Effects of isolation, handling and restraint on growth of rats.

The effects of 3 environmental conditions on physical growth and skeletal maturation were assessed in pair-fed rats. Rats subjected to restraint from ages 28 to 80 days weighed less and were shorter than pair-fed like-sex controls; skeletal maturation was unaffected. The observations cannot be attributed to handling, as those animals were heavier than their controls, or to isolation, which was found to be without effect on any of the measurements. The adverse effects of restraint on physical growth are attributed to increased adrenal cortical activity, reflected in increased adrenal weight.


The inheritance of growth and form in the mouse. IV. Changes in the variance components of weight, tail length and tail width during growth.

A complete diallel cross, including inbreds and reciprocals, was made among six inbred lines of mice. Body weight, tail length and tail width were measured at ages of 1 through 12 weeks. The analysis described by Griffing (1956a, 1956b, 1958) as the modified diallel, method 3, model II was made for each trait at each age, a separate analysis being made for each sex. Inbreds did not contribute to estimates of the effects in the diallel model, but were used to estimate heterosis. Positive heterosis was observed for all three traits. Heritability increased with age for all three traits, although it remained small for tail width; for body weight it was larger in females than for males, while for tail length and width the opposite was true. Non-additive genetic variance was observed for all three traits. Maternal effects variance was virtually non-existent for tail length, but for body weight and tail width exhibited a marked peak around weaning, followed by a gradual decline for body weight and a rapid decline for tail width. Environmental variance exhibited a marked peak at weaning for all three traits and was larger for male body weight and tail length from four weeks onward. Residual reciprocal effects were important for tail length at all ages, but were small or negligible for body weight and tail width. It is concluded that the relative importance of the individual's genotype in determining size increases with age, while that of non-genetic factors declines.


The inheritance of growth and form in the mouse. V. Allometric growth.

A complete diallel cross, including inbreds and reciprocals, was made among six inbred lines of mice. Body weight, tail length and tail width were measured at ages of 1 through 12 weeks. The parameters of 4 longitudinal allometric relations, y = bxa, were determined for each mouse: tail length vs. body weight for weight for weeks 1 through 9 and for weeks 1 through 12, and tail width vs. body weight for the same periods. The estimated value of a was taken as one variable and the value of log y corresponding to a weight of 12 g or 15 g for 9 or 12 pairs of measurements was taken as the other. The allometric equation appears to provide a satisfactory empirical description of the relative growth of tail length and width vs. body weight. The diallel analysis suggests a low heritability for a for both sexes and both periods and an intermediate heritability for the location parameters.


The effect of progesterone on brain and body growth of chick embryos.

It has been suggested that in the embryo hormonal steroids may act also as control factors for the growth of neural systems. In the present work progesterone was introduced onto the chorioallantoic membrane of the chick embryo on day 7 or days 7 and 10 of incubation. The embryo, dissected at day 10, showed significant increases in body weight and cerebral hemispheres weight. The response at day 13 was less pronounced; male embryos responded to progesterone more than the female embryos. Progesterone is a precursor to other corticosteroids, but corticosterone itself had a significant harmful effect on embryonal growth. Several possible explanations of these results have been offered. It appears that progesterone itself promotes the growth of the early embryo, but the effect depends on its age and sex.


Serum electrolyte concentrations in Sinclair(S-1) miniature swine from 1 through 36 months of age.

Venous blood samples were collected monthly from 60 male and 60 female Sinclair(S-1) miniature swine from 1 through 36 months of age. The rate of serum urea nitrogen concentration decreased instantaneously for females and increased instantaneously for males as described in the equation y = aebt. Serum creatinine concentration decreased through 20 months of age and increased from 20 through 36 months of age. Serum calcium, inorganic phosphorus, potassium and sodium concentrations decreased instantaneously through 36 months of age. From 14 through 36 months of age, males had a greater mean serum urea nitrogen concentration than did females.


Control of anticoagulant therapy with a chromogenic substrate.

Prothrombin is determined with the aid of a recently developed assay, based on the amidolysis of a chromogenic substrate. The assay proved to be reliable when it was compared with more conventional coagulation assays in the control of oral anticoagulant therapy, both in the therapeutic range and in a case of overdosage. As is the case in coagulation tests, heparin therapy remains a disturbing circumstance. The prothrombin concentration was measured (a) in the plasma of 50 long-term anticoagulated patients, and the results were compared with those obtained with a one-stage coagulation assay and with those obtained with Thrombotest determinations, and (b) during vitamin K administration in the plasma of a patient with a severe intoxication of a vitamin K antagonist.


Platelet adhesion and platelet thrombus formation on subendothelium of human arteries and veins exposed to flowing blood in vitro. A comparison with rabbit aorta.

Subendothelium of blood vessel segments from elderly patients was exposed in a perfusion chamber to citrated blood under arterial blood flow conditions. The resulting platelet adhesion and thrombus formation was assessed morphometrically. The results show that the time course and the extent of platelet adhesion and aggregation were similar to the results obtained previously with subendothelium from rabbit arteries. The extent of surface-induced platelet aggregation was furthermore governed by both the properties of the exposed surface as well as those of the blood perfusate. No significant differences with regard to platelet reactivity were found between veins and arteries and the extent of surface-induced platelet aggregation was rather low.


Platelet aggregation and antithrombin III levels in diabetic children.

We studied platelet function and antithrombrin III levels in 30 insulin-dependent diabetic children with no clinically evident vascular complications. 9 were in-patients and 21 were out-patients. The disease had been discovered within the previous 10 years. 25 control subjects of comparable age and body weight were studied simultaneously. Template bleeding time, threshold concentrations of ADP  or adrenaline required to induce irreversible platelet aggregation and plasma antiherparin activity (platelet factor 4) did not differ significantly in control and patient groups. In contrast, the immunological levels of plasma antithrombine III were significantly higher in the diabetic group. These results suggest that diabetic children, with no clinical signs of microanigopathy, show no laboratory changes suggesting increased platelet function. The unxpected increase in the antithrombin III level could reflect a very early defense mechanism against activation of the blood clotting system.


Platelet adhesiveness in ischemic heart disease.

The adhesiveness of platelets to collagen and glass was studies ex vivo in groups of patients with ischemic heart disease (IHD) and acute myocardial infarction (AMI). Adhesiveness was increased to glass and normal collagen in both groups of patients. No relation was found between reinfarction rate and adhesiveness in the acute stage of AMI. Electrophoretic mobility of platelets was the same in the AMI patients and a normal control group. It suggested that the increased 'retention' of platelets in IHD patients might be due more to platelet hyperaggregation or to hypersensitivity to platelet aggregating agents than to altered adhesiveness.


The thrombogenicity of 6-azouridine.

The antimetabolite 6-azauridine blocks the de novo synthesis of pyrimidines and causes increased serum levels of several amino acids including homocystine. 6-Azauridine was was withdrawn from clinical use for the treatment of psoriasis because of the occurence of arterial and venous thromboembolic episodes in some psoriatic patients. Utilizing a standard animal model for the recognition of venous and arterial thrombosis, 6-azauridine was demonstrated in this study to cause thrombosis without producing homocystinemia when administered orally or intravenously.


Biotransformations of anthracyclinones in Streptomyces coeruleorubidus and Streptomyces galilaeus.

The ability to transorm biologically exogenous daunomycinone, 13-dihydrodaunomycinone, aklavinone, 7-deoxyaklavinone, epsilon-rhodomycinone, epsilon-isorhodomycinone and epsilon-pyrromycinone was studied in submerged cultures of the following strains: wild Streptomyces coeruleorubidus JA 10092 (W1) and its improved variants 39-146 and 84-17 (type P1) producing glycosides of daunomycinone and of 13-dihydrodaunomycinone, together with epsilon-rhodomycinone, 13-dihydrodaunomycinone and 7-deoxy-13-dihydrodaunomycinone; in five mutant types of S. coeruleorubidus (A, B, C, D, E) blocked in the biosynthesis of glycosides and differing in the production of free anthracyclinones; in the wild Streptomyces galilaeus JA 3043 (W2) and its improved variant G-167 (P2) producing glycosides of epsilon-pyrromycinone and of aklavinone together with 7-deoxy and bisanhydro derivatives of both aglycones; in two mutant types S. galilaeus (F and G) blocked in biosynthesis of glycosides and differing in the occurrence of anthracyclinones. The following bioconversions were observed: daunomycinone leads to 13-dihydrodaunomycinone and 7-deoxy-13-dihydrodaunomycinone (all strains); 13-dihydrodaunomycinone leads to 7-deoxy-13-dihydrodaunomycinone (all strains); daunomycinone or 13-dihydrodaunomycinone leads to glycosides of daunomycinone and of 13-dihydrodaunomycinone, identical with metabolites W1 and P1 (type A), or only a single glycoside of daunomycinone (type E); aklavinone leads to epsilon-rhodomycinone (types A and B); aklaviinone leads to 7-deoxyaklavinone and bisanhydroaklavinone (type C); epsilon-rhodomycinone leads to zeta-rhodomycinone (types C, E); epsilon-rhodomycinone leads to glycosides of epsilon-rhodomycinone (types W2, P2); epsilon-isorhodomycinone leads to glycosides of epsilon-isorhodomycinone (types W2, P2); epsilon-pyrromycinone leads to a glycoside of epsilon-pyrromycinone (types W1, P1). 7-Deoxyaklavinone remained intact in all tests. Exogenous daunomycinone suppressed the biosynthesis of its own glycosides in W1 and P1; it simultaneously increased the production of epsilon-rhodomycinone in P1.


Intra- and interspecific cosynthetic activity of mutants of Streptomyces coeruleorubidus and Streptomyces galilaeus impaired in the biosynthesis of anthracyclines.

