Surgeons in the United States. Practice characteristics. Data on practice characteristics were obtained as part of a national questionnaire study of surgeons in the United States. These included location and organization of surgeons' practices, use of nonphysician personnel, provision of ambulatory care, other professional activities, and variables associated with work load volume. A multivariate analysis was done to examine the relation between operative work loads and various practice characteristics. The variables associated with larger operative work loads were group or partnership practice, principal office not in a hospital, more nonphysician assistants in direct contact with patients, more hospitals in which operations were regularly done, and smaller proportions of nonsurgical patients. Group or partnership practice and nonsurgical practice were found to be most strongly related to operative work load.


A new technique for rapid endoscope-assisted intubation of the small intestine. We describe a simple method for rapid intubation of the small intestine. The method was successful in 13 out of 14 attempts. A forward-viewing fiberscope, two endoscopic biopsy forceps, five rubber bands, and the tube to be positioned are required for the method. It should have broad application for the passage of tubes for small intestinal decompression, jejunal feeding, jejunal biopsy, and biliary and pancreatic drainage studies.


Surgical correction of massive gynecomastia. Massive gynecomastia can produce severe psychological problems for the patient. The surgical techniques employed for simple gynecomastia are not effective in correcting the displaced nipple and excess skin. Utilizing a dermal predicle technique, the excess fat and breast tissue have been removed, along with relocation of the nipple. Satisfactory results and acceptable scars have been obtained in four patients.


Benign gastric ulcer in a patient with betazole-fast achlorhydria. We report a case of benign gastric ulcer that occurred in a 50-year-old man with betazole hydrochloride-fast achlorhydria. The rarity of exceptions to the rule that ulcers in achlorhydric stomachs are malignant (to our knowledge, this is only the sixth reported case) confirms the wisdom of regarding such ulcers as malignant until proved unequivocally to be benign.


Aneurysm formation in an expanded microporous polytetrafluorethylene graft. Microporous expanded polytetrafluoroethylene (PTFE) has recently been proposed as an arterial graft. Although excellent graft patency rates have been achieved both experimentally and clinically, aneurysm formation of the graft has occurred in a small number of cases. This report describes a further case of aneurysm formation in a PTFE graft five months after insertion. We discuss the possible causes of graft aneurysm formation and a newly developed reinforced form of PTFE graft.


Revascularization of the ischemic kidney. Although acute renal artery obstruction causes cessation of kidney function, the viability of the nephron is often maintained by collateral circulation. When renal artery blood flow is restored, filtration is resumed and the resulting acute tubular necrosis is gradually resolved as renal tubular cells regenerate. We have observed several different mechanisms of acute renal artery obstruction resulting in anuric renal failure: temporary suprarenal placement of an aortic clamp during absominal aneurysmectomy, resulting in bilateral renal artery occlusion; embolus, presumably of cardiac origin, to a solitary kidney; and thrombosis of the distal aorta extending to a level proximal to the renal arteries. There is no correlation between the duration of renal artery occlusion and the viability of kidney parenchyma. Viability of the kidney can only be determined by visual inspection at operation and response to revascularization. When vascular obstruction is a possible cause of acute anuric renal failure, immediate angiography is indicated. If a correctable vascular lesion is identified, operative intervention is mandatory.


Evidence for phenotypic mixing between newcastle disease virus (NDV) and a latent virus of BHK 21/WI-2 cells in the early passaged BHK21/WI-2 cells persistently infected with NDV. NDV variants released from the early passaged BHK21/WI-2 cells persistently infected with NDV carry the structural antigen of a latent virus of BHK21/WI-2 cells as a result of phenotypic mixing between NDV and the latent virus.


Further studies on the Cowan strain of Staphylococcus aureus as an aid for the diagnosis of influenza. Standardization of procedures leading to the identification of influenza viruses with the aid of sensitized staphylococci and also comparative studies between coagglutination and HI during 1976/77 influenza season are described.


Persistent infection of primary human cell cultures with rubella variant carrying DNA Polymerase activity. Infection of primary human cells with a rubella variant carrying DNA polymerase activity resulted in persistent infection; infection with wild type virus caused death of the infected cells and a cytopathic effect.


[Effect of different environmental factors on the brain during animal ontogenesis]. The aim of the work was to follow in rats, mice and dogs effects of different environmental factors in certain postnatal periods on the weight indices of the brain. The following factors influenced the brain development: light deprivation, excess of nutrition during suckling period, excess of information. Changes in weight indices are more pronouned if the time of the effect coincides with that of intensive growth and maturation of the brain structure (N. I. Dmitrieva, 1966). Duration of the effects proportionally increases their influence.


Morphogenesis of the nodamura virus in the larbae of the lepidopteran Galleria mellonella (L.). The pathogenesis and morphogenesis of the Nodamura virus, an insect picorna- virus which can also infect vertebrates such as newborn mice, are described in the larvae of G. mellonella. Examination of thin sections of muscle, salivary and moulting glands, hemocytes adipose tissue and hypodermis of the infected larvae of G. mellonella shows in the cytoplasm the accumulation of viral particles either dispersed or in a stringlike or paracrystalline array. These arrays of virions can be within membrane- bound vesicles. Helical filaments of 110 A of diameter can be observed inside the basal membranes and later in the cytoplasm, in relation to the infection of muscular or adipose tissues. The morphogenesis of Nodamura virus in G. mellonella or in suckling mice is very similar to that of the Coxsackie A virus observed in the mouse.


[Effect of hypokinesia and physical loading on the ultrastructure of cardiac myocytes]. The experiments were carried out in rabbits and rats during 1--7.5 months. They demonstrated increasing disturbances in ultrastructure of the protein synthesizing myocardiocyte apparatus. The major and most dangerous disorder is the deficiency in the myocardial apparatus, which is, evidently, the main cause in the reduction of the cardiac functional reserves. Externally, similar reaction of the organism in response to loading (treadmill)--deep fatigue--produces diverse ultrastructural changes in the myocardium depending on the initial adaptive level to motor activity. In rabbits, having satisfactory adaptation to motor activity, the loading (treadmill) results, mainly, in exhaustion of their energy storage. In disadapted animals it produces dangerous lesions in the contractile apparatus of the cardial myocytes.


[Variability of the superficial veins of the dog cerebrum with age]. In 42 dogs of the nine different ages, age changeability of the brain superficial veins is described in details. Topographic-anatomical peculiarities of the dog closely resemble those of the man and, moreover, the dog is often used as an experimental model. The work fills up one of the gaps in age morphology of the experimental animals. Besides, the data represented will help to make further conclusions, comparisons and experiments.


[Multimeasurement analysis of the quantitative spatial organization of epicardial lymphatic capillaries under normal conditions]. Principles of quantitative-spatial organization of the epicardial lymphatic capillaries have been studied in 26 normal dogs' hearts. Multimeasurable systemic models have been constructed to demonstrate how quantitative indices of metrical properties of the capillaries depend on the cardiac size. The possibility is discussed to apply the data obtained in the study of microcirculatory pathology of different genesis.


[Mathematical relationship between the dimensions of the auditory ossicles and fetal age]. Having applied morphometric data obtained on more than 400 auditory ossicles from prefetuses and fetuses at different stages of intrauterine development, the dynamic changes of the greatest size of the malleus, incus and stapes were investigated in age aspect. Increase in size of the auditory ossicles was stated to occur unevenly, every bone having certain periods of the most intensive growth. Mathematical relation of the auditory ossicles growth has been revealed and presented graphically, in an equation. This relation makes it possible to establish mathematically the dementions of the auditory ossicles at any stage of their development. And, according to the auditory ossicles dementions, it is possible to ascertain the fetus age, the data useful for medicolegal practice.


[Ultrastructural features of the interrelationship between nerve fibers and the surrounding tissue in the major arteries of rabbits]. The fine structure of nerve plexus in the rabbit abdominal aorta, ear and coronary arteries has been studied. Four types of the nerve fibre organization corresponding to different levels of sectioning their preterminal and terminal zones have been determined. Axons form large bundles which lose Schwann sheathes and divide into smaller and even single axons as they approach the distal end. Single axons make up contacts with effector cells without forming special synaptic structures. The smalles distance found between axon membranes and smooth muscle cells is 20 nm and 50 nm for the ear and coronary arteries, respectively. In the abdominal aorta, axons lie at a distance of several microns from the muscle sheath. Such arrangement supports the hypothesis of a "distant" nervous influence on the smooth muscle and indicates that the space of nervous influence comprises the tissue surrounding the blood vessel


[Morphologic and histochemical organization of the pericardial nervous apparatus of vertebrates and humans]. It has been stated that the neuronal apparatus of the vertebrate and human pericardium is represented by plexus of myelinated and amyelinated fibers, nerve cells and receptors. The plexus contain both cholinergic and adrenergic neuronal structures. Pericardial neuronal apparatus in the vertebrates and in man reaches its highes development. In the course of human ontogenesis, free diffuse receptors reveal themselves beginning from the 4th month, and more complex incapsulated ones--from the 5th month of the intrauterine development. Neuronal plexus of the fetal pericardium is formed by the 28th week. Cholinergic neuronal elements in the pericardium begin to reveal themselves at the 13th week, and adrenergic ones--at the 14th week of the intrauterine development. The main source of the afferent and vegetative innervation in the pericardium are inferior and superior thoracic cerebrospinal nodes, vagus nerves and branches from the nodes of the sympathetic trunk. Neuronal fibers composing diaphragmal and parasternal nerves and those of celiac plexus reach the pericardium, too.


[Cytophotometric study of the DNA concentration in the supraoptic neurosecretory nuclei of the hypothalamus]. DNA content and distribution in supraoptic neuronal nuclei and in their satellites was studied in human subjects died under different conditions of hypothalamo-hypo-physeal neurosecretory activity: moderate (control) and high. In control observations, prevalence of diploid and paradiploid nuclei both in the secretory neurons and in the nuclei of glial satellites was noted. High neurosecretory activity was connected with a tendency towards increased DNA content in the neuronal nuclei, up to the appearance of some tetraploid elements. In the glial nuclei of the satellites, events of poliploidization were observed, that is, evidently, of adaptive character to maintain active functioning of the neurons under certain intensified conditions.


