Ischemic heart disease in death-discordant twins: a study on 205 male and female pairs with special reference to hereditary factors. From January 1971 to March 1973 all twin pairs in the Swedish Twin Registry below the age of 70, who became death-discordant, were continuously recorded. A total of 205 (78%) of the surviving cotwins were examined with respect to different manifestation of ischemic heart diseases (IHD) and several "environmental" and "biometric" risk factors. Among the death-discordant pairs, the cause of death was IHD in 57 pairs and other than IHD in 148 pairs. Analyses revealed that the prevalence rate of myocardial infarction, angina pectoris, pathologic Q-wave, and ST depressions in connection with exercise, were significantly higher among the surviving cotwins whose partners had died from IHD than those whose partners had died from other causes. The same trends were seen for most of the risk factors measured both singly and in combination, although not very pronounced. The results indicate a substantial genetic influence in the development of IHD. The genetic influence is possibly transmitted not only through some of the risk factors measured, but also through other factors, still unknown.


Coronary heart disease in male twins: seven-year follow-up of discordant pairs. In an investigation in 1967 of about 100 male twin pairs collected from the Swedish Twin Register, discordance with respect to the presence of CHD was found in 37 pairs of which 19 were MZ. The investigation included physical examination, cholesterol measurements, and an interview regarding, among other things, smoking habits. In a follow-up study in 1974 -- seven years after the original investigation -- all but one of the 37 twins regarded in 1967 as free from overt CHD could be traced. Ten of the 36 twins had developed symptoms of overt CHD (angina pectoris or infarction); 18 twins were still healthy, 2 had died from other causes, and 6 had questionable complaints of breast pains. In a comparison of the two groups of twins with and without symptoms of overt CHD, no differences were found with respect to blood pressure, serum cholesterol, or smoking habits, as presented at the 1967 investigation. It is concluded that none of these factors seemed to influence the future development of CHD in twins apparently tainted with a heredity for this disease.


A genetic study on deaf twins.

A genetic study on deaf twins. A clinical and genetic study on 25 twin pairs with at least one deaf member was performed. Concordance rate of hearing loss was 0.88 in MZ and 0.50 in DZ pairs, with an almost complete penetrance (P = 0.94). Consanguinity was found in 32% of cases, corresponding to five times the average population rate in Japan.


Metabolic research in monozygotic twins with diabetes mellitus: progress report. An intravenous and oral glucose tolerance test and an intravenous tolbutamide test have been performed in 11 MZ twin pairs, discordant for diabetes mellitus. Blood sugar, immunoreactive insulin, and free fatty acids were determined. The research aimed at finding out whether prediabetic subjects may show any characteristic parameter which could be suggestive of the hereditary disposition. Three MZ twins of juvenile diabetics showed a normal blood glucose, immunoreactive insulin, and free fatty acids during the glucose and tolbutamide loads within a maximum of 10 years observation.


Genetic factors in myopia.

Genetic factors in myopia. A school population has been screened to locate same-sexed twins with myopia and also to compare intelligence test performance of myopic and nonmyopic individuals. Augmentation of the twin data by a survey of the world literature has led to the identification of a total of 106 MZ twin pairs, 100 of them concordant for myopia, as well as 41 DZ pairs, 12 concordant. Myopic students score eight points higher on IQ tests than nonmyopes, the entire bell shaped distribution curve being shifted to a higher range. The intellectual gain precedes in time the development of nearsightedness.


Congenital malformations in twins.

Congenital malformations in twins. Among 1195 twins born in the Collaborative Perinatal Project, for whom information was available, 219 (18.33%) were found to have malformations, 179 (14.98%) single and 40 (3.35%) multiple. The frequency of malformations among twins was significantly higher than that among singletons from the same population, but the difference was entirely contributed by MZ twins. This holds true for both major and minor malformations. The frequency among Negro twins was higher than among white, and among male twins higher than among female. Twins had more malformations of the central nervous, musculoskeletal, ear, respiratory, cardiovascular, and alimentary systems and fewer malformations of the genitourinary and integumentary systems than singletons. In a significant number of cases when one twin of a pair had a malformation, the cotwin also had a malformation though not necessarily the same as that of the first twin.


The twin condition and the couple effects on personality development. Twin psychology has been studied to a very limited extent. Only few remarkable peculiarities of the twins' development are known for sure, such as delayed intellectual development, language retardation with frequent cryptophasia, difficulties and fragility of self consciousness, reduced sociability. These and other peculiarities may result from a number of different factors: biological, peculiar parental attitude, and especially the twin situation itself, the psychology of the twin as an individual being a function of the psychology of the twin pair. Twin peculiarities have for a long time been ignored. On the one hand, psychology ignored the couple reality (it was a "one-body" psychology), and on the other, the twin method classically postulated that twins are not atypical and may therefore be used as a test for the general population. As a matter of fact, twin psychology opens a new way to science. The twin situation may serve as a paradigm for the general study of the couple effect, namely, for the objective analysis of personality as a consequence of the relations between self and others. For certain traits of personality, it is already known that MZ twins brought-up together are significantly less similar than MZ twins brought-up apart. In fact, couple effects may mask or considerably reduce genetic factors.


The process of identity in twins.

The process of identity in twins. The Blacky Picture Test was administered to a sample of 12 pairs of male MZ twins, aged 17 to 19 years, and to an equal number of singletons. A score for 30 factors was assigned to each protocol. By comparing the scores of the two groups using the Mann-Whitney U test, only one significant difference emerged, relative to the factor concerned with positive identification and fraternal relationship. Twins chose the sibling figure as the identification object significantly less often than singletons did. A more qualitative elaboration was undertaken in order to interpret this result. From the final data, the precariousness of the sense of identity in the twins comes out indirectly in their passive and conformistic acceptance of the paternal model. It would seem that the twin is induced by his relationship with his cotwin, seen as the origin of this uncertainty as to his own identity, to adhere closely to the paternal image.


Language development in young twins: biological, genetic and social aspects.


Twinning frequencies in Baden-Wurttemberg according to maternal age and parity from 1955 to 1972. The decline of the twinning rate in Germany since 1900 is exclusively due to a fall of the DZ rate. The analysis of the birth data in Baden-Württemberg from 1955 to 1972 shows that the decline of the DZ twinning rate can be explained only to a small extent by the shift of the maternal age-parity distribution towards younger mothers and lower parities. It appears reasonable that the greater part of this decline is caused by the lessening prevalence of the more fecundable, DZ twin-prone women due to the growing influence of family planning. Furthermore, it is imaginable that the probability for multiple ovulation is decreased after cessation of hormonal contraception.


Psychopathologic problems in twins during childhood. Some psychopathologic problems occurring during childhood in twins are discussed from the point of view of mental health. On the basis of case history of twins affected by neurologic or psychiatric disorders some typical situations have been examined: (1) psychopathologic problems arising from perinatal death of the cotwin; (2) psychopathologic problems arising from the death of the cotwin during late childhood; (3) psychopathologic problems arising in the pair from organic or neuropsychaitric event in one of the twins; (4) psychopathologic problems of the twins due to disorders of personal identity and the interaction between the twins. The cases are analyzed from a psychodynamic point of view, in relation to the development of personality in the twins, and from a psychosocial point of view, in relation to the cultural stereotype of the twins during the socialization process and in the context of parental dynamics.


Intellectual development of twins -- comparison with singletons. Analysis of mental and motor tests scores and intelligence test performance of twins born in the Collaborative Perinatal Project shows that twins perform more poorly than singletons from the same population and that the differences are greater in Negroes than in whites. The poor performance of twins relative to that of singletons is of complex etiology. It is partly due to poor prenatal environment, for twins brought up as singletons perform at the intelligence level of twins and not of singletons. It may also be partly due to the higher incidence of congenital malformations in twins, especially those of the central nervous system. But the performance of twins, relative to that of singletons, tends to improve as they get older, at least from 4 to 7 years, suggesting that prematurity is also a contributing factor, whose detrimental effects may be reversible.


Specific language disorders in twins during childhood. The delay in the development of the language often found in twins is usually interpreted as being strictly connected with the twinning situation and on the assumption that a model of verbal, tendentially cryptophasic, communication would more easily exist between twins. Two types of language pathology in twins, diverging from this classic framework, are presented: (1) Developmental dyslalia (or developmental dysarthria); in these cases no abnormality could be found in the modality of verbal communication between the cotwin; (2) developmental dysphasia; in these cases not only no tendency toward cryptophasia was observed, but indeed the verbal communication between the twins was markedly reduced. These two types of language disorders, as well as the classic one, are discussed in the light of a neurolinguistic interpretation.


Stuttering and tics in twins.

Stuttering and tics in twins. A total of 63 twin pairs (22 MZ and 41 DZ), with one or both members affected by not organic stuttering and/or tics, have been drawn out of the Mendel Institute's twin file. Concordance of stuttering was observed in 10:12 MZ, but only in 2:19 DZ twin pairs; concordance of tics in 6:10 MZ and in 2:22 DZ twin pairs. Stuttering did not come out significantly associated either with other disturbances of language or with an IQ under the average; almost always it was possible to find out a precipitating factor. Significant relations between stuttering and tics could not be stated. Sex ratio, obtained regarding any affected subject separately, clearly turned in favour of males both in stuttering (32:12) and in tics (27:12). Stutterers and left-handers incidence in the families of stuttering subjects appeared significant in comparison with families of subjects with tics.


The threefold cord of Mothers of Twins Clubs.


A dream come true: the Illinois Organization of Mothers of Twins Clubs.


The problem of genotype-environment correlation in the estimation of heritability from monozygotic and dizygotic twins.


Scope and methodology of twin studies.

Scope and methodology of twin studies.


Fractionation, structure and some properties of yolk granules from unfertilized hen eggs.


Nonhuman primate diploid cells for vaccine production. A cell line was established from male rhesus embryonic lung tissue in 1968. Tests for adventitious agents at every tenth passage were negative. The cells had diploid characteristics, and supported the growth of polio, rubella, and dengue viruses. Tests for latent RNA tumor viruses and tumorigenic potential were uniformly negative. A small clinical trial with rubella vaccine produced in these cells was conducted, and no major adverse reactions were reported. This cell line appears to meet all criteria of acceptability for a safe vaccine cell substrate.


