decrease of chiasma frequency and an increase of univalents at first meiotic metaphase (MI) were confirmed. In the males, diakineses had higher chiasma frequencies (in the range of the female MIs) and fewer univalents than the MIs had. In these male cells there was no decrease of chiasmata or increase of autosomal univalents with age, and there were some interstrain differences. In the older females there was no parallelism between the frequencies of univalents at MI and the chromosome errors that could be identified at second meiotic division; these were fewer than might be expected on the assumption that all the univalents were true univalents. The relevance of this finding to the question of the nature of most of the univalents observed at first meiotic division in aged female mice is discussed.


A child with presumptive monosomy 21 (45,XY,-21) in a family in which some members are Gq-. Presumptive monosomy for chromosome 21 was found in a male child with multiple malformations and severe psychomotor retardation. Chromosome analyses of cells from blood and skin samples were performed at intervals during the first few years of his life. In preparations stained with nonbanding was well as quinacrine, Giemsa, and reverse acridine orange banding techniques, only one No. 21 chromosome could be detected with no apparent abnormalities of the other chromosomes. The proband's phenotypically normal father, paternal grandfather, brother, and paternal aunt have a deletion for a short segment of the long arm of a G-group chromosome. Genetic-marker studies allow the exclusion of a number of blood groups as being associated with No 21. There is inconclusive evidence suggesting that expression of the Duffy blood group, which has been mapped to chromosome 1, may be influenced by genetic information on chromosome 21. This family is of potential value for further gene-mapping studies.


Chromosome banding pattern relationships of hares, rabbits, and pikas (order Lagomorpha). A phyletic interpretation. The chromosome banding patterns of the domestic rabbit, Oryctolagus cuniculus, the brush rabbit, Sylvilagus bachmani, and the snowshoe hare, Lepus americanus, are nearly identical except for minor differences in the amount of constitutive heterochromatin present. The major mechanisms of chromosome evolution in leporid lagomorphs are centric fusion and addition of heterochromatin. The G- and C-banding patterns of the pika, Ochotona princeps, revealed little easily recognized structural homology with the leporid species. Several tentative banding pattern matches were found for segments of some chromosomes of Ochotona, indicating that tandem fusions may have been responsible for structural modification of the early lagomorph genome. Chromosome evolution in the lagomorphs and the use of chromosomal data in studies of mammalian systematics are discussed.


Reduction of blood usage in open heart surgery. A series of 142 adult patients undergoing open-heart surgery were studied. All known blood-conservativing methods were utilized in an attempt to use as little blood as possible. Hemodilution, autologous transfusion, prevention of wasting of blood, and management of postoperative anemia were the measures employed. An average of 2.66 units of blood were given per patient during the entire hospital stay. Twenty patients were not given any blood at all. The patients were removed from cardiopulmonary bypass without difficulty when the hematocrit reading was in the high teens or low twenties. Later in the postoperative period the patients seemed to progress without difficulty with hematocrit readings of 22 to 25 percent.


Diagnosis of gastric aspiration by fiberoptic bronchoscopy. At the time of bronchoscopic observation, 28 of 31 patients proved to have aspirated gastric contents by the presence of gastric contents in the trachea or by direct observation of gastric aspiration followed by respiratory distress and erythema of subsegmental bronchi. Since gastric aspiration is a difficult diagnosis to make and few objective data are available to make the diagnosis, the present study would indicate that early fiberoptic bronchoscopic observation of the tracheobronchial tree is a useful procedure to establish a definitive diagnosis and to allow proper planning for clinical management.


Familial supravalvular aortic stenosis. Report of a large family and review of the literature. Familial supravalvular aortic stenosis has been recognized as a distinct syndrome. A large family with five proven cases and a review of the literature on familial supravalvular aortic stenosis are presented. The diagnosis was substantiated in all 63 cases by cardiac catheterization, surgery, or postmortem examination.


Effect of emotional stress on platelet aggregation in humans. In 16 young house physicians, each of whom presented a case at grand rounds, the effect on platelet function of the emotional stress involved in presenting the case was determined. Platelet-aggregation curves, using adenosine diphosphate and epinephrine, were determined immediately before, immediately after, and seven days after stress. Platelet aggregation was diminished during the stress period in 15 of the subjects. These findings may possibly be of importance in the relationship between stress and myocardial infarction; they also suggest that the emotional state of the patient must be considered when interpreting platelet-aggregation curves.


Unusual electrocardiographic changes in spontaneous pneumothorax. A young woman with spontaneous left pneumothorax had a phasic voltage alternation of her electrocardiogram that resolved with expansion of the lung. Likely explanations for this phenomenon are a respiratory dependent change in cardiac anatomy and a change in the volume conductor with respiration.


Endobronchial tuberculosis progressing to bronchial stenosis. Fiberoptic bronchoscopic manifestations. Severe stenosis of main-stem and segmental bronchi occurred in a 79-year-old woman with previously and adequately treated endobronchial tuberculosis. Symptoms and physiologic abnormalities did not occur until more than three years after diagnosis and initiation of therapy.


Congenital complete atrioventricular block and prolapsing mitral valve. Congenital complete atrioventricular block and prolapsing mitral valve are described in a 41-year-old woman who exhibited ventricular arrhythmias and symptoms initially attributed to her atrioventricular block. The importance of physical examination to elicit clues in the diagnosis of prolapsing mitral valve is emphasized.


Surgical complications of cervical and mediastinal tuberculous adenitis in an infant. An infant whose miliary tuberculosis was resolving after five months of chemotherapy developed a tuberculous cervical lymphatic abscess followed shortly thereafter by life-threatening tracheal compression from enlarged tuberculous mediastinal nodes. Both of these complications required surgical drainage. Chemotherapy alone may be ineffective in the management of lymphadenitis caused by Mycobacterium tuberculosis.


Tracheoesophageal and aortoesophageal fistulae complicating corrosive esophagitis. A 51-year-old man suffered third-degree caustic burns of the esophagus and proximal two-thirds of the stomach. A tracheoesophageal fistula developed, and surgery was performed to exclude the esophagus from gastrointestinal reflux and to divert the oral secretions. An uneventful postoperative course was interrupted on the 27th day after the burn by massive hemoptysis and sudden death. Autopsy revealed an aortoesophageal fistula in addition to a tracheoesophageal fistula.


Posthyperventilation apnea associated with severe hypoxemia. We studied a 14-year-old girl who suffered fractures of her mandible and tegmen following a fall from a balance beam. Thirteen days after hospitalization, she developed severe, protracted, recurrent episodes of hyperventilation; subsequently, she suffered posthyperventilation apnea, which at times was prolonged and association with severe hypoxemia with an arterial oxygen pressure as low as 25 mm Hg. The patient was treated with added dead space and chlorpromazine hydrochloride (Thorazine). Postulated mechanisms for her disorder are discussed. The importance of close clinical and laboratory observation in similar cases is stressed.


Acquired continuous murmur associated with acute pulmonary thromboembolism. Two cases of a continuous murmur following an acute pulmonary embolic episode are presented, and eight previously reported cases with an acquired postembolic continuous murmur (found in a review of the literature) are discussed. This finding is present in both chronic and acute pulmonary embolism and is suggestive of significant embolic obstruction. Although the continuous murmur is an unusual sign in patients with pulmonary embolism, its auscultation is often quite distinctive, and its appearance may lead to more definitive diagnostic studies when the presentation or associated clinical findings are nonspecific.


Ventricular septal defect complicating acute myocardial infarction. Echocardiographic demonstration confirmed by angiocardiograms and surgery. The echocardiographic findings in one patient with a ventricular septal perforation as a result of an acute anteroseptal myocardial infarction are presented. Continuous echocardiographic scanning enabled us to demonstrate a septal discontinuity below the atrioventricular junction. The correct echocardiographic diagnosis was confirmed angiocardiographically. After surgical repair of the ventricular septal defect, the echocardiogram failed to reveal the septal discontinuity previously present. A search of the literature did not disclose any report of similar echocardiographic findings.


