Circular molecules of heterogeneous size from mitochondrial fractions of the petite-negative yeast Schizosaccharomyces pombe.

Size and shape of mitochondrial DNA molecules of Schizosaccharomyces pombe were analyzed by electron microscopy. Besides numerous linear molecules, circular molecules ranging from 0.83 micron to 12.81 micron were found. Depending on the method of preparation, both closed and open circular molecules were found. Most of the circular molecules could be assigned to five major size classes of 0.83 +/- 0.05 micron, 1.7 +/- 0.05 micron, 4.74 +/- 0.04 micron, 5.74 +/- 0.04 micron, and 8.32 +/- 0.07 micron. Possible explanations for the different size classes of mitochondrial DNA molecules are discussed.


Extrachromosomal inheritance in Schizosaccharomyces pombe. VII. Studies by zygote clone analysis on transmission, segregation, recombination, and uniparental inheritance of mitochondrial markers conferring resistance to antimycin, chloramphenicol, and erythromycin.

Crosses involving mitochondrial markers conferring resistance to antimycin (anar, AR), chloramphenicol (capr, CR), and erythromycin (eryr, ER) in cis- and trans-configuration were studied by zygote clone analysis. Mutant anar-8, from which all other drug--resistant isolates were derived, exhibits a highly biased transmission (6.8% anar) in an analysis of 100 individual zygote clones. Important results of zygote clone analyses were:--Zygote clones may contain one, two, three, or four mitochondrial genotypes.--The proportion of the two parental and the two recombinant genotypes in individual zygote clones can vary almost over the entire range of percentages.--Proportions of the two corresponding recombinant types in individual clones are usually unequal.--Transmission rates of markers are higher in trans- than in cis-crosses, indicating additivity of bias by two mutated alleles in coupling.--Transmission rates are different for the three markers both in cis- and trans-crosses, being lowest for CR and highest for ER.--Up to more than 80% uniform clones, expressing only one genotype, can be produced in cis- and trans-crosses. In cis-crosses always the double-sensitive parental type becomes uniform, in trans-crosses this may be the case for parental and/or recombinant genotypes. A tentative map is presented using data from cis- and trans-crosses, including a correction by omission of uniform clones. Phenomena of transmission, segregation, and formation of uniform clones are discussed with special regard to the difference brought about by fission versus budding. A comparison with relevant data from Saccharomyces cerevisiae and other organisms is presented.


Ant-mediated transactivation of early genes in Salmonella prophage P22 by superinfecting virulent P22 mutants.

The virulent mutants P22 virB vy and P22 vy mutants, both insensitive to mnt-repressor, transactivate the early genes of a P22 prophage. The transactivation of early P22 prophage genes depends strictly on the expression of gene ant ("antirepressor"-protein) by the superinfecting P22 mutant and therefore occurs by derepression.


Structure of recombinant plasmids containing synthetic human foetal globin gene sequences.

In vitro synthesized duplex DNA complementary to human foetal globin messenger RNA was integrated into bacterial plasmids and amplified by transformation of Escherichia coli. Recombinants carrying globin DNA were identified by hybridization of foetal globin messenger RNA to bacterial DNA in situ and by liquid hybridization of purified plasmids to specific globin complementary DNA probes. Heteroduplex mapping revealed either a simple insertion loop at the position of the EcoRI site of the parental plasmid DNA. We provide evidence to suggest that these deletions are the result of a site-specific nicking activity of the EcoRI preparations used in the formation of recombinant plasmids.


[Peculiar secretory activity of endometrial cancer cells during progestational therapy].

Effect of progestagen-norsteroids on the cells of endometrial carcinoma was studied. It was established that as an effect of treatment with large doses of progestagen (100 mg/day) in about 4--6 weeks carcinoma cells show a peculiar increased secretory activity. It seems likely, that this secretory activity proceeds on the account of the growth-potencial of tumour cells. Thus, as a result the growth of the tumour ceases, or in optimal cases stops.


[Ultrastructure of the thymus and neuromuscular junction in myasthenic and non-myasthenic patients].

Ultrastructural changes in 35 neuromuscular junctions taken from myasthenic patients (in 2 cases: hyperplasia of the thymus, in 1 case: epithelial thymoma was present) treated with anticholinesterase during 1--2 years, appeared to be similar to those observed in non-myasthenic patients with lymphoid thymoma (getting no treatment with anticholinesterase). Number of the secretory granules in the epithelial cells of the thymus was in accordance with the severity of the disease. It can be assumed, that in the disturbance of the neuro-muscular transmission of the stimuli the activation of the epithelial cells may play a part.


[Current data on toluene toxicity based on liver biopsy studies].

Authors in 1968 performing the periodoc observation of persons, working in toluene-containing athmosphera noticed the presence of hepatomegaly. Laboratory tests performed in 1968--1976 have revealed increase of the level of GOT. At 22 workers out of 170 liver biopsy was performed. By electron microscopy pathologic alterations in the mitochondria and in the rough-surfaced endoplasmic reticulum could be observed, -since these organella contain the two-third of the GOT of hepatocytes. It is assumed that mitochondria as sources of energy take part in the process of the oxydation of toulene, ribosomes of the rough-surfaced endoplasmic reticulum in the conjugation of benzoic-acid with glycine. Authors assume that there is a correlation between the damage of the organella and the detoxication of the toluene by hepatocytes.


[Postmortem studies on Prodectin].

Author described a new method for the postmortem investigation of the active component of a new medicament Prodectin. For the extraction of it from the organs acetic-alcoholic methode was used. Isolation and quantitative determination of the subtance was carried out by layer-chromatography, quantitative determination by UV-sectrophotometry. The distribution of the substance in organs was also investigated.


[Morphological base of Renshaw inhibition studied by light and electron microscopic histochemistry. Topograhic analysis of AChE-positive Renshaw elements].

Light- and electron microscopic structure of Renshaw elements--morphologic representatives of the recurrent spinal inhibition--was investigated by histochemical localization of AChE. Renshaw elements are spindle-shaped segments of the dendrites of the Renshaw cells and endings of the axoncollaterals of AChE-positive motoneurons are situated on them. Examination of serial sections of the L5-segment of the cat spinal cord revealed that the majority of Renshaw elements and the dendrit-arborization of interneurons of 3. type described by MATSUSHITA are lokalized in the same region. The fact that Renshaw elements in greatest amount could be found in that region of the anterior horn, where the Renshaw inhibition can be electrophysiologically elicited, seems to evidence they role in the latter.


[Experimental studies on the compression resistance of the head with special reference to the mechanism of fractures in traffic accidents].

Compressional resistance of the head and its role in the mechanism of fractures in traffic accidents were studied in five formalin-fixed heads. Before and after the experiment X-ray examination was carried out. Because of the variability of fractures coming into being, it was difficult to distinguish definite types. Nevertheless, experimentally produced fractures appeared to be nearly the same, as those seen in clinical practice.


[Ultrastructure of the mouth mucosa in various types of oral leukoplakia].

12 cases of laukoplakia of the oral cavity was studied by electron microscopy. A correlation between the clinical type, histological- and ultrastructure of the leukoplakia was revealed. In types of leukoplakia simplex and verrucosa, where histologically cornification was found, by electron microscopy signs of keratinization (tonifibrils, granules of keratohyalin) were to be observed. In leukoplakias clinically showing erosions, histologically dysplasia, ultrastructural changes were alike those, seen in some carcinomas.


[The role of mastocytes in the development of the adrenergic innervation of the iris].

During the development of the primary adrenerg-plexus in the rat iris presence of mastocytes showing intensive fluorescence can be observed using the method of Falck. After the formation of the primary plexus this phenomenon disappears. By electron microscopy in the early period of the postnatal life authors demonstrated the presence of mastocytes closely related to developing neurofibrils and Schwann-cells. In these mastocytes signs of degranulation were to be observed. On the base of the latter finding one can assume, that substances deliberated from the granules may play a part in the regulation of the development of innervation.


[Ultrastructural changes in the liver and leukocytes of a child with Niemann-Pick disease].

Morphological findings in Niemann-Pick disease of an infant are described. By electron microscopy in the cytoplasma of leukocytes and hepatocytes mostly moderaty electrodense unmature lipid-containing cytosomes were seen. Morphological alterations found in the leukocytes and hepatocytes in contrast to the earlier findings appeared to be similar. Authors stress the importance of electron microscopic investigation of peripheric leukocytes.


[Miltinuclear spermatides observed in varicocele].

Author in the histologically normal testis of a patient aged 31 suffering of varicocele by electron microscopy revealed the presence of polynuclear spermatids and spermiums, i.e. disturbance of the spermiogenesis. The cause of this phenomenon has to be cleared by further studies.


[Effect of long-term progestational treatment on the course of endometrial adenocarcinoma].

Author studied the effect of prolonged--6-8 month--treatment with Hormofort on the cells of adenocarcinoma of the endometrium. Light- and electronmicroscopic studies show, that after the treatment with progestative hormones cells of the adenocarcinoma seems significantly regrediate and simultaneously clinical remission can be observed. These data suggest, that progestative-norsteroids seems to elicit "cytostatic" effect on the endometrical tumour cells.


[Human uterine tubes studied by scanning and transmission electron microscopy].

Six human uterine tube were studied by scanning-and transmission electron microscopy. Ciliated epithelium and epithelium covered by microvilli could be identified by both method. In the area of the fimbriae the majority of cells appeared to be ciliated epithelium, but near to the uterus their number decreased. At every part of the uterine tube cells of the ciliated epithelium were situated deeper than cells covered by microvilli. In the age group studied (20-45 year) no age-dependent differences in the structure of the mucosa or in the number of the different cells could be revealed.


[Fine structure studies in the lungs of infants with idiopathic respiratory distress syndrome].

Authors studied ultrathin cestions of lung of ten newborns died of IRDS in the various stage of the disease. It was established that lamellar bodies are already formed in the initial phase of the disease. In the first two clinical phases by pneumocytes type II structure of the intracytoplasmic and intaraalveolar lamellar bodies differs from the normal, and they can not form air-cell interphase. In the third clinical phase--in the phase of the resolution-mature lamellar bodies of normal structure are formed and get into the alveolar space, thus the condition of formation of air-cell interphase is given.


[Functional morphology of Peyer's patches. Lymphocyte activation in Peyer's patches].

