Residual learning deficit after heavy exposure to cannabis or alcohol in rats. Acute oral administration of cannabis extract to rats (tetrahydrocannabinol dose, 10 milligrams per kilogram) impaired maze learning. The impairment was more marked after ten daily doses of the same size. After 1, 2, or 3 months' pretreatment with the same daily dose, followed by a 25-day drug-free period, no residual learning impairment was found. However, 6 months of daily administration of cannabis (tetrahydrocannabinol, 20 milligrams per kilogram) or alcohol (6 grams per kilogram) produced significant residual impairment of learning of maze and motor coordination tasks, 2 months or more after the last drug administration.


N-nitroso compounds: detection in ambient air. By use of a new, highly selective detection technique for N-nitroso compounds, which is sensitive to picogram quantities and which is based on the catalytic cleavage of the N-NO bond and the subsequent detection of the nitrosyl radical, dimethylnitrosamine has been found in concentrations of 0.02 to 0.96 part per billion in three out of five air samples from Baltimore, Maryland, and 0.014 to 0.051 part per billion in five out of six air samples from Belle, West Virginia. The sensitivity of the analytical procedures used was 1 part in 10(12). The presence of dimethylnitrosamine has been confirmed by using the new detector in conjunction with both a gas-liquid chromatograph and a high-performance liquid chromatograph. In addition, between one and three as yet unidentified N-nitroso compounds were detected in both cities. N-Nitroso compounds were not found in air samples from Philadelphia, Pennsylvania; Wilmington, Delaware; and Waltham, Massachusetts.


Bone cells in culture: morphologic transformation by hormones. Hormones and purine nucleosides and nucleotides induced cultured bone cells to transform transiently from a spherical to a stellate shape. Cytochalasin B also induced the transformation. The change was blocked by colchicine and vinblastine, but not by lumicolchicine or cycloheximide. This morphologic transformation may provide a dynamic model of hormone action and bone cell modulation in vitro.


Aflatoxin production by a variant of Aspergillus oryzae (NRRL strain 1988) on cowpeas (Vigna sinensis). Aflatoxin B1, B2, G1, and G2 are produced when a variant of Aspergillus oryzae (NRRL strain 1988) is grown on cowpeas or rice. The present study indicates that a strain of Aspergillus oryzae approved for use in food processing is variable and the resulting variant, unlike the parent strain, has a propensity to produce aflatoxin.


Ant-aphid association: role of aphid alarm pheromone. When attacked by predators, aphids secrete alarm pheromones that cause nearby aphids to disperse. Ant-associated (myrmecophilous) aphid species disperse less readily than nonmyrmecophilous species. The ant Formica subsericea responds to aphid alarm pheromone in a way that is beneficial to the aphid. These findings support our hypothesis that myrmecophilous aphids depend more on ants for protection from predators than on their own dispersive powers.


Stimulant-related state-dependent learning in hyperactive children. Hyperactive and nonhyperactive children performed a learning task in two states, while being treated with stimulant medication (methylphenidate) and while taking a placebo, and were tested for retention of each class of learned material in both states. Symmetrical state-dependent learning was demonstrated in the hyperactive group but not in the nonhyperactive group. The state-dependent effect was contingent on the presence of drug-induced facilitation during initial learning. This is apparently the first report on record of state-dependent learning with a drug agent that facilitates rather than impairs performance of human subjects.


Analgesia mediated by a direct spinal action of narcotics. Narcotic analgetics administered directly into the spinal subarachnoid space of the rat via a chronically inserted catheter produce a potent analgesia that can be antagonized by naloxone. The narcotics, acting only at the spinal level, changed cord function to block not only spinal reflexes but also the operant response to painful stimuli.


Evolution on the level of communities.

Evolution on the level of communities. According to traditional models, natural selection is largely insensitive to an organism's effect on its community. Effects on the community at large cannot feed back differentially to the organisms that cause them, and, hence, cannot lead to the differential fitness of the organisms. However, if a spatial variation exists in community composition, organisms do differentially feel their own effects on the community, and this leads to a form of evolution on the community level. Without violating the principle of individual selection, the concept of an organism that exists for the "function" its performs in its community may be valid in some cases.


Prospective study of the early course of rheumatoid arthritis in young adults: comparison of patients with and without rheumatoid factor positivity at entry and identification of variables correlating with outcome. The early course of newly diagnosed RA among young adult patients (16-44 yr) is described from results of an ongoing study with a mean follow-up of 3.4 yr. Study diagnosis was based on the judgement of experienced rheumatologists, and data on several hundred variables were obtained on entry and annually for the purpose of defining patterns of onset and course of disease. Race and sex factors, as well as certain entry manifestations, e.g., RF, were found to correlate with onset and course patterns. Females, and especially white females, had significantly greater numbers of swollen upper extremity joints than males at entry and at last observation, with increased likelihood of developing bone erosions. At entry, RF positive patients differed only on few articular manifestations from RF negative patients, but had a higher frequency of positive ANA at entry and more subcutaneous nodules and bone erosions during follow-up. Seropositive white females at entry had significantly more swollen upper joints than their seronegative counterparts, but with no difference found at last follow-up. White females of each serogroup had more joint involvement at last examination than patients of other race-sex groups. Males had more acute onset, especially under age 30, with significantly greater improvement in arthritis and in ESR than did females. The majority (55%) of patients entered as seropositive, converted to seronegative during follow-up, and no correlation of either joint swelling or erosions was noted with this phenomenon. At last visit, RF positively did not correlate with bone erosions, but patients developing bone erosions had higher frequency of ANA and higher mean serum complement levels at last examination. The following entry factors were found to correlate significantly with a better outcome: maleness, acute onset under age 30, less swollen upper joints, and negative RF. Type of drug therapy tended to reflect severity of arthritis, rather than vice versa, and functional capacity improved significantly from entry to last evaluation in both males and females, even though the latter had stable or progressive arthritis. Further study is necessary over long intervals and in wider age range to more adequately interpret the biologic implications of findings of this ongoing study. A better understanding of the pathogenesis of RA may be derived from critical studies of the contribution of host factors, e.g., sex, and other variables predisposing to the development of RF positivity (and ANA), subcutaneous nodules, and bone erosions, particularly in systematic ongoing studies of patients with early diagnosed disease.


Assessment of intrarenal perfusion with radioxenon: a critical review of analytical factors and their implications in man. Radioxenon has achieved wide use for assessing tissue perfusion. Here we review its application to the kidney for assessing mean blood flow and intrarenal perfusion rates. Correlation with alternative methods in animals suggests that the initial disappearance slope provides an adequate measure of mean renal blood flow despite the theoretical limitations of this approach. The stochastic method and compartmental analysis can also provide an acceptable measure fo mean renal blood flow, but only after the slowest flow components have been removed. Compartmental analysis does, however, provide an index of cortical perfusion not available from other methods. The evidence that the rapid component of xenon washout provides an index of cortical perfusion in man is reviewed, along with insights gained from the application of this approach to human disease.


Fiberoptic colonoscopy: diagnostic value in 250 consecutive patients. Endoscopic findings and accomplishments in 250 consecutive patients are presented. Of these patients 72% were found to have polyps, cancer, inflammatory bowel disease or other specific positive findings. In almost half of these patients, no definitive diagnosis had been made before the procedure. In half of the patients, new information was obtained which was not known before the procedure. Indications for colonoscopy are presented to demonstrate the situations in which the procedure was valuable not only to remove polyps, but also to explain nonspecific radiologic abnormalities, unexplained rectal bleeding, or diarrhea, and to detect unknown cancers and polyps.


Unsuspected diabetic glomerulosclerosis. Six patients without overt diabetes mellitus underwent renal biopsy for suspected glomerulonephritis. All were demonstrated to have diabetic glomerulosclerosis and subsequently were found to have abnormal glucose tolerance tests. Electron microscopy was critical in making the correct diagnosis in five of six patients. The reported cases represent 3% of a series of 200 patients who had a renal biopsy to evaluate possible glomerulonephritis. Renal manifestations of diabetes mellitus may antedate glycosuria and other more common presenting symptoms of this disease.


Penetrating injuries of the face and neck. Experience with 547 consecutive cases of cervical and facial penetrating trauma has indicated the value of an individualized approach rather than a firm policy of exploration for all wounds penetrating the platysma. In addition, the accumulated data suggest that the concept of separate classes of carotid injuries based on presence or absence of neurologic deficits bears further evaluation with respect to the advisability of reconstituting carotid artery flow.


A dynamic transpatellar approach to the knee. This paper describes a transverse approach to the knee which gives unequalled access to the joint for extensive synovectomies, extensive surgical debridement, installation of total knee prostheses, or reduction of supracondylar fracture of the femur involving the articular surfaces. The temporary patellar tendon substitution wire is a loop of wire extending through the body of the patella and intrapatellar tendon to the tibial tubercle, which restores the anatomic length of the patella and intrapatellar tendon, having sufficient strength to permit early motion of the joint, since the temporary patellar tendon substitution wire relieves stress from the capsular sutures.


Intradermal 5-fluorouracil in the treatment of basal cell carcinoma of the face. The intradermal or infiltrative use of 5-fluorouracil by hypodermic syringe has resulted in the salvage of treatment failures of multifocal basal cell carcinoma of the face. This method is simple and safe, and the initial results have been excellent. It is an effective modality, especially in infiltrating lesions, and it produces little desquamation or side effects and no damage to the surrounding normal skin. Four cases are presented to illustrate how this method has eliminated the need for ablative surgery.


Long-term levodopa therapy for torsion dystonia. Observation of a 34-year-old woman receiving levodopa for familial torsion dystonia over a four-year period revealed that severe side effects (gastrointestinal problems, dyskinesias, cramps, anxiety) occurred with maximal dosage schedules during the first ten months of treatment. Thereafter, a gradual reduction of the daily dose to 1,500 mg of levodopa gave excellent relief of hypokinesia and rigidity with minimal adverse effects, including abolition of mild akinesia paradoxica which developed after 2 1/2 years of treatment.


Herpes zoster: correlation of age, sex, distribution, neuralgia, and associated disorders. The influence of sex and age on the distribution of lesions, incidence of postherpetic neuralgia, and related disorders in herpes zoster is reported. Results were obtained by reviewing the records of 140 outpatients with herpes zoster seen over a ten-year period. Trigeminal involvement and post-herpetic neuralgia were more common in patients over 50 years of age. The most common sites of lesions in all ages were the thoracic dermatomes, between T-1 and T-8. The distribution of lesions and the incidence of postherpetic neuralgia did not vary between the sexes. High incidences of diabetes and cataracts were found to be associated with herpes zoster infection. Clinical carcinoma of the prostate was a frequent finding in men with herpes zoster over age 50. In those patients with malignancies, there was no correlation between distribution of zoster lesions and location of malignancy.