[Effect of serotonin on the growth and differentiation of the cellular elements of the hippocampus during cultivation]. Dorsal hippocampal fragments taken from newborn rats (1--5 days) were grown in rotating tubes and Maximov's chambers both in a common nutritional medium, consisting of placental human serum, Eagle's medium with embryonal extract and addition of 3 mg/ml serotonin into the medium during the course of cultivation. Experimental and control hippocampal explants were examined 3, 5, 7, 9, 12, 14, 16, 18, 20 and 23 days after cultivation by means of light and electron microscopy. Comparative morphological investigation demonstrated that presence of serotonin in small concentrations in the nutritional medium of the hippocampal experimental cultures not only produced an increased growth and accelerated, comparing with control cultures, cytodifferentiation of neuronal and glial cells but also speeded up, to a considerable degree, the process forming glio-neuronal interrelations, myelinization including, and formation of interneuronal synaptic connections in them.


[Gammagraphic diagnosis of diaphragmatic abnormalities in children]. Hepatic and lung scanning were evaluated as complement methods of congenital defects in the diaphragm, 14 cases were evaluated in which the scan showed alteration on the morphology and function of the liver or lung. On 13 cases correlation was found between the surgical diagnosis and the scan. In 4 cases with diaphragmatic hernia (2 Morgagni and 2 Bochdalek) the scan showed that one portion of the hepatic tissue was localized in the thoracic cavity and in one case of diaphragmatic agenesis in the scan the liver occupied the whole right hemithorax. In 9 cases of diaphragmatic eventration the scan showed alteration of the pulmonary perfussion in large or small areas and generally the hepatic image was displaced towards the thorax. These results showed that the scanning is a trustworthy method and of great help in the diagnosis of congenital diaphragmaic malformations.


[Intestinal pneumatosis. Analysis of 30 cured cases]. The study included 30 patients with gastroenteritis and pneumatosis intestinalis, seen at the pediatric hospital of the IMSS, who followed a satisfactory course. Complications and associated diseases were found in these patients to be less severe than in other patients who died. Lethality in this type of patients (33%) is analyzed together with the clinical records in 33 cases of death from gastroenteritis and pneumatosis intestinalis during the period from January 1974 to April 1975. It was found that the period of hospital stay was shorter than in the group that recovered; that complications leading to death were severe and of acute evolution among which, bronchopneumonia, septic shock, intestinal infarct and others, predominated. Decrease in lethality may be considered to lie in an earlier diagnosis together with prevention and treatment of pneumatosis intestinalis and its complications.


[The Landry-Guillain-Barré-Strohl syndrome]. Landry-Guillain-Barré-Strohl syndrome or polyradiculoneuritis in children is becoming more common. The clinical picture is variable, it may be manifested by motor and sensory findings or by a combination of peripheral and cranial nerve signs and symptoms. This is a report of 60 patients observed at the DIF Children's Hospital between 1971 and 1977. The most significant early predictor of eventual incomplete recovery was the time required for improvement to begin after the maximum involvement was reached.


[Duodenal obstruction in the newborn infant]. The autors present their experience with nine cases of duodenal obstruction in newborns, admitted to this hospital between Janurary, 1972 and January, 1977. Six babies had duodenal atresia and three had stenosis. Two groups were formed based on the patient's weight: Group one (good prognosis) patients with weight above 2.500 g. Group two (poor prognosis) patient's weight under 2.500 g. All the patients of the first group survived and all the patients of the second died. The overall mortality was 4/9. All the patients from the second group (poor prognosis) also showed associated congenital malformations (esophageal atresia, multiple atresias, urological and cardiac disease). Even if the number of cases is not statistically significant, it seems that the weight of the baby and the associated malformations bear on the final outcome of these patients.


[Hemodynamometabolic changes in shock in infants. Report of 2 cases]. Two cases of infants with shock are presented. Cardiac output was determined in both with dilution dye using an auricular oxymeter, with three determinations: at 0, 30 and 60 minutes while receiving intranvenous fluids. At the same time, blood gases and blood lactatewere determined. The first case showed hypodynamic shock secondary to hypovolemia due to severe dehydration, associated to low central venous pressure, low arterial tension, increased peripheral resistance and increased arteriovenous difference of oxygen. The second case was a newborn with sepsis and disseminated intravascular coagulation with hyperdynamic shock with very high cardiac output, low peripheral resistance and low arteriovenous difference of oxygen. Both cases had an initial increase of lactate and a mild decrease at the end of the period of clinical observation.


[Cloverleaf cranial anomaly. Report of 2 cases]. Two cases of cloverleaf anomaly are presented. The first one was associated to complete spina bifida and flexion of elbows and knees, and the second to syndactyly of 3rd and 4th fingers of both hands; short, broad and swerved thumbs; rudimentary bilateral preaxial polydactyly, pes varus with broad first metatarsus. Authors agree with the opinion that this anomaly is a sign which may occur in disorders with early craniosynostosis and emphasise the importance of the identification of the underlying disorder because, knowing its pattern of inheritance, a proper genetic advice may be rendered. The neurosurgical procedure can be useful for cosmetic purposes and for encephalitic decompression, but the results are somewhat unsatisfactory because of the severity of the defect.


Do patients take digoxin?

Do patients take digoxin? Plasma digoxin concentrations on admission to hospital have been compared with levels on day 8 in a group of 50 patients who were maintained on their preadmission digoxin doses for 7 days. In the absence of a change in renal function, 18 patients (36%) had higher levels on day 8 and were considered to be non-compliant: a further 7 patients (14%) had lower levels on day 8 suggesting that before admission they had been taking more than their prescribed digoxin dose. Fifty per cent were, therefore, taking their digoxin improperly. In addition, an incorrect dose of digoxin may have been prescribed in 14 patients (28%) with plasma digoxin concentrations either below 0.8 ng/ml (1.02nmol/l) or above 2.0 ng/ml (2.56 nmol/l) on day 8. Long-term compliance was assessed by comparing day 8 'steady state' digoxin levels with those obtained at outpatient follow-up. Thirty of the original group were studied at 4 weeks when 27 per cent were considered non-compliant, and 20 at 3 months when 30 per cent were non-compliant. These results have serious implications both for drug prescribing and for the treatment of disease, and suggest that a problem of communication exists between doctors and their patients.


[Aplasia cutis congenita].

[Aplasia cutis congenita]. Communication of fifteen cases of Aplasia Cutis Congenita, seen from 1971 to 1977, in the Department of Pediatric Dermatology at the Hospital del Niño DIF (formerly IMAN). Patients of both sexes were equally affected. The scalp was by far the most common location of lesions. Lesiones were usually single and when multiple, they were symmetrical. The family history for the disease was negative. No relationship could be found with obstetric trauma or with the number of pregnancies. Epithelialized lesions were present in fourteen cases and ulcerated lesions in one. The more frequent congenital associated malformations were: cutaneous, neurological, ocular and osseous.


[Organic causes of intestinal intussusception]. Most of the case of intussuception are considered idiopathic, up to 90-95%. In only a small proportion of them an organic cause is identified. The authors reviewed their experience, including 80 cases of intussusception out of which, 14 showed an organic cause. Six cases were lymphomas, four lymphoid hyperplasia of the colon, two Meckel's diverticulum, one enteric cyst and one Henoch's purpura. An organic cause should be suspected in a child with intussusception who is older than the typical idiopathic intussusception age (6-8 months). Also in those cases with a history of a chronic intussusception.


Conducting tissues in congenitally corrected transposition with situs inversus. Three cases of congenitally corrected transposition in situs inversus individuals were characterised by visceroatrial situs inversus, atrioventricular discordance, and ventiruloarterial discordance: one case was studied clinically, and the other 2 were necropsy specimens. The disposition of the atrioventricular conducting tissues was established in each case, in the living patient by intraoperative mapping, and in the necropsy specimens by histopathological investigation. In all, the connecting atrioventricular bundle arose from a normally situated posterior atrioventricular node, normally related to the landmarks of the atrial septum. Though anterior nodes were identified in the necropsy specimens, as reported in congenitally corrected transposition in situs individuals, they differed from those in the latter situation in that they made no atrioventricular connection. These findings have obvious surgical importance. It is suggested that the posterior connection is related to the good septal alignment in these cases which lacked significant septal defects. Posterior connections are not necessarily present in all situs inversus individuals with corrected transposition, particularly when there are malalignment ventricular septal defects: further studies are required in such cases.


Primitive ventricle with normally related great vessels and stenotic subpulmonary outlet chamber. Angiographic differentiation from tetralogy of Fallot. Four patients with primitive ventricle and normally related great vessels with stenotic subpulmonary outlet chamber (Holmes' heart with pulmonary stenosis) are reported. The history, physical examination, and chest x-ray film are not helpful in distinguishing Holmes' heart with pulmonary stenosis from tetralogy of Fallot. Electrocardiogram often provides the first clue to the presence of Holmes' heart; left axis deviation with or without left ventricular hypertrophy is an unusual finding in tetralogy of Fallot, but common in Holmes' heart. Selective ventriculography is diagnostic: the right ventricular outflow chamber overlies the aortic root and aortic valve in the frontal view in Holmes' heart with pulmonary stenosis, but is to the left of the aortic valve in tetralogy of Fallot; no ventricular septum can be identified in Holmes' heart. The diagnosis can be suspected in a child with clinical features of tetralogy of Fallot but atypical electrocardiogram, and can be established by angiography.


Demonstration of pulmonary arteries by contrast injection into pulmonary vein. Pulmonary venous injection of contrast medium in the near-wedge position produced a flow into the pulmonary arterial tree in 15 out of 21 children with cyanotic congenital heart disease. In 5 there was good opacification of both sides from a single injection. The technique provides an additional method of demonstrating the anatomy of the pulmonary arteries where surgical treatment is contemplated.


Prolapsed mitral cusps in atrial septal defect. An erroneous radiological interpretation. Forty patients with simple atrial septal defect had left ventriculograms using cineangiography and/or Elema or Sircam still films. All had open heart surgery and careful scrutiny of the mitral valve by experienced surgeons. Prolapse of the posterior cusp was diagnosed from angiography in 28 patients but was confirmed at operation in only 5. Another 5 had a different mitral valve abnormality and the remaining 18 had no clinical signs to suggest mitral valve dysfunction after operation. It is concluded that though true ballooning or prolapse of the mitral cusps may coexist with simple atrial septal defect, its presence is overdiagnosed from the appearances of left ventriculography on anteroposterior, lateral, and right anterior oblique views. Left ventriculography was equally unreliable in the exact recognition of other anatomical abnormalities of the mitral valve in secundum defect, but accurate when the mitral valve was pronounced to be structurally normal.


