HBsAg and HBcAg in the livers of asymptomatic hepatitis B antigen carriers. Asymptomatic blood donors with persistent HBs antigenaemia have a variety of histological lesions in the liver, and serial biopsies indicate that, in some, these lesions may progress. The immunoperoxidase technique was found to be a sensitive method for the histological demonstration of HBsAg and HBcAg. Livers showing minor histological changes contained more HBsAg than those with active lesions and there appears to be an inverse relationship between the amount of HBsAg in the liver and the severity of the histological damage. In the carriers who had more than one biopsy, the presence of stainable HBsAg, irrespective of the initial histological diagnosis, was associated with a greater likelihood of progression of the histological lesion. HBcAg was found only in the hepatocyte nuclei of carriers with chronic aggressive and chronic persistent hepatitis.


The many faces of food--as seen through the eyes of the artist. Artists through the ages have displayed an interest in food, not only for its nourishing value but also for its aesthetic nature. Consequently, the art world has endowed the field of nutrition with a colorful record of the artistic merits and heritage of food. In this article, the author explores some of the food lore depicted in various famous paintings. Such insights should be rewarding to anyone who enjoys pictorial art as an avocation--and especially to those whose vocation involves food. As knowledge of food and eating customs increases, so also does the appreciation for the theme of a painting, the intent of the artist, and the culture that nourished both his palate and palette.


Relative cumulation of beta-BHC in ecological and biological system. During 1971-1974 a study was undertaken to analyze 1234 samples of different elements of food chain from three regions of Slovakia in order to obtain information on ecological relations of the dynamics of residues of four isomers of BHC compared with p,p-DDT and DDE. In contrast to most literature data, a higher relative cumulation of beta-BHC in animal food products compared to the other isomers was noted. The observed relations between the individual BHC isomers were verified in a model feeding experiment on poultry. Dynamics of the transfer of the BHC isomers between fodder, meat, liver, and eggs were studied in broilers and laying hens. All results of the model feeding experiment confirmed the conclusions of the ecological studies concerning beta-, gamma-, and -delta -BHC. The persistence of the alpha-BHC was not confirmed in this manner.


[Alpha-fetoproteins in maternal serum. Radioimmunologic determination in current obstetrical practice. Analysis of 669 determinations]. The analysis of 669 levels of maternal serum alpha-fetoproteins carried out using a radio-immunological technique with double antibodies has enabled a diagram of normal values to be established on the one hand has shown up certain modifications of levels when different pathological conditions arise in pregnancy on the other hand. Raised levels were found in: intra-uterine fetal death. In some cases the rise preceded death, in twin pregnancies. Low levels were found in: severe pre-eclamptic pregnancies, in low intra-uterine fetal growth after the 32nd week, in threatened premature labour. Finally, the levels of AFP in the maternal serum were found to be normal in two cases where there were neural tube malformations. The existence of variations in the levels of AFP in maternal serum in a variety of pathological features suggests that these levels could be used as a new parameter in the biochemical monitoring of the fetus.


Ultrastructural immunoenzymatic study of alpha-fetoprotein-producing cells in the human fetal liver. Cells producing alpha-fetoprotein in human fetal liver have been studied with specific horseradish peroxidase labeled immunoglobulins. Under light microscopy, the alpha-fetoprotein is strictly localized in the cytoplasm of certain hepatocytes, distributed randomly in the hepatic lobule. Ultrastructural examination of thesame cells shows that the alpha-fetoprotein is present within the cytoplasm. Ultrastructural differences are described in hepatocytes according to whether or not the cell is producing alpha-fetoprotein at the time of sampling. These observations lead to the hypothesis that alpha-fetoprotein may correspond to a particular functional state of the hepatocyte in human fetal liver.


Effects of primary antiserum dilution on staining of "antigenrich" tissues with the peroxidase antiperoxidase technique. The effect of primary antiserum dilution on staining results with the peroxidase antiperoxidase method were investigated using frozen sections of perfused rat cerebellum and optic nerve. Results comparable to formalin fixed and paraffin embedded tissue were attainable only when low antiserum concentrations were used. Optimal staining of antigen rich tissue, such as frozen sections, with the peroxidase antiperoxidase method required low antiserum concentrations apparently to minimize the binding of both antigen-binding fragments of the bridging antibody to the tissue bound antiserum. It appears that low antiserum concentration insures that sufficient bridge antibody molecules will be only singly bound and thus free to attach the peroxidase antiperoxidase complex.


Specificity of the glial fibrillary acidic protein for astroglia. Glial fibrillary acidic protein (GFA) is the main constituent of glial filaments and the close similarity of GFA and neurofilament protein has been recently reported. However, the immunofluorescence staining of peripheral nerve which may be observed with GFA antisera is not due to cross-reaction between GFA and neurofilament protein. Staining of peripheral axons was also observed with control sera obtained by injecting the rabbits with nonimmunogenic GFA preparations isolated with the same procedure. Immune GFA antisera and control sera reacted with sodium dodecyl sulfate extracts of sciatic nerve. However, the precipitin line formed with peripheral nerve crossed the line against GFA protein, thus indicating nonidentity between the two antigens. Buffer extract of sciatic nerves that had been incubated with spinal cord reacted by immunodiffusion with GFA antisera, thus indicating that redistribution of GFA occurred under these conditions.


Staining of rickettsial antigens for microagglutination reaction. Staining of antigens of R. prowazeki, R. canada and R. conori with hematoxylin-Harris for use in MAR was developed. Optimal results were obtained when rickettsial antigens were stained at 4 degrees C for 18 hours. Comparison of MAR with CFR has shown that MAR using stained rickettsial antigens is specific and as sensitive as CFR.


Comparison of microscopic positivity in smears from sputa stained according to Ziehl-Neelsen in different modifications. Some basic factors influencing the detection of microscopic positivity in the sputa of patients with tuberculosis of the lungs, stained according to Ziehl-Neelsen in various modifications, were studied in 9 laboratories in 5 different countries (Bulgaria, Czechoslovakia, Mongolia, German Democratic Republic and Poland). Each laboratory prepared 200 coded slides from 50 suspect-positive sputa. The slides were stained using four different methods and despatched, without examination, to the next laboratory in the series. A total of 1 800 slides from 450 sputa were thus evaluated and each smear was successively examined by 8 different readers. The study has shown that the result of direct microscopy depends primarily on the individual qualities and attentiveness of the workers evaluating the slides while the remaining factors are less important. Mechanical homogenization of sputa before making the smear, carried out by shaking the sputum with glass beads, had a significant effect on the number of detected mycobacteria while homogenization using soda lye did not influence the positivity in any direction. The detection of mycobacteria after hot staining was significantly higher than after a 2-hour action of carbolfuchsin without heating. Additional staining with picric acid or malachite green had no effect on the amount of bacteria detected and the method of examination (in one line or meander-like on selected spots) was found to be completely unimportant.


Distribution of the thy-1 antigen in cellular and subcellular fractions of adult mouse brain. By using a cytotoxicity inhibition assay employing AKR anti-C3H thymocyte antiserum, we have determined the degree of expression of the thy-1 antigen in fractions of adult mouse brain. As expressed as cytotoxicity inhibitory capacity per mg protein with C3H whole brain arbitrarily assigned a value of 1.0, the following values were found: C3H cerebral cortex, 5.8; C3H cerebral cortex synaptosomes, 2.5: C3H whole brain myelin, 0.65; C3H cerebral cortex neurons, 0.16; and C3H cerebral cortex mitochondria 0.10. Neither C1300 neuroblastoma cells nor any AKR neural fraction had detectable levels of thy-1. The findings indicate that the thy-1 antigen is found mainly in mouse cerebral cortex and in synaptosomal fractions, whereas myelin fractions contain lower but perhaps significant amounts of thy-1. Cerebral cortex neurons, isolated by a method requiring a 90-min mild trypsinization at 37 degrees C, did not display significant amounts of the thy-1 antigen. These results lend themselves to further study in the area of differentiation and development of central nervous system components and in the area of central nervous system immunopathology.


A carbohydrate-containing antigen from Trypanosoma cruzi and its detection in the circulation of infected mice. A polysaccharide-containing fraction has been prepared from the water-soluble material of a phenol-water extract of epimastigote forms of Trypanosoma cruzi. Sera from rabbits immunized with this material have been used to detect trypanosome-derived polysaccharide in plasma of mice acutely infected with this parasite. The polysaccharide nature of the circulating antigen is suggested by its heat stability, resistance to proteinase and nucleases, and destruction by sodium metaperiodate, as well as by its periodic acid-Schiff staining and precipitation with concanavalin A. The antigen appears to be present in different strains of the parasite and in different stages in the life cycle of the parasite.


Inhibition of human lymphocyte transformation by human alpha-fetoprotein (HAFP); HAFP monomers and multimers and a resistant lymphocyte subpopulation. We have previously shown that human alpha-fetoprotein (HAFP) inhibits the response in vitro of human lymphocytes to a variety of mitogenic stimuli. In this report we present evidence that HAFP preparations containing dimeric and trimeric forms are no more inhibitory than HAFP monomeric isolates. HAFP isolates of low inhibitory potency cannot impede the capacity of high-potency HAFP to inhibit lymphocyte transformation. Since lymphocyte responses to phytomitogens or anti-human thymocyte antiserum cannot be totally suppressed by increasing doses of HAFP, we conclude that human lymphocyte preparations contain a population of lymphocytes resistant to the inhibitory action of HAFP.


The Tla locus: a new allele and antigenic specificity. Four of 23 H-2 alloantisera screened for anti-TL activity contained such activity. One of these alloantisera, D-35, defined a new TL specificity, TL.5, and a new Tla allele, Tlad. TL.5 has all the characteristics of a TL antigen and has a different strain distribution than previously known ones. This new complexity at the Tla locus and the previous finding of other serologically defined genes in the Tla region indicate that this genetic region cannot be ignored in analyzing antisera produced in strains made congenic for the major histocompatibility complex.