Myocardial infarction in younger women. Associated clinical features and relationship to use of oral contraceptive drugs. In a study of thromboembolism and oral contraceptive drugs, 136 cases of myocardial infarction in women aged 30 to 44 years were identified, a rare disease in women of this age group. Data from their hospital medical records were compared with those of several other groups, including women without chronic disease admitted for various acute or elective conditions unrelated to thromboembolism, patients with thromboembolic disease other than myocardial infarction, and women queried or examined in the National Health Survey. The following attributes were found to be associated with myocardial infarction in younger women: presence of diabetes; hypertension; history of increased cigarette smoking; and hypercholesterolemia. A history of the use of oral contraceptive drugs was found with greater frequency in cases than in controls. The literature on the possible association of myocardial infarction and the use of oral contraceptives was reviewed.


Pulmonary hemorrhage in fiberoptic transbronchial biopsy. Transbronchial forceps biopsy via the flexible fiberoptic bronchoscope is described as a "safe," high-yielding procedure, but the potential danger of serious hemorrhage is of concern to chest physicians. In a collected series of 438 patients, the incidence of mild to "explosive" hemorrhage was 9 percent in "routine" cases, 29 percent (eight) in 31 immunosuppressed patients, and 45 percent (five) in 11 uremic patients. One death resulted from massive hemorrhage. A new "wedge" method of transbronchial forceps biopsy is now being utilized in our bronchoscopic unit. The tip of the flexible fiberoptic bronchoscope is lodged into the appropriate segmental bronchus to tamponade any bleeding and, thus, prevent blood from flooding the airway. Careful screening of patients and competence in procedural techniques are necessary. Otherwise, transbronchial forceps biopsy should be performed through a rigid open-tube bronchoscopicronchoscope or performed through a rigid open-tube bronchoscope or lung tissue should be obtained via thoracotomy.


Flexible fiberoptic bronchoscopy and endobronchial tamponade in the management of massive hemoptysis. Flexible fiberoptic bronchoscopic examination with systematic bronchial lavage was performed in ten patients with massive hemoptysis. Localization of the bleeding to the distal segments of the bronchial tree and endobronchial balloon tamponade were achieved in all cases. The technique is rapid, simple, and effective in controlling life-threatening hemoptysis in patients who are unsuitable for resection due to inadequate pulmonary reserve or other causes.


Autologous blood transfusion during cardiopulmonary bypass. Immediately prior to cardiopulmonary bypass, two units of blood were removed from each of 25 patients undergoing open-heart surgery, and the autologous blood was reinfused after cessation of support with the pump oxygenator.  Pertinent data on blood balance and hematologic measurements were compared to a matched group of control subjects. There were no significant differences in the amount of operative or postoperative bleeding, the requirements for homologous blood and blood products, or the amount of protamine needed for neutralization of heparin.


Natural history of unstable angina with medical or surgical therapy. In order to establish the natural evolution of unstable angina under medical treatment and to determine the possible benefits of revascularization surgery, 113 patients were studied; 51 received medical treatment (24 with intermediate syndrome and 27 with progressive angina), and 62 others received surgical treatment (28 with intermediate syndrome and 34 with progressive angina). After a mean follow-up of 32 months, the mortality in the medically treated groups was 46 percent (11/24) with intermediate syndrome and 7 percent (2/27) with progressive angina (P less than 0.005), and the incidence of myocardial infarction was 38 percent (9/24) and 7 percent (2/27), respectively (P less than 0.01). Moreover, in comparing cases treated medically or surgically, the mortality was as follows: intermediate syndrome treated medically, 46 percent (11/24) vs 11 percent (3/28) in those treated surgically (P less than 0.005); and progressive angina treated medically, 7 percent (2/27) vs 9 percent (3/34) in those treated surgically (P = 0.85). The incidence of myocardial infarction was as follows: intermediate syndrome treated medically, 38 percent (9/24) vs 14 percent (4/28) in those treated surgically (P less than or equal to 0.056); and progressive angina treated medically, 7 percent (2/27) vs 12 percent (4/34) in those treated surgically (P greater than 0.55).


Hospitalization needs during an outpatient rehabilitation program for severe chronic airway obstruction. The number of days of hospitalization for respiratory disease following entry into an outpatient pulmonary rehabilitation program was reviewed for 44 patients with chronic airway obstruction whose hospitalization records were available for the year prior to entry into the program. A significant reduction in the number of days of hospitalization occurred in patients for each of the four years following entry into the program, compared to the year prior to therapy.


A comparison of two bipolar exercise electrocardiographic leads to lead V5. ST-segment depression and slope were compared in three lead systems (V5, CC5, and CM5) and in two groups of patients using both visual analysis of electrocardiographic paper and computerized techniques. Bipolar lead CC5 was found to be comparable to lead V5 when visual analysis of electrocardiographic recordings was utilized. Bipolar lead CM5 was found not to be comparable to lead V5 and to be less sensitive if classic criteria for slope were used. The technique of computerized analysis mad measurements of slope and amplitude to a reproducible level not possible with the standard technique. Statistically significant differences were found between the exercise electrocardiographic leads utilizing computerized electrocardiographic analysis . We conclude that computerized techniques of electrocardiographic analysis require new criteria for defining an abnormal repolarization response. The criteria must be specific for different electrocardiographic leads if the repolarization changes in these leads are to have comparable diagnostic significance.


Long-term efficacy and safety of nebulized metaproterenol solution in bronchial asthma. A 5-percent solution of the sympathomimetic bronchodilator, metaproterenol sulfate (Alupent) was evaluated by comparison with an 0.5-percent solution of isoproterenol in a double-blind crossover study before and after 60 days of inhalation of metaproterenol administered at least four times daily via a hand-bulb nebulizer. Data from tests of pulmonary function obtained in 27 asthmatic patients indicated that metaproterenol sulfate in this dose form surpassed isoproterenol in the duration of effect after seven weeks of continuous administration. Side effects did not necessitate the interruption of metaproterenol therapy. No evidence of the development of tolerance to the drug was shown by any of the patients at the end of the study.


Coarctation of the aorta in children and adolescents. Surgical treatment and review of 120 patients. Between September 1967 and April 1975, a total of 120 patients between one day and 20 years of age underwent surgery for coarctation of the thoracic aorta. Thirty-two patients were below two years of age (group 1) and 88 were above two years (group 3). All patients in group 1 initially had congestive heart failure. Twenty-eight had associated cardiac defects, and 18 had signficant pulmonary arterial hypertension (greater than 50 mm Hg). Operative deaths occurred only in group 1, all in infants below five months of age. Common features in the 13 deaths were congestive heart failure, pulmonary hypertension, patent ductus arteriosus, large ventricular septal defect, concomitant pulmonary arterial bandling or open-heart procedures. The only recurrence occurred in an infant first operated at 14 days of age. Resection of aortic coarctation can be safely performed as an elective procedure; however, it still presents a high surgical risk in infants with associated intracardiac defects. Late follow-up shows the salutary effects of repair of the coarctation on hypertension.


Plug closure of patent ductus arteriosus by transfemoral catheter method. A comparative study with surgery and a new technical modification. Plug closure of patent ductus arteriosus without thoracotomy is reliable and can be a good alternative to surgical closure for selected patients. We report our experiences with plug closure in 87 consecutive patients (age range, 3 to 38 years). Closure was successful in 83 patients (95 percent). There has been no mortality, and the failure in four patients (5 percent) was mainly due to an oversized ductus. A major complication during the procedure was dislodgment of the plug into either the aorta or the pulmonary artery, which occurred in five patients (6 percent). The late results were quite satisfactory, with no recurrence of shunting or any other complications. Comparison of these results with those of 100 patients treated surgically showed that the new catheter method did not seem to carry a higher risk but had certain advantages over thoracotomy. A simpler and less time-consuming method using a single catheter has been devised and successfully used in the most recent nine patients without failure. Simplification of the technique has signficantly reduced the time of the procedure and the dose of radiation.