Hypophysectomy in the treatment of disseminated carcinoma of the breast and prostate gland. Transsphenoidal hypophysectomy offers gratifying palliative relief of pain to patients with metastatic cancer of the breast and prostate. This report represents the results of two years' experience with this procedure at Emory University School of Medicine. The physiologic rationale and clinical indications for hypophysectomy are described, as is the operative technic using the open transsphenoidal microsurgical approach. The series of cases reported here includes 20 men with disseminated prostatic carcinoma and 23 women and one man with metastatic carcinoma of the breast. All 44 procedures were done by the transsphenoidal microsurgical approach. Pain was the preoperative indication for surgery in 41, while three patients were operated on for extensive disease without pain. Satisfactory relief of pain was obtained in 76% of the patients with prostatic cancer and in 83% of the breast cancer patients. While the results are gratifying with regard to relief of pain, the duration of follow-up is not sufficient to comment on the value of the procedure in significantly prolonging life.


Complications of peritoneal dialysis.

Complications of peritoneal dialysis. Peritoneal dialysis is an easily available therapeutic procedure. The complications noted in 490 dialyses over a six-year period in a university hospital have been reviewed. Seventeen major and 624 minor complications occurred. Only four deaths could be attributed to the procedure itself. Peritoneal dialysis is an effective procedure but one with a significant incidence of complications, though few of these are associated with mortality or morbidity for the patient. Various safeguards against these are discussed.


A new synthetic absorbable suture for ophthalmic surgery: laboratory and clinical evaluation. A new synthetic absorbable suture for ophthalmic surgery--glycolactide--was proved superior to chromic collagen in rupture strength and more predictable absorption time in laboratory and clinical studies. The 8-0 glycolactide showed 30% greater initial strength than 8-0 chromic collagen. One week after implantation in rabbit corneas, the glycolactide retained over 90% of its initial rupture strength, while chromic collagen had lost nearly 50% of its strength. After ten days the strength of the glycolactide fell rapidly. By day 21 it began to be absorbed, completely disappearing by seven weeks. Chromic collagen tended to remain in situ longer, although possessing negligible rupture strength. The two materials were compared in suturing comeoscleral wounds of 45 consecutive patients undergoing routine cataract operation. The glycolactide began to disappear only after the fourth week, completely disappearing after nine weeks. Chromic collagen was more variable, some sutures disappearing as early as the third week, while others remained in place for over 20 weeks. Neither suture material excited reaction in the eyes, and the incidence of complications was low.


The syndrome of retroperitoneal hemorrhage and lumbar plexus neuropathy during anticoagulant therapy. A syndrome of retroperitoneal hemorrhage during anticoagulant therapy associated with nerve involvement in femoral nerve or lumbar plexus is described. Twenty-one cases were collected from the English-language literature, and five new cases were added for review and analysis. In these 26 cases spontaneous hemorrhage occurred under iliopsoas fascia in the retroperitoneal space. The clinical picture, involved nerves, laboratory findings of coagulation studies, anemia, and the outcome of these cases are summarized and discussed. Retroperitoneal space may contain a large quantity of internal hemorrhage. Irreversible damage of lumbar plexus or femoral nerve may result from entrapment of nerves in the hematoma. Laboratory coagulation studies may guide effective administration of anticoagulant therapy and minimize hemorrhagic complication, but they will not eliminate the risk of hemorrhage completely.


Acupuncture and sensorineural hearing loss: a review. The use of acupuncture for treatment of sensorineural hearing impairment is a controversial subject among physicians and audiologists. Until recently, sufficient experimental data were not available to guide those who manage hearing-impaired children and adults. The purpose of this paper is to review current research evidence regarding the use of acupuncture technics for treating sensorineural hearing loss. In general, experimental evidence regarding such treatment is not encouraging. Patients should be advised of the questionable value of acupuncture for improving sensorineural auditory deficits.


Ectopic pregnancy: a review of 122 cases. Ruptured ectopic pregnancy constitutes a major gynecologic emergency which may result in death. From 1965 through 1973, 122 patients with ectopic pregnancy were treated at Wilford Hall USAF Hospital. Diagnostic procedures, causative factors, and patient management are reviewed and discussed. The most common symptoms were pain (95%), amenorrhea (79%), and abnormal bleeding (76%). An adnexal mass was found in only 40% of the patients. The treatment of choice was salpingectomy, and there were no deaths in this group of patients.


Technic of deep hypothermia and circulatory arrest in the neonate and infant. Most congenital heart anomalies now can be surgically corrected in a neonate or very young infant. Because their hearts are so small, it is advantageous to work in a bloodless and motionless operative field. Deep hypothermia with circulatory arrest provides this setting. Physiologic problems associated with hypothermia are minimized by inducing general vasodilatation with large doses of methylprednisolone. Surface cooling is done with ice blankets and small sandwich bags filled with crushed ice. The patient's temperature gradually falls to 75.2 F (24 C). After median sternotomy, core cooling can be used to bring the patient's temperature to the desired 68 F (20 C). Circulatory arrest is produced by draining blood into the reservoir and cross-clamping the great vessels and venae cavae. It can be maintained for up to 60 minutes. In infants over six months and over 6 kg (13.2 lb), moderate hypothermia 77 F (25 C) and low perfusion (1/4-1/3 of normal) with short periods (10 to 15 minutes) of circulatory arrest improve operative conditions and allow correction of the most complicated congenital heart defects.


Penetrating injuries of the laryngotracheal area. Penetrating injuries of the laryngotracheal area require immediate maintenance of an adequate airway and prompt surgical exploration and repair. Two basic principles are illustrated by case reports: repairing major vessels before doing the laryngotracheal repair and using adjacent tissues to repair traumatic defects. We suggest a team approach at operation.


Liquid crystal thermography: a measure of therapeutic response to reserpine given intra-arterially. Twelve patients with Raynaud's phenomenon secondary to acrosclerosis and/or systemic sclerosis were evaluated before and after intra-arterial administration of reserpine. The irridescent color changes seen with these liquid crystals support recent evidence for short-term effectiveness of reserpine given intra-arterially.


Hypocalcemia as a complication of jejunoileal bypass for morbid obesity. Hypocalcemia following jejunoileal bypass for morbid obesity is not an uncommon occurrence. Three cases of severe hypocalcemia after bypass operation are presented with emphasis on the altered physiology of calcium homeostasis. Recognition and treatment of bypass hypocalcemia can avert a potentially serious complication.


Influence of tidal volume and pulmonary artery occlusion on arterial oxygenation during endobronchial anesthesia. Arterial blood gases, intrapulmonary right-to-left shunt, airway pressures, and systemic and pulmonary arterial pressures were studied in 20 patients ventilated through a double lumen endobronchial tube during thoracotomy. Inspired oxygen concentration was 98% to 100%. Blood samples for measurement of blood gases and oxygen content were obtained during ventilation of both lungs (VT 15 ml/kg), one lung (VT 15 ml/kg and 8 ml/kg), and after occlusion of the opposite pulmonary artery. Mean oxygen tensions fell significantly, from 310 mm Hg during two-lung ventilation to 155 during one-lung ventilation, and rose again to 280 after pulmonary artery occlusion. Corresponding mean shunt values rose from 25% to 34% of cardiac output and fell again to 25%. When VT was reduced, patients who had had low oxygen tensions (less than 150 mm Hg) at the higher volume showed an increase in PaO2, and conversely. Shunts changed accordingly. Even with this high FIO2, some patients had oxygen tensions of less than 80 mm Hg during lung collapse. PaO2 values during one-lung ventilation were significantly related to patients' preoperative oxygen tensions, as well as to those during two-lung ventilation. In view of the low arterial oxygen tensions found in some patients and the lack of absolute correlation of the PaO2 with tidal volume, an FIO2 of close to 1.0 is recommended during one-lung ventilation, along with frequent or continuous monitoring of the arterial PaO2.


Fractures of the hip in childhood.

Fractures of the hip in childhood. Twenty hip fractures in 19 children aged 2 1/2 to 18 were analyzed in a ten-year retrospective review at the University of Alabama Hospitals in Birmingham, Ala. There was one epiphyseal, one intertrochanteric, 4 subtrochanteric, and 14 intracapsular fractures. The mechanism of injury was usually severe trauma with 31% of the patients sustaining other associated major injuries. Avascular necrosis occurred in three intracapsular fractures (23%), all seemingly related to inadequate internal fixation. Coxa vara occurred in 30% of the patients; all were treated by closed methods, and delayed union and nonunion occurred in 10% of the series. Nine patients developed discrepancies of limb length between 1/2 and 13/4 inches. It was thought that intracapsular fractures should be treated with prompt open reduction and internal fixation with multiple pins; whereas, extracapsular fractures may be treated by either open or closed methods.


Medium and long chain serum free fatty acids in a case of Reye's syndrome. Elevated serum free fatty acids (FFA) have been implicated previously as the agent causing encephalopathy and fatty degeneration of the viscera (Reye's syndrome). This study documents a decrease in medium and long chain FFA from elevated levels (1.35 mEq/liter) to low levels (0.30 mEq/liter) in a patient successfully treated with exchange transfusions.


Minimal brain dysfunction/specific learning disability: a clinical approach for the primary physician. Minimal brain dysfunction is a neurodevelopmental disorder which can be found in nearly 20% of school children. It is characterized by evidences of immaturity involving control of activity, emotions, and behavior, and by specific learning disabilities involving the communicating skills needed in reading, writing, and mathematics. The prime deficits in the classroom are an inability to maintain attention and concentration and an inability to skillfully blend the auditory and visual functions essential in language performance. Medical evaluation will reveal many of the "soft signs" of neurologic involvement, and educational appraisal will indicate a wide scatter in testing scores with a marked discrepancy between evaluated potential and actual classroom achievement. Remedial efforts directed at early detection, relief from pressure and unjust punishment or ridicule from parents and teachers, and adjustment of the educational environment with consideration of the child's individual talents, combined with the judicious use of medications to prolong attention span and improve neurodevelopmental maturity, hold promise of improving the lot of most involved children. There are valid indications that expansion of such programs can do much to prevent these youngsters from developing severe personality maladjustment and delinquent behavior, as well as emotional illness in later life.