Reassessment of changes in leucocyte and serum ascorbic acid after acute myocardial infarction. After an acute myocardial infarction, there is an apparent acute fall in leucocyte ascorbic acid associated with an acute rise in white blood cells and serum cortisol. The apparent fall in leucocyte ascorbic acid is the result of the granulocytosis which occurs after the infarction. Estimations of ascorbic acid disclose that the granulocyte contains approximately half the ascorbic acid of the lymphocyte. When the granulocytosis subsides, the new population of white blood cells is depleted of ascorbic acid for at least 56 days, reflecting tissue desaturation which can be corrected by ascorbic acid supplements. Tissue desaturation is also reflected in subnormal serum ascorbic acid levels which persist also unless ascorbic acid supplements are given. Observations on normal subjects given infusions of tetracosactrin (Synacthen) show that adrenal stimulation can produce a similar rise in white blood cells and an apparent fall in leucocyte ascorbic acid concentration with the exception that the serum ascorbic acid remains unaltered. Therefore, while adrenal stimulation can mimic 'stress' with regard to the changes in the white blood cells, tissue depletion of ascorbic acid as reflected in the white blood cells and serum after a myocardial infarction requires a focus of damaged tissue.


[Myopathy and hypothyroidism].

[Myopathy and hypothyroidism]. Muscular disturbances in hypothyroid children are: generalized muscular weakness of proximal predominance, muscular hypotonicity, pseudohypertrophy (of gastrocnemius muscles chiefly), slow relaxation stage of osteotendinous reflexes, rise of muscular enzymes (CPK andaldolase), unspecific electromyographic changes and histopathologic disturbances comprised by persistent decrease of fibers type II. All these changes are reversible with thyroglobulin therapy; therefore they exert no influence on the prognosis of hypothyroid patients.


[Synovectomy in juvenile rheumatoid arthritis]. Results of 12 late synovectomies in juvenile rheumatoid arthritis (JRA) (6 knees, 5 wrists, 1 hip), have been evaluated. Synovectomies we performed in 5 patients with 7 to 11 years of evolution and with advanced joint lesions at the X-rays. Pain and inflammation disappeared in all synovectomized joints, but one year later the range of motion was slightly decreased in most of them. In the operated hip, the extent of motions decreased at first, but 6 years later it worked better than the opposite. It is concluded that synovectomy in JRA is useful, even with advanced joint lesions. For best results, present day criteria is to perform synovectomy early in the course of the disease.


Critical assessment of diagnostic value of endomyocardial biopsy. Assessment of cardiac biopsy. Right or left ventricular endomyocardial biopsy with the Konno or the Olympus bioptome was attempted in 73 patients aged 5 months to 61 years, with 82 per cent success. Light and electron microscopy showed non-specific features in over half the biopsies with new or diagnostically useful information in only 10 per cent of cases, usually as a result of electron microscopy. The method is safe but is of strictly limited diagnostic value and is likely to be of most help as a research tool in the biochemical study of cardiomyopathies.


Correction of anomalous origin of left coronary artery using left subclavian artery. A case of anomalous origin of the left coronary artery from the pulmonary artery is reported in which surgical correction by anastomosis of the left subclavian artery to the left coronary artery was performed at the age of 6 months. There was a dramatic clinical improvement, and at 22 months repeat angiocardiography disclosed a patent graft and remarkable improvement in left ventricular function. It is recommended that this is the operation of choice for infants in whom cardiac catheterisation fails to show a shunt into the pulmonary artery or the shunt is small.


Technic and complications of percutaneous renal biopsy. A detailed technique to carry out percutaneous renal biopsy is described, together with the complications found in 1,463 procedures. A total of 350 complications (24%) were found, but gross hematuria stood out as the most frequent. In most cases, hematuria was mild and disappeared spontaneously; only 3 patients required transfusion. Following biopsy, 57 cases showed arterial hypertension. One case developed perirenal abscess which was drained surgically. The most important complication was the development of renal pyogenic abscess in a case which ended up in nephrectomy. It is concluded that renal biopsy should be performed only in those cases where the benefit attained by the information surpasses the potential risk. Renal biopsy does not consist only in the taking of a specimen, but also in its adequate study by a specialist with knowledge in renal pathology.


Computer-assisted review of digoxin therapy in the elderly. Current practice with digoxin was assessed in a group of 42 elderly patients by comparing plasma digoxin concentrations attained on previously established maintenance doses with those generated by a computer programme designed to calculate dosage schedules to suit individual patients. Discrepancies between measured and computed plasma levels and between established and computed doses dictated withdrawal of the drug or revision of dosage in 26 patients (62%), with obvious clinical benefit. An important determinant of dosage was renal function; reduction in creatinine clearance provided good evidence for the loss of ability of the elderly kidney to eliminate digoxin. Simple bedside methods are available which permit a reliable estimate of creatinine clearance without a 24-hour urine collection, provoding a rational basis for the choice of digoxin dosage in the elderly.


Postpartum coronary artery dissection.

Postpartum coronary artery dissection. A 27-year-old woman experienced anterior myocardial infarction three weeks after the delivery of her second child. Coronary arteriography subsequently showed primary dissection of the left coronary artery. This patient is believed to be the second reported survivor of angiographically proven peripartal left coronary artery dissection and the only such patient to achieve and maintain asymptomatic status for a prolonged period without operative intervention.


Left cervical aortic arch associated with aortic aneurysm. An aortic arch extending into the neck is a rare congenital anaomaly. Left-sided cervical aortic arch was thought to be much less common than right-sided, but they are now almost equal in incidence in the published reports. This paper describes a case of left-sided cervical aortic arch in an adult, with a previously undescribed association, aneurysm of the descending thoracic aorta. Cervical aortic arch must be considered in the differential diagnosis of pulsatile cervical swellings. The embryological development of the aortic arch is discussed. This is still controversial and it is not possible to be sure of the embryological explanation of this congenital anomaly of the aortic arch from a study of the adult anatomy.


The prostaglandin challenge. Test to unmask obstructed total anomalous pulmonary venous connections in asplenia syndrome. The patient with complex congenital heart disease, severe pulmonary outflow obstruction, and visceral heterotaxia, may have 'silent' obstruction of the pulmonary venous return. Severe reduction of pulmonary blood flow secondary to pulmonary stenosis or atresia in such patients may prevent the usual radiographic appearance of pulmonary oedema. If such obstructed anomalous pulmonary venous connections are not diagnosed before operation, construction of a systemic to pulmonary artery anastomosis will unmask the obstruction, usually resulting in pulmonary oedema and death. We have recently 'challenged' a neonate with dextrocardia, vesceral heterotaxia, presumed asplenia, and complex congenital heart disease including pulmonary atresia, with an infusion of prostaglandin E1 to increase pulmonary blood flow via his ductus arteriosus. This resulted in severe pulmonary oedema which partially resolved after the infusion was discontinued. This was interpreted as consistent with obstructed total anomalous pulmonary venous return. This was confirmed at necropsy. Thus, the infusion of prostaglandin E1 before operation in the patient with asplenia or similar cardiac disease may be of aid in unmasking 'silent' obstructions of the pulmonary veins, and is of obvious value in the preoperative assessment of such patients.


An investigation of the centrally and peripherally mediated cardiovascular effects of etomidate in the rabbit. In the decerebrate rabbit etomidate caused dose-related decreases in mean arterial pressure and preganglionic sympathetic nerve activity. There were no significant alterations in heart rate. Etomidate was found to have no effect on the baroreceptor reflex. In pithed animals the effects of etomidate were of short duration and of a lesser magnitude than in the decerebrate animal. It was concluded that the additional effects in the decerebrate rabbit were a result of depression of central cardiovascular control. It was found that etomidate was largely without effect on the cardiovascular system at normal anaesthetic doses (0.5-1 mg-kg-1). However, larger doses (2-8 mg kg-1) produced marked depression of central cardiovascular control, the myocardium and the peripheral vasculature.


The Bain system: gas flows in small subjects. Rabbits weighing 2-4 kg were ventilated using a Bain type co-axial circuit. Acceptable blood-gas tensions were achieved with a tidal volume of 10 ml kg-1, a frequency of 40 b.p.m., and a fresh gas flow of 3 litre min-1. This technique may be applicable to neonatal anaesthesia.


Effect of pentazocine on renal blood flow. Twenty dogs (weight 8-14 kg) were anaesthetized with sodium pentobarbitone 25 mg per kg body weight and anaesthesia was maintained with nitrous oxide in oxygen. Respiration was controlled with a volume-limited respirator (PaCO2 4.7 +/- 0.4 KPa). Renal blood flow was measured with a square wave electromagnetic flow meter inserted through a left paramedian laparotomy. Renal blood flow decreased transiently following an i.v. injection of pentazocine. The decreases were 81% +/- 10.8 and 77% +/- 3 of the control following the administration of pentazocine 1 mg and 2 mg per kg body weight respectively (P less than 0.01). Renal blood flow returned to control values 10-15 min after the injection of the drug.


A sensitive gas chromatograph assay for thiopentone in plasma. A sensitive flame ionization gas chromatograph assay method has been developed for thiopentone in human plasma. The extraction procedure minimizes desulphuration of the drug while removing most endogenous substances and is limited by a maximum of 50 ng ml-1 in 2-ml plasma samples. There is linearity throughout the 30.0-5.0 microgram ml-1 and 5.0-0.1 microgram ml-1 ranges. Extraction of six replicate 2.5-microgram ml-1 samples resulted in a coefficient of variation of 3.0%. Similar treatment of six 0.20-microgram ml-1 samples afforded a coefficient of variation of 4.6%.


A method of gas chromatography using electron-capture detection for the determination of blood concentrations of halothane, chloroform and trichloroethylene. A method of gas chromatography using electron-capture detection for the determination of the concentration of the halogenated anaesthetic agents halothane, chloroform and trichloroethylene in blood is described. The accuracy of the analysis (measured blood concentration as a percentage of the calculated concentration) was: Halothane (11 blood samples in the range 37.9-6.00 mg/100 ml), mean 100.7 (SD 2.27), range 97.3-104.0; (12 samples in the range 0.164-0.0045 mg/100 ml), mean 98.8 (SD 6.80), range 90.7-111.1. Chloroform (five blood samples in the range 63.6-7.40 mg/100 ml), mean 100.4 (SD 1.30), range 99.3-102.5. Trichloroethylene (five blood samples in the range 20.6-13.2 mg/100 ml), mean 101.6 (SD 1.60), range 99.6-104.0.


