Unsuccessful treatment with levodopa of a parkinsonian patient with calcification of the basal ganglia. A patient aged 67 had suffered from hypoparathyroidism (tetany and cataracts) following thyroidectomy at the age of 20, although treated with AT 10. During the last few years there had been a change of gait to small steps and general retardation. Nocturnal epileptic attacks occurred in the last year which led to the admission to hospital where a well developed parkinsonian syndrome without tremor was observed. X-rays of the skull, including computed tomograms, revealed calcification of the basal ganglia and dentate nuclei. Treatment with levodopa was ineffective. The mechanism for this is discussed.


Central core disease: histochemical and ultrastructural study of muscle biopsies of father and daughter. Two cases of central core disease, father and daughter, of a family with dominant autosomal inheritance, are presented, one with bilateral congenital dislocation of the hip. Muscle biopsy was performed in both cases. Oxidative enzymes evidenced only type I fibers, most of them presenting a central core and not uncommonly more than one. On electron microscopy the cores generally appeared well demarcated from the surrounding fibrils and were characterized by lack of mitochondria and abnormalities of the Z line. Transitional aspects from normal fibers to completely unstructured cores were observed, as well as from well structured and unstructured cores. These findings are discussed in the light of the previous literature and particular attention is paid to the problem of differentiation between central core and multicore disease. The pathogenesis of the muscular alteration is also discussed in relation with the possibility of their neurogenic origin. Eventually, the histochemical and ultrastructural similarities between central cores and target fibers are focused.


Carcinomatous encephalomyelopathy in conjunction with encephalomyeloradiculitis. A man, aged 63, had an illness which lasted 11 months from onset with pain under the left costal margin which radiated to the epigastrium, until his death from cardiac failure. His symptoms consisted principally of parasthesias and proximal weakness of both upper and lower extremities with atrophy of the shoulder and pelvic girdles. He developed pyramidal tract signs, became euphoric, emotionally unstable and mentally retarded. There was no clinical evidence of cerebellar dysfunction. Bronchogenic carcinoma was suspected from a tomograph of the thorax, but, in spite of extensive clinical and laboratory studies, the diagnosis was verified only postmortem. The CSF cell count was high at first but diminished as the disease progressed. Muscle biopsies revealed chronic generalized denervation without signs of myopathy. Neuropathologically, encephalomyeloradiculoneuritis concentrated on the spinal cord was combined with severe rarefaction of the ganglion cells of the anterior horns and with bilateral degeneration of the lateral pyramidal spinocerebellar and posterior tracts. A more diffuse process was obvious in the anterolateral tracts of the lumbar region. Polyneuropathy concentrated in the distal region was accompanied by slight inflammatory reaction in the sciatic nerve. Cerebellocortical degeneration which exceeded physiological age-related rarefaction was also present. The findings are discussed in relation to the literature.


Multiple sclerosis: demyelination and myelination inhibition of organotypic tissue cultures of the spinal cord by sera of patients with multiple sclerosis and other neurological diseases. Sera from 44 patients with Multiple Sclerosis, of three patients with neurological syndromes compatible with Multiple Sclerosis, of 34 patients suffering from other neurological diseases and of 25 pregnant healthy young women were tested for their demyelinating activity in myelinated tissue cultures. In order to leave the investigators unprejudiced, all sera were coded and intermixed with controls of rabbit EAE serum which had a potent demyelinating capacity. Demyelination was graded (from 0--4), heat lability at 56 degrees C (complement dependency?) was also tested with each serum. Only demyelination of a degree of 2 and more, which was abolished by heating to 56 degrees C, was counted as positive. Six of the 44 sera from MS patients (13.6%), 19 of 37 sera from neurological patients and none of the healthy young women demyelinated. Thus, serum demyelination of tissue cultures seems to be a nonspecific indicator of chronic disease of the nervous system and is of considerable general neurological interest, but does not indicate a demyelinating disease. Myelination inhibition was not observed with any of the human sera tested for it.


Microzone electrophoresis of the unconcentrated and concentrated CSF. Concerning the small methodical range of error and the little expenditure of work microzone electrophoresis of the non-concentrated CSF after staining with nigrosine and after evaluation on non-transparent acetate film should have priority to microzone electrophoresis of concentrated CSF. This paper reports a comparison of microzone electrophoresis of non-concentrated and concentrated CSF.


Prolonged impairment of cellular immunity in children with intrauterine growth retardation. Cellular immunity was studied in 17 newborn infants, in eight children aged 1 to 5 years with intrauterine growth retardation, and in age-matched control subjects. At birth T and B peripheral blood lymphocytes were decreased, and delayed cutaneous hypersensitivity to phytohemagglutinin was diminished. In vitro PHA-induced lymphocyte proliferation was similar to that in control subjects but was greater than in healthy adults. In later childhood the numbers of T lymphocytes were normal, but their proliferative capacity was significantly reduced and cutaneous hypersensitivity was minimal or absent. Prolonged impairment of cellular immunity in these children may explain their increased susceptibility to infection and inadequate response to immunization, and predispose to the development of allergic, autoimmune, and neoplastic disease.


Evaluation of alpha-fetoprotein in early infancy. Serum AFP concentrations of normal subjects were statistically analyzed in order to obtain the normal ranges in early infancy. The 95% prediction band would seem to offer a convenient means of evaluating serum AFP in the age range 0-300 days of life. Some illustrative cases, whose AFP values were formerly considered to be abnormally high but later proved to be within normal range, are presented.


Evidence for H2-receptor-mediated feed-back regulation of histamine release from endocrine cells in the rat stomach. 1. Pentagastrin reduces the concentration of gastric mucosal histamine in the rat. This effect is counteracted by large doses of histamine H2-receptor agonists which are particularly effective if infused I.V. 2. After blockade of histamine H2-receptors but not of H1-receptors, the pentagastrin-induced reduction of mucosal histamine is greatly augmented and H2-receptor agonists no longer inhibit the response to pentagastrin. 3. It is suggested that in the rat stomach, H2-receptors occur on the histamine storing endocrine cells as well as on parietal cells and that mobilized mucosal histamine inhibits further release of histamine by way of H2-receptor-mediated auto feed-back.


Resolution and characterization of intracytoplasmic forms of reverse transcriptase from Rauscher leukemia virus-producing cells. The microsomal supernatant fraction obtained from a murine cell line chronically infected with and producing Rauscher leukemia virus (JLSV-10) was found to contain two forms of RNA-directed DNA polymerase (reverse transcriptase). The two enzyme forms, neither of which is detectable in uninfected cells (JLSV-9), were initially partially purified by poly(C)-agarose chromatography, and their separation was achieved by phosphocellulose chromatography. The enzyme form eluting first from phosphocellulose (0.3 M KCl), designated PC I, was found to be identical in all parameters tested to that form isolated directly from purified virions. The second enzyme peak, designated PC II, eluted from phosphocellulose at 0.5 M KCl and was not detectable in purified virions. The PC II enzyme has a molecular weight, determined by velocity sedimentation, of approximately 109,000, as compared with 70,000 for the PC I enzyme, and could not be further dissociated by exposure to high salt or nonionic detergent. Mixing purified virion or PC I DNA polymerase with uninfected cells followed by fractionation did not produce the PC II form, suggesting that it is neither an artifact of purification nor the result of fortuitous complexing of reverse transcriptase with normal cellular component(s). Both PC I and PC II enzyme forms appeared antigenically similar to virion DNA polymerase, demonstrated identical divalent cation requirements for various template-primers, and were capable of copying heteropolymeric regions of rabbit globin mRNA. However, kinetic studies of heat inactivation revealed that the PC II enzyme was far more heat labile than the PC I form, which appeared identical to the virion enzyme in this respect. Furthermore, whereas the PC I and virion-derived reverse transcriptase copied poly(C).(dG)12-18 most efficiently at a template-to-primer molar nucleotide ratio of 25:1, the PC II enzyme preferred a ratio of 5:1 for optimal rates of poly(dG) synthesis. Therefore, by these criteria, there appear to exist two intracellular forms of reverse transcriptase in the JLSV-10  Rauscher  leukemia  virus-producing  murine  cell  line.


Multiple RNase H activities in mammalian type C retravirus lysates. Lysates of Moloney murine sarcoma-leukemia virus [M-MSV(MLV)], a virus complex grown in the rat cell line 78A-1, were found to contain three RNase H species separable by polycytidylic acid[poly(C)]-agarose chromatography. RNase H activity (RNase H I) associated with RNA-directed DNA polymerase eluted at 0.23 M KCI from poly(C)-agarose. RNase H II, which eluted from poly(C)-agarose at 0.12 M KCI and was not associated with DNA polymerase activity, was shown to be identical to an RNase H species (designated RNase H II) previously isolated from M-MSV(MLV) by a different procedure (G. F. Gerard and D. P. Grandgenett, J. Virol. 15:785-797, 1975). M-MSV(MLV) RNase H II was established to be a random exohybridase that requires free-chain termini in its hybrid substrate for activity. Lysates of Rickard feline leukemia virus also contained RNase H activity not associated with DNA polymerase activity that eluted from poly(C)-agarose at 0.12 M KCl. A third species of enzyme from M-MSV(MLV) lysates, called RNase H III, did not bind to poly(C)-agarose in 0.06 M KCl. RNase H III was purified from lysates of M-MSV(MLV) and M-MLV (grown in mouse cells) by sequential chromatography on poly(C)-agarose, DEAE-cellulose, phosphocellulose, and polyuridylic acid-Sepharose. Purified RNase H III (i) was free of any associated DNA polymerase activity, (ii) had an apparent molecular weight of 30,000 determined by Sephadex G-100 gel filtration, (iii) had an absolute requirement for Mn2+ (1 mM optimum) for the degradation of [3H](A)n.(dT)n, (iv) was inhibited by the presence of any salt in reaction mixtures, and (v) was endoribonucleolytic in its mode of action as indicated by the size distribution of limited degradation products of [3H](A)n.(dT)n. RNase H III was inhibited by antisera prepared against Rauscher MLV and simian sarcoma virus reverse transcriptase, and the quantity of RNase H III and RNase H I present in lysates of M-MLV were reduced and increased proportionately if virus was lysed in the presence of the protease inhibitor phenylmethylsulfonyl fluoride. These results indicate that RNase H III is a proteolytic cleavage product of DNA polymerase-RNase H. Substantial RNase H activity that did not bind to poly(C)-agarose in 0.06 M KCl was also found in lysates of Harvey MSV(MLV), Rauscher MLV, and Rickard feline leukemia virus, but not in lysates of avian myeloblastosis virus.