Peyer plaques of rats were studied by morphological methods in order to compare the structure of these organs with the present theories on their function. It was established that near to the follicules of plaques folds perpendicular to the intestinal passage are formed, which are able to direct a part of the bowel-contents into the direction of the follicules. Between the surface of the follicules and large intestinal villi recesses are formed, in which stagnation of the intestinal content takes place. As a result of this antigens and mitogens containing in the intestinal lumen can contact lymphoid cells of through the special epithelial cells the Peyer-plaques. The latter were recently studied by polarized light too, since earlier studies of the authors have shown that birefringence of these cells depends on their functional state. Authors disclosed that birefringence of the cells of the Peyer-plaques is significantly stronger, than that of the cells of spleen, lymph nodes, and thymus. Cells with increased birefringence are situated on the epithelial side of the capsule of follicules. Reported studies evidence, that Peyer-plaques are structures specialized for incorporation of antigens. Lymphoid cells of Peyer-plaques are activated by effects coming from the intestinal lumen.


[Histological, ECG and enzyme studies on dogs following direct current shock applied to the heart region].

Authors using D.C. (direct current)--have produced shock experimentally- at 28 dogs. In the control animals (8 dogs) no histological, EKG and enzymatic changes could be revealed. In the dogs after the application of D.C of 1 X 2.5 W. sec/kg histological and EKG changes were not revealed, although the level of GOT and CPK increased significantly. After the application of D.C. of 4 X 5 W. sec/kg significant increase of the level of the following enzymes occurred: GOT, isoenzyme- LDH5, total-LDH and CPK. In 7 dogs--out of 8 showing histological changes in the myocard--activity of the serum isoenzyme-LDH1 increased and alterations of the EKG occurred. Thoracic musculature of six experimental dogs was investigated histologically. All of them revealed pathological changes. Correlation between the level of the isoenzyme- LDH1, the histological and EKG alterations were found. Increase of the level of serum enzymes seems to be the consequence of the injury of the thoracic-musculature by D.C. shock, and has clinical significance only in cases when pathologic changes of the EKG and increase of the insoenzyme-LDH1 are also present.


[Quantitative morphological studies on the zoma glomerulosa of the rat adrenal gland. I. Basic principles of stereology].

Quantitative morphological study of the zona glomerulosa of the rat adrenal was carried out. Basic principles of the method used are reviewed. The most important stereological methods and correlations described in the literature and used for the study of quantitative relations of the stereological structure on two-dimensional microscopic pictures are discussed.


[Quantitative morphological studies on the zona glomerulosa of the rat adrenal gland. II. Effect of potassium and heparin on the zona glomerulosa].

Authors studied the effect of potassium and heparin on the zona glomerulosa of rats by stereological methods. As the effect of potassium tolerance test the weight of the adrenals, the wideness and volume of the zona glomerulosa, the number and the volume of the cells of it, further the volume of the mitochondria and nuclei in each cell have shown significant increase. After treatment with heparin the wideness of the zona glomerulosa and the volume of the mitochondria appeared to be decreased. Results are in accordance with the aldosterone-level-increasing effect of potassium and with the antialdosteron effect of the heparin.


[Liver adenoma, causing fatal abdominal hemorrhage, after prolonged administration of oral contraceptives].

One case of hepatic adenoma is reported. The tumour occurred after seven years of uninterrupted use of anticonceptive pills and caused fatal abdominal haemorrhage. The adenoma had a connective tissue capsule and regular lobular structure in which at some area peliosis could be observed. In the liver, in several area focal deposites of PAS-positive material occurred.


[Ketamine-induced ultrastructural changes in the retina].

Alterations of the retina caused by ketamin were studied in experiment. After a 60-minutes monoanaesthesia with ketamin ultrastructural changes were observed on the inner members of receptor cells, in the three nuclear layers and in the layer of nerve fibres. Severe damage to the structure of the Müller's glial cells providing nutrition to neural-elements was also revealed. Three days after the anaesthesia beside the regression of these alterations, glycogen deposits could be seen in the Müller's cells. This phenomenon and some side effects caused by ketamin can be explained by increased utilization of oxygen and relative hypoxia.


[Plasmoblastic and immunoblastic sarcoma. Differentiation of immunoglobulin-producing tumors (myeoloma multiplex, plasmacytoma)].

In the Department of the Pathology of the University of Pécs in 1953--1977 autopsy of 58 cases of myeloma multiplex (MM) and plasmacytoma (P) was performed and among them 4 cases of sarcoma was found. In the material of the Cytologic Center of the Academical Commission of Pécs two more cases of sarcoma occurred. According to the authors findings in the MM-autopsy material (I) in addition to the frequent "plasmocytic-plasmoblastic MM" in a few number (II) immunoblastic tumours could also be seen (immunoblastic MM). "Immunoblastic MM" disseminates more frequently (lymph nodes, spleen, kidney, liver) and the patients die earlier than in cases of "plasmocytic-plasmoblastic MM". Since sarcomatous changes appear to be polymorph and disseminated, for the reliable diagnosis examination of tissue specimens taken from several parts of the tumour is necessary. Recent data and the authors studies show, that immunoglobulin-producing tumours differ each other according to the degree of maturity of plasma cells


[Klinefelter's syndrome as cause for excluding paternity].

Authors as legal experts by chromosomal study and testis biopsy revealed the presence of Klinefelter's syndrome. On the base of these findings the paternity of the man in question was excluded. Authors stress the importance of the studies of chromosomes in the forensic medical practice.


[Morphological data on gerontostomatology].

On the base of the study of serial histological sections, freezed-sections and special bone-praeparates senile alterations of the structure of the palatine mucosa and the mandibular bones are discussed, with special regard on the gerontostomatological aspects. After the loss of the teeth the structure of the connective tissue of the gingiva diappears, in the processus alveolaris develops fibrosis. The glandular tissue of individual extension on the edges shows regression. Thickening of the epithelium in some area can be seen. The lamina propria in the anterior third is very thick in the pharyngeal part becomes thinner. Alveolar processes of the maxilla show signs of involution and atrophy of disuse, with a number of defects and assymetries on the palate. On the macrorelief of the mandibula characteristic changes can be observed: in the region of the corpus eburneationg and osteosclerosis of the spongiosa can be revealed.


[Correlation between histological picture, tumor size and age in cancer of the uterine cervix].

Correlation of the histological structure and spreading of the tumour with the age of the patient in the cervix-cancer was studied at 3357 patients. Most of the cases occurred in the 5th decade of the life, independently of the histological type of the cancer. Adenocarcinomas were seen considerably often in elderly ages. Cervix cancer of the III. and IV. stage were more frequent in elderly ages as well. In advanced stages the number of cases of carcinoma planocellulare increased, and the number of anaplastic and adenocarcinomas decreased.


Mutagenicity tests with styrene oxide in mammals.

The capability of styrene oxide to induce chromosome damage in vivo has been tested in the male mouse by examination of bone-marrow cells, by scoring micronuclei in polychromatic erythrocytes, by observation of meiotic chromosomes from treated males and by the dominant-lethality test. Furthermore, studies have been performed on short-term cultures of human lymphocytes in vitro. Whereas an increase in the yield of chromatid and chromosomal aberrations was observed after exposure in vitro, only negative results were obtained in the tests in vivo. One has, therefore, to conclude that styrene oxide is potentially capable of breaking mammalian chromosomes but that an exposure to an acute dose in vivo does not produce visible damage in somatic cells or in male germ cells.


Induction of long-lived chromosome damage, as manifested by sister-chromatid exchange, in lymphocytes of animals exposed to mitomycin-C.

The cytogenetic effects of repeated vs. acute exposure to a chemical mutagen--carcinogen were determined with an in vivo system in which chemicals injected into rabbits induce sister-chromatid exchanges (SCEs). SCE induction can be monitored when the animal's peripheral lymphocytes are cultured in the presence of bromodeoxyuridine (BrdUrd) and then scored for SCE frequency. Mitomycin-C (MMC), 0.5 mg/kg, was injected intraperitoneally once a week for 8 weeks. This treatment initially induced small increases in SCE frequency within one day of injection, followed by a return to control levels within 1 week. After the 4th injection, however, the frequency failed to return to normal. After the 5th injection, however it showed a 4-fold increase over the control which was sustained for the remaining 3 weeks of treatment and for an additional 2 weeks thereafter. The frequency then dropped to twice the control value and remained at this level for more than 4 months. All of the high SCE values after the first 4 weeks were due in part to the appearance and persistence of a population of cells with high SCE frequencies. Exposure to the same total dose given as a single injection resulted in a transient elevation in the SCE frequency and a subsequent return to lower values, with no evidence of a delayed effect such as the increase observed after 4 weeks in repeatedly exposed animals. Overall, repeated exposure is at least as effective as acute exposure in eliciting long-lived SCEs in vivo.


Effects of LSD on human chromosomes.

A number of positive and negative studies have been reported with regard to the damaging effects of LSD on human chromosomes. The present report describes a comparative study of cytogenetic analyses of 200 metaphases of lymphocytes from each of 6 subjects (3 males, 3 females) at varying concentrations of LSD, along with a positive control with mitomycin C and a negative control with sterile water. Results of a small pilot study on the effects of LSD on growth, macromolecular synthesis, mutation, and recombination in bacteria, lambda phage and mammalian cells are also included. The data failed to show any significant differences between chromosome aberrations and LSD. Significant changes in somatic cells and in chromosomes occurred only at high doses of LSD.


Caffeine inhibition of prereplication repair of mitomycin C-induced DNA damage in human peripheral lymphocytes.

Caffeine increases the number of sister-chromatid exchanges (SCE) induced by mitomycin C (MMC) in human peripheral lymphocytes in culture. This enhancement decreases when the treated cells are held in medium before phytohemagglutinin (PHA) stimulation, or when caffeine is added to cultures some time after PHA stimulation but prior to DNA synthesis. There thus appears to be a caffeine-sensitive prereplication repair system, presumably an excision mechanism, capable of repairing a fraction of the MMC-induced DNA lesions.


Factors affecting the induction of micronuclei at low doses of X-rays, MMS and dimethylnitrosamine in mouse erythroblasts.