Role of selected muscles of respiration as influenced by posture and tidal volume. Studies of the activity of accessory respiratory muscles were conducted in 30 normal subjects (15 male and 15 female subjects, age 5 to 62 years). Electromyograms were recorded over the right serratus anterior muscle and the adjacent sixthe intercostal space, and the results were correlated with tidal volume. Phasic respiratory activity in the serratus anterior muscle was detected in every subject but was markedly affected by the prevailing posture and level of ventilation (appearing at mean tidal volumes equivalent to 60.5 percent of vital capacity when subjects were standing relaxed, and equivalent to 35.2 percent of vital capacity when subjects were seated, leaning forward with elbows supported). The activity was predominantly inspiratory in timing but in some subjects extended into early expiration. No significant differences were noted in subjects of different ages, sex, height, or weight. Similar results were recorded from the inspiratory intercostal muscle. On the basis of these findings, we conclude that, contrary to reports, the serratus anterior muscle should be classified as an accessory muscle of respiration, at least at increased levels of ventilation, and that its activity is most pronounced in postures that place the muscles' origin in an advantageous position for moving the ribs.


Severe bullous emphysema. Successful surgical management despite poor preoperative blood gas levels and marked pulmonary hypertension. Surgical removal of giant pulmonary bullae is usually considered inadvisable in patients with either hypoxemia or hypercapnia. A successful operation was performed on a patient with both hypoxemia and hypercapnia. Preoperative and postoperative physiologic data are presented. Those data which suggested a favorable outcome are compared with those which did not.


Double prosthetic aortic valve. Late aortic erosion by Hufnagel valve. This is a case report of a patient who had one of the first Hufnagel ball-valve prostheses inserted in 1954 for severe aortic incompetence. He obtained relief of symptoms for 14 years before recurrence necessitated the insertion of a Starr-Edwards valve. The patients was symptom-free for another seven years before the original valve, which had been left in place, caused his death by eroding through the aorta.


Tracheal obstruction associated with a fungus ball. A case of primary tracheal candidiasis. An elderly patient developed acute respiratory failure secondary to airway obstruction by a Candida fungus ball which probably developed secondary to the use of broad-spectrum antibiotics when the patient had a decreased gag reflex while in a semicomatose state. The frequency of pulmonary fungus balls and their precipitating causes are briefly discussed. This potentially frequent, previously unreported complication should be recognized as a contributing factor in the development of acute respiratory failure requiring management by bronchoscopic techniques, as opposed to intubation.


Pneumonitis and pulmonary abscess associated with Moraxella nonliquefaciens. A 78-year-old man with pneumonitis and pulmonary abscess associated with Moraxella nonliquefaciens is presented. This organism was found by culture of both transtracheal aspirate and sputum. No previous reports have associated M nonliquefaciens with infection of the lower respiratory tract, although sinusitis and bronchitis have been reported. Possible predisposing factors in our patient included carcinoma of the larynx, as well as alcohol ingestion and cigarette smoking.


Tag-along pacemaker.

Tag-along pacemaker. In a R-wave-inhibited pulse generator, an increased interval between pacing artifacts giving an apparently slow rate was not indicative of impending battery failure in two patients. The pacing artifacts appeared as a tag-along phenomenon following a slow idioventricular rhythm as the result of an exit block due to (1) hyperkalemia and (2) perielectrode fibrosis. Simple tests demonstrated a normally functioning R-wave sensing circuit and pacemaker.


Coccidioidal pericarditis.

Coccidioidal pericarditis. A 26-year-old man developed coccidioidomycosis which resulted in myocarditis associated with congestive heart failure. A pericardial effusion developed and progressed to constrictive pericarditis. A pericardiectomy was performed and revealed that the pericarditis was due to Coccidioides immitis. The patient was subsequently treated with amphotericin B and showed marked improvement.


Tonsillar hypertrophy in an adult with obesity-hypoventilation syndrome. The use of the flow-volume loop. A 29-year-old obese man had marked tonsillar hypertrophy, somnolence, hypoxemia, and hypercapnia. Endotracheal intubation followed by tracheostomy relieved the hypoventilation. Weight loss improved the arterial blood gas levels. Sequential upright and supine flow-volume loops were compatible with a fixed upper-airway obstruction (such as would occur) with enlarged tonsils) prior to tonsillectomy. Following surgery, the expiratory flow-volume curve was abnormal in the supine position, consistent with the additional diagnosis of posterior pharyngeal hypotonia. Thus, in this patient the unique combination of tonsillar hypertrophy, posterior pharyngeal hypotonia, obesity, and a depressed respiratory center led to retention of carbon dioxide.


Precocious myocardial infarction after radiation treatment for Hodgkin's disease. A 26-year-old man received extensive cardiac radiation in the course of treatment of mediastinal Hodgkin's disease, and six years later, he experienced an acute myocardial infarction. Angiographic studies demonstrated extensive atherosclerotic abnormalities in the coronary arterial system. It is suggested that radiation-induced injury was a provocation of these precocious arterial abnormalities.


Unusually high pacemaker threshold in severe myxedema. Decrease with thyroid hormone therapy. In a patient with myxedema and complete heart block, an usually high pacemaker threshold was observed initially during transvenous right ventricular endocardial pacing. The pacemaker threshold gradually decreased with thyroid replacement therapy, suggesting that the lack of thyroid hormone in some patients might increase the pacemaker threshold.


Retroclavicular route for electrode placement in endocardial pacemakers. In order to avoid skin erosion and electrode infection in endocardial pacemakers placed through the external jugular vein, we direct the wires from their point of entry into the vessel to the pacing unit placed in the pectoral region by dissecting a retroclavicular tunnel. This can be done under general or local anesthesia, and so far we have not seen any injuries to the subclavian vein. In this way the entire pathway of the cables is deep enough so that they cannot be palpated through the skin, and the dangers of exposure through erosion are minimized.


Geographical variability in the pericentric inversion system of the grasshopper Trimerotropis pseudofasciata. Island and mainland populations of Trimerotropis pseudofasciata from California were compared with respect to the nature and extent of their percentric inversion systems. Island populations generally have more chromosomes polymorphic for centromere position than mainland populations and a considerably higher percentage of the genome in these island populations is in a structurally heterozygous state. Thus, although geographically peripheral, the islands provide habitats capable of supporting denser and more chromosomally polymorphic populations than the mainland. Chiasmata are generally localized to terminal positions in all classes of chromosomes and do not occur in the inverted regions of inversion heterozygotes. Chiasma frequency is highest in inversion homozygotes. It is hypothesized that the inversion system in T. pseudofasciata serves the dual synergistic function of preserving allelic sequences in the inversion region intact through inversion heterozygosity and limiting the generation of variability in regions outside the inversion by increasing terminal chiasmata. Additionally, it is argued that it is the gene sequence on only the inversion chromosome that is important in Trimerotropis. This condition contrasts with the "co-adapted" pattern seen in Drosophila where the gene sequences on both chromosomes in the inversion heterozygote are simultaneously important.


Study of mitomycin C-induced chromosomal exchange. Mitomycin C-induced sister chromatic exchange and quadriradial formation were studied in chromosomes from Muntiacus muntjac fibroblasts and A9, a transformed mouse cell line. We present the first direct cytological evidence for the induction of true somatic recombination involving homologous chromosomes. Analysis of the quadriradials from Muntjac cells indicates a non-random distribution with respect to the chromosomes involved and with respect to the points of conjunction. Sister chromatid exchange and quadriradial formation may reflect the outcome of repair processes involving a high frequency of homologous exchanges in the interphase nucleus.


The site of 5S RNA genes in primates. I. The great apes. A major site of genes for 5S RNA has been localized in representative members of the family Pongidae by means of hybridization in situ. These genes are shown to be concentrated in the most distal bands of the primate chromosome arm homologous to human chromosome 1q.


Nucleoli and ploidy in Potorous cells (PTK2) in vitro. Most cells of the male PTK2 cell line contain one nucleolus, and they are diploid. However, a proportion of cells have more than one nucleolus. Cells with two and three nucleoli were isolated and cloned into viable populations. Greater than 90% of the cells in these clonal populations maintained the abnormal nucleolar number of the originally isolated cell. Karyotype analysis of cells with two and three nucleoli demonstrated that the cells were respectively tetraploid and hexaploid. It was concluded that in PTK2 cells, nucleolarity is a good index of ploidy even if the ploidy level is abnormal. Furthermore, long term monitoring of the tetraploid cells demonstrated virtually no tendency towards reversion to the diploid condition as suggested by other studies in Potorous.