Simian virus 40 (SV40)-specific proteins associated with the nuclear matrix isolated from adenovirus type 2-SV40 hybrid virus-infected HeLa cells carry SV40 U-antigen determinants. The distribution of simian virus 40 (SV40)-specific proteins in nuclear subfractions of pulse-chase-labeled HeLa cells infected with nondefective adenovirus type 2 (Ad2)-SV40 hybrid viruses was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The SV40-specific proteins of Ad2+ND1, Ad2+ND2, and Ad2+ND5 specifically associate with the nuclear matrix and are virtually absent from the high-salt nuclear extract. In Ad2+ND4-infected HeLa cells, the SV40-specific proteins with molecular weights of 64,000 (64K) and lower also specifically associate with the nuclear matrix. The SV40-specific 72K, 74K, and 95K proteins were found both in the nuclear matrix and in the high-salt nuclear extract. Analyses of the nuclear matrices isolated from hybrid virus-infected cells by immunofluorescence microscopy showed that SV40 U-antigen-positive sera from SV40 tumor-bearing hamsters react with SV40-specific proteins integrated into nuclear matrices of HeLa cells infected by Ad2+ND1, Ad2+ND2, and Ad2+ND4, but not with nuclear matrices of HeLa cells infected by Ad2+ND5. This suggests that SV40-specific proteins of Ad2+ND1, Ad2+ND2, and Ad2+ND4  integrated into the nuclear matrix carry SV40 U-antigen determinants. The apparent discrepancy in the subcellular localization of SV40-specific proteins in hybrid virus-infected cells when analyzed by biochemical cell fractionation procedures and when analyzed by immunofluorescence staining is discussed.


Chemical hypophysectomy for relief of bone pain in carcinoma of the prostate. A series is presented of 10 patients with intractable pain secondary to diffuse metastatic prostatic carcinoma. These patients underwent pituitary ablation by a new method of chemical hypophysectomy, which consisted of multiple injections of absolute alcohol into the pituitary gland under stereotaxic control. Of the 10 patients 9 had good to excellent pain relief. There was no operative mortality. The sequelae are those associated with pituitary destruction, the most significant being diabetes insipidus. Preoperative and postoperative hormonal studies failed to reveal any significant hormonal changes despite good and almost immediate pain relief.


Accuracy of Gram's stain in identifying pneumococci in sputum. We prospectively examined the accuracy of Gram-stained sputum for identifying pneumococci in 42 patients with community-acquired pneumonia. We considered the Gram's stain positive if a preponderant flora or more than ten Gram-positive lancet-shaped diplococci were seen per oil immersion (x1,000) field. These criteria were met in 18 (62%) of 29 specimens that actually contained pneumococci as determined by a positive quellung reaction, or culture on plates or in mice. The Gram's stain was negative in 11 of 13 specimens that did not contain pneumococci. Of the 20 specimens yielding positive Gram's stains, 18 contained pneumococci. A positive Gram-stained smear of sputum strongly suggests the presence of pneumococci, but will miss 38% of specimens containing pneumococci. Deviation from these criteria substantially reduces the overall accuracy of the test.


Composition of gall-stones-histochemical staining. Twenty Six mixed infective and 2 cholesterol gall-stones were stained for cholesterol, calcium, fat and mucoproteins. Calcium and cholesterol were found to be the main constituents of all the calculi. Calcium was found mainly in the centre and mucoprotein in the peripheral layers. The fine crystals of cholesterol were demonstrated in those biliary calculi which did not contain mucoprotein. It appeared that calcium might have acted as a cementing force rather than mucoprotein in this study.


Cell cycle dependent response and combined treatment of tumor. Attempt was made to summarize data indicating cell cycle dependence of survival response to various antitumor agents. Normalized patterns of survival response permitted us to group agents into two major categories. It was known that effect of agents on cell progression was not only related to respective periods of the cell cycle but also rather specific for each category of agents. The extent of progression inhibition was not compared on a quantitative basis. On the basis of above findings a rational combination and a scheduled administration of agents for effective sterilization of tumor cells were considered.


Combined therapy with bleomycin and selective intra-arterial infusion of mitomycin C in lung cancer. Bronchial artery infusion of mitomycin C might be very effective in treating minor tumors but, as a rule, less effective in the treatment of larger tumors. In order to achieve improved effect of treatment, 21 cases (stage II-III/TNM) were given supplementary chemotherapy with bleomycin or vincristine-bleomycin. Preoperative treatment was given to 11 cases in which indications for surgical treatment were primarily uncertain or absent. The other group consisted of 10 patients with inoperable lesions. Combined treatment has proved to have a strong but mainly local effect. Repeated courses (up to 5 times) were more effective than a single one. The regional effect, i.e: on overgrowth onto the mediastinum, pericardium or thoracic wall was weak. The system effect was negligible. Penetrating data about objective response are given.


Effects of n-decylamine and toluidine blue on the electric capacitance of isolated rat mast cells. The electric capacitance of isolated rat mast cells and its change under the influence of either n-decylamine or toluidine blue was investigated. Since the electric circuit employed in the detection unit is the one merely sensitive for the capacitance changes, output signals pertain to the capacitance of the tested cell alone. N-decylamine released histamine without accompanying degranulation; and it caused a marked swelling of mast cells and a striking decrease of capacitance, although electric capacitance is usually proportional to the size of the cell. Morphological changes induced by toluidine blue are seemingly correlated with the changes in capacitance. At the concentrations (25-50 microgram/ml) in which the mast cell became enlarged, electric capacitances exceeded the control value. However, at the concentrations higher than 100 microgram/ml in which the cell became shrunken, the capacitance values were less than control value. Pretreatment with DNP (0.1 mM) or oxyphenbutazone (0.05-0.2 mM) was of little effect in inhibiting the histamine release, morphological alterations and capacitance changes due to n-decylamine, but pretreatment with either prevented all of those changes produced by toluidine blue. The mechanism of the capacitance changes in mast cells induced under influence of those compounds is discussed.


[The function of the retina in malattia leventinese (dominant drusen) (author's transl)]. Malattia leventinese was studied clinically and by electroretinography in 27 members of an affected family and in two additional cases. Typical changes in the central fundus consist of agglomerations of drusen, varying in size, number and localization. These distinct ophthalmoscopic changes occur in young adults, but characteristically remain asymptomatic for one to five decades. Then, metamorphopsia  and diffuse color vision deficiency introduce a rapid decay in visual acuity. These changes in function are observed in parallel with large fields of confluent drusen, atrophy of the pigment epithelium and of the retina and with patchy pigmentations in the central fundus. The electroretinogram (ERG) of the subjects with drusen revealed "low normal" amplitudes of the b-waves of both, the cone- and rod system. These ERG-data suggest discrete but widespread functional abnormalities in the outer and middle layers of the retina well before the onset of the clinical symptomatology. In contrast, subnormal ERGs (b-wave amplitudes below 2 standard deviations of normal controls) were recorded in the advance cases, and reflected the severity of functional and structural changes.


The production and use of an attitudinal film in birth control education. In order to help improve the effectiveness of birth control education programs, a film "It Couldn't Happen to Me" was produced focusing on the psychological motives involved in the non-use of birth control among teenagers. Preliminary evaluation of the film took place with five sample groups: high school students, university students, nursing students, health educators, and Planned Parenthood workers. Survey results indicate that the film is relevant for each of these groups. Pre and posttest measures of the attitudes of the university and nursing samples indicate that the film makes viewers more aware of the psychological factors involved in the non-use of birth control.


Larynx cancer: a therapeutic policy at the Madras Cancer Institute. We studied 145 cases of larynx cancer in relation to their etiology, methods of treatment, and results. It was found that better results were obtained with a combination of radiotherapy and surgery. Any postradiational edema of the larynx should subside within 3 months. If this edema persists or progresses, it always means residual disease in the submucosal plane. We have now improved our results by using intravenous Bleomycin concurrently.


Common antigens found on fetal cells and viral transformed adult prostatic tissue. In vivo and in vitro immunologic cross reactivity between SV40 virus transformed prostatic tissue and fetal antigens of LVG/LAK strain hamsters has been studied. The hamsters immunized with fetal antigens demonstrated significant resistance to tumor growth. Complement-dependent humoral cytotoxicity of target SV40 tumor cells in microtest plates was used to demonstrate the presence of significant antibody titer in fetal-immunized hamsters. When the immune sera were absorbed with SV40 transformed prostatic tissue, cytotoxicity indices were markedly lower than with the unabsorbed immune sera. The transformed prostatic tissue was found to have an elevated tartrate inhibited acid phosphatase indicative of the presence of epithelial components in the transformed tissue. These experiments demonstrate in vivo and in vitro cross reactviity between fetal antigens and tumor associated antigens of transformed prostatic tissue. This study suggests a similarity between fetal antigens and antigens of a specific organ tissue (prostate) transformed by a DNA oncogenic virus.


Anterior-horn cell degeneration and gross calf hypertrophy with adolescent onset. A new spinal muscular atrophy syndrome. A new variant of spinal muscular atrophy (S.M.A.), characterised by adolescent onset, gross hypertrophy of calves, and a slowly progressive clinical course, was found in 5 patients, 3 of them in a series of 102 cases being studied in North-East England. Biopsy and electrophysiological studies indicated the presence of chronic progressive degeneration of anterior-horn cells.


Non-occupational exposure to asbestos and malignant mesothelioma in females. A study of the occupational histories of 52 females with malignant mesothelioma and certain of their relatives, carried out to measure the risk of this disorder attributable to indirect asbestos exposure, showed that a significantly greater number of husbands and fathers of cases than of controls worked in asbestos-related industries, and the relative risk for this factor was 10. The frequency of parental cancer, especially gastrointestinal malignancy, was also significantly greater for cases than for their controls. This raises the possibility of a genetic predisposition to malignant mesothelioma.


Clostridium difficile and the aetiology of pseudomembranous colitis. Bacterial isolates from 5 patients with pseudomembranous colitis (P.M.C.) were screened for toxin production. Strains of Clostridium from 4 patients produced in vitro a toxin similar to that found in P.M.C. faecal suspension. These were identified as C. difficile. Use of the strains from 2 patients induced a fatal enterocolitis when inoculated orally into hamsters pretreated with vancomycin. The C. difficile that produced the toxin in vitro was then re-isolated from hamster caecal contents. These findings suggest that P.M.C. results from infection with C. difficile and that previous antibiotic therapy produces susceptibility to infection.


Oral cromoglycate in treatment of adverse reactions to foods. 20 subjects with adverse reactions to foods were given oral cromoglycate and placebo separately for seven days each. While on each medication they were given, for four consecutive days, a food to which they were sensitive. Adverse reactions were prevented in 14 subjects. These results suggest that oral cromoglycate is of value in the treatment of some patients with adverse reactions to foods.