In erythrocytes from mouse bone marrow the time schedule of micronucleus formation in relation to the last DNA synthesis was investigate by [3H]thymidine labelling in the autoradiographic technique. The results suggest that micronuclei can be produced both in the G 2 and S periods by X-irradiation. Furthermore, X-rays had a delaying effect on the cell cycle leading to a pronounced under-estimation of the dose-effect curve at higher dosages. Even when the cells were harvested as late as 30 h after irradiation, the full effect had most likely not yet appeared at dosages over 100 rad. Combined treatment with caffeine did not influence the dose-effect curve of X-rays, indicating no influence of a caffeine-sensitive repair mechanism. The induction of micronuclei by MMS, in contrast with the effect of X-rays, seems to have been restricted, at least predominantly, to the period of DNA synthesis. The dose-effect relation of MMS was characterized by a threshold giving a weaker effect than expected at low doses. Pretreatment with caffeine enhanced the effect of MMS at high but not at low doses, suggesting an error-free repair process operating at low doses and an error-prone and caffeine-sensitive repair at higher doses. The extent of alkylation in the bone-marrow cells was linear with respect to injected dose of MMS both in the presence and absence of caffeine. Pretreatment with phenobarbital reduced the effect of MMS sixfold, which can be explained by a reduction of alkylation found in the bone marrow. This result is in agreement with the enhanced excretion of MMS or its metabolites into urine and bile after pretreatment of the mice with phenobarbital. DMN had no measurable effect on the frequency of micronuclei. However, in the presence of caffeine a significant effect was observed, which was roughly of the same magnitude for the two dosages used. Pretreatment with phenobarbital also indicated a synergistic effect between DMN and phenobarbital. The treatment with DMN, phenobarbital and caffeine together gave a frequency of micronuclei not different from the control level, suggesting some antagonistic action between phenobarbital and caffeine. The indication that DMN is caffeine-sensitive at low dosages, whereas MMS is not, might be related to the difference in the alkylating properties of these chemicals.


The effect of the mode of administration of nitrogen mustard and cytosine arabinoside on the production of chromosomal aberrations in mouse bone marrow and ascites tumour cells.

The cytogenetic effects of intraperitoneally (i.p.) and subcutaneously (s.c.) administered nitrogen mustard (HN2) and cytosine arabinoside (ara-C) on bone-marrow and ascites tumour cells of mice were studied. Ehrlich ascites tumour-bearing mice were treated with the mutagens, and cytological preparations were made from ascites tumour and bone-marrow cells of the same animal. The following parameters were investigated: frequencies of mitotic and chromosomal aberrations, time of aberration maxima and aberration spectra. HN2 (0.68 mg/kg b.w.), when given i.p., induced in ascites tumour cells a strong inhibition of mitotic frequency and very high aberration rates, whereas in bone marrow no aberrant chromosomes were observed. On the other hand, after s.c. administration, the same dose induced more aberrant metaphases in bone marrow than in tumour cells. Ara-C (315 mg/kg b.w.) resulted, after s.c. administration, in higher aberration frequencies both in ascites and bone-marrow cells compared with i.p. treatment. All ascites tumour cells showed higher aberration requencies than bone-marrow cells. In bone marrow the aberration maximum occurred as soon as 6 h after treatment. Furthermore, clear differences with respect ot the types of aberration found in the two systems were evident. The differences caused by the different modes of administration in two different types of cell are discussed in terms of metabolic inactivation and differences of the two tissues with respect to karyotype, cell cycle time and repair capacity.


Cytogenetic effects of cis-platinum(II)diamminedichloride on human lymphocyte cultures.

Human lymphocytes were treated with the antitumor agent cis-platinum)II)diamminedichloride (PDD) during either the last 24 h or 48 h of incubation. A dose-dependent effect was observed for both inhibition of mitotic activity and increased frequency of metaphases with chromosomal aberrations. The aberrations observed consisted primarily of chromatid breaks. Statistical analysis of 3244 PDD-induced breakpoints demonstrated a significantly nonrandom distribution of breakpoints between chromosomes. The pattern of distribution varied with the type of aberration. Only chromosome number 9 had a significant increase of breakpoints for each type of aberration analyzed. The breakpoints were located predominantly in lightly staining G-gands. Certain individual bands had relatively high frequencies of breakpoints, indicating a specific interaciton occurs between PDD and the DNA of human lymphocytes in vitro.


Antibodies to type II collagen in relapsing polychondritis.

Relapsing polychondritis is a disorder of unknown cause characterized by the destruction of cartilage. To test the hypothesis that immunologic mechanisms are involved in the pathogenesis of relapsing polychondritis, we analyzed the serum of 15 patients for the presence of antibodies to cartilage. Antibodies to Type II (cartilage) collagen were found in the serum of five patients at the time of acute symptoms. No antibodies were detected either to cartilage proteoglycan or to other collagen types. The antibodies were detected at the onset of the disease and their titers appeared to correlate with severity of disease. Circulating immune complexes were also detected in the serum of these patients. Our findings support an immunologic involvement in this condition.


Coronary vasospasm as a possible cause of myocardial infarction. A conclusion derived from the study of "preinfarction" angina.

To investigate the pathogenesis of myocardial infarction we undertook a systematic study of patients with angina at rest, a syndrome known to evolve frequently into infarction. Among 187 consecutive patients, 37 had infarction, all in the area that showed electrocardiographic changes during angina. In all 76 patients who underwent hemodynamic monitoring, 201thallium myocardial scintigraphy or angiography during angina, a vasospastic origin of the attacks was documented. In six patients with infarction shortly after these studies and in two in whom the infarction developed during hemodynamic monitoring or during angiography the onset of infarction was indistinguishable from the onset of anginal attacks. One patient in whom spasm was observed at the onset of infarction died six hours later; at post-mortem examination, a fresh laminar thrombus was found at the site of the spasm. After infarction, complete thrombotic occlusion of the branch shown to undergo vasospasm was documented in two patients by angiography.


Estrogen receptors and responses to chemotherapy and hormonal therapy in advanced breast cancer.

To determine the correlation between the estrogen-receptor status and responses to chemotherapy or hormonal therapy, we retrospectively analyzed the clinical data of 143 patients with advanced breast cancer. Receptor contents were determined by a sucrose-gradient method and designated arbitrarily as "rich" or "poor". The response rate to chemotherapy was significantly higher in receptor-rich tumors (86 per cent) than in receptor-poor tumors (36 per cent) (P less than 0.001). Patients with receptor-rich tumors also responded favorably to hormonal therapy. However, there was no correlation between the responses to hormonal therapy and to chemotherapy when they were used sequentially, a phenomenon that may be attributed to the changes in tumor receptor content during the clinical course. These data suggest that separate factors associated with the response to chemotherapy may coexist with estrogen receptors in breast cancer.


Hemodynamic assessment of amrinone. A new inotropic agent.

Amrinone, a new bipyridine derivative, exerts a positive inotropic action in experimental preparations and is effective when administered orally to dogs. To assess its immediate effects in man, we studied by cardiac catheterization the hemodynamic responses to amrinone (1.85 to 3.5 mg per kilogram given intravenously) in eight patients with congestive heart failure already receiving full doses of digitalis. the following statistically significant (P less than 0.01) effects were noted: cardiac index increased from a mean +/- 1 S.D. of 1.8 +/- 0.3 to 2.6 +/- 0.3 liters per minute per square meter; peak rate of left ventricular pressure rise rose from 849 +/- 233 to 1206 +/- 456 mm Hg per second; left ventricular end-diastolic pressure fell from 25 +/- 9 to 14 +/- 7 mm Hg; pulmonary-capillary pressure fell from 28 +/- 8 to 15 +/- 4 mm Hg; and right atrial pressure fell from 12 +/- 6 to 7 +/- 5 mm Hg. Mean heart rate was unchanged, and aortic mean pressure declined slightly (86 +/- 10 to 80 +/- 7 mm Hg, P less than 0.025). No toxicity was observed. Amrinone, whose mechanism of action has not yet ben defined, warrants further study as a possible treatment for heart failure.


Clinical usefulness of red cells preserved in protein-poor mediums.

Blood is normally collected into a combined anticoagulating and preserving medium. We performed a study to ascertain whether improvements could be made by separation of these two functions. Addition of saline-adenine-glucose solutions (40 to 100 ml per blood unit) to buffy-coat-poor red-cell concentrates allowed storage for as long as 35 days with 24-hour erythrocyte post-transfusion survival of 83 +/- 6.8 per cent (+/0 S.D.). Potassium leakage was lower, and in vitro hemolysis somewhat higher than that of whole blood. The microaggregate content after 21 days was 16 per cent of that in whole blood. In over-pressure transfusions the flow rate of red cells was the same with red-cell concentrates to which 80 to 100 ml of suspension medium had been added (hematocrit less than or equal to 60 per cent) as with whole blood. Removal of the buffy coat was essential to reduce hemolysis. We conclude that red cells can be successfully stored in a simple protein-poor medium.


Fallacy of the five-year survival in lung cancer.

Patients with lung cancer can be treated by either surgical extirpation or radiation. The former may offer increased five-year survival and prolonged life expectancies as compared to the latter, but subjects patients to the immediate risk of thoracotomy. We interviewed patients with "operable" lung cancer and found that they were quite averse to taking risks involving the possibility of immediate death. When these data about patients' attitudes were combined with data about survival after both radiation therapy and operation, it appeared that radiotherapy would be the preferred therapeutic plan for several of these patients. These results emphasize the importance of choosing therapies not only on the basis of objective measures of survival but also on the basis of patient attitudes.


Aspergillus penicilloides and Eurotium halophilicum in association with house-dust mites.

Aspergillus penicilloides Speg., Eurotium halophilicum Christensen et al. and other xerophilic fungi were isolated from house dust. The isolates of E. halophilicum are described and compared with the type strain of this species. A. penicilloides appeared to be rather common. The species concept of this species is broadened to accomodate some variable forms with different colony characters and conidophore structures. The role of both species is discussed in connection with house-dust mites, house-dust allergy and skin diseases.


Mating behaviour of Nannizzia otae (=Microsporum canis).

One hundred and ninety-eight isolates of Microsporum canis, obtained from humans and animals in 12 countries, were paired with the two Japanese tester strains of Nannizzia otae (= M. canis), VUT 74037 (CDC B-2094+) and VUT 74039 (CDC B-2095-). One hundred and forty-one (72%) produced either gymnothecia or pseudogymnothecia in crosses with VUT 74037. Fifty-seven (28%) were nonreactive. None of the paired isolates reacted with VUT 74039. The number of nonreactive isolates decreased to 17% when 104 of the 198 isolates were paired with one additional tester strain of each mating type. All sexually reacting strains, however, belonged to the (-) mating type. Crosses between nonreactive isolates did not result in ascocarp formation. The F1 generations from three different strongly reactive crosses were all characterized by poor ascospore germination. Most of the monoascospore progeny that germinated to form mature colonies were nonreactive in crosses to determine their mating type. Others reacted predominantly as the (+) mating type, thereby precluding the likelihood of an associated lethal factor accounting for the lack of this mating type in our clinical isolates. Several explanations for this phenomenon are presented.


