Fertility and land availability in rural Brazil.

Differences between the marital fertility of the agricultural frontier and that of the more settled rural areas of southern Brazil are analyzed in this paper. Fertility rates derived from 1970 census data appear to decrease as the degree of settlement increases, suggesting an experience parallel to the decline in U.S. rural fertility in the late nineteenth century, which Easterlin and others have attributed to increased scarcity of land for starting new farm households. Multivariate analysis of the Brazilian data shows parallels between the two situations but also reveals that the importance of literacy, child survival, and access to land is relatively greater than that of the availability of land for explaining fertility differentials in Brazil.


Factors related to the intention to have additional children in the United States: a reanalysis of data from the 1965 and 1970 national fertility studies.

Reproductive intentions of white mothers with no more than three children in 1965 and in 1970 were analyzed for their stability and change with respect to such factors as parity, age of the youngest child, wife's employment, and husband's education. Parity and age of the youngest child were found to have a much more important effect on the intent to have additional children than were such socioeconomic variables as wife's employment and husband's education. Parity and the interval since the latest birth (or the age of the youngest child) were found to have a nonlinear effect and to interact in affecting the reproductive intention. This suggests a convergence to a two-child family as the threshold size and that the lenght of childspacing is contingent on the parity. Change during 1965--1970 in this direction was found to be greater among mothers with husbands having college or higher educations.


A comparison of the probability of the dissolution of first and second marriages.

This paper applies the techniques of multiple decrement life tables to marriage histories collected as part of the 1973 National Survey of Family Growth, in an attempt to examine differences in pattern and level of marriage dissolution by marriage order. The paper considers the process of marriage dissolution in two stages--marriage to separation and separation to divorce--in addition to considering the composite of these two, marriage to divorce. Second marriages are more likely to reamin intact only for blacks. For all subgroups of whites, second marriages are either as likely or more likely to dissolve than first marriages. For both first and second marriages, blacks are considerably less likely to obtain a divorce after separation.


Marital dissolution, remarriage, and childbearing.

Earlier models of fertility hypothesize that marital dissolution and remarriage influence subsequent childbearing. This issue is examined by comparing the fertility of those in disrupted marriages with that of those in stable marriages. The results indicate that, by transferring women into a nonmarried status, marital dissolution decreases childbearing. The data also suggest that discord reduces fertility even before separation occurs--separated women had reduced fertility during the two years just before separation. It was found that marital dissolution without remarriage operates to truncate childbearing, thus decreasing family size. Dissolution followed by remarriage, however, lengthens the childbearing span of whites and has no inflences on average family size; remarrying white women are able to make up for the childbearing lost between marriages. For nonwhites, we found that dissolution and remarriage increase the average time to childbirth, but, even more importantly, these events greatly decrease the number of children born.


Contextual and ideological dimensions of attitudes toward discretionary abortion.

This study examines the contextual and ideological dimensions of attitudes toward discretionary abortion using two national surveys. The abortion attitudes are dichotomized in terms of consistent opposition versus consistent support. Discriminant analysis, partial correlations, and stepwise regression procedures are used in the analysis. Findings indicate that education and attendance at religious services are the two most significant contextual dimensions and sexual permissiveness and fertility ideology are the two most significant ideological dimensions for explaining attitudes toward discretionary abortion. Implications of these findings are discussed.


An estimate of a rare population group: the U.S. Jewish population.

High, middle, and low estimates for a rare population group, the Jewish population of the United States, are presented together with their root mean square errors. These estimates are based upon a national sample whose essential survey design features are outlined. The features indicate that difficult-to-find populations can be sampled in adequate numbers if some sort of a list can be developed with a fair proportion of the population. To this list must be added an integrated area sample.


Replication of mouse mammary tumor cells in monolayer cultures stimulated with embryo extract.

A particulate fraction derived from homogenized chicken embryos was added to primary monolayer cultures of mouse mammary tumor cells. All culture media contained fetal calf serum (10%). After 4 days, the extract had stimulated a twofold increase (relative to controls lacking the extract) in (1) total DNA per culture; (2) the rate of incorporation of labeled DNA precursors; (3) epithelial cell number, and (4) total protein. This integrated growth activity is discussed in terms of the nature and exogenous regulation of neoplastic growth.


Cytophotometric study of the DNA content in experimental pulmonary granuloma.

Pulmonary granulomas were induced in rabbits with Freund's complete adjuvant. Histologic alterations, the mitotic index and Feulgen-DNA amounts determined by a cytophotometric method were studied. The mitotic index and DNA amounts increased significantly within the first hours and reached peak values on the 3rd day, then showed a tendency to decrease after the 7th day. After the 3rd day, a certain dissociation was noted between the mitotic index and Feulgen-DNA amount. The change in Feulgen-DNA content reflects the functional alterations that characterize pulmonary granuloma.


Phagocytosis of latex particles in relation to the cell cycle in 3T3 cells.

Cultures of 3T3 cells, synchronised by serum deprivation, were shown to phagocytose latex beads of 0.81 micrometer diameter more avidly in the G1 phase of the cell cycle. The maximum rate of about 0.12 particles/cell/hour was recorded 12 h after stimulation with 10% fetal bovine serum. After 24 h, when mitosis was beginning, the uptake fell to just above the unstimulated level of 0.06 particles/cell/hour. Exocytosis was linear and only 7% of the total cell-associated latex was released in 30 h. Internalisation of latex beads was demonstrated by electron microscopy. No uptake was detected in experiments conducted at 4 degrees C.


Acute monoarticular presentation of osteoarthrosis of the knee.

A study of 387 patients aged 65 years and over presenting with an acute hot painful swollen joint as the major or only presentation of osteoarthrosis of the knee is discussed. Short-term phenylbutazone therapy is evaluated. Eighty-nine per cent of patients obtained good to complete relief of acute symptoms within 14 days.


A double-blind study of cimetidine in patients with duodenal or gastric ulcer in Greece.

The results of a double-blind study comparing oral cimetidine with placebo in the short-term treatment of endoscopically proven gastric and duodenal ulceration are presented. Cimetidine was used at a dosage of one gram per day and treatment continued over a period of 4 weeks. Greek patients' tolerance of the drug has been recorded. The outcome of treatment was significantly better for the group of patients who received cimetidine treatment.


Lack of influence of povidone-iodine on tests of thyroid function.

The external application of povidone-iodine, an antiseptic agent, was tested for its influence on thyroid function. Previous workers have described some in vitro changes in thyroid function tests following its use. In the present study topical application of povidone-iodine did not affect thyroid function as measured some days later using both in vivo and radio-active iodine in vitro test methods, despite the fact that the latter are notorious for being influenced by exogenous iodine.


Immunoreactive glucagon responses to oral glucose, insulin infusion and deprivation, and somatostatin in pancreatectomized man.

In a group of pancreatectomized subjects, immunoreactive glucagon (IRG) concentrations were normal after an overnight fast, increased after oral glucose, were not suppressed by somatostatin (SRIF) or insulin, and in two of four subjects they rose with an arginine infusion. Even though the SRIF infusion failed to lower IRG, there was a fall in plasma glucose concentration in both subjects. In two subjects, endogenous hyperglycemia occurred during insulin withdrawal without a rise in IRG, and, in one subject, mild diabetic ketoacidosis developed with only a minimal rise in IRG. These results support the presence of an extrapancreatic source of IRG in man. Secretion from these extrapancreatic alpha cells appears to be regulated differently than secretion from pancreatic alpha cells.


Somatostatin in maturity-onset diabetes.

Plasma FFA, glucagon, insulin, glucose, and growth hormone were followed every hour during 24 hours of saline infusion, 24 hours of somatostatin (4mg.) infusion, and three hours without infusion in six nonobese and six obese maturity-onset diabetic men. Somatostatin induced the same changes in the parameters of both groups of diabetic patients: A rise in plasma FFA, which gradually disappeared after some hours of infusion, a suppression of plasma glucagon and insulin, and an augmentation of plasma glucose both postprandially and during the night. Plasma growth hormone was suppressed in the nonobese patients, but somatostatin could not further suppress the low and nonfluctuating plasma growth hormone concentration in the obese maturity-onset diabetics. The results indicate that a preparation with a pattern of hormone suppression like that of somatostatin will not be useful in the control of  maturity-onset diabetes, because it suppresses insulin and elevates the blood glucose concentration.


A model of glucose-insulin homeostasis in man that incorporates the heterogeneous fast pool theory of pancreatic insulin release.

Current physiologic knowledge about glucose-insulin homeostasis in liver, brain, pancreas, kidney, peripheral tissues, and central vascular organs has been synthesized to form a whole-system mathematical model of glucose metabolism in normal, ideal man. In addition to data of other workers, results from more than 100 intravenous glucose tolerance tests, including variable dosage, variable duration of infusion, and double pulse studies, were used to determine model structure and parameters. Model and clinical testing have focused particularly on the fast phase of insulin response to vascular glucose. The model incorporates blood circulation and equilibration of substances between vascular and interstitial spaces, and it assumes constant fractional clearance of insulin by liver and kidney. Studies using a double pulse of glucose suggest that the time derivative of glucose level is not the sole or predominant influence on fast phase insulin release, but that preinfusion glucose level and/or previous glucose exposure of the pancreas are also important. Variable dosage glucose studies suggest that the amount of insulin released during the fast phase rather than the insulin release rate is regulated by the glucose level. A two-pool, heterogeneous threshold mechanism for beta cell response to glucose is presented that is compatible with the clinical results.


The functional state of sympathetic nerves in spontaneously diabetic mice.

I investigated biochemical parameters of sympathetic nerve function in spontaneously diabetic mice(C57 BL/KsJdb/db) and in their lean littermates. The concentration of norepinephrine (NE) in organs innervated by sympathetic nerves was significantly reduced in the heart, kidney, and salivary glands of mice (24 weeks old) with severe diabetic-like symptoms (blood glucose is greater than 300 mg./100ml.). In the spleen, vas deferens, and adrenal glands of the same animals the NE levels were not changed in relation to control. Other measurements of NE in young (six weeks old) diabetic mice revealed no differences between diabetic and nondiabetic controls. The turnover of NE, a measure of the functional state of sympathetic nerves, decreased significantly in the heart and salivary glands of 24-week-old mice but remained unchanged in the kidney and spleen. In young, diabetic mice the rates of NE turnover in several organs were similar to those found in age-matched controls. The hearts of 24-week-old diabetic mice contained significantly less dopamine-beta-hydroxylase (DBH), an intraneuronal enzyme active in the terminal step of NE biosynthesis. The kidney of the same animals was hypertrophic and showed a massive elevation of monoamine oxidase (MAO), an enzyme that degrades NE to inactive products. Other experiments showed that the regeneration of sympathetic neurons that follows the reversible chemical denervation with 6-hydroxydopamine was comparable in diabetic and nondiabetic animals. It appears that mice with spontaneous diabetes show changes of sympathetic nerve function similar to those noted in diabetic patients with autonomic neuropathy.