Drug-induced immunological neutropenia.

Drug-induced immunological neutropenia. Antineutrophil antibody capable of opsonising normal neutrophils was detected in the sera of 16 neutropenic patients receiving various drugs. A single drug was involved in 10 cases, multiple medication in 6. 4 patients received semisynthetic penicillins, 8 some form of antimicrobial, and 2 antithyroid agents. Neutrophil counts rose, and antineutrophil antibody activity declined or disappeared, after drug therapy was stopped. Opsonisation related to the semisynthetic penicillins was independent of complement but dependent on drug concentration. Complement-dependent opsonic activity was demonstrated in 2 patients (1 receiving methimazole and 1 receiving multiple medication) and in the patient receiving methimazole this activity was shown to reside in the IgM serum-fraction. In another patient receiving multiple drugs, a complement-independent IgG antibody was demonstrated.


Is skin preparation necessary before insulin injection? The effect of routine skin preparation on skin bacterial flora was measured in thirteen insulin-dependent diabetic patients. 5 seconds of skin cleansing of sites on the leg, arm, and abdomen with 70% isopropyl alcohol reduced bacterial counts by 82-91%. During a 3-5 month observation period the subjects omitted skin preparation before insulin injection every other week. More than 1700 insulin injections were given without skin preparation. No signs of local or systemic infection were observed. These results indicate that routine skin preparation with alcohol before insulin injection markedly reduces skin bacterial-counts but may not be necessary to prevent infection at the injection sites.


Acid hydrolases in monocytes from patients with inflammatory bowel disease, chronic liver disease, and rheumatoid arthritis. A sensitive technique was used to estimate two acid hydrolases--N-acetyl-beta-glucosaminidase (N.A.G.) and beta-glucuronidase (B.G.)--produced by peripheral-blood monocytes. Enzyme levels were measured after in-vitro incubation of monocytes with or without stimulation by zymosan and endotoxin. Compared with controls, enzyme production and release in inflammatory bowel disease, chronic liver disease, and rheumatoid arthritis were markedly raised. It is suggested that various stimuli, including immunological ones, may be responsible for the release of such enzymes from monocytes and that such release may be a factor in the production of the chronic inflammation seen in these disorders.


Does pregnancy protect against ovarian cancer? A clear inverse relation between average completed family size and mortality from ovarian cancer in different populations of women is seen from one country to another; for successive generations of women living within the same country; in married and single women; and in different social, religious, immigrant, and ethnic groups. The findings suggest that pregnancy--or some component of the child-bearing process--protects directly against ovarian cancer. This protection seems to persist throughout life. The more-than-twofold increase in the age-standardised ovarian-cancer death-rate in England and Wales since 1931 can be explained largely by changes in the average completed family size.


Cigarette consumption and deaths from coronary heart-disease. There is a positive association between cigarette smoking and coronary heart-disease (C.H.D.). In non-fatal myocardial infarction a dose-response relation persists even after the effects of additional variables have been controlled for. The relation between cigarette consumption and deaths from C.H.D. was investigated in a matched-pair case/control study. The overall simple matched-pair risk ratio (R.R.) between current smokers and non-smokers was 1.9 (95% confidence limits 1.5-2.4). For smokers of fewer than 20 cigarettes per day, the R.R. was 1.2; at a level of 21-40 cigarettes per day, the R.R. was 2.3; and for smokers of 41+ cigarettes per day, the R.R. was 4.0. A similar relation was found after adjustment for additional variables. These results suggest that the heaviest smokers could halve their risk of death from C.H.D. by reducing their tobacco consumption to an intermediate level; and that benefit of a similar order would be experienced by smokers of 21-40 cigarettes per day who cut down to less than one pack (20 cigarettes) daily.


Comparison of fixed doses of chenodeoxycholic acid for gallstone dissolution. 96 patients with gallstones have been treated for up to four years with chenodeoxycholic acid in daily doses of 500, 750, or 1000 mg. None of the patients started on 500 mg daily showed complete gallstone dissolution. 8 out of 41 patients on 750 mg daily had complete dissolution of their radiolucent gallbladder stones after six or more months, and a further 4 showed partial dissolution. 5 out of 28 patients on 1000 mg daily had complete dissolution of their radiolucent gallbladder stones after at least six months, and a further 9 showed partial gallstone dissolution. The mean duration of therapy was greater on 750 mg than on 1000 mg/day (1.27 vs. 0.58 years), and when results were analysed after the first six months' therapy the total response-rate was significantly greater for the 1000 mg dose (12 out of 28) than for the 750 mg dose (9 out of 41). The individual response of radiolucent gallabladder stones to therapy could not be predicted from stone size, weight of patient, dosage/kg, orchange in biliary lipids. Treatment of radiolucent gallstones with chenodeoxycholic acid should start at 1000 mg daily.


Prophylaxis against postoperative pulmonary embolism and deep-vein thrombosis by low-dose heparin. The prophylactic effect of low-dose heparin on postoperative fatal and on clinically apparent but non-fatal thromboembolic complications was studied in a double-blind, prospective, randomised study comprising 1296 patients. 16 out of 653 patients in the placebo group had such complications within the treatment period of 1 week, compared with 4 out of 643 in the heparin group. This difference was statistically significant (P less than 0.05). 4 cases in the placebo group and 1 in the heparin group were fatal. After prophylactic treatment had been stopped at the end of the first postoperative week, the rate of thromboembolic complications was equal for the 2 groups. Low-dose heparin prophylaxis is thus effective and should be given routinely in patients aged over 40 years; it should also be given for more than 1 week in patients not ambulant by then.


Antibodies to synthetic polyribonucleotides in spouses of patients with inflammatory bowel disease. Serum from patients with inflammatory bowel disease (I.B.D.) and their unaffected spouses bound significantly more synthetic single-stranded (poly.rA) and double-stranded (poly.rA.poly.rU) R.N.A. but not KB cell D.N.A. than did serum from age-matched controls and their spouses. Binding activity resided in Ig fractions and was predominantly of IgM class. A significant corelation was observed between the amount of double-stranded but not single-stranded R.N.A. bound by serum from patients and from their respective spouses. These findings provide indirect support for the presence of R.N.A. viruses in patients with I.B.D. and the transmission of such agents to their close personal contacts.


Escherichia coli strains that cause diarrhoea but do not produce heat-labile or heat-stable enterotoxins and are non-invasive. Three enteropathogenic Escherichia coli (E.P.E.C.) strains (O127:K63:H6, O128:K67:H2, and O142:K86:H6) isolated from outbreaks of infantile diarrhoea and one strain from the "normal" colonic flora (E. coli HS) of a healthy adult were fed in doses of 10(6), 10(8), and 10(10) organisms in NaHCO3 to adult volunteers. The strains, which had been stored for 7--9 years, gave negative results in sensitive tests for heat-labile (L.T.) enterotoxin (Y-1 adrenal-cell test), heat-stable (S.T.) enterotoxin (infant mouse assay), invasiveness (guineapig eye test), and gross fluid accumulation (infant rabbit assay). Two strains (O142 and O127) caused diarrhoea. L.T. or S.T. enterotoxins were not found in E. coli stool isolates from individuals with diarrhoea and no one had a rise in L.T. antitoxin titre; the findings suggest that L.T. and S.T. enterotoxins were not involved in pathogenesis of the diarrhoea. Non-invasive E.P.E.C. strains probably induce diarrhoea by a mechanism (presumably an enterotoxin) distinct from L.T. or S.T. enterotoxins.


Elevated metabolic rates in obesity.

Elevated metabolic rates in obesity. The resting metabolic rates (R.M.R.s) of 69 obese patients were measured during a period of weight stability. All except 4 women had a rate, in megajoules per 24 hours, in excess of that for subjects of normal weight. This increased R.M.R. is obscured by the traditional method of expressing R.M.R. per unit surface area. The high R.M.R. in the obese state was related not to the excess fat but to a 36% and 32% increase in the lean body mass of the men and women respectively. The R.M.R.s of 30 patients measured during weight-loss fell. The increase in R.M.R. in obesity is an important mechanism for achieving energy balance, whereas the progressive fall in R.M.R. during slimming demonstrates the need for a permanent reduction in food intake if energy balance is to be maintained on reaching normal weight. Measuring only the R.M.R. in the obese state is unlikely to help in understanding the pathogenesis of obesity.


Total support of the circulation of a patient with post-cardiotomy stone-heart syndrome by a partial artificial heart (ALVAD) for 5 days followed by heart and kidney transplantation. A patient with acute bacterial endocarditis in whom ischaemic contracture of the left ventricle (stone-heart syndrome) developed during aortic and mitral valve replacement had an emergency implantation of an intracorporeal partial artificial heart (an abdominal left-ventricular assist device of ALVAD). This device functioned as a total artificial heart for nearly 6 days, while a donor heart for transplantation was sought. The ALVAD was then removed, and the patient received allografts of a heart and a kidney. The transplanted heart functioned well, but the patient died 15 days later from gram-negative sepsis. There was no evidence of cardiac or renal allograft rejection.


Canine distemper virus and multiple sclerosis. Serum samples from patients with multiple sclerosis (M.S.), patients with subacute sclerosing panencephalitis (S.S.P.E.), and controls were examined for virus-neutralising antibodies against measles virus (M.V.) and 2 strains of canine distemper virus (C.D.V.). M.S. and S.S.P.E. patients had higher M.V. antibody titres than controls. In contrast, no significant differences were observed in mean C.D.V.-neutralising antibody titres between M.S. patients and controls. The results, though obtained from a small number of patients, fail to implicate C.D.V. in the aetiology of M.S.


Early prenatal diagnosis of neural-tube defects by ultrasound-guided fetoscopy. In three fetuses with neural-tube defects (N.T.D.s) the lesions were clearly seen by fetoscopy in the second trimester. In a fourth fetus, in which the diagnosis of N.T.D. was suspected because of raised amniotic-fluid alpha-fetoprotein, spina bifida was excluded by fetoscopic examination and a normal baby was delivered at term. Ultrasound-guided fetoscopy has a place in the diagnosis of N.T.D.s when the results of other investigations are conflicting or inconclusive, and may be useful in assessing the severity of a lesion.


Small-intestinal mucosal antibodies against antigens of non-pathogenic luminal or mucosal bacteria in young children with and without diarrhoea. Duodenal mucosal antibody against non-pathogenic bacteria, grown either from the luminal juices or the mucosa itself, was demonstrated for the first time in 7 of 8 children with diarrhoea and only 2 of 7 without diarrhoea. Neither group showed significant histological abnormalities on duodenal biopsy. An aetiological relation between the antibody and the persistence of postenteritis diarrhoea is possible.