Isoniazid inactivation in Black patients with tuberculosis. A 27% incidence of slow INH inactivator (acetylator) status was observed in a group of 100 Black tuberculotic patients. It is suggested that the incidence of INH toxicity may be high in this group of patients and that clinical cognisance of this problem is desirable.


Immunological studies in children with chronic pulmonary infection. Twenty-three children with chronic pulmonary symptoms following acute lower respiratory tract infection were investigated with a view to establishing their immune status. Cell-mediated immunity was depressed in the majority. Serial testing over some months showed improvement in some and fluctuation or non-recovery in others. The leucocyte function, gamma-globulin and immunoglobulin levels were normal.


Placental lactogen in pregnant Natal Indian diabetic patients. The plasma levels of human placental lactogen (HPL) in healthy and in diabetic pregnant Natal Indians were studied. The plasma HPL pattern in the control group was similar to that recorded in the literature and reconfirmed the increase in HPL during normal pregnancy. The plasma HPL of the pregnant diabetics was usually within 1 standard deviation of the mean normal value for that duration of pregnancy. HPL excess could not be incriminated as a cause for the disturbed metabolism in the women with diabetes.


A Poisons Reference Centre for children. A statistical analysis of poisoning cases treated at the Red Cross Children's Hospital is presented. The organisation and functioning of the Poisons Reference Centre is described and an analysis made of the poison ingestions reported to the Centre.


Defective bicarbonate secretion in response to duodenal acidification in patients with chronic gastric or duodenal ulceration. Histamine infusion studies were performed in 54 healthy persons, in 58 patients with duodenal ulcers and in 29 patients with gastric ulcers. The acid load entering the duodenum was estimated by measuring the loss of an intragastric marker, phenol red. The volume of duodenal juice that had refluxed into the stomach and which was aspirated with the gastric juice was estimated by the sodium content of the aspirate. The bicarbonate concentration of the refluxed  duodenal juice was calculated from the relationship between neutralisation and total electrolyte concentration, since the reaction of one bicarbonate ion removes two ions from the resultant mixture. The mean bicarbonate concentration of the refluxed duodenal juice in the control group was 116,4 (+/- 9) mEq/1, and the individual bicarbonate concentrations showed the expected dependence on  the magnitude of the intraduodenal acid load. The mean bicarbonate concentration in patients with duodenal ulcers was 84,6 (+/- 9) mEq/1, which was significantly lower than in healthy persons. In patients with duodenal ulcers and in those with gastric ulcers, the reflux bicarbonate concentrations were independent of acid load. These results confirm previous reports of an impaired pancreatic bicarbonate secretion in response to duodenal acid load in patients with duodenal ulcers, and indicate a similar response in patients with gastric ulcers.


Oesophageal atresia and tracheo-oesophageal fistula. The operative management of oesophageal atresia is reviewed. The operative technique and the approach to management, based on antomical classification of oesophageal atresia and classification into 3 different risk groups, are stressed. The embryology, aetiology, clinical features, symptoms and signs and radiological diagnosis of this condition are also briefly discussed.


Emergency management of acute myocardial infarction by the general practitioner. In the Cape GP Emergency Coronary Care Project, 129 general practitioners (GPs) collaborated over a 14-month period. The objectives were to reach all patients with symptoms of acute myocardial infarction as promptly as possible, and to institute therapy according to a simple protocol, where the emphasis was on the prophylactic administration of antidysrhythmic drugs. The results showed that 38% of a total of 333 patients received treatment within 1 hour of the onset of their symptoms, and 75% within 4 hours. The mortality at the end of 1 month was 15% in 333 patients of all ages, and 10,7% for 272 under the age of 70 years. The over-all community death rate from coronary heart disease in the patients of the participating GPs was 28,3% in 445 patients of all ages, and 23,3% in 356 patients under 70 years of age. These death rates are well below those reported in other comparable series. There was a low incidence of arrhythmic death, and only 1 death among patients who had received appropriate antidysrhythmic therapy. No ill-effects of complications occurred after the routine prophylactic administration of antidysrhythmic drugs. It is concluded that in the prehospital phase of acute myocardial infarciton, the Cape GPs were able to administer a service which compared favourably with that of a mobile intensive coronary care unit, at almost no extra cost to the community, and with very little extra strain on their practices.


Splenectomy and myelofibrosis.

Splenectomy and myelofibrosis. Two patients are reported in whom splenectomy during the course of myelofibrosis was followed by rapid deterioration in the function of a previously involved liver, and was characterised by refractory ascites, increasing jaundice, and death. It is important to recognise this complication, since ectopic haematopoiesis can be demonstrated on liver biopsy and, perhaps, controlled with radiotherapy or cytotoxic chemotherapy.


Pneumopericardium complicating amoebic liver abscess. A case report. Pneumopericardium arises most commonly as a result of a bronchial or oesophageal neoplasm which erodes the pericardial cavity. A case of pneumopericardium associated with amoebic liver abscess, a complication of invasive amoebiasis not previously reported, is described.


Focal dermal hypoplasia (Goltz syndrome) in a male. A case report. A 3-year-old boy presented with the clinical and histological features of focal dermal hypoplasia. Radiological examination showed the longitudinal parallel striations of osteopathia striata. As far as can be ascertained this is the fifth recorded case in a male patient.


Late deaths from endometrial carcinoma.

Late deaths from endometrial carcinoma. An analysis has been made of all the patients with endometrial carcinoma who were seen in our department between 1959 and 1968. A total of 155 patients with a minimum follow-up period of 5 years were evaluated. About 20% of the patients who die, do so more than 5 years after diagnosis and treatment of the primary cancer. A disconcertingly high incidence of death from active tumours is found when patients are followed up for long enough, i.e. 1 in 3 patients who do not die of intercurrent disease. Late deaths are even caused by poorly-differentiated tumours, and also by haematogenous spread. When the results of different treatment regimens are compared, it will thus be necessary to take 10-year survival rates into account.


[Radiology in cases of trauma--an obligatory investigation]. The radiology of trauma is of increasing importance in South Africa, where the treatment of victims of motor accidents forms a major part of emergency medical practice. All practitioners should be aware of the medical and legal obligations that they have to fulfil in this investigation, which nowadays is regarded as part of clinical medicine. The most important principles in the radiology of trauma are briefly discussed.


Osseous manifestations of congenital syphilis. The re-emergence of syphilis as a medical problem in most parts of the world makes it necessary to reinstate the congenital osseous manifestations as an important element in the differential diagnosis of the disease in infancy. The previously well-known snuffles, pseudoparalysis and bizarre radiological changes should now be brought to the attention of perhaps more than one generation of physicians who underwent their medical training at the time when the disease was a rarity.


Lipotoma of the breast diagnosed by film and xeromammography. Five cases of the relatively uncommon intramammary lipoma and 4 cases of the rare adenolipoma were found in more than 5,000 patients who underwent mammography. The mammographic features of the intramammary and paramammary lipomata are given and the characteristic xeroradiographic appearance of adenolipomata is described. The 4 adenolipomata were only visualised by xeroradiography. The reason for these neoplasms being visible on xerograms and not on film mammograms is not clear, but we surmise that it is owing to the 'edge enhancement' phenomenon inherent in the xeroradiographic process. The question whether adenolipomata of the breast are true invasive tumours or mixed neoplasms is discussed.


Insulin secretion in pregnant diabetic Indian women in Natal. A study was undertaken to establish the plasma insulin response to an oral glucose load of 100 g in pregnant diabetic Indian women living in Natal. Eighty-three patients were investigated during the second and third trimesters of pregnancy and during the postpartum period. Although absolute mean plasma insulin values were lower than those found in non-diabetic controls, these patients exhibited compensatory hyperinsulinism typical of late pregnancy. This feature is not present in juvenile onset pregnant diabetic women. Metabolic control of the diabetic syndrome by insulin therapy is mandatory in the latter patients, whereas the former usually respond to the beta cell-stimulating sulphonylureas throughout pregnancy.


Insulin secretion in healthy pregnant Natal Indians. The pattern of insulin release in healthy pregnant Natal Indian women was determined. Progressive hyperinsulinaemia associated with advancing pregnancy was confirmed, together with evidence of a decreased sensitivity to insulin at a cellular level. The plasma insulin response returned to normal in the early puerperium.


Excessive Siamese twinning in Southern Africa. Twelve sets of conjoined twins have been born in Southern Africa since February 1974. This possibly represents a significant increase in the incidence of Siamese twinning and may be the result of unknown environmental agents. Several of the sets of twins were diagnosed antenatally. In view of the current circumstances a high index of suspicion is probably justified in the presence of maternal hydramnios or fetal malpresentation.


Induction of labour with oral prostaglandin E2. Oral prostaglandin E2 was used for inducing labour in 37 patients without initial rupture of membranes. Two dosage regimens were used: in the one 0.5 mg of oral PGE2 was given hourly, and in the other the dose of oral PGE2 was doubled hourly, starting with a dose of 0,5 mg and increasing to a maximum single dose of 2,0 mg. The incremental dosage regimen was found to be more successful in inducing labour than the constant dosage regimen. The success rate was 94,95%. Side-effects were found to occur rarely and to be dose-related. Fetal distress did not occur in this study.


Aorto-oesophageal fistula complicating tuberculous aortitis. A case report. A case of massive upper gastro-intestinal haemorrhage in a Black woman owing to tuberculous aorto-oesophageal fistula is reported. The literature is reviewed and the clinical presentation discussed. This possibly represents only the second case of aorto-oesophageal fistula complicating postprimary tuberculosis to appear in medical literature.


Scalp ringworm among Black children in South Africa and the occurrence of Trichophyton yaoundei. The prevalence of tinea capitis among 153 children who were selected by overt signs of scalp infestation from among 658 Black schoolchildren, was studied in two rural areas of the Transvaal. In both areas (Eastern and Northern Transvaal), Trichophyton violaceum was the predominant dermatophyte species which was isolated. Microsporum audouinii was isolated in both areas from a total of 4 children, but M. canis was the cause of only 1 infection, and that was in the Eastern Transvaal. Five infections caused by T. yaoundei, all of which occurred in the Northern Transvaal, were recorded. They are the first documented cases of endothrix scalp ringworm caused by this species in South Africa.