Cosynthesis of anthracycline compounds was followed in five phenotypic groups of mutants of Streptomyces coeruleorubidus (A--E), blocked in the biosynthesis of the daunomycine complex, and in two mutant types of Streptomyces galilaeus (F, G) blocked in the biosynthesis of glycosides of epsilon-pyrromycinone and aklavinone. Glycosides of daunomycinone and 13-dihydrodaunomycinone were produced in combinations A+B, A+C, A+D, A+E and A+F, epsilon-rhodomycinone was synthesized in combinations A+E, A+F, B+E and B+F. During the cultivation of types B--E with type G or F non-anthracycline compounds, typical of S. galilaeus, were cosynthesized. No cosynthesis could be observed in other combinations of the mutant types. Negative results were also obtained with combinations of mutants of the same group and during cultivation of all mutant types with streptomycetes not producing anthracyclines. A scheme illustrating metabolic pathways leading to the biosynthesis of daunomycinone, aklavinone, epsilon-rhodomycinone in S. coeruleorubidus and S. galilaeus was constructed.


Growth of Candida tropicalis 2838 cells on straw hydrolyzates.

Improved strain of Candida tropicalis 2838 grows on nonseparated straw hydrolyzates with no addition of vitamins and trace elements at a specific growth rate mu = 0.34 and 44% yield coefficient (referred to reducing substances). The reducing substances in hydrolyzates contain predominantly monosaccharides (xylose, glucose, arabinose, mannose). Cells grown in this way are rich in proteins (62%) and essential amino acids (lysine, phenylalanine, leucine, threonine and valine). The product obtained under industrial conditions by fermentation of the nonseparated hydrolyzates contains 8--9% of proteins and it is a suitable supplement of fodder mixtures for monogastric domestic animals. Nutrition tests on rats and pigs indicated that this product can substitute the hay-flour, and, partially, blood-flour barley, and that the strain used is nonpathogenic.


Formation of DL-alanine by Corynebacterium sp. 9366-EMS/270.

After a 4-d cultivation in a medium containing 7.5% glucose, 0.6% ammonium nitrate and 0.5% peptone, the leaky mutant Corynebacterium sp. 9366-EMS/270 stimulated in its growth by arginine, was found to accumulate 12.2 g DL-alanine per litre medium.


Genetic mapping of the bacteriophage PS8 of Agrobacterium tumefaciens.

Genetic mapping of the chromosome of the bacteriophage PS8 of Agrobacterium tumefaciens using temperature sensitive (ts) mutants of the bacteriophage is described.


Formation of L-alanine by Streptomyces coelicolor 3-19.

Fermentative preparation of L-alanine by Streptomyces coelicolor 3-19 was developed under laboratory conditions. In a medium containing glucose, corn-steep and mineral salts, the strain accumulated 9 g L-alanine per litre after four days of cultivation.


Distribution of type A and type B monoamine oxidase activity in hypothalamic nuclei of the rat.

The regional distribution of type A, type A and B and type B activity of monoamine oxidase (MAO) in individual nuclei of the rat hypothalamus was studied according to quantitative micromethods with clorgyline as a specific inhibitor of type A MAO. As results, type A and type B MAO were distributed differently in the rat hypothalamus. It is suggested that type B MAO acts differently from type A MAO in regard to the function of the hypothalamus.


Effects of acute and chronic ethanol administration on amino acid metabolism in rabbit brain and blood.

Acute administration of ethanol increased the cerebrocortical amino acids derived through the tricarboxylic acid cycle except for GABA and decreased the plasma alanine, valine, isoleucine, leucine, and phenylalanine whereas chronic administration of ethanol caused no significant changes in the cerebrocortical amino acids and increased the plasma glutamic acid, glutamine, glycine, and ornithine, with decreases in taurine and phenylalanine. Result of this experiment suggests that the CNS-depressant effect of ethanol is related to changes in the GABA system and increased uptake by the brain of the branched-chain amino acids while the development of tolerance to ethanol is associated with cellular adaptation in the CNS.


Experimental chronic lead poisoning.

In the peripheral nerve, the distal part of the nerve fibers was remarkably damaged--periaxial segmental demyelination--while the proximal part of nerve fibers was only slightly affected. In the CNS, perivascular edema of the small blood vessels and capillaries was observed in the cerebral cortex and cerebellar cortex. All endothelial cells of these blood vessels showed a high electron density with many pinocytotic vesicles and ribosomes. Following these changes, the nerve fibers adjacent to the edema were destroyed. The above-mentioned findings seem to indicate that lead induces a toxic effect on the blood vessel and produces perivascular edema in the CNS of adult animals. This may induce brain dysfunction.


A recent trend of drug dependence in Kurume district (southern Japan).

With the intention of grasping the trend of drug dependence in recent years, a comparative study was made of the relative prevalence of three different types of drug dependence, i.e., the sociopathic, neurotic and iatrogenic types, in each of the three postwar decades among patients seen at the neuropsychiatric clinic of Kurume University. As a result it was found that the recent trend of drug dependence has the following features: (1) multiplicity of drugs involved, (2) a continuing high incidence of the iatrogenic types, (3) resurgence of the sociopathic type, making the recent pattern of drug dependence similar to that prevailing in postwar years, and (4) prevalence of dependence or abuse among the younger generation. Consideration was also given to the sociopathologic significance of these recent features of drug dependence.


An autopsy case of multiple leucoencephalitis showing hemiatrophy of the brain.

A 39-year-old female died 25 years after the onset of epileptic seizure. In the clinical course, she suffered epileptic seizures, left hemiparesis and muscular atrophy of the left upper extremity, psychological character change, dementia, forced laughter and hallucinatory and delusional states. Pathologically, severe changes were found  in the right hemisphere consisting of lesions of white matter with myelin loss, especially in the frontal, temporal and occipital lobes. Gliosis was diffusely observed in the white matter excepting areas with severe changes. In some parts of the cortex, the cytoarchitecture was destroyed and in this area, blood vessels numerously increased. In the left occipital white matter, perivascular infiltration mainly consisting of lymphocytes was observed with numerous fat granule cells and gemystocytic astrocytes around them. The present case may belong to the category of multiple leucoencephalitis, however, it had many characteristic features, such as a long clinical course (25 years) and pathologically revealed hemiatrophy of the brain.


Hallucinatory and delusional states in connection with blood pressure and EEG.

Twenty-two patients who had low blood pressure with hallucinatory and delusional states were examined. Nineteen cases showed low voltage fast waves in EEG. By treatment with haloperidol the symptoms as well as the blood pressure and EEG showed improvement. From the above findings, the hallucinatory and delusional states observed in this study may have a close connection with dysfunction of the lower brain or disharmony of function between the upper and the lower brains.


Paroxysmal dysesthesia in multiple sclerosis.

Seven cases of multiple sclerosis with paroxysmal dysesthesias of an upper extremity were reported. This seizure characteristically is a purely sensory one induced by movements and is not accompanied by convulsions or a disorder of voluntary movements. In other ways it shares some features with other paroxysmal manifestations seen in MS. Clinical observations with subsequent neurophysiologic considerations have led to the hypothesis that paroxysmal dysesthesias are segmental symptoms with their foci lying in or about the spinal cord.


Cardiac lesions in intravenous drug addicts.

Postmortem findings in 25 intravenous addicts of centrally stimulating amines and centrally depressive narcotics (opiates) have been analysed with special reference to the presence of pathologic findings in the heart, and the cause of death. Most cases exhibited myocardial lesions of varying age, consistent with various phases of myofibrillar degeneration, such as hemorrhages, contraction bands, focal necroses, granulation tissue, stromal condensation, and scarring, indicating an active chronic process in the myocardium and the subendocardium, with a bias toward the conduction system of the heart. The lesions have been found in drug addicts who died immediately following an injection of narcotics as well as in those who, irrespective of their drug influence, have died following intervening injuries or disease. Cardiac lesions in drug addicts seem to have a variety of causative factors: infections, toxic influence, hypersensitivity, influence of catecholamines and general hypoxia. The authors feel that the two latter suggested causes appear most regularly and deserve special attention. The significance of these heart lesions seems to vary, but at times they may be the determining factor in the fatal outcome of a case.


The histology of myocardium in malignant hyperthermia: a preliminary report of 11 cases.

The preliminary results of a retrospective examination of the myocardium from 11 patients who responded to general anaesthesia with malignant hyperthermia are presented. Light-microscopical examination of the sections revealed no specific changes due to malignant hyperthermia. Contraction bands were demonstrated in 4 cases and it is concluded that the present investigation does not support the suggestion that a specific myofibrillar damage is responsbile for the arrhythmias seen in malignant hyperthermia.


An international comparison of mortality in middle-aged men from cardiovascular diseases during 1970--1974.

An international comparison of mortality rates in middle-aged men (35--54 years) from cardiovascular diseases (CVD) during the period 1970--1974 was made. The material for this study was obtained from the statistics of the WHO (World Health Statist. Ann. 1970--1974, Vol. I, Vital Statistics of Causes of Death. WHO, Geneva, 1973--1976). The mean death rate of middle-aged men from all CVD and ischaemic heart diseases was clearly higher in Finland than in any other country in the world during the 5-year period. The mortality rates according to all ICD (International Classification of Diseases) main groups of diseases were determined for a selected group of countries containing all the Scandinavian countries, the United States, Canada, Hungary, Australia, Scotland, and Czechoslovakia. The death rates of all natural (ICSI-XVI) and unnatural causes (ICDXVII) were higher in Finland than in the other selected countries. Also the proportion of cardiovascular deaths as a percentage of all natural deaths was clearly higher in Finland than in any of the above countries, whereas in these countries proportionally more deaths were due to neoplasms than in Finland, especially in men aged 35--44. Only in Hungary did infectious diseases account for about 4.5% of all natural deaths; in the other countries they accounted for only about 1--2%. In the United States, Sweden, Czechoslovakia and Canada a clearly higher relative number of deaths (about 9--13%) were due to diseases of the digestive system than in the other countries (about 3--9%), whereas the relative numbers of deaths from respiratory and genitourinary diseases were uniform among all selected countries. Only in Denmark and Norway was a prominent proportion of the deceased (3.5--9.5%) certified as having died due to some symptom or ill-defined condition. About 90% of all middle-aged men died in each country from various diseases of the above six main ICD categories. As a whole, the above single deviations from the general trend were so small that the present results do not support the view that the differences in certifying and coding practices could explain the significant differences found in cardiovascular mortality of middle-aged men between various countries.


The epidemiology of autopsies in cardiovascular deaths of middle-aged men in Finland in 1973.