Humoral immunostimulation. VII. Sialic acid masks antigenic sites on an antibody-selected bariant cell line. Variant cell lines (LC1, LC2) obtained by growth of mouse L cells (L) in cytostimulatory and cytotoxic doses, respectively, of rabbit anti-L cell antiserum AL) were found previously to be altered in many ways relative to the parent cell line. A major change was the reduction of those surface membrane antigens that AL recognizes. These cell variants have now been found to have increased membrane sialic acid relative to L. Treatment of intact variant cells with neuraminidase (50 units/ml, 37 degrees C, 1 hr) greatly restored the susceptibility of LC1 to lysis with AL. In the presence of 1/100 dilution of AL and 5% complement the viability indices (1.00 = no cell kill) of untreated and neuraminidase-treated cells were respectively: L 0.10 and 0.03 and LC1 0.91 and 0.40. Neuraminidase-treated LC2 cells retained their resistance to AL. Parallel studies with 125I-ALIgG showed increased binding to neuraminidase-treated LC1 relative to native LC1. These findings suggest that the altered membrane sialic acid content affects the immunologic behavior of this cell variant by masking the original cell surface antibody-binding sites. This represents a possible mechanism for tumors to escape immunologic control.


Colonic tumor membrane-associated glycoprotein: isolation of antigenically-active peptides after chemical cleavage. A membrane-associated glycoprotein fraction, referred to a CEA-M was isolated from human colonic tumor tissue by sodium dodecyl sulfate extraction of membrane fragments followed by wheat germ agglutinin affinity chromatography, Bio-Gel A-1.5 gel filtration and preparative slab gel electrophoresis. With a m.w. of approximately 200,000, isoelectric point of about 4.2 and carbohydrate:protein ratio of 2:1, this glycoprotein has physiocochemical and antigenic similarities to carcinoembryonic antigen, CEA. Immunochemical studies have shown that antiserum developed for this glycoprotein possesses relative specificity for human colonic carcinomas. Chemical cleavage of this glycoprotein by 2-nitro-5-thiocyanobenzoic acid resulted in three major Coomassie Blue and two periodic acid Schiff stainable fragments (one of which stains with both). It was found that one of the glycopeptides, labeled as TA, isolated by affinity and covalent chromatography, contained 77% carbohydrates and possessed antigenic determinants recognized by at least 70% of the antibody population raised against the total glycoprotein fraction; purified antibodies to this region of the molecule seem promising for the development of a specific assay for gastrointestinal tumors.


Expression and function of I region determinants on immunocompetent cells. I. Selective expression of I-C region determinants on immune cells. We have examined the cytotoxic activity of anti-Iak serum and complement on various immune functions of BALB/c (H-2d) cells. Since the cytotoxic action of this antiserum on H-2d cells defines specificity Ia.7, an I-C region product, we have looked at the selective expression of this antigen. We have mainly used the in vitro anti-Lac2 response to study the cells involved in the induction and regulation of antibody. The data presented here show that Ia.7 is present on both IgM and IgG precursor B cells and in lesser amounts on plaque-forming cells. The antiserum also recognizes with less efficiency a product on specific T suppressor cells, which is possibly coded for by the adjacent I-J subregion. Both fluorescence and functional tests indicate the absence of Ia.7 on macrophages. It is also lacking on T helper cells. When we tested the antiserum on the in vitro cytotoxic responses to alloantigens, we found that neither T effector cells nor their precursors were affected.


Regulation of the immune response to tumor antigens. III. Characterization of thymic suppressor factor(s) produced by tumor-bearing hosts. Immunosuppressor T cells (IST),6 capable of inhibiting the rejection of a methylcholanthrene-induced fibrosarcoma (S1509a) in A/Jax mice immune to this tumor, produced soluble factors with similar suppressive activity. The immunosuppressive factor(s) (ISF) has been shown to be immunologically specific, as demonstrated by the complete loss of suppressive activity after absorption with S1509a cells, but not with cells of an unrelated syngeneic tumor. From its behavior on gel filtration, the size of ISF was deduced to be less than 70,000 daltons. The ISF was not removed by passage through a rabbit anti-mouse F(ab')2 reverse immunosorbent and, hence, it was concluded that ISF was not likely to be an immunoglobulin. The (immunosuppressive) activity of ISF was destroyed by treatment with Pronase, but not with RNase. The ISF was found to share the antigenic determinant(s) of the product(s) of the K end of the major histocompatibility complex of the mouse. Moreover, antibodies to ISF were induced by immunization with ISF-tumor cell complexes. Thus, IST and their factor(s) appear to play an important role in the regulation of the immune response to tumor antigens.


Functional heterogeneity among the T-derived lymphocytes of the mouse. VII. Conversion of T1 cells to T2 cells by antigen. The T1 subpopulation of peripheral T cells was defined in mice by its short half life, insensitivity to anti-thymocyte sera (ATS) in vivo, and slow kinetics of response to antigen. The T2 subpopulation was defined by its long life time, elimination by ATS in vivo, and rapid response to antigen. Mice containing only T1-type T cells were constructed by adult thymectomy (ATx) followed immediately by the elimination of T2 cells by ATS treatment. Immunization of these mice with SRBC led to the production of memory helper cells in the T2 subpopulation. This process depended on the presence of T1 cells and for the most part required SRBC immunization, although a few SRBC-specific T2 cells reappeared in the mice in the absence of antigen. We conclude that T1 cells can give rise to T2 cells in an antigen-driven step and that the two populations correspond to virgin and memory T cells, respectively.


Pilot studies on recombinant cold-adapted live type A and B influenza virus vaccines. Recombinant live attenuated type A and B influenza virus vaccines derived from standardized cold-adapted parent strains were given singly and in combination to volunteers. The vaccine viruses were well tolerated, functioned as good antigens, and failed to spread to intimate household contacts. Thirty-nine isolates that were recovered after a single passage in humans appeared genetically stable. The results of histopathologic studies in ferrets encourage development of an animal model for attenuation of the virus.


Microgranulocytotoxicity.

Microgranulocytotoxicity. The microcytotoxicity assay technique has been extensively refined to permit the use of granulocytes as target cells in an effort to identify neutrophil-specific antigens. Virtually every aspect of the test required revision to obtain clear, reproducible results.  The most radical modification was the adoption of double-fluorescent vital staining to detect cytotoxicity. The reactions detected with this new assay did not correlate with defined human histocompatibility systems (e.g., HLA, ABH, NA, NB, NC), nor were the target antigens detected on lymphocytes or platelets. Cytotoxicity was highly specific and was produced by the immunoglobulin fraction of alloantisera only in the presence of complement, thus implicating an antigen-antibody phenomenon rather than variable viability of the ephemeral PMN's in vitro. These specificities may have an impact on some aspects of human transplantation (especially of bone marrow) as well as playing a role in some febrile transfusion reactions. Of perhaps greater import is the suggested role of the antigens in immunoneutropenias and therefore in the response of myelosuppressed patients to adjunctive leukocyte transfusion therapy.


The use of immunoabsorbents for the purification of mycobacterial antigens. Affinity chromatography using immunoabsorbents prepared from goat antisera has been applied to the purificaton of antigens from culture filtrates of Mycobacterium tuberculosis. The optimum conditions for the preparation and use of these immunoabsorbents have been determined. Urea has been studied as an eluant, and it has been found that antigen can be eluted with 4M urea at pH 9 with satisfactory yields, minimal loss of antigenicity, and minimal disruption of the immunoabsorbent.


Superadditive cytostatic effects after combined administration of vincristine, bleomycin and methotrexate to Yoshida sarcoma. Vincristine, bleomycin and methotrexate are three cytostatic drugs which are particularly effective in epidermoid carcinoma of the head and neck region. As their dose-limiting side effects differ from one another, it appeared reasonable to combine them. To examine in vitro whether this combination increases cytostatic activity, the three drugs were administered to Yoshida sarcoma. It could be demonstrated that the growth inhibition activity and the cell disturbance activity were much higher with combination therapy than with single drug therapy. From this, it follows that beneficial results in the treatment of head and neck carcinomas can be expected.


A subvariant of concealed bigeminy.

A subvariant of concealed bigeminy. A subvariant of the "even variant" of concealed bigeminy was studied in two patients. The typical pattern consisted of two types of sequences of conducted sinus beats between extrasystoles. One pattern was bigeminal, i.e., alternating sinus beats and extrasystoles. Between bigeminal sequences were intervals in which there were more than one conducted sinus beat between extrasystoles. In such longer sequences, the numbers of sinus beats were almost invariably even. In the bigeminal sequences, the coupling intervals progressively diminished for each successive extrasystole in the sequence. The proposed explanation for the subvariant was based on a reentry loop in which there were three sites of block: proximal, intermediate, and distal. Block was postulated to take place at the proximal site after those extrasystoles with the shortest coupling intervals, at the intermediate site after odd-numbered conducted sinus beats in the non-bigeminal sequences, and at the distal site ("concealment") after the even-numbered sinus beats in these longer sequences.


Spontaneous gap phenomenon in atrioventricular conduction produced by His bundle extrasystoles. A gap in atrioventricular conduction is a zone within the cardiac cycle during which premature impulses are blocked in the conduction system, while impulses of greater or lesser prematurity are conducted. This has previously been produced only by atrial or ventricular stimulation techniques. This report demonstrates a spontaneous gap produced by His extrasystoles.


Distribution of immunoglobulin determinants on the surface of Xenopus laevis splenic lymphocytes. The distribution of surface immunoglobulin (Ig) determinants on Xenopus laevis splenic lymphocytes after combination with divalent rabbit anti-Ig coupled to ferritin was studied. The electron micrographs showed the presence of immune complexes in 67% of lymphocytes treated at 0 degrees C-4 degrees C. The complexes were located all around the membrane and uniformly distributed in a random fashion. The variation of ferritin grain counts on cell sections is such, that the existence of two major subclasses of Ig-positive cells may be suggested. Raising the temperature produced a rapid interiorization of the complexes in vesicles without any previous aggregation to form a "cap" having occurred.


Cell generation and type C virus expression in the human embryonic cell strain HEL-12. The spontaneous expression of a type C virus in a diploid strain of human embryonic lung fibroblast-like cells (HEL-12) was examined during serial culture. Virus antigen expression was determined by indirect immunofluorescenc with antisera to disrupted simian sarcoma virus and the 28000 mol. wt. internal antigen of the endogenous cat virus RD-114. Virus production was examined by reverse transcriptase assays of culture fluids. Virus antigens were not detected for 25 days after frozen, primary HEL-12 cells were reinstated in culture. The cells expressed virus antigens but did not release virus particles between 25 and 80 days. Spontaneous virus release and maximal antigen expression occurred in cells grown for 80 to 120 days. Virus particles were not detected after 120 days although virus antigens persisted until the experiment was terminated. The HEL-12 virus was infectious for cell cultures of human, rhesus monkey, dog and rabbit cells. The proportion of SiSV-like and RD-114-like antigenic components of HEL-12 virus were altered by passage through heterologous cells suggesting heterogeneity of the HEL-12 virus population.