Angio-immunoblastic lymphadenopathy. A report of 3 cases. Angio-immunoblastic lymphadenopathy (AILD) was diagnosed in 3 Black patients, AILD is a non-malignant disorder which resembles a malignant lymphoma clinically and morphologically. It is thought to represent an abnormal response of B lymphocytes to antigenic stimuli which are often therapeutic agents. The disorder usually affects adults of the older age group and the clinical course can be rapidly fatal, particularly if vigorous chemotherapy is given. Of the 3 patients with AILD, 2 died from complicating infections within 6 months after the initial diagnosis. The third patient was completely cured after short courses of prednisone and vincristine. It appears that in some patients the disorder may be completely reversible but whether these patients are at a greater risk of eventually developing a lymphoma is uncertain at the present time, and remains to be ascertained by their long-term follow-up.


[Carcinoma of Vater's ampulla diagnosed by operative cholangiography: a case report]. A case is reported in which carcinoma of the ampulla of Vater was diagnosed during operation by means of routine cholangiography.


The influence of lateral tilt on limb blood flow in advanced pregnancy. Blood flow of the forearm and calf were measured in 20 expectant mothers by means of strain gauge plethysmography. Measurements were made with the patients initially lying supine, then tilted to the right or left side with a 15 degrees foam rubber wedge and, finally, after returning the subjects to the supine position. Blood flow of the forearm was unaltered by changes in maternal posture. Lower limb perfusion usually increased significantly when the mothers assumed the right or left lateral tilt position, and decreased when the patients again lay supine. The significance of these findings in relationship to aortocaval occlusion by the gravid uterus is discussed. We conclude that lateral tilt of the patient during Caesarean section should contribute significantly to the safety and welfare of both mother and infant.


Tuberculous renal artery aneurysm: a case report. Tuberculous renal artery aneurysm in a 36-year-old Black man is reported. This is thought to be the first case reported in the English language medical literature. The literature is reviewed with regard to presentation and management of renal artery aneurysm in general, with specific reference to tuberculous arterial infection.


[Giant cell tumor (osteoclastoma): a case report]. The history is presented of a 21-year-old woman with an osteoclastoma (giant cell tumour) which was treated with total local excision and an elbow prosthesis. A 5-year follow-up report, the problems of treatment and the different grades of malignancy, are discussed briefly, and the value of histological grading is shown.


The bonds of behaviour.

The bonds of behaviour. Of all the theories purporting to uncover the roots of childhood behaviour and its extension into adult behaviour, the most cogent relates to the physical and psychological bonds of attachment between infant and mother. It is helpful to divide the human lifespan into three periods, each of which has alternating phases of attachment and detachment.


Post-traumatic intestinal obstruction.

Post-traumatic intestinal obstruction. The roentgenographic and pathologic findings in three patients with delayed post-traumatic intestinal obstruction are described. The pertinent literature also is reviewed to delineate the variable pathophysiology of the clinical phenomenon. As a result of the increasing incidence of blunt trauma in our society, the problem of occult intra-abdominal injury resulting in subsequent clinical disease always should be considered in the differential diagnosis of patients presenting later with intestinal complaints. Once considered, routine roentgenologic evaluation usually is diagnostic, and arteriographic evaluation should be considered if the diagnosis is strongly suspected in the face of normal contrast studies. If intestinal obstruction is diagnosed, operative treatment is indicated, simple, and effective.


Clinical experience with modified human umbilical cord vein for arterial bypass. Umbilical veins were removed from human cords, tanned with gluteraldehyde, and surrounded by a polyester fiber mesh. Arterial bypasses were performed with this material in eight persons with threatened limb loss and for whom no other graft material was available. The distal anastomoses were to the small vessels of the leg or to the popliteal artery below the knee. Limb salvage and function were obtained in five patients. Three of these also required early thrombectomy to obtain success. This complication may be related to the presence of gluteraldehyde oligomers and polymers of free aldehyde groups. Morphologic evaluation of the graft suggests that human umbilical cords are a potentially valuable source for vascular substitutes.


The optimal level of anticoagulation for decreasing experimental metastases. Anticoagulation with warfarin is effective in decreasing experimental metastases, presumably by preventing the fibrin coagulum demonstrated to be necessary for the lodging of tumor cells. To determine the optimal level of anticoagulation for maximal antimetastatic effect, two similar experiments were completed with a methylcholanthrene-induced sarcoma in C57Bl mice. Footpad tumors were produced by tumor cell injection and the mice were divided into four equal groups: control, and groups on 1, 2, and 3 mg. per liter of warfarin, respectively. Control and anticoagulated mice were amputated at the same interval. Three weeks after amputation, all were killed and their metastases were quantitated. Prothrombin times ranged from 10 seconds in the control to 30 seconds in the 3 mg. per liter group. In Experiment 1, there was a significant reduction of pulmonary metastases at all levels of anticoagulation. The controls showed a mean number of 7.7 metastases per mouse, as compared to 2.9 (p less than 0.002) at 1 mg. per liter, 2.1 (p less than 0.0035) at 2 mg. per liter, and 0.7 (p less than 0.002) at 3 mg. per liter. In Experiment 2, the significant effect was found only at the 3 mg. per liter dose, with those mice having 2.3 metastases per mouse as compared with 5.5 in the controls (p less than 0.0001). We conclude that full anticoagulation in the range of 2.5 to 3 times normal is required for a maximal antimetastatic effect.


Shunting, release, and distribution of nine and fifteen micron spheres in myocardium. The shunting, release, and transmural distribution of 9 and  15 mu radioactive microspheres were compared in isolated hearts and intact hearts with and without adenosine triphosphate (ATP) vasodilation. ATP vasodilation caused increase shunting of 9 mu spheres but not 15 mu spheres (p less than 0.05). The transmural distribution of 9 and 15 mu spheres in left ventricle and septum were significantly different (p less than 0.01) and the difference was characteristic for the isolated heart and the nonvasodilated intact heart. There was no difference in distribution across the right ventricle. There appear to be significant differences in regional shunting as well as distribution in the intact heart. We found no systematic correction for comparing flows measured with 9 and 15 mu spheres.


The response of diastolic myocardial tissue pressure and regional coronary blood flow to increased preload from blood, colloid, crystalloid. An increase in the left ventricular end-diastolic pressure (LVEDP), resulting from the intravenous administration of blood, a colloid solution, or a crystalloid solution, was accompanied by an increase in both the inner:outer left ventricular wall flow ratio and the diastolic myocardial tissue pressure gradient. With a normal left ventricular end-diastolic pressure, the normal inner:outer flow ratio was just above unity and the minimum diastolic myocardial tissue pressure in the subepicardium was twice as high as in the subendocardium. When the left ventricular end-diastolic pressure was raised, the subepicardial tissue pressure rose earlier and to a higher degree than the subendocardial; thus a gradient which encourages subendocardial flow was increased. This paper correlates the changes in diastolic myocardial tissue pressure and in inner:outer flow ratios which occurred when eight dogs were transfused with blood, seven with colloid, and seven with lactated Ringer's solution. Regional diastolic myocardial tissue pressure was measured by the flow-cessation technique and regional flow by radioactive microspheres. The gradient in diastolic myocardial tissue pressure, which is a major contributory factor to adequate subendocardial perfusion under normal conditions, is of even greater importance when LVEDP is raised.


Plasma levels of secretin in man and dogs: validation of a secretin radioimmunoassay. We have developed and validated a secretin radioimmunoassay that is sufficiently sensitvie to measure circulating levels of secretin in the plasma of man and dogs. At a final dilution of 1:50,000, the antibody bound 30 percent to 40 percent of radioiodinated (125 I) 6-tyrosyl synthetic secretin. Pure natural porcine secretin was used as a reference standard and a linear dose-response curve was generated with 10 to 1,000 pg. of the polypeptide. Little or no cross-reactivity was found when graded doses of other gastrointestinal polypeptides were assayed in the radioimmunoassay and immunoreactive secretin (IRS) in volumes of serum up to 300 mul could be measured accurately.


Alterations in high-energy phosphates in hemorrhagic shock as related to tissue and organ function. Hemorrhagic shock was produced in conscious rats by cannulating the subclavian arteries and bleeding the animals to a mean arterial pressure of 40 mm. Hg, which was maintained for one hour (early shock) or 2 hours (late shock). Analysis of diaphragm (working muscle) showed that there was a significant decrease in adenosine triphosphate (ATP), adenosine diphosphate (ADP), and creatine phosphate levels beginning with early shock, whereas in soleus muscle (resting muscle) these changes were not observed until late shock. Decreases in adenine nucleotides of diaphragm were less than in working organs such as liver and kidney in early shock. This suggests that the extent of decrease in adenine nucleotides during shock may be related to the metabolic activity of the organ.


Splenic abscess.

Splenic abscess. A review of autopsy files and clinical case reports demonstrates two categories of splenic abscess. First, the abscesses discovered at postmortem usually are multiple, small manifestations of widespread, lethal infection in immunologically crippled hosts. A clinical diagnosis seldom is made. Second, the splenic abscesses encountered by the clinician are usually solitary, large, and challenge his diagnostic skills. Recognition is of vital importance, for therapy can be highly successful. Left untreated, the mortality rate is very high. The features, clinical management, and pathogenesis of splenic abscesses are discussed.


Evaluation of a prototype therapeutic system for prolonged, continuous topical delivery of homosulfanilamide in the management of Pseudomonas burn wound sepsis. The ability of homosulfanilimide (HS) delivered from two different dressing vehicles to limit bacterial proliferation was evaluated in burned animals deliberately infected with virulent Pseudomonas organisms. Treatment consisted of once daily topical application of one of two vehicles: (1) an experimental prototype system that utilized micronized HS in a hydrophobic, bioerodible, polymeric matrix, impregnated on a fabric backing; or (2) a commercially available dressing that contained the same mass of drug in a hydrophilic cream base impregnated on the same backing. Wounds on control animals were covered with fabric backing with or without the bioerodible matrix. The experimental system was designed to maintain a finite local concentration of HS on the burn wound for at least 24 hours. It is known that the cream base presents a rapidly decreasing concentration of drug to the burn surface. HS delivered from the experimental system produced a significant reduction in deaths compared with the HS delivered from the cream base. In addition, the new method of delivering HS provided better control of local and systemic infection, and better wound hydration and also promoted earlier eschar separation. The experimental system was at least as convenient to apply as the cream and had an advantage with respect to inspection of the wound, since it could be removed and reapplied easily.


Monitoring of intramuscular pressure.

Monitoring of intramuscular pressure. Increased pressure within an osteofascial compartment may produce a compartmental syndrome, one of the principal causes of local circulatory compromise in traumatized extremities. In certain instances, monitoring of intracompartmental pressure may be a valuable adjunct in the clinical evaluation of patients at risk for this syndrome.