There were 414 certified deaths from cardiovascular diseases (CVD) in men aged 35--44, and 1372 at ages 45--54, in Finland during 1973. A detailed analysis of the examination of the cause of death in these cases was made by paying specific attention to the autopsy epidemiology. In men aged 35--44 years 68.6% of all cardiovascular deaths and 55.2% at ages 45--54 was verified by autopsy. The autopsy rate of cardiovascular deaths in these two populations of deceased males (1) was in 1973 about three times higher than it had been 10 years earlier, (2) decreased significantly with the age of the deceased population, (3) was higher in urban than in rural areas, (4) was markedly higher in Helsinki than anywhere else in Finland (at ages 35--44 the rate in Helsinki was 94.9% and at 45--54 76.2% in 1973), (5) was dependent on the actual place of death, (6) was higher than the mean rate recorded for all natural deaths in these two groups of male deceased, (7) was higher in the category of cerebrovascular deaths and lower in deaths from ischaemic heart diseases than the mean rate recorded for all cardiovascular deaths, and (8) was composed mainly of medicolegal autopsies, when the cause of death was some ischaemic or functional heart disease; mostly a clinical autopsy was made when the death was due to some other category of CVD. In addition, 76% of the deceased 35--54-year-old males who died from CVD were either autopsied and/or treated in a hospital before death. This result and the quite high national autopsy rates among the deceased young and middle-aged populations give support to the reliability of the national mortality statistics at these ages.


[Immunology and gastroenterology].

Immunology and gastroenterology are associated due to the part of the gastrointestinal tract with respect to the maturation of the immune system and because of the abundance of immunocytes within the mucosa. Therefore on the one hand a deformity is followed by immune deficiency, on the other hand contact between antigens and the immune system may cause different types of hypersensitivity. Autoimmunopathy, however, develops without known exogenous factors. It may be a primary disease of the gut but also a partial manifestation of a generalized reaction. Finally, each malignant immunoproliferative disease may strike the gut. So the diversity of interaction between the gastrointestinal tract and the immune system causes a variety of immunological disease.


[Clinical significance of bile acids].

During the last years bile acids have gained more and more clinical importance. They play a decisive part in intestinal fat resorption. Increased bile acid content in the colon will result in diarrhea. By determination of serum bile acids the liver function can be judged exactly. It seems probable that bile acids take part in the pathogenesis of gastritis gastric ulcer and colonic cancer. By administration of chenodeoxycholic acid and ursodeoxycholic acid dissolution of cholesterol stones within the gall bladder is possible.


Definitions of ischaemia, infarction and necrosis.

Definitions of the terms ischaemia, infarction and necrosis are presented and their significance in connection with sudden cardiac death is discussed. Morphological features of acute myocardial fibre degeneration are reviewed and the significance of such findings are considered.


[Antilipemic agents available after the ban on clofibrate: clinical-pharmacological view].

Among the various available hypolipidemic agents only clofibrate-related substances, d-thyroxine and nicotinic acid are capable of lowering serum lipid values together with a relative or absolute rise of HDL. By that means one atherogenic risk factor is eliminated and compensated by an anti-risk factor. There are differences concerning the incidence and the seriousness of side-effects between the recommended hypolipidemic agents. Considering actual conditions attempts to find further factors that are associated with HDL level are the natural next step in efforts to develop effective lipid lowering drugs that decrease atherogenic lipoproteins, particularly LDL, and increase vasoprotective HDL.


Drug-induced myocarditis: a report of two cases.

Two patients are reported with hypersensitivity myocarditis. One, a 71-year-old female, was being treated with methyldopa at the time of her death and the second, a 67-year-old female, was receiving tetracycline for a respiratory tract infection.


[The cancer patient, an interdisciplinary problem: aspects of pediatric oncology].

The number of childhood malignancies in West Germany amounts to 1500 per year. The relative success of the treatment requires a therapy concept with curative intention. Diagnosis and treatment during the intensive phase should be centralized in special pediatric oncology departments to guarantee the best possible results. It is emphasized that the patients must be treated after the intensive phase on an outpatient basis. Unavoidable side effects of the treatment demand a "life long" follow-up of the patients in pediatric tumor centers.


[Somatic disorders in cardiac phobia].

The paper is concerned with the implication of vertebral complaints in connection with cardiac neurosis and the reinforcement mechanism which maintains the symptom pattern. 31 psychiatric patients with cardiac symptoms and 10 patients with solely vertebral symptoms were examined neuro-orthopedically as well as by clinical and psychological tests. The results indicated that patients with distinct organic signs as muscle hypertension, blocked vertebrae and tenderness on pressure appear to be more anxious, tensed and irritated in the paper pencil tests. This leads to the hypothesis that the organic patients are more sensitive to external and internal stimuli, which causes a higher inclination for muscle tension and therefore vertebral alteration. These alterations again are responsible for internal stimuli like pain and discomfort in the cardiac region. So a cycle is established which can be interrupted by different therapeutic steps, especially cognitive behavioral approach.


[Secondary hyperaldosteronism in patients with liver cirrhosis, frequently caused by therapy].

Plasma angiotensin II and plasma aldosterone was measured by radioimmunoassay in 78 patients with cirrhosis of the liver (group I: untreated, without ascites, n = 21; group II:untreated, with ascites, n = 25; group III: with ascites, during saluretic therapy, n = 32). From the obtained results it was concluded: (1) Excluding any pretreatment on the outpatient basis in most cirrhotics with or without ascites unaltered plasma levels of angiotensin II and aldosterone were found. (2) In contrast to previous suggestion secondary aldosteronism seems to be a minor determinant of hepatic ascites formation. (3) In untreated patients the 24-h-urinary excretion of electrolytes (Na+/K+ less than 1) represents an insufficient index of hyperaldosteronism. Obviously the kidney retains considerable amounts of sodium independent of circulating aldosterone levels. (4) Far above other mechanism hyperaldosteronism is most often induced by saluretic treatment of ascites and edema. The increased aldosterone secretion might indicate an adaptation phenomenon to restore total body sodium content. Certainly, the established concept of ascites therapy remains unimpaired by this physiological reaction.


[Uremic pancreopathy. Clinical and experimental studies of its pathogenesis].

Uremia results in complex metabolic disturbances of exocrine pancreatic function which increase with the severity of renal insufficiency. This uremic pancreopathy is not identical with the pancreatitis of classical type. Its important clinical indicator is an elevation of serum lipase activity (more than 60% in nondialyzed renal insufficiency; hyperlipasemia was also detectable in chronic hemodialyzed patients (45%). The pathogenesis is heterogenous, its concept based on clinical and experimental studies involves several components: hormonal alterations (calcitonin etc.), catabolic protein metabolism in uremia, systemic disturbances (hemodynamics, hypoxia, acidosis etc.), direct impairment of the pancreatic cells induced by uremic toxins.


[Hyperthyroidism in the elderly].

In patients older than 60 years it is more difficult to establish the diagnosis of thyrotoxicosis because 1. the classical symptoms are either less pronounced or totally absent, 2. complaints of symptoms of the digestive system are more striking and suspicious of a carcinoma (diminished appetite, weight loss, constipation), 3. symptoms like hypertension and cardiac arrhythmia are often to be found in elderly people and therefore not of great diagnostic significance, 4. in a high percentage of cases a selective T3-thyrotoxicosis is to be found.


[Gallstones - cause of mechanical ileus].

Between 1964 and 1978 8748 operations had been performed because of benign diseases of the extrahepatic biliary tract, 413 cases of mechanical intestinal obstruction had been operated, out of these 30 patients with gallstone ileus. The frequency, pathogenesis, symptomatology, diagnostic procedure and therapy are described, the own results are discussed.


[Mechanical ileus. Therapeutic results in 455 patients].

After presentation of the causes, pathophysiology, diagnostic procedures and therapy, the results of treatment of 455 patients with mechanical ileus operated in the period 1964--1978 are presented.


[Postoperative abdominal hernia and its treatment. Results in 438 patients].

The postoperative incisional hernia can be found after any incision, any suture, and also when the technique was as subtle as possible. The frequency ranges from 1--5%. The causes, the frequency, the suture-techniques, and the methods for reparation of an incisional hernia are described. In our clinic in 18 years (1.5. 1960--30.4. 1978) 438 patients were operated with an incisional hernia. The localizations, preoperative diseases, and the methods of operations applied are described and discussed. We were able to get postoperative information of 277 patients, information by letters and own investigations as well. The results are discussed. As far as we know our figures represent the greatest number of cases published. The own late results of operated hernias are described. In other publications a frequency of 15--20% of recurrencies is quoted. In respect to this our own results with "edge-to-edge-technique" and "doubling of the fascia" are satisfacotry.


[Clinical transcutaneous measurement of oxygen pressure during the induction of anesthesia with barbiturates].

Intravenous injection of barbiturates is followed by a depression of the respiratory centre depending on the dose. Blood carbon dioxide increases. This can be measured continuously in the expired air. In the same time blood oxygen modifies. The hypoxia produced by this depressant action was determined by a non-invasive transcutaneous blood gas measurement technique during the induction of anesthesia.


[The possibility of isolated joint transplantation with microsurgery of the blood vessels].

The transplantation of isolated joints with intact blood supply and good biomechanic conditions is possible. Biomechanical and neurotropic disturbances lead eventually to progressive degenerative alterations. The regularly seen periarticular adhesions with reduced joint mobility may also reduce the clinical application. Considering our very good results of joint-replantation also good clinical results of the transplantation with vascular and neural anastomoses may be expected. Microsurgery has a proven place for bridging great bone defects with vascular bone fragments. Histological examinations show a prompt and regular bone metabolism in the transplanted bone.


[A new method for the preparation of special alloplastic implants for partial replacement of the pelvis].

Partial replacement of the pelvis by special prosthesis after resection for malignant lesions becomes more and more a rewarding alternative to the mutilating amputive procedures. A new method is recommended facilitating the forming of suitable prostheses. With computerized axial tomography it is possible to construct an actual sized three-dimensional model of the patients pelvis. This model is a very useful aid in preparing the special prosthesis as it corresponds exactly with the anatomic shape of the resected part.


[Therapy of breast cancer. Results and prognosis after treatment with different surgical methods].