Oligoclonal gamma-globulin banding of cerebrospinal fluid in patients with subacute sclerosing panencephalitis. Comparison of the electrophoretic pattern with that in multiple sclerosis and congenital infections. Lumbar cerebrospinal fluid (CSF) of 8 patients with subacute sclerosing panencephalitis (SSPE) was examined by agarose gel electrophoresis. In comparison with normal controls and children with different neurological diseases (including infections, tumours and degenerative diseases) the quantitative evaluation of the pherograms by an analog computer revealed an extreme change of the gamma-globulin profile. All cases showed 6-7 abnormal subfractions consisting of 2-4 tall, markedly protruding spikes and several small intermediate fractions. The oligoclonal gamma-globulin contributed 20.1-42.5% to total protein. This particular gamma-globulin profile seems to be highly indicative of the diagnosis of SSPE. It can be distinguished from the oligoclonal pattern in patients suffering from multiple sclerosis (MS) and congenital infections. The CSF protein profile of 13 patients with MS was different from that in SSPE in that it showed 1-5 monoclonal gamma-fractions in every case with none or only one peak protuding more markedly. The percentage of all subfractions amounted to 4.5-23.8% of total protein. As in MS, the aspect of oligoclonality in 9 children with congenital infections (cytomegalic inclusion body disease, toxoplasmosis and rubella) was quite variable, as again 1-5 abnormal subfractions were detected. Their relative concentrations, on the whole ranging from 0.6-12% of total protein, was considerably lower than in SSPE.


Maturation and anaplasia in neuronal tumors of the peripheral nervous system; with observations on the glial-like tissues in the ganglioneuroblastoma. Six cases of peripheral ganglioneuroblastoma are described and analyzed; in general these contained neuroblasts, mature ganglion cells and cells of intermediate degrees of maturity. Portions of the tumor resembled the glial tissues of the central nervous system, but this is spurious, no glial cells or fibers being present. Such tissues contained cells of intermediate maturity, immature axons which characteristically stain poorly with silver stains for axons, and a paucity of connective tissue fibers. These tumors exhibit a tendency for continued maturation with decreased malignancy, and for anaplastic change with increased malignancy. These opposing tendencies make it difficult to predict the outcome with complete certainty, except possibly in those cases in which maturation is complete. Schwann cells are present in those tissues which have matured to form neurons with axonal processes. The Schwann cells are probably reactive, not neoplastic. The presence of Schwann cells in such mature tissues is most readily explained on the assumption that Schwann cells are mesenchymal in character, and have been formed by differentiation of multipotential primitive reticular cells in response to the formation of axons by the maturing neurons.


Focal lesions of muscle in peripheral vascular disease. Lesions in skeletal muscle resulting from ischemia caused by peripheral vascular disease in two patients were essentially identical to the early muscle lesions of Duchenne muscular dystrophy (DMD) patients and carriers of that disease, as well as to the early muscle lesions of experimental animals with aorta ligations plus a small dose of 5-hydroxytryptamine (serotonin). The one similarity is harmonious with, although does not necessarily advance, the ischemia hypothesis of DMD, and the other supports the ischemia mechanism proposed in the animal model.


Persistently abnormal brain scintigraphy after cerebral infarction. The current literature indicates nuclear brain images typically return to normal within two to three months following an episode of cerebral infarction. In this report, two patients are described who demonstrated no significant change in their brain scan abnormalities 11 and 17 months following their strokes. Computed tomography confirmed the clinical impression that the persistent brain scan abnormalities were due to cerebral infarction rather than to neoplastic process.


Correlation between the clinical picture, the EEG and cerebral blood flow after partial occlusion of the middle cerebral artery in man. Quantitative measurements of global and regional cerebral blood flow were performed in 18 patients 1 to 3 days after the onset of symptoms of acute cerebral ischemia due to partial occlusion of the middle cerebral artery and were repeated 21 days thereafter. The first rCBF measurement revealed either an extensive ischemic focus or an ischemic focus with simultaneous reduction of the global blood flow within the corresponding hemisphere in all patients. The later measurements indicated no change in blood flow in the ischemic focus in any case, but there was a slight increase of global cerebral blood flow in 1/3 of the cases. The measurements of cerebral blood flow were correlated with the neurological, psychopathological and EEG findings and in spite of an unaltered cerebral blood circulation, all patients showed a distinct clinical imrovement. Various hypotheses for the return of neurological functions in patients with persistent cerebral ischemia are discussed.


[The management of urinary and fecal incontinence due to a neurinoma of the cauda equina with an electrode implanted in the pelvic muscles (Caldwell) (author's transl)]. A woman, aged 49, had a complete sensory and motor deficit of the S2-5 segments with urinary and fecal incontinence due to a neurinoma of the cauda. A Caldwell electrode was implanted surgically into the muscles of the pelvic floor in April 1974. The patient was observed for 2 years thereafter and had an excellent result. The medical and technical problems of treating urinary and fecal incontinence due to a lower motor neuron lesion of S2-5 can be handled satisfactorily with an implanted electrode.


A morphological and chemical study of calcification of the pineal gland. A general scheme of analysis for the investigation of minute calcification is presented. After low temperature ashing, the samples are subjected to chemical, structural and morphological study, using atomic absorption spectrometry, infrared spectrometry, X-ray diffraction and scanning electron microscopy. Details about the calcification of the human pineal gland are given. The content of trace elements is very high, but within the limits found in other biological apatites. It is concluded that calcification of the pineal is a more general occurence than has been realized.


The oxytalan fiber system in the mandibular periodontal ligament of the lathyritic mouse. Experimental lathyrism was produced in young albino mice with a diet containing 50% sweet pea seed (Lathyrus odoratus). After 7 days on the lathyritic diet, sections of themandibular molar and incisor periodontal ligaments, when oxidized and treated with aldehyde fuchsin, demonstrated enhanced staining of the oxytalan fibers and numerous vessels. At this time aldehyde fuchsin or orcein also revealed marked pathological changes in the periodntal ligament of all molars. When athyrism was prolonged for 12 weeks, both the molar and incisor oxytalan systems were still readily identifiable although the molar periodontal ligament continued to be serverely affected by lathyrism. The oxytalan fibers retained their characteristic tooth-vascular association in all of the lathyritic mice. Oxytalan fibers of the lathyritic and control animals showed similar reactions to enzyme digestion with beta-glucuronidase, elastase, and pepsin. However, gingival elastic fibers reacted in a different way from oxytalan fibers with beta-glucuronidase and elastase treatment. These findings indicate that in the lathyritic mouse the oxytalan fiber system of functioning teeth possesses a high degree of permanence and is metabolically distinct from collagen and elastic fibers.


Evaluation of an electronic device for gingival fluid quantitation. A number of factors which might affect the readings of the HAR-600 GCFM were studied: 1. The readings were higher when the filter paper strips were placed between the fron halves of the upper and lower counterparts than when they were placed between the rear halves. No differences in readings were observed when the strips were placed in the middle, the left, or the right areas of the counterparts. 2. The higher the fluid viscosity the lower the reading. Salt water (0.9% NaCl) gave a lower reading than deionized water. 3. Increased room temperature or relative humidity led to higher readings, especially when the fluid volume exceeded 0.2 microliter. 4. More reading time was required for high viscosity fluid, low temperature, and high relative humidity. The HAR-600 GCFM readings and the lengths of ninhydrin-stained areas were compared. Both methods were able to reflect the amounts of serum absorbed.


Comparative pharmacokinetics of coumarin anticoagulants XXIV: Effect of treatment with phenobarbital on serum protein binding of warfarin and dicumarol in rats. Rats were treated with the enzyme inducer phenobarbital to determine if it would affect the serum protein binding of warfarin and dicumarol, possibly by changing the rate of formation or elimination of endogenous inhibitor(s). Daily administration of phenobarbital, 75 mg/kg, for 4 days increased relative liver size (a concomitant of enzyme induction) but had no apparent effect on the serum protein binding of warfarin and dicumarol.


Effects of innervation on the distribution of acetylcholine receptors on cultured muscle cells. 1. Myotomal muscle cells from embryos of Xenopus laevis were cultured as a monolayer either alone or together with neural tube cells from the same embryos. 2. Spontaneous twitching and contractions evoked by electrical stimulation of neural perikarya were observed only in nerve-contacted muscle cells, and could be abolished by curare or alpha-bungarotoxin. 3. Within 2 days in culture muscle cells not contacted by nerve developed one or more discrete patches of acetylcholine (ACh) receptors as revealed by staining with fluorescent conjugates of alpha-bungarotoxin. Similar patches were also seen when staining was carried out after paraformaldehyde fixation, suggesting that they were not induced by the dyetoxin conjugate. 4. Radioautography after labelling with [125I]alpha-bungarotoxin revealed patches with grain densities approximately twenty-five-old greater than over the remainder of the cell. 5. Fluorescent stain on innervated cells was restricted to the path of nerve-muscle contact and sometimes extended for greater lengths than the largest patches seen on non-contacted muscle cells. 6. Similar long bands of stain associated with nerve--muscle contacts were observed when cultures were grown in high concentrations of curare and carbachol which prevented spontaneous twitching. They were also seen in cultures in which the addition of neural tube cells was delayed for 2-3 days. 7. It is concluded that innervation caused receptors to accumulate at sites of nerve-muscle contact and that this process can operate independently of muscle activity.


Nerve-induced and spontaneous redistribution of acetylcholine receptors on cultured muscle cells. 1. Theree-day-old cultures of myotomal muscle, obtained from embryos of Xenopus laevis, were stained with fluorescent conjugates of alpha-bungarotoxin and maintained in native toxin in order to ensure that ACh receptors subsequently inserted into the sarcolemma would not be stained. Neural tube cells were then added to the cultures. 2. When cultures were exmained 1-3 days later fluorescent stain was found to be associated with sites of nerve-muscle contact. In some cases the stain along the path of contact extended for greater distances than the patches of stain seen on non-contacted muscle cells. 3. The development of new areas of fluorescent stain at sites of nerve-muscle contact was confirmed by making successive observations on the same muscle cells over a period of a day. 4. Similar experiments on muscle cells not contacted by nerve revealed the formation of new receptor patches, usually in areas of cell growth. 5. The majority of fluorescent pathes on non-contacted muscle cells did not undergo changes in size or shape over the course of 1-2 days. However some examples of enlargement, shrinkage and disappearance were observed. 6. On the basis of these findings it is concluded that ACh receptors aggregate within the sarcolemma, spontaneously as well as in response to innervation. In the latter case extrajunctional receptors accumulate at the site of nerve contact thereby contributing to the development of high receptor density in the subneural muscle membrane. This process of receptors redistribution occurs in the absence of synaptic or contractile activity. 7. Possible mechanisms involved in the redistribution of ACh receptors are discussed in relation to those which appear to modulate ligand-induced changes in the distribution of lectin and immunoglobulin receptors.