On the occurrence of Microsporum persicolor in Montreal, Canada.

A case of Microsporum persicolor skin infection in a casual employee of a veterinary clinic in Montreal, Quebec, Canada, is reported. A survey of 80 wild rodents in the Montreal area resulted in the isolation of M. persicolor from two voles (Clethrionomys gapperi) and one deer mouse (Peromyscus maniculatus). One of the voles, heavily infested with parasites including ticks, had obvious lesions on the nose. This is the first report of M. persicolor in rodents in North America.


Examination and evaluation of germination and protonemal development for Onoclea sensibilis fern spores treated with aflatoxin B1.

Experiments were designed to test the effects of aflatoxin B1 (AFB1) on germination and subsequent development of the gametophytes of the sensitive fern Onoclea sensibilis. AFB1 concentrations used were 0, 2.5, 5.0, 7.5, 10.0 and 12.5 muM. Preliminary studies indicated that, under all AFB1 concentrations tested, germination was maximum after 144 hrs. Additional studies revealed that during this time period protonemal growth was in the log phase. Percent germination was inhibited by increasing concentrations of AFB1; A 50% inhibition was noted at 12.5 muM. In addition, increasing concentrations of AFB1 caused a reduction in the total number of cells per protonema. Preliminary analysis indicated that this was caused by a reduction of the rate of cell production rather than total inhibition of cell division. A comparison of the dose-response curves for both of the above effects demonstrated that sensitivity to AFB1 starts at 2.5 muM. This may indicate that AFB1 is acting on a process common to both phenomena. The fern spore germination system could be a "simple" model system in which to study the site and mode of action of AFB1.


Aflatoxin is degraded by heated and unheated mycelia, filtrates  of homogenized mycelia and filtrates of broth cultures of Aspergillus parasiticus.

Steaming one-half of a lot of 9-day-old mycelia of Aspergillus parasiticus NRRL 2999 for 6 min resulted in little or no subsequent degradation of aflatoxin B1 or G1 by these mycelia. The other half of these mycelia was not heat-treated and degraded aflatoxins B1 and G1. Filtrates of the growth substrate which remained after the mycelium was removed from 8- to 15-day old cultures of A. parasiticus NRRL 2999 did not degrade substantial amounts of aflatoxin B1 or G1, whereas mycelia originally produced on these filtrates degraded substantial amounts of both aflatoxins. The supernatant fluid from homogenates of 9-day-old mycelia of A. parasiticus NRRL 2999 degraded aflatoxins B1 and G1 when 0.1 M or 1.0 M phosphate buffer, pH 6.5, was used to suspend the homogenate. These data support the hypothesis that the aflatoxin degrading factor(s) present in the mycelium of A. parasiticus is/are enzyme(s) or at least influenced by enzyme(s).


Nucleotide sequence of bacteriophage G4 DNA.

The 5,577 nucleotide long sequence of bacteriophage G4 DNA has been determined using the 'plus and minus' and chain termination methods of DNA sequencing. This sequence has been compared with that of the closely related bacteriophage phiX174 (refs 1, 55). In the coding regions there is an average of 33.1% nucleotide sequence differences between the two genomes, but the distribution of these changes is not random and the sequence of some genes is more conserved than others. There is less sequence similarity between the untranslated intergenic regions of G4 and phiX174, but despite this the sequences of the J/F, F/G and H/A untranslated spaces in both genomes have similar sized hairpin loops, which may be related to their function.


Effect of phentolamine, alprenolol and prenylamine on maximum rate of rise of action potential in guinea-pig papillary muscles.

Effects of phentolamine (13.3, 26.5 and 53.0 micron), alprenolol (3.5, 7.0 and 17.5 micron) and prenylamine (2.4, 4.8 and 11.9 micron) on the transmembrane potential were studied in isolated guinea-pig papillary muscles, superfused with Tyrode's solution. 1. Phentolamine, alprenolol and prenylamine reduced the maximum rate of rise of action potential (.Vmax) dose-dependently. Higher concentrations of phentolamine and prenylamine caused a loss of plateau in a majority of the preparations. Resting potential was not altered by any of the drugs. Readmittance of drug-free Tyrode's solution reversed these changes induced by 13.3 micron of phentolamine and all conconcentrations of alprenolol almost completely but those induced by higher concentrations of phentolamine and all concentrations of prenylamine only slightly. 2. .Vmax at steady state was increased with decreasing driving frequencies (0.5 and 0.25 Hz) and was decreased with increasing ones (2--5 Hz) in comparison with that at 1 Hz. Such changes were all exaggerated by the above drugs, particularly by prenylamine. 3. Prenylamine and, to a lesser degree, phentolamine and alprenolol delayed dose-dependently the recovery process of .Vmax in premature responses. 4. .Vmax in the first response after interruption of stimulation recovered toward the predrug value in the presence of the above three drugs. The time constants of recovery process ranged between 10.5 and 15.0s for phentolamine, between 4.5 and 15.5s for alprenolol. The time constant of the main component was estimated to be approximately 2s for the recovery process with prenylamine. 5. On the basis of the model recently proposed by Hondeghem and Katzung (1977), it is suggested that the drug molecules associate with the open sodium channels and dissociated slowly from the closed channels and that the inactivation parameter in the drug-associated channels is shifted in the hyperpolarizing direction.


Absence of a relationship between sympathetic neuronal activity and turnover of serum dopamine-beta-hydroxylase.

The effects of pharmacological alteration of adrenergic transmission on the rate of entrance of dopamine-beta-hydroxylase (DBH) into the circulation were assessed in rats by an immunological method in which the kinetics of recovery of serum DBH activity were measured after depletion of the enzyme by treatment with anti-rat DBH antiserum. Neither alpha-receptor blockade with phenoxybenzamine nor ganglionic blockade with clorisondamine altered the rate by which DBH enters the bloodstream although both treatments markedly altered serum catecholamine levels. Prolonged treatment of newborn rats with guanethidine produced a severe peripheral sympathectomy but only a moderate decrease (30%) in serum DBH levels. In the sympathectomized rats, the rate of entrance of DBH into the circulation was significantly reduced whereas the half-life and rate of degradation of the enzyme was unchanged. These results indicate that the major portion of serum DBH does not enter the circulation by means of exocytotic release of the soluble enzyme.


Evidence for glucagon-releasing activity of vasoactive adenosine analogues in the conscious dog.

An investigation was carried out in conscious dogs concerning the effects of three adenosine derivatives substituted at the 5'-(744-96) or 2'-, 3'-, and 5'-positions (744-98, 744-99), with pronounced and long-lasting coronary dilator activity, on glucagon release. All three compounds (10 microgram/kg i.v.) induced a sustained increase in plasma glucose and a decrease in plasma FFA concentration; concomitantly, plasma glucagon levels rose 2--3 fold. Changes in plasma insulin concentration were relatively small and of no statistical significance. A simultaneous fall in arterial blood pressure was also observed. A lowering of blood pressure of similar magnitude by sodium nitroprusside infusion in control experiments failed to show any significant effect on plasma glucagon level. These results point to a specific effect of vasoactive adenosine derivatives on glucagon release.


Effects of GABA, dopamine, and substance P on the release of newly synthesized 3H-5-hydroxytryptamine from rat substantia nigra in vitro.

The effects of GABA, substance P and dopamine on the release of newly synthesized 3H-5-HT were investigated, using slices of rat substantia nigra superfused with L-3H-tryptophan in vitro. GABA (50 micron) had no inhibitory effect on the potassium-evoked-release of 3H-5-HT. Substance P (50 micron) and eledoisin (50 micron) stimulated the spontaneous release of 3H-5-HT. This effect seems to be indirect and is possibly mediated by dopaminergic neurones, since the dopamine antagonist drug alpha-flupenthixol (1 micron) abolished the substance P-evoked release of 5-HT. Furthermore, it was found that substance P (10 micron) stimulated 3H-dopamine release from nigral slices in vitro and the dopaminergic agonist apomorphine (50 micron) also stimulated 3H-5-HT release. Substance P may, therefore, activate nigral dopaminergic neurones which then release dopamine from their dendrites. The release of dopamine may in turn stimulate 5-HT release from terminals of the raphe-nigral pathway.


Renal handling of oxalate. A micropuncture study in the rat.

Clearance and micropuncture experiments were performed in rats to study the renal handling of oxalate. The 14C-oxalate to 3H-inulin clearance ratio (Cox/Cin) was 1.36 +/- 0.04 and was lowered by probenecid (200 mg/kg) to 1.11 +/- 0.03 (+/- S.E., n = 6, P less than 0.005). An attempt was made to localize the assumed secretion of oxalate in three different micropuncture protocols. In free flow micropuncture experiments single nephron clearance of oxalate was not different when obtained from proximal or distal tubular puncture sites. The fractional delivery of oxalate averaged 0.84 +/- 0.03 regardless of the puncture site from mid-proximal to late distal. This finding indicates a net outflux of oxalate in an early proximal loop since oxalate is freely ultrafilterable. In microperfusion experiments the mean recovery of oxalate ranged from 79--90%. The outflux of oxalate correlated linearly with the tubular load (r = 0.95). The results suggest that no net secretion occurs in superficial nephron segments accessible for micropuncture. Since whole kidney clearances of oxalate always exceeded glomerular filtration rate, it is concluded that net addition of oxalate into the tubular fluid can occur at sites beyond the superficial late distal tubules or is due to higher delivery of oxalate by deep cortical nephrons.


Effects of ozolinone, a diuretic active metabolite of etozoline, on renal function. I. Clearance studies in dogs.

The renal action of 3-methyl-4-oxo-5-piperidino-thiazolidine-2-ylidine (ozolinone), a metabolite of the diuretic etozoline (Elkapin), was studied in anaesthetized dogs after i.v. injection and compared with the renal effects of furosemide. The diuretic action of ozolinone was rapid in onset and of short duration. The smallest effective i.v. dose was 1 mg . kg-1. Maximal diuretic capacity was reached at 50 mg . kg-1 i.v. Fractional tubular sodium reabsorption was depressed to 67% at maximal effective doses. Ozolinone had similar renal actions to those of furosemide. Like furosemide, ozolinone increased renal blood flow, slightly decreased glomerular filtration rate, depressed tubular chloride reabsorption more than sodium reabsorption, increased potassium excretion, lowered the pH of urine, decreased urinary osmolarity towards isotonicity and depressed tubular PAH secretion. As regards the effective doses and the maximal changes of tubular sodium excretion, ozolinone was somewhat less potent than furosemide.


Differential inhibition of biphenyl hydroxylation in perfused rat liver.