Configurational changes in chromatids from helical to banded structures. Induction of configurational changes in the helical chromatids of air dried chromosomes was used to explore the mechanism of G-banding. From the water-Giemsa stained metaphase spreads of Chinese hamster cells, chromosomes having clearly helical chromatids were selected and photographed. Then the chromosomes were decolorized, treated with trypsin, and restained with saline-Giemsa (1X SSC). Such procedures were repeatedly carried out upon the same chromosomes. Subsequent examination of the chromosomes showed that configurational changes from a helical structure to a banded structure had occurred. Some chromosomes revealed a variety of transitional changes between these two configurations. During the repeated G-banding treatments, the distances between bands along the same chromatids changed each time. The results obtained seem to indicate that the G-banding results from locally induced compaction of chromosomal materials along the chromatids.


The organization of repeated DNA sequences in the human genome. The arrangement of repetitive and non-repetitive DNA sequences was studied in the human genome. By Ag+-Cs2SO4 density gradient centrifugations of human DNA at different fragment size reannealed to different Cot values and c-RNA hybridization experiments, we have shown the presence of two repetitive DNA fractions, called fast and slow intermediate DNA, with different pattern of sequence organization. The fast intermediate DNA sequences (6% of the genome; CsCl density in renatured form: 1.703 g/ml) are in part clustered in fragments greater than 24,000 nucleotide pairs and in part in fragments ranging from 1,800 to 600 nucleotide pairs spaced with longer more complex sequences. The slow intermediate DNA sequences (30% of the genome; CsCl density in renatured form: 1.707 g/ml) appear to be finely interspersed with non-repetitive sequences. At a DNA fragment size of 600 nucleotide pairs only a third of the slow intermediate DNA sequences are free of unique sequences, while the other two thirds are still organized with unique sequences. It has also been shown that a great amount of the repetitive DNA sequence transcripts in heterogeneous nuclear RNA of HeLa cells are complementary to slow intermediate DNA sequences.


In vitro transcription by isolated nuclei of Rhynchosciara americana salivary glands. Characteristics of incorporation and inhibition by alpha-amanitin. A method for the isolation of polytene nuclei from salivary glands cells of the Diptera Rhynchosciara americana is described. The stage-specific morphological pattern of the chromosome is maintained during the isolation. The isolated nuclei show two distinct RNA polymerase activities, namely I and II, characterized on the basis of ionic requirements and alpha-amanitin sensitivity. Studies of the product under the incubation conditions show that the system allows the synthesis of high-molecular weight RNA, beside a low molecular weight peak which may comprise pre-4S and 5S RNAs. Autoradiographic studies carried out in the presence or absence of the toxin alpha-amanitin showed that micronucleoli contain products of RNA polymerase type I activity (ribosomal RNA) and that the DNA puffs are engaged in alpha-amanitin sensitive RNA synthesis and thus are sites of polymerase type II activity.


Sister chromatid differentiation and exchanges in adult mudminnows (Umbra limi) after in vivo exposure to 5-bromodeoxyuridine. An in vivo system for the detection of sister chromatid exchange (SCE) in the central mudminnow, Umbra limi, is presented. Sister chromatid differential (SCD) and SCE were demonstrated by fluorescent and Giemsa procedures 5 to 6 days after the fish were injected with 500 mug/g of BrdU. The exchange rate was found to be 2.64 SCEs metaphase in the intestines and 2.42 SCEs/metaphase in the gills. SCE analysis in U. limi should be a useful tool for measuring the mutagenicity of water-borne chemicals.


Satellite DNA in the kangaroo Macropus rufogriseus. Two distinct satellite DNAs, amounting to 25% of the total DNA, were isolated from the nuclei of the red-necked wallaby, Macropus rufogriseus. The physical properties of native, single-stranded and reassociated molecules were studied in buoyant-density gradient centrifugation. The homogeneity of each satellite fraction was examined using melting characteristics of native and reassociated DNA, and renaturation kinetics. These data suggest that sequence heterogeneity exists in both fractions. Each satellite fraction was found by in situ hybridization to be localized in heterochromatin of interphase nuclei and in the centromeric regions of metaphase chromosomes. The chromosomal distributions of the two satellite DNAs differentiate the sex chromosomes, which have sequences of only one satellite, from the autosomes which have sequences of both satellites in the centromeric heterochromatin. Giemsa C-banding techniques also showed a differentiation of the centromeric regions of sex chromosomes from those of the autosomes.


Karyotype differences in the crenaticeps-group of Atractomorpha (Orthoptera, Acridoidea, Pyrgomorphidae). The four known species of the crenaticeps-group of the genus Atractomorpha have 2n (male)=18+X0. All members of the complement are rod-chromosomes and the smallest autosome (no. 9) is megameric. The four species have similar amounts of euchromatin but differ markedly in the amount of heterochromatin present in their genomes. In A. similis, A. crenaticeps and the unnamed species, "Species-1", there are distinct proximal segments of heterochromatin in the eight large autosomes. In A. similis these chromosomes also have prominent distal segments of heterochromatin. The fourth species, A. australis, has no visible heterochromatin in its eight large autosomes except for a small segment at the proximal end of autosome 4. In all four species, the heterochromatic segments influence chiasma frequency and chiasma position. Moreover the overall chiasma frequency is lowest in A. similis with most heterochromatin and highest in A. australis with least heterochromatin.


Telomeric satellite DNA functions in regulating recombination. Molecular and cytogenetical analyses of three sibling species of Australian grasshopper, Atractomorpha australis, A. species-1 and A. similis, resolves one of the long standing problems of highly repeated DNA. In this system satellite DNA functions in regulating the level and position of recombination, irrespective of whether the repeated DNA is located in telomeric or centric regions. Even though the three species do not differ in their euchromatic genome sizes, their relative DNA contents are 1.00/1.10/1.41, the difference in genome size being due solely to visible centric or telomeric blocks of heterochromatin. Antibiotic analytical and preparative ultracentrifugation, in situ hybridization and renaturation kinetic analyses reveal that a large cryptic satellite of A. similis constitutes the heterochromatic telomeric blocks of nearly all autosomes and that the DNA of this satellite is highly repeated. Comparison of these grasshopper data with published literature of heterochromatic rearrangements in Drosophila and with heterochromatin distribution and recombination patterns in diploid plant species reveals that in every case heterochromatin is implicated in some form of alteration in the meiotic recombination system.


Population cytogenetics of the genus Caledia (Orthoptera: Acridinae). II. Variation in the pattern of C-banding. The distribution of constitutive heterochromatin has been investigated in four chromosomal races of the grasshopper Caledia captiva (2n=23 male/24 female) by the C-banding technique. Each of the four races was found to have a distinctive banding pattern which is associated with the inter-racial differences in chromosomal rearrangements. The "Ancestral" race has a telocentric chromosome complements with large procentric C-bands which are structurally double on six pairs of chromosomes. The centromeres are unstained. The "General Purpose" race has a C-banding pattern very similar to that seen in other Acridine grasshoppers with the majority of its chromosomes showing a centromeric localisation of the bands. The two southern races, which show a complex polymorphism for presumed pericentric inversions on all twelve chromosomes, also show an unusually high level of interstitial and terminal C-bands. The different locations and numbers of these bands allow unambiguous identification of all the chromosome pairs within the complement. In two cases, there is good evidence to indicate that a C-band redistribution between acrocentric and metacentric chromosomes has occurred by pericentric inversion. Furthermore, C-band variation on the long arm of the metacentric X-chromosome indicates the presence of a large paracentric inversion. This double inversion system has involved over 95% of the X-chromosome. The interstitial and terminal C-bands probably have not resulted from heterochromatin movement within the complement but, more likely, have arisen by saltatory duplication of pre-existing sequences on the chromosome. A new nomenclature system for banded chromosomes is proposed which allows most kinds of chromosomal restructuring and rearrangement to be adequately enumerated.


Outline of chronohygiene.