Heat loss during anaesthesia.

Heat loss during anaesthesia. The superficial and deep body temperatures of 23 patients were studied during prolonged anaesthesia for microscopic surgery of the fallopian tubes. The patients were divided randomly into three groups, receiving either halothane 0.5%, halothane 1% or low-dose fentanyl as a supplement to nitrous oxide, oxygen and myoneural block. Other variables were kept constant, and the theatre temperature was maintained at 24 degrees C. Temperature changes were unrelated to both the type of anaesthesia and the percentage of subcutaneous fat to body weight. Halothane 1% decreased the rate of heat loss in the 3rd hour. Large heat losses occurred on transfer to the recovery room, where the total heat produced increased rapidly and was unrelated to shivering.


Effects of a diazepam-fentanyl mixture on cerebral blood flow and oxygen consumption in man. The effects of a mixture of diazepam and fentanyl on cerebral blood flow (c.b.f.) and cerebral metabolism of oxygen (CMRo2) were studied in eight normal subjects and 13 patients with organic brain disease. The coupling of flow and metabolism and the carbon dioxide responsiveness of the c.b.f. were studied also. In the normal subjects the injection of the mixture resulted in a significant decrease in c.b.f. (34%), and a similar decrease in CMRo2 (34.5%). The vasoreactivity of the brain to carbon dioxide was maintained. C.b.f. decreased in all patients with intracranial pathology.


High spinal nerve block for large bowel anastomosis. A retrospective study. In a retrospective study, 68 large bowel anastomoses carried out on patients under subarachnoid or extradural spinal nerve block with light general anaesthesia were compared with 26 anastomoses on patients receiving general anaesthesia alone. Dehiscence occurred in 7.4% of anastomoses performed under spinal nerve block compared with 23.1% in the control group. In patients receiving morphine, anastomotic dehiscence occurred after 15.2% of operations, compared with 5.9% in patients receiving pethidine. These differences are not statistically significant. However, the findings indicate the need for larger prospective studies.


Hyperglycaemic effects of Hartmann's solution during surgery in patients with maturity onset diabetes. The metabolic effect of infusing 1.0-1.5 litre of Hartmann's solution to normal subjects and those with maturity onset diabetes has been studied during surgery. It was found that the use of Hartmann's solution after operation was associated with a 7.5 mmol litre-u increase in plasm glucose concentration compared with an increase of 2.1 mmol litre-1 in diabetic patients who received no i.v. fluids. In non-diabetic subjects who received Hartmann's solution the increase was 2.5 mmol litre-1. It is suggested that Hartmann's solution may be metabolically disadvantageous in diabetic patients.


Suxamethonium-induced muscle contracture following traumatic denervation in man. The effects of the systemic and of the i.v. regional administration of suxamethonium were investigated in 23 patients with traumatic nerve injury. Following the systemic administration of suxamethonium 100 mg, normally innervated muscles showed muscle fasciculations initially, followed by muscular relaxation. On the other hand, denervated muscles did not fasciculate and, in 21 patients, manifested suxamethonium-induced contractures. In the other two patients no response was observed. In 10 of the patients, the i.v. regional administration of suxamethonium 5 mg was followed by a contracture of the denervated muscle which was maintained until the tourniquet was deflated. No systemic reaction to suxamethonium, other than mild ptosis, followed the release of the tourniquet.


Fracture of a float catheter. A case report. Fracture of a balloon-tipped flow-directed catheter is described. The circumstances associated with the fracture are discussed, but no definite cause could be determined.


A concept of diffuse actinic arteritis. The role of actinic damage to elastin in 'age change' and arteritis of the temporal artery and in polymyalgia rheumatica. Actinic damage (actinic elastosis) affecting the internal elastic lamina appears to be the prime cause of 'age change' and arteritis of the temporal artery. Resorption and removal of altered elastin (elastolysis) is an integral part of the pathology of actinic damage. Actinic irradiation is probably responsible for the destruction and disappearance of a vast number of arterioles in elastotic skin. The intimate connection between temporal arteritis and polymyalgia rheumatica prompts the belief that the vascular and other internal malign components of the temporal arteritis/polymyalgia rheumatica syndrome might likewise be due, albeit indirectly, to the same actinic cause. Actinic elastotic damage at the body surface could have this effect by provoking a state of systemic elastolysis. Although ultraviolet (uv) light is often regarded as the sole cause of actinic elastosis, penetrating infrared (heat) irradiation may deserve a large or even a dominant share of the blame.


Penicillamine pemphigus and the nephrotic syndrome occurring simultaneously. Proteinuria and the nephrotic syndrome are well known to occur as complications of penicillamine therapy, but reports of penicillamine-induced pemphigus have been relatively few. This is the report of a case in which both complications occurred simultaneously.


A new apparatus for the delivery of high intensity UVA and UVA+UVB irradiation, and some dermatological applications. A new apparatus consisting of a 200 W super pressure mercury lamp and a flexible light guide with a liquid light-conducting core is presented. Its transmission for UVA irradiation is more than threefold as compared to conventional quartz fibre optic bundles. The light guide is capable of transmitting density levels exceeding I W/cm2. UVA and UVB are transmitted. By inserting a filter platelet (WG 345) into the light guide the UVB is cut off. The output of the unfiltered guide is 700 mW (3570 mW/cm2), of the filtered guide 400 mW (2040 mW/cm2), centered mainly at 366 nm. The light apparatus proved useful for several dermatological applications. It replaces in many respects conventional Kromayer lamps, especially because the flexible light guide, which is 160 cm long and weighs only 210 g, can be brought into direct contact with the skin. Results of determining the minimal erythema dose (MED), of phototesting (8-MOP photoallergy, persistent light reactor, erythropoietic protoporphyria) and of photochemotherapy are given.


Tests to establish the diagnosis in cholinergic urticaria. Methods for establishing the diagnosis in cholinergic urticaria are reviewed and compared. Provocation by exercise or hot bath is more effective than local provocation by intradermal tests. Of the intradermal tests, responses to nicotine acid tartrate and acetyl beta methylcholine chloride are positive only in patients with the more severe, readily induced eruptions. Furthermore, intradermal testing is not always reproducible in the same patient. In our patients, exercise proved the simplest, most effective diagnostic test.


Oral psoralen photochemotherapy of atopic eczema. Oral administration of 8-methoxypsoralen followed by exposure to a high-intensity longwave ultraviolet treatment system resulted in clearing of atopic eczema in 15 patients. Paired-comparison studies demonstrated that this treatment was superior both to conventional ultraviolet light therapy and to no treatment. Short-term observation suggests that regular therapy is necessary to maintain remission of the disease.


Myocardial infarction, androgen and the skin. Various indices of masculinity were compared in 48 men who had recovered from myocardial infarction and in their age-matched controls. We found little evidence to support the idea that myocardial infarction is related to increased androgenic stimulation. The patients with myocardial infarction had no increase in plasma testosterone, muscle thickness, sebum excretion rate, maximal sweat secretion rate, male pattern alopecia or density of terminal body hair, but as a group they had a slight increase in skin and bone thickness compared with the controls.


Gluten-free diet in dermatitis herpetiformis. II. Morphological and immunological findings in the skin and small intestine of 12 patients and matched controls. Twelve patients with dermatitis herpetiformis whose skin condition responded to a gluten-free diet (GFD) were re-examined after diet treatment. The findings were compared with those in matched patients on a normal diet. Jejunal histology revealed morphological improvement in every patient on a GFD whereas all patients on a normal diet continued to have villous atrophy. Intra-epithelial lymphocyte counts were normal in 8 patients on a GFD in contrast to one on a normal diet. Immunofluorescence examination of the jejunal mucosa revealed that the numbers of cells containing IgA and IgM were increased significantly in the normal diet group. The figures were lower in the GFD group but these also exceeded the values in the controls. IgA deposits were found in the uninvolved skin of every patient irrespective of the diet treatment, but the fluorescence seemed to be less intense in patients on a GFD. A clear difference was found in the occurrence of C3 deposits in the uninvolved skin. Three patients on a GFD had C3 deposits; two of these did not follow a strict diet. However C3 was found in 8 patients on a normal diet. Circulating dietary and auto-antibodies were found in two patients on a GFD and in 9 on a normal diet. Serum immunoglobulin (IgG, IgA, IgM) and complement (C3, C4) levels were within normal limits in both patient groups.


Psoriasis in Sri-Lanka--a computer analysis of 1366 cases. A clinical and epidemiological study of psoriasis in Sri-Lanka is presented. The prevalence in the population is estimated to be over 0.4%. The clinic incidence was 8.7%; of these 53.2% were male, and 46.8% female and 8.3% reported a family history of the disease. The mean age at onset was 25.2 years. The frequency distribution for the age at onset was bimodal with peaks at the second and fifth decades. The age at onset was significantly low in females, in patients with a family history of the disease, in those affected by weather changes and in patients whose disease was precipitated by sore throats. The existence of natural subpopulations of patients is suggested. Clinical types and complications of the disease were not essentially different from those observed in the West.


Lymphocytotoxicity in mycosis fungoides. The phenomenon of lymphocytotoxicity was demonstrated in 29 patients with mycosis fungoides, using a newly described epithelial cell culture system and an isotope marker, 125Iododeoxyuridine (125IUdR). Lymphocytotoxicity was demonstrated in patients in the generalized plaque and the erythroderma phases of the disease (P is less than or equal to 0.05). No significant lymphocytotoxicity was demonstrable in patients who were in the limited plaque (early) phase of the disease. It is hypothesized that this demonstration of lymphocytotoxicity in patients may be a manifestation of a delayed hypersensitivity response to an as yet unidentified antigen in the epidermis.


A randomized controlled trial of selective planned delivery. A prospective randomized controlled trial designed to investigate selective planned delivery is reported: 264 obstetrically normal women in the 38th week of pregnancy were admitted to this trial and 184 completed it. The infants of mothers in the planned delivery group had higher serum bilirubin levels on the fifth day post partum than control infants but no baby required treatment for hyperbilirubinaemia. Mothers in the planned delivery group required significantly greater amounts of pethidine while control mothers had a significantly higher incidence of meconium staining of the amniotic fluid. However, the infants in the two groups had similar Apgar scores at birth. There was one stillbirth in the control group; this was due to unrecognized fetal hypoxia during labour induced at 42 weeks for postmaturity.