Vascular lesions associated with impotence in diabetic and nondiabetic arterial occlusive disease.

Translumbar aortographies performed in 91 patients for limiting leg ischemia were reviewed, and stenosis was graded by points from one (normal vessel) to five (complete occlusion) for each vessel. Of 62 nondiabetic patients, 18 (29 per cent) were impotent, while of 29 diabetics, 17 (58.6 per cent) were impotent (p less than 0.01). Significantly greater stenosis (p less than 0.005) was found in the internal pudendal arteries of impotent patients when compared statistically with potent patients. This was true for the group as a whole, for diabetics and nondiabetics, and for patients over 50 years old both with and without diabetes. There was no significant difference in the extent of stenosis of the iliac arteries (common and internal) between potent and impotent patients. There was also no significant difference in the pattern of stenosis between diabetic and nondiabetic patients in the group as a whole and also in the potent and impotent subgroups analyzed separately. Neither diminished femoral pulses nor aortographic evidence of external iliac and common femoral arterial stenosis correlated significantly with impotence. These observations indicate that vascular lesions are as important in diabetics as in nondiabetics in the genesis of impotence. Clinical implications regarding diagnostic investigations and treatment are discussed.


The role of calcium in glucagon release. Studies with verapamil.

The role of calcium transport into the pancreatic A2-cell in release of glucagon was studied in the perfused in vitro rat pancreas exposed to the organic calcium-antagonist verapamil (10 and 20 microns). As judged by the inhibitory effect of verapamil, a sufficient influx of calcium was required for glucagon release to be stimulated by either arginine (10 mM) or a lowering of the glucose concentration from 16.6 to 3.3 mM. However, such was not the case for glucose to inhibit the release of glucagon or when the A-2-cell was established in a stimulated state during prolonged exposure to a low, 3.3 mM, glucose concentration. These findings suggest that the role of inwardly directed transport of calcium in the secretory process of the A2-cell is of a complex nature, being dependent on the type of stimulus employed (arginine or glucose) and, in the case of glucose, on the static or dynamic state of the cell. The intimate mechanisms by which calcium exerts such complex effects on the secretory process in the A2-cell remain to be elucidated.


Diabetic retinopathy and pregnancy.

Diabetic retinopathy was found to be present in 12 out of a group of 67 diabetic patients supervised by us during 92 pregnancies, and 3 further pregnant diabetics were referred to us because of retinopathy. The mean duration of diabetes was 13 years (range 3--25 years). Nine patients had minimal retinopathy, 2 had background retinopathy, and the remaining 4 proliferative retinopathy. The cases with minimal retinopathy showed no progression during pregnancy. In 1 patient with background retinopathy there was deterioration. Of the 4 patients with proliferative retinopathy 1 showed regression during the pregnancy, 2 showed advance and were treated with photocoagulation (these 2 patients now have normal vision), while the patient with extensive retinitis proliferans, with retinal detachment in both eyes and previous photocoagulation remained unchanged. The prognosis during pregnancy for patients with diabetic retinopathy is reasonable and has been improved by the advent of photocoagulation.


Effect of insulin on amino acid transport in isolated rat hepatocytes.

The effects of insulin on amino acid transport were studied in freshly prepared suspensions of isolated hepatocytes from adult rats. Insulin stimulated the active transport of alpha-aminoisobutyric acid by increasing the influx. The onset of the insulin effect was delayed by thirty to sixty min. Insulin increased by Vmax of transport by about 60% without affecting the Km. Cycloheximide and actinomycin D inhibited hormonal action by 60 to 80%. Only the "A" system of transport was affected by insulin. Half-maximal stimulation of transport was observed with insulin at 2 to 3nmol/l, a concentration which also occupies about 50% of insulin-specific binding sites at steady state. Insulin did not antagonize the stimulatory effect of glucagon on amino acid transport.


A modified assay system for collagen glucosyltransferase.

A simplified assay procedure has been developed for the determination of collagen glucosyltransferase activity in tissue extracts. Using degraded gelatine as acceptor it was possible to isolate the reaction product by precipitation on to a glass fibre disc. Under our conditions degraded gelatine is glucosylated with a reaction rate which is 3--4 times lower compared with the glucosylation of basement membrane derived glycopeptides. Good reproducibility is demonstrated by the coefficient of variation of 4% in the same assay and an interassay variation coefficient below 8%. As the assay allows the testing of large numbers of samples in a few hours, it should prove a useful tool to determine the enzyme level in the tissue of diabetic animals. In humans the activity of the glucosyltransferase could provide a biochemical parameter related to diabetic microangiopathy.


The effects of chlorpropamide and insulin on serum lipids, lipoproteins and fractional triglyceride removal.

The effects of chlorpropamide on serum lipids, lipoproteins and fractional triglyceride removal have been studied over 12 months on 10 maturity onset diabetics not controlled on diet alone. Similar studies were carried out in 6 maturity onset diabetics who had failed to respond to sulphonylureas and 6 new insulin requiring diabetics. In the chlorpropamide treated patients there was an initial fall in serum and VLDL triglyceride but this effect was lost at 12 months. There was no change in fractional triglyceride removal. At 12 months there was a fall in LDL and a rise in HDL choelsterol. An initial improvement in glucose tolerance and insulin secretion was maintained at 12 months. In the insulin treated group the initial fall in serum and VLDL triglyceride was maintained at 12 months and was accompanied by an increase in fractional triglyceride removal. There was also a fall in LDL and a rise in HDL cholesterol at 12 months. The failure of chlorpropamide to maintain the reduction in serum and VLDL triglyceride could be of importance in the genesis of coronary heart disease in maturity onset diabetics. The fall in LDL and rise in HDL cholesterol found both with chlorpropamide and insulin might be beneficial.


Osteopenia in insulin treated diabetes mellitus. Its relation to age at onset, sex and duration of disease.

Bone mineral content was measured by photon absorptiometry in 215 insulin treated diabetic out-patients aged 7--70 years. As bone mass increases until the age of 20--25 years, patients were so selected that all remained within the same phase of bone mineral storage throughout the entire course of their diabetes. Other criteria for exclusion were diseases or drugs interfering with mineral metabolism and previous use of oral antidiabetic agents. As a group the patients demonstrated a bone mineral deficit of 9.8% compared with sex- and age-matched controls (P less than 0.001). Comparison between patients who had developed diabetes before the age of 20 years and after that of 25 years revealed deficits of 14% and 7%, respectively (P less than 0.001). Sex differences were not observed. The initiation of osteopenia seemed to coincide with the onset of clinical diabetes mellitus, and significantly reduced bone mineral content was observed after 2 years of diabetes (P less than 0.001). After 3--5 years the osteopenia appeared to attain a stable level.


Pilot study of self-measurement of blood glucose using the Dextrostix-Eyetone system for juvenile-onset diabetes.

Self-measurement of blood glucose was performed by eight insulin-dependent juvenile-onset diabetics. The patients were well motivated and improved control of diabetes was obtained. The method would seem to be useful for juvenile-onset diabetics, especially of the unstable type and for pregnant diabetics.


Influence of phenformin and metformin on exercise induced lactataemia in patients with diabetes mellitus.

The effect of long-term treatment with phenformin and metformin respectively on blood lactate concentrations in relation to submaximal muscular exercise has been examined in 21 maturity-onset diabetics, using a cross-over method. At similar degrees of diabetic control the mean blood lactate concentration during exercise and shortly thereafter was significantly higher when the patients had received phenformin. The mean fasting lactate concentration was 1.07 mmol/l with phenformin and 1.03 mmol/l with metformin and the peak concentration was 2.56 mmol/l and 2.19 mmol/l respectively. The mean fasting blood glucose concentration before the exercise was 11.2 mmol/l with phenformin and 11.3 mmol/l with metformin; the glucose output in the urine during the preceding 24 hours was 93 mmol and 105 mmol respectively. The mean work load during exercise was 60 watts.


Characterisation of the effect of intravenous infusion of glucose and tolbutamide on the insulin delivery rate in man.

Serum insulin response to a single bolus of IV glucose or tolbutamide was measured in eight healthy subjects. Insulin disappearance rate was assessed by deconvolution from the serum insulin levels, using the measured insulin disappearance rate. The mean rate constant of insulin disappearance was 0.238 +/- 0.005 min-1 (mean +/- SEM). Basal insulin delivery rate was 8.0 to 9.0 mU/min and the delivery rate following glucose injection (0.5 g/kg body weight) showed a biphasic response, whereas that after tolbutamide injection (15.6 mg/kg body weight), a monophasic response. After glucose injection, 1.7 +/- 0.3 U of insulin was delivered during the first phase (0--10 min) and 5.6 +/- 1.6 U during the second phase (11--60 min). After tolbutamide injection, 1.5 +/- 0.3 U of insulin was delivered during the first 10 min. Between 11 and 40 min, 1.6 +/- 0.5 U of insulin was delivered. The results thus confirm and also quantitate biphasic insulin secretion after a bolus of glucose with a monophasic response after tolbutamide. The method is suitable for studies of the insulin secretogogues in man.


Diminished gastrointestinal potentiation of insulin secretion in human pregnancy.

In order to investigate whether an increased gastrointestinal potentiation of glucose-induced insulin release might be involved in the enhanced insulin response to oral glucose in pregnancy, seven normal women were subjected to an oral glucose tolerance test (OGTT) and an IV glucose infusion test (IVGI) in the last trimester of pregnancy and again four to ten weeks post-partum. The amount of glucose administered intravenously was adjusted to obtain plasma glucose concentrations similar to those of the preceding OGTT. By this technique it was possible to quantitate the amount of insulin release attributable to gastrointestinal factors. Contrary to expectations, the results revealed that the gastrointestinal potentiation of insulin secretion was reduced by more than 75% in late pregnancy (p less than 0.05). The hyperinsulinaemia of pregnancy is therefore not explained by an increased activity of the entero-insular axis. Moreover the results confirm a substantially increased beta cell sensitivity to a glycaemic stimulus in pregnancy.