Production and control of live oral poliovirus vaccine in WI-38 human diploid cells. Production of live poliomyelitis vaccine in human diploid cells WI-38 can be carried out successfully on a continuous basis. Starting at the 8th population doubling level it is possible to produce 128 ampoules, each containing 1 ml of cell suspension at the 16th level. Each of these cell seed ampoules will yield 85 bottles each with a surface area of 1400 sq. cm at the production level (P29) together with 85 Roux bottle cultures which act as controls. A further passage from the control cells yields a sufficient supply of cells for karyology, tumourigenicity and other tests. Virus yields of the Sabin strains are rather lower than those obtained in primary monkey kidney cells, but this is compensated for by the very much lower reject rate. Karyological characterisation is undoubtedly the most demanding of the testing procedures both in time and expertise. Other tests for contamination, other than bacteriological have yielded uniformly negative results. There is urgent need for standardization of the assay systems used in different laboratories and there is perhaps a case for the use of reference vaccine produced in homogeneic cells.


The testing of cell invasiveness in embryonic tissue and in cell culture. The subcutis of 11-day-old chick embryos, 15- to 18-day-old mouse embryos and the skin muscle tissue of human fetus were stretched on lens paper in a Petri dish and seeded with a piece of LED-Widr or HDC cell sheet. Mem + 10% FCS was added. After three days incubation the material was fixed, sectioned and H-E stained. In the second part of our investigation several cell lines were prepared on cover slips. When confluent, the cultures were inoculated with 1-2 drops of cell suspension of another cell line. Three days after the seeding of cell suspension on the confluent cell sheet the cultures were fixed and stained. It can be seen in the organ cultures that LED-Widr cells closely adhere to the embryonic tissue which in some places they are invading. In tissue culture examination we found that heteroploid cells seeded on a confluent sheet of diploid cells adhered but that a diploid cell seeded on epithelial-like heteroploid cells would not adhere. The testing of invasiveness in embryonic tissue in organ culture showed that it can be a useful model. By seeding suspended cells of fibroblast lines on a confluent sheet of heteroploid cell lines their contact inhibition or their invasive ability can be determined. The seeding of heteroploid cell lines on diploid cell lines can be used as a model for the study of the mechanism of invasion into normal tissue and for the in vitro study of invasion inhibiting properties of certain substances.


Delay in the appearance of clamp connection in Schizophyllum commune by inhibitors of microtubule protein assembly.


Growth characteristics, cytogenetic stability and virus susceptibility of cell lines from New Zealand rabbits. We have initiated and established over 90 cell cultures from tissues of embroynic New Zealand rabbits. These cell lines show a very varied growth pattern when compared to cell lines initiated from human embryonic tissues. The type of medium used to grow the cells influences the chromosome stability of rabbit cells. Cultures initiated from kidney tissue rarely grow more than 10 passages unless the medium is supplemented with lactalbumin hydrolysate. In turn, analyses of metaphase chromosomes from the kidney cultures, revealed they were aneuploid as early as passages 15. Cultures established from skin and lung tissues will remain diploid at least 60 passages when grown on Eagle's Basal Medium supplemented with 10% fetal bovine serum. However, rarely do rabbit cell lines go into senescence.


The use of foetal, calf and adult bovine sera for the growth of serially subcultivated diploid cells. Medium CMRL-1969 supplemented with either foetal calf, calf or adult bovine sera, or a combination of the various sera, was used to subcultivate diploid cells for the preparation of substrates for vaccine production. Supplementation with calf or adult bovine sera gave satisfactory cell yields for at least 3-4 population doublings. The finite lifespan of the diploid cells grown in media supplemented with foetal calf was always longer than with calf or adult bovine sera. However, a combined supplement of adult serum plus a low concentration of foetal calf serum gave results equally as good as foetal calf serum alone. Sera obtained aseptically from adult animals kept in isolation and monitored constantly for health are more desirable than sera obtained from abattoirs. Selection of donor animals and pooling of certain serum batches were found to be important for the preparation of serum supplements. The final protein concentration of the cell culture medium should not exceed 0.8% when adult bovine sera are used. For the growth of WI-38 or MRC-5 cells the use of foetal calf serum can be reduced or eliminated.


The development of rabbit diploid cell lines. The authors describe briefly studies on the development of diploid cell lines from fetal tissues (origin: four inbred rabbits). Some lines have been maintained in continuous serial culture for over three years. The Lung 16 may represent a qualifying rabbit diploid cell line when used between cell passages 48 and 100; during this period it has shown a minimum deviation from the normal diploid rabbit karyotype; it supports the growth of rubella virus, is non-tumorigenic and might be useful as a substrate for human vaccine.


Development of a diploid cell line from fetal calf lung for virus vaccine production. Details of isolation and replication of a fetal calf diploid cell (FCDC) is given. From the karyological point of view, the fairly large number of chromosomes existing in metaphase spreads made counting rather tedious. Lack of practical classification was another problem which made reference to individual chromosomes difficult. By increasing the population doubling of this cell, a tendency of telocentric chromosomes to undergo centric fusion was observed. Susceptibility of FCDC to different viruses is described.


The infertile couple: evaluation and treatment.


Angioblastoma of the posterior fossa in childhood.


Methods for reducing the serum requirement for growth in vitro of nontransformed diploid fibroblasts. The amount of serum protein required for clonal growth of normal diploid human and chicken fibroblasts has been reduced more than 90% by development of improved synthetic media and culture conditions. The following has contributed significantly to the reduction: (1) replacement of specific serum proteins with defined small molecular nutrients; (2) precise quantitative balance of all defined nutrients for optimal growth of single cells of each type under consideration; (3) modification of the culture substrate; (4) improvement of the cell harvesting technique. By combining these improvements, optimal growth of human fibroblasts (fetal lung, newborn foreskin, amniotic fluid) and chicken embryo fibroblasts occurs in synthetic media supplemented with 500 microgram/ml dialyzed fetal bovine serum protein [equivalent to 1% (v/v) whole serum]. The human fibroblasts form large colonies at a suboptimum rate at 25 microgram/ml dialyzed serum protein [equivalent to 0.05% (v/v) whole serum] and several divisions can be obtained in the complete absence of serum protein. Human and chicken fibroblasts differ both in their quantitative requirements for defined nutrients, and in the type and number of incompletely characterized serum components that they continue to require under the improved growth conditions. The improved systems provide a sensitive assay for the remaining undefined growth-promoting components of serum and other biological extracts.


Tissue specificity of myocardial glycopeptides synthesized during early embryonic development. [3H] Glucosamine-labeled glycopeptides synthesized by hearts from stage 14-16 chick embryos were separated on DE-52 by ion-exchange chromatography and compared to those synthesized in other parts of the embryo at the same stage. Relatively few molecular species were present in all tissues, and they appeared closely homologous. There were no glycopeptides unique to any embryonic region examined, suggesting that tissue specificity may result from quantitative rather than qualitative differences in glycopeptides.


Effect of graded coronary stenosis on regional myocardial blood flow and left ventricular function. Dogs with 70% stenosis of the left circumflex coronary artery showed a reduction of myocardial blood flow with a minimal impairment of left ventricular wall motion. Eighty to ninety percent stenosis produced a marked reduction of flow and wall motion, and ST elevation close to 100% occlusion, but delayed antegrade run-off was found. The effectiveness of collaterals to protect against left ventricular dysfunction was supported.


Electrical properties of cultured heart cells.


Molecular mechanisms in genetic transformation. Molecular mechanisms of recombination of genetic material are most readily studied in microorganisms; a great deal is known about recombination of transforming DNA, introduced into the cell from the medium, with DNA inside bacteria. At present it is doubtful that this type of transformation will be of use in improving crop plants. However, a new technique of making recombinant DNA molecules from two or more highly divergent organisms may turn out to have great practical importance for agriculture.


Role of acetaldehyde in the pathogenesis of alcoholic cardiomyopathy. Rats given both ethanol and tolbutamide showed decreased oxidative phosphorylation of the myocardial mitochondria as compared with rats given only ethanol. There were no differences in ethanol consumption and blood ethanol levels between the two groups. The concentration of acetaldehyde tended to be higher in rats given both ethanol and tolbutamide than in rats given ethanol alone. It is concluded that acetaldehyde plays a more important role in the production of alcoholic cardiomyopathy than does ethanol itself.


Lowering of blood acetaldehyde levels-a possible approach to prevention of alcoholic cardiomyopathy. Based on the assumption that circulating acetaldehyde (AcH) is cardiotoxic, D-penicillamine was administered to dogs given alcohol orally, or given AcH intravenously. Paralleling the increase in plamsa norepinephrine (NE) and epinephrine (E) induced by AcH infusion, hemodynamic measurements showed a positive inotropic response with increase in pulse, blood pressure, left ventricular contractility, and cardiac output. Infusion of D-penicillamine abruptly lowered circulating levels of AcH and catecholamines, which was accompanied by an appropriate hemodynamic response.


Early corpus luteum formation (corpus haemorrhagicum) in a 3--3/12-year-old "senile" mouse. In a female mouse sacrificed at the age of 3--3/12 years, corpus heamorrhagicum and arteric corpora lutea were found in the ovaries, apart from smaller follicles. No evidence could be found in the literature for their presence at this age. Based on these findings, aspects of basic gerontological research are discussed.


The serum opacity reaction of Staphylococcus strains: general properties of the Staphylococcus factor (SOF).


Effect of different doses of x-ray irradiation on Bulinus truncatus snails and eggs.


Avian aldolases. I. Comparative study on the purification, structural and kinetic properties of chicken and pigeon breast muscle fructose-1,6-diphosphate aldolases.


Mechanisms of spontaneous and induced heteroploidization and polyploidization. Mechanisms of heteroploidization and polyploidization were studied in tissue cultures, using various methods and cell lines. In untreated populations cells with different chromosome number are formed by mitotic non-disjunction. Mononuclear polyploid cells are formed by repeated DNA synthesis (endoreduplication) and polynuclear giant cells by postmitotic fusion of the daughter cells. These phenomena occur more frequently in cell populations treated with cystostatic drugs. Most polyploid cells are not viable.


A study of pharmacologically active factor in the human seminal fluid.


Subcutaneous phycomycosis in India.

Subcutaneous phycomycosis in India.


Maduromycotic mycetoma from Pondicherry.


Intussusception in idiopathic thrombocytopenic purpura.