Breast carcinoma is the most frequent form of cancer in women. In Switzerland 1265 women died of it in 1975, the mortality rate is rising slowly, the cause of this being unclear. There is no uniformity about the best treatment of breast cancer. We analyzed 454 carcinomas, operated in the years 1961--1971 according to Halsted, Patey and McWhirter. We found similar 5- and 10-year survival rates with the Halsted and the Patey method of operation, however, decidedly worse results with the simple mastectomy. Today we recommend the modified radical excision of the breast after Patey at all stages; in addition we treat all patients with postoperative X-ray therapy or prescribe an adjuvant cytostatic therapy based on the experimental study of the SAKK (Swis Therapy Group for Clincal Cancer Research).


[Results of treatment with DoloVisano for non-specific pain syndrome related to body movement. Concluding report on a field study of 3326 patients by 314 orthopedists].

The effectiveness of ColoVisano with view to the nonspecific pain syndrom of the locomotor system, particularly of the back, was proven on 3,326 ambulant patients. Three weeks after starting of treatment the majority of the patients was found free of pain. Considering the duration of the disease, the result of treatment with DoloVisano is remarkable: 66% = very good--good, 17% = moderate, only 12% = without success. Only in 15% of the cases side effects were found, which never led to an interrupture of the treatment. When listing the side effects, gastric pain with 6% and trousiness with 50% are ranging among the first places. The field study, performed by 314 orthopedic doctors in practice shows the high effectiveness of DoloVisano not only in patients with non-specific pain syndrom resulting from the spine but also with rheumatic syndrom, especially fibrositis and degenerative diseases.


[Vaccinations during hyposensitization of allergic patients].

The well known or presumed immunbiologic mechanisms of atopic-anaphylactic reaction, hyposensitation and active immunization are discussed. With regard to this discussion, recommendations are given concerning the vaccination of allergic patients during hyposensitation.


[Therapy of acute schizophrenic attacks. High dosage haloperidol therapy compared with a two component treatment].

In a controlled open study 18 patients were treated with high doses of haloperidol (Haldol-Janssen) from 50 to 100 mg daily and 15 patients with a combined therapy of 10 mg haloperidol and 150 to 300 mg levomepromazin (Neurocil). The high-dosed sample a significantly rapid decrease of the productive symptoms and improvement of the general condition were found. The medians of the rating scales and self-rating scales showed similar courses. Within the high-dosage group especially after the beginning of therapy, there was an unexpected significant increase in extrapyramidal signs (dyskinesias), which did not appear any more after starting with an initial dose of at least 50 mg Haldol-Janssen. Other side effects could not be found, the tolerance was good.


[Xerophthalmia].

Xerophthalmia results from an insufficient supply of vitamin A to the eye. Primary signs of xerophthalmia are conjunctival xerosis, Bitôt's spots with conjunctival xerosis, corneal xerosis, corneal ulceration with xerosis, keratomalacia. Secondary signs of xerophthalmia are night blindness, xerophthalmia fundus and corneal scars. According to the WHO 20 000--100 000 children in developing countries are struck annually with blindness due to xerophthalmia. With regard to the treatment immediate therapy with 100 000 I.U. vitamin A intramuscularly and 200 000 I.U. orally on the following day are advised in all cases of active disease. The doses should be reduced by half for children less than one year old. Prior to discharge from the clinic and additional dose of 200 000 I.U. vitamin A (children under the age of one year 100 000 I.U.) orally should be administered.


[Idiopathic polyneuritis. Course, prognosis and electrodiagnostic findings].

In acute idiopathic polyneuritis, the slowing of nerve conduction velocity does not allow prognostical statements. However, a marked reduction of muscle potential amplitude after stimulation and recording points implies a large number of damaged axons. This effect occurs earlier and is more reliable than pathological spontaneous activity in the EMG. Following complete or almost complete loss of indirect muscle excitability, improvement of function can be expected only after sprouting of nerve fibers--therefore after some months at best; permanent defects must bei anticipated especially in distal muscle groups. We experienced this most commonly--but not exclusively--in cases with highly acute courses which led to tetraparalytic syndroms. Clinical courses with slowly progressive disease during months and recurrent courses of idiopathic polyneuritis can also lead to permanent paresis.


[The ellipsoid heart. Construction and animal experimental findings of a new kind of artificial heart].

In order to avoid thrombi generation within artificial ventricles the Ellipsoid heart is built with a one-piece membran in enddiastolic position. This allows to have an optimal washout of all inside surfaces during the cardiac cycles, in enddiastolic position the cross sectional veiw of the membran is circle-shaped. 82% of the filling volume can be used for the maximal stroke volume, which is 120 ml. The maximal cardiac output is 16 l/min. The Ellipsoid heart is evaluated as design for total heart replacement and assisted circulation. As total artificial heart the survival times were in calves experiments up to 40 days, in assisted circulation in parakorporeal position up to 83 days. The cardiac assistance with the Ellipsoid heart (E-LVAD) is performed due to implanted canula in the left ventricle via the left atrium and a connection to the ascending aorta. This technique was applied in 14 clinical cases with cardiac failure after open surgery. The E-LVAD could support the failing heart; it could be removed in 4 patients. The aim to avoid thrombiformation within artificial ventricles could be achieved with the Ellipsoid heart in calve experiments as well as clinically--the membrane was constantly clean and free of any thrombidepositions.


[Results in the documentation for pregnancy surveillance].

Some results from the pregnancy surveillance booklet documentation are discussed in this paper. These results were gained on the basis of data from a representative random sample taken in Rheinland-Pfalz in 1977. Unfortunately, the risk factors section in the pregnancy surveillance booklet does not receive sufficient medical documentation. Apparently, its structure is too complex and its second part is not on the proper place. Contrary to the risk factor check list, which has been answered poorly, the entry of the observations on the course of the pregnancy obviously has carried out regularly. Only half of the pregnant women take advantage of at least 10 preventive medial examinations. Frequency of these examinations and date of the first medical examination in pregnancy depend on social conditions. In case of unfavourable general conditions pregnant women go less often, and later, to the prenatal examinations and the state of health of the new-born child depends on the "social strata" factor. Seen especially from the viewpoint of a greater centralization in obstetrics, the measures taken in prenatal care should be decentralized and varied and should include a revision of the pregnancy surveillance booklet.


[Coronary vessel abnormalities of aortal origin].

Anomalies of aortal origin of the coronary vascular system are found in approximately one percent of the population and can be exactly documented by coronary angiography. Although such variants of origin and in the coronary vascular course are not associated with an increased incidence in coronary sclerosis, it is important that they be known for several reasons: 1. in order to avoid false interpretations of the coronarogram that can be of grave consequence, 2. for the selection of the correct incision at heart surgery, 3. a very rare anomaly, the origin of the trunk of the left coronary artery in the right Valsalva's sinus, is clearly related to sudden cardiac death in children and youths. A correct diagnosis can be life-saving.


[Extended elbow synovectomy in primary chronic polyarthritis. Long-term results].

In 50--70% of the rheumatoid patients arthritis of the elbow joint can be found. Early results after surgical treatment are very successful. The late results after 29 synovectomies, partly with resection of the head of the radius and neurolysis of the ulnar nerve, are presented. The follow-up time averages 6 years. We found a good relief of pain and a moderate, but persisting gain of movement. The importance of an early operation and a consequent physical therapy is pointed out.


[Medical care on board ship. Cruise-medical experiences].

Cruise medicine has general, tropical and industrial medical aspects. Surgery is less important than in former days. Ship doctors treat crew and passengers. Already the physician's presence gives security to the often old, sometimes sick tourists coming to cruise. Seasickness can be treated successfully in an active way.


[Effect of uric acid lowering drugs in low dosage in patients with  hyperuricemia and hypertriglyceridemia in a randomized group study].

The serum uric acid lowering effects of 100 mg Allopurinol (A), 20 mg Benzbromarone (B) and the combination of both were tested in a randomized block-trial in 12 male patients suffering from hyperuricemia and hyperlipoproteinemia type IIb/IV. Therapy periods lasted 4 weeks each. Allopurinol lowered the uric acid concentrations from 7,54 mg/100 ml to 5,95 mg/100 ml, Benzbromarone from 7,54 mg/100 ml to 6,11 mg/100 ml and the combination from 7,54 mg/100 ml to 4,90 mg/100 ml, all three significantly. The difference between the effect of the combination drug and Allopurinol and Benzbromarone respectively was also significant. An additive effect of both components is evident. Serum creatinin concentration remained constant. Uric acid and creatinin excretion could not be evaluated because of failure of patient compliance in the collecting of urine.


[Long-term therapy in ulcerative colitis and Crohn's disease].

The remission period of patients with ulcerative colitis was extended by long term treatment with 2-3 g sulphasalazine daily. Proctocolectomy should be performed if no remission can be obtained on continued medical therapy. Moreover, in these cases the operation is suggested to avoid the unwanted side effects of the drugs and the increased risk of cancer.


[Irritable colon. Possibilities for an objective diagnosis and its value for the therapy].

Diagnosis of functional gastrointestinal disorders consists mainly in exclusion of organic diseases. A more positive diagnosis may be established by the identification of characteristic symptoms. Myography and manometry within the colon sigmoideum reveal significant patterns in irritable bowel patients, which also may allow control of therapy.


[Fibroadenoma in an accessory breast. A case of polythelia and fibroadenoma in the left breast region and a perivulvar accessory breast].

The case of a 32-year-old female patient with multiple malformations (hare-lip, polythelia, fibroadenoma in an accessory mammary gland) and independent of these, another fibroadenoma in the breast is reported. The fibroadenoma developing in the accessory breast around the vulva, diagnosed by means of aspiration biopsy cytology, should be payed special attention. This case also confirms the applicability in preoperative diagnostics of aspiration biopsy cytology, a method which has proved to be effective for years.


[Hyperthelia in young men].

Out of a group of 500 young men (aged 17 to 29) 23 persons had one or several supernumerary nipples. Different types with respect to the degree of their development are to be distinguished.


[Value of the dilatation of the anal sphincter].

Anal sphincter dilatation with forefinger and middle fingers of both hands for a two-minute period under strong pressure results in a measurable tonus-decrease of the sphincter ani over a period of 2-3 weeks. This tonus-decrease is of therapeutic advantage in numerous diseases, particularly in those of the anal area. At the same time, the stretching may well be used to protect anastomoses in the colon or to dilate the operative access in transanal operations. Complications arising from the stretching described are insignificant.