Altered theophylline pharmacokinetics during acute respiratory viral illness. The plasma half-life of theophylline was determined during and 1 month after serologically confirmed upper-respiratory-tract viral illness in six children with chronic asthma. In this group the plasma-theophylline half-life (mean = 419.8 min) was significantly longer during the acute stage of their illness than 1 month later (mean 249.9 min). There was no appreciable change in half-life in 4 patients who were febrile but in whom seroconversion did not occur. These preliminary results suggest that certain upper-respiratory-tract viral infections may affect theophylline metabolism.


Clinical outcome of the first ten years of ulcerative colitis and proctitis. 269 patients with ulcerative colitis and a history of less than 6 months when first seen at St. Mark's Hospital in the decade 1966--75 have been followed for up to 11 years. The outcome has been correlated with the maximum extent of the disease observed within 3 months of presentation. 75 patients required hospital admission, 56 within a year of presentation. Extensive colitis developed in 60 patients. The cumulative probability of the disease being extensive was 21% +/- 3% at 5 years and 29% +/- 4% at 10 years. 25 patients required surgical treatment. The cumulative probability of operation was 8% +/- 2% at 5 years and 15% +/- 4% at 10 years. 19 patients are known to have died. The expected number of deaths was 19.2.


[The mode of action of bleomycin-cell kinetic investigations (author's transl)]. Chemotherapy of malignant ENT tumours with Bleomycin (BLM) alone is not very successful. In the last time however several authors pointed out much better therapeutic results when BLM therapy has been combined with radiation treatment It is farly unknown why this combination should cause a greater therapeutic effect. Therefore we investigated the following questions: 1. In what manner does BLM influence the kinetics of cell proliferation of malignant tissues? 2. Does BLM synchronize the tumour cells or is the greater therapeutic success of a combination of BLM and X rays only depending an an additional effect? 3. Can we find a connection between the effect of BLM and the histology of the tumour? With cell kinetic methods (authoradiography, cytophotometry, mitotic index) and histological technics we examined these problems in 5 human ENT tumours and got the following results: 1. BLM initially causes a partial synchronization of the tumour cells (blockade in the S-phase). During a continuous therapy with BLM however the tumour cells will be collected in the late S- and mainly in the G2-phase. But this peak of cells in G2 is not the expression of synchronization because a lot of these cells are blocked irreversible and will leave the cell cycle (hyperceratotic cells). Ffrom those cells which thereupon have entered the mitotic phase a further part of them will by endomitosis or endoreduplication. Only a small group of the cells originally collected in the G2-phase will devide and enter the G1-phase again. Furthermore we observed a distinct recruitment of G0-cells back into the cell cycle (for details see fig. 9). 2. The greater effect of radiation therapy following the application of BLM is not the result of synchronization but of an additional destruction of premitotic G2-cells which properly would have undergone mitosis. BLM and X rays therefore act additionally. 3. The greater therapeutic success of the combination of BLM and radiation treatment comes true only in keratinizing squamous cell carcinoma. The reason is that BLM destroys the tumour cells by hyperkeratosis and polyploidy. Thus BLM must be ineffective in carcinoma without the ability of keratinizing.


[Distribution studies of 111In labeled bleomycin in the intratumoral and peritumoral treatment of advanced squamous cell carcinomas in the oto-rhino-larygnological region (author's transl)]. The localization of 111In labeled Bleomycin was studied in 9 patients with advanced squamous cell carcinomas. The dosis was injected either peritumorally or intramorally. Accumulation of Radiobleomycin in tumor tissue, in blood and in urine was tested. We found a very high accumulation in tumor tissue for a short time within 2 hours, a very rapid excretion of Radiobleomycin in urine and concomitant slowly decrease of 111In Bleomycin in blood was observed.


57Co-bleomycin imaging study of tumors of the head and neck. 57Co-Bleomycin (57Co-BLM) was used to visualize malignancies of the head and neck because it does not present the disadvantages of many other radiopharmaceuticals. In a series of 21 patients with 9 control subjects and 12 cases of tumors. 57Co-BLM showed a high and rapid uptake in primary site and metastases of malignant tumors of various histologic types, but not in benign tumors such as angiofibromas. Compared to 67Ga-citrate. 57Co-BLM has many advantages for tumor imaging in the areas of nose, pharynx and larynx: No background activity due to the concentration of 57Co-BLM in normal structures of the head and neck has ever been observed, as opposed to what happens with 67Ga-citrate. Furthermore, the blood clearance of 57Co-BLM is much more rapid than that of 67Ga-citrate, so that an early study may be performed in a 6-24 hr. interval instead of 48-72 hr. with 67Ga-citrate. 57Co-BLM scintigraphy is an easy, non-invasive and sensible diagnostic technique in determining the extent of malignant tumors in ORL patients.


[Transurethral prostatic resection by cold punch technique. Indication and results (author's transl)]. In men of advancing age benign prostatic hypertrophy is the most frequent cause of obstructive urinary symptoms. Transurethral prostatic resection has been demonstrated as a suitable method to lastingly cure patients with this disease, even if they belong to a high age group or to a so-called high risk group. This report is based on 1490 patients who were operated upon by transurethral prostatic resection utilizing the cold punch technique. The average age was 70.9 years. 5.7% of the patients were 80 years or older. In 38.1% the operative risk was increased. The indication for performing a transurethral prostatic resection is discussed and technical differences between the cold punch technique and the better known electroresection are pointed out. Early and late results as well as complications of the procedure are reported.


Quantitation of differential sensitivity of human-tumor stem cells to anticancer drugs. With a direct in vitro tumor-colony assay developed to measure sensitity of human-tumor stem cells to anticancer drugs, we performed 32 retrospective or prospective clinical studies in nine patients with myeloma and nine with ovarian cancer treated with standard agents that were tested in vitro. The results were clearly correlated (P is less than 0.00001). Unique patterns of sensitivity and resistance to the six drugs tested were observed for individual patients. In eight cases of myeloma and three of obarian carcinoma in vitro sensitivity corresponded with in vivo sensitivity whereas in one case of myeloma it did not. In vitro resistance correlated with clinical resistance in all five comparisons in myeloma and all 15 in ovarian cancer. We conclude that this assay shows sufficient promise to warrant larger-scale testing to determine its efficacy for selection of new agents and individualized cancer chemotherapy regimens.


Lung cancer and air pollution.

Lung cancer and air pollution. The relationship between incidence of lung cancer and the volume of traffic as indicated by auto exhaust concentration was examined; the results, though suggestive, did not yield consistent evidence of the association between them. Traffic jams in Nagoya began 15 years ago, a period that may not be long enough to provide definitive data on the incidence of lung cancer. The high standardized mortality ratio (SMR) of lung cancer was observed in cities with a population of less than 1 million and guns (rural areas) along the coast, although those in the metropolitan areas with populations of more than 1 million were average. The SMR did not correlate with various socioeconomic conditions and industrial air pollution. Meteorologic or geologic conditions and ocean currents were not associated with SMR of lung cancer by city and gun. The population of a gun or of some cities was not large enough to be statistically significant, and the mortality rate of lung cancer was not always stable.


Development of acquired resistance precipitating antibody in rabbits experimentally infested with females of Haemaphysalis longicornis (Ixodoidea: Ixodidae). The resistance to the ixodid tick, Haemaphysalis longicornis (parthenogenetic Okayama strain), manifested as a reduction in engorged body weight, developed in rabbits subjected to a series of adult female infestations. A single infestation with females always produced resistance in hosts. This production appeared to depend little on the number of ticks per infestation. Unlike the previous papers, this study revealed that there was no reduction in the mean recovery rate of engorged females when ticks fed on a rabbit repeatedly infested with the ticks. A series of infestations were carried out comparatively to investigate the major biological characters of ticks, such as feeding, oviposition, and hatchability of eggs. As a result, there were no marked differences in these characters among the infestations. Especially, no differences were noticed in the concentration of ingested blood meal in detached females among the infestations. Precipitating antibodies were found in the sera of rabbits resistant to the tick-bite. They were subjected to fractionation by Sephadex G-200 chromatography and tested for sensitivity to 2-mercaptoethanol. As a result, they were proved to be of immunoglobulin of 7 S class.


Ethanol-induced alterations in histamine content and release in the rat hypothalamus. In the rat hypothalamus, histamine content and histidine decarboxylas: activity are enhanced significantly after acute administration (80--160 mg/100g body weight) of ethanol. The effects are less pronounced after chronic treatment (15% v/v in drinking water for 4 weeks). Histamine methyltransferase is unaffected in either case. In hypothalamic slices preloaded with 3H-histamine and superfused with amine free solution the basal and K+-induced efflux of 3H-histamine are inhibited by alcohol. The inhibition of histamine release along with the increased levels of histamine may play an important role in the central effects of alcohol.


Effects of microfilament-active drugs, phalloidin and the cytochalasins A and B, on exocytosis in mast cells evoked by 48/80 or A23187. Rat peritoneal mast cells were used as a model system to study the effect, on exocytosis, of three agents known to interact with microfilaments. Mast cell secretion was evaluated by fluorimetric assay of histamine and by ruthenium red staining, the latter method allowing a direct visualization and quantitation of exocytosis at the light microscopic level. Phalloidin, in concentrations up to 300 microgram/ml, was without effect on either spontaneous or 48/80-evoked secretion, even after cells were exposed to the drug for 28 h. The failure of even high doses of phalloidin to influence cellular morphology and exocytosis in the mast cell may reflect the absence of a specific membrane receptor. Cytochalasin B was likewise without effect on the response to 48/80 in normally respiring cells; but inhibited this response in the presence of Antimycin A. This inhibitory effect probably reflects the ability of cytochalasin B to block glucose transport. In normally respiring cells, neither phalloidin nor cytochalasin B affected the active expulsion of granules from exocytotic pits. Cytochalasin A, without concomitant treatment with Antimycin A, completely inhibited secretion in response to both 48/80 and A23187, and did so in low concentration. Whether this striking inhibitory effect results from an interaction with microfilaments is uncertain for the inhibition could be mimicked by nonpenetrating thiol-oxidizing agents and prevented by impermeant thiol-protecting agents suggesting that cytochalasin A may inhibit histamine release by thiol-oxidation at the cell surface. Possible surface sulfhydryls are important for membrane rearrangements accompanying exocytosis.