Abdominal aortic aneurysm and renal hamartoma in an infant with tuberous sclerosis. A case is presented of an infant with tuberous sclerosis admitted with status epilepticus. When the seizures were controlled, it was found that the child was hypertensive. A large renal tumor and an abdominal aortic aneurysm was found during the hypertensive evaluation. She underwent abdominal aortic aneurysm resection and radical nephrectomy, and vascular continuity was re-established sucessfully with a Dacron prosthesis. The technique is illustrated. The reconstruction is patent one year following reconstruction. The etiology of the aneurysm is discussed.


Malrotation of the bowel in infants and children: a 15 year review. One hundred and fifty-nine patients with malrotation treated in the Children's Hospital Medical Center between 1951 and 1967 are presented and analyzed with regard to the factors contributing to the success or failure of their management. There were 28 deaths, the majority of which occurred in patients who were less than one month old, had multiple congenital anomalies, or had volvulus of the small bowel with gangrene and perforation. Some of the points we have found most helpful in making the diagnosis are reviewed and the disease as it presents in older children is considered briefly.


Multifactor evaluations of surgical trainees and teaching services. Surgical education has been exposed to increasing challenges as students have moved from the highly structured environment of a university hospital into a variety of clinical settings within the community. Presented with a general surgical service that uses ten relatively autonomous teaching services in seven hospitals, we have developed a computer-based evaluation system designed to provide quality control and a feed-back loop for trainee, teacher, and service. Trainees were rated by comparing them to their peers, with the chief resident as a reference standard. Profiles of each teaching service also were developed and compared one to the other. The results of both studies over a one year period are presented.


Quality assurance: the cost of utilization review and the educational value of medical audit in a university hospital. The components of mandated quality assurance, that is, utilization review (UR) and medical audit, have been analyzed to determine their cost-effectiveness and educational value in a university hospital. At Ths in 1975 were $205,272--$6.71 per admission or $0.69 per patient day. The average costs per admission and per patient day in teaching hospitals in the New York area in 1975 were $10.42 and $0.93, respectively. It is anticipated that these costs will increase markedly in 1976 because of admission review. Since 1972 approximately 9,500 hospital charts have been reviewed annually to identify an average of six patients per year who required the intervention of the UR committee because of unnecessarily prolonged length of stay. The cost of identifying each patient was $33, 212. In the university hospital, the active participation of the graduate (house) staff in patient care renders the requirements for certification/recertification of the need for hospital services or admission review superfluous. From September, 1973, through December, 1975, 15 studies of evaluation of medical care (medical audit) have been completed at an average cost of $4,788 per audit. In ten audits the principal criticism was inadequate documentation of data in the hospital record. Nine audits were critical of excessive use of laboratory services and deviations of practice were identified in seven audits. Medical audit has failed to achieve its objective to identify the educational needs of the hospital staff. It is suggested that a more satisfactory and less costly form of medical audit should be devised. Clinical studies, published in scientific journals, should be considered in the context of medical audit.


The role of prostaglandin E in the hemodynamic response to aortic clamping and declamping. The infrarenal aorta was occluded for one hour in 11 control dogs and in eight dogs in which biosynthesis of prostaglandin E (PGE) was inhibited by administration of indomethacin (2.5 mg. per kilogram). The mean arterial pressure (MAP) in the indomethacin group was significantly (p less than 0.001) higher than in the control group at the end of 60 minutes of aortic occlusion (187 +/- 3 vs. 137 +/- 4 mm. Hg, mean +/- S.E.M.) and remained higher (p less than 0.001) after declamping. However, the decline in MAP at the time of aortic declamping was essentially the same for both groups. Total peripheral resistance (TPR) was higher in the indomethacin group than in the control group at the end of one hour of occlusion (159 +/- 13 vs. 124 +/- 12%, p less than 0.001) and remainded higher throughout the period following occlusion. The plasma concentration of PGE in the control group increased significantly (p less than 0.05) above control (630 +/- 110 to 1,299 +/- 261 pg. per milliliter) during the 60 minute period of occlusion with further increases to 1,447 +/- 389 and 1,523 +/- 256 pg. per milliliter (p less than 0.001) at 10 and 60 seconds after declamping, respectively. In the indomethacin group, PGE remained essentially unchanged throughout the clamping and declamping period and therefore was significantly (p less than 0.05) lower than in the control group. A similar pattern was observed in the tissue levels of PGE. This study suggests that PGE is released during and after infrarenal aortic occlusion and may be responsible for maintaining reduced TPR and MAP. However, hypotension after declamping is not affected by inhibition of PGE biosynthesis.


Melanoma of the trunk: the results of surgical excision and anatomic guidelines for predicting nodal metastasis. From 1958 through 1969, inclusive, 418 patients with melanoma of the trunk were treated at the M. D. Anderson Hospital and Tumor Institute. Of these, 128 patients (31%) had Stage I disease and were treated by excision with observation of regional nodes in all except five patients. Retrospectively these Stage I patients were analyzed regarding (1) survival, (2) sites and timing of treatment failures, (3) the relation of the primary site to eventual nodal metastasis, and (4) the variables of sex, size, and location on the trunk, which also were correlated with disease control. The results show: (1) actuarial survival rate of 65.7% and 55.7% at 5 and 10 years, respectively; (2) positive regional lymph nodes (RLN) evolved in 34 patients (28%), systemic metastases in 18 patients (15%), local recurrence (LR) in four patients, LR plus RLN in one patient, and intransit metastases in three patients as the first evidence of failure. Over 90% of LR and positive RLN developed within 24 months. Many intransit recurrences and systemic metastases occurred later and account for much of the biologic variability attributed to melanomas: (3) the anatomy of the lymphatics of the trunk as described by Sappey is an excellent guide to the site of first nodal metastasis, (4) a midline or near-midline primary site correlated with regional failure (p less than 0.05). More men failed regionally than did women (p less than 0.05). In retrospective calculation, 184 regional node dissections would have been required for probable salvage of 13 patients (10%) if surgical treatment for subclinical disease had been used routinely.


The effects of pulseless perfusion on the distribution of renal cortical blood flow and on renin release. The effects of pulseless perfusion on the distribution of renal blood flow and on release of renin were studied in anesthetized dogs. The distribution of renal blood flow to four cortical layers was determined with the radioactive microsphere technique during pulsatile control conditions and after one and 2 hours of pulseless perfusion, without significant changes in mean arterial pressure and mean total renal blood flow. Simultaneously, renal vein blood samples were analyzed for renin (radioimmunoassay technique). During pulseless perfusion there was a consistent and progressive redistribution of blood flow toward deeper cortical layers with the outer cortical layer falling from 36.9 to 25.3% p less than 0.001) and the juxtamedullary cortex increasing from 14.5 to 25.4% (p less than 0.001) after 2 hours. In addition, there was a progressive increase in renal venous concentration of renin, which was 20.91 +/- 6.6 ng. per millimeter per hour after 2 hours of pulseless flow compared to 5.06 +/- 1.16 ng. per millimeter per hour during control conditions (p less than 0.05). These changes in cortical blood flow and in release of renin were not observed in sham-operated controls. The results indicate that pulseless flow alone produced both a significant increase in renal production of renin and a significant redistribution of renal cortical blood flow, due to the greater vasoconstriction in the outer cortex when compared to the juxtamedullary cortex.


Myocardial utilization of hypertonic glucose during hemorrhagic shock. Awake pigs were rapidly bled 40% of total blood volume to induce hemorrhagic shock. Immediately after the induction of shock, all pigs received a single intravenous injection of radioactive-labeled glucose-U-14C. Simultaneously with glucose-U-14C injection, ten pigs received single central intravenous injections of unlabeled 50% glucose, four pigs received equiosmolar 25% mannitol, six did not receive either 50% glucose or mannitol, and two received 50% glucose plus insulin. Mean arterial pressure with 50% glucose was 89.9 mm. Hg at 15 minutes of shock and significantly higher than without 50% glucose, 48.3 mm. Hg or after mannitol, 46.7 mm. Hg (P = 0.05). Mean cardiac output at 10 minutes of shock with 50% glucose was 2.24 L. per minute and significantly higher than with mannitol, 1.34 L. per minute, or without 50% glucose, 0.94 L. per minute (P = 0.05.). Evidence for increased anaerobic myocardial utilization of the administered unlabeled 50% glucose was shown by a 12% greater production of unlabeled lactate in the venous coronary sinus blood from unlabeled 50% glucose in contrast to those not given 50% glucose at 10 minutes after shock (P = 0.05). Also, 50% glucose significantly increased mean arterial pressure, cardiac output, and survival over both control groups.


The maintenance of gastric mucosal barrier during the early erosive gastritis component of stress ulceration. The spectrum of gastric stress ulceration includes early erosive gastritis, which develops within 48 hours of injury, as well as a late ulcerative component. Previous clinical studies with young healthy volunteers as controls have implicated increased back diffusion of hydrogen ions in the pathogenesis of stress ulceration. The present study compares the gastric mucosal integrity of injured patients to an age-matched control population of patients who had undergone elective intra-abdominal operations. These control patients suffered operative injury similar to that of the injured patients and yet, unlike injured patients, they did not develop clinically overt stress ulceration. The patients were studied during the first 2 days following injury and/or operation. No differences were found in the gastric mucosal permeability to hydrogen ions, as measured by back diffusion of hydrogen ions (H+BD) and by absorption of lithium (delta(Li/PSP), between the injured patients and their age-matched controls, despite the subsequent development of clinically overt stress ulceration in 25% of the injured patients. Likewise, there were no differences between the traumatized patients who developed stress ulceration and either their age-matched controls or the remainder of the traumatized patients. These date suggest that increased back diffusion of hydrogen ions cannot be implicated in the erosive gastritis which is the early component of stress ulceration.