A differential inhibition of biphenyl hydroxylation by alpha-naphthoflavone and metyrapone was observed in isolated perfused rat liver. alpha-Naphthoflavone inhibited 2- and 4-hydroxylation in livers from beta-naphthoflavone-pretreated animals but had no effect on both reactions in livers from phenobarbital-pretreated animals. Metyrapone inhibited 2- and 4-hydroxylation in phenobarbital-stimulated livers, but only insignificant inhibition of 2-hydroxylation and a slight enhancement of 4-hydroxylation by metyrapone was observed in beta-naphthoflavone-stimulated livers. Conjugation of 2-hydroxybiphenyl and 4-hydroxybiphenyl by isolated perfused livers was also studied. 4-Hydroxybiphenyl preferentially formed sulphates in livers from untreated animals but after induction glucuronidation was as effective as sulphation or even exceeded sulphation. Only glucuronic acid conjugates of 2-hydroxybiphenyl were detected.


Inhibitory effects of 4,4'-diisothiocyano stilbene-2,2'-disulfonic acid (DIDS) in the response of isolated hepatocytes to phalloidin.

4,4'-Diisothiocyano stilbene-2,2'-disulfonic acid (DIDS) inhibits the typical development of protrusions, regularly seen after treatment of isolated hepatocytes with phalloidin. The degree of inhibition depends on the time of preincubation and on the concentration of DIDS, but not on the concentration of phalloidin. DIDS is more effective than H2DIDS. The inhibition by both compounds is irreversible. The binding capacity of hepatocytes for H2DIDS is much higher than that of the phalloidin-insensitive hepatoma cells. Gel electrophoresis of lysates from cells, pretreated with 3H2DIDS demonstrates that actin binds very little of the inhibitor. Our results suggest that a protein structure on the surface of hepatocytes, needed for the response to phalloidin, is influenced by DIDS or H2DIDS.


A benzodiazepine derivative and praziquantel: effects on musculature of Schistosoma mansoni and Schistosoma japonicum.

The benzodiazepine derivative (Ro 11-3128) which has central nervous effects similar to other benzodiazepines, and praziquantel (PZ), are two new antischistosomal drugs. At low concentrations these drugs will produce a marked spastic paralysis of male Schistosoma mansoni musculature. An analysis of the action of these drugs on the parasite's musculature shows that Ro 11-3128 and PZ produced a rapid rise in the tension of the musculature of male schistosomes. Various compounds known to interact with the schistosome's neuroreceptive sites did not block of potentiate the action of these drugs. Removal of Ca2+ or addition of Mg2+ to the incubation medium blocked the action of these drugs on the schistosome's musculature. Uptake studies of inorganic cations by male schistosome's indicate that Ro 11-3128 and PZ decrease the influx of K+ but stimulate the influx of Ca2+ and Na+ into the male schistosome. It is suggested that this interference with inorganic ion transport mechanisms causes the contraction of the schistosome musculature.


A proposed mechanism for reduced creatinine excretion in severe chronic renal failure.

Creatinine appearance, defined as the sum of daily creatinine excretion in urine (average over 5 days) plus accumulation in body water, measured over the same interval, was calculated in 27 patients with severe chronic renal failure (creatinine clearance less than 0.15 liter/kg/day). Creatinine appearance per kg body weight in patients with the lowest clearances decreased to values as low as one third of values predicted from age and sex. The absolute value of measured cratinine accumulation was only 11 +/- 2% of creatinine appearance and thus could not account for such deficits in appearance and therefore renal excretion. One explanation for these results is that extrarenal clearance, CM, remains constant, that is, that the quantity of creatinine degraded, M, is proportional to serum creatinine, S: CM = M/S. When the values for extrarenal clearance necessary to account for the measured deficit in creatinine appearance were calculated, they were found to be quite constant: 0.042 +/- 0.004 liter/kg/day (SEM, n=13) in males and 0.041 +/- 0.004 liter/kg/day (SEM, n=14) in females. Renal creatinine clearance in these patients, predicted from age, sex, serum creatinine, and the assumed constant value for extrarenal clearance, corresponded closely to observed clearance (r = 0.93). From these calculations, decreased creatinine appearance (and excretion) of uremic patients may be explained by a constant extrarenal clearance, indicating degradation.


Sweating treatment for chronic renal failure.

Sweating was induced in 3 uremic patients in an ordinary bathtub for 3 h per day to examine whether clinically significant amounts of urea could be removed. Blood urea concentrations fell in all 3 patients, and 2 of the patients had improvement in uremic syptoms. Clearances of urea by a forearm collection technique in 2 patients were 20.9 +/- 3.7 and 11.6 +/- 3.9 ml/min. Average sweat volumes were 813 +/- 62 and 566 +/- 160 ml/h. Sodium concentrations were 52 +/- 47 and 76 +/- 12 mEq/l. This removal of urea, water and salt suggests that sweating could be used to treat uremia in conjunction with charcoal hemoperfusion, in patients awaiting vascular access, or during the interdialytic interval in patients with problems with overhydration.


The renin-aldosterone system and thiazide-induced depletion of total body potassium in essential hypertension.

15 patients who had benign, uncomplicated essential hypertension, were treated with chlorthiazide (500 mg twice a day) with or without propranolol (10--20 mg 4 times a day), and the effect of the treatment on plasma renin activity (PRA), urinary aldosterone excretion, total body potassium (TBK) and plasma sodium and potassium was evaluated. TBK depletion was significant mathematically (more than 5% of TBK lost) in 7 patients, but not significant physiologically (less than 15% of TBK lost) in any except in one, who may have had other reason for TBK depletion. Although propranolol prevented the increase in PRA and aldosterone excretion, it did not prevent the modest TBK depletion. Dietary potassium intake may have some importance in the maintenance of normal body potassium during chronic treatment with thiazides for hypertension.


Some hemodynamic and hydroelectrolytic alterations of chronic salt deprivation.

Male Wistar rats were fed for 1 month on a low salt diet and compared with control animals. The body fluids are decreased, and this diminution takes place due to the decrease of the total water, extracellular space, intracellular space, plasma volume and interstitial liquid. In the muscle, the alterations in the water composition were similar to the modifications observed in the whole animal. The electrolytic composition of the muscle showed a decrease in the sodium content; no modifications were found in the chloride content and there was a slight decrease in the potassium content. The cardiac rate was increased and the arterial pressure and heart weight also showed a slight augmentation. The infusion of antibodies against angiotensin II provoked a similar decrease in arterial pressure in both groups of animals. These results show an alteration of the hydroelectrolytic metabolism in salt-deprived rats and that the circulatory function is adapted to this new situation.


Peritoneal dialysis clearances. A practical approach to the measurement of small- and middle-molecule clearances.

This study was designed to (1) develop a simple technique of estimating 'middle-molecule' clearances in peritoneal dialysis patients using vitamin B12 as a marker; (2) evaluate changes in small- and middle-molecule clearances during a single 24- or 36-hour peritoneal dialysis, and (3) determine if using 4.25% rather than 1.5% dextrose exchanges alters the clearances of small and middle molecules. Measurement of clearance following the intramuscular injection of vitamin B12 was found to be a reliable method of estimating the clearance of middle molecules. Small- and middle-molecule clearances remain constant throughout an individual 24- or 36-hour dialysis. In addition, small-molecule clearances increase significantly with 4.25% dextrose dialysate but return to prior values when 1.5% dextrose dialysate is reinstituted.


Influence of ultrafiltration on plasma renin activity and adrenergic system.

The influence of efficient ultrafiltration without dialysis fluid was compared to the standard dialysis technique in two groups of 4 patients with chronic renal failure on maintenance haemodialysis. Supine plasma renin activity (PRA), plasma concentration of noradrenaline (NA), and adrenaline (A) and the Valsalva manoeuvre were determined before and after the period of ultrafiltration at the beginning and at the end of the experiment. The behaviour of these parameters was related to changes of blood pressure and body weight. The rapid weight loss was well tolerated during ultrafiltration only, with a significant increase of plasma catecholamines concentration; in contrast, patients treated with ultrafiltration and dialysis showed no significant increase of NA and A levels and they frequently became hypotensive. No relationship was observed between changes in PRA and those in body weight and blood pressure. Our data suggest that rapid removal of catecholamines during standard dialysis hinders the compensatory increase of the adrenergic activity and is responsible for hypotension.


Juxtaglomerular cell tumor.

A 15-year-old female with primary reninism presented with benign hypertension, normokalemia, normal aortagram and normal intravenous pyelogram. The diagnosis was suggested only by a remarkably elevated plasma renin activity (PRA). Selective catheterization of renal vein branches was necessary to make the diagnosis of a tumor. A local resection of the tumor resulted in normalization of blood pressure and PRA. Prior to the definitive surgery, oral propranolol was effective in lowering PRA and blood pressure.


Acute effects of salmon calcitonin on renal electrolyte excretion in intact, thyroparathyroidectomized and sulfacetylthiazole-induced uremic rats.

Acute effects of salmon calcitonin (CT) on renal electrolyte excretion were investigated in intact, thyroparathyroidectomized (TPTX) and uremic rats. Glomerular filtration rate did not change during CT infusion and there was no volume expansion in any experimental group. Plasma calcium levels gradually fell below the control period in each experimental group. Urinary calcium excretion increased at the early period in both intact and TPTX rats but fell below the control period with the continuous infusion of CT. In uremic rats, a decrease in plasma calcium was followed by a decrease in calcium excretion. Plasma phosphate gradually decreased and simultaneously measured phosphate excretion increased in both intact and TPTX rats. In uremic rats, however, there was no change in phosphate excretion and only a slight decrease of plasma phosphate. Phosphaturia is the result of the predominant renal action of CT and occurs even when the filtered load of phosphate decreases. In uremic animals, there appears to be a resistance to exogenous CT which manifests itself by the absence of natriuretic, calciuric and phosphaturic responses.


Effect of prostaglandin A2 on RNA synthesis in embrionic mouse erythroid cells.

Prostaglandin A2 (PGA2) is shown to stimulate RNA synthesis in 12-day embryonic mouse liver cells, thus expressing an erythropoietin-like effect. This effect was found to be dose-dependent. There was no significant difference between the results observed with patients' plasma before and after dialysis and with or without addition of PGA2. Although the baseline activity of RNA synthesis in the presence of uremic plasma is less than that with normal plasma, the almost equal potentiation of RNA synthesis in erythroid cells incubated with both normal and uremic plasma obtained with PGA2 favors a direct, and not an erythropoietin-mediated, effect of this substance.