Studies on the release of histamine from isolated guinea pig mast cells stimulated by ionophore A23187 or by the anaphylactic reaction. The divalent cation ionophore A23187 was found to produce a dose-dependent release of histamine from isolated mesenteric mast cells of the guinea pig. The process showed a specific requirement for calcium ions and was blocked by inhibitors of glycolysis. The effect of cAMP, theophylline, sympathomimetic amines and DSCG on the histamine release induced by the ionophore or by the antigen-antibody reaction was compared. In both cases, the release was inhibited by Bu2cAMP and by theophylline but higher concentrations were required with the ionophore. Adrenaline, isoprenaline and DSCG were effective only in the anaphylactic system. These results are compared with those previously reported for human leucocytes and rat peritoneal mast cells in which the release produced by the ionophore was found not to be inhibited by cAMP and its analogues. On the basis of these findings, the possible role of cAMP in the modulation of histamine release is discussed.


[Study of the neurons of the supraspinal systems of the cat brain using the method of retrograde axonal transport of horseradish peroxidase]. Horseradish peroxidase (HRP) was injected into cervical, thoracic, lumbar and sacral segments of 18 cats. In all the cases HRP was transported retrogradely to the brain stem neurons in the medial reticular formation, vestibular complex and the red nucleus. The present findings demonstrate that, in addition to the above mentioned groups, there exist several other groups of neurons. Many labelled neurons are present in the locus coeruleus and the nucleus subcoeruleus, ipsilaterally. These neurons seem to be located in the same position as the monoaminergic (catecholamine-containing) neurons. Labelled HPR-positive neurons are present in the retroambiguous nucleus and in the upper pontine tegmentum adjoining the rubrospinal tract, mainly contralaterally, in the bulbar raphe, the mesencephalic central gray and the hypothalamus, mainly ipsilaterally. The occurrence of retrograde-labelled neurons in the locus coeruleus and the dorsal hypothalamus after HRP injections as far caudally as the lumbar segments, indicates that these cell groups give rise to descending fibres which pass almost the entire length of the spinal cord.


[Study of the pathways of the cat spinal cord using the method of experimental retrograde axon transport of horseradish peroxidase]. Funicular trajectories of descending brain stem pathways in the cat were identified by means of retrograde horseradish peroxidase (HPR) transport. In sixteen cats TH1 HRP injections preceded by a large C6-C7 lesion sparing the ventral or ventrolateral funiculi and by such a lesion sparing the dorsolateral funiculus were made. It was found that the descending fibres from the nucleus locus coeruleus and the nucleus subcoeruleus are distributed ipsilaterally through the ventrolateral funiculus. The fibres from the hypothalamus which descend throughout the spinal cord are located mainly in the lateral funiculus, but some of them also descend through the ventral and dorsolateral funiculi. A diagram summarizing the distribution of the descending fibres from the various brain stem cell groups over the different C6-C7 funiculi is presented.


Serum beta2-microglobulin in the assessment of renal function. This study was undertaken to compare the serum beta2-microglobulin (beta2-m) as a test of renal function with the plasm creatinine and the glomerular filtration rate as estimated by the 24 hour endogenous creatinine clearance and the single injection 51Cr EDTA clearance method. Of the 33 patients with a variety of renal diseases and the four healthy volunteers studied, an excellent correlation was found between the serum beta2-m concentration (measured by radioimmunoassay) and the plasma creatinine, the creatinine clearance and the 51Cr EDTA clearance. When a more simple and less expensive method becomes available for the measurement of serum beta2-m it could prove a useful test of renal function. The assay of beta2-m in the urine could prove valuable for assessing whether proteinuria is glomerular or tubular in origin.


Alpha-fetoprotein content of amniotic fluid in normal and abnormal pregnancies. Elevation above the normal range of alpha-fetoprotein (AFP) concentration in amniotic fluid occurs in the presence of certain fetal anomalies. The value of a new method for radioimmunoassay of APF in amniotic fluid was tested by an analysis of 486 samples taken by amniocentesis at various stages of pregnancy. The normal range of concentrations during pregnancy was established by 348 samples from healthy women with normal pregnancies. This was compared with the levels found in the presence of various fetal malformations--Rh-isoimmunization, maternal diabetes, chromosomal anomalies, and fetal death in utero. The findings and their implications are discussed.


Reverse transcription of tRNA.

Reverse transcription of tRNA. The 3' terminus of tRNA was enzymatically elongated by an oligo(A) tail. A fragment of DNA polymerase I (E. coli) was used in the presence of manganese to phase and synthesize a cleavable primer at the oligo(A)-tRNA template. When the threedimensional structure of oligo(A)-tRNA is being unfolded under conditions where the primer is still hybridized at the oligo(A) tail, the DNA polymerase I fragment transcribes oligo(A)-tRNA into DNA. Reverse transcription is slowed down and its fidelity suspended by the 1-methyladenine in oligo(A)-tRNAPhe(yeast). The reaction is stopped by the highly modified Y-base present in this template. Approximately full length transcripts can be obtained from oligo(A)-tRNA3Gly(E.coli). The transcription products were characterized by sequence analysis.


Species-dependent immunological differences between vertebrate brain tubulins. The antigenic similarities and differences between highly purified brain tubulins from lamb, mouse, and chick embryo have been examined using rabbit antisera prepared against each of these tubulins. These antisera are capable of binding 125I-labeled tubulin in homologous or heterologous combinations, demonstrating immunological similarity between the tubulins. However, there are quantitative differences in the maximum amount of binding observed. Differences between the tubulins were further resolved by radioimmunoassays, comparing the ability of each of the tubulins to inhibit the binding of each 125I-labeled tubulin to each antiserum. Competition curves generated for all possible combinations revealed quantitative immunological differences between the tubulins that imply different densities of shared antigenic determinants on all three tubulins and a unique determinant on the chick tubulin molecule.


[Attitude of mothers towards physical punishment as a counseling problem in small children with developmental disorders]. Using the questionnaire that has been specifically developed to obtain data on parental educational behavior, 294 mothers of 2-year-old children were studied and their attitudes towards corporal punishment correlated with characteristics and symptoms of children as well as with psychosocial factors. Low level of education and lack of domestic happiness proved to be essential conditions for acceptance of corporal punishment. Children with developmental disorders are especially endangered only because of their particular liability to disorders, but on account of the fact that they do not receive the same amount of clemency as do children who are liable to infections. Problems of maleducation should receive greater attention in the elimination of environmental dangers to healthy development of children as well as in counseling.


[Comparative study of the plasma levels of alpha-1 fetoprotein and carcinoembryonic antigen in chronic liver diseases and malignant neoplasias (author's transl)]. We have measured the plasma levels of alpha-1 fetoprotein (AFP) and carcinembryonic antigen (CEA) by RIA in 98 chronic liver diseases (20 chronic aggressive hepatitis and 75 cirrhosis), in 46 subjects with several varieties of malignant neoplasias and in 30 normal controls.  In cirrhosis levels higher than the media +/- 2 DS of controls were found in 25.3% for AFP (Max. value 250 ng/ml) and in 36.0% for CEA (Max. value 150 ng/ml). Only in 6 cases of cirrhosis we found high levels of AFP and CEA contemporaneously. High levels of AFP were found in 10/13 primary liver cancers and only in 1 patient with colonic carcinomata. High levels of CEA were found in 4/13 primary liver cancers (1 AFP positive too), 3/4 metastatic liver cancers, 7/17 colonic primary cancers, 3/6 bronchogenic carcinoma, and 3/6 other malignancies.


The immune responses to antigenic variants of Babesia bigemina in the bovine. Four Babesia bigemina stabilates were used to determine the immune response of cattle to acute and chronic blood- and tick-borne infections. Thirty-two intact calves were divided into 16 groups of two  and each calf was inoculated with infective B bigemina erythrocytic stabilates. Twenty-eight days later they were challanged with homologous and heterologous stabilates, and monitored for an additional 20 days. The hosts' apparently reduced response to homologous challenge but marked immune response to heterologous challenge indicated antigenic differences between the isolates and confirmed the conclusions reached by examination of the serological data.


[Structural characteristics of the blood group N determinant, tested with anti-N lectin from Vicia graminea]. Crude extracts of Vicia graminea seeds agglutinate human N erythrocytes as anti-N immunsera. The anti-N lectin is purified after precipitations with ammonium sulphate of crude extracts, DE52 Whatman chromatography and sephadex G150 gel filtration. Its homogeneity is demonstrated by physical and immunological methods. The structure determinant for the Vicia graminea anti-N activity was investigated: --with the major glycoprotein of N erythrocytes. --with glycoconjugates isolated from urine of normal human N-blood group as urinary glycoconjugates are probably related to the membrane glycoprotein catabolism. Purification and characterization of glycoconjugates are undertaken by gel filtration and non-exchange chromatography. This purification is checked by hemagglutination-inhibition test with V. graminea lectin. Biochemical characterization of active glycoconjugates gives way to the carbohydrate determinant recognized by anti-N antisera and Vicia graminea lectin.


[Study of alpha 1-antitrypsin and alpha 2-macroglobulin in workers exposed to byssinogenic dusts]. The level of IgG, IgA, IgM, alpha1-antitrypsin and alpha2-macroglobulin was determined by radial immunodiffusion in 27 workmen in the flax processing industry, exposed to the risk of byssinosis and 33 retired workmen with a diagnosis of byssinosis. The control lot included 26 blood donors. A significant increase in IgM, alpha1-antitrypsin and alpha2-macroglobulin levels was noted in the active workmen; the increase was not significant in the retired workmen. The high IgM levels was brought about by the immunological processes taking place under the influence of the antigenic components of the dust inhaled; the increase in antitrypsin and alpha2-macroglobulin was considered as an acute protein reaction to the presence of inflammatory proteases.


[Radiotherapy of brain metastases (author's transl)]. Brain metastases of malignant extracranial tumors are usually multiple. Very often they require an effective palliative treatment. Radiotherapy of the entire cranium produces improvement of the neurological and psychic symptoms in 80-90% of the patients. The survival time cannot be extended by this treatment. There is no optimum radiation scheme. Indications for the surgical removal of brain metastases are tabulated.


Mycobacterium leprae specific antibodies detected by radioimmunoassay. A radioimmunoassay was developed for demonstration of antibodies against M. leprae specific antigenic determinants. The specificity of the assay was tested with hyperimmune rabbit antisera against other mycobacteria and shown to be very high. The titre of M. leprae specific antibodies in a  lepromatous serum pool was 10(5). Sixty-one of sixty-two lepromatous sera, all of twelve borderline sera and twenty of forty-eight tuberculoid sera were positive in the assay, whereas all of thirty-eight control sera from tuberculin positive individuals from a leprosy non-endemic area were negative. Aplication as a diagnostic test for subclinical infection with M. leprae is discussed. The principle of the test appears promising for serological distinction between pulmonary infection with M. tuberculosis and other mycobacteria.