Somatotrophic diabetes: insulin release responses to arginine and glucagon in dogs.

Growth hormone injected daily in 6 dogs for 6 days caused a 20-fold elevation in fasting serum immunoreactive insulin (IRI) without appreciable change in serum glucose in 1 day. In the somatotrophic diabetes that occurred after 2 days, the hyperinsulinaemia was maintained and the serum IRI/glucose (I/G) ratio declined from the early high level but remained elevated. During this treatment, in response to glucose infusion, the rise in serum IRI above the initially high fasting level was 16 times the normal. In response to glucagon, the rise in IRI was twice the normal and the rise in glucose was more prolonged, resulting in a decline in the I/G ratio. In response to arginine infusion, the rise in serum IRI was 8 times the normal and the rise in the I/G ratio was twice normal. Following a meal, the rise in serum IRI was 8 times the normal. Thus, with growth hormone treatment the insulin secretory responses to these stimulating factors were magnified over the already elevated fasting level of secretion. The insulin content of the pancreas was reduced to less than 10% of normal by growth hormone treatment for 6 days, due apparently to elevation of the rate of secretion over the rae of formation of insulin.


Effect of 5-bromodeoxyuridine on differentiation. II. The effect of early BUdR treatment on gastrulation of sea urchin embryos.

BUdR treatment of early cleavage stages is more effective on gastrulation the earlier the drug is administered before the 16-cell stage. The distribution of percentages of embryos gastrulating is in good agreement with the theoretical calculated values presented in part I and permit the assumption that BUdR may act by preventing normal transcription at, or shortly after, the 16-cell stage.


The ectomesenchymal-endodermal interaction system of Triturus alpestris in tissue culture: morphological and histochemical characterization of developing neural derivatives.

In the ectomesenchymal-endodermal interaction system (EEIS), a hanging drop culture in which an explant of neural fold from behind the prospective ear region of a Triturus alpestris neurula together with a piece of ventrolateral pharynx endoderm is cultivated, the differentiation of a variety of neural crest-derived cells (nerve cells, pigment cells, cartilage cells, perichondrial cells, Schwann cells) can be followed. While cartilage cells develop only in contact to pharynx endoderm, the differentiation of neural crest-derived neuroblasts, rhombencephalic brain derivatives and epidermis which segregate from the explant of neural fold, does not depend on the presence of pharynx endoderm. The development of neural derivatives was studied with respect to morphology and histochemistry. Outgrowing axons may be observed 2-3 days after the beginning of cultivation. The fibres increase in thickness and length during further development and frequently make contact with other cells. Cytophotometric measurements of Feulgen-stained neural crest cells in the EEIS revealed that 72% of cells had a 2c and 9% a 4c DNA content while 18% were in S phase. Nerve cells had a 2c DNA content and prospective chondroblasts were in S phase. About 60-70% of S phase and 4c cells were observed at the margin of the culture. Neural crest-derived neuroblasts and melanoblasts obviously reacted catecholamine-positive upon formaldehyde-induced fluorescence (FIF), while axons from the brain derivative were catecholamine-negative but acetylcholinesterase (AChE)-positive. Neural crest cells prior to visible differentiation and neural crest-derived neuroblasts were AChE-negative. Catecholamine-positive (= fluorescing) cells can be recognized as either neuro- or melanoblasts prior to displaying phenotypic features. In cultures incubated with 3H-Dopa, freeze-dried, treated with the FIF-procedure, and subjected to autoradiography, only melanoblasts specifically accumulated the label.


Effect of 5-bromodeoxyuridine on differentiation. I. Probability distribution of BUdR-containing DNA-strands in subsequent divisions.

The consequences on transcription of BUdR substitution of the normal thymidine in nuclear DNA are analyzed from a probabilistic point of view. The probability that at any stage subsequent to the administration of BUdR, a randomly chosen cell will be able to make good transcripts is calculated both under the assumption that incorporation of BUdR is complete and under the assumption that incorporation is partial. In the latter case both gradually increasing and decreasing incorporation rates are considered. The presented calculations may be of value for the investigation of any type of differentiating cells. Using the example of the sea urchin embryo it is shown how to calculate the probability that a particular group of cells, which in further development differentiate to a certain organ, will inherit as sufficient number of essential genes unaffected by BUdR in order to ensure a normal development. It is shown that the probability that the four macromeres (or micromeres) in the vegetal half of the 16-cell stage of the sea urchin embryo will contain at least one, two or four plus (or minus) strands of DNA uninfluenced by BUdR gradually decreases the earlier BUdR is administered. The theoretical calculations are in agreement with experimental observations on sea urchin embryos (described in part II).


[Surgical management of ventricular septal defect and coarctation of the aorta. Observations on 40 cases, with particular references to infancy (author's transl)].

Forty patients with V.S.D. and coarctation of the aorta were operated on at Department of Cardiac Surgery, Ospedali Riuniti Bergamo. Surgical management of infants with V.S.D. and coarctation depends on the magnitude of the left to right shunt. Patients may therefore be divided into two groups: 1) those with aortic coarctation and a small V.S.D., who have normal or slightly elevated pulmonary artery pressure. If surgery is required, these patients can be successfully treated by repairing the coarctation alone. Ten cases in our series were operated on using this approach without deaths; 2) patients with coarctation and large V.S.D. and pulmonary hypertension. The management of these infants is controversial. One stage repair was used in four cases without deaths. On the other hand, nine out of 11 patients in whom the V.S.D. was left unrepaired at the same operation died, giving a 81.8% mortality rate. Repair of coarctation with simultaneous banding of the pulmonary artery was equally affected by high mortality. With this approach in 13 patients there were seven deaths, giving a 53.8% mortality rate.


[Primary repair of large ventricular septal defects in the first year of life (author's transl)].

It has been our policy at Harefield Hospital since 1971 to perform primary repair of large ventricular septal defects in the first year of life if there is severe intractable cardiac failure or persistent pulmonary hypertension in infants approaching the first year of age. Twenty-six infants underwent repair; their ages were between one and twelve months. One child died early. The remaining 25 have been followed up for between 6 and 78 months (mean 30.3 months). There have been no late deaths and all children are asymptomatic. Late, postoperative cardiac catheterization was performed in 17 patients. This showed that in all the patients the pulmonary artery pressure was normal and there were no residual shunts. It is concluded that primary repair of large ventricular septal defects in the first year of life gives good results and appears to prevent pulmonary hypertension.


[The coarctation of the aorta in the adults. Long term results over 10 years (author's transl)].

From May 1964 through December 1976, at the Department of Cardiovascular Surgery, University of Padova, Medical School, 148 patients underwent surgery for coarctation of the aorta; 62 of them where 18 years of age or older. The Authors deal particularly with the clinical symptoms, the operative findings, the surgical technique and the postoperative complications of their series. The early (only three operative deaths) and late results are considered satisfactory, and are discussed according particularly to the type of surgical intervention.


[Histological study of the coronary arteries during the first six months of life (author's transl)].

The Authors report on the results of a preliminary study on the histological aspects of the coronary arteries during the first six months in the life of the infant. After having reviewed the data relative to the distribution according to sex and age, the causes of death and the localization of the alterations, they draw attention to the discordant opinions still held to date on the pathogenetical interpretations of the medical reports under their observation particularly in reference to the connections with coronary arteriosclerosis in the adult.


[The control of the atrio-ventricular reciprocating tachyarrhythmias. A preliminary electrophysiological study and comparison between amiodarone and verapamil (author's transl)].

The effects of amiodarone (2.5 mg/Kg i.v.) and of verapamil (0.1 mg/Kg i.v.) on refractory periods and on conduction of structures interested in the reciprocating circuit, as well as on the possible echo zones, were comparatively evaluated through electrophysiological test in 8 patients, four of which with W.P.W. from Kent bundle, and four with double A-V pass with reciprocating supraventricular tachicardia (RST) documented crises. None of the two drugs seems to have the theorical requirements of balanced effect to be chosen for the antiarrhythmic prophylaxis in patients with ventricular pre-excitement. In patients with double A-V pass, while both drugs have a sufficiently balanced and regular action on refractory periods and on conduction the irregularity of their effects on echo zones appears to restrict their validity in chronical therapy. According to the Authors, the only useful criteria for the choice of an antiarrhythmic drug for the prophilaxis of R.S.T. to be derived through extrapolation from these electrophysiological tests are: 1) the functional suppression of a circuit structure; 2) the evaluation of effects on echo zones; 3) the possibility or not the evoking R.S.T.


[Doppler echocardiography in the diagnosis of tricuspid anomalies (author's transl)].

Doppler echocardiography has been applied in a study of the tricuspid and central venous blood velocity curves in a number of cases, including eleven cases of insufficiency, six cases of stenosis, five cases of steno-insufficiency of the tricuspid valve and one case of Ebstein's disease. The tracings were compared to normal reports and to those appartaining to a few patients with right ventricular failure from different causes. For six patients the venous blood velocity curve was recorded contemporaneously with the right atrioventricular pressure curves. Doppler echocardiography has proved that it can offer useful indications on tricuspid anomalies. The analysis of the central venous and tricuspid blood velocity curve allows us to detect hemodynamic alterations characteristic of this valvular disease.


[Rheumatoid heart: report of a case with endomyocardial injury and severe arrhythmias (author's transl)].

The Authors describe the case of a 61 year old man suffering from rheumatoid arthritis; the diagnosis of "rheumatoid heart" was made on the basis of the humoral findings and of the clinico-ecgraphic picture of endocardial (mitral incompetence) and myocardial injuries. The different complications impairing the heart rhythm (FA, tachycardia S.V., and episodes of tachycardia V., torsade de pointes type) and the A-V and the I.V. conduction (RBBB phase 3, LBBB phase 4, BAV 1st, 2nd and 3rd degree) which determined the recurrence of episodes of heart block and required adequate intensive cardiological treatment, are described. In conclusion, the significance of the persistance of the L.A.D. in the course of complete LBBB and the discovery of an unusual type of escape-capture bigeminy in the course of 2nd degree BAV is discussed.


[Stimulation by automatic scanning in the long-term treatment of hyperkinetic arrhythmias (author's transl)].