[Glucose, pyruvate and lactate concentrations in the cerebrospinal fluid in patients with cerebral infarction].

The determinations were performed in cerebrospinal fluid of 50 patients with recent cerebral infarction in the 1-st, 3-rd and 10-th day of disease. Spectrophotometrie methods were used for the determination of lactate and pyruvate and a colorimetric method for glucose determination. A statistically significant increase of glucose in the cerebrospinal fluid on the 1-st day after cerebral infarction and of pyruvate, lactate and lactate: pyruvate index on 1-st and 3-rd day after cerebral infarction was found. The results obtained point to intensification of the anaerobic pathway of glucose metabolism.


[Blastic transformation test in vascular diseases of the central nervous system].

The reported investigations were carried out in 99 cases. In 73 cases acute vascular diseases of the central nervous system were recognized, and 26 subjects served for control. In all cases the test of PHA-stimulated blastic transformation of the blastic index suggest reduced resistance of the organism and they may be group of patients was compared with the control group. The quantitative data were analysed statistically using the test of Student and the t T test of Student for paired samples. The obtained results showed that the proportion of lymphocytes undergoing blastic transformation after stimulation with PHA was in the control group 66.1% on the average, while in the group of patients it was decreased to 55.2%. These differences were significant statistically. The low values of the blastic index suggest reduced resistance of the organism and they may be used as a valuable indicator informing about the resistance of the patient.


[Statistical analysis of mortality from stroke in hospitalized patients].

The authors analysed mortality from brain strokes in 1366 patients hospitalized at the Department of Neurology, Silesian Medical Academy in Katowice and Zabrze and in the 8th Municipal Hospital in Katowice in the years 1970--1974. The number of cases with lethal outcome was 437. The mortality was highest in cases of cerebral haemorrhages, particularly in women. The mortality increased with increasing age and was highest in the first 24 hours of treatment.


[Cervical discopathy, cervical migraine and vertebrobasilar arterial insufficiency: Clinical correlations].

The pathogenesis of cervical migraine may suggest that a connection exists between it and cervical discopathy and also vertebrobasilar arterial insufficiency. This correlation was studied in a group of 103 patients subjected to clinical observations. In 83 of them cervical discopathy was found, in 69 cervical migraine and in 40 vertebrobasilar insufficiency were present. Among those with discopathy migraine was present in 63.6% of cases, and vertebrobasilar insufficiency in 31%. In patients with cervical migraine degenerative changes of the type of cervical discopathy were present in 90% of cases, although in only 56.5% of cases clinical signs were present connected with these changes. Vertebrobasilar insufficiency was present in 45% of patients with cervical migraine, that is more frequently than in discopathy. In the group with vertebrobasilar insufficiency radiological changes in the cervical spine were present in 77.5% of cases and the same proportion of patients in this group had cervical migraine. These numbers confirm the connection between cervical migraine and radiological changes and clinical manifestations of discopathy, and they indicate also that cervical migraine may be a successive stage of vascular changes leading to circulatory failure in the area supplied by vertebral arteries. This failure may have a different course and pathological mechanism. In 12.5% of patients in this group no cervical migraine or radiological changes were demonstrated. The term "cervical migraine" seems inappropriate since this type of headache has another substrate and mechanism than true migraine.


[Therapeutic efficacy of pyridinolcarbamate (Anginin) in patients with combined cerebral and peripheral arteriosclerosis].

A group of 20 patients (average age 55.5 yrs) with advanced arterioscleorosis obliterans and cerebral thrombosis were treated with pyridinolcarbamate. Anginin was given for 6 months, 1,5--2 g. per day. Observation period before, during and after the treatment lasted 2 yrs. Medical and psychological examinations were performed; laboratory test included: sphigmooscylography, photoplethysmography, EKG, EEG, cholesterol, triglyceridis and other routine biochemical blood tests. All data are statistically evaluated. Results. During Anginin treatment clinical improvement was noted in 8 cases, in 9 there was no change in neurological examination; 3 cases--deteriorated. Control examination 6 to 12 months after discontinuation of the treatment revealed no changes in 13 patients; 1 patient deteriorated and 6--died. There was improvement in blood circulation as shown by plethysmography and sphigmooscylography in patients with less advanced vascular changes and no change in cases with more advanced disease. In 75% of the patients there was statistically significant (p less than 0.001) decrease of cholesterol and in 50% of triglicerids (not statistically significant). In patients with advanced disease there was no clinical and EEG improvement, on the contrary 1/3 of them deteriorated clinically and in EEG. In cases with less advanced disease clinical improvement was recorded. Anginin seems to be a good drug for patients with moderately advanced combined peripheral and central arteriosclerosis.


[Lithium treatment of chronic Horton's headaches].

The authors used lithium carbonate in treatment of 7 patients with Horton's headaches of primarily or secondarily chronic character. In all patients the blood level of lithium was determined and it was found to reach therapeutic levels. Disappearance of attacks was achieved in 3 cases, significant improvement in 2, and in 2 cases treatment was ineffective. The mechanism of lithium action in this disease is discussed. The authors recommend lithium as worthy of use since other drugs are ineffective in this disease or they cannot be used, eg. steroids or indomethacin, in view of frequent coexistence of paptic ulcer.


[Effect of phenytoin on peripheral motor neurons].

The author reports the results of investigations on the effect of Phenytoin Polfa on the peripheral motor neuron in relation to the serum drug levels. The investigated group included 42 epileptics treated for 7 to 30 years with phenytoin in daily doses of 300--400 mg. In all cases neurological examination was done, the serum phenytoin level was determined, basic EMG investigation, conduction velocity measurement in motor fibres of peripheral nerves, and stimulation test for disclosing myasthenic fatiguability were performed. In the conclusion the author states that phenytoin in the doses used caused no changes in conduction velocity in the motor fibres. Changes suggesting possible lesion of the peripheral motor neuron were found in only 7.1% of basic EMG records. Evidence of fatiguability in stimulation test was found in 28.6% of cases, they were not correlated with the serum drug level duration of treatment, subjective changes and objective findings.


[Changes in cerebrospinal fluid protein concentration in children following surgery for cerebellar medulloblastoma].

In 10 children after operations for cerebellar medulloblastoma treated with intrathecal injections of methotrexate changes were studied in the concentration of total protein in the cerebrospinal fluid and in different electrophoretic fractions of proteins. The investigations were begun 1 to 3 months after the operation and were continued usually at monthly time intervals. In each child considerable variations were observed in the concentration of total protein as well as in the proportions of protein electrophoretic fractions in the period of treatment lasting from 14 to 59 months after the operation. Significant individual variations were observed also in the level of total protein fractions pattern in the cerebrospinal fluid. Out of 116 electrophorograms in 42 the protein fraction pattern in the cerebrospinal fluid approached very much that found in patients with cerebellar medulloblastoma before the operation, with a significant rise in the proportion of albumins. The origin of cerebrospinal fluid proteins is discussed.


[Anti-epileptic and side effects of Didepil].

The action of the new antiepileptic preparation Didepil which is a combination of the anticholinergic agent procyclidine (dl-1-cyclohexyl-1-phenyl-3-pyrolidinopropane-1-ol hydrochloride) with phenobarbitone was evaluated in a group of 20 patients of either sex, mean age 28.5 years. These patients had mostly (14 cases) two types of seizures occurring up to several times daily. The mean duration of epilepsy was 12.5 years, the aetiology of the disease was different, and the patients were usually refractory to previously used drugs. Didepil was administered during 3 months, on the average, in doses of 3--4 tablets daily as the only antiepileptic drug or in combination with other anticonvulsants. The duration of follow-up of the patients before, during and after treatment was from 6 to 15 months. In each repeated EEG investigations, biochemical investigation of the blood, liver function tests, and urine analysis were performed. improvement was observed in cases of grand mal as well as temporal lobe seizures in 70% of patients, EEG improvement was found in 50% of patients. Side effects including oral dryness, accomodation disturbances developed in 17 patients but were usually slight and transient, in only 4 cases they were sufficiently severe as to justify reduction of dosage. Improvement of mood and contact with surroundings was noted in 60% of cases. Didepil seems to be an effective antiepileptic agent in maximal generalized seizures as well as in temporal lobe seizures.


[Cerebral bioelectrical activity disorders in acute hydrazine poisoning].

The authors report changes in the bioelectric activity of the brain in acute, severe, suicidal poisoning with hydrazide. The observed group comprised 10 patients, 9 were admitted in coma, 7 had convulsions. Normal EEG tracing was found in a case of combined poisoning with hydrazide and diazepam. Low-voltage tracings with a tendency for bioelectric inactivity development were observed in 2 cases with lethal outcome. In the remaining cases high-grade diffuse changes were present, in three of them seizure activity was present additionally. Full evolution of bioelectric changes was observed in 5 patients. The time of return of normal activity ranged from several days to several weeks. Very slow improvement with incomplete normalization was found in mixed intoxication (hydrazide, barbiturates) treated with haemodialysis. The authors think that in cases with persistence of EEG changes despite regression of acute signs of poisoning intensive treatment with vitamins B should be continued.


[Value of rheographic studies in the diagnosis of epileptogenic foci in temporal lobe epilepsy].

Using a type II Siemens rheograph 100 patients with temporal lobe epilepsy aged 18--36 years were investigated. In each case rheographic investigation was done in sitting and lying position, at rest and after hyperventilation in both these positions. The shape of the descending arm of the main wave of the averaged rheoencephalographic curve was analysed in detail. In 89 cases unilateral presence of h1 wave was found, which was absent in the rheograms of healthy subjects, and h2 wave was present also. The shape of the remaining rheographic curves in this population was not different from the records obtained in healthy subjects. In 92 patients EEG investigations demonstrated focal changes were found, in 8 bilateral changes were present, prevalent on one side. In 85 cases h waves were present on the side of the epileptogenic focus, and in 4 cases it was present contralaterally but only in patients with bilateral EEG changes. The results of these investigations point to differences in the haemodynamic conditions in the temporal lobes in healthy subjects and in most patients with temporal lobe epilepsy on the side of the epileptogenic focus. Rheographic investigations was found to be useful for determination of the side of the epileptogenic focus.


[Changes in cerebrospinal fluid pressure in patients with hydrocephalus of various intensities].

In 12 patients with hydrocephalus caused by posterior fossa tumours continuous measurements of intraventricular CSFP were done before and after implantation of ventriculoatrial valve and after tumour removal. A fall of the mean CSFP from 31.57 mm Hg to 15.32 mm Hg was observed after valve implantation, and a further fall of the mean CSFP to 10.55 mm Hg after removal of the tumour. After valve implantation pathological A and B waves disappeared. Absence of improvement after different stages of treatment indicated poor functioning of the valve, but it was observed also in patients with inoperable tumours.