Reactivity of a rabbit antiserum against highly purified HLA-DR antigens. A rabbit antiserum has been raised against highly purified, detergent-solubilized HLA-DR antigens. Externally or internally labelled surface glycoproteins from B-lymphocytes, epidermis, macrophages, and B-lymphoma cell lines reacted with the antiserum which precipitated polypeptide chains with the molecular weights 28,000 and 34,000. Such polypeptide chains were not observed when the antiserum was reacted with T-lymphocytes, T-cell lymphoma lines, kidney, brain, thymus and spermatozoa. Fab-fragments of the antiserum completely abolished the cytotoxic action of HLA-DR allantisera but had no effect on the cytotoxicity mediated by HLA-A,B and C loci antisera. Moreover, the rabbit antiserum reacted with the same molecules as the HLA-DR alloantisera. Fab-fragments of the rabbit antiserum completely abolished the MLR response and from the kinetics of the inhibition it is concluded that the Fab-fragments may interfere primarily with the initial recognition phase of the MLR.


Natural and immune antibodies to rabbit erythrocyte antigens. Natural agglutinins to rabbit erythrocytes were found in all human sera studied. In the newborn, the antibodies were of IgG class; in the 6-month-old infants they were mainly of IgM class. Older children and adults had both IgG and IgM antibodies. Agglutinins to rabbit erythrocytes were also found in serum from fourteen of fifteen other species studied. The trichloroacetic acid extract from rabbit erythrocyte stromata (TCA-preparation) contains at least three different antigenic determinants: one which we hitherto to have found only on rabbit erythrocytes, one which is closely related to human blood group B antigen, and one which is closely related to the I antigen. The TCA-preparation did not elicit delayed hypersensitivity skin reactions in humans in spite of high titred agglutinins in serum, but did so in immunized guinea-pigs.


Reactions and crossreactions of a rabbit anti-H2 antigen serum. A rabbit antiserum raised against highly purified, papain-solubilized H-2d antigens contained two sets of non-crossreacting antibodies directed against each one of the two H-2 antigen subunits. The antiserum recognized only 12,000 and 47,000 dalton polypeptide chains when splenocyte membrane glycoproteins were analysed. Among the molecules precipitated with the rabbit antiserum all H-2K and D antigens were present. In addition to regular H-2K and D antigens minor amounts of material with the typical H-2 antigen subnit structure, but lacking alloantigenic determinants, were precipitated by the antiserum. These 'non-H-2 antigens' were produced in relatively greater amounts by T-cells than by B-cells. Both sets of antibodies in the rabbit antiserum reacted with the TL antigens demonstrating that there is an immunological crossreactivity between the classical alloantigenic H-2 antigen chain and the alloantigenic TL antigen chain. The F9 cell line, believed to represent cells at the morula stage, display H-2 antigen-like structures as revealed by the rabbit antiserum.


Specificity of Fc-receptors on lymphocytes and monocytes for guinea-pig IgG1 and IgG2: phagocytosis of erythrocytes. The capacity of guinea-pig IgG1 and IgG2 antibodies to induce lymphocyte (K-cell) mediated lysis or monocyte/macrophage mediated phagocytosis of erythrocytes was studied with both human and guinea-pig effector cells. For both species, induction of K-cell mediated lysis was restricted to IgG2 whereas both IgG1 and IgG2 could induce monocyte/macrophage mediated phagocytosis. In competitive inhibition experiments, only complexed IgG2 inhibited lysis mediated by K-cells. The results suggest that the fc-receptors on K-cells only recognize IgG2. In contrast, complexes of both subclasses inhibited phagocytosis by human monocytes, regardless of the subclass of the inducing antibodies. Inhibition of guinea-pig macrophage mediated phagocytosis by IgG2 complexes was also independent of the inducing antibody. Hence, Fc-receptors common for IgG1 and IgG2 seem to be involved in themonocyte/macrophage mediated effector reaction. Free IgG1 was significantly less ingibitory than free IgG2 for human monocytes and hardly at all for guinea-pig macrophages. However, free IgG2, which was cytophilic for these cells, was more aggregated than IgG1. Thus, both molecular structure and state of aggregation determine interaction of IgG with cellular Fc-receptors.


[Atypical mycobacterial infection due to Mycobacterium fortuitum]. The case is presented of a 48-year-old woman who, in association with repeated septic temperatures, developed abscesses in the region of the right shoulder and in the right ankly. Histological examination from excisates revealed caseous tuberculoid granulomas. Mycobacterium fortuitum was isolated from the pus of both abscesses. Although the Mycobacterium fortuitum was resistant to nine commonly used tuberculostatics, it was found to be sensitive to ethionamide and capreomycine. The use of these two drugs in combination with local measures proved successful.


Primate HLA antibodies are specifically mitogenic for human lymphocytes and act synergistically with beta2m antibodies. A monkey antiserum against HLA-A28 was raised by immunization with papain-solubilized antigens. The titre of this serum was 1/370 for beta2-microglobulin (beta2m) 1/750 for A28 and 1/200 for the cross-reacting HLA-A2 determinant. This serum was highly mitogenic for human blood lymphocytes. Mitogenicity was reduced or abolished after absorption of the serum on a beta2m-spharose column. Column-eluted anti-beta2m antibodies were not mitogenic. However, mitogenicity was restored by reconstitution with unabsorbed and absorbed antibodies. Mitogenicity was target cell specific. Tuhs, cells from all individuals were activated by the unabsorbed serum. The absorbed anti-A28 serum was mitogenic only for target cells carrying A28 and/or the cross-reacting determinant A2, but not for cells lacking either of these antigens. A definite gene-dose effect was recorded, since target cells homozygous for A2 responded better to polyclonal activation by the primate serum than cells which were heterozygous.


Combination chemotherapy including bleomycin in the treatment of advanced Hodgkin's disease. Fifty-six patients with advanced Hodgkin's disease were treated with a combination of nitrogen mustard, a vinca alkaloid (vincristine or vinblastine), procarbazine, prednisone and bleomycin, given in repeated cycles. Complete remission was achieved in 33 out of 53 evaluable patients (62,5%). The complete remission rate in patients who had received prior radiation therapy alone (65%) was similar to that in previously untreated patients (73%). Patients who had previously received combination chemotherapy, either alone or together with radiation therapy, responded less well to this regimen of therapy, with a complete remission rate of less than 40%. The complete remission rate was not influenced by the histological subtype of the Hodgkin's disease. Twenty-three of the 33 responders (70%) remain in continuous complete remission. The median for this group has not been reached but will be in excess of 24 months. Major bleomycin toxicity was not encountered in this study. Lung function was monitored throughout but no consistent changes were encountered. The degree of haematological toxicity caused by treatment was no greater than would have been expected without bloemycin. Although the results obtained with the 5-drug combination were satisfactory, the follow-up to date does not suggest that the addition of bleomycin to the convention 4-drug regimen has significantly affected the outcome.


In vitro effects of bleomycin on a carcinoma of the oesophagus cell line. A dose of 10 microgram/ml bleomycin inhibited the growth of oesophageal carcinoma cells and non-squamous cells in vitro. Drug concentration, density of cells and the time of exposure to the drug were important variables. The oesophagus cancer cells increased in volume by 2,5 +/- 0,2% per hour until the onset of lysis at 96 hours. The effects of the drug were irreversible even when the exposure time was only 24 hours. A certain proportion of the cell population was resistant to bleomycin and these cells remained resistant when the drug was removed for 48 hours and then replaced. No drug inactivation or uptake could be detected with the use of microbiological assay after 4 days of incubation with 3 cell types. There is poor correlation between in vitro and in vivo results.


Cryosurgery for recurrent carcinoma of the vulva: a case report. Cryosurgery in the palliative treatment of recurrent carcinoma of the vulva is described. A plea is made for the greater use of cryosurgery for this condition in peripheral hospitals.


Carcinoma of the proximal bile ducts.

Carcinoma of the proximal bile ducts. The records of 31 patients with carcinoma of the proximal bile ducts were reviewed and the operative procedures, results, causes of deaths and autopsy findings were analyzed and correlated. Ten poor risk patients were treated by external drainage and died of jaundice or abscesses of the liver within six months. However, one patient survived 13 months after effective bilateral drainage. Twelve patients underwent intubation through the tumor into the hepatic ducts with or without postoperative irradiation. Four patients with irradiation survived 42, 15, 15 and ten months, while eight patients without irradiation died within six months. Autopsy findings of two patients who survived 15 months revealed metastases to the various organs. Four patients underwent resection. A patient who underwent resection of the common hepatic duct and hepaticoduodenostomy died of ascending cholangitis nine months postoperatively, while a patient treated by resection of the common hepatic duct with hepaticojejunostomy died of a recurrence 25 months postoperatively. Two patients underwent left hepatic lobectomy and resection of the right hepatic duct followed by hepatojejunostomy. One patient survived 25 months and died of a reccurrence, while the other patient died of abscesses of the liver ten months postoperatively.


[Evaluation of the antigenicity of heart valve leaflets using inbred rat strain combinations (author's transl)]. Experiments with large, non-inbred animals yield no reliable evidence in the antigenicity of heart valves. With inbred strains of rats, however, it is possible to obtain evidence on the immunological reactions of heart valve leaflet transplants. Our experiments were undertaken on the inbred rat strains (CDR, LEW, CAP and BD5, using combinations as follows: syngeneic strain combination (CDF leads to CDF), weakly allogenic (RtH-1-identical) strain cimbination (LEW leads to CDF), strongly allogeneic (RtH-1-incompatible) strain combination (CAP leads to CDF). Strain BD5 was used for the control skin grafts. Either one or two heart valve leaflets were heterotopically intra-aortally transplanted. Sensitization was verified humorally by transplantation antibody titers and cellularly by subsequent donorspecific skin transplants. The following results were achieved: Allogeneic heart valve leaflets are antigenic. Intravascular grafting of one heart valve leaflet induces the same degree of sensitization as the grafting of two leaflets. In the RtH-1-identical system, sensitization is revealed only by subsequent skin grafting, whereas in the RtH-1-incompatible system, sensitization is humorally demonstrated as well. This indicates that in heart valve leaflet transplantation cellmediated reactivity is a more sensitive indicator than the humoral one. The greater the immunological difference is, the clearer the sensitization will be. In the strongly allogeneic system, the sensitization is even demonstrated humorally; skin grafts are rejected as "white grafts". Improved long-term results may be expected in allogeneic vital heart valve transplants if consideration is given to the HLA compatibility between donor and recipient; the appearance of delayed insufficiency could be greatly lessened or even deferred.