The use of programmed stimulation in the long-term treatment of re-entry tachycardia offers encouraging perspectives. Among the others proposed the "scanning" system seems to be the most effective. However, an implantable stimulator with such pictures is not yet available and a temporary electrode is thus required. These difficulties have been overcome utilizing the radiofrequency as a sincronizing and stimuli-producing means. An implantable appliance was therefore designed which is triggered by the patient himself and automatically researches the zone of interruption of tachycardia by exploring the R-R cycle. The program of external transmitter which can produce one or two sincronized impulses, seams the cycle with progressive steps of 10 msec each; when tachycardia is interrupted, further stimulation is inhibited. The implanted part of the appliance connected with a normal endocavitary electrode, does not have any power supply and thus is very small. The efficacy of this method has been shown in 4 junctional reciprocating and 1 ventricular recurrent chronic tachycardias, resistent to conventional pharmacologic therapy.


Computed body tomography and gray scale ultrasonography: anatomic correlations and pitfalls in the upper abdomen.

From over 1,000 computed body tomographic and 10,000 gray scale ultrasonographic studies of the abdomen, a number of close anatomic relationships leading to the commonest pitfalls in diagnosis are reviewed. Scanning techniques developed to prevent interpretive errors are described.


Pancreatic pseudotumors: computed tomography.

Although pancreatic disease is suspected initially by historical or biochemical findings, the nature of the pathologic process in the past was frequently established only through invasive procedures. Inferences can be drawn from routine roentgenologic examinations, but visualization of the pancreas has only recently been achieved. Of the currently available noninvasive imaging procedures, computed tomography, in our opinion, is the screening procedure of choice. Care in the interpretation of pancreatic masses must be exercised since some of the findings can be attributed to anatomic variants, normal adjacent structures, or other neighboring pathologic processes.


Ultrasonic evaluation of the pancreas.

With the advent of new gray scale imaging techniques, ultrasound plays a major role in the diagnosis of pancreatic lesions. As a noninvasive, nonionizing, accurate, and inexpensive diagnostic modality that directly images the pancreatic gland, ultrasound can be used as a primary screening tool. It is helpful in confirming the diagnosis of acute pancreatitis and in detecting and following pseudocysts and other complications. Neoplasms can be detected with a high rate of accuracy, and by assessing the presence of ascites or metastatic foci in the liver, ultrasound can aid in the staging of the neoplastic process. Bowel gas and obesity remain serious limitations to adequate examination, and in these patients computed tomography offers a complementary modality.


Hepatobiliary disease: a comparative evaluation by ultrasound and computed tomography.

Ultrasound and computed tomography (CT) are both relatively new techniques for evaluating gallbladder and biliary disease. Ultrasound is more sensitive than CT for detecting the presence of gallstones because of partial volume averaging errors which occur with CT. Both modalities are sensitive methods of differentiating jaundice due to intrahepatic disease from extrahepatic obstruction. However, CT should not be considered a screening test at the present time and should be reserved for selected cases where ultrasound is unable to produce diagnostically acceptable information.


Ultrasonography of abdominal fluid collections.

Ultrasonic examination of abdominal fluid collections sometimes allows identification of the nature of the contained fluid. Abscesses, hematomas, and lymphoceles tend to be ellipsoidal unless confined by particularly resistant structures. Abscesses often contain fine debris. Hematomas develop coarse clumps of strongly echoing material as they age. Lymphoceles have sharp walls and are echo-free. Ascites has an irregular outline, a sharply defined wall, and is echo-free. There may be bowel loops floating in it. Pseudocysts have a widely variable appearance. Bowel loopes that are distended with fluid often show peristalsis. Ultrasonically directed fine needle puncture allows confirmation of the nature of the fluid.


Ultrasound and gallium for the diagnosis of abdominal and pelvic abscesses.

Two hundred and twenty-two patients presented with clinical suspicion of an abdominal or pelvic abscess. Abscesses tend to locate in the perihepatic spaces or the pelvis, and these areas can easily be examined by ultrasound, using the liver or the urinary bladder as acoustic windows. Thirty-eight of 42 abdominal abscesses, and 32 of 33 pelvic abscesses were correctly diagnosed and located by ultrasound, giving a sensitivity of 93.3%. Of the 145 patients without abscesses, 143 were correctly excluded, giving a specificity of 98.6%. Thirty of these patients also underwent gallium 67 examination. This detected all 7 true negatives and all 10 abscesses, 1 of which was missed by ultrasound. Of the remaining 13 patients with positive gallium results, 10 had nonspecific uptake in diffuse inflammatory conditions, and 3 were false positives with uptake in bowel or in a surgical wound. In those patients with nonspecific gallium uptake, ultrasound was valuable in documenting the absence of an abscess cavity. Conversely, gallium detected a left subphrenic abscess missed by ultrasound. For reasons of economy, speed, and high sensitivity, we believe that ultrasound should be the initial screening procedure for patients with clinical suspicion of abdominal or pelvic abscess. Gallium should be reserved for patients with equivocal ultrasound results of those with septic foci not revealed by ultrasound.


Computed tomography in the diagnosis and management of abdominal abscesses.

Computed tomography (CT) is effective in demonstrating abdominal abscesses and their relation to surrounding structures. The CT signs of abscess are not unlike those demonstrable radiographically and include an abnormal mass, obliteration and displacement of surrounding organs, inappropriate gas, and peripheral enhancement after intravenous contrast. Axial imaging permits selection of safe approaches through which percutaneous needle aspiration can be performed for diagnosis and therapy. When techniques similar to those employed in angiography are used, a catheter can be inserted, the abscess evacuated, and the catheter left in place as a drain. Combined with intravenous antibiotics, this method of abscess drainage has been successful in curing abscesses without surgery. Representative examples are shown.


Ultrasound demonstration of lesions of the gastrointestinal tract.

An ultrasonographic pattern of mass lesions with strong central echoes appears to be specific for lesions of the luminal GI tract. Three lesions from different portions of the GI tract showing this appearance are presented. Although ultrasound is not the technique of choice in the diagnosis of lesions of the luminal gastrointestinal tract, it is sometimes preferable to perform ultrasound prior to barium studies, and hence it is important to recognize this characteristic appearance.


Endoscopic retrograde cholangiopancreatography. A review of the rewards and indications.

Indications for endoscopic retrograde cholangiography (ERCP) have been poorly defined. We studied the symptoms in 161 patients who underwent ERCP and evaluated the results from four groups of indications: cholestasis, pancreatitis, suspected carcinoma of the pancreas, and pain of unknown etiology. The likelihood of finding abnormalities is discussed.


Endoscopic retrograde pancreaticocholangiography in chronic diseases of the pancreas and in papillary stenoses.

The extensive experience of the authors in endoscopic retorgrade pancreaticography is correlated with data in the literature to illustrate the spectrum of characteristic changes and diagnostic accuracy in several entities. These include chronic pancreatitis, calculous pancreatitis, necrotizing lesions and pseudocysts, carcinoma of the pancreas, and papillary stenosis, spasm, and carcinoma.


Detection of pancreatic pathology by ultrasonography and endoscopic retrograde cholangiopancreatography.

Retrospective evaluation of the results of endoscopic retrograde cholangiopancreatography (ERCP) and pancreatic ultrasonography in identifying those patients with a normal pancreas and those with a pancreatic abnormality revealed ultrasonography to have an overall accuracy of approximately 73%, whereas ERCP had an 85% accuracy, and both modalities had a combined accuracy of 92%. Both procedures were most accurate in the identification of patients with no disease, and both were least accurate in the identification of patients with chronic pancreatitis.


Radiology of papilla of Vater stenosis.

The radiographic characteristics of the terminal pancreatic and biliary ducts were analyzed by endoscopic retrograde cholangiopancreatography in 25 patients with documented benign stenosis of the papilla of Vater. Demonstration of marked hypertrophy of the distal sphincter, mucosal hyperplasia or mucosal redundancy of the distal common bile duct, dilatation of the ducts, and prolonged retention of contrast media suggest papillary stenosis. The diagnosis of benign papillary stenosis, however, ultimately depends on physiologic measurements and response to therapy.


Choledochocele: radiologic diagnosis and endoscopic management.

A case of choledochocele, missed during exploratory laparotomy but managed by endoscopic biliary surgery, is presented.


Radiation exposure in patients undergoing endoscopic retrograde cholangiopancreatography and endoscopic papillotomy.

Radiation exposure was studied in 327 patients undergoing endoscopic retrograde cholangiopancreatography, or endoscopic papillotomy taking into account fluoroscopy time and incident area exposure. The mean fluoroscopy time was 238 +/- 152 seconds and the incident area exposure 3,730 +/- 2,790 R X cm2. These results were compared with standard exposures in upper GI series and colon examinations as found in the literature.


Role of Clostridium difficile in antibiotic-associated pseudomembranous colitis.

Tissue cultures were performed on stools from 189 patients to detect a cytopathic toxin which is neutralized by Clostridium sordellii antitoxin. Specimens satisfying these criteria were considered positive in the tissue culture assay. Stools from 26 of 27 patients with antibiotic-associated pseudomembranous colitis were positive and 16 of these specimens showed toxin titers of 10(-3) dilutions or greater. The tissue culture assay was positive with specimens from 9 of 63 patients with antibiotic-associated diarrhea without documented pseudomembrane formation. Stools from patients with neonatal necrotizing enterocolitis, ulcerative colitis, and healthy controls were uniformly negative in this assay. Cultures were performed on stools from 38 patients with antibiotic-associated diarrhea or colitis to detect clostridia which produce a cytopathic toxin in vitro. Clostridium difficile was recovered from 6 of 8 specimens which were positive in the tissue culture assay and 5 of 30 which were negative in this assay. C. sordellii was recovered in a single specimen. One hundred and nine clostridia strains were tested in the tissue culture assay and C. difficile was the only species which produced a cytopathic toxin. All strains of this organism were positive in the tissue culture assay and, in each instance, cytotoxicity was neutralized by C. sordellii antitoxin. These results indicate that C. difficile is the major cause of antibiotic-associated pseudomembranous colitis and offer an explanation for previous studies showing that the cytotoxin of stools from these patients is neutralized by C, sordellii antitoxin.


Experimentally induced intestinal metaplasia in Wistar rats by X-ray irradiation.

The gastric region of 5-week-old female Wistar rats was irradiated daily with 500 rad of X-ray up to a total of six times. Goblet cells and marker enzymes of the small intestine, such as lactase, trehalase, and maltase, appeared in the pyloric region of the glandular stomach of the rats from the 1st week after final irradiation. Intestinal type crypt without Paneth cells was observed from the 8th week. Sucrase activity appeared from the 26th week. Intestinal metaplasia with Paneth cells appeared from the 71st week. The number of goblet cells, intestinal type crypts, and Paneth cells increased with age. Gastric adenocarcinoma did not develop after irradiation.