[The efficacy of Vita-Dor as a sleep inducing and hypnotic drug].

Vita-Dor is a drug inducing sleep and acting as an intermediate type of a hypnotic. Regarding the dosis the age of the patient has to be considered. As an average dose for adults 2 sugar coated tablets are recommended to be administered in the evening. Elderly patients should start with 1 tablet in the evening.


Implantable pacemakers for management of tachyarrhythmias.

Attempts have been made to control tachyarrhythmias with implantable pacemakers since the late 1960's. The basic approaches considered were: a) maintenance of a basic rate following surgical division of the conducting system, b) pacing to prevent onset of tachyarrhythmias, and c) pacing to terminate episodes of tachyarrhythmias. The earliest approaches required conscious patient interaction in effecting therapy. Emergence of newer technologies has allowed development of flexible, automatic pacing systems which overcome some of the limitations of earlier approaches.


The surgical management of ventricular tachycardia.

A better understanding of the mechanisms of chronic ventricular arrhythmias has led to the development of new surgical techniques for their management with promising results. Simple ventriculotomy is particularly useful in idiopathic ventricular tachycardia (19 cases). Ventricular tachycardia complicating myocardial infarction may be a special indication for an encircling subendocardial ventriculotomy (12 cases).


[Reconstruction of the right ventricular outflow tract in tetralogy of Fallot with a Hancock valve containing ventriculo-pulmonary conduit (author's transl)].

Between June 1975 and August 1978, 22 cases of anatomically and functionally severe tetralogy of Fallot were corrected with a valve bearing ventriculo-pulmonary Hancock conduit. The indication for use of the Hancock conduit was atresia of the pulmonary valve ring and main pulmonary artery (classified according to Sommerville and Jefferson as types I and II respectively) in 5 patients, severe hypoplasia of the pulmonary valve ring, the right ventricular outflow tract (RVOT) and the main pulmonary artery in 10, 1 patient with an abnormal right coronary artery and an acquired obstruction of the infundibulum subsequent to Waterston-Cooley anastomosis in 4 patients. Hancock conduits (KHP) were also employed in two patients with severe pulmonary insufficiency after patch insertion across the pulmonary valve ring. Early mortality was 9%. Very good hemodynamic results were achieved in 15 patients (with pRV/pLV ratios less than 0.4 in 8 and between 0.4 and 0.5 in 5 patients). Good results (as indicated by pRV/pLV ratios between 0.5 and 0.7) were found in 7 patients, while only in 2 patients a ratio greater than 0.7 indicated an insufficient hemodynamic result. The valve bearing ventriculo-pulmonary Hancock conduit is the surgical method of choice for various types of atresia of the RVOT. As opposed to transanular reconstruction of the RVOT which, dependent on the extent of hypoplasia, consistently leads to some degree of pulmonary insufficiency, the use of the Hancock conduit can prevent pulmonary regurgitation.


Effect of glucagon and glomerulopressin on the renal function of the dog.

Glucagon was infused through the porta or through the left renal artery in dogs. Another group of dogs were infused with glomerulopressin through the left renal artery. It was observed that glucagon when infused through the portal vein enhanced the glomerulopressin production and the glomerular filtration rate (GFR). When glucagon was infused intrarenally it did not alter GRF but it had a direct tubular action decreasing sodium reabsorption in the proximal tubule. Glomerulopressin infused intrarenally increased GRF and potassium excretion. The results suggest that the increase in GFR was due to increase in glomerulopressin activity. There are three reasons for this statement: a) GRF increased when glomerulopressin activity was high, but not when there was a low activity, 5) intrarenally infused glomerulopressin produced a very significant change in the GFR of the infused kidney, while the GRF of the contralateral kidney remained unchanged and c) intrarenally administered glucagon had no effect on GFR.


Activation of pyruvate dehydrogenase by insulin in isolated brown fat cells.

Isolated fat cells from rat brown adipose tissue in vitro respond to insulin with an increase of pyruvate dehydrogenase (EC 1.2.4.1) activity due to conversion of the inactive form of the enzyme (PDHb) to the active form (PDHa). Like in white adipocytes this effect depends on the presence of glucose or 2-deoxyglucose in the medium. The interrelationship between the steady state of the PDH-system and the phosphorylation state of the adenine nucleotides was studied in white adipose tissue. While insulin in the presence of 2-deoxyglucose caused a large fall of the tissue ATP/ADP ratio which could explain the increase of PDHa activity, the ATP/ADP ratio remained unchanged during incubations with insulin and glucose. Thus it appears that other factors than the ATP/ADP ratio are involved in the regulation of PDH activity by insulin the nature of which remains to be elucidated.


In vitro effect of branched chain amino acids on the ribosomal cycle in muscles of fasted rats.

1) The effect of a single i.p injection of branched chain amino acids on ribosomal profiles of psoas muscles was studied in rats after a 48--96 hour fast. Experimental and control animals received glucose and insulin 1--2 hours before killing. 2) The ratio of polysomes to subunits and monomers decreased progressively during the fast. 3) The administration of the three branched chain amino acids together or leucine alone significantly increased the proportion of polysomes. 4) This effect was not observed in rats fed ad libitum. 5) It is suggested that the branched chain amino acids and specifically leucine may be required for the full protein anabolic response of muscles to insulin during a prolonged fast.


Effect of nembutal on LH release in baboons.

Regularly cycling female baboons were selected and maintained under a diurnal light schedule from 0500 to 1900 hr (CST). Beginning three days prior to the expected LH peak, blood was collected daily at 0800 and 1600 hr for 6 days in 5 baboons under light sedation for radioimmunoassay of plasma LH and estrogen. The plasma level of LH increased linearly and reached a peak in the afternoon of the second day. The peak in plasma estrogen appeared prior to the LH peak. In order to examine the critical period of LH surge in baboons, nembutal was injected daily at 1300 hr beginning a few days prior to expected LH relase. Initial dose of nembutal was 35 mg/kg body weight, but a supplementary dose was later required for a full 5 hours of anesthesia. Blood was collected at 1600 hr from 4 baboons during nembutal injections and after cessation of nembutal injections for radioimmunoassay of plasma LH and estrogen. It was found that nembutal injections suppressed LH release in 2 baboons, and caused a delay of LH release in 2 baboons. However, the plasma level of estrogen declined immediately after initiation of nembutal injection and remained lower. The evidence illustrates the nature of the neural components of LH release which became effective in the afternoon during the ovulatory phase. In addition, a linear increase in plasma level of LH, which is due to accumulation of circulating LH, is necessary for induction of ovulation in baboons.


Similar serum concentrations of thyroid hormones in two geographically separate populations on disparate iodine intake.

Serum thyroid hormones were measured in Montreal, Canada (urinary iodine 446 +/- 164 micrograms/day) and Zagreb, Yugoslavia (urinary iodine 108 +/- 32 microgram/day). The serum concentrations of thyroxine and triiodothyronine in the two populations were almost identical. We conclude that dietary iodine, within accepted normal limits, is not a factor in determining serum thyroid hormone levels. The wide differences in reported serum triiodothyronine concentrations are related to methodological problems.


Effects of actinomycin D and estrogen priming on decidual growth in ovariectomized mice.

Ovariectomized mice were primed for 2 days with estradiol and/or actinomycin D. In order to evaluate the effects of these treatments on endometrial cell proliferation, colchicine and [3H]-thymidine were administered shortly before killing groups of animals at days 4 and 5 after priming (the latter groups received 500 micrograms progesterone plus 10 ng estradiol 24 h before killing). The same priming treatments were administered 3 days before starting hormonal treatment eliciting uterine sensitivity to decidualization (incuded by intrauterine oil injection). The comparison of labeling and mitotic indices and of decidual tissue weights between experimental groups showed that under such conditions: (1) actinomycin D only partly inhibits the effects of estrogen priming: the increase in cell division obtained on day 4 after priming remains unchanged in all three endometrial components while the increase in stromal mitotic activity at day 5 and further decidual growth are reduced, (2) since the inhibition rate of these parameters is greater in non-primed than in primed animals, it appears that estrogen priming counteracts the antagonistic action of actinomycin D.


The biological activity of dimeric testosterone, a new long-acting androgen, and of testosterone enanthate in the castrated male rat.

The long-term effect of single intramuscular injections of various doses of dimeric testosterone and of testosterone enanthate into castrated male rats upon serum testosterone, luteinizing hormone (LH), pituitary LH, and on the weight of the seminal vesicles, the ventral prostate and the levator ani muscle, was investigated. The effect of the enanthate was characterized by a rapid onset and a protracted androgenic action and a suppression of serum LH, while the dimeric testosterone brought about only a moderate but very even depot effect. The injection of 5 mg of the dimeric testosterone caused a positive feedback effectu upon LH release for 16 weeks. The results indicate that the dimeric testosterone may exert is hormonal effects as intact ester.


18-Hydroxy-11-deoxycorticosterone in hypertensive uremic patients during hemodialysis.

The present study was carried out in 25 hypertensive uremic patients on regular 4 h dialysis, 3 times a week. Plasma 18-hydroxy-11-deoxycorticosterone (18-OH-DOC), aldosterone (PA) and corticosteroids were determined by radioimmunoassay and competitive protein binding technique before and at the end of the 1st, 2nd and 3rd hour of hemodialysis. Plasma 18-HD-DOC was normal before dialysis and did not change significantly during hemodialysis, whereas body fluids and electolytes decreased progressively. No correlation was observed between blood pressure and 18-OH-DOC during dialysis. 18-OH-DOC did not correlate with PA which decreases progressively during hemodialysis and was correlated to plasma corticosteroids only at the 3rd hour of dialysis, probably on account of the enhanced influence of ACTH on the adrenal cortex.


The structure of the enterocyte in relation to its position on the villus in childhood: an electron microscopical study.