Transient osteoporosis of the hip.

Transient osteoporosis of the hip. Osteoporosis in a painful hip is usually a sign of inflammation or tumor. There exists, however, a self-limited clinical entity that presents with pain in the hip and where the only roentgenological manifestation is osteoporosis. Eight patients with this disease are described: five men and three women, ranging in age from 29 to 50 years. In four patients, the onset of disease was related to sprain, pregnancy, or delivery. Laboratory analyses and the clinical course of the disease excluded inflammation or a neoplasm as the cause. All patients fully recovered with 12 month, with no sequelae. The etiology of the disease remains unknown.


Stereoscopic anatomy: evaluation of a new teaching system in human gross anatomy. Traditionally, human gross anatomy teaching has revolved around anatomical dissection. Unfortunately, during the last decade a number of medical schools have experienced a decrease in the number of hours allotted to gross anatomy instruction compounded by a shortage of anatomical donors. This, in turn, has served to increase the difficulties of providing students with truly effective anatomical instruction. To help overcome this problem, a stereoscopic slide-based auto-instructional program has been developed as a substitute for dissection. Evaluation data suggest that this program, while having minor limitations in terms of anatomical orientation, does provide a viable alternative to dissection.


Stereospecific opiate binding in human erythrocyte membranes and changes in heroin addicts. Stereospecific opiate binding has been demonstrated in human erythrocyte membranes, having a Kd of 9-10(-9) M. In most respects the binding characteristics resemble those of synaptic membranes. These included the correlation of binding affinity and pharmacological potency of opiates; competition by naloxone; inhibition by Ca2+ and Na+; and sensitivity to phospholipases and trypsin. A comparison of stereospecific opiate binding in control human subjects and heroin addicts revealed a 43% increase in the addict group.


Distribution and expression in mammals of genes ralated to an endogenous type C RNA virus of Odocoileus hemionus. An endogenous type C virus recently isolated from the Columbian black-tailed deer (Odocoileus hemionus) was used as a molecular probe to study the distribution of virus-related nucleotide sequences in cellular DNAs of mammalian species. By DNA-DNA hybridization, the most extensive homology was demonstrated between the viral complementary DNA and cellular DNA isolated from Odocoileus species. DNAs of representatives of other genera within the same family, Cervidae, were partially related to the virus, consistent with the phylogenetic relationship of these species to Odocoileus. O. hemionus viral sequences were also detected within cellular DNAs of members of a more distantly related artiodactyl family, Bovidae. These findings suggest the genetic transmission of type C viral genes within cervids and bovids for a period of at least 25 to 30 million years. There was no detectable nucleotide sequence homology between O. hemionus virus and representatives of other major groups of mammalian type C viruses. These results indicate that despite the known antigenic relatedness of mammalian type C viruses, the O. hemionus virus has diverged sufficiently to be considered the prototype of a separate group. By radioimmunological techniques, it was possible to detect and partially purify, from normal tissues of cervid species, antigens related to the major structural protein of the O. hemionus virus. The present findings, that O. hemionus virus has been genetically transmitted for millions of years and yet has maintained the ability to be expressed as infectious virus, argue for positive evolutionary selective pressures for the maintenance of type C viral genes.


Proteins of Rous-associated virus type 61: polypeptide stoichiometry and evidence that glycoprotein gp35 is not a cleavage product of gp85. The two glycoproteins, gp85 and gp35, of Rous-associated virus type 61 (RAV-61), were isolated from radiolabeled virions by gel electrophoresis and digested with trypsin. The chromatographic profile of the gp35 digest revealed no peaks in common with that of gp85; therefore, the smaller glycoprotein is not a cleavage product of gp85. The stoichiometry of radiolabeled RAV-61 proteins was studied by quantitative gel filtration and gel electrophoresis. Among the 11 polypeptides identified were 4 minor ones, including the beta(p91) and alpha(p64) chains of reverse transcriptase and two unidentified chains, p76 and p35; the latter two were unmasked by removing the virions' surface glycoproteins with a protease, bromelain. Virions contained some 15 to 30 molecules of reverse transcriptase.


DNA polymerase activities in growing cells infected with simian virus 40. Growing CV1 cells were infected with simian virus 40 (SV40), and the levels of DNA polymerases-alpha, -beta, and -gamma were analyzed in the cytoplasm, nuclear Triton wash, and nucleus. In the cytoplasmic fraction, the amount of alpha-, beta-, or gamma-polymerase remained unaltered after SV40 infection. The activity of DNA polymerase-alpha increased five- to sixfold in the nuclear Triton wash and threefold in the nuclei and then remained enhanced only inside the nuclei. That of DNA polymerases-beta and gamma increased mostly in the nuclei after infection. These results suggest that DNA polymerase-alpha could be the major enzyme involved in SV40 DNA replication.


Phosphorylation and nucleic acid binding properties of m1 Moloney murine sarcoma virus-specific pP60gag. The pP60gag polyprotein of the feline leukemia virus pseudotype of m1 Moloney murine sarcoma virus [m1MSV(FeLV)] was previously shown to be MSV specific and to contain murine p30 and smaller structural polypeptides. This protein was detected in m1MSV-transformed cells, and in pulse-chase studies it was found to be stable. In this study virion P60 was shown to contain murine pp12, to be phosphorylated, and to bind to nucleic acids. 32P-labeled m1MSV[FeLV) was fractionated by guanidine agarose chromatography and analyzed by gel electrophoresis. Both P60 and pp12 were found to be the major phosphoproteins, phosphorylated in both serine and threonine residues. Virion P60 bound preferentially to single-stranded DNA and RNA in a competition filter binding assay, using 125I-labeled single-stranded calf thymus DNA and various unlabeled nucleic acids. Similar phosphorylation and DNA binding properties were demonstrated for cellular P60. Thus, immunoprecipitation of cellular extracts showed that P60 was phosphorylated in both producer and nonproducer transformed cells, indicating that phosphorylation occurs independently of virus assembly. Moreover, P60 from cytoplasmic extracts was retained on single-stranded DNA-Sepharose columns, demonstrating that cellular P60 binds to DNA.


In vitro transcription of the avian oncornavirus genome by the RNA-directed DNA polymerase: effect of actinomycin D on the extent of transcription. The minus-strand component of double-stranded DNA synthesized by the avian oncornavirus RNA-directed DNA polymerase in vitro represents as much of the nucleotide sequences of the viral genome as single-stranded DNA synthesized in the presence of actinomycin D. Since actinomycin D inhibits doublestranded DNA formation, we propose that the principal effect of the drug on RNA-directed DNA synthesis is the reduction in synthesis of plus-strand DNA, thereby allowing single-stranded minus-strand DNA to accumulate. This effect, rather than increasing the extent of genome transcription, is responsible for the more uniform nature of the DNA transcripts synthesized in the presence of actinomycin D.


Expression of endogenous retroviral genes in leukemic guinea pig cells. The expression of guinea pig retrovirus (5-bromodeoxyuridine[BUdR]-induced GPV) was studied in guinea pig L(2)C leukemic lymphoblasts by use of molecular hybridization of viral complementary DNA (cDNA) to cellular RNA. It was found that L(2)C leukemic lymphoblasts, leukemic spleen, and BUdR-induced virus-producing cells contain virus-specific RNA: 0.05% (800 to 960 copies per cell), 0.02% (360 copies per cell), and 0.3% (5,120 copies per cell), respectively. Adult normal liver and spleen, on the other hand, contain less than 0.2 copy of viral RNA per cell. Both BUdR-induced cells and L(2)C leukemic lymphoblasts contained 14S, 22S, 35S, and 70S RNA species of total and cytoplasmic virus-specific RNA as determined by sucrose velocity gradient analysis and hybridization of sucrose gradient fractions to cDNA. Virus-specific mRNA was identified in both BUdR-induced cells and L(2)C leukemic lymphoblasts by the criterion that it cosedimented with purified polyribosomes in a sucrose gradient and that it changed to a lower sedimentation value if polyribosomes were disaggregated with EDTA prior to centrifugation. Virus-specific mRNA obtained from either the polyribosome region of purified polyribosomes or the released messenger region of EDTA-disaggregated purified polyribosomes consisted of 14S, 20S, and 35S species in both BUdR-induced cells and L(2)C leukemic lymphoblasts. Hybridization of cDNA to the RNA of L(2)C leukemic lymphoblasts and BUdR-induced cells was essentially complete. Additionally, leukemic lymphoblast RNA could displace 95% of the hybridization of BUdR-induced GPV 70S RNA to guinea pig DNA. The midpoints of thermal denaturation of hybrids formed between GPV cDNA and the RNA of either L(2)C leukemic lymphoblasts or the 70S RNA of BUdR-induced GPV were both 89 degrees C in 2x concentrated 0.15 M NaCl plus 0.015 M sodium citrate. These results show that BUdR-induced GPV genes are essentially completely expressed in L(2)C leukemic lymphoblasts and that virus-specific mRNA is present, although fewer copies of RNA are present in L(2)C leukemic lymphoblasts than in BUdR-induced cells.


Squirrel monkey retrovirus: an endogenous virus of a new world primate. Squirrel monkey retrovirus (SMRV) was isolated by cocultivation of squirrel monkey lung cells with canine cells. 3H-labeled 60-70S SMRV RNA, isolated from virus grown in canine cells, hybridized to the same extent and to the same Cot1/2 value to the DNA of all tissues of all squirrel monkeys tested; Cot1/2 values show that SMRV proviral sequences are present in the low repetitive range. No SMRV proviral sequences were detected in tissues from a variety of other New World monkeys, Old World monkeys, or apes. Murine, feline, bovine, and canine cells also contain no detectable SMRV proviral sequences. Competitive molecular hybridization studies revealed no detectable sequence homology between the 60-70S RNAs of SMRV and Mason-Pfizer virus (MPV). The virion-associated DNA polymerase of SMRV is similar to that of MPV in that it has a molecular weight of approximately 80,000 and prefers magnesium as a divalent cation using oligo(dG)-poly(rC) as primer-template. The virion-associated DNA polymerase of SMRV can be clearly distinguished from those of MPV and the mouse mammary tumor viruses, however, by its preference for manganese as a divalent cation in the presence of high salt.