Outline of chronohygiene. Since chronotherapy already manipulates rhythmical functions, it is the important task of chronohygiene to outline the object of therapy i.e. health, from chronobiological points of view. Only on such a basis can chronohygiene be extended to the preventive provisions of health care and health education in regard to the biological time structure. Health can be characterized as an optimal state of harmonious time structure and its integration into the temporal orders of the environment. The circannual variations of an organism establish a seasonal risk cycle changing the inner preconditions of therapy as well. Moreover, chronohygiene must raise the question of whether the biological circannual rhythm is an integrating component of the human time organization, or if it may be levelled by civilization. Circadian variations of the organism not only modify the preconditions of therapy, but in particular those of activity and efficiency. The nocturnal maximum of functional economy normally is protected against exploitation by a simultaneous minimum of vigilance, which provides the nightly recovery. Therefore the destruction of this phase relationship by night-work must worsen recovery conditions. The disturbance of the time structure in the organism by night-work not only affects the circadian system, but faster rhythms as well. The phase position of the circadian rhythms is closely related to the individual responsiveness of the autonomous system as well as to the pulse-respiration-ratio. The latter can serve as a chronobiological criterion for evaluating suitability or risk of night- and shift-work. The effort of chronohygiene is based on the fact that disturbances of the time structure represent just a complementary aspect to disturbances of the spatial structure of the organism.


Circadian periodic response of Phaseolus vulgaris l. to 2,4-dichlorophenoxyacetic acid. The susceptibility of bean plants, Phaseolus vulgaris L., cv. Executive, to 2,4-dichlorophentoxyacetic acid (2,4-D) appeared to depend upon the time of application. Oscillations in response to 2,4-D were evident in plants subjected to conditions of alternating light and dark spans, continuous illumination or darkness. The fresh and dry weight of plant material was generally less when 2,4-D was applied to plants near the later portions of the light span.


Advances in human chronopharmacology.

Advances in human chronopharmacology. Regular and thus predictable changes in biologic susceptibility and response to a large variety of physical as well as chemical agents can now be viewed as rather common phenomena. Chronopharmacology involves both the investigation of drug effects as a function of biologic timing and the investigation of drug effects upon rhythm characteristics (the period, tau, the acrophase, phi, the amplitude, A, and the mesor, M). Illustrative examples of circadian (tau congruent to 24 hrs) chronopharmacology in man are summarized in up-dated tables, keeping in mind that the objective demonstration of chronopharmacologic facts demands the use of an appropriate methodology. Circadian changes in the effects of various chemical agents have been documented: histamine, sodium salicylate, acetylcholine, halothane, prostaglandin F2alpha, reserpine, cyproheptadine, ethanol, insulin, chlorothiazide, oxymetholone, orcinprenaline and SCH 1000 (the latter being bronchodilators), Indomethacin, lignocaine, ACTH, cortisol and various synthetic corticosteroids. Despite that pharmacological facts are well documented in man for circadian rhythms, studies are not only restricted to the 24-h period but have been already extended to rhythms of periods of e.g. approximately 30 days as well as approximately 1 year. For a better understanding of chronopharmacologic findings, three new concepts must be considered: a) the chronokinetics of a drug, defined as both rhythmic (circadian) changes in the drug bioavailability (and/or pharmacokinetic effects) and its excretion (urinary, among others); b) the chronesthesy of a biosystem to a drug, or the circadian change in the susceptibility of any biosystem to a drug (including organ systems, tumors, parasites, etc.); and c) The chronergy of a drug, or the rhythmic change in the overall effects and the effectiveness of a drug. This term takes into consideration the chronokinetics and the chronesthesies of the organismic biosystems involved. Presently, one of the aims of chronopharmacology is to solve problems of drug optimization, i.e. to enhance the desired efficiency of a corticosteroid or other medications, while reducing undesired effects. In the human organism, among other animal species, the metabolic fate of a pharmacologic agent (as well as that of a nutrient) is not constant as a function of biological time. The metabolic pathways are neither open permanently, nor open with a constant patency along the 24-h scale, among other bioperiodic domains. Thus, the chronobiologic approach concerning pharmacologic phenomena involves a lesser risk of errors and/or false information than the conventional homeostatic approach.


Stromal atypia in anal papillae.

Stromal atypia in anal papillae. This report describes the occurrence of stromal atypia in anal papillae. The atypia occurred in two of 15 papillae studied and was present in the larger ones. The stromal atypia is similar to that described to occur in vaginal polyps and in entities such as pseudosarcomatous fasciitis, atypical fibroxanthomas of the skin, radiation dermatitis, and giant-cell cystitis. The atypia is considered to be reactive or reparative.


Adenocarcinoma of the appendix: an unusual case and review. Primary adenocarcinoma of the appendix is the rarest form of malignant tumor of the appendiceal stump is described. As with other malignancies, surgical treatment is described. As with other malignancies, surgical treatment is most effective during the early stages of disease. In our series most of the patients who had metastatic disease had fairly rapid downhill courses. The choice of right hemicolectomy with node dissection in all cases is suported.


Fibroma of the cecum: report of a case.

Fibroma of the cecum: report of a case. A woman suffering from recurrent attacks of abdominal pain was found at operation to have a fibroma of the cecum. The clinical, operative and pathologic findings are described. The medical literature was reviewed and the lesion was found to be uncommon. The importance of specific histologic stains to distinguish the true fibroma from other spindle-cell tumors is stressed.


Elective resection for recurrent sigmoidal volvulus: report of a case. A patient with recurrent sigmoidal volvulus who was treated by elective sigmoidal resection is reported. The symptoms and radiologic findings are sufficient for a confident diagnosis to be made before the onset of a major obstructive epidose. The value of barium-enema examination even in the quiescent phase is emphasized. Definitive treatment by sigmoidal resection in the absence of obstruction is safe and should be undertaken as an elective measure. Awareness of the disease and its occurrence in young patients will aid its recognition and reduce mortality from intestinal obstruction.


Retrorectal herniation of the sigmoid colon: report of a case. A rare retrorectal hernia of the sigmoid colon associated with diverticulitis and a presacral abscess is reported. The anatomy of the retrorectal space is reviewed. The value of routine lateral fluoroscopy and overhead films is emphasized.


Sliding colonic Maydl's hernia: report of a case. An unusual variety of Maydl's hernia (hernia-in-W) in which all the herniated loops were colon is reported. The unusual anatomy of the hernia and its variations are described. It is important to examine the intraperitoneal intestine between the incarcerated loops in an effort to avoid leaving a nonviable segment of intraperitoneal intestine after repair of the hernia.


[Oesophageal function in patiensts with angina (author's transl)]. Oesophageal functions were measured in 18 patients with angina, 13 healthy volunteers and 29 age-matched patients with reflux disease. Acid clearance was as abnormal in angina patients (88 +/- 46 swallows) as in those with reflux disease (97 +/- 45). The pressure in the lower oesophageal sphincter was low in patients with angina (13 +/- 8 mm Hg). The incidence of hiatal hernia, subjective symptoms during acidification of the oesophagus and results of the reflux provocation test were similar in patients with angina pectoris and healthy controls.


[Atrial fibrillation and flutter as a complication of acute myocardial infarction (author's transl)]. Among 909 patients with acute myocardial inarction treated in an intensive care unit between 1970 and 1974, atrial flutter and (or) fibrillation occurred in 124 (13.6%). The incidence of these arrhythmias rose with increasing age and predominantly in paroxysmal form (78%). The clinic mortality of patients with arrhythmias was 42%, while in the remaining 785 it was only 26% (P less than 0.001). Patients with atrial fibrillation and (or) flutter had a higher mean age, more frequently cardiac failure (P less than 0.001) - especially in the prognostically unfavourable severe forms with pulmonary oedema (P less than 0.05) and combined right and left heart failure (P less than 0.001) - and other disorders of impulse conduction or formation and chronic arterial hypertension (P less than 0.01).


[Penicillamine-induced myasthenia in chronic rheumatoid arthritis (author's transl)]. A myasthenic reaction developed after an average latency of seven to eight months in 12 female patients (average age 51 years) treated with penicillamine for chronic rheumatoid arthritis. In most of them only the purely ocular form was noted, but generalisation of various degrees also occurred. When penicillamine had been discontinued the myasthenic signs were almost always fully reversible, recurring once again when treatment with penicillamine was started. In some instances a transitory symptomatic treatment with cholinesterase inhibitors was necessary. The occurrence of the myasthenic signs in these circumstances is probably similar to the anti-basal membrane nephropathy induced by penicillamine.