Coronary and cardiovascular dynamics and oxygen availability during acute normovolemic anemia. The hematocrit of 12 dogs was reduced from 43 to 30 and then to 20% by bleeding and simultaneous infusion of lactated Ringer's solution. At each level of anemia, blood volume, heart rate, cardiac output, left and right pressures, left ventricular (LV) work, aortic mean pressure, and systemic vascular resistance were at prebleeding values. Pulmonary arterial saturation decreased from 76 to 67 and 50%. LV coronary venous saturation fell from 46 to 31% at hematocrit 30, with no further reduction at hematocrit 20. Electromagnetically measured left coronary mean flow was 120 and 185% of control at hematocrits 30 and 20. Coronary flow reserve, or the ratio of peak increase in flow after 10 second occlusion to preocclusion flow, was 3.8 at hematocrit 43, 3.0 at 30, and 1.9 at 20. The change in ratio was due to increased resting flow with anemia, whereas peak reactive hyperemia flow did not change with hematocrit. Acute normovolemic anemia is not associated with significant changes in cardiac work. Despite lowered blood viscosity, systemic resistance is maintained by vasoconstriction. Systemic oxygen availability (Cardiac output X arterial O2 content) is decreased, but uptake is maintained by increased O2 extraction. LV O2 consumption is maintained by maximally increasing the already high myocardial O2 extraction and by increasing coronary flow. At half-normal hematocrit, coronary reserve is compromised significantly, indicating cardiac vulnerability at these levels of anemia, especially if coronary occlusive disease or higher work demands on the heart should coexist.


Temporal factors in the reduction of myocardial infarct volume by methylprednisolone. With a canine model of myocardial infarction [ligation of the left anterior descending (LAD) coronary artery] and an intracellular stain for lactic dehydrogenase (LDH) to directly measure size of infarction, the influence of 30 mg. per kilogram of methylprednisolone sodium succinate was evaluted. The intravenous administration of a pharmacologic dose of methylprednisolone one, 2, or 3 hours after the onset of myocardial infarction significantly reduced the ultimate extent of myocardial necrosis, with the greatest reduction seen following the injection of the drug one hour after ligation. The left atrial pressure was significantly decreased by corticosteroid administration, whereas the cardiac index and peripheral vascular tone were improved insignificantly. Inconsistent and/or insignificant effects were observed in the systemic and coronary sinus blood gases and in those indices of myocardial metabolism which were determined. The potential impact of these findings on the clinical applicability of methylprednisolone sodium succinate in acute myocardial ischemia is discussed.


Total thyroidectomy and parathyroid autotransplantation for radiation-associated thyroid cancer. In seventy patients with nodular thyroids and a history of radiation exposure, total thyroidectomy disclosed a 54% incidence of carcinoma; more than half of them had cervial node metastases; four had distant metastases. Fourteen patients required radical neck dissection. The carcinoma was multicentric (both lobes) in 45%. In four patients the carcinoma was found in the lobe contralateral to the one containing the palpable nodule. These findings support the advocates of total thyroidectomy for patients with a nodular thyroid and a history of radiation exposure, provided this operation can be performed with a low incidence of recurrent nerve palsy and hypoparathyroidism.


Acute gastric mucosal ulcerogenesis is dependent on the concentration of bile salt. Studies on animals implicating reflux of bile salts in formation of "stress ulcer" often are suspect because of the inordinately high intragastric concentrations of bile salts used to induce experimental acute gastric mucosal damage. We studied reflux of bile salt in 11 patients after operation. Nine refluxed bile salts in a mean intragastric concentration of 1.87 +/- 0.24 mM. (range, 0.34 to 4.88 mM.). In the present study, therefore, the ulcerogenic potential of physiologic concentrations of bile salts was evaluated. With use of vascularized, chambered canine gastric mucosa, groups of animals were studied during three consecutive periods. Group A = topical acid test alone (ATS) during periods 1, 2, and 3; Group B = (1) ATS, (2) ATS, (3) ATS + vasopressin (VP = 0.1 U per Kg.-min. via the splenic artery); Group C = (1) ATS, (2) ATS + topical 1 mM. sodium taurocholate (TC), (3) ATS + 1 TC + VP; Group D = (1) ATS, (2) ATS + 2 TC, (3) ATS + 2 TC + VP; Group E = (1) ATS (2) ATS + 5 TC, (3) ATS + 5 TC + VP. Parameters evaluated were (1) net fluxes H+, Na+; (2) electrical potential difference  (PD); (3) clearance of aminopyrine, a measure of mucosal blood flow (MBF); and (4) formation of lesions, graded zero to six by an independent observer who used photographs. In nonischemic mucosa, bile salts produced no ulcers, a significant concentration-dependent increase in H+ "back diffusion" and fall in PD, and a noncentration-dependent increase in MBF. In ischemic mucosa, the combination of topical acid, topical bile salts, and mucosal ischemia was acutely ulcerogenic. The severity of mucosal injury was dependent on the concentration of bile salt (y = 0.108 + 1.53x, r = 0.90, p less than 0.01). These data indicate that acute mucosal damage occurs in the presence of physiologic concentrations of bile salt, i.e., those routinely found in the gastric contents of postoperative patients.


[A differential diagnostic abnormality (?) with regard to diarrhoea in calves (author's transl)]. The following article describes the "case-history" of a newborn calf suffering from ordinary calf-diarrhoea. Because the therapy was not successful the animal was examined again. The result was a dichloorvos intoxication caused by a Vaponastrip that was hung up in close contact with the patient.


[A study on the bacteriological aspect of fresh beef. I. Effect of the slaughter of cattle (author's transl)]. In slaughter-houses in the Netherlands the bacteriological contamination of beef-carcases was determined immediately after slaughter. The highest aerobic bacterial count as well as the largest numbers of Enterobacteriaceae were found to be present on the carcases at those sites at which the skin or meat had been cut. It is likely that bacteria are carried from the skin to the meat during cutting. Differences in bacteriological contamination of carcases are attributed to the difference in transmission from the skin. Mechanization of the dressing-line did not have any perceptible effect on the degree of contamination.


[A study on the bacteriological aspect of fresh beef. II. Effect of storage of carcases in slaughter-houses (author's transl)]. Beef carcases were stored in the chilling rooms of seven slaughter-houses for periods varying from ten to thirteen days and bacteriologically examined at regular intervals. At best, the bacteriological state of the carcases continued to be acceptable for nearly two weeks; under adverse conditions, it was acceptable for barely a week. The bacteriological keeping qualities were markedly affected by the temperature and, if to a far less extent, by contamination during slaughter and loss of weight due to evaporation. The importance of these factors as well as that of the method adopted in sampling is stressed.


[Sperm examination of the boar (author's transl)]. During the last ten years the stock of pigs in the Netherlands has doubled. The number of adult boars on pig farms there has in that time trebled. Sperm examination of boars by the Gezondheidsdienst voor Dieren (Veterinary Health Service) in the Dutch province of North Brabant have increased from 83 boars in 1968 to 2045 boars in 1974. The data of boars examined in 1972, 1973, and 1974 have been used to provide an idea of the effects of breed, age, and season on the reasons for the examination and on the quality of the sperm. The group of boars offered for an informatory examination prior to being used has increased relatively strongly in number.


[The most suitable time for mating of the bitch (author's transl)]. The literature on the oestrous cycle in the bitch is briefly reviewed. 283 bitches were studied in order to develop a procedure by which to determine the time of ovulation, i.e., the optimum time for mating or insemination. Examination of vaginal smears, clinical observations of the bitch and sugar tests of the vaginal discharge showed that the sugar test is the most satisfactory method in dog-breeding and, particularly, that it is simple to use. The mean conception rate of the bitches which were inseminated was 71 per cent.


[Investigation of the incidence of Salmonella in the Faeces, mesenteric lymph glands, and intestinal wall (Peyer's patches) of normal pig carcases (author's transl)]. The faeces, mesenteric lymph glands, and intestinal wall (Peyer's patches) of two hundred clinically normal pig carcases were examined. Of these, 115 (57.5%) were found to infected with Salmonella in the following combinations: lymph glands only, 6; intestines only, 14; faeces only, 13; lymph glands + intestines, 7; lymph glands + faeces, 11; intestines + faeces, 20; lymph glands + intestines + faeces, 44. The supposition that Salmonella can be detected in the lymphoid tissue of the intestine (Peyer's patches) far more frequently than in the faeces was not confirmed. The presumably still rising number of clinically healthy butcher's pig which are actually infected with Salmonella is pointed out.


[Rupture of the uterus during gestation (author's transl)]. The case of rupture of the uterus in a heifer approximately seven weeks before parturition is reported. The history suggested a disorder of the digestive tract. In view of the results of clinical studies in conjunction with examination of the blood, rupture of the uterus was suspected. This was verified by post-mortem findings.


No indication of postnatal selection at the HL-A loci. When the HL--A allele frequency and the distribution of 2, 3 and 4 different antigens, respectively, in children and old people were compared no differences could be observed between the two groups. The data thus disprove a simple model by which HL--A heterozygosity should enhance surveillance.


Genetic independence between the HL--A system and deficits in the first and sixth components of complement. From two families, one with Clr deficiency and the other with C6 deficiency, evidence was obtained suggesting genetic independence between the transmission of a 50% deficit in the functional activity of these two complement components and the inheritance of the HL--A system, the ABO system, and the sex of individuals.


[Gonadal load in the radiotherapy of benign diseases. I. Degenerative joint diseases]. The gonadal load was measured during radiation therapy of humeroscapular periarthritis, coxarthrosis, diseases of the vertebral column and of the sacro-iliac joint (disease Bechterew) for different irradiation techniques. All measurements have been performed by LiF dosimeters and with an Alderson phantom using 250 kV X-radiation. The gonadal dose with respect to the surface dose was in the range of tenths of one per mill in case of humeroscapular periarthritis and reached values up to about 30 per cent in coxarthrosis and Bechterew disease. Measurements during irradiation of the vertebral column yielded most differing values of the gonadal load depending on gonadal distances from the region exposed.


[Radiogenic nephritis in relation to splenectomy and irradiation of the spleen bed]. Five cases are reported where under curative aspects the splenic region was irradiated during radiation therapy of lymphogranulomatosis. In the course of this treatment, a radiation load amounting to 3000 up to 4200 R focal dose occurred to the upper pole of the left kidney. A LESION OF THE LEft kidney was diagnosed not earlier than nine or twelve months afterwards in three of the patients. Two patients could be followed up as yet only four or five months. As for verification of the circumscribed radiogenic nephritis, renal scintigraphy proved the best technique to provide information. Short-term check-up examinations are necessary for the purposes of early recognition and efficient therapy of this complication, the prognosis of lymphogranulomatosis being on the whole relatively good.