Characterization of molecular species carrying gross cell surface antigen. The Gross cell surface antigen (GCSA), associated with expression of endogenous Gross-type murine leukemia virus (G-MuLV) in tissues of mice, is defined by the cytotoxic reaction of a C57BL/6 antiserum, anti-AKR spontaneous leukemia K36, with cells of the Gross virus-induced C57BL/6 leukemia, Emale symbolG2. Sequential lactoperoxidase-catalyzed radioiodination of Emale symbolG2 cells, Nonidet P-40 lysis, precipitation with anti-K36 serum, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis identified molecules with properties of polyproteins encoded by the gag region of the viral genome. These cell surface species could also be labeled by in vitro culturing of Emale symbolG2 with radioactive glucosamine. The viral specificity of these molecules and their participation in the GCSA typing system were established as follows. (i) Absorption of anti-K36 serum with GCSA(+), but not GCSA(-), leukemias led to a marked decrease in precipitation of these proteins. (ii) The same Emale symbolG2 cell surface proteins were also precipitated by antisera against the MuLV virion proteins p30 and p15. (iii) Anti-K36 was shown to possess antibodies against Gross virus p30 and p15. (iv) "Clearing" the Emale symbolG2 lysate of molecules reactive with anti-p30 or anti-p15 sera removed molecules reactive with anti-K36 serum. (v) Absorption of anti-K36 serum with disrupted G-MuLV virions or with Gross p30 or p15 removed GCSA cytotoxic antibodies; partial absorption was achieved with disrupted Rauscher-MuLV (R-MuLV) or with R-MuLV p30, and no absorption was found with R-MuLV p15. These data show that Emale symbolG2 cells express, on their surfaces, MuLV core polyproteins that apparently can be glycosylated and on which the determinants of GCSA are located.


Identification of the Gross cell surface antigen associated with murine leukemia virus-infected cells. The Gross cell surface antigen (GCSA) is produced by cells that are either exogenously infected with murine leukemia virus (MuLV) or are expressing endogenous MuLV genomes. In immune precipitation assays, GCSA was resolved into two serologically distinct 85,000- and 95,000-dalton viral proteins. These antigenic components are glycosylated forms of the polyprotein precursors of the MuLV internal structural proteins.


Structure of hepatitis B Dane particle DNA and nature of the endogenous DNA polymerase reaction. The circular DNA of hepatitis B Dane particles, which serves as the primer/template for an endogenous DNA polymerase, was analyzed by electrophoresis before and after a polymerase reaction and after digestion by restriction endonuclease or single-strand-specific endonuclease S1. The unreacted molecules extracted from the particles were electrophoretically heterogeneous, and treatment with S1 nuclease produced double-stranded linear DNA ranging in length from 1,700 to 2,800 base pairs (bp). After an endogenous DNA polymerase reaction, two discrete species of DNA molecules were found: a circular form and a linear form 3,200 bp long. The reaction resulted in a population of molecules with an elongated and more homogeneous double-stranded region. These results suggest that the circular molecules in Dane particles have single-stranded regions of varying lengths that are made double stranded during the DNA polymerase reaction. The endogenous DNA polymerase was found to initiate apparently at random in a region spanning more than a third of the molecule. Analysis of restriction endonuclease cleavage fragments of the fully elongated DNA revealed that although the molecules were of a uniform length, they were somewhat heterogeneous in sequence. The sum of the sizes of the 10 major endonuclease Hae III-generated fragments, detected by ethidium bromide, was 3,880 bp. Two additional fragments (B and G) detected by autoradiography after an endogenous DNA polymerase reaction with (32)P-labeled deoxynucleoside triphosphates made the total 4,910 bp.


Characterization of a retravirus isolated from squirrel monkeys. A new retravirus (SMRV) isolated from a squirrel monkey, Saimiri sciureus, has an Mg2+-dependen reverse transcriptase and a buoyant density of 1.17 g/cm3 in sucrose and 1.21 g/cm3 in cesium chloride, similar to the mouse mammary tumor virus and the Mason-Pfizer monkey virus. The polypeptide patter of SMRV as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis was distinct from the reported polypeptide patterns of known retraviruses. Four major polypeptides of molecular weights 40,000, 20,000, 14,000 and 8,000 were resolved in virus propagated in human, mink, and canine cells. In A204 human rhabdomyosarcoma cells, a protein of 73,000 daltons (gp73) represented the major viral glycoprotein as determined by [3H]glucosamine labeling. Additional proteins were also observed, but their presence depended on the cell type in which the virus was propagated. In both species-and interspecies-specific assays, no antigenic relatedness was observed between SMRV and Mason-Pfizer monkey virus, mouse mammary tumor virus, baboon endogenous virus (BaLV), woolly monkey virus (SSV-1), murine leukemia virus, endogenous feline type C virus (RD-114), bovine leukemia virus, and equine infectious anemia virus. These findings indicate that SMRV represents a new retravirus and the first isolate from a New World monkey.


Two species of type C viral core polyprotein on AKR mouse leukemia cells. Two species of glycosylated type C viral core polyprotein were identified on the surface of AKR spontaneous leukemia cells. One of these cell surface polyproteins was shown by immunoprecipitation to have antigenic determinants of murine leukemia virus p30, p15, p12, and p10; the other had murine leukemia virus p30, p15, and p12, but not p10, determinants. Both species were also expressed on thymocytes from 6-month-old, preleukemic AKR mice.


Biochemical and immunological characterization of the major envelope glycoprotein of bovine leukemia virus. The major envelope glycoprotein of bovine leukemia virus was isolated by lectin-bound Sepharose and DEAE-cellulose column chromatography. This protein was shown to have a molecular weight of about 41,000 and to lack detectable immunological cross-reactivity with glycoproteins of other oncornaviruses. Sera obtained from 100% of cattle examined with clinically diagnosed lymphosarcoma contained high-titered antibody to 125I-labeled bovine leukemia virus glycoprotein, whereas sera from animals in a disease-free herd were antibody negative.


[Long-term ECG recording and cardiac rhythm disorders in patients with different conditions of the coronary arteries (according to the angiographic data)]. The results of long-term continuous ECG recording during 24 hours in 50 patients are presented. A comparison of these data with the results of a clinical examination and selective coronary angiography has revealed that patients with chronic ischaemic heart disease and distinct atherosclerotic changes in the coronary arteries have rhythm disorders twice as often as those free from ischaemic heart disease. The employment of the method of long-term continuous ECG recording during normal patients' activity will permit to evaluate the effect of different factors on the development of cardiac rhythm disorders.


[Various aspects of individualization of drug therapy of extrasystole]. The clinical experience of drug therapy of 673 patients with extrasystole of different genesis has demonstrated that the nature of the underlying pathology and the topical characteristics of the extrasystole produce a comparatively moderate effect upon the antiarrhythmic action of Novocainamide, Chinidine, Obsidan, Isoptine, Bellataminal. Of certain importance in this context is the determination of the degree of prematurity of the extrasystole, their stability, as well as the periodic structure of the sinus rhythm as shown by the rhythmogram.


[Parasystolic arrhythmias].

[Parasystolic arrhythmias]. The observation was conducted in 24 patients with parasystolic arrhythmias, 13 of them having parasystolic extrasystoles, and 11--paroxysmal and non-paroxysmal parasystolic tachycardia. Ventricular parasystole was found in 21 patients, atrial--in 3, atrioventricular--in 2; three patients had double parasystole with two ectopic centers. In the majority of patients their parasystole took a persistent, but relatively benign course, however one patient with ventricular parasystolic tachycardia persisting for many years had repeated ventricular fibrillations. For the treatment of supraventricular parasystolic arrhythmias beta-adrenergic receptors blocking agents, Isoptine, cardiac glycosides were used; in ventricular parasystole the more effective drugs are Lidocain, Novocainamid, Ajmalin.


[Postextrasystolic depression of sinus rhythm during electroimpulse therapy of auricular fibrillation]. In 95 patients treated by electroimpulse techniques for their cardiac fibrillation the incidence and diagnostic importance of postextrasystolic depression of the sinus rhythm were studied. Two groups of patients were singled out for a comparative study of the value of different prognostic criteria of the stability of the restored sinus rhythm: group 1--53 patients with unsatisfactory results of treatment (the sinus rhythm was preserved for not more than 1 month), and group 2--21 patients with good late results (the sinus rhythm persisted for over 6 months). A study of the distribution of the incidence of different prognostic signs in either of these groups showed that their prognostic value may be presented in the following succession: presence of intraventricular conductivity, severity of cardiac insufficiency, frequent postconversion extrasystoles, history of cardiac fibrillation of over 3 years, presence of a postextrasystolic depression of the sinus rhythm.


[Study of the effectiveness of cordaron in different types of arrhythmia]. The employment of Cordaron (Amidaron) in 50 patients with different arrhythmias proved effective in 86% of the cases. Cordaron was most effective in the treatment and prevention of paroxysmal tachycardia, ventricular extrasystole, paroxysmal cardiac fibrillation. It decreases the pulse rate and moderately decreases the arterial pressure without imparing the patients' state. The drug has practically no toxic effect, is well tolerated, convenient for administration and dosage. Cardiovascular insufficiency is no contraindication for its prescription. Carefulness is needed in prescribing Cordaron to patients with atrioventricular conductivity disorders.


[Cytospectrophotometric study of glycoproteins of the erythrocyte membrane in renal and spontaneous hypertension in rats]. Spontaneously hypertensive rats (SHR), aged 10 weeks, and rats with renovascular hypertension (25-30 weeks) demonstrated, in contrast to the controls, a different pattern of erythrocytes staining with paraldehyde-fuchsin used in histochemistry for demonstrating glycoproteids. The erythrocytes were found to respond to intravenous glucose injections by changing the optic density. The erythrocytes response of SHR differs from the normals, but no difference was revealed in rats with renovascular hypertension. The authors suggest that the changes in the tinctorial properties of the erythrocytes with reference to paraldehyde-fuchsin indirectly reflect the state of the insulin receptors of the erythrocyte membrane.


[Effect of total fasting on serum protein concentrations (author's transl)]. During a period of total fasting restricted to three weeks, haptoglobin, transferrin and beta1A-globin showed a marked, continuous decline. The complement was finally distinctly below the reference range. Macroglobulins and coeruloplasmin rised until the tenth day and decreased thereafter. IgG globulin remained essentially unchanged while immunoglobulins gammaA and gammaM showed an increase. On account of the considerable fluctuations observed in the protein fractions fasting in this form at least beyond a period of 21 days does not seem justified.