An electron study of histologically normal small intestinal mucosa taken from 10 children has shown, on morphological grounds, that the mid-region of the villus is best adapted for digestion and absorption. Microvilli in the mid-region were tallest, and presented the maximal surface area. In contrast the upper region of the villus exhibited a reduction in microvillous surface area and some cellular damage. Cellular extrusion was observed near the base of the villus as well as near the tip. The occurrence of cellular alterations in the oldest and more exposed regions of normal mucosa in childhood may be symptomatic of a natural epithelial ageing process but may also be the result of an adverse luminal effect on the enterocytes. These findings differ from some of the observations made on adult small intestinal mucosa where it has been reported that the microvilli present a maximal surface area and the enterocytes are most active at the tips of the villi rather than in the mid-region.


Postmastectomy lymphangiosarcoma: a reappraisal of the concept--a critical review and report of an illustrative case.

The syndrome of postmastectomy lymphangiosarcoma (LAS) has been universally accepted since it was first outlined by Stewart & Treves (1948), except for a small number of authors who concluded that the neoplasms arising in the chronic lymphoedematous arms were in fact due to retrograde spread from the original breast carcinoma (Laffargue, Pinet & le Go 1960, Giannardi, Pelù & Zampi 1960, Giannardi & Pelù 1961, Delarue 1962, Salm 1963, Laugier, Olmos, Hunziker & Orusco 1973), but their views have been largely ignored. A case is reported in whom neoplastic arm lesions appeared 27 years after mastectomy and were due, in our opinion, to recent metastases from a new primary Carcinoma of the lung. The validity of the entire concept of LAS is re-examined.


Mucosal hyperplasia in clonic diverticula.

Benign, nonpolypoid mucosal hyperplasia has been consistently observed adjacent to colonic carcinomas. In order to determine the specificity of this association we looked for this type of mucosa in diverticulosis with or without diverticulitis, a disease thought not to be causally related to carcinoma. Nonpolypoid mucosal hyperplasis was frequently found within diverticula suggesting that this mucosal abnormality is, in some instances, unrelated specifically to malignancy.


Fertility in psychiatric outpatients.

The fertility rates of 223 female schizophrenic outpatients and 479 female nonschizophrenic outpatients were compared to a probability sample of 300 women residing in the same geographic area, metropolitan Atlanta, and from the same social strata as the patients. Age- and race-adjusted comparisons showed that the mean number of children per woman and levels of unwanted and unplanned fertility did not differ in the different diagnostic groups. Furthermore, the rates were not lower for the psychiatric patients than for the general population. In order to reduce an important source of psychiatric morbidity, those in the mental health professions need to pay more attention to the family planning desires of their patients.


Physical examinations in psychiatric practice in Ohio.

In 1974 members of the Ohio Psychiatric Association were surveyed to determine the extent to which psychiatrists performed physical examinations and their attitudes toward conducting such examinations. Responses from 222 psychiatrists showed that most believed psychiatric patients should have a physical examination, but that it should be conducted by a physician other than a psychiatrist. Those who felt more confident in their diagnostic skills tended to perform examinations more frequently than psychiatrists who were unsure of their skills. Regardless of whether they performed examinations, the respondents were almost universal in the belief that their medical training and experience added an important dimension to their skills.


Patterns of utilization of a neuropsychiatric assessment unit.

During a one-year period an inpatient psychiatric ward specializing in the evaluation of neuropsychiatric disorders admitted 306 patients for neurodiagnostic services and 119 general psychiatric patients for brief treatment. About half the neurodiagnostic patients were referred by sources not affiliated with the unit, and about a quarter came from outside the immediate area, indicating that a variety of community agencies relied on the unit as a referral facility. In nearly 60 per cent of the cases evaluated, suspected medical or neurologic abnormality was confirmed and the probable etiology determined, while in only a small percentage was a previously unsuspected abnormality detected; this combination of outcomes suggests that most referrals were appropriate and that the unit's main function was to clarify etiologic relationship and design treatment plans.


A model for acute psychiatric inpatient treatment of latency-age children.

Beginning with the premise that acute inpatient treatment of severely disturbed latency-age children offers enormous advantages over other types of interventions, the author describes a model for such treatment. The model consists of three phases: initial, working-through, and termination. It has a psychoanalytic basis and takes into account changing factors, such as the child's symptoms and the attitudes of both the child and his parents throughout different stages of the hospitalization. A case history illustrates the various phases and the treatment interventions used.


Staff and patients evaluate their therapeutic community.

A committee of staff and patients conducted an informal evaluation of a therapeutic community on a 16-bed psychiatric unit. The committee reviewed the history, original intent, current purpose, and effectiveness of meetings held on the unit; when problems were identified, suggestions for change were formulated. The evaluation served to increase the efficiency of meetings and to counteract what the authors termed the "drift phenomenon," or the tendency of the original purpose or structure of a meeting to change over time. The process also fostered an atmosphere of mutual respect and an enhanced sense of purpose among the patients and staff who worked on the committee.


HMOs and hospitals: what are the options?

Each individual hospital must assess the relationship it wishes to have with HMOs/It is clear, however, that hospitals should get involved in the effort to deliver comprehensive health care services to their communities.


Competitive approach may ease problems in delivery system.

Experts believe that the absence of effective market forces in the health care field removes incentives for efficiency from both providers and consumers of health care/In today's climate, the authors say, it may be that competition, not regulation, may help solve our current problems.


Shaky start overcome by Illinois HMO.

Trying to provide too much too soon, early HMO nearly is bankrupted, but infusion of sound management practices turns it around.


Lessons learned through hospital involvement in HMO.

The major considerations that affect hospital participation in HMOs are motivation, governance, medical staff involvement, financing, and planning and operations/These considerations are discussed in general and as they apply to one particular hospital's experience.


HMOs: a look back, a look ahead.

It is now eight years since federal legislation recognized HMOs/The author overviews progress in that period, describes present challenges, and looks to the future.


Dramatic rise in national growth of HMOs.

Studies show that HMOs have been able to lower hospital utilization rates and are introducing new elements of competition into the health care system.


Gearing up for primary care.

Although hospitals have long been involved in the provision of primary care services, a new opportunity now exists for hospitals to take the lead in better organizing these services.


Should a hospital consider construction management?

Although the construction management technique can produce substantial savings, it can also, if not implemented properly, offer little advantage.


Where does the owner fit in the construction management process?

The construction management approach enables the owner to be involved in the building project from the initial design stage through project completion. He participates in cost-benefit decisions, helping to ensure that the best possible building is constructed at the lowest possible cost.


Construction managers provide vital services for building projects.

A construction manager can be selected on the basis of his qualifications, rather than only on the basis of a low bid. He participates in the construction phase of a project as a team member, rather than as an adversary.


Logical thought process key to corporate plan.

Corporate planning allows an organization to determine where it is going and how it will get there. There are two major phases that make up this planning process.


AHA looks at nurse credentialing.

AHA's National Conference on Categories or Nursing Practice explores the weaknesses and strengths of the credentialing system and the ramifications of proposed changes.


Shared-service paging clears the air waves.

Radio-paging channel congestion can be reduced if inhospital and areawide paging are distinguished, and if the proper equipment is used for the separate functions.


CHA survey of central management services organizations.

Catholic multihospital systems with central management services organizations (CMSOs) constitute a significant percentage of total Catholic hospitals and acute care beds. Results of a recent CHA survey provide a base for future analyses of the CMSO and reveal the potential for further system development.


A pioneering full-service agency for older Americans.

As the over-60 population in America becomes a sizable majority with recognizable needs, ways are sought to serve those men and women who do not need to be institutionalized but who do need some kind of help in order to live independently. The Cardinal Ritter Institute in St. Louis offers "creative care for the older person," putting special emphasis on home health care and health maintenance.


The public debate on social justice and health care: an opportunity for evangelization.

The most difficult moral choices arise at the point where social justice questions and medical-moral questions intersect. In an age of increasing technological advances and government intervention, Catholic health care facilities ought to shape a coherent moral policy that affirms human dignity and conforms to the Church's moral teaching.


Educating the Christian physician: being Christian and being a physician.

Christian health workers need a common code of Christian medical mortality equal to the complex challenges of a secular society. By example and through formal teaching, the Christian student must learn the ethics, theology, and philosophy necessary to understand and justify clinical decisions.


Using consumer evaluations of health care.

Patient evaluation data are valuable to hospital administrators because they indicate what quality of care means to the people the hospital serves and which aspects of care management can alter to avoid patients' negative responses.


Loneliness--the genesis of solitude, friendship, and comtemplation.

Living creatively with loneliness means learning who we are in solitude, experiencing health healthy friendship, and responding to God's invitation to comtemplation.


Unstable ring Y chromosome in an aspermic male.

A ring Y chromosome was found in a male showing growth retardation and aspermia but normally developed external genitalia. The ring does not display either the characteristic brilliant Y fluorescence or the typical late-replicating heterochromatin.


Monosomy 10qter.

An 11-year-old girl with 10q26qter deletion is described and compared with another patient reported in the literature. The most characteristic features of monosomy 10qter seem to be: severe mental retardation; growth retardation; microcephaly; and facial dysmorphism with a long and triangular facies, a broad and prominent nasal bridge, a poorly developed tip of the nose, a short philtrum, and flattened angles of the mandible. Several of these features are opposed in type and countertype to features of trisomy 10qter.


Partial trisomy of the short arm of chromosome 3 (3p25 to 3pter). A distinct clinical entity.

Two profoundly mentally retarded brothers with partial trisomy for the distal part of the short arm of chromosome 3 (3p25 to 3pter) are described. Their anomaly arose as a segregation product of a balanced t(3p-;18q+) translocation in the mother. Compared with the other cases of partial 3p trisomy reported up to now, the present patients display a similar craniofacial dysmorphism with hypertelorism, broad nasal tip, short upper lip with prominent philtrum, and a large mouth with down-turned corners. Other stigmata, such as a prominent, high forehead with frontal bossing and full cheeks, were present during childhood but progressively disappeared.


Partial trisomy 4q: two cases with a familial translocation t(4;18)(q27;q23).

Clinical and cytogenetic data of two related patients, both trisomic for the segment 4q27 to qter, are reported. Familial studies determined that the mothers of the two probands were carriers of the same balanced translocation between chromosomes 4 and 18. Altogether, two partial trisomies 4q, five balanced karyotypes, and one 45,X0 karyotype were found in the family. The 18 cases reported to date are reviewed with respect to the karyotype-phenotype correlation.