[Consideration of large in homogeneous regions of the computation of electron dose distributions]. A simple method, suggested by Laughlin and Pohlit for calculation of dose distribution in electron beams which is considering the nonhomogeneous structure of the body, has been examined with regard to its accuracy within the energy range up to 42 MeV. Thereby, the dose distributions calculated and measured over nonhomogeneous thorax phantoms were compared. The method is based on the dose in homogeneous muscular tissue for a depth of area-weight identical to that in nonhomogeneous tissue with corrections being made according to the law of squared distances. Thus, only the loss of electron energy but not the scattering is considered. Smaller nonhomogeneous zones are completely neglected, larger ones treated as regions of equal density. The present study of the region of the lung and previous papers concerning bones [13] and cavities [11] show that the method, apart from near surface cavities, yields a satisfying exactness of the calculated dose distributions. If larger inhomogeneities - especially of the lung - are regarded, their mean tissue density, their shape, size and location ought to be known as exactly as possible.


Dose contribution to regional lymph nodes from gynecological remote afterloading cobalt-60 sources. Dose contribution to the regional lymph nodes from high dose rate gynecological intracavitary technique was studied. For computer, calculating radiation dosage, rectangular lymphograms were taken. The average dose to point B and obturator nodes was nearly equal, 29-28% of point A dose. The common iliac nodes received the lowest dose, 14% of point A dose on the average. Due to the wide variation in the position of the uterus (deviation and dislocation), the dose at each of the two corresponding points or nodes (right and left side) was never equal. The effect of the uterus deviation and dislocation on the dose distribution was also studied in computer model display. We managed to describe this effect by an exponential curve. Because of the wide variation in the position of the uterus, only the individual dose calculation to the lymph nodes makes it possible to determine the most accurate amount of additional external irradiation.


[Uric acid balance in radiotherapy].

[Uric acid balance in radiotherapy]. Administration of uricostatics within the scope of radiotherapeutic treatment is indicated in all cases of manifest primary gout; in cases of latent primary gout, uricostatics should be given especially after administration of high integral doses or in case of large tumors with distinct radiation sensitivity. The decision depends on the renal function, as an increased output of substances to be eliminated by urine may induce an attack of gout in cases of latent gout, or, otherwise, may cause renal lesions followed by acute uric acid nephropathy.


A radioprotective effect of calcium chloride in combination with cystamine, mexamine, and hypoxemic hypoxia in mice. A mild protective effect of a solution of CaCl2 (3.21 g%) injected in a volume of 0.2 ml i.p. 30 minutes prior to irradiation was demonstrated in experiments with male mice in the strain C 57 B1/10. The pre-irradiation administration of CaCl2 increased the LD50/30 by approximately 60R as compared with control animals, to which an isoosmotic NaCl solution was injected. A more pronounced decrease of the post-irradiation mortality of the animals was reached by combined administration of CaCl2 with chemical protectors- cystamine or mexamine administered in relatively low s.c. doses, as well as by a combination of CaCl2 with the protective action of hypoxemic hypoxia. Under the conditions of combined protection, the administration of CaCl2 increased LD50/30 by approximately 100 to 130R. A higher rate of formation of endogenous spleen hematopoietic colonies was observed in the animals protected by calcium. Possible mechanisms of the radioprotective effect of calcium on the level of the hematopoietic stem cells are discussed.


[Electron microscopy studies on the pinocytosis activity of Ehrlich ascites tumor cells in monolayer culture]. During the phase of exponential growth ferritin was added to the culture medium of monolayer cell cultures from the Ehrlich ascites tumor in order to observe the pinocytosis phenomenon in these cells by means of electron microscopy. After a phase of adsorption, the ferritin arrived in vesicles and vacuoles of the cytoplasm - probably by ligature of coat invaginations. Within larger-sized vesicles, which might have been formed by fusion of smaller ones, less electron-dense ferritin-free internal compartments are resulting possibly from interaction with primary lysosomes; this is interpreted as a sign of interior digestive phenomena. Sometimes, this internal compartment was coated with a structure similar to a membrane. In the further course, concentration of the electron-dense zones containing ferritin occurred in the marginal zone of the vacuoles. Some vacuoles comprised two or three of the less electron-dense compartments. Vacuoles containing ferritin were also observed comprising residual membranes. The formation of these transition stages to residual bodies is regarded as an interaction and fusion of heterophagocytic or autophagocytic vacuoles with primary lysosomes.


[Animal experiments on the use of ozone in irradiated and non-irradiated tumors. III. Ehrlich-ascite carcinoma cells in vitro]. Measurements carried in vitro were carried out concerning the effectof ozone either by itself or combined with X-ray therapy (single dose of 2000 R) on the reproductive capacity of Ehrlich-ascites cancer cells. The strongest combination effect is stated when ozone is administered after irradiation. The findings and results of this study are compared with hypotheses and results described in the corresponding literature.


Sterols of scallop. Part II. Structure of unknown sterols by combination gas-liquid chromatography and mass spectrometry. Four sterols, isolated from the scallop Pacopecten magellanicus have been identified as 24-nor-5alpha-cholest-22-en-3beta-ol; 24-norcholest-5-en-3beta-ol; 5alpha-cholest-22-en-3beta-ol; and (E) -24-propylidenecholest-5-en-3beta-ol. These bring to seventeen the total number of sterols identified in this marine mollusc. A fifth newly detected sterol, closely similar in its mass spectrometric properties is 22-cis and trans-cholesta-5, 22-dien-3beta-ol, was clearly distinguished from these by its shorter retention time by GLC.


Oxidation of 17-methylene steroids by thallium (III) and mercury (II) acetates. The reaction of 17-methylene steroids with T1 (OAc)3 in hot AcOH results in the formation of a mixture of allylic compounds. Oxymercuration in t-BuOH followed by reductive demercuration affords 17-methylene-16beta -hydroxyderivatives as the major products.


Total synthesis of diazasteroids (1).

Total synthesis of diazasteroids (1). Contrary to previous reports, the condensation product of 8-aminoquinoline (1) and 2-carbethoxycyclopentanone (2) undergoes ring closure with polyphosphoric acid to give the 1, 11-diazasteroid 5. Catalytic hydrogenation reduced the A ring and the double bond to produce 6. 8-Aminotetrahydroquinoline (7) and 3-carbethoxy-2-piperidone condense to a tricyclic intermediate (11), which could not be cyclized to a steroid, however.


Pregnanetriolone, a normal steroid metabolite: its excretion by normal, Cushing's syndrome and congenital adrenal hyperplasia subjects. Synthesis of 3H-pregnanetriolone permitted the estimation of pregnanetriolone in urine with a sensitivity in excess of most previous claims. A good correlation (r = +0.97) was obtained between the values from gas liquid chromatography and those of a double isotope derivative method. In contrast to previous reports, these methods indicated that pregnanetriolone is excreted by normal adults. Urinary pregnanetriolone levels were 18-59 mug/24hr for normal subjects, 35-290mug/24hr in Cushing's syndrome and 250-7000 mug/24hr with congenital adrenal hyperplasia. It is concluded that pregnanetriolone is a normal steroid metabolite and its occurrence in Cushing's syndrome does not necessary indicate an abnormal steroid biosynthetic pathway.


Syntheses and ultraviolet absorption of aza-steroids. A series of aza-steroids was synthesized containing chromophoric groups, such as a, beta-unsaturated ketones and doubly unsaturated conjugated and monoconjugated heteroannular dienones with the heteroatom in the D ring at the 20 and 17a positions. The effect of an appositely placed electronegative center in these molecules upon their ultraviolet absorptions was studied. In order to obtain a basis for the observed spectral changes, the corresponding carbocyclic compounds were also synthesized. The maximum absorptions of the aza-steroids were hypsochromically shifted relative to the carbocyclic compounds in all cases (n=8). The displacement caused by the electronegative center on absorption maximum of the chromophores is, however, highly dependent on its location within the molecules.


Cholesteryl sulfate and sterol sulfatase in the human reproductive tract. Cholesteryl sulfate is a component of human seminal plasma (avg. 445 mug%) and spermatozoa (15 mug/10 (9) cells) and represents more than 85% of the sterol sulfate fraction. This conjugate is avidly  bound by spermatozoa when compared to other steroids or steroid sulfates. Autoradiographic localization of CS associated with the spermatozoa revealed a greater accumulation of the radioactivity in the acrosomal region in many, but not all, of those cells examined. Semen is not a site of metabolism of the sterol sulfate but the enzyme, sterol sulfatase, is present in the human female reproductive tract. This cleavage enzyme was detected in Graafian follicles and the activity in the endometrium was ten-fold that found in the Fallopian tube. These findings lead to the proposal that cholesteryl sulfate, an amphipathic molecule ideally suited for interaction with membrane components and implicated in erythrocyte membrane stabilization, may be involved in membrane modifications of the spermatozoa during the process of fertilization.


The molecular structure of 3-methoxy-9 (10 leads to 19) abeo- 1,3, 5, (10)-estratrien-17-one. The crystal and molecular structure of 3-methoxy-9(10 leads to 19)abeo-1,3,5(10)-estratrien-17-one has been determined by X-ray analysis in order to ascertain the configuration at C(9). The seven-membered B-ring has a chair conformation and this causes the molecule to bow towards the alpha-face rather than towards the beta-face as in estradiol.


Synthesis of 18-substituted steroids Part II (1). Improvements in the preparation of 18-hydroxyprogesterone. 18-Hydroxyprogesterone is conveniently prepared from 3beta-acetoxypregn-5-en-20beta-ol by a modified route. 3beta-Acetoxy-18-iodopregn-5-en-20-one, obtained by the hypoiodite-photolysis procedure and oxidation, is treated with methanolic silver acetate to give the 18, 20-epoxy-20-methoxy derivative, which crystallises directly without need for chromatography. Hydrolysis of the 3-acetate, and a modified Oppenauer oxidation, gave 18-hydroxy-progesterone in 24% over-all yield.


Proton magnetic resonance spectra of tetracyclic triterpene alcohols under the influence of a lanthanide shift reagent. The proton magnetic resonance spectra were measured for four series of tetracyclic triterpen-3beta-ols, i.e. 5alpha-lanostane, 5alpha-euphane, 5alpha-tirucallane, and 5alpha-dammarane series, in the presence of a molar equivalent of tris (dipivalomethanato) europium, a lanthanide shift reagent. The spectral pattern measured in the presence of the shift reagent was found useful for distinguishing each series and also for characterizing each skeletal isomer of tetracyclic triterpene alcohols.