Differentiation of plasma and myeloma cells of man. Combined planimetric and cytophotometric studies. Plasmacytoid cells in the bone marrow of 3 patients with myeloma and plasma cells in the bone marrow of a 6-year-old boy with an infectious disease were assessed cytophotometrically, first after Giemsaand second after Feulgen staining. The cell and nuclear surface and the nuclear/cytoplasmic ratio were determined from the number of measuring points. The nuclear DNA content of individual cells was registered and the distribution of DNA within the nucleus was assessed by the distributional error. Both the mean nuclear/cytoplasmic ratio and the distributional error of myeloma cells varied from patient to patient but could not be used to differentiate between normal plasma cells and myeloma cells. It was not possible either to differentiate these cell types by multiplying the mean nuclear/cytoplasmic ratio with the mean distributional error of the nuclear DNA. A strong correlation between cell and cytoplasmic surface area was observed both in normal plasma cells and in myeloma cells.


[Fluorescent test of mycoplasma colonies by agar diffusion technique (author's transl)]. An agar diffusion test to directly stain mycoplasma colonies using a new fluorochrome 4,6-diamidino-2-phenyl-indol (DAPI) is described. Next to a colony in question a well is punched into the agar and filled with DAPI. 30 min later the colonies in the diffusion zone show a light yellow - light green fluorescence. Due to the high affinity of DAPI to DNA it is easily possible to distinguish between granular mycoplasma colonies and unspecific substances e.g. proteins and lipids from clinical material.


The symbolism of drinking; a culture-historical approach. The historical symbolic connections between alcoholic beverages and blood, milk and water are discussed, with the conclusion that alcoholic beverages were often symbolically interchangable with these life-giving substances. Many cultures thus saw drinking as a positive and reinforcing part of their societies, rather than solely in a negative or tension-reducing aspect.


The detoxication of alcoholics-aspects of myth, magic or malpractice. Disadvantages of nonmedical detoxication centers are discussed.


Malignant obstruction of the superior vena cava and its palliation: report of four cases. Four cases of obstruction of the superior vena cava caused by inoperable bronchogenic carcinoma are presented in which the signs and symptoms were disabling. Palliation was achieved by placing a 10 mm. Dacron prosthetic bypass graft between the left innominate vein and the right atrial appendage, resulting in prompt relief. All patients were given warfarin for anticoagulation and subsequently deep x-ray therapy and diuretics were added. There was no operative or hospital death or morbidity. Two of the patients died of distant metastases at 14 and 6 months, respectively, postoperatively. The other two are alive and well at 11 and 5 months after the operation. Venous obstruction has not recurred to date in any of the four patients. A relevant review of the literature has been made.


Aspiration biopsy cytology.

Aspiration biopsy cytology. After the presentation of the technique of the aspiration biopsy and the mode of preparation and staining of the smears, the author discusses the usefulness and limitations of this procedure in the diagnosis of benign and malignant lymph node lesions. Studies on blastocytic transformation in short-term tissue cultures in the presence of phytohaemagglutinin have indicated that the cells are unimpaired by the needling and/or the negative pressure used in the aspiration. Since the patient experiences little discomfort from fine needle biopsy, the aspiration biopsy of lymph nodes can also be used for sampling cell material in clinical research. The problem of dissemination of tumor cells via the needle track or efferent lymph or blood vessels is also discussed. The use of fine needle aspiration biopsy in diagnosis of malignant tumors does not appear to involve a risk of tumor spread.


Alcohol and blood lipids. The cooperative lipoprotein phenotyping study. Data from five study populations participating in the Cooperative Lipoprotein Phenotyping Study indicate strong relations between reported alcohol consumption and blood-lipids. Alcohol consumption was positively associated with high-density-lipoprotein cholesterol level in all populations (r from 0-16 to 0-30), the lipid level appearing to be a graded response even over the low levels of alcohol consumption reported. Less strong but consistently negative correlations were found with low-density-lipoprotein cholesterol. Plasma-triglycerides showed a modest positive correlation with alcohol. The five populations were those of the Albany, Evans County, Framingham, Honolulu, and San Francisco Studies.


Asymptomatic autoimmune thyroiditis and coronary heart-disease. Cross-sectional and prospective studies. Cross sectional and prospective surveys of thyroid autoimmunity have been performed in two cohorts of men, 280 living in west Finland and 269 in east Finland. In both populations, aged 50 to 69 years at the first survey, risk factors for coronary heart-disease (C.H.D.) were common. The incidence of C.H.D. was shown to be related to the presence of thyroid antibodies. The results of the cross-sectional studies were not conclusive. The five-year follow-up study emphasised that in both areas asymptomatic thyroid autoimmunity, independently of other known risk factors, was a predictor of subsequent development of C.H.D. The importance of asymptomatic autoimmune thyroid-itis as a risk factor for C.H.D. increases with age.


Prolonged maintained remissions of adult acute non-lymphocytic leukaemia. Maintenance chemotherapy consisting of weekly oral 6-thioguanine and intramuscular cytosine arabinoside was administered to 24 adult patients with acute non-lymphocytic leukaemia in complete remission. The median duration of complete remission was 16-5 months, with 9 patients (38%) still in their first remission after 18--56 months. 33% of the patients have been in continuous remission for over 2 yr, 21% for over 3 yr, and 12-5% for over 4 yr. Median survival so far is 22-5 months. This maintenance regimen is well tolerated, is easily administered on an outpatient basis, and produces substantial numbers of long-term remissions.


Structural properties of double-stranded helical poly (gamma-benzyl-D-L-glutamate) in solution. Comparison with some solution properties of linear gramicidin. The double-stranded helical conformations of alternating PBD-LG found in the solid state have been studied in infrared, circular dichroism, and NMR techniques in solution in methylene chloride, chloroform dioxane, and collidine. The infrared and CD properties of the solutions, transconformations between single- and double-stranded helices and transconformations within the family of double helices, support the hypothesis that the conformation in solution is the same as that found after evaporation of the solvent, namely the pi pi DL 7.2, pI pI DL 9.0, and pi pi DL 10.8 helices, depending on the solvent. An attempt to identify the conformation of linear gramicidin is made on the basis of the CD spectra and the infrared frequencies conformation relationship established for PBD-LG. However, owing to the great number of different conformations observed for the antibiotic, no firm conclusion can yet be drawn, except for the probable existence of the double antiparallel helical structure.


Cerebral blood-flow in polycythaemia.

Cerebral blood-flow in polycythaemia. Cerebral blood-flow (C.B.F.) has been measured in 16 patients with polycythaemia of differing severity. The mean C.B.F. was 37-9 ml/100 g/min, which is significantly below the normal level of 69-1 (S.D. 9-3) ml/100 g/min (P less than 0-001). C.B.F. measurement was repeated after venesection in 15 of the patients. Lowering the haematocrit from a mean of 0-536 to a mean of 0-455 was associated with a 73% increase in mean C.B.F. (P less than 0-001) and a 30% reduction in whole-blood viscosity. Low C.B.F. was found at haematocrit levels between 0-46 and 0-52. Haematocrit levels that are currently acceptable in the management of polycythaemia may therefore be too high.


Antibody-drug synergism: An assessment of specific passive immunotherapy in bronchial carcinoma. Patients with bronchial carcinoma who had had radical resection of the primary tumour were treated with a combination of drugs and tumour-specific immunoglobulin (antibody-drug synergism, A.D.S.). The antisera were raised in goats by immunisation with tumour cells from patients, and given to those patients after absorption to remove antibody against normal human tissues. 32 patients received A.D.S. treatment and 37 patients received chemotherapy only. Although the differences are not statistically significant there have been 22 recurrences including 15 deaths in the chemotherapy group and 8 recurrences including 6 deaths in the A.D.S group. There was only one clinically significant reaction to heterologous immunoglobulin.


Inhibition of cholecystokinin-pancreozymin release by somatostatin. To determine the effect of somatostatin on cholecystokinin-pancreozymin (C.C.K.) release, serum-C.C.K. concentrations were measured in normal volunteers after intraduodenal olive oil, with and without a simultaneous intravenous infusion of somatostatin. After instillation of the olive oil there was a rapid rise in serum-C.C.K. (integrated response 19 682+/-5632 pg min ml-1). This rise was completely abolished by somatostatin (integrated response -373+/-330 pg min ml-1, P less than 0-005) and rebound hyper-secretion was seen after the infusion had been stopped. These findings indicate that somatostatin may be involved in regulating C.C.K. release after meals, and suggest a possible explanation for the profound steatorrhoea seen in a patient with a somatostatin-producing tumour.


Nuclear oestrogen receptors and treatment of breast cancer. In an attempt to improve the predictive value of oestrogen-receptor measurements in breast-tumour biopsy specimens, oestrogen receptor was measured at both cytoplasmic and nuclear levels. Although 33% of patients had receptors at both levels, another 17% had cytoplasmic but no nuclear receptors. Theoretically, this latter group would not be expected to respond to hormone therapy. 7% had nuclear but not cytoplasmic receptors. The six-month follow-up data for the group of patients with receptors at both cytoplasmic and nuclear levels suggests qualitatively that this group has a good chance of responding favourably to hormone therapy. Much larger numbers must be accumulated before quantitative conclusions can be reached.


Chloride-transport stimulatory factor in urine of chronically sodium-chloride loaded man. Urinary extracts (in methylene dichloride) of subjects on high sodium-chloride (NaCl) intake produce net Cl- efflux (active transport) in isolated short-circuited frog skin. Activity is not found in the urine of NaCl-deprived normal subjects or NaCl-loaded subjects with adrenal insufficiency. These findings suggest that presence of an adrenocortical steriod which participates in adaptation to high salt intake. We describe here a lipid-soluble factor extracted from urine of chronically salt-loaded subjects which stimulates active Cl- transport in isolated frog skin. Our findings indicate that the factor is of adrenal origin and that it induces active ion transport in the direction opposite to that stimulated by the adrenal hormone, aldosterone. Aldosterone produces NaCl conservation in states of salt deprivation. We expect this new factor to produce NaCl excretion in states of excess salt ingestion.