Immune responses in human colon cancer. I. Microcytotoxicity assay for measuring killing of adherent human colon cancer cell lines.

A short term microcytotoxicity assay system using radioisotope release as an index of target cell damage has been developed to evaluate immune killing of cultured adherent human colon cancer cell lines. Using this assay system, complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and spontaneous cell-mediated cytoxicity of adherent human colon cancer cell lines can be assessed in 4 hr or less. An essential step in the development of this system was the successful 51Cr-labeling of human colon cancer target cells with subsequent low spontaneous release. This was achieved through careful attention to cellular growth phase and medium pH during the labeling and assay period. In this microsystem, labeled colon cancer cells spontaneously released 51Cr at a mean rate of 2% per hr during the assay, a level low enough not to obscure specific cytotoxic responses. Complement-dependent cytoxicity was measured most conveniently over a 2-hr period, whereas antibody-dependent cell-mediated cytotoxicity and spontaneous cell-mediated cytotoxicity were optimal when measured over a 4-hr period.


Comparison of intravenous amino acids in the stimulation of gastric secretion.

This study was undertaken to compare the potency of L- and D-isomers of natural amino acids (AA's) infused intravenously for stimulation of gastric acid secretion in 3 dogs with Heidenhain pouches (HP) and gastric fistulae. L-Isomers of all natural AA's were found to stimulate acid secretion from the HP, whereas D-isomers were significantly less effective. The most potent L-isomers of AA's were histidine, phenylalanine, glycine, tryptophan, and alanine, which caused an increase in acid output reaching, respectively, 63, 45, 42, 39, and 33% of the maximal response to histamine. The stimulation of acid secretion was not accompanied by any significant change in serum gastrin level. Distention of the HP during intravenous infusion of L-histidine or L-phenylalanie solution caused a pressure-related increase in acid output reaching a peak at 30 cm distention pressure. Decreasing the luminal pH of the HP in sequential order from 7.0 to 2.5 resulted in a stepwise reduction of the HP response to intravenous histidine or phenylalanine, falling at pH 2.5 to about 20% of the peak response achieved at pH 7.0. Metiamide caused a profound reduction of histidine but had only a slight effect on acid secretion induced by intravenous infusion of other AA's suggesting that histidine excites the oxyntic cells mainly through the transformation to histamine and activation of H2-receptors. Atropine also suppressed gastric acid secretion stimulated by intravenous AA infusion, suggesting a role of a cholinergic mechanism in this stimulation. We conclude that L- and, to a lesser degree, D-isomers of natural AA's infused intravenously cause stimulation of gastric acid secretion by a gastrin-independent mechanism sensitive to distention pressure and pH of gastric content.


Effects of somatostatin on the external secretion of the pancreas of the rat.

The effects of somatostatin on the secretions of the exocrine pancreas were studied in anesthetized and conscious fistula rats. Somatostatin resulted in a dose-dependent decrease of basal secretion (flow, bicarbonate, protein) in conscious rats. In anesthetized rats, basal secretion was initially augmented by bolus injections of 10 to 50 microgram per kg and was subsequently decreased by venous infusions of somatostatin at 1.5 to 100 microgram.kg-1.hr-1. This inhibition, which was poorly dose dependent, was greater for protein secretion than for that of water and electrolytes. Somatostatin inhibited caerulein-stimulated protein secretion by 40 to 50% but had no effect on secretion stimulated by exogenous and endogenous secretin. Somatostatin markedly inhibited secretion stimulated by 2-deoxyglucose and by electrical stimulation of the vagus nerves in a dose-dependent fashion (protein and bicarbonate exhibited a maximal inhibition of 85%). Acetylcholine-stimulated secretion was also inhibited by somatostatin, but the maximal inhibitions observed were only 505 for protein and 60% for bicarbonate. These findings agree with the hypothesis that somatostatin infusion leads to both a decrease of acetylcholine release at nerve endings and to a direct inhibition at the level of pancreatic effector cells.


Hepatic iron clearance from serum in treated hemochromatosis.

Hepatic iron uptake from transferrin has been studied in 7 patients with treated hemochromatosis. When compared with a control group with similar serum iron and transferrin saturation the hemochromatotics had a significantly higher 4-hr iron uptake value. Uptake in the precirrhotic and cirrhotic hemochromatotics was not significantly different, suggesting the existence of a cellular abnormality of hepatic iron metabolism in this disease. The results provide an explanation for the development of siderosis in some patients with idiopathic hemochromatosis and a normal serum iron concentration.


Hepatitis B surface antigen carriers--to biopsy or not to biopsy.

In order to assess the frequency of significant liver disease in hepatitis B surface antigen carriers with normal liver tests, 54 such individuals were identified and prospectively followed for 4 to 48 months with monthly liver tests. Upon testing, 4 were found to carry e antigen and 14 carried e antibody (anti-e). During follow-up, only 4 patients, none of whom were e antigen-positive, developed persisting abnormalities in liver tests. Of the 23 patients who underwent percutaneous liver biopsies, normal histologies were found in 2, nonspecific changes (ground glass hepatocytes, focal necrosis, fatty changes, etc.) in 18, and chronic persistent hepatitis (with or without other nonspecific changes) in 3. Chronic active hepatitis and/or cirrhosis, lesions which may carry more serious prognostic implications, were not seen in any biopsies. Two of the 4 e antigen-positive patients consented to biopsy, both of whom had chronic persistent hepatitis. All 6 patients with anti-e who underwent biopsy had ground glass hepatocytes, which were found in only about 50% of the remaining patients. It is concluded that hepatitis B surface antigen carriers should be followed with serial liver tests, and those whom tests remain normal should not be considered for liver biopsy.


Dane particles-associated hepatitis B core antigen in patients with HBsAg-positive chronic hepatitis.

Dane particles-associated hepatitis B core antigen (HBcAg) was determined by radioimmunoassay in 61 patients with hepatitis B surface antigen (HGsAg)-positive chronic hepatitis. HBc antigenemia was observed in 61% of patients, especially in those with epidemiological risk factors. Patients with chronic active hepatitis as well as those with chronic persistent hepatitis may have HBc antigenemia. The highest levels of HBcAg were observed in male homosexuals. Follow-up determinations indicate the general tendency of HBcAg to decrease or disappear. HBcAg-positive patients with chronic active hepatitis had a poor prognosis, whereas HBcAg-negative patients frequently had a favorable clinical course of the disease (P less than 0.001). The assay of HBcAg in the serum of patients with HBsAg-positive chronic active hepatitis is a useful parameter with both clinical and epidemiological importance.


Full and empty Dane particles in chronic hepatitis B virus infection: relation to hepatitis B e antigen and presence of liver damage.

Circulating complete and defective hepatitis B virus forms, as represented by full, DNA polymerase-positive and empty, DNA polymerase-negative Dane particles, respectively, were investigated in sera from patients with chronic hepatitis B virus infection and related to the presence of e antigen and antibody and to the histological findings on liver biopsy. Complete hepatitis B virus particles were detected in the serum of all patients postive for e antigen, their percentage ranging from 15 to 61% of the total Dane particle population. Although most of these cases had chronic persistent or chronic active hepatitis, complete viral particles were also found in serum of 3 healthy carriers of hepatitis B surface antigen who had e antigen. These results indicate that e antigen is a marker of active virus replication and support its association with infectivity. It is also associated with liver damage because production of complete virus is a feature of chronic hepatitis. In the presence of anti-e, detection of Dane particles in serum appeared to be related to the histological findings. Most of the healthy carriers had no Dane particles in serum, whereas 80% of the cases with chronic liver disease had circulating Dane particles. However, in contrast to the cases with e antigen, 98 to 100% of Dane particles in these cases appeared to be defective in nucleic acid material on electron microscopy after positive staining. All of the patients with chronic active hepatitis in this group had progressed to cirrhosis and it is possible that production of complete virus particles is reduced in the later stages of the illness.


Liver copper levels in intrahepatic cholestasis of childhood.

Liver copper concentration was studied in four groups of age-matched patients and in 9 patients with Wilson's disease of comparable age. Neutron activation analysis of hepatic copper concentration revealed markedly elevated hepatic copper levels, comparable with those in Wilson's disease, in 13 of 15 patients (P less than 0.001) with intrahepatic cholestasis of childhood. In 1 patient, autopsy confirmed very high liver copper values, whereas other tissues, including brain and kidney, gave normal results. Total plasma copper values were elevated in 11 of 13 patients with intrahepatic cholestasis of childhood (P less than 0.001); 24-hr urinary copper excretion was normal in 7 of 12 patients and slightly elevated in 5 (P less than 0.001). Kayser-Fleischer rings were sought in 10 patients and were absent. Hepatic copper concentration was not accurately predicted by plasma copper or 24-hr urinary copper. However, increased urinary copper excretion was associated with hepatic copper concentration greater than 250 microgram per g. It is concluded that copper metabolism is abnormal in intrahepatic cholestastis of childhood and can be distinguished from Wilson's disease. If hepatic copper concentration is greater than 250 microgram per g, copper chelation therapy should be considered.


Nocturnal gallbladder storage and emptying in gallstone patients and healthy subjects.

Nocturnal hepatic bile is supersaturated with cholesterol, and increased storage of this "lithogenic" bile in gallstone patients might explain why they more frequently have supersaturated fasting state gallbladder bile than patients without gallstone disease. To test this possibility, we measured the fraction of nocturnal hepatic bile stored in the gallbladder in 5 patients whose gallstones had been previously dissolved by chenodeoxycholic acid, in 5 control subjects without gallstone disease matched for age, sex, and weight, and in 5 young healthy males. We developed a new method based on the use of indocyanine green as a bile marker. The hourly rate of input into the duodenum of indocyanine green was measured during its constant, prolonged intravenous infusion. When gallbladder storage occurred, indocyanine green input was less than the infusion rate; when gallbladder emptying occurred, input exceeded the infusion rate. The method was validated by showing that duodenal output of indocyanine green was identical to intravenous input of indocyanine green in 2 cholecystectomized patients. When the method was applied, emptying of the gallbladder with meals was documented, and calculations showed that more than half of the bile secreted at night bypassed the gallbladder in both gallstone patients and control subjects. No difference in "cholecystodynamics" was observed between gallstone patients, matched control subjects, and young healthy men. Our results validate a method for quantitating gallbladder storage and emptying in men, but fail to support the speculation that an important pathogenetic step in gallstone formation is increased storage of supersaturated nocturnal bile in the gallbladder.