[Isolated temporary pharyngeal paralysis in childhood. Viral neuroinfection with a mild course?].

The authors describe a boy aged 14 years who had identical signs as those described in 1976 in cases of isolated temporary pharyngeal paralysis (Edin et al). In this syndrome Sullivan and Carlson (1976) observed a rise in the titre of antibodies to Herpes simplex virus, and Nussey (1977) found in it infection caused by Coxsackie type A9 virus. In the presently reported case full serological and virological investigations were not done.


[Short-lived semi-atrophy of the tongue].

The author describes a 47-year-old patient in whom lingual hemiatrophy developed one month after angina. The development of hemiatrophy was preceded by occipital headaches and pain behind the ear on the side of hemiatrophy. In the differential diagnosis the author excluded inflammatory processes neoplasms and developmental anomalies and thinks that the cause of this short-lasting hemiatrophy might have been tonsillitis with compression of the nerve by the oedematous inflamed tissues with action of bacterial toxins on the nerve.


[Myeloscintigraphic findings in a case of intradural leptomeningeal cyst].

The authors report the application of myeloscintigraphy in a case of intradural leptomeningeal cyst. Only 16 such cases have been described as yet in world literature. Myeloscintigraphy was found in this case a more objective and accurate method than myelography and permitted not only the compressing mass to be recognized but it determined also the upper and lower limits of the mass which is important for surgical intervention.


[Case of subdural hygroma].

A 7-month-old boy with postnatal jaundice was operated upon at the age of 3 months for hypertrophic pyloric stenosis associated with water and electrolyte metabolism disturbances. During induction of anaesthesia cardiorespiratory arrest occurred. The child was resuscitated successfully. After the operation bilateral pneumonia developed. After 3 months of relatively good health signs of increased intracranial pressure developed with high-grade papilloedema. Ventriculography with subdurography demonstrated presence of an extensive subdural hygroma about 2 cm thick. One year after treatment the condition of the child and his development are completely satisfactory.


[Case of hemiphlegic migraine with atypical angiographic findings].

Hemiplegic migraine was observed in a boy aged 16 years. The family history was unquestionable and the duration of hemiplegia was prolonged. Carotid angiography after regression of clinical signs showed a particularly profuse passage of the contrast to the contralateral side and to the area of vascularization of the basilar artery. It is supposed that particularly favourable connections existed in this case in the arterial vascular bed of the brain, with possible hypotonia of the arterial walls in this area.


[A case of giant aneurysm at the posterior cerebral artery (author's transl)].

Giant aneurysm of the posterior cerebral artery was very rare. The authors could seek only 6 cases in published literature. We experienced one case of the giant aneurysm at the posterior cerebral artery. The case was 25 years old female. She occasionaly complained of headache and nausea for 4 years before administration. Cerebral angiogram revealed a giant aneurysm of the right posterior cerebral artery with slightly dilated ventricle. CT scan revealed a ring shape high density area and its high density area enhanced by Conray infusion. A clipping of posterior cerebral artery at the just proximal point of the aneurysmal neck was done, because adhesion of the aneurysm to the brain stem was very tight and the aneurysmal neck was very broad. After the operation, giant aneurysm was not seen on both angiogram and CT scan. Patient did not complain of headache any more and any defect of the visual field.


[Surgical treatment of upper cervical chordoma (author's transl)].

Treatment of upper cervical chordoma is generally considered to be difficult one, because of serious troubles in supporting cranio-spinal junction after the surgery and at the recurrence. Clinical course of a 22-year-old man with chordoma originated from C2 vertebral body was reported, and the operation for such a condition were discussed with emphasis on the mode of craniovertebral fixation. Simple subtotal removal of the vertebral chordoma was carried out by posterior approach at the first operation. The second one was necessary fourteen months later for recurrence of the tumor. At the second surgery, in addition to the tumor removal, posterior fusion between the occipital bone and the C4 lamina was performed with homologous iliac bone graft, the center of which was kept slightly lateral to the lesion. This procedure of fixation not only enabled a sufficient removal of the residual tumor without loosening the bone graft, but also shortened the bedridden time following the subsequent operations for the recurrence, and finally resulted in an excellent recovery in his clinical symptoms. It is considered to be important to select the most adequate approach of surgery, including fixation technique, according to the extension of the tumor. We would emphasize the usefulness of paramedian posterior fusion of the cranio-spinal junction for such a condition of wide tumor invasion in the high cervical region.


[Brain metastases from primary cardiac myxosarcoma--report of a case (author's transl)].

A very rare case of a myxosarcoma with metastases to the brain is reported. A 33-year-old female was admitted to our hospital because of lassitude, fever, slight left hemiparesis, headache and other signs of intracranial hypertension and cardiac symptoms such as dyspnea and palpitation. She had the cardiac symptoms once 14 years before, which reappeared and rapidly aggravated two months before the admission. Cerebral angiography revealed a mass in the right temporal lobe and physical and laboratory examinations revealed mitral value failure and hyperthyroidism. On the next day, March 19, 1976, a grossly cystic 60 gm tumor was totally removed which was largely imbedded in the subcortex of the right temporal lobe. The symptoms except for the cardiac symptoms and disseminated intravascular coagulopathy rapidly improved, but headache and left hemiparesis returned 13 days postoperatively. She died suddenly 18 days after the operation due to acute cardiac failure. Autopsy revealed two separate hard and solid tumors both attached to the mitral valve and occupied the whole left atrium and another metastasis to the frontal lobe which had not been diagnosed before the death. Microscopic examinations including electronmicroscopic study established the diagnosis of myxosarcoma in all the four tumors.


Immunosuppressive therapy in chronic liver disease.

Immunosuppressive treatment with prednisolone and/or azathioprine has been assessed in three chronic liver diseases with immunological features, namely chronic active hepatitis, cryptogenic cirrhosis and primary biliary cirrhosis. In chronic active hepatitis, controlled prospective clinical trials have shown clinical, biochemical and hepatic histological improvement when prednisolone with or without azathioprine is employed. Azathioprine alone has no advantage over placebo tablets. Cirrhosis is probably not prevented. Selection of patients for treatment, the response and therapeutic regimes are discussed. Patients with hepatitis B surface antigen positive chronic active hepatitis have a worse therapeutic response than those patients with chronic active hepatitis who are HBsAg negative. In primary biliary cirrhosis, corticosteroid treatment is contra-indicated on account of bone thinning. Azathioprine has been used in controlled clinical trials and is of only marginal benefit.


[Immunodepressive therapy of hemoblastosis].

If the Burnet's hypothesis of the antieoplastic "immunological surveillance" is strictly interpreted, it would result unappropriate to speak of "immunosuppressive therapy" in malignant hemoblastoses and allied neoplastic diseases, although the treatment of such affections consists of the administration of mostly immune system-depressing agent. Such an effect is strictly associated with the antiproliferative and cytotoxic action. Thus, according such theories, consequent immunological depression should be considered as an "unwanted effect" related to a treatment that had been started for quite different purposes. Neverthelese recent medical literature reports several works which seem to evidence the immunological barrier insufficiency against neoplastic illnesses. Thus the above mentioned theories have been often criticized. After such considerations the Author emphasizes that also the treatment now used in some chronic lymphatic affections may be considered as an immune system depressing cure. The same is true for drugs used against autoimmune occurrences observed during malignant hemoblastoses. In a next future such a treatment will be in all probability followed more extensively, if more specific anti-lymphocyte drugs will be discovered, and in relation with recent attempts of transplantating normal bone marrow into leukaemic patients.


[Gas chromatographic determination of urinary 17-ketosteroids in normal adults of various ages].

The excretion of individual urinary 17-ketosteroids, pregnanediol and pregnanetriol, as measured in 98 healthy adults subdivided into groups according to age and sex, by means of a gas chromatographic analysis method based on enzymatic hydrolysis, extraction with ethyl ether, and conversion of the extracted steroids into trimethylsilyl ethers. The results showed that age and sex substantially influence the steroid pattern. Metabolites with 5-alpha configuration are predominant in young subjects; those with 5-beta configuration are pre-eminent in the more advanced ages, particularly in women. Metabolites with definite androgenous significance (C19O2-17KS) decline rapidly with advancing age, while the C19O3-17KS undergo a lesser decrease.


[Angioimmunoblastic lymphadenopathy with dysproteinemia. Clinical case report].

The clinico-histologico-biological picture of a recently identified haematological condition distinguished by marked superficial generalized adenomegaly, a typical lymph node biopsy report (lively immunoblastic and angioblastic proliferation, deposits of PAS-positive eosinophil homogenous material) and hypergammaglobulinaemia (polyclonal gammopathy) and defined as angio-immunoblastic lymphadenopathy with dysproteinaemia, is described. On the basis of numerous reported cases and the clinical case in question, the pathogenetic interpretation whereby the condition is considered as a reaction in similar fashion to what is already known for the so-called GvHr (transplant to host reaction), independently of the as yet unknown and perhaps many-sided aetiological factor, is upheld. The condition is substantially benign, although the possibility that it will become malignant cannot be excluded. It is highly sensitive to radiant, cytostatic and cortiocosteroid therapy although there are profound prognostic reservations about its great susceptibility to infections, particularly at respiratory level.


[Pharmacokinetic and clinical research on a new aminoglycoside antibiotic: sisomicin].

Results obtained with sisomycin in 10 cases of purulent meningitis and 4 of bronchopulmonitis showed good tissue diffusion, together with CSF concentrations sufficient to inhibit the main aetiological agents in these forms: MIC 0.02 mg/ml for both D. pneumoniae (I-ATCC 6301) and N. meningitidis (C-ATCC 13101), i.e. liquor transfer of the antibiotic more than sufficient to handle these agents.


Fetal breathing movements. Characteristics and clinical significance.

Ultrasonic real-time B-mode technique was used to record fetal breathing movements (FBM) in 100 consecutively examined women in late pregnancy. During the "inspiratory" phase of the FBM cycle, the diaphragm of the fetus contracts and moves in caudal direction. The diaphragmatic movement is accompanied by a retraction of the thorax with maximum inward movement of the lower sternum and by an expansion of the fetal abdomen. During "expiration" all structures return to their initial position. The incidence of FBM found in 24 pregnancies with various disorders was significantly lower than that in the 76 uncomplicated pregnancies (P less than 0.001). In 92% of the observations in which FBM were present for more than 5 minutes within 30-minute recording, this finding indicated an unaffected pregnancy at the time of the examination. No correlation was found between the FBM results and the subsequent course and outcome of the pregnancies.