Spectrum of thyroid function in patient's remaining in remission after antithyroid drug therapy for thyrotoxicosis. Thyroid function was assessed in 110 patients who were in remission for a period of 7-6 +/- 0-6 years (mean +/- S.E.) (range 0-25--25 years) after the withdrawal of antithyroid drug therapy for thyrotoxicosis. On the basis of clinical examination and on the results of thyroid-function tests, the following group of patients were identified: (I) euthyroid with normal plasma-total thyroxine (T4) and triiodothyronine (T3) concentrations, but an absent or subnormal response of plasma-thyrotrophin (T.S.H.) to thyrotrophin-releasing hormone (T.R.H.) (16%); (II) euthyroid with normal concentrations of plasma total T4 and T3 and a normal plasma-T.S.H. response to T.R.H. (59%); (III) euthyroid with normal concentrations of circulating thyroid hormones and a normal basal plasma-T.S.H., but an exaggerated plasma-T.S.H. response to T.R.H. (13%); (IV) euthyroid with normal plasma total T4 and T3 concentrations, but a raised basal plasma-T.S.H. concentration and an exaggerated plasma-T.S.H. response to T.R.H. (6%); (V) hypothyroid (6%). Although the need for short-term follow-up to identify those patients treated with antithyroid drugs who will relapse is well recognised, 16% of all patients in remission for longer than 4 years (10-8 +/- 0-7 years) in the present study showed some degree of thyroid failure. Evidence of hypothyroidism was associated with an increased frequency of thyroid microsomal antibodies. If the morbidity of the late development of hypothyroidism is to be avoided, patients who have been treated with antithyroid drugs should have long-term follow-up, as do patients treated surgically or with radioiodine.


Disease-surveillance and decision-making after the 1976 Guatemala earthquake. In the first 3 weeks after the 1976 earthquake in Guatemala a system for collecting, analysing, and disseminating information of medical importance was instituted in the disaster area. Data on cases of selected diseases, number of available hospital beds, and medical supplies were collected, and reported epidemics were investigated. The system functioned well despite the limited numbers of trained personnel. Collection and analysis were quick enough for data to be used immediately in decision-making. No epidemics of communicable diseases were observed in the affected area. The number of dog bites in Guatemala City increased but no cases of rabies were reported. The success of the surveillance system in Guatemala suggests that immediate use of epidemiological methods should be an integral part of disaster relief.


Dietary fibre, transit-time, faecal bacteria, steroids, and colon cancer in two Scandinavian populations. Report from the International Agency for Research on Cancer Intestinal Microecology Group. A comparison of dietary intake and faecal characteristics in population samples from two areas of Denmark and Finland with 4-fold variation in colon-cancer incidence suggests that the aetiology of colon cancer may be multifactorial and is not associated in a simple manner with dietary fat, neutral steroids, acid steroids, or their bacterial metabolites. However, meat consumption was greater in the high-incidence areas. Higher intakes of dietary fibre and milk in the low-incidence area suggest a possible protective effect, unrelated to mouth-anus transit-time. Further careful dietary and metabolic studies are needed to clarify the relationships between possible carcinogenic and protective effects of diet.


Hyperprolactinaemia and antihypertensive effect of bromocriptine in essential hypertension. Identification of abnormal central dopamine control. Plasma-prolactin concentration was up to four times higher in male patients with essential hypertension than in normotensive controls. Oral administration of bromocriptine, a dopaminergic agonist, suppressed plasma-prolactin and lowered arterial pressure. It is proposed that in the hypertensive patients the raised prolactin levels reflect a defect in central dopamine control which is normalised by bromocriptine. The antihypertensive effect of bromocriptine suggests that the dopaminergic system is involved in blood-pressure regulation and that reduced central dopaminergic activity may be a factor in the maintenance of essential hypertension.


Levamisole-induced immunostimulation in spondylarthropathies. The term "seronegative spondylarthritis" (S.S.A.) has been assigned to rheumatic disorders with closely related clinical features, defined by seronegativity and HLA-B27 phenotype. Its pathogenesis may be linked with a genetically controlled defective immune response. Therefore, 37 men with S.S.A. were treated with levamisole (150 mg/day, 3 days/wk) to stimulate the immune reactions. In a randomised controlled crossover study these patients also received a placebo; each period ran for 12 wk. Symptomatic therapy was continued through the entire 6 mo. Serious side-effects led to withdrawal of the active drug in 9 patients. Clinical response was measured in terms of a cumulative joint index, spondylometry, morning stiffness, and a pain scale. Treatment with levamisole resulted in a significant improvement in these parameters. Radiological evidence of sacroiliitis was present in 48.6% before and after levamisole, and joint scanning with 99Tc-pyrophosphate also revealed no progress in the disease. After levamisole treatment, IgM levels fell significantly (P less than 0-014). Likewise, the previously high percentage of antibodies with weak cytotoxic activity against lymphocytes was reduced after levamisole (P less than 0-049), and an increased rate of leucocyte-migration inhibition (L.M.I) was found in the levamisole-treated group. Thus, the immunostimulating properties of levamisole may interfere with defective immunoregulation in S.S.A. and, by improving the clinical conditions, lead to a change in the course of this disease.


Hepatitis-B virus in bedbugs (Cimex hemipterus) from Senegal. Bedbugs of the species Cimex hemipterus (F) were collected on four separate occasions from the bedding in the huts of village dwellers in Senegal, West Africa. Hepatitis-B surface antigen (HBSAg) was detected in unengorged nymph and adult bedbugs in each of the first three collections. 3 of 28 such specimens were HBSAg(+) in the first collection and 3 of 17 specimens were positive in the second collection. In the third, 6 of 9 were HBSAg(+) when the bed occupant was known to be HBSAg(+). 2 of these 6 positive insects did not contain human serum proteins. Bedbugs in the fourth collection were captured and kept alive without a blood meal for 30 days. 3 of 89 of these samples were HBSAg(+). These are the highest field infection-rates of hepatitis-B virus reported in any insect species. The bedbug must be considered a potential vector of hepatitis-B virus.


Cerebral atrophy. An immunological disorder? Patients with cerebral atrophy of unknown origin, patients with nuclear forms of schizophrenia or neurosis, and normal subjects were skin-tested with human brain and liver proteins. The frequency of positive delayed skin-sensitivity reactions to brain proteins was significantly higher in the cerebral-atrophy group than in other groups, thus suggesting a correlation between cerebral atrophy and cell-mediated immunity.


Effect of triac on the developing heart. Triac (diethanolamine salt of triiodothyroacetic acid) was administered by intramuscular injection to 12 pregnant female rats. These were divided into a control group and three other groups, each receiving different doses of triac. The effect of triac on the hearts of their offspring was studied morphologically. Histological examination showed evidence of only mild hypertrophy, but ultrastructurally, disarray of myocardial fibrils and other changes similar to those observed in patients with hypertrophic cardiomyopathy were found in the litter of the group receiving the highest dose. It is suggested that thyroid function should be studied in patients with obscure cardiac disease.


Activation of IgE regulatory mechanisms by transmucosal absorption of antigen. The development of immediate hypersensitivities depends essentially on the production of IgE antibodies--usually to common environmental antigens. It has been suggested that atopic individuals produce IgE antibodies as a result of overstimulation with antigen and that this occurs through IgA deficiency which by default allows the absorption via the mucosae of abnormally large amounts of antigen. However, work with laboratory animals indicates a mechanism which is the antithesis of the overstimulation concept: that quantities of antigen sufficiently large to activate IgE immunoregulatory mechanisms, particularly suppressor T cells, are normally absorbed across the mucosae and that, where other conditions for the activation of these cells are appropriate, inhibition rather than stimulation of IgE responses results. In this way allergies arise through a defect of one or more components of the immunoregulatory mechanism. The fact that atopic individuals do not become allergic to all ubiquitous antigens and that they may be hyposensitised is evidence that the defect is relative rather than absolute.


Gastroenteritis: a continuing problem of child health in Britain. A paediatric gastroenteritis unit had 608 admissions over 2 years. The children admitted were mostly under 6 months of age, had often been in hospital previously and were, as a group, underweight for their age. Severe biochemical disturbances, early complications, and death were significantly related and were almost entirely confined to the children under 6 months of age. There were 8 deaths (1-3%), 5 (0-8%) of which were associated with serious underlying disorders. Late complications related to food intolerance were found in 3%. Young infants with gastroenteritis are best cared for in units experienced in the management of acute metabolic disturbances in such patients, though highly specialised renal and gastrointestinal services are not essential. These units should provide continuing paediatric supervision.


Suicide prevention by the Samaritans. A controlled study of effectiveness. To test the hypothesis that Samaritan services prevent suicide, the trends in suicide-rates of county boroughs with Samaritan services have been compared with trends in matched control boroughs without Samarian services. The suicide-rate for both groups of boroughs has decreased progressively and to the same extent. This finding is not consistent with suggestions that Samaritan services prevent suicide.


Liver damage from long-term methyltestosterone. Of 60 patients (42 female transsexuals and 18 impotent males) receiving long-term therapy with methyltestosterone 50 mg three times a day, 19 had abnormal liver-function tests and 33 out of 52 had abnormal liver scans, particularly those who had been treated for more than a year. Liver biopsy specimens showed accumulation of hepatocytes in the liver cords and within the walls of centrilobular veins, and early peliosis hepatis. One patient had a hepatic adenoma. Of the androgens, only 17alpha-alkylated steroids seem to be implicated in the development of cholestatic jaundice, peliosis hepatis, and liver tumours.


Enzyme-linked immunosorbent assay (ELISA) for detection of human reovirus-like agent of infantile gastroenteritis. An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of the human reovirus-like agent of infantile gastroenteritis in human stools. The results of the assay can be read either with a simple colorimeter or the naked eye. Investigations with 143 samples from children with gastroenteritis and 75 samples from children with other illnesses showed that the ELISA was as sensitive as electron microscopy or radioimmunoassay for detection of this agent. In addition, the ELISA was simple to perform and, when read visually, did not require sophisticated technical equipment. These advantages make it suitable for field work.


Maternal serum-alpha-fetoprotein measurements as an early indicator of low birth-weight. In a prospective trial of 4224 pregnancies, 103 women had serum-alpha-fetoprotein (A.F.P.) above 2-3 times the median value for their stage of gestation. 10-7% of these delivered infants with birth-weights less than 2-5 kg. This was significantly greater than the rate of 4-2% for low-birth-weight infants in the general population. At higher multiples of the median serum-A.F.P. value the proportion of pregnancies leading to low-birth-weight infants was even greater. It is suggested that early identification of pregnancies with high risk of premature delivery may be an important corollary of maternal serum A.F.P. screening.


Maternal serum-alpha-fetoprotein and low birth-weight. High maternal serum-alpha-fetoprotein (A.F.P.) concentrations in the first half of pregnancy were associated with prematurity and high perinatal mortality. 94 singleton pregnancies without neural-tube defects but with A.F.P. levels equal to or greater than three times the normal median resulted in the birth of infants weighing, on average, 357 g less than controls (P less than 0-001). The mean head circumference of the infants was also smaller than that of the controls. The 1 stillbirth and 3 neonatal deaths yielded a mortality-rate more than three and a half times that for singleton births without neural-tube defects at the same hospital in the years 1974-76. The results suggest that some pregnant women who will deliver low-birth-weight infants at high risk of perinatal death may be identified by means of serum-A.F.P. measurement early in pregnancy.