Prostaglandins in the human umbilical circulation at birth. Prostaglandin E (PGE), prostaglandin F (PGF) and 13, 14-dihydro-15-keto-prostaglandin F (PGFM) have been measured in umbilical cord plasma obtained immediately after delivery of the baby before clampiing of the cord. In general the prostaglandin levels followed the pattern PGFM greater than PGE greater than PGF. A significant arterio-venous difference was demonstrated only for PGE with raised venous levels (P less than 0.01). In cord blood samples obtained from infants whose mothers had received epidural anaesthesia, no arterio-venous difference for PGE could be demonstrated although the mean levels were not significantly different from controls. The concentrations of prostaglandins in umbilical cord plasma proximal to the placenta were found to rise continuously from the time of delivery of the baby with no significant changes after cord clamping or placental delivery. The possible physiological significance of these findings is discussed.


The distribution of arachidonic acid in plasma and tissues of patients near term undergoing elective or emergency Caesarean section. The distribution of arachidonic acid in both the free and the bound state was measured in the maternal circulation, the fetal circulation and tissues within the pregnant uterus in 16 patients undergoing Caesarean section. Half of the patients had an elective Caesarean section and half had a Caesarean section during labour. No differences in arachidonic acid concentrations were found between the maternal or fetal circulations in women having elective Caesarean section and those having a Caesarean section in labour. The total and bound values of arachidonic acid in myometrium were higher in patients undergoing Caesarean section in labour. There was also an increased amount of arachidonic acid when expressed as an arachidonic acid/palmitic acid ratio between the fetal circulation and the maternal circulation, suggesting an active transport mechanism for arachidonic acid across the placenta. Levels of free arachidonic acid were in microgram quantities in both plasma and tissues, suggesting that the availability of free arachidonic acid was not the limiting factor in prostaglandin production.


The effect of pregnancy and two different contraceptive pills on serum lipids and lipoproteins in a woman with a type III hyperlipoproteinaemia pattern. We report a woman who had a moderate elevation of serum triglycerides with a type III pattern of hyperlipoproteinaemia when taking a normal diet. She developed eruptive xanthomata with a grossly raised serum triglyceride concentration and chylomicronaemia when pregnant and also when taking a combined oral contraceptive pill containing 50 microgram of oestrogen. The xanthomata cleared and the triglyceride level fell when the combined oral contraceptive pill was changed to one with a lower oestrogen content, clofibrate was prescribed and the diet was restricted in carbohydrate and fat. Persistent chylomicronaemia is a serious complication of pregnancy because of the risk of pancreatitis and the potential risk of fetal malnutrition. Treatment with diet and clofibrate is indicated. High oestrogen-containing contraceptive pills appear to be contraindicated in patients with type III or other hypertriglyceridaemic states.


Inhibition of lactation and inhibition of prolactin release after mechanical breast stimulation in puerperal women given tamoxifen or placebo. Tamoxifen was given orally to 60 puerperal women to inhibit lactation. Twenty control puerperal women were given placebo. Fifteen women receiving tamoxifen and 15 women receiving placebo were studied before, during and after the use of a breast pump under basal conditions and after five days of treatment. Tamoxifen was effective in inhibiting lactation; no rebound phenomena were observed. Its administration was free from side effects. This drug was capable of preventing the prolactin release induced by mechanical breast stimulation. Placebo failed to inhibit lactation and had no effect on prolactin release induced by the use of a breast pump.


Serum prolactin, gonadotrophin and oestrogen levels in women receiving hormone replacement therapy. Prolactin, oestrone, oestradiol, FSH and LH concentrations have been determined in postmenopausal women receiving different forms of hormone replacement therapy. While the serum oestrogen levels achieved were sufficient to cause a significant decrease in circulating FSH and LH levels, no significant change in prolactin concentrations was found. Two other findings are of interest: despite the absolute concentrations achieved, the ratio of FSH to LH and the ratio of oestradiol to oestrone did not change significantly on any of the hormone formulations used; and while FSH and LH were both suppressed to a significant degree on therapy neither was suppressed to premenopausal values suggesting the possibility of a 'female inhibin' in the normal regulation of gonadotrophin secretion.


Effects of nifedipine on myometrial activity and lower abdominal pain in women with primary dysmenorrhoea. The effects of the calcium antagonist nifedipine on uterine activity and lower abdominal pain were studied during the first menstrual day in 10 women with severe primary dysmenorrhoea. Intrauterine pressure was recorded at three different levels by means of microtransducers. Nifedipine, 20 to 40 mg given orally, within 10 to 30 minutes effectively reduced the myometrial activity and relieved the pain. A moderate increase in heart rate, and a transient facial flushing were noted. In some patients receiving 30 or 40 mg this was associated with a slight headache. Otherwise no side effects were observed. It is suggested that calcium antagonists can be used to treat primary dysmenorrhoea and other conditions in which an inhibition of uterine activity is desirable.


Spontaneous voiding after surgery for urinary incontinence. Eighty patients with urinary incontinence were treated by colposuspension and bladder neck plication. Fourteen patients had difficulty in establishing normal micturition postoperatively. Of these, 10 patients took longer than 21 days to void and had reduced peak urine flow rates after surgery; the other four patients voided within ten days of surgery but had reduced peak urine flow rates before and after surgery and all had residual urines in excess of 100 ml following surgery. The value of the preoperative diagnosis of pre-existent bladder dysfunction by symptomatology and the peak urine flow rate is discussed.


Haemorrhage into the anterior pituitary during pregnancy after induction of ovulation with clomiphene. A 34-year-old woman with secondary amenorrhoea and primary infertility became pregnant after treatment with clomiphene. She developed pre-eclampsia. Visual symptoms were experienced due to rapid enlargement of the anterior pituitary gland. The patient was delivered by Caesarean section. At subsequent craniotomy the patient was found to have haemorrhage into the pituitary gland, but histological examination of the pituitary tissue which was removed revealed no tumour tissue. One year after delivery the patient was still amenorrhoeic and had galactorrhoea with hyperprolactinaemia indicating that she probably had a small pituitary adenoma which was incompletely removed during neurosurgery.


Axillary and vulval breasts associated with pregnancy. A patient with accessory breasts in the vulval and axillary regions is presented. There was very little change in accessory breasts during and after pregnancy.


Risk of pre-term delivery in patients with previous pre-term delivery and/or abortion. Patients with a history of two or more pregnancies which ended spontaneously before 37 weeks gestation had an increased risk of spontaneous pre-term labour and delivery in future pregnancies. This increased risk related mainly to previous second trimester abortions and not to previous first trimester abortions. Patients with one previous spontaneous pre-term labour and delivery had a 37 per cent risk, and those with two or more pre-term deliveries a 70 per cent risk of again delivering pre-term. There appeared to be no beneficial effect of cervical suture on the incidence of pre-term delivery in these patients.


Effect of maternal glucose ingestion on fetal breathing and body movements in late pregnancy. Fetal breathing movements and fetal whole body movements were observed over 2 hours in 22 normal singleton pregnancies between 34 and 38 weeks gestation using a real time ultrasonic B scan method. The proportion of time fetuses spent making breathing movements increased from 9.9 per cent to 48.3 per cent within one hour of their fasting mothers taking a 50 g glucose drink. Fetal whole body movements were not increased after maternal glucose ingestion. Arousal of the fetal central nervous system seems dependent on the level of fetal blood glucose.


Non-pregnant maternal plasma volume and fetal growth retardation. The hypothesis that low maternal blood volume is an aetiological factor in fetal growth retardation was considered. It was found that a high proportion of women who had repeatedly given birth to small-for-dates babies had a low non-pregnant plasma volume.


Pulsed oxytocin infusion in the induction of labour. A randomized controlled trial was mounted in which induction of labour at term was successfully accomplished in 12 patients by amniotomy and intermittent (or pulsed) oxytocin, compared with 16 patients receiving continuous oxytocin. In the pulsed group, oxytocin was infused for one minute in every ten using a modified Cardiff Infusion System Mark III in the automatic setting. Compared with the control group the induction-delivery and induction-to-full-dilatation intervals were similar but the total dose of oxytocin required was significantly lower in the pulsed group than in the control group.


Anion diffusion selectivity in a pore model. The phosphatidylcholine-water lamellar phase. The diffusion coefficients D(cm2.s-1) of the sodium salts of a series of hydrophilic mono- and dicarboxylic acids, have been measured in the hydrophilic layers of phosphatidylcholine-water lamellar phases, as a function of phase hydration. At pH 9.0, the diffusion rates of the anionic (RCOO-) form of the acid exhibit a prominent increase within a narrow range of water content, specific to each anion. This high diffusion rate seems to occur when the Stokes diameter of an anion is equal to the thickness of the aqueous layer between the two planes formed by the quaternary ammonium groups of the choline phosphate dipoles of two facing layers of phosphatidylcholine molecules. This phenomenon demonstrates the importance of the spatial organization of successive binding sites in the rate constant of diffusional processes in hydrophilic channels.


Charge-pulse relaxation studies with lipid bilayer membranes modified by alamethicin. Charge-pulse relaxation studies with the alamethicin-lipid membrane system reveal a triphasic decay of membrane voltage. At short times (resolution time 2 microseconds), where a voltage decay due to the orientation of alamethicin dipoles from the interface into the membranes interior ("gating current") could possibly be expected, only a slow decrease with a time constant determined by the bare membrane conductance occurs. After approximately 1 ms (depending on the experimental conditions) the formation of alamethicin pores starts, leading to an increase in the voltage decay rate. When the characteristic voltage Vcpc is approached, pores close and after passing Vcpc the voltage decreases slowly again according to the bare membrane conductance. Vcpc is determined as a function of the initially applied voltage Vo, alamethicin and KCl concentration. Since the membrane voltage decreases continuously, the system does not reach the equilibrium states obtained at constant voltages. Taking the presented experimental results into account the estimate of the electrical potential at the functional membrane of photosynthesis induced by a saturating single turnover flash of deltaphio approximately 105-135 mV (Zickler, Witt and Boheim (1976) FEBS Lett. 66, 142-148) is changed to deltaphio approximately 200 mV.