[Unusual course of traumatic intracranial bleedings (author's transl)]. Intracranial bleedings occurred in three patients as complications of h-ad trauma, without any initial acute disturbance of consciousness. Only careful observation, which revealed slow deterioration in consciousness, made it possible to establish the diagnosis of intracranial haemorrhage, confirmed angiographically in all three instances.


[Results of surgical treatment of early carcinoma of the stomach (author's transl)]. From 1961 to 1975, 53 patients were operated on for early carcinoma of the stomach, 24 of the total of 57 cancer sites being limited to the mucosa, 33 having already infiltrated into the submucosa. Macroscopically, most of them were ulcerative carcinoma, while histologically the intestinal type predominated. The cumulative five-year survival rate (excluding hospital deaths) was 86.5%, while after "typical" carcinoma resection by the Billroth II procedure with removal of the greater and lesser omentum it was 100% for mucosal and 93% for submucosal carcinoma.


[Cytological classification of bronchial carcinoma (author's transl)]. Reliability of cytological classification of tumours from material obtained from sputum or bronchial secretion was tested on 116 histologically confirmed cases of bronchial carcinoma. Squamous-cell carcinoma and small-cell undifferentiated carcinoma were most often correctly classified, results being less good with large-cell undifferentiated carcinoma, adenocarcinoma taking an intermediary position.


[Myocardial infarction after accidents (author's transl)]. In a 27-year-old man blunt chest-wall trauma after a car accident gave rise to several retrosternal pain. Coronary angiography demonstrated severe generalised coronary arteriosclerosis. The history revealed heavy smoking (60 cigarettes daily for ten years). Although it must be assumed that there was severe generalised coronary arteriosclerosis without angina pectoris before the accident, the infarction was considered to be a direct consequence of it: it prematurely precipitated the infarction. In a second case, of a 37-year-old woman, severe precordial pressure and contusion of the thorax occurred after a collision. Cardiac symptoms developed two months later and two weeks after this acute myocardial infarction occurred. Coronary angiography demonstrated isolated sub-total occlusion of the anterior interventricular branch in the upper third of the septum without other abnormalities. Because of the two month symptom-free interval, trauma and subsequent myocardial infarction are thought not to be causally related, especially as the patient was a heavy smoker and taking oral contraceptives.


[Yersinia arthritis (author's transl)].

[Yersinia arthritis (author's transl)]. Yersinia arthritis is an acute oligo- or, more rarely, polyarthritis. It occurs after pyrexic diarrhoea of several days, often associated with right-sided lower abdominal pain. The disease is caused by Yersinia enterocolitica and four such cases, confirmed serologically in three, are described. In one case fluid from the knee-joint was antibody-positive. It was not possible to culture the causative organism, probably because all patients had previously been treated with an antibiotic. Rheumatic fever and Reiter's disease must be considered in the differential diagnosis. Because pharyngitis, transitory ECG changes and conjunctivitis may occur in the early stages of Yersinia arthritis, the diagnosis may be missed. Prognosis of Yersinia arthritis is good, with complete cure within weeks or months. Demonstration of HLA-B 27 in all four cases points to a genetic disposition.


[Traumatic subluxation of the head of the radius (author's transl)]. Radial-head subluxations were noted in 194 patients in the course of two years. It was more frequent in girls than boys (57.7% and 42.3%). The highest incidence was between the first and fourth year of life, with a peak in the first and second years. It no longer occurs after the seventh year. In 82.5% of cases the history was typical: a sudden longitudinal pull of the affected arm. In the remaining 17.5% no exact event could be ascertained. A questionnaire sent to the attending doctors provided replies in 82 cases (42.3%). Reposition by pull and pressure on the head of the radius, supination and acute flexing achieved repositioning in 92.7%, while in 7.3% repeat repositioning was necessary on the same or the next day. After successful repositioning complete absence of symptoms occurred in 98.8%. Incidence of recurrence was 30.5% during a follow-up period of up to a year and a half. The diagnosis had at first been had at first been missed 9.8% of cases.


[Kearns' syndrome (author's transl)].

[Kearns' syndrome (author's transl)]. Kearns' syndrome, a rare cause of chronic progressive ophthalmoplegia was observed in three patients aged 15 to 54 years. Apart from the chronic progressive external ophthalmoplegia the syndrome consists of retinal changes and cardiac conduction defects in all cases, as well as other signs indicating damage to the nervous system. High tone deafness and vestibular damage as well as an increase in CSF protein are common. Endocrine disorders and skeletal anomalies may occur. The cause is unknown. The ophthalmoplegia may be of neurogenic origin. Adams-Stokes attacks following disturbances of cardiac rhythm may be prevented by timely implantation of a cardiac pacemaker.


[Carcinoid tumours of the rectum (author's transl)]. In three patients aged 21 to 65 rectal polyps diagnosed at rectoscopy were removed by diathermy loop. Histology showed them to be carcinoid tumours, one of tubular type, two of mixed type. Rectal carcinoid rarely presents with typical clinical symptoms. Polyps discovered by digital examination or rectoscopy should be considered to be potentially malignant and removed in toto. The size of the tumour is of decisive prognostic importance. Tumours with a cross section over 2 cm should be treated as malignant. The histological investigation generally gives no indication of clinical prognosis or of the possibility of metastases. Despite invasive growth and despite local or distant metastases carcinoid tumours can be judged more favourably than carcinoma. The plan of treatment should be according to the clinical findings as well, and not only to histological results. Postoperative follow-up is considered imperative.


[Continuous monitoring of pO2 by means of intravascular indwelling oxygen electrodes (author's transl)]. Two intravascular oxygen electrodes (of the International Biophysics Corporation and Roche) were tested in vitro and in long-term monitoring of arterial oxygen partial pressure in 19 patients. There were no complications. Both electrodes proved suitable for use for monitoring in an intensive-care situation. But both could still be improved by having greater stability and a shorter response time. Some of the indications for continuous monitoring of pO2 are mentioned: incipient respiratory failure, shock-lung, pulmonary oedema, and artificial ventilation. Haemorrhagic diatheses and arterial occlusive disease are contra-indications to its use.


[Anomalous aortic origin of a coronary artery: cause of sudden death in a 10-year-old girl (author's transl)]. A ten-year-old girl suddenly died on a playground, after repeated syncopal attacks during the preceding two years. Post-mortem examination revealed the left coronary artery to have arisen by a separate ostium from the right sinus of Valsalva, then coursing to the left between the route of the aorta and the pulmonary trunk where it divided as usual. There was no narrowing of the coronary-artery lumen and the wall was normal. The sudden death is explained by a rise in pressure in the root of the aorta with valve-like closure of the coronary artery. This anomaly should be thought of in other wise unexplained syncopal attacks in children or juveniles during physical exertion. The exercise ECG is apparently not helpful diagnostically. Operative treatment is possible.


Management of the acute attack of asthma in general practice. Many acute attacks of asthma respond readily and completely to aerosol and/or parenteral bronchodilators, and subsequent management of asthma should try to prevent a further acute recurrence. Explanation of drug administration techniques and of the general nature of asthma are of great value in achieving good control. Severe, prolonged attacks require energetic measures, with transfer to units with intensive care facilities. These life-threatening situations are generally not hard to recognise.


Clonazepam: a review of its pharmacological properties and therapeutic efficacy in epilepsy. Clonazepam or 5-(2-chlorphenyl)-1, 3-dihydro-7-nitro-2H-1,4benzodiazepin-2-one, is a close structural and pharmacological relative of nitrazepam. It has a broad spectrum of activity against the various types of epilepsy, and is effective in many patients whose condition has proved resistant to other antiepileptic drugs. Its chief uses are in status epilepticus, in which intravenous clonazepam may replace diazepam as the drug of first choice, and in the minor motor seizures of childhood, particularly petit mal absences, the Lennox-Gastaut syndrome and infantile spasms. Clonazepam is also at least as effective as current treatment in psychomotor and myoclonic epilepsies, but seems unlikely to replace phenytoin and the barbiturates in the treatment of grand mal or focal motor seizures except in patients resistant to standard therapy. Initial success with clonazepam can be followed by loss of effect, but benefit can often be restored, at least initially, by temporary interruption and re-institution of treatment. Side-effects are common with clonazepam. Most patients experience drowsiness and fatigue, which are frequent causes of withdrawal, together with lesser incidences of ataxia, dystonia, hypotonia, and hyperactivity. These effects usually disappear with continued therapy, and are minimised by gradual introduction of the drug over 2-4 weeks. Hypersalivation and excessive bronchial secretion may be a problem in children and infants.