[The carcinoembryonic antigen (CEA) in bronchial carcinoma before and after operation (author's transl)]. In 53 p.c. of 175 patients with bronchial carcinoma the carcinoembryonic antigen (CEA) was elevated at the time of diagnosis. In patients with small well bordered tumors (T 1/2) 31 p.c. proved pathological CEA-values in comparison to 80 p.c. in patients with heamatogenic metastases. After radical tumor resection (36 patients) elevated CEA-levels returned to normal ranges within 5 weeks. No decrease could be observed after palliative operations (16 patients). If there existed haematogenic metastases normal CEA-values increased postoperative. Such an increase occured up to ten weeks before metastases could be found by other methods. In cases of bronchial carcinoma CEA-measurements are usefull to evaluate the effect of operation and in the follow up time. It should be carried out on principle in those patients which can be considered for a surgical therapy.


Can anti HLA-A and -B antibodies inhibit the MLC test? Eleven lymphocytotoxic pregnancy sera were tested for inhibition in the MLC test. Responder inhibition and stimulator inhibition were analyzed separately by using cells from the serum producer as stimulator and responder respectively. Only three sera showed inhibitionof responder function, whereas all sera showed inhibition of stimulator function. The specificity of the latter inhibition was at least in part attributable to antibodies directed to specificities other than B-cell specificities (presumed to be coded for in the HLA-D region). This was deduced from the fact that platelet eluates devoid of anti B-cell antibodies effectively inhibited in MLC.


Tissue typing of cells in culture. III. HLA antigens of established human cell lines. Attempts at typing by the mixed hemadsorption technique. Thirty established cell lines from solid human tumors were typed by the mixed hemadsorption technique with respect to the HLA-A and HLA-B and partly also the HLA-C series. All cultures exhibited unique antigenic patterns. The discriminatory potential was further increased very much taking into consideration one as yet undefined antigen series tentatively named Ek-1 to Ek-11. Sixteen cell lines not designated as HeLa cells but on various non-immunological indications suspected to be HeLa cell contaminants, all gave, with our present test, the same antigenic composition as HeLa cells or clones thereof. The mixed hemadsorption reaction is a highly sensitive and convenient method for immunological typing of cells in monolayer cultures. Some important implications of this are discussed.


Tissue typing of cells in culture. IV. Cell surface antigens of tumor cell lines, not obviously belonging to the HLA-system. Studies on the HLA pattern of several human tumor cell lines by the mixed hemadsorption test and also studies on the discriminative patterns formed by a collection of sera on a number of cell lines and diploid cells have been reported elsewhere. It was noted during these studies that some sera reacted in a fashion indicating that they did not represent any of the HLA-A or -B series and probably not the HLA-C series either. The corresponding antigenic determinants were tentatively designated Ek-1 to Ek-11. The pattern of these antigens among the cell lines is given in a table and it seems apparent that the Ek-series considerably increases the cell identification potential of the typing results. So far, five of the sera determining the Ek-antigens have failed to be blocked by anti-beta-2-microglobulin, indicating that the antigens do not belong to the HLA-A, B or C series. Preparatory work for HLA-D typing is under way.


Genetic control of B-cell alloantigens: evidence for gene(s) linked to the HLA-A locus. Families with known HLA recombinant individuals were typed for B-lymphocyte alloantigens. The B-cell alloantigens were found to be inherited with the intact HLA haplotypes. However, the results of the typing of the recombinant individuals indicated that specific antigens are associated with the HLA-A locus and/or with the HLA-B locus. These studies indicate that more than one gene initiates the expression of these antigens and that some of these genes may map between the HLA-A and HLA-B loci.


Subdivisions of the HLA-B5 and Bw35 complex. Population studies in 579 individuals, previously phenotyped to be B5 or Bw35, were carried out with 23 HLA antisera defining the B5-Bw35 complex. The inheritance of five subdivisions in this complex, B5.1, B5.2, B5.y, Bw35 and BHR were tested in 23 families. Differing frequencies of these specificities were observed in American Indians, Blacks, Caucasians, Chinese, Filipinos, Japanese and Mexican Americans.


Effect of lindane on pregnancy in the rabbit and rat. There was no evidence of any teratogenic effect of lindane when administered during pregnancy at levels equivalent to 5, and 15 mg/kg body weight to New Zealand White rabbits from days 6 to 18 inclusive, or to CFY rats from days 6 to 16 inclusive. These findings are consistent with the negative teratogenicity results in mice mutagenicity studies and 3-generation rat reproduction studies already reported.


Effects of feeding lindane to dogs for periods of up to 2 years. Lindane was administered to male and female Beagle dogs at dietary levels of 25, 50 and 100 ppm for 104 weeks, and of 200 ppm for 32 weeks. One death at 25 ppm and one at 200 ppm were not considered to be related to the test compound. At 100 and 200 ppm, SAP levels were raised and the livers were dark, friable and slightly enlarged but without any detected histopathological change. HVSA changes, possibly indicative of non-specific neuronal irritation, were recorded in the EEG tracings at 200 but not at 100 ppm. There were no other indications of an adverse effect of lindane. The negative findings at 50 ppm are consistent with a 'no-effect level' for this species of 1.25 mg/kg body weight, comparable with for the rat, and with proposed human ADI of 0.0125 mg/kg body weight.


[Palliative radiotherapy with Strontium-89 in case of extended formation of skeleton metastases (author's transl)]. In order to allay pains or make them cease, fifteen patients with extended tumors and generalized formation of skeleton metastases were submitted in 1976 to an internal palliative radiotherapy. They received between 0.8 and 2.7 mCi of Sr-89, five patients were treated again after four to five months because the pains had reappeared. The results were relatively good. Two patients showed a prompt effect and were completely free of pains within 48 hours, three patients did not present any demonstrable effect. The analgetic effect remained from four days to four months. Due to the utilization of the pure beta emitter Sr-89, the radiation doses measured in the patients after the application are relatively small: after the application they amount at most to 0.5 mR/h in a distance of 1 m.


[Change in the brain neuron structure of man and other mammals in edema and swelling of the brain substance]. A correlation was made between literature and obtained light microscopy data relative to the problem concerning the central neuron involvement at edema development and brain tissue swelling at different etiological backgrounds. A polymorphism of neuronic variations was demonstrated determined by a variety of causes including specificity of individual reactivity of central nervous system. Attention is drawn both to the non-identity of the notions: "hydropic variation (edema) of a neuron" and the "brain edema", and to a non-characteristic nature of "hard variation" of nerve cells for histological picture of edema-swelling brain tissue at neurooncologic affection, and to the absence of a strict proportionality between the degree of cerebral edema-swelling and variation intensity of the neuron structure.


[Method of differential staining of sister chromatids for the study of the effects of gamma rays on the frequency of sister chromatid exchange in human lymphocytes]. Human lymphocytes were incubated during two cycles of replication in the presence of 5-bromodeoxyuridine, fixed after a 96 hours cultivation, stained with fluorescenct compound "Hoechst 33258", illuminated with sunlight and repeatedly stained with azureosine. After such a treatment, the two chromatids of metaphase chromosomes are stained with different intensity revealing numerous sister chromatid exchanges (SCE) which could be exactly recorded. In spite of the use if tge standard technique, the frequency of SCE was different in two donors. Irradiation after a 47 hours incubation (mainly G2 stage of the first cycle) increased the frequency of SCE, whereas the irradiation 2 hours before fixation (G2 stage of the second cycle) decreased it. The change of the frequence of SCE produced by irradiation was not proportional to the chromosome length.


The diagnostic value of serum copper levels and other hematochemical parameters in malignancies. An increase in the serum copper (Cu++) level has been described as a sensitive index of disease activity in several hematologic and nonhematologic malignancies. In order to explore the diagnostic value of Cu++ compared to other hematochemical parameters frequently abnormal in malignancies, Cu++, serum alpha2 globulin (alpha2), plasmatic fibrinogen (Fibr), the erythrocyte sedimentation rate (ESR), and serum iron (Fe++) have been detected and evaluated in 267 patients affected with the following diseases: Hodgkin's lymphoma (HL), non-Hodgkin's Lymphomas (NHL), Acute Leukemias (AL), Chronic Myeloid Leukemia (CML), Chronic Lymphocytic Leukemia (CLL), Myeloma (MM), and Breast Cancer (BC). The best correlation between Cu++ increase and disease activity has been found in HL, NHL, AL, and BC. In these diseases, when the considered parameters were compared, Cu++ and ESR showed a similar pattern, i.e., a high frequency of abnormalities in active disease. It is concluded that Cu++ represents a good complement to some other aspecific parameters in evaluating the activity and diffusion of neoplasias and the therapeutic results, particularly in HL, NHL, AL and BC.


[Direct vision cold knife internal urethrotomy (author's transl)]. Direct vision cold knife internal urethrotomy avoids injury to neighboring structures with greater certainty than blind urethrotomy and is possible with all urethral strictures regardless of type or origin. The surgery is also easily performed, usually with local anesthesia, and on an ambulatory basis. The recurrence rate of 12% is relatively low and reoperation is easily performed. An important factor is the postoperative therapy, which requires good patient cooperation.


[Comparative evaluation of the methods of treatment of acute thrombosis of the main veins]. The experience with antithrombotic conservative treatment of 102 cases of acute thrombosis in the inferior vena cava system and in the deep veins of the lower extremities is generalized here. The suggested method permits to do away with thrombotic condition of hemostasis at a minimal risk of the occurrence of hemorrhagic complications.


[Alpha-fetoprotein serum level in healthy persons]. Seventy five clinically healthy subjects, aged 12 to 80 (38 males and 37 females) were tested for serum level of alfa phetoprotein in Bulgarians through a radioimmunologic method. The mean values established were 5,16 ng/ml, the upper limit admitted to be up to 12 mg/ml, and positively elevated--values over 15 ng/ml.


[Characteristics of the proteinuria in diabetic nephropathy]. Considerable deviations, qualitative and quantitative, in patients with nephropathy were found with the examination 38 patients with various stages of diabetic nephropathy and 14 other diabetic patients as well as 37 healthy subjects. The urine of those patients is characterized by high content of albumin, transferrin and immunoglobulins G, A and M and to lesser degree--of alpha 2-macroglobulin. The selectivity of proteinuria is most frequently decreased, especially in the advanced stages of diabetic nephropathy. Tubular components (light chains, alpha 2- and beta-microglobulins) were also found in the urine of the same patients.