Biochemical characterization of the submicrosomal membrane of the rat brain. Selective solubilization of the components of the light smooth-surfaced membrane by lysophosphatidylcholine. The light smooth-surfaced membrane, one of the three membrane fractions derived from the rat brain microsomal fraction, was fractionated into its soluble and insoluble parts by the use of lysophosphatidylcholine and the chemical composition of these was investigated. Under the condition whereby the maximal amount of the membrane protein was solubilized by lysophosphatidylcholine (0.5% lysophosphatidylcholine at 37 degrees C for 10 min), the insoluble residue, which accounted for approximately 30% of the membrane protein, was ultracentrifugally homogeneous and showed a granular structure under the electron microscope. The lipid composition of the soluble and insoluble fractions, as well as their protein composition, revealed a preferential and limited solubilization of the constituents of the membrane by lysophosphatidylcholine.


Anion transport in relation to proteolytic dissection of band 3 protein. Sulfate efflux was measured in inside-out vesicles obtained from human red cells. Inhibition was observed in vesicles derived from cells pretreated with DIDS (4,4'-diisothiocyano-2,2'-stilbene disulfonate) or after addition of dipyridamole to the vesicles, both agents being specific and potent inhibitors of anion transport in cells. Trypsinization of the cytoplasmic side of the membrane in order to release a 40 000 dalton fragment from band 3 (the purported anion transport protein) had no effect on sulfate efflux. Further degradation of band 3 to a 17 000 dalton segment, by trypsinization of inside-out vesicles derived from cells that had been pretreated with chymotrypsin, also showed little reduction in transport activity. Furthermore, such vesicles derived from DIDS pretreated cells were inhibited by over 90%. In DIDS-treated cells, the agent is highly localized in band 3. In trypsinized inside-out vesicles, it is largely found in a 55000 fragment and in trypsinized vesicles derived from cells pretreated with chymotrypsin it is largely located in the 17 000 fragment. The data suggest that both the anion transport and inhibitor binding sites are located in a 17 000 transmembrane segment of band 3.


The effects of bioregulators upon amino acid transport and protein synthesis in isolated rat hepatocytes. Isolated rat hepatocytes prepared by an enzyme perfusion technique possess a functional amino acid transport system and retain the capacity to synthesize protein. Amino acid transport was studied using the non-metabolizable amino acid analog alpha-aminoisobutyric acid. The transport process was time, temperature and concentration dependent. Similarly, leucine incorporation into protein was time and temperature dependent being optimal at 3m degrees C. Amino acid, fetal calf serum, growth hormone and glucose all produced small, reproducible increases in protein synthesis rates. Bovine serum albumin diminished the uptake of alpha-aminoisobutyric acid and leucine incorporation into protein. The amino acid content on either side of the cell membrane was found to affect transport into or out of the cellular compartment (transconcentration effects). High cell concentrations decreased transport and protein synthesis as a result of isotopic dilution of labelled amino acids with those released by the hepatocytes. This was consistent with the capacity of naturally occurring amino aicds to compete with alpha-aminoisobutyric acid for uptake into the hepatocyte. In order to define more precisely the effects of bioregulators on transport and protein synthesis it will be necessary to define and subfractionate cellular compartments and proteins which are the specific targets of cellular regulation.


Transport noise in membranes. Current and voltage fluctuations at equilibrium. A formulism is described for the treatment of noise resulting from the transport of ions in channels containing an arbitrary number of activation energy barriers. The analysis is based on Nyquist's theorem and is therefore restricted to fluctuations around the equilibrium state. Within this limit the spectral intensities of current and voltage noise are given by the frequency-dependent admittance, which in turn is closely linked to the relaxation-time spectrum of the transport system. Explicit expressions for the spectral intensity of current noise are derived for channels with two and three energy barriers. The analysis may be used to predict the spectral intensity of noise from the gating system in nerve.


Location of the cooperative melting regions in bacteriophage fd DNA. Differential melting profiles of the linear replicative form (RF-III) DNA of bacteriophage fd, of the fragments obtained by the restriction endonuclease R.HinHI and of those obtained by R.Hga were investigated. With these results a physical map which locates the cooperative melting regions on the DNA was constructed, and compared with the genetic map.


The synthesis of presumptive procollagen messenger ribonucleic acid in the calvaria of the developing chick embryo. The presumptive messenger RNAs for type I procollagen were isolated from chick embryo calvaria at various stages of development. Poly(A)-containing RNA fractions from denaturing sucrose gradients directed protein synthesis in a cell-free system derived from wheat germ. Procollagen mRNA activity was detected in a region of about 26 S. Approx. 80% of the labeled proline incorporated into cell-free product was susceptible to digestion by purified bacterial collagenase. The synthesis of procollagen mRNAs was followed during development. Comparison of the in vitro labeled mRNAs from calvaria of day 12--16 embryos indicated that the 26 S component was most pronounced at day 13 and decreased progressively towards day 16. In addition, incubation of calvaria with tritiated nucleosides for 1.5--25 h revealed that 26 S mRNA was significantly labeled only after prolonged periods. The results suggest that procollagen mRNA is a relatively stable species with a prolonged half-life compared to the majority of mRNAs in this tissue.


Role of prolactin and glucocorticoids in the expression of casein genes in rabbit mammary gland organ culture. Quantification of casein mRNA. Milk synthesis is initiated solely by prolactin in the pseudopregnant rabbit and glucocorticoids potentiate this action of prolactin. In organ culture, prolactin, in the presence or in the absence of insulin, enhances casein synthesis and cortisol (inactive alone) amplifies this action. Measurements of casein mRNA concentration in total cellular RNA, by hybridization with DNA complementary to casein mRNA, revealed that the stimulation of casein synthesis by the glucocorticoid is accompanied by an increase in the amount of casein mRNA. A systematic comparison of variations of these two parameters indicated that the major effect of glucocorticoids on lactogenesis in the rabbit at this stage of mammary gland development is mediated through an increase in the quantity of casein mRNA available for translation. No simultaneous control of casein mRNA translation by cortisol was observed.


The course of the assembly of ribosomal subunits in yeast. The course of the assembly of the various ribosomal proteins of yeast into ribosomal particles has been studied by following the incorporation of radioactive individual protein species in cytoplasmic ribosomal particles after pulse-labelling of yeast protoplasts with tritiated amino acids. The pool of ribosomal proteins is small relative to the rate of ribosomal protein synthesis, and, therefore, does not affect essentially the appearance of labelled ribosomal proteins on the ribosomal particles. From the labelling kinetics of individual protein species it can be concluded that a number of ribosomal proteins of the 60 S subunit (L6, L7, L8, L9, L11, L15, L16, L23, L24, L30, L32, L36, L40, L41, L42, L44 and L45) associate with the ribonucleoprotein particles at a relatively late stage of the ribosomal maturation process. The same was found to be true for a number of proteins of the 40 S ribosomal subunit (S10, S27, S31, S32, S33 and S34). Several members (L7, L9, L24 and L30) of the late associating group of 60-S subunit proteins were found to be absent from a nuclear 66 S precursor ribosomal fraction. These results indicate that incorporation of these proteins into the ribosomal particles takes place in the cytoplasm at a late stage of the ribosomal maturation process.


Effects of polyamines and methylglyoxal bis(guanylhydrazone) on Escherichia coli ribonucleic acid polymerase and the template activity of hepatic cell nuclei in vitro. Escherichia coli RNA polymerase was assayed with 4 mM Mg2+ and 1 mM Mn2+ using native DNA, heat-denatured DNA, histone-nucleate and isolated rat liver nuclei as the template source. With purified DNA and either or both divalent metal ions, 0.1--5 mM amine stimulated enzyme activity. Spermidine resulted in the greatest stimulation (1.7-fold at 5 mM); whereas, spermine or methylglyoxal bis(guanylhydrazone) first stimulated, then above 3 mM inhibited, the reaction. The addition of unfractionated histone to purified DNA inhibited the reaction by 90%. The subsequent addition of amines resulted in a slight stimulation in incorporation (1.5-fold) in the range of 1--3 mM amine. Alternatively, when enzyme was combined with DNA before histone, only a 20% inhibition was observed and this could be completely prevented by 3 mM spermidine. The addition of amines to isolated nuclei resulted in marked alterations in ultrastructure and Mg2+ content; however, relatively small effects on RNA polymerase activity were observed. With the E. coli enzyme, 0.1--1.0 mM amine stimulated RNA synthesis (1.5-fold) whereas, none of the amines stimulated endogeneous activity in the absence or presence of 300 mM (NH4)2SO4.


Action of heparin on mammalian nuclei. II. Cell-cycle-specific changes in chromatin organization correlate temporally with histone H1 phosphorylation. The interaction of the polyanion heparin with the inner histones of chromatin has been used to detect changes in chromatin organization associated with cell-cycle traverse. Synchronized populations of Chinese hamster cells were obtained either in early G1 or near the G1/S boundary. The rate of interaction of heparin with chromatin-associated inner histones was measured using nuclei isolated from synchronized cell populations in different phases of the cell cycle. A G1-specific decrease in rate of interaction of heparin with inner histones was observed and found to be independent of the presence of hydroxyurea during traverse of G1. A further decrease in heparin-inner histone interaction occurred in late S and G2. These changes correlate temporally with the interphase phosphorylation(s) of histone H1. This correlation is discussed within the framework of current models of higher order chromatin structure (i.e. organization above the nucleosome level). Analysis of the cooperativity of interaction of heparin with inner histones was performed using the kinetic analog of the Hill equation. This analysis suggests that the organization of inner histones on chromatin does not undergo large variations during the cell cycle.


A purine nucleoside unequivocally constrained in the syn form. Crystal structure and conformation of 8-(alpha-hydroxyisopropyl)-adenosine. Crystals of 8-(alpha-hydroxyisopropyl)-adenosine dihydrate, C13H19N5O5.2H2O, belong to the monoclinic space group P21. Cell dimensions are a = 8.259 (1), b = 11.117 (2), c = 9.663 (1) A, beta = 109.65 (2) degrees. Intensity data were collected on a four-circle diffractometer and the structure was solved by direct methods. Block diagonal least-squares refinement led to R = 0.031 for 1467 reflections. The glycosyl torsion angle chiCN is 241.4 degrees, corresponding to a syn conformation. The conformation of the exocyclic C(4')-C(5') bond is gauche-gauche and the sugar pucker is C(2') endo. It is considered that the bulky, tetrahedral, neutral 8-substituent, with an effective van der Waals radius of 3.5--4.0 A, provides an adenosine analogue which should exhibit the syn conformation about the glycosidic bond in solution as well as in solid state, irrespective of the nature of the sugar pucker. It should therefore be suitable for studies of interactions with enzyme systems requiring the anti conformation of the nucleoside or nucleotide.