[Results of routine treatment with Clomiphen (author's transl)].

After 15 years of clinical experiences with Clomiphen treatment it seemed desirable to investigate the efficiency of this kind of therapy under routine conditions in a crowded out-patient clinic. 314 patients treated from 1972--1974 have been included in this study. From 242 sterility patients 730 cycles could be followed. 80.2% were ovulatory, but 23.5% had an insufficient luteal phase and 11.9% of these cycles ended with an anovulatory bleeding. The overall pregnancy rate was 30%. Side-effects were recorded in 4.5% but all of them were harmless, no overstimulation occurred. After discontinuation of Clomiphen therapy 8% of all patients had spontaneous cycles. In 36 patients with eugonadotropic secondary amenorrhea with a total of 115 treatment cycles ovulation was recorded in 58%. Pregnancy rate was 25%, the intensity of treatment 3.1. In 54 patients with anovulatory cycles 156 cycles (72,3%) became ovulatory, pregnancy rate was 24%, the intensity of treatment 3.5. In another group of 19 patients with oligomenorrhea ovulation occurred in 39 of 42 cycles, 4 patients became pregnant. In 108 patients with luteal phase defects in 338 cycles ovulation was found in 90.2%, with 26.6% of these cycles being still insufficient. The pregnancy rate was 18.5%, the intensity of treatment 3.7. 9.8% of these 338 cycles became anovulatory during clomiphen treatment. In 27 patients with "insufficient cycles" in 104 treatment cycles nearly all of them were ovulatory but 20% of them were found to have an insufficient corpus luteum phase. The pregnancy rate was 30%. The highest pregnancy rate was found during the first 3 treatment cycles (26%). It is consequently our policy to treat patients 4 to 6 times with clomiphen and when no pregnancy can be achieved, these patients should be treated with HMG/HCG. 65 of 73 pregnancies were followed, 52 patients were delivered with healthy babies, 12 patients aborted. Of the total number of 54 babies born, 47 were single, 6 were twins, 2 babies were stillborn. The sex ratio (male to female) was 2.2. No malformations were found. In our group of patients other factors besides ovarian dysfunction contributed to the relatively low pregnancy rate. Thus, in 116 out of 244 patients one tube was occluded, while adhesions were found in 99 treated with clomiphen as a diagnostic step to convince the patient, that stimulation of ovarian function will be possible whenever the patient desires to become pregnant. The ovulation rate in this group was 38% in addition 37% responded with anovulatory bleeding, thus, 74% of all patients experienced a positive reaction from their point of view. After discontinuation of clomiphen administration 18% of these patients continued to bleed with (7.5%) or without (10.6%) clinical signs of ovulation. A further observation is the obvious fact that clomiphen therapy free intervals can be interposed without risk of a lower success rate, compared to patients receiving continuous cycle to cycle treatment.


[The value of determinations of human chorionic gonatrophin, human placental lactogen, progesterone and oestriol in women with threatened abortion (author's transl)].

During the antenatal care of 604 women 1629 blood samples for hormonal tests were collected. The values in 417 women with normal pregnancies were used to establish a normal curve with 99% tolerance for the serum concentrations of human chorionic gonatrophin (HCG), human placental lactogen (HPL), progesterone and oestriol. Of the 604 women 187 had bleeding during the first half of the pregnancy. Of these 187 women 57 carried the pregnancy to term and 130 had a miscarriage. Women with the symptoms of threatened abortion who carried the pregnancy to term had normal serum hormone values. The HCG values in this group were higher than normal at the time of bleeding. In 90% of the women with threatened abortion who miscarried prior to 16 weeks gestation (N = 87) and in all patients with a missed abortion (N = 16) 1 or more serum hormone concentrations were below normal. Women with early pregnancy bleeding and late abortion between 17 and 28 weeks (N = 27) showed 1 or more low hormone concentration in only 25% of the cases. Our findings show that the quantitative determination of HCG and progesterone give the most valuable tests for the evaluation of the endocrine system in the first trimester of pregnancy. In the second trimester HCG determinations are of value only in trophoblast disease. To a lesser degree determination of HPL and oestriol are of prognostic value in the second trimester of the pregnancy.


[The effects and side-effects of the intra-cervical application of prostaglandin F-2 alpha during early pregnancy (author's transl)].

In order to avoid the traumatic dilatation of the cervix for therapeutic abortions 200 micrograms of prostaglandin F-2 alpha were injected into the cervix. The effect on dilatation of the cervix was compared with the injection of normal saline in the control group. Without side effects the injection of prostaglandin F-2 alpha resulted in dilatation of the cervix and softening of the cervix. Normal saline had no effect. At present it is unknown whether the dilatory effect of prostaglandin F-2 alpha on the cervix is local or secondary to uterine contractions.


[Comparative studies on the termination of intact and disturbed pregnancies by intramuscular application of 15(s)-15-methyl-prostaglandin F2alpha (author's transl)].

15(S)-15-Methyl-Prostaglandin F2alpha was applied intramuscular to end 27 intact pregnancies mainly in the second trimenon and to induce abortion in 5 cases of disturbed pregnancy. The results showed a similar success of 90 percent in the cases of interruptions compared with the natural prostaglandins applied either extra- or intraamniotic; in the mean induction-abortion-interval of 16 hours the 15(S)-15-Methyl-Prostaglandin F2alpha is better than natural prostaglandins. It is much simpler to apply, the dosage is less. The initial dose is 250 mcg intramuscular, further doses depend on the success achieved, the effect on the bowel activity may be used as indicator. The intramuscular method avoids complications connected with the intraamniotic application, infections of the intracervical catheter lying for a long time and the severe side effects of the intravenous application. In cases of missed abortion and hydatidiform moles, where the use of natural prostaglandins is problematic, the use of 15(S)-15-Methyl-Prostaglandin F2alpha is a progress in this form of therapy.


[Cervical smears in women under 30 years age (author's transl)].

A report is given about the results of cytological examinations of cervical smears taken from women under 30 years age living in smaller towns or rural areas. Of 113 585 smears taken between 1968 and 1977 11 717 (10,35%) belonged to the mentioned age group. 29 smears were pathological. When examined histologically 19 (0,15%) showed a carcinoma in situ or a microcarcinoma. The situation in smaller towns or rural areas is the same as in urban areas. In respect of these findings the authors are asking for routinely screening of women between 20 and 30 years of age.


[The role scalene node biopsy in the treatment in carcinoma of the cervix (author's transl)].

Of 75 scalene node biopsies 18 (24%) were positive. In 56 metastasizing carcinomas of the cervix 11 (20%) scalene node biopsies were positive. In primary inoperable cases (57%) or in recurrent spreading cases (54%) of carcinoma of the cervix the scalene node biopsy is valuable for the treatment plan. Irrespective of treatment the patients with metastases to the scalene node survived a mean of 10--11 months. The scalene node biopsy has few complications (6.7%). In the less than 3% carcinomas of the cervix confined to metastases in the lesser pelvis, the scalene node biopsy is not necessary. 2/3 of the prescalene lymph node metastases can be palpated by an experienced examinar.


[Desire for therapeutic abortion in the dependents of foreign workers. Outpatients psychiatric evaluation (author's transl)].

The change in paragraph 218 of the criminal code regarding abortion was responsible for new guidelines for the psychiatric evaluation regarding a therapeutic abortion is reported. The commonest indications were medical reasons such as exhaustion, and reactive depression. There was one case of schizophrenia, one case of affective psychosis, two attempted suicides, twenty reactive depressions, one character disorder, and one case of cerebral seizures. Five applications were approved. The follow-up evaluation of the women with the approved and dismissed applications for therapeutic abortions showed no physical or psychic abnormalities. A comparison with 88 German applicants showed similar results. The stringent evaluation of applications for therapeutic abortion is still necessary even after the change of the law.


[Influence on haemostasis exercised by Prostaglandin F2alpha in missed abortion (author's transl)].

The changes in the coagulation and the fibrinolytic system which may be related to the dead fetus syndrome indicate an interference of the activation of both coagulation and fibrinolysis. During termination of missed abortion and missed labour disorders of the haemostasis may occur acutely. In 16 patients with intrauterine death coagulation studies were performed inducing labour with PgF2alpha intraamniotically or i.v. No essentiel changes in the plasmatic system of coagulation and fibrinolysis were found. After i.a. application of PgF2alpha, the ADP- and collagen-induced as well as the spontaneous platelet aggregation didn't change. Using PgF2alpha i.v. a diminuation of the initially increased platelet aggregation was found in all parameters, whereas desaggregation was increased. These changes may influence an already existing latent consumption of coagulation factors in a favourable way. A further advantage of prostaglandins consists in the fact that smaller traumata occur, compared with curettage, so the possibility of liberation of thrombo-plastic material is reduced.


[The diagnosis of fetal atrio-ventricular block (author's transl)].

The case is reported of a primigravida who was found to have a fetal bradycardia of 70 per minute. A caesarean section was done with the differential diagnosis intrauterine hypoxia or fetal arrhythmia. The infant was found to have a single ventricle, single atrium, a hypoplastic aortic arch and a coartation of the aorta. The infant died neonatally.--The case was reported to emphasize the necessity of fetal electrocardiography in continual antenatal monitoring to rule out an atrio-ventricular block prior to caesarean section.


Changes in the relative amount of surface antigens on the living cells after treatment with insoluble protease derivatives.

Relative amount of surface antigen was compared on L 1210 leukaemia cells treated with soluble or insoluble derivatives of trypsin and papain. Trypsin or trypsin insoluble derivative do not change the amount of antigen significantly as compared with control. However, papain insoluble derivative decrease the relative amount of antigen within 45 min to the value of 0.43 or 0.55 respectively as compared with the control specimen.


125I-labeled cell surface as a marker in preparation of microsome fraction by gel filtration.

The microsomal fraction was isolated from homogenate of 125I-labeled leukemia L 1210 ascites cells by filtration of postmitochondrial supernatant through a Sepharose 4 B column. It was found that the particles are labeled with iodine and show 5'-nucleotidase activity suggesting the presence of cell membranes in the fraction. The soluble proteins fraction were retarded on the column showed lactate dehydrogenase activity, and low activity of soluble beta-D-glucuronidase.


Stereologic analysis of mitochondria of hepatocyte from fasted rats in the course of digestion.