Psychophysiologic and psychologic characteristics in twins in reaction to stress situations.


Nutritional factors affecting the biosynthesis of retinol-binding protein in the liver and its release into plasma.


Polymerized micelles and their use as adjuvants in immunology. A polymerization process is described for the preparation of hydrophilic micelles containing solubilized drug molecules in a colloidal aqueous system of dissolved monomers. A hydrocarbon medium constitutes the outer phase. After secondary solubilization with the aid of selected surfactants, polymerization of micelles under different conditions takes place. The formulation of drugs including labile proteins in the ultrafine polymer components ("nanoparts") and their isolation are possible without noticeable destruction of the encapsulated molecules. Entrapped tagged material (human 125I-immunoglobulin G) shows a stable fixation in such nanoparts during long-term in vitro liberation trials. Nanoparts are visible with the aid of an electron microscope. They are mostly spherical in shape and smaller than 80 nm in diameter. They form real colloidal aqueous solutions. Nanoparts are suitable to embed antigenic material (tetanus toxoid and human immunoglobulin G) for parenteral use. These preparations show intact biological activity and high antibody production in animals.


Reinvestigation of disulfiram-like biological activity of Coprinus atramentarius (Bull. ex Fr.) Fr. extracts. A ninhydrin-positive aqueous fraction isolated from Coprinus atramentarius (Bull. ex Fr.) Fr. showed significant disulfiram-like activity in mice. The isolation of the fraction from the mushroom crude extract and a convenient pharmacological test for following the physiological activity in each fraction are described.


Burkitt's lymphoma of the ovary in association with pregnancy. Two case reports. Burkitt's lymphoma of the ovary, occurring in association with pregnancy, is rare, only one case having been previously reported. Two cases are reported here and the possible effect of pregnancy discussed.


Menstruation per urethram. A case report. The case history is presented of a 24-year-old woman who had a uterus duplex, grossly underdeveloped cervices, absent vagina and who menstruated regularly through a communication between one cervical canal and the urethra.


Argon laser photocoagulation treatment for retinal disease.


Scanning electron microscopic observation of hatching in some diphyllobothriid cestodes.


D-penicillamine therapy of neonatal jaundice: comparison with phototherapy. A total 330 newborns suffering from haemolytic disease of the newborn and hyperbilirubinaemia was treated with D-penicillamine. The therapy resulted in a significant decrease in the frequency of exchange transfusions and of high serum bilirubin levels among preterm and fullterm babies with or without sensitization. Concerning the drug's mechanism of action, reduction of the bilirubin level is achieved by means of the copper stored in the liver. The intravenous route is suggested for application of the drug. In preterm infants D-penicillamine treatment proved more effective than phototherapy.


Purification of interferon by adsorption chromatography on controlled pore glass. Human fibroblast and mouse L929 cell interferons can be purified by adsoprtion to and subsequent elution from Controlled Pore Glass. Purification of 40 to 90-fold to specific activities of 1 to 5 times 10(6) units/mg of protein can be achieved in a single step, with good recovery of activity. Human leukocyte interferon does not bind to the glass and cannot be purified in this way.


A new method for assessment of fetal lung maturity. A new method for evaluation of fetal lung maturity in utero is described. The method is based on the fluorescence polarization (P) of the lipids in the amniotic fluid after labelling with a special dye. Tests performed with 49 amniotic fluid samples drawn from 33 pregnancies clearly demonstrated a decrease in P during gestation which correlated with the increase in the lecithin/sphingomyelin ratio (L/S) in the fluid. During gestation the P value at 24 degrees C decreased steadily from about 0-4 to 0-2 and the value of P (24 degrees C) = 0-310 has been tentatively chosen as the threshold above which respiratory distress syndrome may develop. The described method, which requires a specially designed instrument, offers a series of important advantages over the presently available methods. It is simple, rapid, highly accurate and reproducible, and independent of amniotic fluid volume. The P value reflects the microviscosity in the whole lipid assembly of amniotic fluid and is not confined specifically to lecithin.


Galactose oxidase: applications of the covalently immobilized enzyme in a packed bed configuration. Galactose oxidase (E.C. 1.1.3.9) was covalently immobilized to chemically modified porous silica particles by reaction of the native enzyme with pendant benzoyl azide groups on the carrier. The enzyme loading on the carrier was 100-150 units per milliliter. The immobilized enzyme was incorporated into a hardware assembly suitable for the determination of galactose or lactose concentrations in complex biological fluids. The prototype instrument as described is suitable for continuous, on-line monitoring or discrete sample analysis. Reaction conditions can be readily provided which maintain global first order kinetics within the reactor and strict linearity of the procedure over a wide range of sample concentrations. Auto-inactivation of the immobilized enzyme can be prevented by K3Fe(CN)6 and long-term reactor stability can be achieved by the periodic application of the reagent to the enzyme reactor in situ.


Can hepatitis B be transmitted sexually.


Baghdad--frontier city of medicine.

Baghdad--frontier city of medicine.


Morphine withdrawal reactions in male and female mice. In the present study we have used the morphine implantation method to investigate the intensity of the abstinence syndrome in both male and female Swiss Webster morphine-dependent mice. It is evident from our data that naloxone induced no significant difference in the jumping behavior of both morphine-dependent male and female mice when weight variables were controlled.


The dilemmas of coordinating treatment with criminal justice. Problems the Abraxas Foundation encountered in accommodating therapeutic community practices to the justice system in order to develop an alternative for courtstipulated drug offenders are reviewed. First, traditional expectations for prospective clients' motivation proved to be unrealistic. Second, courts' needs for information on their clients' progress appeared to conflict with client confidentiality laws. Finally, Abraxas resented what it initially took to be the courts' intrusion into program affairs. In response, Abraxas has sensitized its staff to the courts' role, established a uniform policy on progress reports, promoted communications with external agencies, and emphasized coordination of treatment effort with court officials.


Effect of L-dopa on pituitary gonadotropic function.


Prolonged eradication of urogenital mycoplasmas after administration of tetracycline to men in the Antarctic. Meatal swabs were obtained at intervals over 1 year from 23 men in the Antarctic. A 5-day course of tetracycline was given to twelve of them. In retrospect it was found that the antibiotic had been received by two men who were harbouring ureaplasmas, one of whom also had M. hominis. After treatment, these organisms  were not found in any of the swabs taken over the next year, except in a swab from one of the men following sexual contact after this time. One of the twelve men developed N.S.U. just before arriving in the Antarctic. He responded clinically to a shorter course of tetracycline and ureplasmas were not recovered from a meatal swab immediately thereafter. However, without further sexual contact, ureaplasmas and disease recurred about a month later. This time, after a 5-day course of tetracycline, disease was not seen, and ureaplasmas were not isolated, over the next year. In contrast, ureaplasmas were isolated consistently over a year from two men who were not given the antibiotic. The evidence strongly suggests that, under natural conditions, the most likely cause of mycoplasmas, particularly ureaplasmas, recurring in the genital tract after apparently adequate tetracycline therapy, is re-infection as a result of sexual re-exposure.


Effects of stress upon the oxidative metabolism and its correlation with gastric ulcer formation: the role of sex. The metabolic-oxidative activity of different nervous and glandular structures (amygdala, hypothalamus, lateral-frontal cerebral cortex, adrenal glands) in male and female rats under acute stress caused by physical immobilization, was determined. The sexual cycle of the female rat was controlled by examination of their vaginal frotis. One experimental group during estrus and another one during diestrus were selected. At the same time ovariectomy was performed on an experimental group in order to eliminate the hormonal influences of the ovary. Results show there are no significant differerneces in the oxidative metabolism. Nor in the numbers of ulcers. Hypothalamus-hypophyseal-adrenocortical activation was made manifest on obtaining significant differences in the weight of the adrenal glands, a fact long ago reported in a number of studies. Necropsy showed severe gastric hemorrhages and ulcer in the stomach. Nevertheless, no significant differences between the distinc experimental groups were obtained. The likely participation of sexual hormones in female rats is discussed in the light of our results.


Shigellosis. Another sexually transmitted disease? Following the clinical observation that there appeared to be an association between shigellosis and male homosexuality, the medical records of 113 patients at The New York Hospital were reviewed retrospectively. Of the 38 males studied who were between the ages 19 and 61, seventeen were homosexual (44-7 per cent.). Only one of the matched controls was homosexual. Of the men with shigellosis who had a history of foreign travel, 10 per cent. were homosexual; however, among the patients without a travel history, 57-1 per cent. were homosexual (P less than 0-05). For male patients with shigellosis who do not have an appropriate travel history, the physician should expand his epidemiological investigation to include sexual contacts. Men and women who perform rectal intercourse should be cautioned to abstain from this activity until their stool cultures are negative for shigella. If a male patient with shigellosis is homosexual, he should be screened for other sexually transmitted diseases such as syphilis, gonorrhoea, hepatitis B, and amoebiasis.


Successful therapy with methotrexate of a multicentric mixed lymphoma of the central nervous system. Primary lymphoma of the central nervous system (CNS) is extremely rare. A case of mixed histiocytic lymphocytic lymphoma of the CNS that initially occurred in the spinal cord is reported. Multicentric recurrence following radiotherapy was successfully treated with intrathecal methotrexate and the patient remains free of disease after 4 years. The role of intrathecal methotrexate as alternative therapy following irradiation failure is discussed.


Methotrexate pneumonitis induced by intrathecal methotrexate therapy: a case report with pharmacokinetic data. A patient with adenocarcinoma of the breast metastatic to the leptomeninges was treated with 10 doses of intrathecal methotrexate (MTX) administered at intervals of 2 days. Following these treatments she developed fever, hypoxemia, and bilateral pulmonary infiltrates without documented pulmonary infection. Autopsy findings were consistent with the pneumonitis that has been associated with intermittent oral, intramuscular, and intravenous MTX therapy. It is suggested that this patient's pulmonary process represented MTX pneumonitis following intrathecal MTX. Cerebrospinal fluid and serum MTX concentrations determined retrospectively on frozen samples reflect an atypically rapid transport of MTX from this patient's cerebrospinal fluid to a slowly decaying systemic pool. Because of this, serum MTX levels probably exceeded 10-8M during the entire 20-day course of therapy, thus exposing the pulmonary parenchyma to significant drug concentrations for a prolonged interval. It is suggested that these unfavorable pharmacokinetics may have contributed to this patient's susceptibility to MTX pneumonitis.