Hepatic injury in adult coeliac disease. In an attempt to determine the frequency of liver injury in adult coeliac disease (A.C.D.) the case records of 74 consecutive patients were examined. In 13 cases histological sections of the liver were available and in 5 of these there were signs of reactive hepatitis. Histological signs of distinct hepatic injury with cirrhosis and/or chronic active hepatitis were found in 7 other patients. In 5 of these serum-IgA was normal, whereas 16 out of 20 control patients with liver cirrhosis not associated with A.C.D. had raised serum-IgA. Serum-aspartate-aminotransferase and serum-alanine-aminotransferase were determined in 53 patients; 29 had raised concentrations. In 19 patients serum-aminotransferases were repeatedly determined before and during the dietary regimen and there was a significant reduction in enzyme concentrations during treatment. The median concentration of serum-alkaline-phosphatase was also reduced during treatment but not significantly. The histological evidence of liver injury in 16% and the abnormal liver-function tests in 39% of the patients indicate that hepatic injury is common in A.C.D. Since liver-function tests or liver biopsy specimens were available for only about two-thirds of the patients, liver damage in A.C.D. may be more common than indicated by these results. The effect of a gluten-free diet on aminotransferase concentrations indicates that the liver injury may be reversible and suggests that in some A.C.D. patients progressive liver damage may be prevented by suitable treatment. Since A.C.D. is not always recognised, the diagnosis should be considered in patients with liver disease of unknown aetiology.


Immediate post-placental insertion of intrauterine contraceptive devices. Insertion of one of three types of intrauterine contraceptive device--the Lem, copper 7, and 'Progestasert' system--was carried out in 274 obstetric patients. These devices were all inserted within 20 min of delivery of the placenta and membranes, with a special 25 cm inserter. The expulsion-rate was low (less than 7%), and there were no uterine perforations. There was no difference in puerperal morbidity between these patients and a matched control group, and no cases of pelvic sepsis developed.


Elevation of plasma-prolactin by monoamine-oxidase inhibitors. Plasma-prolactin levels doubled in depressive patients treated with the monoamine-oxidase inhibitors, clorgyline and pargyline. The absence of significant changes in plasma-cortisol in the same patients suggests that the increases in prolactin are not attributable to non-specific effects of stress.


Pituitary secretes to brain. Experiments in sheep. Because vascular casts of the pituitary demonstrated that there are a few venous connections from the adenohypophysis to the juxtaposed cavernous sinus, it was predicted that some portal vessels must carry blood from the adenohypophysis back to the neurohypophysis. Physiological studies confirmed this prediction and verified earlier observations that blood-flow within the neurohypophysis can be towards the median eminence. In the present study, increased concentrations of prolactin and growth hormone were found in blood sampled from intracranial vessels (internal carotid artery and sagittal sinus). It was concluded that the neurohypophyseal capillary bed not only receives trophic hormones produced in the adenohypophysis but, under certain physiological circumstances, delivers those hormones directly to the brain.


Child-resistant packaging and accidental child poisoning. From Jan. 1, 1976, all children's aspirin and paracetamol preparations were required to be presented either in child-resistant containers or in dark-tinted unit packaging. In two areas hospital admissions of children under 5 years for accidental ingestion of aspirin were monitored from 1974 to 1976 to assess the effectiveness of this measure. There was a highly significant fall in admissions for accidental salicylate poisoning (129 in 1975 to 48 in 1976, P less than 0-001). Admissions fell throughout 1976 as old stocks were used up. Further analysis of cases in one area suggests that the fall in admissions from accidental salicylate poisoning was due to the packaging of one preparation of junior aspirin in child-resistant containers.


Strokes: A complication of mitral-leaflet prolapse? During a prospective trial of platelet-inhibiting drugs in patients with transient ischaemic attacks (T.I.A.s), 14 patients had serious neurological dysfunction and normal cerebral angiograms. The patients (mean age 37 years) had neurological episodes over a period of 1-4 years consisting of acute non-progressive strokes with residual symptoms. In 3 patients, the two cerebral hemispheres were involved on different occasions. Cerebral angiograms showed no significant atheromatous disease in the intracranial or extracranial vessels. 3 patients had mid-systolic clicks, 5 had systolic murmurs, and 2 patients had both a click and a murmur. Holter electrocardiographic monitoring revealed atrial, junctional, or ventricular extrasystoles (5 patients), paroxysmal atrial fibrillation (3), and paroxysmal ventricular tachycardia (1). Left ventricular angiography confirmed mitral-leaflet prolapse in all the patients. The focal nature of the T.I.A.s suggests an embolic event, the embolus arising from the abnormal mitral valve. In a patient not included in this series, a small antemortem left atrial thrombus was found at necropsy.


Factors affecting the outcome of cadaver renal transplantation in Newcastle upon Tyne. In an analysis of a series of 186 consecutive first cadaver renal transplants in Newcastle upon Tyne, the most significant finding was the improved graft survival in patients who received pre-transplant blood-transfusion. This apparent benefit was not dependent on the number of units of blood received nor on the interval between transfusion and transplantation. A significant advantage was also shown when there was identity between donor and recipient at the HLA-B locus. This advantage outweighs any disadvantage resulting from the extra time required to transfer kidneys from one centre to another and indeed cold-ischaemia times up to 18 hours did not adversely affect graft survival. It is suggested that the present national distribution of cadaver kidneys in the U.K. is fully justified, but preference should be given to B-locus identity in determining selection.


Detection of acute myocardial infarction by radioimmunoassay for creatine kinase MB. A radioimmunoassay for the MB isoenzyme of creatine kinase (myocardial isoenzyme) has been developed based on an antibody to the B subunit. The antibody cross-reacts with MB but exhibits no cross-reactivity with MM C.K. even when present in 20 000 molar excess over MB C.K. unlabelled MB but not MM (up to 85 000 mI.U./ml) competitively displaces precipitable counts. This sensitive and specific radioimmunoassay accurately detects MB in a concentration of 0-01 mI.U./ml. Plasma MB C.K. in 100 healthy controls averaged 1 mI.U./ml+/-0-6 (S.D.), similar to results in 20 patients with chest pain without infarction. In contrast, in 50 patients with myocardial infarction MB C.K. values averaged 97+/-30 mI.U./ml. When hourly blood-samples from 10 of these patients admitted within an hour of chest pain were analysed by R.I.A., a 100% increase in MB was detectable within four hours of the onset of chest pain, generally before total C.K. exceeded the normal range. Development of an R.I.A. suitable for assay of an isoenzyme in plasma provides a specific and sensitivity assay of MB C.K., facilitating analysis of multiple samples and early detection of myocardial infarction. It may also serve as a prototype for radio-immunoassay of multiple forms of other enzymes of clinical importance.


Chromosome aberrations and sister-chromatid exchange in workers in chemical laboratories and a rotoprinting factory and in children of women laboratory workers. Cultured lymphocytes from 73 workers in chemical laboratories and the printing industry were found to have a significantly increased frequency of chromatid and isochromatid breaks, in comparison with 49 control subjects (42 adults and 7 children). An increase of the same magnitude was also found in 14 children, aged 4 days--11 yr, of 11 women laboratory workers who had worked during pregnancy. A significant correlation between age and frequency of chromosome aberrations was noted for both the exposed and control children but not for the adults. The frequency of sister-chromomatid exchange was significantly increased in 12 technicians working in laboratories performing hormone analysis. 4 children of 2 female technicians working during pregnancy also had a significnatly increased frequency of sister-chromatid exchange. The cause and biological significance of these findings are not yet known.


Familial studies of type-I and type-II idiopathic diabetes mellitus. A study of 296 diabetics demonstrated an association between the type of diabetes in the propositi and their first-degree relatives (aged 40 to 89 yr), the type of diabetes being defined as insulin-dependent (type I) or insulin-independent (type II). This association was significant at the 1% level and was still maintained when only the propositi in whom the diabetes was diagnosed at the age of 30 years or later were considered. The findings also suggest that there is a greater genetic independence between these two types than was previously supposed and that the disease should be subdivided into type according to the treatment needed rather than by the age of onset.


Plasma renin and angiotensin II in acute renal failure. The role of raised plasma renin and angiotensin-II concentrations in the development of acute renal failure in man was examined in patients in shock from various causes and in patients in whom hypotension was used to promote haemostasis. Ten of the thirteen patients in shock had raised angiotensin-II concentrations in peripheral blood and acute renal failure manifested by oliguria, increasing serum-creatinine, a urine osmolality of less than 400 mos-mol/kg and a urine/plasma osmolality ratio of less than 1-5. Although patients who were hypotensive for periods of 1 h 45 min to 4 h to promote haemostasis during surgery had similarly raised plasma-renin activity and angiotensin-II concentrations in peripheral venous blood, they did not have acute renal failure. It is concluded that high plasma-angiotensin-II concentrations do not explain the pathogenesis of acute renal failure in patients in shock.


A membrane-bound enzyme in rabbit aorta capable of inhibiting adenosine-diphosphate-induced platelet aggregation. A membrane-bound enzyme that is capable of inhibiting adenosine-diphosphate (A.D.P.)-induced platelet aggregation has been found in rabbit aorta. This inhibition is caused by degradation of A.D.P. to products (adenosine monophosphate and adenosine) which can also inhibit aggregation. The enzyme could be important in regulating haemostasis and thrombosis.


Topical thrombin and control of wound haematoma. The frequency of wound haematoma was investigated in 45 prophylactically heparinised patients undergoing abdominal surgery. Thrombin was applied locally to the wound in 15 patients, and in these patients wound haematoma was significantly less common than in the controls.


A new factor that may control collagen resorption. Specific collagenases responsible for the initial enzymic step leading to degradation of the collagen fibrils of connective tissues have been found in both latent and active forms. The most important factor controlling the local activity of collagenase extracellularly may be an inhibitor that is synthesised by connective tissues, and it is proposed that latent enzymes are all enzyme-inhibitor complexes.


Munchausen syndrome by proxy. The hinterland of child abuse. Some patients consistently produce false stories and fabricate evidence, so causing themselves needless hospital investigations and operations. Here are described parents who, by falsification, caused their children innumerable harmful hospital procedures--a sort of Munchausen syndrome by proxy.