Changes of the configurational states of the rat's hepatocyte mitochondria after 18 hours fasting and then one, two, three, four hours after feeding were investigated with stereological methods. Among others morphometric parameters coefficient of share (E) was introduced to express external or internal mitochondrial compartment volume per unit of surface area of the internal membrane. For parameters variation analysis Kruskal-Wallis test was used. Application of stereological methods reveals subtle changes lying beyond the power of visual observation and make possible the recognition of ultrastructural configuration of mitochondria in hepatocyte in the course of fasting and digestion connected with the various metabolic state.


On the application of thalidomide as a block of functional groups of proteins in histochemical investigations.

An attempt was made to apply thalidomide as a block of functional protein groups in histochemical investigations. It was found that thalidomide slightly oxidizes thyrosine and blocks the SH groups mainly in the cytoplasm of rat liver. Contrary to N-ethyl-maleimide, thalidomide does not block the SH groups irreversible, and they can be reactivated with BAL. It is suggested that the teratogenic effect of thalidomide can be connected with the possibility of inactivation of the SH groups by this compound.


The influence of pharmacological agents on the accumulation of egzogenic noradrenalin in nervous tissue cultivated in vitro. I. Effect of desipramine.

The authors investigated absorption of noradrenalin by neurons and glia cells cultivated in vitro. Material was taken from locus coreuleus of 3, 6, 12, 18, 24, and 36 days old rats. On the basis of observations, the authors found out that absorption of egzogenic noradrenalin changes with the growth of animals. In animals less than 24 days old, noradrenalin is absorbed not only by neurons but also by glia cells. Desipramin affects the egzogenic noradrenalin absorption clearly over the 12th day of life.


Approximative molecular weight of the active component in toxoplasmin.

The approximative molecular weight of toxoplasmin -- a skin reactive extract from Toxoplasma gondii -- was estimated by ultrafiltration through different Amicon membranes. The activity of the filtered and unfiltered product was compared with the aid of intradermal test on humans. The results indicate that the molecular weight of an active component in toxoplasmin is in the range from 10 000 to 50 000.


[Effects of various drugs on the lipolytic actions caused by catecholamines and methylxanthine derivatives in white adipose tissues. 1. Effects of procaine and xylocaine (author's transl)].

Effects of procaine and xylocaine on the lipolytic actions caused by catecholamines and methylxanthine derivatives in white adipose tissues from rats were investigated. Both procaine and xylocaine remarkably inhibited the lipolyses caused by norepinephrine, epinephrine, caffeine and theophylline. Xylocaine inhibited the lipolysis more strongly than procaine, and also inhibited the basal lipolysis. The inhibition by either procaine or xylocaine appeared 60 minutes after the addition of the norepinephrine-induced lipolytic action. The antilipolytic action of procaine was evident in medium containing 2 mM EDTA instead of Ca2+, and its antilipolytic action was accelerated by increasing Ca2+ concentration in the medium. From these positive results, we suggest that both procaine and xylocaine have an antilipolytic effect, and this effect is closely dependent on the Ca2+ concentration in the medium.


[Pharmacological properties of N-(3',4'-dimethoxycinnamoyl) anthranilic acid (N-5'), a new anti-atopic agent. (3).--Influence on homologous passive cutaneous anaphylaxis mediated by homocytotropic antibody (author's transl)].

N-5' shows a potent inhibitory action on the homologous passive cutaneous anaphylaxis (PCA) in rats mainly through the inhibition of histamine release from mast cells. The present experiment was an attempt to clarify in detail the pharmacological properties of N-5'. Inhibition of PCA was most potent at 30 or 60 min pretreatment with N-5', and negligible at 240 min pretreatment. Given p.o., N-5' produced a dose-dependent, potent inhibitory action at 30-min pretreatment. On the other hand, disodium cromoglycate (DSCG) had little effect on PCA when given orally. On the case of i.v. administration, N-5' (20 mg/kg) and DSCG (5 mg/kg) showed a most potent inhibition of PCA at 5 min pretreatment. The inhibitory action of DSCG was, however, shorter lasting than that of N-5'. Median effective doses (ED50) of DSCG and N-5' on the PCA were estimated to be 0.79 and 8.8 mg/kg i.v., respectively. Inhibitory activity of N-5' in the adrenalectomized rat did not differ from that in sham operated animals. N-5' had a more potent inhibitory action on the PCA in infant rats than in adults. Inhibitory activity of N-5' in the case of 1, 2, 3 and 4 weeks of successive administration was equipotent to that with a single administration.


[Effects of diazepam on evoked potential recorded from basal medial amygdaloid nucleus, lateral hypothalamus and midbrain reticular formation (author's transl)].

The evoked potential in the lateral hypothalamus (LH) recorded by stimulation of basal medial amygdaloid nucleus (Abm) showed a triphasic pattern and diazepam (2 mg/kg, i. p.) decreased the late component. The evoked potential in the midbrain reticular formation (MRF) recorded by stimulation of Abm showed a fast component with a relatively short latency followed by a biphasic late component and diazepam decreased the late component. Though the evoked potential in the Abm recorded by stimulation of LH showed a triphasic pattern, diazepam had no influence on the amplitude. Diazepam increased markedly the amplitude of evoked potential in the MRF recorded by stimulation of LH. Diazepam was ineffective on the evoked potential in the Abm recorded by stimulation of MRF. Diazepam decreased markedly the late component of evoked potential in the LH recorded by stimulation of MRF. These results suggest that the depression of emotional behavior by diazepam may be particularly related to the fact that the evoked potential in the LH recorded by stimulation of Abm was decreased by diazepam.


[Effects of gamma-oryzanol and atropine on gastric secretion stimulated by insulin or 2-deoxy-D-glucose (author's transl)].

The inhibitory effects of gamma-oryzanol and atropine on the gastric secretion were studied using insulin and 2-deoxy-D-glucose as vagal stimulants. Pretreatment with gamma-oryzanol (100 mg/kg, s.c., once daily x 5) depressed the gastric secretion stimulated by insulin or 2-deoxy-D-glucose, but the potency was less than that with atropine (10 mg/kg, s.c.). gamma-Oryzanol had no effect on decrease in the serum glucose level or on increase in the gastrin level induced by insulin injection, while atropine enhanced these responses. From these results, it is considered that the inhibitory action of gamma-oryzanol on gastric secretion may be due to depression of the vagus system but the mode of action is different from that of atropine.


[Mechanisms of contraction and relaxation in the response to 5'hydroxytriptamine of isolated rat ileum (author's transl)].

The action of 5-hydroxytryptamine (5-HT) in the rat ileum was analysed pharmacologically. In the isolated rat ileum, either mono or biphasic contraction was induced depending on the concentrations of 5-HT. The former was induced by lower concentrations of 5-HT (less than 6.25 X 10(-7)M) and the latter by higher concentrations of 5-HT (greater than 2.5 X 10 (-6)M). The monophasic contraction and the tonic contraction in response to 5-HT were blocked by methysergide (MTG). The phasic contraction in response to 5-HT after inhibition of muscular receptor with MTG was potentiated by physostigmine and blocked by mecamylamine (MC) or tetrodo-toxin (TTX). The response to 5-HT changed from a contraction to a relaxation by preincubation with MTG plus hyoscine. The relaxation was inhibited by TTX but not by MC and such was provoked even in the ileum from rats treated with 6-hydroxydopamine. Therefore, the inhibitory neuronal receptor for 5-HT does not appear to belong to the adrenergic nervous system. At lower concentrations of 5-HT, relaxation was induced with MTG which was only partially inhibited by TTX. These results indicate that the stimulatory response to 5-HT were caused by activations of muscular receptors and of intramural parasympathetic ganglion cells while inhibitory responses were caused by activations of non-adrenergic inhibitory nerve terminals and of non-neuronal elements.


[Pharmacological studies on supersensitization (IV). Site and mode of action of cocaine to potentiate acetylcholine in isolated tracheal preparation of rat (author's transl)].

Effects of cocaine on acetylcholine-induced contracture of isolated rat tracheal preparation were determined. The sensitivity of the preparation to acetylcholine but not methacholine and carbachol was increased by cocaine. The maximum responses induced by choline esters were not augmented by cocaine. The potentiation of acetylcholine was remarkable in calcium-deficient medium and cocaine augmented acetylcholine-contracture of the preparation suspended in calcium-free Tyrode solution. Calcium-contracture of the preparation susspended in isotonic 60 mM- or 100 mM-K+ Locke-Ringer solution was not augmented by cocaine. Extrapolating the time course of decrease in acetylcholine-contracture in calcium-free Tyrode solution, rates of calcium movement from and into calcium-stores were determined and it was found that cocaine did not change the calcium-content and rate of calcium-efflux but the rate of calcium-uptake was apparently increased with cocaine. The contribution of anticholinesterase activity of cocaine to potentiation of acetylcholine appeared negligible and the affinity of acetylcholine-receptor to acetylcholine and atropine was not changed with cocaine. Thus, cocaine increases acetylcholine-induced calcium-release and potentiates acetylcholine-contracture of isolated rat tracheal preparation.


[Effects of oral hypoglycemic agents, gliclazide and tolbutamide, on the cardiovascular system (author's transl)].

Recent clinical studies have suggested an association of tolbutamide (TB) therapy with an increased incidence of cardiovascular deaths. In this study, the effects of a newly synthetized hypoglycemic agent, gliclazide (GC), on the cardiovascular system were investigated, and compared with those of TB. Results are as follows: GC was found to be about ten times as active as TB in decreasing blood glucose in rabbits. GC and TB produced a dose-dependent increase in blood pressure and little change in heart rate in rats and rabbits. In driven left rat and rabbit atria, these agents produced a positive inotropic effect. The positive inotropic effects of these drugs were not altered by pretreatment with propranolol, or theophylline. These agents produced little change in the rate in spontaneous beating rat, rabbit and guinea pig atria. Higher doses produced a slightly negative chronotropic response. Neither agent potentiated the intropic effects of isoproterenol on the rabbit and guinea pig left atria. In isolated perfused working rabbit hearts, these compounds produced a slight decrease in coronary flow. It is concluded that GC and TB possess positive inotropic effects on isolated atria, and these effects are not mediated either through adrenergic mechanisms or the cyclic AMP system.


[Pharmacological actions of timepidium bromide on the motility of visceral smooth muscles and the secretion of digestive juice in experimental animals (author's transl)].