A comparison of cyclophosphamide, vincristine, and prednisone (COP) with nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP) in the treatment of nodular, poorly differentiated, lymphocytic lymphoma. This study was designed to test the efficacy and toxicity of COP (cyclophosphamide, vincristine, and prednisone) and MOPP (nitrogen mustard, vincristine, prednisone, and procarbazine) in 13 previously untreated patients with disseminated, nodular, poorly differentiated, lymphocytic lymphoma, and to test for patient cross-resistance to the regimens. Complete remission was initially achieved in six of eight patients on COP and three of five on MOPP. Three patients were crossed over to the alternative induction regimen because of progressive disease after an initial partial response; one was crossed over because of toxicity. On crossover, four patients achieved complete remission, two on either regimen. Durations of unmaintained complete remission range from 6-46+ months, with 8/13 still in their first complete remission. Only one patient has died, while in remission, from progressive Kaposi's sarcoma; one was lost to follow-up while in complete remission at 44 months; the others (85%) remain alive 33-54 months from the initiation of chemotherapy. MOPP was significantly more toxic with respect to thrombocytopenia, duration of myelosuppression, and cumulation of toxicity. Because of its more acceptable toxicity, COP is recommended as initial therapy for patients with nodular, poorly differentiated, lymphocytic lymphoma. MOPP or another regimen of non-crossresistant combination chemotherapy would be more appropriate for primary treatment failures.


Phase II evaluation of VP-16-213 (NSC-141540) and cytembena (NSC-104801) in patients with advanced breast cancer.


Effects of an antiandrogen, cyproterone acetate, on the kidney of the three-spined stickleback (Gasterosteus aculeatus L.). The fine structure of the kidney is studied in the sexually mature male three-spined stickleback after administration of an antiandrogen, cyproterone acetate. Under these conditions, the dedifferentiation of renal tubules is characterized by the same involutive processes as those induced by castration, with the difference that cyproterone acetate only begins to act after 14 days whereas after castration the first signs of involution are visible after 7 days. The ultrastructural modifications affect the nucleoli, the rough endoplasmic reticulum and the Golgi apparatus. They reflect an inhibition of the secretory process. The results obtained demonstrate that administration of cyproterone acetate to male sticklebacks has an inhibitory effect on renal target cells, apparently indistinguishable from the changes induced by lack of male sex hormone, and that this drug may be a valid substitute for castration in fish.


A multi-centre general practitioner assessment of butriptyline hydrochloride ('Evadyne'). A multi-centre open study in general practice was carried out to assess the efficacy of and incidence of side-effects with the tricyclic antidepressant, butriptyline. Of a series of 153 patients with non-psychotic depression, with or without anxiety, 105 (69%) were judged as having a good or fair response to treatment with 75 mg to 150 mg butriptyline daily. Side-effects of an anticholinergic nature were seen in 13.7% of patients, but the incidence decreased to less than 4% in the 101 patients receiving treatment for over 7 weeks.


Circulating immune complexes in Graves' disease. Circulating immune complexes in Graves' disease sera were detected by the 125I Clq deviation test. High titers of immune complexes were detected and correlated significantly with the microsomal antibody but not with the thyroglobulin antibody titer nor with serum thyroxine levels. Serum fractionation studies in a patient with high titer of immune complexes revealed these to be heterogeneous in size, sedimenting in 19S, intermediate and 7S regions. The data suggest a role for immune complexes in the pathogenesis of Graves' disease.


Biosynthesis of enniatin B.

Biosynthesis of enniatin B.


Questions to the supply of young infants with fat and fatty acids. II. Fat content and fatty acid pattern in milk formulae for healthy infants in the first 6 months of life. The fat content and the fatty acid pattern were analyzed in 30 commercially prepared milk formulae for healthy infants in the fisrt 6 months of life. We found an average fat content of 3.4 g or 3.6 g/100 ml in "partly adapted" and "adapted" milk formulae, between 1.4 g and 3.3 g/100 ml in "not defined" milk formulae. We regard a fat content lower than 3.0 g/100 ml and more than 4.0 g/100 ml as not advisable. In most milk formulae the ratio of saturated: unsaturated fatty acids is similar to the ratio in human milk fat. This ratio is obtained from a mixture of cow's milk fat with vegetable oils or by a mixture of various vegetable fats. The difference in the fatty acid pattern between the milk formulae and the fatty acid pattern in mature human milk are demonstrated and discussed. The tolerance of milk formulae for young infants is not influenced in an unfavorable manner by butyic acid. A high portion of lauric acid in mild formulae seems undesirable. The importance of the position of palmitic acid in the triglycerides of milk formulae for infants is discussed, and it is referred to the advantage of a mixture of cow's milk fat with vegetable fats. A linoleic acid content of 3 kcal% in the minimum and 7 kcal% in the maximum in milk formulae for infants is regarded as advisable.


Changes in erythropoiesis and renal ultrastructure during exposure of mice to hypoxia. During hypoxia, elevated ESF levels occur which are accompanied by increased erythropoietic activity resulting in progressive elevation of the haemoglobin and haematocrit concentration. An attempt has been made to correlate ultrastructural changes in the kidney with changes in serum ESF concentrations and the erythropoietic state of mice exposed to continuous hypoxia for 3 weeks. A series of changes in the epitheloid and proximal tubules cells occurred which may be related to the biogenesis of erythropoietin. However, no detectable ESF or renal erythropoietic factor could be extracted from the kidneys at the time of maximal ultrastructural changes. Although some ESF-inhibitory material was demonstrated, it could not be extracted into lipid solvents. It is suggested that the failure to consistently extract an erythropoietic factor from the kidneys of hypoxic mice may be related to the absence of renal storage at the onset of increased peripheral demand. Other levels and durations of hypoxia may help to elucidate the role of the kidneys in regulating serum ESF levels.


Ox-spleen erythropoietic factor: chromatographic investigations and dosages.


Effect of localization of L-asparaginase as the concanavalin A conjugate on anti-tumor activity. A method potentially capable of enhancing the effectiveness of therapeutic enzymes such as L-asparaginase was investigated. The method was suggested by the following properties that have been observed for lectins injected into tissues: (1) six lectins with differing specificities were retained near the site of injection in the feet of mice 10 to 100 times longer than several non-lectin proteins. Prolonged retention of 125I-labelled concanavalin A was also observed in other normal and malignant mouse tissues. (2) The retention of 125I-labelled concanavalin A was not affected by prior immunization against concanavalin A. (3) Electrophoresis of tissue extracts on sodium dodecyl sulfate-poly-acrylamide gels followed by radioautography indicated that the 125I-labelled concanavalin A retained in the tissue remained as intact in form as prior to injection. Since the therapeutic efficacy of many enzymes may be enhanced by localization at the intended site of action, in principle it should be possible to enhance the effectiveness of therapeutic enzymes by combining the tissue-localizing properties of a lectin with therapeutic effectiveness of the enzyme. A conjugate of E. coli L-asparaginase and concanavalin A has been prepared by covalent cross-linking with glutaraldehyde and has been shown to be retained in mouse tissue 90 times longer than the free enzyme. However, it is completely ineffective in the treatment of the L-asparaginase-sensitive lymphosarcoma 6C3HED in C3H/HeJ mice. The ineffectiveness of the conjugated enzyme may be associated with the interiorization of the conjugate by the cells of the tumor.


The immunospecificity of altered initial arrest patterns of circulating cancer cells in tumor-bearing mice. The early arrest patterns of a methylcholanthrene-induced fibrosarcoma were determined after injection of 125IUdR-labelled cells into the systemic circulation of mice bearing transplanted lymphosarcomas, and of normal animals. Similar experiments were performed using radiolabelled lymphosarcoma cells and normal or fibrosarcoma-bearing mice. The results showed that shifts in normal distribution patterns previously observed in tumor-bearing animals injected with cells of the same type as that borne by the animal, were not detectable when cells of a different tumor type were injected. Peritoneal exudate cell migration inhibition assays showed little immunologic cross-reactivity between the two tumors and, together with the results of the distribution studies, indicated that alterations of early arrest patterns in mice sensitized to their tumor is an immunologically specific phenomenon.


Infection of a nonspecific urethritis patient and his consort with a pathogenic species of nonspecific urethritis Corynebacteria, Corynebacterium genitalium, N. SP. A patient with nonspecific urethritis (NSU) and his consort were examined for infection with NSU corynebacteria, mycoplasmas, and gonococci. No classic and T-mycoplasmas or gonococci were cultured, but one species of NSU corynebacteria was isolated not only from the patient's urethral discharge during three episodes of NSU but also from his consort. It was not isolated after successful treatment of the patient with tetracycline and the use of condoms prevented reoccurrence of urethritis. This NSU corynebacterium was isolated previously from one epididymitis patient and two NSU patients but not from any of the normal male and female subjects examined. Therefore, this strain is considered to be one of the etiologic agents of NSU and female subjects are asymptomatic carriers. In consequence, it is suggested that NSU corynebacteria which are commensals and pathogens of the male and female urogenital tracts should be incorporated in a new species, of the Coryneform group, and that this strain should be the type species, Corynebacterium genitalium n. sp.


Reactions to "employing electric shock with autistic children".


The reliability and diagnostic validity of the physical and neurological examination for soft signs (PANESS). Twenty-one children, mean age of 8 years, were each examined on separate occasions by two pediatric residents, blind to diagnosis, using the neurological examination (PANESS) included in the group of instruments recommended by the National Institute of Mental Health for psychotropic drug studies in children. Half the children were hyperactive/aggressive, one quarter were normal, and one quarter had histories or signs strongly presumptive of brain damage. Many of the signs, though reliable, did not occur in the majority of children. Examiners did achieve a high level of agreement about global neurological status. It was concluded that the neurological examination probably contains a substantial number of non-contributory items and should be regarded as experimental rather than definitive.


Autistic children exhibit undetectable hemagglutination-inhibition antibody titers despite previous rubella vaccination. The etiology of autism is unknown, but autism has been associated with a number of diseases, including prenatal rubella. Rubella vaccine challenge was used in an attempt to retrospectively diagnose prenatal rubella in autistic children. This test was selected because unresponsiveness of antibody titer has been reported as helpful in retrospective diagnosing of prenatal rubella. Fifteen autistic children and 8 controls matched for age were challenged with rubella vaccine. Rubella vaccine challenge did not differentiate autistic children from the control subjects. However, 5 of 13 autistic children had undetectable titers despite previous vaccine; all control subjects had detectable titers. This finding of undetectable titers in autistic children suggests these children may have an altered immune response.