Molecular orbital studies on the conformations of 8-amino- and 8-dimethylaminoadenosine 5'-monophosphate. The quantum mechanical PCILO method has been applied for the determination of conformational properties of 8-amino- and 8-dimethylaminoadenosine 5'-monophosphate. Contrary to other 8-substituted nucleotides the amino derivative shows a preference for an anti arrangement about the glycosidic bond. This conformation is stabilized by an intramolecular hydrogen bond between the purine and the exocyclic group. 8-dimethylamino-adenosine-5'-monophosphate adopts the syn conformation with slightly rotated dimethylamino group. There is, however, a local minimum for the anti form associated with the unusual value of chiCN = 300 degrees. This minimum is probably populated when the nucleotide is bound to lactate dehydrogenase apoenzyme. No particularly strong interactions are necessary for the stabilization of the anti form. The computations account satisfactorily for the available experimental data.


Spin-orbit couplings in the DNA base pairs. The radiative lifetimes of the phosphorescent states of the adenine.thymine (A.T) and guanine.cytosine (G.C) base pairs were calculated on the basis of the singlet-triplet transition probability induced by spin-orbit couplings. The calculated radiative lifetimes averaged over the triplet sublevels of spin state were in the order of G.C less than A.T and in good correlation with those of the composite bases. On the whole the results suggested an important role for thymine triplet having a relatively long lifetime during the course of the triplet localization in DNA, in agreement with the experimental observation that the concentration of triplet is remarkably enhanced with increase in A+T content.


Kinetics of uptake and activity in mouse liver of glutaminase coupled to desialated orosomucoid. Desialised orosomucoid (alpha-1-acidic glycoprotein) was coupled to Pseudomonas 7A glutaminase-asparaginase by glutaraldehyde, iodinated and injected into mice. The half-life of radioactivity and glutaminase activity in plasma was about 7 min. Radioactivity and glutaminase activity in the liver reached a peak at about 20 min. The radioactivity in liver then declined with a half-life of about 20 min. Enzyme activity in liver declined with a half-life of about 10 min. The ratio of enzyme activity to radioactivity was lower in the liver than in plasma at all times during the experiment, indicating rapid hepatic inactivation of the enzyme. Uptake into the liver could be blocked by excess desialised orosomucoid. Glutamine levels in the liver were about 10% of normal for 44 min but returned to 50% of normal by 93 min. Intestines, kidney and spleen failed to exhibit any appreciable uptake of desialated orosomucoid glutaminase-asparaginase.


Some regulatory properties of purine biosynthesis de novo in long-term cultures of epithelial-like rat liver cells. De novo synthesis of purine nucleotides and some regulatory properties of this pathway were studied in cultured epithelial-like rat liver cells. It was found that the physiological 5-phosphoribosyl 1-pyrophosphate (P-Rib-PP) concentration in these cells is limited for purine synthesis de novo. Increase of P-Rib-PP availability, achieved by activation of P-Rib-PP synthetase at high Pi concentration, resulted in acceleration of purine synthesis. The effects of increasing cellular ribose 5-phosphate (Rib-5-P) availability, by methylene blue-induced acceleration of the oxidative pentose phosphate pathway, on P-Rib-PP availability and on the rate of the novo purine synthesis were also studied. It was found that at the Pi concentration prevailing in the tissue at extracellular physiological Pi concentration, Rib-5-P availability is saturating for P-Rib-PP generation and therefore also for purine synthesis.


Reduced glucose transport and increased binding of insulin in adipocytes from diabetic and fasted rats. 1. Animals made diabetic by injection of streptozotocin or animals after 3 days of fasting show decreased insulin levels and a decrease in mean cell diameter of adipocytes from epidydymal fat pads in comparison with cells from normal animals. 2. 14CO2 production from D-[U-14C]glucose is impaired in diabetic and fasted animals both in presence or in absence of a concentration of insulin stimulating 14CO2 production maximally. 3. Insulin binding is increased in adipocytes from diabetic and fasted animals due to changes in affinity. 4. Transport studies show that basal and insulin stimulated 2-deoxy[1-14C]-glucose transport is decreased in absolute terms due to a decrease in V and an increase in Km. 5. The relative stimulatory effect of insulin is impaired in adipocytes of diabetic and fasted animals. 6. A shift of the maximal effect of insulin to lower insulin levels is seen in these cells.


Direct measurement of pure absorbance spectra of living phototrophic microorganisms. The pure absorbance of turbid cell suspensions of various phototrophic microorganisms were determined by collecting the scattered light. A conventional spectrophotometer was used, equipped with an intergrating sphere as receiver unit, which allowed precise measurements of the absorbance in the range from zero to 0.1. In the wavelength range 300--1100 nm, where photosynthesis occurs, light scattered only once by a bacterial cell retains predominantly the forward direction. This allows measurements of pure absorption, when the concentration of cells which the light has to pass through is small. For example, by comparison of measurements of pigmented and nonpigmented cell suspensions of Rhodopseudomonas acidophila, it was shown that the total sum of scattered light can be collected. The best results were obtained using cuvettes with a light path of 0.1 cm or 0.2 cm to measure cell suspensions of about 0.2 mg dry weight per ml. For R. acidophila this corresponds to 1--3 cell layers. Extinction-, absorbance- and scattering spectra for R. acidophila are presented, in addition to the absorbance spectra for Rhodospirillum rubrum, Aphanocapsa and Scenedesmus.


An approach to the study of intracellular proteins related to the excitability of the squid giant axon. The technique for covalently labeling proteins with 125I-labelled Bolton-Hunter reagent was used to determine the quantities of proteins released from the axoplasmic side of the squid axon membrane. The reagent could be introduced into the interior of the axon by the technique of intracellular perfusion, the radioiodination reaction being carried out in situ. Alternatively, the reaction could be carried out in vitro, i.e., by mixing the reagent with samples of proteins dissolved in the intracellular perfusion fluid collected from the axon. This technique was found to be sensitive enough to permit analysis of a large number of protein samples collected from a single axon. By the method of sodium dodecyl sulfate polyacrylamide gel electrophoresis, it was found that proteins of approx. 56 000 daltons were released into the perfusate when a solution of potassium chloride or potassium bromide was introduced into the interior of an axon. Suppression of axonal excitability was associated with this release of proteins. The significance of these findings in relation to the structure and function of the axon is discussed.


Protein secretion from parotid glands of vitamin D deficient and glucocorticoid-treated rats. The rate of isoproterenol stimulated secretion of protein from parotid glands of vitamin D deficient rats and rats treated with methylprednisolone was increased compared to the secretory response of tissue from control rats. It is suggested that the increased secretory response is secondary to a decreased capacity of mitochondria from the tissue of these animals to take up and store Ca2+; i.e. the mitochondria are less efficient buffers of cytoplasmic Ca2+. Under these conditions any process, such as protein secretion, which requires an increased cytoplasmic Ca2+ concentration will operate more effectively.


The temperature dependence of the visible/ultraviolet spectra of some cobalt, vitamin B-12 model, compounds. The visible/ultraviolet spectra of aqua- and pyridine-alkyl(10-hydroxyimino-3,9-dimethyl-4,8-diazaundeca-3,8-dien-2-oneoximato,-N,N',N'',N''')cobalt perchlorates have been found to be very sensitive to temperature. The phenomenon fits the explanation of an equilibrium between two forms of complex, one with a short and the other a long cobalt-ligand bond.


Separation and partial purification of central nervous system peptides from Limulus polyphemus with hyperglycemic and chromatophorotropic activity in crustaceans. 1. Crude extracts of Limulus CNS cause hyperglycemia in Orconectes immunis and expand chromatophores in Uca pugilator. 2. The hyperglycemic action is due to a previously unknown polypeptide (LHGF) with an estimated molecular weight of 6400 daltons. LHGF is inactivated by hydrogen peroxide, pepsin, and protease, but unaffected by trypsin and brief boiling.3. The chromatophorotropic activity is due to the previously reported substance, LUC. LUC is shown to be a peptide with an approximate molecular weight of 1850 daltons; it is inactivated by hydrogen peroxide, protease, pepsin, trypsin, chymotrypsin, and thermolysin. 4. LUC and LHGF activity can be readily separated by gel filtration on a Sephadex G-25 column. 5. The similarity of LUC and LHGF to known crustacean hormones is dicussed.


[Comparative characteristics of cold- and fever-induced tremor]. Experiments were conducted on anesthetized and unanesthetized cats. On the basis of identity of distribution of cold and fever tremor in the muscle groups, its electromyographic picture and the same sensitivity to neurotropic agents a conclusion was drawn that in the cooling of the organism and during fever the same mechanism of the shivering thermogenesis regulation was activated.


[Endogenous pyrogen formation by bone marrow cells]. The cells of the rabbit bone marrow produced endogenous pyrogen in response to stimulation with bacterial lipopolysaccharide. Incubation of the cells in medium No 199 containing a 15% homologous serum is optimal for the release of pyrogen. It is supposed that the cells of the bone marrow take part in the formation of endgenous pyrogen and in the mechanism of pyrexia in the organism.


[Rat hemoglobulin normally and under hypoxic action]. The hemoglobin (Hb) pattern of adult and newborn rats, as well as of chronically hypoxic rats was studied by the method of electrophoresis on starch gel. It was shown that the experimental animals were Hb polymorphic. The slow-moving bands of Hb pattern were more pronounced and the alkali resistance was greater in newborns as compared to adults. In the course of adaptation to hypoxia there occur some shifts in the quantitative ration of the fractions in favour of one of the slow-moving fractions; however, this phenomenon does not follow the enhancement of the fetal Hb synthesis, as it is generally accepted. There were no changes in the electrophoretic mobility of the fractions. Mildness of the changes revealed under hypoxic conditions suggests that the Hb synthesis in rats is rather stable.


[Hypophyseal-adrenocortical system reaction to the prolonged action of low doses of selenomethionine-75Se that form during internal contamination]. A method of radiometry in vivo was applied to study the regularities attending distribution of the absorbed dose and its formation in the course of one year after the administration of 0.033 muCu/g of selenomethionine-75Se to rats, as well as the functional condition of the adaptive hypophysis-adrenal glands system by the determination of plasma corticosterone. A high tropicity of this preparation to the endocrine system organs was demonstrated. Intensification of the functional activity of the adaptive system was indicated by an increase of the blood plasma corticosterone concentration following the administration of a, radioactive preparation and its statistically significant increase (in comparison with control) 3, 6, and 10 months from the beginning of the experiment. The action of acute stress (histamine and formalin) 10 months after the administration of selenomethionine-75Se caused no sharp elevation of the plasma corticosterone concentration characteristic of control rats, this indicating an extreme strain of the hypophysis-adrenal gland system and its incapacity to respond to additional loads. It is supposed that analysis of functional condition of the adaptive system could serve as the key in the assessment of the biological effect of low radiation doses.