Suppression of the estradiol receptor system by progesterone in the oviduct and uterus of the cat. Four weeks or more after being spayed, cats were either left untreated or treated with various regimens of estradiol (E2) and progesterone (P) in silastic implants. Oviducts and uteri were then removed and examined for morphological changes as well as for the amount and compartmentalization of the estrogen receptor. E2 treatment restored a full complement of ciliated and secretory cells to the oviduct, and subsequent P treatment (with or without continuous E2) of an E2-restored oviduct produced an atrophied epithelium equivalent to that resulting from E2 withdrawal. In the uterus, P treatment after E2 priming did not lead to E2-withdrawal symptoms but rather to a new stage of differentiation characterized by altered and increased secretory activity. In both organs E2 caused dramatic elevations in the E2-receptor content in the nuclear as well as in the cytoplasmic compartments. Also (in both organs) P treatment after E2 priming reduced the E2-receptor content in the nuclear and cytoplasmic compartments to the levels present in spayed cats. The degree of suppression caused by P in both organs was similar to that induced by E2 withdrawal. Suppression of the E2-receptor system by P correlated with suppressed function inthe oviduct but with increased growth and secretory activity in the uterus.


Relationship between membrane potential and progesterone release in ovine corpora lutea. When slices of ovine luteal tissue were perfused with medium containing luteinizing hormone (LH), the output of progesterone was increased significantly (P less than 0.01) in eleven of twelve experiments. However, addition of LH to the medium did not influence the luteal cell membrane potential. The addition of 47 mM potassium to the medium resulted in increased progesterone output (P less than 0.01) and depolarization of the luteal cell membrane within 2 min. Progesterone output decreased to approximate pretreatment levels within 2 min of the return to normal potassium levels in the perfusion medium. High levels of potassium further increased the output of progesterone from tissue stimulated with LH. Perfusion of the slices with sodium-free medium also resulted in increased (P less than 0.01) progesterone output within 2 min, which returned to pretreatment levels within 2 min after normal sodium levels were restored to the medium. Perfusion of the slices with sodium-free medium did not influence the membrane potential. Perfusion of the tissue with LH, 47 mM potassium, or sodium-free medium had no effect on progesterone output if the medium was calcium-free and/or contained 2 mM EGTA. These data suggested that the calcium ion plays an important role in mediating the steroidogenic response of ovine luteal tissue to LH. A second series of experiments was designed to ascertain if luteal cells were coupled electrically. Sixty-six pairs of luteal cells separated by 150-300 mum were penetrated with electrodes and the membrane potential of both cells was studied. One cell of each pair was hyperpolarized by passage of 0.4 nA current into the cell, but in no case was there an effect on the membrane potential of the other penetrated cell. Likewise, when five cells were injected iontophoretically with Procion Yellow there was no evidence of diffusion of the dye to adjacent cells. There was no evidence obtained in this study which suggested that ovine luteal cells were coupled electrically.


Adrenal mitochondrial and serum corticosteroid studies in rats resistant to adrenal-regeneration hypertension (ARH). Female rats of the Wistar-Furth (W/Fu) strain appear to be resistant to the development of adrenal regeneration hypertension. At a time period, after adrenal enucleation, when Holtzman female rats had elevated serum 11-deoxycorticosterone levels and were hypertensive, none of the W/Fu rats became hypertensive. In vitro adrenal studies after quiescent kills of W/Fu rats indicated that cholesterol side chain cleavage activity was greater in mitochondria from regenerating adrenals than from controls. Both serum deoxycorticosterone and corticosterone levels were significantly greater in the adrenal-enucleated group. These studies were repeated in animals which were given a standard ether anesthetic stress. Ether stress increased cholesterol side chain cleavage activity comparably in control and adrenal-enucleated rats and also increased their serum deoxycorticosterone and corticosterone levels. Adrenal-enucleated Wistar-Furth rats had higher serum deoxycorticosterone levels than controls, whereas controls had higher serum corticosterone levels than the adrenal-enucleated group after the ether stress. These results indicate that although the adrenal-enucleated W/Fu rats have increased serum deoxycorticosterone levels, none of these rats develop frank hypertension. This suggests a resistance to deoxycorticosterone-induced hypertension in this strain of rat.


Mechanism of interaction of digitalis with estradiol binding sites in rat uteri. Digitalis preparations have a weak estrogenic effect in man. The data in animals are equivocal. We have studied.the biologic effect of both digitoxin and digoxin on the rat uterus in vivo and the interaction of these drugs with the rat uterus estrogen receptor in vitro. Digitoxin and estradiol significantly increased the uterine weight of immature rats, while digoxin did not. The interaction of digitoxin and digoxin with the rat uterus estrogen cytosol receptor was studied using protamine sulfate precipitation and dextran-coated charcoal (DCC) assays. Both methods gave a Kd for the estradiol-receptor interaction between 0.8-3.1 X 10(-9) M (n = 20). Digitoxin at concentrations of 0.5-2.0 X 10(-6) M significantly inhibited the binding of estradiol to the specific or saturable binding sites with minimal inhibition of hormonal binding to nonspecific sites. The binding was competitive with a calculated Ki for digitoxin of 5.2-7.8 X 10(-7) M (n = 18). Digoxin failed to inhibit estradiol binding to the receptor protein in vitro. We conclude that digitoxin probably acts directly as a weak estrogen and that this effect probably explains the estrogen-like side effects seen with digitoxin therapy in man.


Effects of spironolactone, canrenone and canrenoate-K on cytochrome P450, and 11beta- and 18-hydroxylation in bovine and human adrenal cortical mitochondria. Effects of spironolactone, canrenone and canrenoate-K on adrenal cytochrome P450 (P450) and corticosteroid biosynthesis were examined by studying difference spectra, P450 reduction and corticoid hydroxylation in mitochondrial preparations isolated from zona fasciculata and zona glomerulosa of bovine adrenals and from adrenal adenoma and hyperplastic adrenal cortex removed from patients with hyperaldosteronism. All three agents bound to P450 producing type I difference spectra and underwent hydroxylation. They all inhibited 11beta-hydroxylation in bovine adrenal at 30 muM and higher concentrations. Canrenone, the most potent inhibitor, blocked enzyme activity by 60% at a concentration of 60 muM. Spironolactone stimulated P450 reduction. The order of potency of inhibition was found to correlate with the order of affinity of these agents for P450. 11beta-Hydroxylase in human adrenal appeared to be less sensitive to canrenone. All three agents or their hydroxylated metabolites blocked 18-hydroxylation in bovine adrenal at lower concentrations. Canrenoate-K, being the most effective, inhibited 52% at 20 muM. Low concentrations of canrenone (2.5-5.0 muM) were without effect on 11beta-hydroxylase but markedly inhibited 18-hydroxylation (62-76%) in hyperplastic human adrenals. The inhibitors produced mixed type inhibition of 11beta-hydroxylation and competitive type inhibition of 18-hydroxylation. These findings indicate that at low concentrations spironolactone and its major metabolites, canrenone and canrenoate-K, or their hydroxylated metabolites, can directly interfere with the biosynthesis of aldosterone in bovine and certain human adrenal cortical tissue.