16-sulfates of estriol in body fluids of human pregnancy at term. A method was developed for the assay of estriol-16-sulfate (E3-16S) and estriol-3, 16-disulfate (E3-3,16-diS) in maternal serum, cord serum and amniotic fluid at delivery in human pregnancy. Tritiated E3-16S and E3-3,16-diS are added to the fluid being analyzed. The conjugates are separated and purified by sequential chromatography on alumina, Celite and Sephadex LH-20. Each conjugate is hydrolyzed with Glusulase and the released estriol is quantified by radioimmmunoassay. E3-3,16-diS was found in each fluid, most concentrated in the cord serum. Small amounts of E3-16S were found in some amniotic fluids, and this conjugate was virtually absent from the sera. These new estriol conjugates comprise less than 1 percent of total, estriol, apparently too low to be of diagnostic value in human pregnancy.


Endogenous concentration of progesterone and 2 slpha -pregnane-3,20-dione in rat decidula tissue. The endogenous concentration of progesterone (P) and 5 alpha-pregnane-3,20-dione (5AP) were determined in the dedicual tissue of mature rats by radiommunoassay. On the 4th day of pseudopregnancy the uterine concentration was 281 +/- 28 ng/g for P and 266 +/- 41 ng/g for 5AP. Horns were traumatized on the 4th day of pseudopregnancy. On the 4th day following trauma the endometrial concentration of P was 100 +/- 7 ng/g and for 5AP was 104 +/- 10 ng/g. Plasma concentrations were 35.5 +/- 4.1 ng/g. For P and 16.1 +/- 4.9 ng/ml for 5AP. When one horn was removed and the contralateral horn was traumatized, there was direct correlation between the endogenous concentrations of P and 5AP in the previously removed utraumatized horn and the amount of decidual tissue in the contralateral horn 4 days following trauma (r2 = .8949). These experiments indicate the endometrial response to progesterone is a complex process determined in part by local metabolsm and the ability of the uterus to concentrate P.


A rapid specific radioimmunoassay for unconjugated estriol in plasma. A rapid, non-chromatographic radioimmunossaay for unconjugated estriol in pregnancy plasma has been developed which utilizes a commonly available antiestrogen antisera. Estradiol-17beta and estrone demonstrate 135% relative cross-reactivity with our antiserum, as compared with 100% for estriol. Specificity is achieved by purification of estriol with solvent partitioning using benzene: petroleum ether (1:1). The results obtained using this method are similar to a radioimmunoassay utilizing a highly specific, but commercially unavailable, antiestriol antiserum. The method is precise, with coefficients of variation ranging from 3.0 to 8.2%.


Synthesis of estrogen methyl ethers by extractive alkylation. A rapid method for the quantitative preparation of a number of estrogen methyl ethers is described. Estrogen in aqueous base is extracted as an ion pair with the tetrahexylammonium oin into methylene chloride where irreversible alkylation (extractive alkylation) by methyl iodide occurs. Gas chromatography (GC) - mass spectrometry (MS) provided the basis for identification of the methylated products. Estrone (1) and estradiol were easily 3-0-methylated whereas estriol gave a dimethylated product. Further experiments suggested that dimethylation of 2-hydroxyestrone in reasonable yield was possible.


Decomposition of 11-deoxycorticosterone and corticosterone in soda-lime glass. When methanolic solutions of tritiated 11-deoxycorticosterone or corticosterone (0.1 to 300 ng) were evaporated to dryness with a stream of nitrogen in soda-lime test tubes only 8-24% of the radioactivity was recovered as the parent steroid. Evaporation in borosilicate test tubes led to a recovery of 90% or more. With ethyl acetate as solvent no decomposition occured in soda-lime test tubes.


Radioimmunoassays for free and conjugated trienbolone and for trienbolone acetate in bovine tissue and plasma samples. A specific, sensitive, precise and accurate radioimmunoassay has been developed for the quantitation of the synthetic anabolic steroid trienbolone acetate (TBA) and its major metabolites, free and conjugated trienbolone (TBOH) in bovine tissues and plasma. With the extraction procedure described unspecific interference with the antigen-antibody reaction could be ruled out. The assay can significantly detect amounts of more than 40 pg TBOH and 70 pg TBA. 0.1 - 2.0 g tissue and 0.1 - 1 ml plasma are sufficient for 1 determination. Residues (range 0.1 -2.0 ng/g) were still present in calves 69 days after implantation of "Revalor" (20 mg estradiol-17beta and 140 mg TBA) with the highest concentrations found in liver and TBA could only be quantitated in fat.


Derivatives of the insect moulting hormone for affinity chromatography, and their biological activities. Several derivatives of the arthropod moulting hormone have been synthesized which were coupled to AH Sepharose 4B yielding about 2 mumole ligand per g wet gel. As an indication of the suitability of the ligands for biological work the puff inducing capacity of their methyl esters was tested. The methyl ester of inokosterone-C-26-carboxylic acid possesses the highest biological activity; lower activities were obtained with the esters of ecdysterone-C-6-CM-oxime and ecdysterone hemisuccinates. Therefore, inokosterone-C-26-carbocylic acid should be a useful ligand for affinity chromatography of ecdysone recptors from insect tissues.


Effect of anticoagulants and inhibitors of platelet aggregation on thrombotic occlusion of endarterectomized cat carotid arteries. Cat carotid arteries measuring 1.8 to 2 mm in diameter were endarterectomized under the operating microscope over a 1-cm segment and the arteriotomy was closed with a 9-0 monofilament nylon suture. Vessels exhibiting significant narrowing of the lumen due to faulty closure of the arteriotomy were excluded from the study. The vessels were divided into six groups according to the method of treatment of the animals: control, aspirin, Coumadin, Coumadin plus aspirin, heparin for less than four hours, and heparin for four to eight hours. All vessels in the untreated group subjected to simple arteriotomy and closure remained patent. Only heparin demonstrated an apparent beneficial effect after endarterectomy with 100% of the vessels treated more than four hours and 30% of those treated less than four hours remaining patent. This is contrasted to a 0% patency in other endarterectomized vessels.


How often are brain infarcts caused by hypotensive episodes? Of 135 patients who were resuscitated after cardiac arrest and who died from one day to several weeks later with morphological signs of systemic cerebral anoxia, there were seven patients (5.2%) with brain infarcts probably caused by hypotensive episodes during or after the resuscitation. There was almost no increase in the frequency of recent brain infarcts with an increasing degree of cerebral atherosclerosis (P greater than 0.90). In contrast, the distribution of ten old brain infarcts in the same material showed a significant correlation to the degree of cerebral atherosclerosis (P less than 0.05). The findings suggest that the combination of cerebral atherosclerotic stenoses and hypotensive is not a major cause of brain infarcts in elderly people. It is suggested that the risk of precipitating brain infarcts by lowering BP in hypertensive patients is not much greater in atherosclerotic than in nonatherosclerotic subjects.


Distribution of cardiac output in dogs during intravenous infusion of betahistine. Cardiac output (CO), arterial blood pressure (ABP), heart rate (HR), blood gases and blood flow (BF) to the brain, heart, kidney and skeletal muscles and other cephalic tissues in five dogs were studied before and at 30 minutes of betahistine infusion (0.12 to 0.2 mg per minute per kilogram). The particle distribution method using radioactive labeled 141Ce (15 mu) and 85Sr (15 mu) microspheres was utilized to quantitate and assess BF and CO. In the five dogs, the increase in CO averaged 20.8%, ABP remained constant, and HR increased in all but one exception where it decreased slightly concomitant with a decrease in Paco2. Brain BF increased (+ 29.6%) in the dogs whose Paco2 reamined constant. The BF increased to the heart (25.4%) and skeletal muslce (80%), while BF to the kidney and other tissues did not change. The change in HR appears to account for the change in CO. The dilating effect of betahistine on blood vessels, in the skeletal muscle, brain and heart could reduce peripheral resistance and decreace ABP. Thus, the increase in HR may be mediated through baroreceptor mechanisms rather than by a direct effect of betahistine. In addition, a decrease in Paco2, is more effective for decreasing cerebral BF than betahistine is for increasing blood flow.


The "richness" of sympathetic innervation. A comparison of cerebral and extracerebral blood vessels. The number of adrengeric nerves was quantified, on both cerebral and femoral blood vessels. No difference was found between the two vascular beds. The data failed to establish a "richer" innervation of cerebral vessels. This is in agreement with my previous, extensive, subjective, and unpublished impression. Consequently, the suggestion of others, which ascribes certain features of cerebrovascular behavior to an unusually rich vascular innervation, remained unproved.


Clinical implications of the Doppler cerebrovascular examination: a correlation with angiography. A directional Doppler ultrasound cerebrovascular examination was compared with angiographical findings of 152 internal carotid arteries. The Doppler examination was abnormal in 36 of 38 (95%) arteries with occlusion or stenosis greater than 75%. Of 63 arteries with lesser degrees of stenosis, the Doppler examination identified only four. There were no false-positive Doppler examinations. If the decision to perform angiography had been predicated exclusively on the presence of abnormal Doppler findings, 61 of 101 (60%) carotid lesions of potential clinical significance would have been overlooked. While the Doppler ultrasound cerebrovascular examinations is the most useful noninvasive technique available for the evaluation of certain specific categories of patients with cerebrovascular disease, the technique is based on hemodynamic alterations of pressure and flow, and cannot be expected to identify the relatively large number of non-hemodynamically significant carotid lesions that are still clinically significant as sources of emboli. This paper illustrates that in the routine evaluation of patients with symptomatic cerebrovascular disease, the Doppler examination should not play a part in the decision to proceed with angiography.


Pial arteriolar responses in the mouse brain revisited. Arteriolar responses were measured on the cerebral surface of the mouse using an image splitter and TV monitor. The response to locally applied norepinephrine (NOR) was significantly more frequent for vessels greater than 30 mu I.D. than for smaller vessels. However, even the smaller vessels were frequently constricted by NOR in doses of 5 mug per milliliter. Reserpine (5 mg per kilogram) failed to alter the response to NOR at either 24 or 72 hours after reserpinization. At 48 hours the threshold dose of NOR was reduced, but the effect was slight (two-tailed, P = 0.08). Both propranolol (10(-6) M3 and phentolamine (10(-5M) blocked responses to 5 mug per milliliter of NOR, but neither agent altered resting arteriolar diameter. Isoproterenol, tyramine, and histamine had no effect. Serotonin (5HT) constricted the arterioles but did not potentiate the response to NOR. Additive or potentiated effects were not observed with NOR 5HT or histamine in any combination. These data indicate the presence of alpha-adrenergic receptors in murine cerebral surface arterioles, but do not establish a significant tonic effect of norepinephrine. The existence or role of a beta-receptor in these murine cerebral surface arterioles remains an unsettled question.