Multiple factors in short-term behavioral control of protein intake in rats. The availability and concentration of dietary protein was varied in an examination of the nature of the day-to-day intake of protein solutions by 60-day-old male rats. It was found that the rats consumed a remarkably constant absolute amount of protein each day, adjusting overall caloric intake to maintain protein at a roughly constant proportion of total calories. Factors such as the time of access to a protein source or the extent of prior experience with a protein source were seen to influence the overall constancy of protein intake, whereas daily shifts in preference between two available concentrations of protein did not interfere with such short-term control. The mechanism for this behavioral control is likely to be different from mechanisms mediating the conditioned response to dietary protein, as in the response to dietary amino acid imbalance.


Intussusception in the older child- suspect lymphosarcoma. Examination of the records of 378 children with intussusception at our institution revealed that 29 cases were caused by an identifiable intestinal lesion. A Meckel's diverticulum was the causative agent in 21 children, all of whom were under 2 yr of age. A previously undiagnosed ileal lymphosarcoma produced the intussusception in six other children, all between 6 1/2 and 9 yr of age. Our experience indicates that any child over 6 yr of age with the clinical findings of colicky abdominal pain, bloody stools, and a palpable mass plus the radiographic evidence of intussusception must be considered to have ileal lymphosarcoma until proven otherwise. Hydrostatic reduction of the intussusception must be accompanied by extensive small bowel reflux of barium in order to effectively rule out a small intestinal lesion. If this is not accomplished, surgery should be planned with the suspicion that a malignancy may be present. If this suspicion is confirmed by frozen section, the operation procedure should include wide surgical excision of the lesion along with the regional lymph nodes.


The operational implications of resistance of malaria vectors to insecticides in Iran.


Incidence and identification of phospholipase C-producing bacteria in fresh and spoiled homogenized milk. Bacteria which produced phospholipase C were isolated from 13 of 34 fresh and 15 of 35 spoiled samples of homogenized milk. No single off flavor was assigned consistently to samples with phospholipase producers, but 75% of them were bitter. Pseudomonads constituted 62% of the isolates. Other phospholipase C-producing genera and their numbers were Acinetobacter, two; Alcaligenes, three; Bacillus, two; Citrobacter, one; Enterobacter, three; and Flavobacterium, two. Two unidentified yeasts also were isolated.


The content of 90Sr in the bone tissue of the population of the Soviet Union. (1959-1971) (The basic laws of its accumulation and distribution). On the basis of the results of long-term observations, general laws have been identified determining the dynamics of 90Sr concentration in the bone tissue of the population of the USSR in 1959-71, the peculiarities of 90Sr accumulation in different age groups and the connection and dependences between the intake and the contect of the isotope in human organism. It has been found that maximum 90Sr concentration occur in children born in the year when nuclear tests were carried out. The type of distribution of the frequency of occurrence of cases showing different levels of 90Sr content in uniform population groups was determined. Characteristic features of 90Sr distribution in different bones of the skeleton and its changes in the course of time were demonstrated.


Catechol-O-methyltransferase activity in psychotic children. Catechol-O-Methyltransferase (COMT) activity was studied in three groups of institutionalized children: (1) a group of schizophrenic children; (2) a heterogeneous group of chronic psychotic children characterized by severe symptomatology and onset before 5 years of age; (3) a group of acting-out but nonpsychotic children. Erythrocyte COMT activity was found to be significantly lower among the schizophrenic subjects in contrast to the greater activity in both the other groups--the nonpsychotic and chronic psychotic children. The difference in COMT activity between psychotic groups appeared to be related to diagnosis and age of onset of disorder. Generality of findings is limited by the small sample size (N = 42) and by the difficulties inherent in the diagnosis of severe mental disorder in children. However, this preliminary study suggests that enzymatic activity may be associated with the development of schizophrenia in children.


The electrophysiologic effects of tolamolol (UK-6558-01) on the passive membrane properties of mammalian cardiac Purkinje fibers. Tolamolol (UK-6558-01) is a relatively cardioselective beta receptor antagonist which is effective clinically in the treatment of supraventricular and ventricular arrhythmias. Animal studies suggest tolamolol may have significant antifibrillatory properties. The effect of tolamolol on the passive membrane properties of sheep cardiac Purkinje fibers was studied using multiple microelectrode techniques. In sodium-deficient Tyrode's solution, we measured the resting transmembrane voltage (Vr) at differing external potassium concentrations (K+]0, investigated current-voltage relationships and per formed cable analysis. Tolamolol was found to hyperpolarize the membrane in the presence of a large driving force [i.e., when (Vr - VK) was significantly greater than zero, where VK is the potassium equilibrium voltage ]; to hyperpolarize fibers with a Vr decreased due to stretch at [K+]0 = 4.0 mM; to increase membrane chord and slope potassium conductance; to decrease the membrane length constant; and to decrease the membrane time constant. In normal sodium Tyrode's solution, tolamolol could suppress automaticity. These results suggest that tolamolol increases membrane potassium conductance within the range of the pacemaker potential. This action can account, in part, for its ability to suppress automaticity and for its ability to prevent reentrant arrhythmias. In normal sodium Tyrode's solution, tolamolol suppressed oscillatory and sustained rhythmic activity occurring at a low transmembrane voltage which may be related to its alleged antifibrillatory effects.


Correlation between analgesia and the decrease of acetylcholine turnover rate in cortex and hippocampus elicited by morphine, meperidine, viminol R2 and azidomorphine. In rats, an ED50 for analgesia of morphine, meperidine, viminol R2 or azidomorphine decreases the turnover rate of acetylcholine (TRACh) in cortex and hippocampus. These four analgetics fail to change to TRACh in striatum when given in a dose range from ED30 for analgesia up to a cataleptic dose. Viminol S2, a nonanalgesic stereoisomer of vimonol R2, fails to decrease the TRACh in cortex and hippocampus. Naltrexone, an opiate antagonist, also fails to change the cortical and hippocampal TRACh but it antagonizes the decrease in cortical and hippocampal TRACh elicited by the four analgetics. Since the ED50 of these four analgetics fails to change the TRACh in striatum which contains a high density of opiate receptors and intrinsic cholinergic neurons, but decreases the TRACh in hippocampus and cortex which contain a low density of opiate receptors, it can be inferred that opiate receptors are not exclusively involved in the regulation of TRACh. However, the results suggest that certain cholinergic pathways participate in the mediation of analgesia.


In-vitro fertilization of ova from senescent mice and hamsters.


Bioavailability assessment under quasi- and nonsteady-state conditions III: Application. The applicability of bioavailability assessment at quasi- and nonsteady state is illustrated with data from a study comparing two formulations of amitriptyline hydrochloride in humans. Relative bioavailability as a function of the observed mean plasma concentrations may be expressed in closed form, provided the affected intervals begin and end in the log-linear region. Alternatively, numerical, graphical and/or electronic computational techniques may be used to stimulate the appropriate [Cp(i)]sim, the proximity of which to [Cp(i)]obs is a function of relative bioavailability and omega. If a model can be found to fit the data adequately, it would be sufficient that only one sampled interval end in the log-linear phase.


Effects of pituitary graft and 2-bromo-alpha-ergocryptine on mammary DNA synthesis in mice in relation to mammary tumorigenesis. 3H-thymidine incorporation into mammary DNA as an index of mammary DNA synthesis in C3H/He virgin females was significantly higher at proestrus than at estrus and diestrus. The rise in incorporation at proestrus was completely blocked by the administration of 2-bromo-alpha-ergocryptine (Bromocriptin) 1 day before proestrus. The incorporation was maintained at a higher level than that at proestrus by pituitary grafts. The results supported the view that mammary DNA synthesis, which is stimulated by prolactin, is an important factor for mammary tumorigenesis.


Species of gastro-intestinal nematodes of sheep from Iran.


Interaction of estrogen and prolactin in spontaneous mammary tumorigenesis of the mouse. Daily treatment for 12 months of young nulliparous C3H mice with 0.1 mg 2-bromo-alpha-ergocryptine (CB-154), an effective suppressor of prolactin secretion, significantly reduced and in some instances virtually eliminated the incidence of spontaneous mammary tumors. The CB-154-treated mice had normal body weight gains and normal estrous cycles. Ovariectomy of young nulliparous C3H mice also reduced mammary tumor incicence, but appeared to be slightly less effective than treatment with the ergot. Chronic administration of 17beta-estradiol for 12-19 months (via drinking water) to young nulliparous intact or ovariectomized-hysterectomized C3H mice significantly increased mammary tumor incidence. Concurrent administration of 0.1 mg CB-154 to the estrogen-treated mice significantly reduced the incidence of mammary tumors when compared with mice treated with the steroid alone. Chronic sc administration (0.1 mg/mouse, twice weekly for 20 months) of Enovid to young, nulliparous, intact C3H mice significantly increased mammary tumor incidence, whereas concurrent administration of 0.1 mg CB-154 to the Enovid-treated mice significantly reduced the incidence of these tumors. Thus significant inhibition of spontaneous or estrogen- or Enovid-induced mammary tumorigenesis by concurrent drug-induced prolactin suppression has been demonstrated in these studies.


Preventing bubbles in intravenous tubing.


Fluorouracil as an adjuvant to colorectal cancer surgery.


Polyps of the colon.

Polyps of the colon.


Arthroscopy of the Knee.

Arthroscopy of the Knee. Two hundred and twenty-one consecutive arthroscopic examinations of the knee are reviewed to establish diagnostic accuracy based on subsequent arthrotomy and the clinical course in the absence of arthrotomy. One hundred and nine knees showed an arthroscopic accuracy of 89.9 per cent at subsequent arthrotomy. Ninety-five patients who did not have an arthrotomy revealed 73.7 per cent clinical improvement between 9 months and 4 years after arthroscopy. Arthroscopy is a simple diagnostic procedure which, with experience, can be done safely and accuratly with minimal morbidity and, in this series, allowed 33.5 per cent of patients to avoid arthrotomy.


Breast prostheses.

Breast prostheses.


Quinacrine ochronosis.

Quinacrine ochronosis.