Two cases of trisomy 12p due to rcpt (12;21)(p11;p11) inherited through three generations.

Two cases of trisomy 12p due to a familial translocation t(12;21) (p11;p11) inherited through three generations are presented. The clinical features of both affected individuals are consistent with those previously reported. Study of the NORs by silver staining showed translocation of the NOR from chromosome 21 onto the der(12) and suggested that the activity of this site has been suppressed in some carriers.


Two cases of familial paracentric inversion in man associated with sex chromosome anomaly. 47,XXY,inv(5)(q21q32) and 45,X,inv(7)(q11.3q22.3).

A paracentric inversion of chromosome 5 was detected after RHG banding in a subject affected by Klinefelter's syndrome. The inversion was also observed in the patient's mother, and was confirmed by QFQ- and RBA-banding techniques. A second paracentric inversion affecting chromsome 7 was detected in a woman with Turner's syndrome. The same structural anomaly was found in her father and her half-brother. The possible relationship between sex chromosome nondisjunction and paracentric inversion is discussed. Furthermore, the inversion of chromosome 7 reproduces exactly the chromosome 7 of the gorilla, which is presumed to be ancestral to the human 7. This therefore appears to be the first reported case of reverse chromosomal mutation.


Characterisation of the isoenzymes of phosphoglucomutase (PGM) determined by the first (PGM1) and second (PGM2) locus observed by isoelectric focusing.

The existence of four alleles of phosphoglucomutase (PGM1) in human red cell lysates has previously been demonstrated by isoelectric focusing (Bark et al., 1976; Kühnl et al., 1977; Sutton and Burgess, 1978). Experiments are now described in which the position of each of the first-locus (PGM1) and second-locus (PGM2) isoenzymes is defined, thus extending and confirming the original proposal made by Bark et al.


The likely region of overlap (LRO) method for physical assignment of loci.

Numerical analysis is applied to physical assignments of loci, providing point estimates, an LRO confidence interval, and a chi(2) test of consistency whether there is a smallest region of overlap (SRO) or not. Results are given for two examples and summarized for 81 loci in man.


Chromatographic components of beta-hexosaminidase in I-cell disease (mucolipidosis II).

Isozymes of N-acetyl-beta-D-hexosaminidase in body fluids, culture medium, postmortem organs, and cultured fibroblasts from patients with I-cell disease were resolved by ion exchange column chromatography. The elution pattern was compared in detail with that of the isozymes in control samples. This approach revealed no qualitative differences between the isozymes from the two sources. There is a relative increase of the neuraminidase-sensitive components of hexosaminidase in I-cell disease. This phenomenon is probably related less to the unknown primary defect of the disorder than to the quantitative change in the distribution of hexosaminidase components between the intra- and the extracellular compartment.


C'3 polymorphism in Italy.

C'3 phenotype and gene frequencies observed in two Italian samples are reported. The allele frequencies resemble those reported for other Caucasian populations. Five different rare variants are described.


Electrophoretic demonstration of heterozygosis in hereditary pyruvate kinase deficiency. An unusual method.

The defective PK variant of a patient with a severe form of hemolytic anemia was characterized by its inability to undergo a normal 'proteolytic maturation.' In obligatory heterozygotes it could be proved that red cells contained different PK species, some of them sensitive and the others partially resistant to the action of trypsin.


Chromosome aberrations in psoriatic patients treated with arsenic.

A significantly increased frequency of chromosomal aberrations was found in lymphocytes from eight psoriatic patients previously treated with arsenic than in lymphocytes from eight psoriatics with no such previous treatment. In most patients the arsenic therapy was discontinued more than 15 years ago. In the arsenic-treated group a statistically significant heterogeneity was found with respect to the frequency of aberrations. The frequency of sister chromatid exchange was not increased in the arsenic-treated patients.


Periodic hypokalemic paralysis transmitted by an unaffected male with negative family history: a delayed mutation?

A pedigree is described that includes three cases of periodic hypokalemic paralysis. Apparently, the disease has arisen by de novo mutation in a father of two affected daughters, who, however, is not affected himself. This is unexpected, since in males the disorder is generally inherited as a fully dominant trait. Therefore we propose that these findings result from an early somatic or a half-chromatid mutation.


Los Angeles variant of galactose-1-phosphate uridyltransferase (EC 2.7.7.12) in a Mexican family.

Enzymatic activity and electrophoretic mobility of galactose-1-phosphate uridyltransferase (EC 2.7.7.12) were assayed in a Mexican family (8 sibs and their parents) with two galactosemic members. Normal, galactosemic and Los Angeles enzyme variants were identified. A survey of the ethnological backgrounds of the individuals reported to date with the Los Angeles variant showed multiple origins that could be explained by an ancient and widespread gene mutation or, more probably, by further biochemical heterogeneity.


Interstitial deletion of the long arm of chromosome 8. Karyotype: 46,XY,del(8)(q21).

This report describes a polymalformed 18-month-old male with an interstitial deletion of the long arm of chromosome 8. His karyotype is: 46,XY,del(8)(q21).


Fragile site long arm chromosome 16.

A fragile site at the long arms (q21) of chromosome 16 was found in two persons, each of whom became the parent of a child with a de novo structural chromosome abnormality--a balanced autosomal translocation and an autosomal deletion. The question of an increased risk of structural chromosome abnormalities in the offspring of persons with fragile site long arm 16 is discussed.


Partial long arm deletion of one X chromosome in a patient with secondary amenorrhea.

A partial long arm deletion of one X chromosome was observed in a patient with secondary amenorrhea and with no features of Turner's syndrome. It was shown that the deleted X chromosome was the inactivated one in all metaphases of the lymphocyte culture and of the tissue culture from gonadal biopsy. The patient was detected during a cytogenetic study of secondary amenorrhea of ovarian origin.


A case of long arm deletion of the X chromosome in a patient with secondary amenorrhea.

This paper presents the clinical and cytogenetic findings in a female patient with secondary amenorrhea and normal phenotype. Some difficulties related to karyotype-phenotype correlation are discussed.


Regional assignment of red cell acid phosphatase locus to band 2p25.

Cytogenetic and enzyme studies of a child trisomic for 6p and monosomic for band 2p25 are reported. A tentative assignment of the ACP1 gene locus to band 2p25 is suggested by a 50% decrease in red cell acid phosphatase activity.


Relationship between alpha-L-fucosidase deficiency in plasma and alpha-L-fucosidase activity in leukocytes.

After testing a population sample of 185 hospitalized Italian children for the plasma alpha-L-fucosidase deficiency and establishing an approximate threshold value between heterozygotes and wild-type homozygotes, we analyzed by two statistical methods the distribution of the two genotypes. The results obtained by probit analysis agree with threshold and average values expected on the basis of the Hardy-Weinberg equilibrium. In addition, the level of alpha-fucosidase in leukocytes of 12 individuals with deficiency of alpha-fucosidase in plasma was found to be significantly lower than that of 61 controls (P less than 0.005). These results indicate that the mutation(s) causing a deficiency of alpha-fucosidase in plasma is (are) also expressed in leukocytes.


Characteristics of galactokinase and galactose-1-phosphate uridyltransferase in cultivated fibroblasts and amniotic fluid cells.

The kinetic characteristics of galactose-1-phosphate uridyltransferase and galactokinase in cultivated fibroblasts and amniotic fluid cells were investigated. The Km values of galactokinase for galactose at 2.0 mM ATP are 0.34 mM in amniotic fluid cells and 0.48 mM in fibroblasts. The Km values for ATP at 0.5 mM galactose are 1.25 mM and 2.10 mM. Transferase and galactokinase activities and protein content increase logarithmically during the growth of cultivated cells. The specific activity of both enzymes also increases and reaches a maximum level 10--15 days after subculture. The specific activity of transferase increases faster than that of galactokinase in the case of amniotic fluid cells. In the case of fibroblasts the specific activity of galactokinase increases faster than that of transferase.


The constitutional fragility of chromosome 12 in a case of 46,XX,var(12)(gh',RHG,CAG,CBG).

The constitutional fragility of chromosome no. 12 in a female infant with unspecific clinical signs is described. RHG, GAG, and CBG methods were used to localize the fragile point. The breaks seem to be in 12q1.3, and always within an R band. A possible correlation between the phenotypic modifications and the chromosome variant is discussed.


18Q - syndrome resulting from a tdic(14p; 18q).

A case of 18q- syndrome due to a de novo tdic(14p;18q) is presented. The interest of this observation lies in the rarity of stable dicentric chromosomes arising from reciprocal translocations between autosomes.


Abnormal childhood phenotypes associated with the same balanced chromosome rearrangements as in the parents.

Three patients have been detected because of abnormal phenotypes. Balanced chromosome rearrangements were found in their karyotypes, and in one of the parents in each case. In these three families the association of an abnormal phenotype and a balanced chromosome rearrangement may either be a chance happening or be induced by a submicroscopic loss of chromosome material, for which different position effects may be responsible, according to the case in question. These observations prompt us to ask what decision should be made relative to termination of pregnancy if such a rearrangement is found in amniotic cells in a family with a previous abnormal child.


Sister chromatid exchange and cell cycle in fibroblasts of Bloom's syndrome.

Sister chromatid exchange (SCE) has been studied in the fibroblasts of five Bloom's syndrome patients, one heterozygote, and two normal individuals. The high frequency of SCE already known in the lymphocytes of Bloom's syndrome was also found in the fibroblasts of all five patients. However, populations with low and high frequency of SCE were not found. In addition, chromosome aberrations appeared with a lower frequency. The cell cycle duration in the Bloom's fibroblasts appeared to be similar to that in the normal cell line, and the difference in the growth pattern appeared to be due to the variation in the mitotic index. The cell cycle lasted about 24 h in at least four of the Bloom's lines studied during the present experiments.


Single Cd band in dicentric translocations with one suppressed centromere.

Six human dicentric translocations involving the presence of a suppressed centromere were studied: one case of t dic(9;22), one of t dic(13;18), one of t dic(14;15), and three of t dic(13;14). All exhibited chromatid separation at an acrocentric centromere and were demonstrated to have two regions of centromeric constitutive heterochromatin. The four that were available for retrospective study showed a single Cd band, with absence of the Cd band at the suppressed centromere.