Effects of timepidium bromide (TB) on the motility of various smooth muscles and the secretion of digestive juice were examined and the activity was compared with those of hyoscine-N-butylbromide (HB) and atropine sulfate (Atr). In dogs, TB inhibited the spontaneous and bethanechol-induced motility of various regions of the gastrointestinal tract, the activity being almost the same as that of Atr but stronger than that of HB. All these drugs exhibited a similar inhibitory effect on the motility of the gallbladder. On the contrary, the inhbitory effect of TB on the spontaneous motion of urinary bladder was somewhat weaker than those of HB and Atr, while this effect on the bethanechol-induced motility was nearly equal the effects of HB and Atr. It was also evident that TB inhibited the gastric acid secretion induced by bethanechol: the activity was stronger than that of HB, while it was weaker than that of Atr. Similar effects on the gastric acid secretion were also found in rats. In the case of salivary secretion, however, TB and HB produced much weaker inhibitory actions than Atr. TB even at a higher dose produced little significant effect on the pancreatic and biliary secretion of rats. The uterine contraction induced by methacholine was inhibited by all these drugs. The mydriatic activity of TB in mice was found to be the weakest among the drugs tested.


[Action of 4-amino-alpha-](tertbutylamino) methyl]-3, 5-dichlorobenzylalchol hydrochloride (N-AB 365, clenbuterol) on the respiratory system (author's transl)].

The bronchodilating effect and other related pharmacological properties of N-AB 365 were studied in comparison with those of isoproterenol, salbutamol and clorprenaline. N-AB 365 was found to produce a bronchodilating effect 1/20 approximately 1/100, 1/10 approximately 1/40 and was 2 to 5 times as strong as effects of isoproterenol, salbutamol and clorprenaline, respectively. The bronchodilating effect of N-AB 365 was sustained more than 10 times as long as those of isoproterenol and salbutamol, and in particular with oral administration, was much more potent. The bronchodilating effect of N-AB 365 seems to be due mainly to excitation of the adrenergic beta2-receptor and partially to papaverine-like action. N-AB 365 showed an inhibitory effect on experimentally induced bronchial asthma by spraying of bronchoconstrictors and the effect by oral administration was much stronger than those of isoproterenol and salbutamol. N-AB 365 affected neither the volume output of respiratory tract fluid nor the tracheal ciliary movement with the doses around ED50 in bronchodilating action, however, it increased ciliary activity and decreased the volume output of respiratory tract fluid with large doses. Antitussive effect was also demonstrated only with the large doses. N-AB 365 induced a moderate decrease in blood pressure through vasodilatation but did not influence respiration. The effect of N-AB 365 on heart rate varied. There were cases of no change, slight increase or slight decrease in heart rate.


[Studies on the influsion speed and acute toxicity of amino acid solutions in rats (author's transl)].

Relationships between the infusion speed and lethal dose of several amino acid solutions of various concentrations were studied in male Sprague Dawley rats. When the amino acid solutions were continuously infused at various speeds, a functional relationship between the dose producing a cardiac arrest (DCA) and infusion speed was established. The DCA/infusion speed was characterized by two ranges with an increasing DCA as increase or decrease of infusion speed and by its intermediate range of a flat minimum with a practically constant DCA regardless of varying the infusion speed. A practically constant LD50 was obtained in the infusion of each amino acid solution within the infusion speed in the intermediate range. The LD50 of each amino acid solution was dependent on the crystalloid osmotic pressure.


[Simple and easy method for measurement of ambulatory activity in mice (author's transl)].

A hand-made apparatus which is easily manipulative, cheap, durable and clean was used to measure ambulatory activity of a mouse. The apparatus was assembled with the same type of two plastic round basins commercially available (25 cm in diameter) put one upon another. A pivot was fixed at the center of the outsurface of the inner basin (A), and its open end was inserted into the open socket fixed at the center on the bottom of the outer basin (B). Three microswitches equipped on the brim of (B) at equal intervals were activated and the counts were recorded according to the tiltings of (A) through the movements of the mouse. In order to examine accuracy of the measurement, effects of d-amphetamine (1.25 approximately 5.0 mg/kg), methamphetamine (1.0 approximately 4.0 mg/kg), cocaine (10 approximately 40 mg/kg) and morphine (5.0 approximately 20.0 mg/kg) on the ambulatory activity were investigated. Marked accelerating effects were observed dose dependently after the administrations of all the drugs. Furthermore, the patterns of the activity showed characteristic properties of each drug. This method is especially useful to measure the acute effect of drugs on the ambulatory activity in mice, and many units can be set up at the same time.


[Persistent erection in thiamine deficient rats (author's transl)].

Male Wistar rats weighing 75 to 85 g and maintained on a thiamine deficient diet for 33 days showed growth inhibition with the principal manifestation of significant weight loss from about the 28 day of experimental feeding. Symptoms of polyneuritis were also evident. On the 20th day of feeding and thereafter, rats on the thiamine deficient diet had a persistent erection. This was observed in 7% of the rats on a thiamine deficient group on day 20, 30.7% on day 25, 63.6% on day 30, and 100% on day 33. Effects of thiamine hydrochloride, in a single dose of 1 mg/kg given subcutaneously on the symptoms of thiamine deficiency were investigated. The treated rats recovered from the polyneuritic symptoms, and persistent erection disappeared in one out of 5 rats on the 3rd day and in 2 more rats on the 7th day. Persistent erection disappeared completely in rats maintained on a thiamine sufficient diet 3 days after single subcutaneous administration of thiamine HCl. These observations suggest that persistent erection was brought on as a consequence of thiamine deficiency.


Spontaneous segregation of a heterozygous diploid of Aspergillus niger.

A case of spontaneous segregation of a heterozygous diploid was observed with Aspergillus niger, giving rise to a somatic recombinant. Assuming an independence of markers, its genotype is suggested to be brw+lys pab+brw lys+pab.


Xylan-degrading activity in yeasts: growth on xylose, xylan and hemicelluloses.

The ability to grow in liquid media with D-xylose, xylan from decidous trees, and hemicelluloses from conifers was tested in 95 strains of 35 genera of yeasts and yeast-like organisms. Of 54 strains thriving on xylose, only 13 (genera Aureobasidium, Cryptococcus and Trichosporon) utilized xylan and hemicelluloses as growth substrates. The árowth media of these strains were found to contain xylan-degrading enzymes splitting the substrate to xylose and a mixture of xylose oligosaccharides. The ability of these yeasts to utilize the wood components (hitherto unknown in the genus Crytococcus) makes them potential producers of microbial proteins from industrial wood wastes containing xylose oligosaccharides, xylan, and hemicelluloses as the major saccharide components without previous saccharification.


Microcycle sporulation in the Claviceps purpurea 244.

The mutant strain Claviceps purpurea 244 forming hyphae composed mainly from sclerotium-like cells was found to sporulate both in liquid and solid media, particularly in the form of terminal chlamydospores (4.0 x 6.5 micrometer). Chlamydospores produced during submerged cultivation germinated, new chlamydospores being formed directly from germ tubes, or, occasionally, conidia (the so-called microcycle) or new vegetative mycelium were formed. The ultrastructures of the chlamydospores and vegetative cells was identical. The cytoplasm was filled with ribosomes and contained lipid inclusions and vacuoles with membrane invaginations. Strain 244 cultivated under submerged conditions produced 150 microgram/ml clavins, with elymoclavin predominating (82%). The parent strain Claviceps pururea 129 only produced chlamydospores on the vegetative mycelium, whereas no microcycle was detected; under submerged conditions it produced mainly agroclavin (85%) at a concentration of 4 mg/ml.


Inhibition of Tritrichomonas foetus by vermiculine in vitro.

The macrolide aglycosidic antibiotic vermiculine, added to the cultivation medium to a concentration of 30 micogram/ml, has an in vitro inhibitory effect on Tritrichomonas foetus. The agent interacts rapidly with the cells, causing irreversible changes after several hours of action. The changes are not repaired on removing the agent; the cells suffer from a rapid inhibition of nucleic acid synthesis, the protein synthesis remaining intact.


Effect of volatile substances released from Origanum majorana and Ocimum basilicum on the rhizosphere and phyllosphere fungi of Phaseolus vulgaris.

Differences were found in the counts and occurrence of fungi in the phyllosphere and thizosphere of two representatives of the Lamiacea family, Origanum majorana and Ocimum basilicum, and in the phyllosphere and rhizosphere of Phaseolus vulgaris growing separately or in coenosis with O. majorana or O. basilicum. Both the volatile substances released from ground leaves of the two latter plant species and the root exudates affected considerably spore germination of isolated phylospheric and rhizospheric fungi. The results indicated a possible role of root exudates and volatile substances released from leaves in colonization of rhizosphere and/or phyllosphere by fungi, especially in associations of various plants.


[Electroresection and electrocoagulation as therapy for vulvar neoplasms].

A survey of the results attained by the most prominent authors of the individual therapy methods is given. After electro-resection and -coagulation of the vulvar tumor followed by roentgen or telecobalt irradiation, patients are almost without pain. The primary mortality in 332 patients was 1,5% (= 5 cases) because lymphonodectomy was performed in only 66 cases (20%). The period of hospitalization lasts about four weeks and cosmetic healing is excellent. This therapy method can also be recommended for largely extended tumors as lack of local symptoms can be achieved up to 97%. Of the 332 patients treated at our hospital, almost equal numbers of patients were seen with carcinoma stage I and II and stage III and IV. In stage I and II (negative lymph nodes) 74,5% and in stage III and IV (positive lymph nodes) 38,4% were cured. 80% were aged between 61 and 90 years. In spite of this negative selection of patients which was also combined with the intercurrent mortality rate of 13% (= 43 cases), 193 of the 332 patients or 58,1% survived five years or longer. In the last five years the survival rate was even 62,2%. A survey of the results obtained by electrocoagulation in the last 30 years is given. Especially the enormous increase of high risks as diabetes (42,2%) and the great number of over-aged patients (83,3%) are emphasized.


[Hormone dependent, functional gynecologic morphology in infancy and adolescence presented on the example of the cervix uteri].

Signs of different activities in the dynamic morphology of the epithelium and mucus of the cervix uteri are demonstrated in the female fetus, newborn, child and adolescent. Besides the morphological description of the ectropium, transitional zone, s.c. "reserve-cells", squamous cell nodes and production and secretion of mucus other investigations were done by allometry, caryometry and histochemistry. The examinations allow insight into the hormonal activities specially of the estrogenes in different periods of female life.