Does juvenile temporal arteritis exist.

Does juvenile temporal arteritis exist.


Bronchial artery embolization for massive hemoptysis. Improved angiographic techniques have proved that therapeutic embolization is effective in controlling massive hemorrhage in selected sites of the gastrointestinal tract and central nervous system. We have controlled massive hemoptysis in five cases with use of our improved techniques and bronchial artery embolization. Because mortality due to massive hemoptysis in both benign and malignant disease is high, therapeutic bronchial artery embolization is the preferable approach in some cases.


Job specifications for the President of a County Medical Society or how the Establishment remains established.


Y-chromosomal genes in a phenotypic male with a 46XX karyotype. A number of patients with a male phenotype and a female (46XX) karyotype have been described. Although there is little or no evidence for the presence of a Y chromosome in their cells, these individuals resemble patients with Klinefelter syndrome (47XXY). Using a new serological assay for the presence of H-Y antigen, a cell surface component associated with the Y chromosome, we have demonstrated the presence of Y-chromosomal genes in a 46-year-old man with an XX karyotype. In addition, using standard cytological technique, we have located a minor population of XXY cells as well as cells bearing and abnormal chromosome 17 among the blood leukocytes of this individual.


Undernutrition. Cultural diagnosis and treatment of "runche".


Severe transient pancytopenia associated with procainamide ingestion. A 73-year-old woman was found to have clinically significant pancytopenia in association with procainamide hydrochloride ingestion. The syndrome, resembling systemic lupus erythematosus, which has been reported to develop in patients treated with this agent, is characterized by mild to moderate anemia and mild to moderate granulocytopenia. Severe granulocytopenia in patients taking procainamide and unrelated to a lupus syndrome has not previously been reported in association with significant thrombocytopenia. The clinical severity of this patient's presentation, suggesting an aleukemic leukemia, and its complete remission after cessation of procainamide administration occasional this report.


Mycoplasmemia in adult male patients.

Mycoplasmemia in adult male patients. Mycoplasma hominis mycoplasmemia was associated with obstruction, manipulation, or surgery of the genitourinary tract in five adult men. A four-fold increase in specific antibody titer against M hominis was demonstrated in serial convalescent serum obtained from one patient. Two patients became afebrile after treatment with tetracycline; a third recovered without therapy for a Mycoplasm infection. The two remaining patients died of thier underlying diseases.


Hemiparesis in cervical spondylosis.

Hemiparesis in cervical spondylosis. Two patients with hemiparesis were thought to have intracranial lesions. Cervical spondylosis was discovered, and the condition of both patients improved after laminectomy. Although it has been rarely emphasized in the past, cervical spondylosis should be considered in the differential diagnosis of hemiparesis.


Lead poisoning from cocktail glasses. Observations on two patients.


Sarcoidosis presenting as multiple pulmonary nodules.


Popliteal vein aneurysm with recurrent pulmonary thromboemboli.


Transient paralysis of the phrenic nerve associated with head injury.


Nutrition instruction in Medical Schools--1976.


"Runche": cultural problems of deprivation.


Diagnosis by deduction: reprise.

Diagnosis by deduction: reprise.


Management of cancer.

Management of cancer.


Hypertension screening.

Hypertension screening.


Echocardiography and tumor invasion of the heart.


Cancer and diet.

Cancer and diet.


Halothane arrhythmia.

Halothane arrhythmia.


Carotenemia vs jaundice.

Carotenemia vs jaundice.


Monitoring temperature during anesthesia.


Expectoration of bronchogenic tumor tissue.


Egregious errors in the management of hypertension.


Intrinsic asthma in adults. Association with gastroesophageal reflux. Of 28 patients with severe asthma routinely examined with upper gastrointestinal (UGI) x-ray films, 18 (64%) were found to have hiatus hernia and 13 (46%) were found to have demonstrable gastroesophageal reflux. These prevalences differed significantly (P less than .001) from those seen in a control population (19% and 5%, respectively). These data suggest that aspiration of gastric acid is a frequent incitant to severe asthma and that it should be routinely sought in the treatment-resistant asthmatic patient. Intensive medical regimens directed against reflux and acidity may bring notable improvement in asthma symptoms. Surgical restoration of effective lower esophageal spincter function has proved to be curative in other reported studies.


Multiple epiphyseal dysplasia. A family case report. Six cases of multiple epiphyseal dysplasia were found in a 30-member kindred. The kindred showed an increased incidence of other joint abnormalities. A dominant pattern of inheritance was not confirmed.


Syphilis surveillance. Failure to screen in a university hospital. Of 5,954 adult inpatients consecutively discharged from a university hospital during a three-month period, only 8.4% had serologic tests for syphilis performed during hospitalization. The testing rate was 20.1% on patients admitted to a medical teaching service and 1.4% on a surgical teaching service. In patients tested, a positive rapid plasma reagin test result was obtained in 6.2% and the diagnosis was confirmed by further testing, but effective therapy was not always given. On 9 of 30 patient records listed syphilis as a diagnosis on discharge. We conclude that serologic testing for syphilis is routinely omitted in the evaluation of hospitalized patients; even when tests are positive, the results are often ignored.


Patient complaints against physicians in the Richmond area during 1973.


Adverse reactions in treatment with lithium carbonate and haloperidol. Hospital records of 425 patients who had been treated simultaneously with lithium carbonate and haloperidol were examined. Adverse reactions in these patients were the same as in patients given lithium alone or haloperidol alone. None of the patients developed a syndrome resembling that described by others in patients treated with a lithium and haloperidol combination.


Destructive bone disease in early syphilis. Although destructive bone disease is a well-known complication of tertiary syphilis, osteitis or osteomyelitis are not commonly recognized as complications of early (primary or secondary) syphillis. A patient with secondary syphilis characterized by generalized lymphadenopathy, perianal condyloma lata, and positive rapid plasma reagin (RPR) and fluorescent treponemal antibody-absorption (FTA-ABS) tests also complained of headache, right should pain, and right anterior chest pain and swelling. Roentgenograms showed mottled osteolytic lesions consistent with previously described luetic bone disease. Biopsy confirmed the diagnosis of syphilitic osteomyelitis, and treatment with penicillin resulted in prompt resolution of symptoms.


Nonsurgical closure of large arteriovenous fistulas. We report a nonsurgical closure of large postnephrectomy arteriovenous fistulas in two patients. To out knowledge, this method has not previously been attempted because of the large size of the communication and the risk of pulmonary embolization. However, the development of new embolization techniques makes a nonsurgical approach feasible and safe.


Colonoscopy. Inefficacy for early carcinoma detection in patients with ulcerative colitis.


Multiple squamous papillomas of the esophagus diagnosed by endoscopy.


Metronidazole and hepatic abscess. A false-positive response.


Digital gangrene.

Digital gangrene.


Another form of latrogenic hypokalemia.

Another form of latrogenic hypokalemia.


Who or what developed.

Who or what developed.


The patient with acute diarrhea. An algorithm for diagnosis.


Joint effusions in sickle cell-beta-thalassemia disease.


Asthma, ephedrine, and Olympic eligibility.


Serum cholesterol.

Serum cholesterol.


The plutonium controversy.

The plutonium controversy.


Individualization of phenytoin therapy.

Individualization of phenytoin therapy.


Anesthesia for elective termination of pregnancy.


Arteriovenous fistula after femoral vein catheterization.


Medical education in the United States 1975-1976.


Blood cultures drawn through catheters.

Blood cultures drawn through catheters.


Recent events of special interest to medical education.


Health Professions Educational Assistance Act of 1976.


"Primary care" and graduate medical education.


Education and medical licensure.

Education and medical licensure.


Mandatory continuing medical education.

Mandatory continuing medical education.


Faculty responsibility for the competence of new physicians.


Incidence of galactorrhea.

Incidence of galactorrhea.


Thyroid supplements and breast cancer.

Thyroid supplements and breast cancer.


Successful protection of humans exposed to rabies infection. Postexposure treatment with the new human diploid cell rabies vaccine and antirabies serum. Forty-five persons severely bitten by rabid dogs and wolves in Iran were treated after exposure with a new rabies vaccine produced in cultures of human diploid cells. All except one also received one injection of rabies immune serum. This treatment, in contrast to past experience with other vaccines, resulted in protection of all individuals against rabies. Thus, almost a century after the postexposure treatment of humans was initiated, an effective tool for protecting man against rabies has finally been developed.


Identifying patients at risk for thromboembolism. Use of 125I-labeled fibrinogen in patients with acute myocardial infarction. Fibrinogen labeled with iodine 125 was used to detect deep vein thrombosis (DVT) in 35 patients during their course and convalescence from acute myocardial infarction. Clinical status was assessed and scored with the use of a modified coronary prognostic index. According to the prognostic scores, patients were allocated to one of two groups. Of 27 patients in good clinical condition, DVT developed in only one patient, whereas thromboembolic complications occurred in seven of eight patients who were severely ill--a highly significant difference. Prophylactic anticoagulation is advisable in patients at risk.


Unexpected cardiac arrest during anesthesia and surgery. An environmental study. Medical and legal records of 41 cases of cardiac arrest that occurred during surgery were supplied by a professional liability insurance company and a review was undertaken in an attempt to identify recurring or common factors. The majority of patients in this study were healthy and required relatively routine elective surgical procedures. Only three of the patients survived the cardiac arrest and returned to normal activities. The remaining patients either died in the hospital or had a major central nervous system deficit. Hypoxia from hypoventilation and low levels of inspired oxygen appeared to be the chief cause of cardiac arrest in this study. Because of the unknown frequency of cardiac arrest during surgery, we recommend the establishment of a national registry of cardiac arrest cases that occur in surgical patients, in order to monitor incidence, causes, and outcome. Only in this way will it be possible to lessen the frequency of this disastrous event.


Patients' response to tubal division.

Patients' response to tubal division. Of the 187 women who underwent laparoscopic tubal division at the Massachusetts General Hospital between September 1969 and June 1973, one hundred thirty-nine were interviewed in a follow-up study. The mean age was 33.9 years; the mean gravidity was 5.0 and mean parity 3.8. Most women were married, with religious affiliations reflecting those of the general hospital population, and most underwent tubal division because they felt they had had enough children. The majority (85.6%) were satisfied with their decision and reported similar or improved mental and physical health and sexual activity. Almost all (93.5%) said that they would make the same choice again, and more than half (54.7%) would have liked to have had this operation earlier. Those ambivalent or regretful about their decision could not be readily identified by any preoperative characteristics such as age, parity, and marital status.