The interrelation of renin and iron binding capacity. When rats are subjected to hypoxia, an increase in serum angiotensinogen concentration occurs which is accompanied by the appearance of serum erythropoietin (EP) during the first 24 h. Subsequent increases in EP reach maximum values 24 to 48 h after increases in packed cell volume (PCV) and serum renin levels. The current experiments were designed to determine if a decrease in iron stores is the stimulus for renin production when rats are rapidly expanding their red cell volume in a hypoxic environment. Young rats fed McCall's low iron diet were paired with rats fed the same diet supplemented with ferric citrate (6 g/kg diet). After two weeks at ambient pressure, they were subjected to hypoxia (0.48 atm) for 1 to 10 days. After 5 days at the reduced pressure, a fraction of the rats on the low iron diet were fed the iron-supplemented diet. At the time of sacrifice, serum was assayed for total iron binding capacity (TIBC) and renin. Rats that were fed the low iron diet showed an increase in TIBC, an increase in serum renin and a positive correlation between serum renin and TIBC. Rats that were fed a normal iron diet under the same conditions had lower TIBC, lower serum renin and no correlation between serum renin and TIBC. When low iron diet rats were supplemented with iron, TIBC and serum renin decreased. These experiments may have a clinical counterpart. The total iron binding capacity, renin and angiotensinogen were measured in the serum of women during the first 19 weeks of pregnancy. Women during early pregnancy showed an increase in TIBC, an increase of renin and angiotensinogen in the serum and a positive correlation between TIBC and renin concentration. It is suggested that the increased concentration of renin in the serum of women during the first 19 weeks of pregnancy and in the serum of rats that are rapidly expanding their red cell volume are related to a decrease in iron stores.


Follicle stimulating activity of human chorionic gonadotropin: effect of dissociation and recombination of subunits. The follicle stimulating activity (FSA) and interstitial cell stimulating activity (ICSA) of highly purified human chorionic gonadotropin (hCG), its alpha and beta subunits, and hCG generated by subunit recombination were determined by ovarian weight and ventral prostate weight bioassays. Whereas highly purified hCG exhibited both FA and ICSA, its separated subunits were essentially devoid of both activities. ICSA and FSA, indistinguishable from that of the highly purified hCG, were restored by recombination of the hCG subunits. These observations are consistent with the hypothesis that the FSA and ICSA found in highly purified hCG preparations are properties of the hCG molecule.


Stimulation of aromatization of exogenous and endogenous androgens in ovaries of hypophysectomized rats in vivo by follicle-stimulating hormone. The role of follicle-stimulating hormone (FSH) in the regulation of estrogen biosynthesis in vivo has been investigated in immature hypophysectomized rats, utilizing uterine weight and histologic responses, and ovarian estradiol-17beta concentrations as indicators of estrogen secretion. A highly purified FSH preparation produced only borderline increases in uterine weights and in ovarian estradiol-17beta contents when administered alone at 2.5 mug/day for 3 days. Testosterone or androstenedione (5 mg/day), when administered in the absence of FSH, produced typically androgenic stimulation of uteri, and did not increase ovarian estradiol-17beta concentrations. When administered concomitantly with FSH, the uterine weight-stimulating activity of these aromatizable androgens was substantially increased, accompanied by marked hypertrophy of the endometrial mucosal cells, and ovarian estradiol-17beta concentrations were increased 20- to 200-fold. The administration of the non-aromatizable androgen, 17beta-OH-5alpha-androstan-3-one (DHT) (5 mg/day, by itself produced uterine weight increases similar to those caused by testosterone alone; however, no evidence of increased estrogen secretion resulted from the combined treatment of DHT wtih FSH. A highly purified luteinizing hormone (LH) preparation was equally as effective as exogenous androstenedione in increasing ovarian concentrations of immunoreactive androgen (testosterone + DHT) but evoked none of the above signs of estrogen secretion unless administered together with FSH. The weights of ovaries were not affected by the administration of LH or of any of the androgens by themselves, but were approximately doubled by FSH alone. Ovarian weights were increased still further when FSH was administered concomitantly with LH, testosterone , or androstenedione, but not with DHT. It is concluded that FSH and LH regulate ovarian estrogen secretion in vivo by acting at biochemically distinct sites--LH stimulating the synthesis of C19-steroids, which are then converted to estradiol-17beta under specific stimulation by FSH.


Progesterone metabolism by the ovary of the pregnant rat: discrepancies in the catabolic regulation model. The intraovarian site of 20 alpha-hydroxysteroid dehydrogenase activity (20 alpha-OH-SDH) was determined biochemically by measuring enzyme activity in homogenates of the whole ovary, or of isolated ovarian compartments, during the last third segment of pregnancy in the rat. In agreement, with previously reported histochemical evidence, an increase in 20 alpha-OH-SDH activity was observed in isolated corpora lutea, but not in the non-luteal compartment of the ovary. Enzyme activity in corpora lutea was low between days 16 and 22 of pregnancy, but increased markedly (4-6 fold) on day 23. Between days 17 and 20 of pregnancy, serum concentrations of progesterone declined from 130 +/- 3 to 80 +/- 3 ng/ml, while 20 alpha-hydroxypregn-4-en-3-one (20 alpha-OH-P) concentrations declined from 34 +/- 3 to 18.5 +/- 3 ng/ml. Only later, between days 20 and 22 of pregnancy, was a significant decline in serum progesterone concentrations associated with an increase in serum 20 alpha-OH-P concentrations (50 +/- 15 ng/ml at 0800 h and 128.5 +/- 15 ng/ml at 1400 h on day 22). Thus the decline in progesterone concentration late in pregnancy can be explained only partially by conversion of progesterone to 20 alpha-OH-P. Further, a dissociation between changes in enzyme activity and in serum concentrations of 20 alpha-OH-P was also observed. A marked increase in serum levels of 20 alpha-OH-P on day 22 preceded any increase in enzyme activity by at least 10 h, and continued increases in enzyme activity on day 23 were not associated with any steady increase in peripheral 20 alpha-OH-P levels. We conclude from these observations that luteal regression is a more complex phenomenon than the regulation of a single enzyme, 20 alpha-hydroxysteroid dehydrogenase, and may involve regulation of both the synthesis and degradation of progesterone.


Pituitary thyrotropin (TSH) rebound phenomenon and kinetics of secretion in the goitrous rat: differential effects of thyroxine on synthesis and release of TSH. The protein metabolism and [3H]-uridine uptake of thyroid and adenohypophysis and the kinetics of pituitary TSH rebound (PTR) were studied in goitrous female rats (fed propylthiouracil, PTU: for 7-12 weeks) following single, iv injections of L-thyroxine (T4: 0.8 to 200 mug). Goitrogenesis was associated with reduced protein concentration and enhanced uptake of [3H] uridine in both glands. Plasma levels of TSH were invariably elevated but stores in the adenohypophysis were consistently reduced. Small doses of T4 (4 mug) induced significant TSH repletion in the pituitary within 2-6 h following injection. Accumulations of pituitary TSH to supranormal levels (15-fold increases) were achieved with 20 mug T4 at 6 and 24 h; higher doses (100-200 mug) inhibited the PTR at all time intervals tested (0.5-24 h). Administration of puromycin or actinomycin D did not influence the PTR. Protein content and labeled uridine uptake of the pituitary bore no apparent relationship to T4-induced TSH repletion in the gland. Blood clearance rate of exogenous rat TSH was measured prior to and during PTR. Plasma half-life was determined to be 13.6 and 19.9 min in euthyroid and chronically hypothyroid rats, respectively; it was not significantly altered from the latter during rebound (18.7 min). Calculations of theoretical TSH secretory rates prior to (50.5 +/- 4.4 mU/h) and after rebound with 20 mug T4 (25.4 +/- 4.2 mU/H) revealed that the reaccumulation of TSH in the pituitary induced with T4 cannot be attributed solely to inhibition of release, but may also involve enhancement of synthesis. It is concluded that T4 administration at high dose levels inhibits both synthesis and release of TSH from pituitary thyrotrophs, whereas low critical doses of T4 suppress release, but augment synthesis and/or facilitate conformational change in a pituitary precursor(s) molecule which renders it detectable by bioassay.


Effect of surgical disconnection of the medial basal hypothalamus on postcoital reflex ovulation in the rabbit. The effects of hypothalamic transections of varying lengths on reflex ovulation in the rabbit are reported. Circular cuts which surgically isolated the medial basal hypothalamus (MBH) from the remainder of the brain did not prevent copulation 4 to 24 h later, but did block reflex ovulation. On the contrary, hemicircular cuts of either the rostral, caudal or one lateral haf of the circular cut did not prevent reflex ovulation. These results suggest that coital stimuli reach the MBH through a diffuse network of fibers and that only very extensive deaferrentation of the MBH can cause blockade of ovulation in rabbits. These data are compared with results of other investigators in which anterior deafferentation of the MBH blocked reflex and spontaneous ovulation in rats.