Terminal long-arm deletion of chromosome 1 in a male infant.

The clinical findings in a child with a terminal deletion (1) (q42 leads to qter) is described and compared with three cases with a similar chromosomal anomaly.


Three cases of ring chromosome 2, one derived from a paternal 2/6 translocation.

Two cases of primary ring chromosome 2 and one case of a ring secondary to a paternal 2/6 translocation are described and compared with a fourth case of ring 2 from the literature. The breakpoints in two cases are identical and the same as the breakpoint on chromosome 2 in the composite 2/6 ring. The three primary rings have a number of symptoms in common, but other cases are needed to identify a possible deletion syndrome. The levels of the enzyme MDH-1 were within the normal range in Cases 1 and 2. Thus we localised the locus for MDH-1 to segment 2p23 leads to p25; this had previously been localised to segment p23 leads to pter.


Sex-linked inheritance of cleft palate.

A family pedigree is reported in which males in four generations are affected with midline isolated cleft palate. This is the second report of cleft palate inherited as a sex-linked recessive trait, and it emphasizes the importance of careful pedigree construction when counseling families of children afflicted with this disorder.


Translocation of a supernumerary Y to a 15: study of six cases (three males and three females) in three generations.

We present a family in which six members (three males and three females) carry a translocation of the fluorescent part of a supernumerary Y to a 15. The carriers do not have any impairment of fertility or any malformation.


Investigation of associations between ABO blood groups and coagulation, fibrinolysis, total lipids, cholesterol, and triglycerides.

To investigate possible associations between ABO blood system and coagulability levels, fibrinolysis, total lipids, cholesterol, and triglycerides, the plasma and serum of 300 Rh-positive male blood donors were tested. The tests performed were: RT, PTT, K-PTT, PT, F.V, F.II, F.VII, Complex II, VII, and X, TGT, fibrinogen, HAE 0.2, HAE 0.5, ELT, LIP, Col.1, Col.2 and TRI. Analysis of the laboratory data shows a lower coagulability in O blood group individuals. This result was obtained in coagulation tests (RT, PTT, and K-PTT) specific for factor VIII level. In addition, a higher sensitivity to the in vitro heparin anticoagulant effect in O group individuals was confirmed. Nevertheless, these conclusions are specific for Negroids, the same effects not being observed in Caucasians. None of the other laboratory tests revealed any differences related to either blood group or race.


The occurrence of DChi and new D and B transferrin variants among caste groups of Andhra Pradesh (S. India).

Serum samples from a total of 862 unrelated individuals belonging to seven Hindu endogamous caste groups residing in Hyderabad and Warangal cities of Andhra Pradesh were examined for electrophoretic variation of transferrin (Tf). In four caste groups, namely, Brahmin, Vysya, Padmashali, and Kapu, the Mongoloid genetic marker DChi was found, with polymorphic frequencies in Brahmin and Vysya groups. The two new D variants found in individuals of Madiga and Mudiraj castes were designated as DMadiga and DMudiraj. Similarly, two new B variants found in individuals of Goldsmith and Madiga castes were designated as BGoldsmith and BMadiga, respectively. These findings suggest a widespread transferrin variation in caste groups of Andhra Pradesh and in the tribal populations of this region.


Direct duplication 2p14 to 2p23.

A malformed male newborn was first diagnosed as having Smith-Lemli-Opitz syndrome. Extensive cytogenetic studies, including Q, G, C, R and T banding and BudR treatment, were applied, finally leading the authors to conclude that the patient had a partial 2p trisomy caused by direct duplication 2p14 to 2p23. This was a de novo chromosome abnormality, as both parents had normal karyotypes.


Partial trisomy 13 as a result of de novo (6p;13q) translocation.

A newborn infant with the clinical features of the Patau syndrome was found to have excess chromosome 13 material present as a tandem translocation involving the short arm of chromosome 6 and the long arm of an extra chromosome 13: 46,XY,t(6;13)(p24;q12). The major part of the long arm of the extra chromosome 13 was attached linearly (tandem translocation) to the short arm of chromosome 6. Both parents were phenotypically and karyotypically normal.


Decision on the control of a dietary carcinogen -- aflatoxin.

The sequence of events is described whereby decisions are made by the scientific community and national or international legislative bodies in evaluating a dietary carcinogen. This is proposed on the basis of experience gained from the aflatoxins. Suspicion arose first after the deaths of large numbers of poultry and fish; the agent was soon identified as aflatoxins. This was followed by laboratory investigations of their toxic and carcinogenic effects in experimental animals, which showed them to be the most potent liver carcinogen known to experimentalists. Field studies were established to assess a possible association with liver-cell cancer in humans, and a significant correlation was found. An intervention programme was therefore set up to lower exposure and to observe the trend of cancer incidence. Aflatoxins are found in many cereals and nuts exposed to humidity; thus, the staple foods of most of the developing world are at risk. The severity of the economic problem for some countries if prejudice should continue to develop against peanuts as a basis for animal feeds is illustrated. Decisions about control of aflatoxins thus fall into two groups: control measures to prevent contaminated foods from reaching the populations of industrialized countries, and primary prevention for the millions in the developing world. Regulatory actions have been taken in various industrialized countries, but their effect is to make developing countries safeguard exports and still to ignore the hazard within the country. The main problem is thus protection of food supplies, for the indigenous populations of those countries that grow and consume the bulk of the susceptible cereals, by improved husbandry.


Residues of carcinogenic animal drugs in food: difficulties in evaluation of human safety.

The indisputable need to intensify animal production in order to provide an adequate food supply for the world population involves the use of substances that are highly potent pharmacologically and toxicologically. The history of regulatory action with regard to such additives is similar to that for other substances: first, no regulation; next, an over-reaction; and now decisions based on judicious evaluation of scientific facts. One factor that differentiates the chemicals used in animal production from other food additives is that both the parent compounds and their metabolites appear in edible products, posing problems both for the analytical detection and safety evaluation of such residues. It would be unrealistic to propose 'zero' tolerances for these additives, even if they are carcinogenic. The benefits gained from drugs that cure and prevent infections and parasitic diseases in food-producing animals, and the fact that analytical methods can now detect very small quantities make the presence of low levels of these substances in food unobjectionable.


Carcinogenic risk of products used in the pharmaceutical and related industries.

The pharmaceutical industry is perhaps most subject to rules and regulations in the majority of countries. Legislation in France in this regard is flexible and relatively easily adaptable; in addition, the pharmaceutical industry has established its own ground rules. One of these requires that a product be harmless under normal conditions of use; carcinogenicity checks are only mandatory under certain conditions. If they were to be made compulsory, a less unwieldy test system would be required. The use to which a product is put should be taken into consideration in regulating it.


Review of pesticide carcinogenesis data and regulatory approaches.

Carcinogenicity data are presented for compounds used as pesticides which have been evaluated in the IARC Monograph series. These pesticides have been both poorly and scantily tested for carcinogenicity. Additional tests have been carried out under the NCI Carcinogenesis Program, and detailed results of the bioassays are published in the NCI Carcinogenesis Technical Report Series. A prpcedure was developed whereby 'preliminary reports' could be made in the Federal Register. In the second part of the paper, regulatory approaches to pesticides are described. International activities are outlined; and examples are given of factors, such as public concern, scientific work and governmental response, which are highlights in the development of approaches to such regulations. The problem of risk assessment has been approached from many sides but remains largely unsolved. Besides risks and benefits, an essential component in evaluation is the analysis of technological alternatives. Two other factors are public documentation of the process of evaluation and registration of environmental carcinogens and their uses. Reduction of exposure to environmental carcinogens to a 'minimum feasible level' depends on social, economic and temporal factors and implies the acceptance of a finite level of risk.


Research related to the herbicide buvinol, especially for possible carcinogenicity.

The Budapest Chemical Works (Hungary) has conducted a study on a new herbicide called 'Buvinol', containing 2,4,5-trichlorophenoxyethanol (TCPE). In long-term carcinogenicity testing, the oral administration of the maximum tolerated dose of TCPE (70 mg/kg), containing 0.1 ppm 2,3,7,8-tetrachlorodibenzo-para-dioxin, increased the incidence of liver tumours in male mice, while smaller doses (1/10 and 1/100) did not. Dioxin in the dose range used (0.1--10 ppm) did not influence tumour frequency. Exposure of workers to TCPE during its production or use should be controlled and reduced.


The role of laboratory animal studies in estimating carcinogenic risks for man.

The extent to which biological processes predict those in humans is discussed and illustrated by analysis of data presented in the first 16 volumes of the IARC Monograph series. Other examples are given to show that if there is sufficient evidence that a chemical is carcinogenic in appropriate animal test systems it must be treated as if it were carcinogenic in humans. A quantitative correlation between data in animals and in humans is more difficult to establish, although there is tentative evidence that such a relationship exists. Society should attempt to keep 'inevitable' exposures to carcinogens to a minimum; social need should be balanced against social risk. Biomedical research can help to estimate this role.


An overview of the problem of thresholds for chemical carcinogens.

Toxicological evaluation in quantitative terms of substances that have been shown to be carcinogenic is very difficult, mainly because, for the great majority of environmental carcinogenic chemicals, the available data, both from experimental studies in animals and from epidemiological studies in humans, on dose-effect relationships, especially at low levels, are very limited. There is an urgent need for research in this area. At present, the most sensible approach is to try to determine no-effect levels by long-term investigation of the effects of low levels in animal species that are most similar to man in their metabolic potential and their sensitivity. Very low safety factors (2500 to 5000) should be applied to the values thus obtained, in order to be as far as possible on the safe side in establishing pragmatically acceptable limits. At present, since all chemical carcinogens pose a hazard, human exposure to them must be reduced to the feasible minimum.


'Human' and 'animal' carcinogens.

A clarification is made of the meanings of the terms 'human carcinogen' and 'animal carcinogen' in cancer research, cancer prevention and legislative actions. A chemical proven to have carcinogenic activity in animals should be considered to represent a risk to humans. However, non-experts tend to consider that 'animal carcinogens' produce cancer only in animals and can be neglected with regard to the human situation. The use of these terms should thus be avoided or they should be used as standard terms based on generally accepted and available definitions.