Critical elements in the diagnosis of alcoholism. A national survey of physicians.


Reversible renal failure and myositis caused by phenytoin hypersensitivity. A 38-year old woman receiving phenytoin (diphenylhydantoin) noticed maculopapular erythema as the first manifestation of a syndrome that included acute renal failure and myositis in addition to fever, lymphadenopathy, exfoliative dermatitis, and hepatitis. Prednisolone sodium phosphate therapy resulted in resolution of this hypersensitivity reaction, and she recovered from renal insufficiency. The occurrence of renal failure and myositis in the spectrum of phenytoin hypersensitivity reactions is discussed, and the importance of a morbilliform rash in a patient receiving phenytoin is emphasized.


Hyperkalemia with cardiac arrhythmia. Induction by salt substitutes, spironolactone, and azotemia. In two patients, severe hyperkalemia and serious cardiac arrhythmia developed after excessive use of potassium-containing salt substitutes. Both had impaired ability to handle and excrete additional potassium load due to chronic congestive heart failure, azotemia, and administration of spironolactone. Prompt recognition of the arrhythmia and immediate restoration of the cardiac rate and rhythm by pacemaker support followed by intensive regimen to lower the serum potassium prevented a potentially fatal outcome. These cases emphasize the potential danger of salt substitutes when used by patients who are predisposed to retain potassium.


Massive hemolysis caused by acetaminophen. Positive determination by direct Coombs test.


Metastatic melanoma in the breast masquerading as fibroadenoma.


Postoperative choledochoscopy via the T-tube tract.


Transient cerebral ischemia and mitral-valve prolapse.


"Toot-toot" and health to boot.

"Toot-toot" and health to boot.


The autonomous heart in diabetic autonomic neuropathy.


Pneumoperitoneum and right upper quadrant gas in a diabetic man.


The physician's estate. Part III.

The physician's estate. Part III.


Hyperthermia and cellular immunity.

Hyperthermia and cellular immunity.


Science and clinical medicine.

Science and clinical medicine.


Scuba diving.

Scuba diving.


Meat-wrappers' asthma.

Meat-wrappers' asthma.


Interpretation of article disputed.

Interpretation of article disputed.


Oral contraceptives after intestinal bypass operations. A study was conducted on 7 fertile women (ages 19-44) after end-side jejunoileostomy for obesity.  The peak plasma norethindrone (norethisterone) and levonorgestrel (formerly known as d-norgestrel) levels were measured during separate 24-hour norethindrone or levonorgestrel loads using conventional oral contraceptives (OCs).  Compared to normal control patients, the intestinal bypass patients had severely reduced mean levels.  The levels were 5.0 versus 20.8 ng/ml for norethindrone and the levels were 1.63 versus 4.25 ng/ml for levonorgestrel.  Investigation of the patients' sex steroid binding globulin levels showed markedly reduced levels, implying a defective hepatic synthesis of this globulin rather than malabsorption as the most important factor.  The data shows a reduced plasma level of OC in patients operated in this way, and OCs cannot be considered safe after intestinal bypass.


Human umbilical cord. A new source for vascular prosthesis. Reconstructions were performed to the popliteal, tibial, and peroneal arteries employing a modified umbilical cord vein prosthesis. The latter was obtained from human cords and was made available as an onshelf graft for surgery following glutaraldehyde tanning. The early patency and limb salvage rates are equivalent to those obtained with autogenous saphenous veins. Additional benefits include significant decreased operative time and morbidity. It is also probable that this new graft may be resistant to biodegradation and therefore may obviate many of the causes for late failure that occur with the use of living biologic tissues or collagen tubes. Long-term follow-up and study are essential to validate the results obtained thus far and  to assess the potential of this new graft in a variety of vascular reconstructions.


How to deal with poor medical care.

How to deal with poor medical care.


Shoulder enlargement as the presenting sign in syringomyelia. Report of two cases and review of the literature. Two adult patients had painful enlargement of the shoulder and complete destruction of the humeral head. Angiograms of the shoulder showed highly vascular lesions in both patients. Both patients had syringomyelia, for which the swollen shoulder was the first manifestation.


Phrenic nerve injury from subclavian vein catheterization. Diagnosis by electromyography.


Occult rupture of the spleen: a dilemma in diagnosis.


Retroperitoneal fibrosis and avascular necorsis of the femoral head.


Evaluation of a new aerosolized steroid for asthma therapy: beclomethasone dipropionate (Vanceril inhaler). Beclomethasone dipropionate, an esterified derivative of betamethasone, can be given in small doses in aerosol form to patients with severe asthma whose symptoms cannot be controlled with nonsteroidal agents (bronchodilators and cromolyn). Many asthmatic patients who previously required systemic steroids can be transferred to this safer anti-inflammatory agent. In usual doses, beclomethasone produces few, if any, systemic side effects. The only susbstantial reaction is Candida infections of the oropharynx and larynx.


X-ray diffraction studies of lecithin bilayers.


NDV-O agglutinins and heteroagglutinins in sera of blood donors. In sera of healthy blood donors advancing age was accompanied by a decrease in the levels of agglutinins against human group O erythrocytes modified by Newcastle disease virus (NDV-O agglutinins) and of heteroagglutinins against sheep, guinea-pig and rabbit erythrocytes. Significant correlations of titres existed between the different heteroagglutinins, but not between these and the NDV-O agglutinins. The origins and interrelations of the natural agglutinins are discussed.


Changes in cholesterol synthesis and excretion when cholesterol intake is increased. The metabolic responses to increased amounts of dietary cholesterol include, in man, a reduction in the synthesis and an increase in the re-excretion of cholesterol. The effectiveness of these compensating mechanisms in preventing increases in the plasma cholesterol concentration was studied in nine subjects. Cholesterol absorption, the excretion of bile acids, the excretion of endogenous neutral steroids, and the cholesterol balance (synthesis) were measured twice during intakes of cholesterol of about 250 and 750 mg/day. The serum of the compensating mechanisms (reduction in synthesis and increase in excretion of cholesterol) almost equalled the increase in absorbed cholesterol when the intake was raised by 500 mg (mean change in compensation, 226 mg/day; mean changes in absorption, 230 mg/day). In three subjects in whom re-excretion of cholesterol was predominant and compensated for absorbed cholesterol, the plasma cholesterol levels rose substantially. In five others, in whom the predominant change was reduction in cholesterol synthesis, the rise in plasma cholesterol levels was not significant. At moderate intakes of cholesterol both compensating mechanisms prevented retention of dietary cholesterol in the body, though a rise in the plasma cholesterol level was prevented only when cholesterol synthesis was suppressed.


Retrolental fibroplasia and sudden infant death syndrome.


Drugs for athlete's foot and tinea cruris.


Soy-based formulas for infants.

Soy-based formulas for infants.


Emergency, Inc.

Emergency, Inc.


Growth and synthesis of rubratoxin by Penicillium rubrum in a chemically defined medium fortified with organic acids and intermediates of the tricarboxylic acid cycle. A sterile glucose-mineral salts broth was fortified with equimolar concentrations (10--3 M) of various organic acids and intermediates in the tricarboxylic acid cycle. Appropriate media were neutralized with 2 N NaOH, inoculated with spore suspensions or mycelial pellets of Penicillium rubrum and incubated quiescently for 14 days or with shaking for 5 days. Rubratoxins were recovered from culture filtrates by ether extraction and resolved by thin-layer chromatography. Toxin formation in quiescent cultures was enhanced by malonate but was not markedly affected by ethyl malonate, shikimate, and acetate or by isocitrate or oxaloacetate added in the presence of malonate. Citrate, cis-aconitate, alpha-ketoglutarate, succinate, fumarate, and malonate when present in the medium alone or in conjunction with malonate caused a 15 to 50% reduction in rubratoxin formation. Acetyl-CoA (10--5 M/flask) caused an 80% increase in toxin yield. Rubratoxin formation in shake cultures was not affected by succinate and malonate. All other combinations of intermediates and malonate caused a 10 to 50% reduction in toxin formation. At 10--3 M, citrate enhanced rubratoxin B formation and stimulated rubratoxin A production by as much as 100%. Above 10--3 M, citrate inhibited toxin production. Incorporation of [2-14C]acetate into rubratoxin was enhanced by malonate, fumarate, and malonate. A combination of pyruvate and malonate produced a 40% increase in [2-14C]acetate incorporation into rubratoxin. The highest reduction of labeled acetate incorporation (36%) was caused by succinate or alpha-ketoglutarate combined with malonate.


Treatment of fibrocystic disease of the breast with a prolactin inhibitor: 2-Br-alpha-ergocryptine (CB-154). In order to evaluate the importance of prolactin in the pathogenesis and clinical evolution of fibrocystic disease of the breast, serum prolactin levels were determined in 7 patients affected by this condition before and during treatment with a prolactin inhibitor, 2-Br-alpha-ergocryptine (CB-154). Serum prolactin levels were found to be low or normal before treatment. During treatment with CB-154 there was an improvement in all patients but 2. The results of the study do not allow any conclusion on the possible relation between serum prolactin levels and fibrocystic disease of the breast but they indicate that CB-154 may be useful for treating patients with this disorder.


Pregnancy of the wife of a complete paraplegic by homologeous insemination after an intrathecal injection of neostigmine. A case of successful pregnancy following artificial insemination following intrathecal neostigmine injection in the wife of a complete traumatic paraplegic (T7-T8 to T11-T12) is described.


The problems of the venereal diseases in general practice.


Venereal disease and the homosexual.

Venereal disease and the homosexual.


The increased release of 3H-5-hydroxytryptamine by d-para-methoxyamphetamine and d-amphetamine in vivo.


Shock lung and respiratory function.

Shock lung and respiratory function.


The use of a technicon SMA 12/60 multichannel biochemical analyzer in veterinary clinical pathology. This article has described many of the advantages of using a sequential multichannel autoanalyzer to obtain a biochemical profile on animal blood specimens and how this profile can be used in assessing the patients biochemical status. Precautions concerning the collection of blood samples to avoid spurious results have been emphasized. Hemolysis should, in particular, be avoided. Ideally, plasma should be separated from cells shortly after collection and refrigerated. If this is not possible, storage of whole blood under refrigeration (4 degrees C.) is permissible for a short period. In these cases minor changes in blood glucose, total CO2, and calcium may be expected. Also presented are some of the statistical calculations and manipulations that are possible utilizing a data bank containing the data from the SMA 12/60. This information is being used to update much of our knowledge of veterinary clinical pathology.