Standardization of sonar cephalometry and gestational age.

At present a large number of different charts are used for prediction of gestational age from sonar biparietal diameter (BPD). In this report the reasons for these observed differences are presented. Additionally, the usefulness of all these charts is questioned because a) the mean differences in 7059 BPDs derived by the B-scan from four large fetal population studies are not significantly different from zero and b) BPDs obtained by B scan are statistically comparable to gray-scale or real-time BPDs if medium gain is used. Thus, it is our suggestion that a chart showing the composite mean BPD values of all four studies be used universally for prediction of fetal age. Finally, the guidelines of using sonar BPD as an index of gestational age are presented and the role of the obstetrician in interpreting BPD data is emphasized.


Changes of serum immunoglobulins IgG, IgA, IgM, and IgE during pregnancy.

The serum levels of immunoglobulins at various times throughout pregnancy were measured in 11 healthy women. The concentrations of IgG, IgA, and IgM decreased significantly in the second and third trimesters, the mean decreases at the second trimester being 18, 13, and 9%, respectively. When the decreases were expressed on the basis of serum total protein, the decreases in IgG and IgA were significant but the decrease in IgM was not. The level of IgE either decreased or increased during pregnancy. Maternal age, emesis, ABO-incompatibility, and the sex and weight of the baby at birth were not related to the initial concentration or to the extent of decrease of immunoglobulins during pregnancy. In a case of Rh incompatibility, increase of immunoglobulins was observed concomitantly with the transient appearance of anti-Rh(D) antibody. Immunoglobulin depletion in pregnancy seems to result from both immune suppression and hemodilution.


Prostaglandin F2alpha levels in human ovarian plasma in pregnancy and in a case of Halban's disease.

It has been demonstrated that the ovary bearing the corpus luteum in the human is responsible for the major portion of prostaglandin F2alpha (PGF2alpha), total estrogen, and progestin production during the luteal phase of a normal menstrual cycle. This study was performed with the intent to gain more information about the secretion of PGF2alpha in conditions that prolong the life span of the corpus luteum, such as pregnancy and Halban's disease. Utilizing a specific radioimmunoassay for PGF2alpha, ovarian venous plasma levels were measured in 7 pregnant women and in a patient with Halban's disease. During the first and second trimester of pregnancy, PGF2alpha values in plasma from the active and inactive ovary were comparable and were significantly lower than concentrations in plasma from the active ovary during the luteal phase of the normal cycle. In a patient with persistent corpus luteum or Halban's disease, PGF2alpha concentrations of venous plasma from the ovary bearing the corpus luteum were significantly lower than those obtained from the contralateral ovary. These observations indirectly support the hypothesis that prostaglandins produced within the ovary may have a role in luteal regression.


Comparison of prostaglandin and hypertonic saline for termination of pregnancy.

The abortifacient efficacy and complication rate of the administration of hypertonic saline intraamniotically to 796 women were compared with those following administration of various prostaglandins by several routes to 3783 women. Intraamniotic administration of 2.5 mg 15-methyl-PGF2alpha or repeated vaginal administration of 15-methyl PGF2alpha methyl ester were both highly effective. The interval from treatment to abortion following prostaglandin administration was significantly shorter than that following hypertonic saline. The frequency of complications varied with prostaglandin compound and route of administration but was generally of the same magnitude as that following hypertonic saline administration. None of the prostaglandin-treated patients experienced epileptic seizures, and no maternal deaths occurred.


Oral contraceptive estrogen and plasma lipid levels.

Blood samples were obtained from 20 women, aged 18 to 30 years, before and during the use of selected oral contraceptives. The contraceptive preparation containing 100 microgram mestranol induced increases in triglycerides, esterified cholesterol, free cholesterol, and phospholipids. Ethinyl estradiol with norgestrol, on the other hand, tended to decrease the lipid levels, while preparations containing only 50 microgram mestranol produced no significant change in the levels of the four substances. The levels produced by each of these three preparations did not exceed the normal limits. A cyclic fluctuation was observed in the monthly cycles.


Relaxing effects of Nifedipine on the nonpregnant human uterus in vitro and in vivo.

The effects of the calcium antagonist Nifedipine were investigated on isolated human myometrium and on uterine activity in healthy women during their first menstrual days. Nifedipine (0.01-1.0 microgram/ml) had a concentration-related inhibiting effect on spontaneous activity of the myometrial strips, and relaxed preparations contracted by potassium. In vivo, Nifedipine (20-30 mg) given orally, effectively and rapidly reduced uterine activity, decreasing both amplitude and frequency of uterine contractions, and reduced basal tone. A moderate increase in heart rate and a transient facial flushing were noted, but otherwise no side effects were observed. Calcium antagonists like Nifedipine represent a new approach to the problem of relaxing the myometrium, and might be an interesting therapeutic alternative in situations where inhibition of unwanted uterine activity is desirable.


Bromocriptine. Clinical experience in the induction of pregnancy in amenorrhea-galactorrhea syndrome.

This study included a group of 50 women with amenorrhea-galactorrhea who were treated with bromocriptine (2-bromo-alpha-ergocryptine). Forty-two of these patients ovulated, and 36 conceived within 8 months of treatment. The pregnancies of 30 women reached a duration of 20 weeks or longer following ovulation induced by bromocriptine. Except in 1 case which ended in 10-week spontaneous abortion, the pregnancies of 26 patients terminated in 24 single, one twin, and one triplet births. All of the 29 newborns were healthy, and no congenital malformations were detected. The main side effects during treatment were transient constipation and nausea. Following delivery, return to pretreatment status was noted in all patients, which supports the fact that bromocriptine is not a curative agent.


Circulating pituitary-gonadal hormones in clomiphene-induced cycles.

Plasma follicle stimulating hormone (FSH) and luteinizing hormone (LH), prolactin (PRL), estradiol (E2), progesterone (P), testosterone (T), and dihydrotestosterone (DHT) were measured by radioimmunoassay in 7 patients who had ovulation induction with clomiphene citrate and human chorionic gonadotropin. Six of the 7 patients ovulated. There was higher increase in FSH than LH in 3 patients who also showed a midcycle FSH and LH peak. Plasma PRL was initially elevated in 2 patients, remained normal (less than 25 ng/ml) throughout the cycle in one patient, and showed an increase in the late luteal phase in 3 patients. Plasma E2 showed a good response at the end of clomiphene intake, with a subsequent preovulatory surge. Plasma P increased to more than 25 ng/ml in patients who ovulated and reached higher levels than in normal ovulatory cycles. Plasma T increased and decreased in a similar pattern to plasma E2 and was higher with clomiphene therapy than in the normal menstrual cycle. Plasma DHT remained similar to concentrations found in normal menstrual cycles. The findings are discussed in relation to the effect of clomiphene and these hormones on the pituitary-ovarian axis, ovulation rate, and conception rate.


Extent of columnar epithelium on the ectocervix between the ages of 1 and 13 years.

Among 103 girls between the ages of 1 year and the prepubertal period, who came to autopsy, the incidence of columnar epithelium on the ectocervix was 42.7%. The extent of this change was mostly small, exceeding 30% of the length of the ectocervix in only 9 subjects. In some girls, only areas of squamous metaplasia or residual columnar structures (glands, channels, nabothian cysts) were present. The diagnosis of columnar epithelium in photographs at low magnification or by colposcopy is least exact among older girls. Such diagnostic difficulties appear to be related mainly to the small extent of columnar epithelium and to the diminished structural difference between areas of the original squamous epithelium and the columnar epithelium on the ectocervix.


Comparison of histologic and colposcopic findings in DES-exposed females.

A study was undertaken to evaluate the histologic alterations associated with two of the most abnormal colposcopic findings, mosaicism and punctation, that are commonly found in the vaginas and cervices of young women who have been exposed prenatally to diethylstilbestrol (DES). Four-fifths of 215 biopsy specimens from 171 exposed subjects with mosaicism or punctation disclosed metaplastic squamous epithelium, the presence of which is thought to reflect the repair of vaginal adenosis and cervical ectropion. Hyperkeratosis was observed in one-fifth of the specimens and was more frequent in lesions colposcopically graded I than II. Mild dysplasia was encountered in only one specimen. The findings indicate that the presence of squamous cell dysplasia cannot be predicted by the finding of Grade I or II mosaicism or punctation in the DES-exposed female despite the fact that these abnormal colposcopic patterns are associated with dysplasia in about 10% of cases when encountered in the cervix of the unexposed woman.


Cooperative approach to the treatment of cervical cancer.

This study covers 20 years' experience in the treatment of carcinoma of the cervix. Improved results and a decreased rate of major complications are seen as a result of a cooperative approach in treatment planning and careful dosimetry. Comparisons are made with large treatment centers as well as with national survival rates. Preliminary results with improved radiotherapeutic techniques continue to show improvement in survival rates.


Renal hamartoma (angiomyolipoma) with spontaneous rupture during pregnancy.

A 25-year-old pregnant patient at term with spontaneous rupture of the kidney and massive retroperitoneal hemorrhage from a renal hamartoma is described. A discussion of the case and a brief review of the literature on this rare tumor is included.


Intestinal laceration secondary to clamping of an occult omphalocele.

An omphalocele is a congenital defect of the abdominal wall, through  which intestines and other intraabdominal organs protrude outside the abdominal cavity. The defect in the abdominal wall is covered by a translucent sac composed of peritoneum internally and amniotic membrane externally, through which the viscera can be seen. Such an anomaly is obvious and easily recognized at birth when the defect in the abdominal wall is large, but a small defect, also designated as umbilical cord hernia, is often unnoticed and may, when the cord is clamped, result in an iatrogenic laceration of the gut. We report such an encounter to alert the physician and suggest a method to prevent the iatrogenic misadventure. A careful follow-up of the child, including developmental evaluation, is presented and compared with her healthy twin. A review of the relevant literature shows that the anomaly is not rare and that there is often a delay of several days in establishing the correct diagnosis, leading to a fatal outcome in some cases.


Hilus cell tumor of the ovary and endometrial carcinoma.

A case of hilus cell tumour of the ovary was found in a patient with adenocarcinoma of the endometrium, the sixth such case reported in the literature. Serum levels of estradiol-17beta, progesterone, and testosterone were measured before and after surgical removal of the tumor and after dexamethasone suppression in the postoperative period. Only testosterone appeared to be related to the presence of the hilus cell tumor; its levels decreased after removal of the tumor.