[Misinterpretation of alpha-fetoprotein (AFP) values in amniotic fluid due to fetal hemorrhage (author's transl)]. The AFP concentration in the amniotic fluid is elevated after contamination of the sample with fetal blood during a traumatic amniocentesis. Though the calculation of AFP due to fetal hemorrhage is possible by counting the fetal red cells there may be execssive errors resulting from the variability of fetal red cell count, amniotic volume, fetal serum AFP concentration, AFP concentration in the amniotic fluid changing with fetal age. Therefore it is impossible to interpretate elevated AFP values from a sample stained with fetal blood. A repeated amniocentesis is unavoidable. The correct time to do a second punction is still a matter of question.


[Methods for the detection of drug allergies]. The following in vitro methods are predominantly discussed: Specific IgE determination (RAST). The test can be used to detect allergies of the immediate type such as anaphylactic shock and urticaria. Antibodies can be detected to a limited number of drugs such as penicillin, ACTH, TSH, insulin, asparaginase and proteins of animal sources. Degranulation of basophil leucocytes and histaminliberation have been used for many years. The practical value of the test has been limited but improved methods for analysis have given the tests hopes for a come-back. Cellular tests like lymphocyteproliferation and macrophage inhibition test (MIF) do not yet give such information which make them helpful as practical tests to detect drug allergy.


[The manual extrathoracal stimulation of the heart. Technique and effect of the precordial thump (author's transl)]. The findings of the manual extrathoracal stimulation of the heart (precordial thump) among 50 persons, healthy individuals and patients with pacemakers, are reported. By all persons it was possible either to cause "extrasystoles" through single blows or to maintain a continuous heart action through a rhythmic stimulation up to 6 minutes ("Temporary stimulation"). Through a manual overstimulation the basic rhythm could be blocked out. -To induce a depolarisation through a thump the locally induced pressure or tension on the heart muscle is of primary importance. For this to occur, the precordial chest thump must develop a rise in pressure of at least 15 to 20 mm Hg in the right ventricle. The location at which the precordial thump can best be effective is on the left border of the sternum in the lower third. That is the region where the heart (right ventricle) is nearest to the chest wall. -Subjective or objective side effects were not observed during our investigations and--in particular--there were no ectopic rhythm or conduction disturbance. -The precordial thump is of importance not only as "initial blow" at the beginning of cardiac resuscitation but also in form of the temporary stimulation in various causes of asystole. It was demonstrated that the manual stimulation of the heart has the same effect as the electrical stimulation and can be used by certain patients by themselves.


[The Sudeck-Leriche syndrome as a disturbance in distant regions of the body, clinical picture, and histology (author's transl)]. On the whole, every Sudeck-Leriche syndrome represents a serious complication. The causal noxae are various in nature. In a large case material during a period of observation extending over 26 years a Sudeck-Leriche syndrome was observed as a disturbance in distant regions of the body only in rare cases, for example after herpes zoster, apoplexy, and confusion of the cervical part of the medulla, with cervical and lumbal root irritations, etc. Histological findings in the case of Sudeck-Leriche syndrome are very rarely presented in literature. Histological investigations by the author carried out on muscle tissue in the case of Sudeck-Leriche syndrome yielded remarkable findings with a transition from functional to morphologically irreversible alterations. These alterations were present both in vessels and muscle fibers.


[Time-dependant changes in the protein spectrum of blood from living and dead persons by means of electrophoresis in cellulose acetate (author's transl)]. Protein electrophoresis on cellulose acetate shows that with increasing hemolysis of ante- and postmortem blood an extragradient in the alpha2-globulin field is created, which influences the relative ratio in the electropherogram. Strong hemolysis causes a fusion of the alpha2- and beta-globulin chains. In order to make a diagnostic interpretation of postmortem blood by means of electrophoresis, it is therefore essential to take into account the degree of hemolysis. Changes in the electrophoretic pattern due to hemolysis correlate best with the period of storage. With regard to timing for forensic purposes, the value is, however, limited.


[Incidence of a persisting prostatic duct following transvesical adenomectomy]. 32 patients underwent an after-examination one to five years after transvesical adenomectomy. In 25 cases thare was a persisting lodge of the prostate. 6 patients with persisting lodge had urethrographically a narrowing in the region of the posterior urethra. There were no pathological values of the residual urine and pathological findings of the urine. In 7 cases a complete retrogression of the lodge to the size of the urethra could be proved radiologically. The healing after adenomectomy without retrogression of the lodge of the prostate is regarded as a normal variant of healing.


[Early catheter removal in water-tight bladder closure following transversical prostatic adenometomy]. It is reported on 124 patients in whom after a transvesical adenomectomy an early removal of the catheter was aspired to. A watertight closure of the urinary bladder is one of the most important prerequisites. The 5th day after operation seems to be best suited for the removal of the catheter. A temporary fistulisation lasting 2 days occurred only in one case. Secondary infection of the wound as well as epididymitis could not be observed. 96% of the patients could be discharged with sterile urine. Advantages of the early removal of the catheter: 1. Shortened hospitalisation and shortened convalesence. 2. Reduced danger of a secondary infection of the urinary tract 3. Early symptom-free subjective condition of the patient.


[Use of Raveron in adenomectomies].

[Use of Raveron in adenomectomies]. The loss of blood during adenectomies was quantitatively measured in 25 prostatic patients with or without Raveron-premediaction. The result in the 11 patients pretreated with Raveron was in comparison to the 14 untreated patients a reduction to one half of the blood lost by gram of the tumour tissue removed. Furthermore we observed a better demarcation of the tumour-tissue and operability together with a postoperative recovery without complications in patients treated with Raveron.


New strains of Clostridium botulinum subtype Af. Two new strains of Clostridium botulinum subtype Af have been isolated from soil samples of Mendoza Province, Argentina. Some serological and other biological properties of these new isolates have been studied in comparison with the prototype 84-SC2 strain. No differences in morphology and biochemical activities were found among these three so far known strains of this subtype. Neither serologic differences have been recorded, suggesting that the bispecificity and the type A to type F serologic ratio (A:F) is a stable genetic trait of subtype Af. The three strains were found in well separated areas. None of the type A strains isolated either from soil samples or from human botulism outbreaks in Mendoza have shown such a high degree of toxigenicity as that shown by Af strains. All these facts suggest that this peculiar type is not the product of a recent genetic relationship between types A and F. Rather, it represents a stable type in nature.


[Staining of sulfate-reducing bacteria with hexacyanoferrat-compounds (cultural and cytochemical evidence of Fe) (author's transl)]. Hexacyanoferrat-compounds are suitable 1. to indicate the valence of Fe-ions in cultures of desulfuricants (Desulfovibrio spec., Desulfotomaculum) in fluid and solid medium before and after inoculation; 2. stain directly the sulfate-reducing bacteria in presence of Fe-ions and give a colour-reaction of those parts of the cell containing Fe-compounds, e.g. FeS. Therefore they act as a cytochemical indicator system. The chemical base of the reactions are as follows: (1) 4HS + SO42 leads to H2S + 2H2O + OH- H2S leads to H+ + HS- leads to 2H+ + S2- (in the bacteria) (2) FeIII-salt + S2-leads to Fe2S3 leads to 2FeIIS + S 2FeIIS + FeIII(CN6) leads to FeIIIFeII(CN)6 (blue complex-compound).


[Protection against infection with Bordetella pertussis by an oligopeptide from Bordetella pertussis (author's transl)]. We have isolated from Bordetella pertussis an oligopeptide with characteristic amino acid composition. This peptide was applied to mice in standardized tests for pertussis immunization. In three tests with three independent isolates of peptide, a significant and dose dependent protection was observed. One microgram of peptide per mouse produces the same protective effect as 0.1 IU of pertussis vaccine. It is important to note that similar peptides can be isolated from other bacteria and other DNA containing cellular organisms which have specific amino acid compositions and which are antigens specific for the organism from which they were isolated. The antigens are very potent, e.g., one ng of Mycobacterium tuberculosis peptide is equivalent to one unit of tuberculin. It is conceivable that immunizing effects such as those observed for pertussis are common to the peptides of this group. Since all such peptides are isolated from a group of low molecular weight ribonucleoproteins, as first reported by WILHELM, we propose the term nucleopeptides for this group. Oligopeptides of the nucleopeptide group are now available for sequence analysis. We expect that synthetic peptides of this group will become available in time for diagnosis, prophylaxis and therapy of a number of diseases.


[Therapy of cancer of the cardia].

[Therapy of cancer of the cardia]. The paper contains analysis on 120 patients with malign neoplasms of cardia and lower third of the esophagus, who have been medicaly treated at the II surgical clinic of the Medical Faculty in Belgrade. Diagnose methods are presented and pointed out importance of early diagnosis and indications for operative (surgical) treatment. Criterious of radical and palliative surgical intervention are stated. Radicaly treated patients were 64 (53,4%). Palliatively treated and not operable patients were 56 (46,6%). There were decided that only by resection of gaster and seized esophagus i.e. by remoting of sick tissue radical treatment can be reached. There were stated postoperative complications and early results of palliative treated patients (mortality 19,8%) and radicaly operated patients (postoperative--hospitality mort. 23,4%).


Immunofluorescence studies on localization of actin-like protein in the mouse brain. Localization of actin-like protein in the mouse brain was studied by the immunofluorescence method using FITC-labeled antiactin antibody. Antibody against actin was prepared according to Lazarides (1974). The problem of poor antigenicity and the presence of contaminants in the antigen preparation was circumvented by way of denaturation of the protein with sodium dodecyl sulfate (SDS) and subsequent purification of the antigen by SDS polyacrylamide gel electrophoresis (Lazarides, 1974). Intense specific fluorescence against actin was noted in the cytoplasma of the epithelial cells of the choroid plexus, of the ependymal cells of the ventricles, and a little less one in arachnoidea and in leptomeninges, as well as in the muscle layers, endothelial linings, and adventitia of the arteries. Diffuse but weak fluorescence was noted also in the neuropil of the grey matter of the brain. Among the latter, fluorescence in the granular layer of Ammon's horn and of the cerebellum appeared clearer than the diffuse one in the rest of the grey matter. Functional significance of the presence of actin-like protein in the above tissues was discussed.


Clinical, hormonal and ultrastructure studies of a virilizing hepatoblastoma. Virilizing hepatoblastoma was found to be the cause of precocious puberty in a 3 1/4-year-old boy. Both human chorionic gonadotropins and alphafetoprotein in increased amounts were detected in serum and tumor tissue. These substances disappeared from the blood after removal of the tumor. Ultrastructure studies revealed the presence of dense, membrane bound, secretory granules responsible for the hormone production.