Laboratory diagnosis of pleural and peritoneal effusions.


The first international standard for human urinary FSH and for human urinary LH (ICSH), for bioassay. This paper describes the preparation and nature of the First International Standard for Human Urinary Follicle Stimulating Hormone and for Human Urinary Luteinizing Hormone, for Bioassay, and of two batches of working standard which were prepared from the same material. A collaborative study of these materials was carried out by six laboratories in six different countries. The FSH and LH activities of the Standard were assayed in terms of those of the Second International Reference Preparation of Human Menopausal Gonadotrophins, Urinary, for Bioassay, which it replaces. The results from 20 valid FSH assays and 30 valid LH assays (using four different methods) obtained in this way gave a weighted combined potency estimate for FSH of 53.7 IU, with 95 % fiducial limits of 47.2-61.1 IU, and for LH of 46.2 IU, with 95 % fiducial limits of 43.3-49.3 IU. Accelerated degradation studies of the Standard stored at elevated temperatures suggested that the stability of both FSH and LH activities under normal storage conditions would be satisfactory. The FSH and LH activities of the two batches of working standard (WS-A and WS-B) were compared with those of the Standard and were not found to differ significantly, except for the LH activity of WS-B which appeared to be slightly higher than that of the Standard. Accelerated degradation studies did not show any significant differences in stability between the Standard and batches of working standards. On the basis of these results the Standard has been established by WHO and allocated a potency for FSH of 54 IU per ampoule and for LH 46 IU per ampoule. The International Units for FSH, Human Urinary, for Bioassay and for LH (ICSH), Human Urinary, for Bioassay are thus defined as the activities contained in 0.1138 mg and 0.13369 mg of the International Standard, respectively.


Prolactin in the ram: seasonal variations in the concentration of blood plasma from birth until three years old. Peripheral prolactin levels were measured by radioimmunoassay in nine Ile de France rams, born in autumn and reared under natural conditions of light and temperature until three years old. During December, when the rams were 80-100 days old, a brief and transitory peak of prolactin occurred (70 ng PS6/ml plasma +/- 10 ng). During each following year, the prolactin level fell in winter to approximately 20 ng/ml. However, in summer the prolactin was 4 times higher than the winter level during the first year and 11 times higher during the 2nd and 3rd years. A possible role of prolactin variation throughout the breeding season is discussed.


Dynamic study of post-natal thyroid function in the rat. The thyroid function in development was investigated in post-natal rats. The thyroid iodine content rapidly increased from birth (137 +/- 26 ng iodine/mg thyroid) up to day 10 (338 +/- 42 ng iodine/mg thyroid) then increased more slowly up to day 30 (425 +/- 34 ng iodine/mg thyroid). The maximal plasma concentration of thyroxine was observed on day 16 (56.9 +/- 3.5 ng T4/ml) and of iodide on day 10 (110.2 +/- 12.6 ng I-/ml). The turnover rate constant of extrathyroidal thyroxine was higher at birth (8.0 +/- 2.3 %/h) than at any older age studied (average 6 %/h). Thyroxine secretion by the thyroid was more intense before weaning (37 ng hormonal iodine/h/100 g body weight on days 10 and 20) than after weaning (22 +/- 6 ng hormonal iodine/h/100 g body weight in 30 days old rats). The peripheral deiodination rate of thyroxine represented about 90 % thyroxine secretion rate in newborn and 10 days old rats and only 40% in adult females. In pre-weaning rats, after a single injection of both [131I]L-T4 and [125I]Na, extrathyroidal radioactivity disappeared more slowly than in 30 days old rats and adult animals. This suggests that iodide concentrations of extrathyroidal tissues are higher before than after weaning.


Thyroid hormone response to varying doses of TSH. Fifty-five normal subjects were studied following intravenous injection of increasing doses of bovine thyrotropin (b-TSH) from 0.5 to 250 mU/kg. Serum triiodothyronine (T3) and thyroxine (T4) were measured 1, 2, 3 and 4 h after the TSH injection. Dose-related increments in serum T3 and T4 were demonstrated with doses of b-TSH = 2.5 mU/kg and a maximum response was obtained after approximately 100 mU/kg. The fractional increase in serum T3 was greater than in serum T4, but the ratio between the increase in serum T4 and serum T4 and serum T3 (21.3/l ng/ng) was independent of the dose of b-TSH and time after TSH stimulation. The T3 response was reproducible and unaffected by sex and age.


Antigoitrogenic effect of casein.

Antigoitrogenic effect of casein. Epidemiological findings from the city of Cali, Colombia, support the hypothesis that water supply and iodine intake are not the only dietary factors which influence the magnitude of the goitre endemia. Experiments were conducted in rats to determine whether casein has a counteracting effect on the goitrogenic and antithyroid activities of methimazole (MMI) and goitrogenic water extracts (GWE) from the endemic area of the Cauca Valley. Female albino rats (Charles River, DC strain) 100-110 g initial weight, receiving 12 mug of iodine daily, were divided into three groups annd put on special diets: protein-free, 8 % casein, or 60 % casein, respectively. Each group (24 rats) was then divided into three subgroups. Subgroup one received goitrogen-free water and was used as a control. Subgroup two was administered MMI, 50 mug/day/rat. Subgroup three was given per animal a daily amount of GWE equivalent in antithyroid potency to 50 mug of MMI. At 77 days, the thyroid glands were studied for weight, 131I uptake, and 127I concentration. Animals on the protein-free diet showed significantly (P less than 0.05 - less than 0.01) larger thyroid glands per 100 g body weight and lower thyroidal 4 h 131I uptake and 127I-concentrations than rats on casein diets. These differences were significantly increased (P less than 0.01) by the administration of MMI and GWE. All the effects were completely reversed by the 60 % casein diet showing no differences between control rats and those on MMI or GWE. Rats on 8 % casein showed intermediate values between those of animals on protein-free and 60 % casein diets; differences were still present between the control as against the MMI or GWE groups, The results indicate that under these experimental conditions, a poor-protein diet impairs the thyroidal transport of iodine, decreases its concentration in the thyroid and is accompanied by an enlargement of the gland. Under these circumstances, the action of thiourea-like antithyroid agents is enhanced. The administration of protein reverses these alterations and decreases the action of such antithyroid agents. Whether the changes observed are due to a direct action of casein on the thyroid and/or to effects of malnutrition on the metabolism of antithyroid compounds remains to be determined.


The distribution of blood flow to the reproductive tract of anaesthetized ewes near oestrus. Radioactive microspheres were used to measure the rate and distribution of blood flow to the reproductive tract of anaesthetized sheep. Seven sheep were examined on day 14, 6 on day 15 and 10 on day 16 of the oestrous cycle: oestrus is normally on day 16 or 17. The rate of blood flow to the myometrium, endometrium and oviducts increased by 2-fold from day 14 to 15: the weights of these organs increased on day 16. Blood flow to the vagina and cervix increased by over 10-fold from day 14 to 15 but vaginal and cervical weights remained unchanged. Thirty minutes after the administration of 1200 IU PMSG, blood flow increased in the vagina and cervix on day 14, the myometrium on day 15 and the vagina, cervix and oviducts on day 16. However, these results must be viewed with caution since there were substantial, though not significant changes in the controls. The results favour the hypothesis that, near the end of the oestrous cycle, oestrogen has a dominant role in the control of blood flow to the reproductive tract of sheep.


The effect of atropine on the insulin release caused by oral and intravenous glucose in human subjects. Oral and intravenous glucose tolerance tests were performed on normal fasting subjects, with and without atropine. Insulin release after oral glucose was significantly diminished by atropine, and this effect could not be ascribed to the drug delaying glucose absorption. However, insulin release brought about by intravenous glucose was not altered by atropine. Possible interpretations of these results are discussed.


Cytosol and nuclear [3H]oestradiol binding in the foetal tissues of guinea pig. The formation of [3H]oestradiol macromolecule complexes was studied in vivo and in vitro in the kidney, lung and liver of intact foetal guinea pig. Specific binding of [3H]oestradiol was demonstrated in the cytosol and nuclear fractions of foetal kidney. Intensive binding was found in the cytosol of foetal lung but most of the bound radioactive material (70 %) was [3H]oestrone. Some binding was found in the cytosol of foetal liver but not in the nucleus of this tissue. In the in vivo experiments, the binding of radioactive material to plasma proteins was studied: 22 % of the plasma radioactivity was bound of which 67 % was identified as oestrone sulphate. Oestradiol sulphate represented 7% and unconjugated oestradiol only 0.6 % (0.1 % of the total plasma radioactivity). On the other hand, 2-3 % of the foetal plasma radioactivity was found as unbound [3H]oestradiol. In the kidney, the formation of [3H]oestradiol complexes in the cytosol fraction does not depend on temperature while nuclear [3H]oestradiol complexes increase with increasing temperature. Maximal formation of [3H]oestradiol complexes in the cytosol fraction and the 0.1 M TRIS and 0.3 M NaCl nuclear extracts was reached after 15 min but binding in the 1 M NaCl nuclear extract continued to increase up to 30 min. After incubation of purified nuclei of foetal kidney with 1.1 x 10(-7) M [3H]oestradiol, specific binding was found in the different nucelar fractions. Specific binding was also detected in isolated nuclei previously extracted by 0.1 M TRIS and 0.3 M NaCl before being incubated with 1.1 x 10(-7) M [3H]oestradiol. The Kd of binding of [3H]oestradiol in the renal cytosol fraction is 2.5 x 10(-10) M with n = 4.5 x 10(-14) moles/mg protein. Incubation of isolated 1 M NaCl nuclear extract from foetal kidney with [3H]oestradiol gives a Kd of 3.3 x 10(-10) M with n = 2.5 x 10(-14) moles/mg protein. It is concluded that the nuclear complexes in the foetal kidney could be formed either through an intermediate cytosol complex or that the "two step" mechanism could take place in the nucleus. Furthermore, direct binding of [3H]oestradiol with high affinity was observed in the 1 M NaCl nuclear extract.