[Spermine and spermidine polyamines in the brain and liver of rats under hyperoxic action]. The effect of hyperbaric oxygenation (6 atmospheres) on the content of polyamines spermine and spermidine in the rat brain and liver was studied. A decrease of the spermidine content in the brain and liver during oxygen convulsions and four hours after decompression was revealed. The spermine content in the brain during oxygen convulsions decreased as well, but four hours after decompression it increased significantly not eaching the control level. The spermine content in the liver failed to alter during oxygen convulsions, but the next four hours rose sharply. The role of polyamines in the regulation of protein biosynthetic processes under hyperoxia is discussed.


[Electrophysiological characteristics of the aortic baroceptors]. The presence in the left aortic nerve of rabbits of medullated and nonmedullated fibres with conduction velocities of 12--30 m/s and 0.9--1.2 m/s, respectively, was demonstrated. In experiments on the isolated aortic arch preparation the electrophysiological characteristics of the aortic baroceptors with the medullated and non-medullated fibres were studied by means of a selective block of conduction in these fibers. Baroceptors with the non-medullated fibers had a higher threshold pressure and a wider functional range.


[Steroid hormonal interaction with hepatocyte and erythrocyte membranes]. Absorption and passage through the dense layer of plasma membranes of rat hepatocytes and rabbit red blood cell ghosts, steroid hormones labelled with 3H were studied. The degree of absorption of steroid hormones by plasma membranes decreased in the following succession: progesterone greater than testosterone greater than oestrone greater than prednisolone greater than oestriol. The degree of the hormone absorption correlated with the solubility in lipids and with the effect of the enzyme release from the lysosomes. At the same time it is in inverse ratio to the speed of passage through the dense layer of the membranes. The nature of absorption of the steroid hormones is independent of the origin of plasma membranes.


[Change in the antinociceptive effect occurring on stimulation of the midbrain under the action of analgesics and tranquilizers]. It was shown in chronic experiments on cats that analgetics in subanalgetic doses not only revealed the antinociceptive effect under subthreshold stimulation of the midbrain, but also enhanced the analgetic effect of the central stimulation. The tranquilizers promoted only the analgetic action under the subthreshold stimulation of the midbrain. Possible causes of different effect of the drugs under study are discussed.


[Changes in the electrical activity of the cerebral cortical neurons in the rabbit under the effect of diazepam]. The microelectrode technique was applied in the study of changes in the electrical activity of the neurons of the sensory-motor cortex of the rabbit at various time after a single intravenous injection of diazepam (1--5 mg/kg). Several seconds after the injection there was revealed a marked depression of the neuronal activity spontaneous an that induced by stimulation of the sciatic nerve and also an increase in the duration of the inhibitory pause in the neuron responses to the afferent stimulation and direct stimulation of the cortical surface. These changes largely decreased 15 to 60 minutes after injection of the preparation. The results obtained were compared with the data of other investigators who studied clinical and pharmacokinetic effects of benzodiazepines. A conclusion was drawn on the association of the depressive influence of diazepam on the cortical activity with the sedative, amnestic and anticonvulsive effects of the agent, and also on the important role of psi-aminobutyric acid in the realization of these effects.


[GABA system as a factor facilitating the development of compensation of disordered cerebral hemodynamics]. Shifts in the system of GABA transformation in ischemia and specific inhibition of GABA-transaminase under conditions of quantitative measurement of the blood circulation by means of hydrogen clearance permitted to establish a definite association between the increased GABA level in the brain and the tissues of the wall of its arteries, and the development of compensation of disturbed cerebral circulation. Consequently, one of the principal manifestations of an increased amount of endogenous GABA in deficiency of the brain blood supply was GABA capacity to improve the cerebral circulation.


[Experimental effect of alloocimene on soft tissue wound]. The action of alloocymen--a representative of carotinoid polyens--metabolism stimulants, active drugs normalising the trophic process, on wound healing by secondary tension of soft tissue was studied. Alloocymen increased the intensity of healing of skin and skin-muscle wounds, accelerated in a number of cases complete wound healing, produced an ntiinflammatory action on the wound and the adjacent zones, eliminated or limited edema, hypermia, maceration, hemorrage, prevented the development of acute inflammation. The applied methods of quantitative analysis of these alloocymen effects make possible evaluation of it's positive actions on trophic process in the course of wound healing.


[Relative stability of the central mechanisms that determine the depth and frequency of respiration]. Not only an intensified respiration, but also an increase in inspiratory discharges can be caused by hypercapnia in vagotomized cats. With the deepening of anesthesia an increase of the inspiratory discharges persists, whereas an increased frequency of respiration disappears. This testifies to the presence of two different central mechanisms for the regulation of the rate and depth of respiration; the first is subject to the suprabulbar influences more than the second.


[Duration of the mitotic cyle of mouse liver cells at different stages of carcinogenesis induced by ortho-aminoazotoluene]. Orthoaminoazotoluol was administered to mice for a period of 9 months. The duration of the G2-and S-periods of the mitotic cycle determined by the autoradiographic method, and mitotic duration--by the stathmokinetics technique with the use of colchicine in the intact liver, the cells of the adenoma nodes, and primary hepatomas. The duration of the S-period of the intact hepatocytes and adenoma nodes proved to be equal (13.8 hours, respectively). As to the primary hepatoma cells--it decreased to 12.8 hours. The duration of the G2-period showed no essential change during the carcinogenesis, and was equal to 2.2--2.7 hours. An average mitotic duration in the course of 24 hours was also constant and was approximately equal to 1 hour. A rise in the number of mitoses and PNA-synthesizing cells in the hepatomas occurred as a result of entering in mitosis and the S-period of a greater number of cells, but not as a result to prolongation of the duration of the S-and M-periods of the mitotic cycle.


[Reduction of the prereplicative period of the mitotic cycle in hepatocytes on repeated stimulation of divisions]. Repeated stimulation of division soon after the primary one (2--3 days later) induces a shorteining of the prereplicative phase of the mitotic cylce of hepatocytes to 9--10 hours in the regenerating rat liver. The cells dividing repeatedly after one stimulation were found to pass through the G1-phase of the second mitotic cycle during the same period. It may be suggested that the cells with the minimal duration of the prereplicative phase failed to pass through the transformation period. With increase of the time interval between the successive stimulation of divisions (to 4--5 days) increases the resting time state for most hepatocytes, and they lose the capacity to pass through the reduced prereplicative phases.


[Autotransplantation of previously denervated muscles in the rabbit]. Whole gastrocnemius muscles of rabbits, preliminarily denervated, were grafted. At the moment of grafting (60 days after the operation) the muscles were in the state of deep atrophy attended by distrophic changes. The autotransplantated muscles took at the site of grafting, their further reorganization provided progressive development of the muscle tissue within the transplant, its growth, and formation of definitive muscle fibers with nerve terminals. After a definite time some degenerative changes were observed in the transplant muscle tissue; as a result the muscle tissue was substituted by connective tissue. These data support the statement founded before on feasible free grafting of preliminary denervated whole muscles. However, deep denervation atrophy seems to influence the remote results of the transplantation.


[Characteristics of the estradiol receptor system of the anterior hypothalamus and adenohypophysis in guinea pigs]. The presence of a specific receptor system (E2-R) wthith low capacity and high stability of the E2-R complex formation was shown in the guinea pig adenohypophysis and anterior hypothalamus cytozols under the vivo and in vitro conditions. Some parameters of the physico-chemical properties of the E2-R system in these tissues differed. The adenohypophysis and the anterior hypothalamus receptor complexes formed at different temperatures were not identical.


[Characteristics of the estrogen receptor system of the oviducts in guinea pigs]. Kinetic and thermodynamic parameters of the estradiol receptor (E2-R) interact in the guinea pig oviduct cytozol were studied. Specificity of the receptor system was characterized by measurment of the affinity of 14 compounds to the system. It was shown that the guinea pig oviduct R-system had a high affinity to E2 and a limited capacity. Free energy change value (52 KJ/mol) indicated stability of the complex formed. Activity of the steroid-receptor (S-R) complex formation is determined by the presence of the intact hydroxils in positions 3 (phenolic) and 17-beta of the steroid molecule; dependence of the S-R interaction rate on the different steroid molecule modifications at a number of positions supports this point. Besides, the immediate enviroment of hydroxils in positions 3 and 17 beta also influences the S-R interaction rate. Some properties of the nonsteroid diethylstilbestrol estrogen attract attention.


[Effect of gnotobiotic conditions on the histophysiology of liver and spleen tissues]. The liver and spleen of gnotobiotic Wistar rats were examined by histochemical methods; the liver was also studied by electron microscopy. Under conditions of gnotobiotic animal existance the activity of succinic dehydrogenase, non-specific esterase in the liver was found to be decreased; fatty infiltration was intensified in the cytoplasm of hepatocytes and Kupffer's cells; a part of them is subject to fatty dystophy. At the same time both the activity of acid phosphatase of hepatocytes and the contents of lysosomes in the biliary poles of hepatocytes became increased. Decomposition of erythrocytes in the spleen, as well as release of free iron and pigments which stimulated excretion of bile in gnotobiotes were enhanced.


[Reparative processes in the liver and adrenal cortex of rats following an experimental vascular crisis]. Reparative processes in the liver and the adrenal cortex of hemiadrenalectomized female rats, which sustained an acute circulatory disturbance as a result of orthostasis, were investigated by means of quantitative methods (cytometry, kariometry, nucleolometry, determination of cell content calculation of nucleo-cytoplasmic, nucleolo-nuclear ratios). Common features in regeneration of the organs under study were found. During the first days of the experiments the count of the dying cells increased and simultaneously the quantity of amitoses and binucleated cells in the liver grew. The cell composition of the organs was stabilized by the 15th day in the adrenal gland and by the 45th day in the liver. During the first week after orthostasis mitotic activity of epithelial cells rose in both the organs. Later the regeneration took place at the intracellular level (activation of the nuclear apparatus and hypertrophy of the cell cytoplasm).