Cyclotron-produced Zn-62: its possible use in prostate and pancreas scanning as a Zn-62 amino acid chelate. Zinc-62 is a positron emitter that localizes in pancreas, prostate, and liver. Cyclotron-produced Zn-62 was separated by column chromatography and evaluated in vivo as the chelate of five amino acids and also as 62ZnCl2. Tissue-distribution studies were done in normal animals from 0.7-23 hr after intravenous administration. Pancreas-to-liver ratios (per gram) of about 1.0 were found at 1.5 hr in studies on rats, dogs, and monkeys. Pancreas was as difficult to separate from liver in Zn-62 (amino acid) images as in [75Se] selenomethionine images. Some studies were done with Zn-65 to determine the effects of carrier zinc and molar ratios of ligand. The highest ratio of pancreas to liver in these studies was 1.44. This uptake ratio decreases with increasing amounts of histidine, but the ratio is increased by adding carrier zinc because there results a decrease in liver uptake and no change in the pancreas uptake. There is sufficient specificity of pancreas and prostate uptake to make feasible emission computed tomography with Zn-62.


Preseasonal IgE ragweed antibody level as a predictor of response to therapy of ragweed hay fever with intranasal cromolyn sodium solution. Intranasal administration of a 4% solution of cromolyn sodium for the treatment of ragweed hay fever was tested in an 8-week double-blind matched-pair study involving 66 patients. Patients on active drug received 5.2 mg into each nostril 6 times daily; control patients received a placebo spray. The treated group showed a significant reduction in mouth breathing (p less than 0.001), stuffy nose (p less than 0.002), runny nose (p less than 0.003), and postnasal drip (p less than 0.035). Patients receiving the active drug also reported fewer sneezing episodes (p less than 0.003) and nose blowing episodes (p less than 0.015). One patient using cromolyn solution developed nasal ulceration, tongue swelling, coughing, and wheezing. Other side effects were minimal and occurred with equal frequency in both groups. In the treated group relief of symptoms was most marked in patients with high preseasonal levels of IgE ragweed antibody. Intranasal 4% cromolyn solution appears to be an effective drug for the treatment of ragweed hay fever; measurement of the preseasonal level of IgE ragweed antibody is a useful screening test to identify patients most likely to achieve a maximal beneficial response to treatment.


Airway mucosal permeability in the Ascaris suum-sensitive rhesus monkey. The permeability of the airways to technetium 99m-labeled albumin was measured in Ascaris suum-sensitive rhesus monkeys. All 8 animals were skin-sensitive to Ascaris suum (AA) antigen, 4 being respiratory responders (R) and 4 nonresponders (NR) to aerosolized antigen. In the absence of antigen challenge there were no differences in the accumulation in the blood of radioactive material from the tracheobranchial tree between the R and NR animals. After a five-minute challenge with aerosolized AA, there was a threefold increase in the rate of accumulation of radioactive material in the blood over control for the R group with no effect noted in the NR group. Gel filtration data indicated that the radioactivity in the blood most likely represented low molecular weight albumin fragments, resulting from spontaneous degradation of Tc-albumin, that crossed the mucosa and partially bound to circulating albumin. It is concluded that hyperpermeability of the airway mucosa probably is not a factor that contributes to the selective responsiveness of the R group to aerosolized antigen, and that airway permeability is increased consequent to the allergic reaction mediating acute bronchoconstriction.


Utilization of hospital in-patient services by the elderly. A survey was made of the patterns of hospital admission for patients aged 65 or older in an urban practice under the management of a primary care team composed of a family physician, nurse, and medical social worker. Results showed that the elderly used a higher percentage of in-hospital facilities than did the younger age groups. However, admission rates were significantly lower than the local national rates, and involved relatively fewer cases of long-term illness. No patients over 65 were admitted for psychiatric care during the one-year period of observation. This was attributed to the provision of planned domiciliary programs for supervision of patients with long-term illness within a coordinated framework of primary medical care.


The nature and control of myopia.

The nature and control of myopia. There is a growing body of evidence to support the belief that most myopia develops as a result of prolonged exposure to nearpoint activities. This paper summarizes the most important studies that have been done and postulates a mechanism by which prolonged accommodation can result in myopia. Possible means of arresting or preventing the development of myopia are discussed.


Genetic polymorphism of the sixth component of complement (C6) in the rhesus monkey. With isoelectric focusing, the complement protein C6 has been shown to be genetically polymorphic in the rhesus monkey. Three codominant alleles of a single autosomal locus, Rh C6, have been recognized: C6A, C6B, and C6R, with gene frequencies of 0.592, 0.354, and 0.053 in a random rhesus monkey population. Hardy-Weinberg analysis of the phenotypic frequencies in this population yielded observed values very close to those expected. Both natural mating between individuals carrying the various alleles and artificial combinations of sera of the different C6 types demonstrate patterns consistent with this model. Analysis of several families of monkeys confirmed the Mendelian autosomal codominant inheritance with numbers of offspring very close to expected values and no offspring types inconsistent with the mating pair types.


The structural basis of rabbit VH allotypes: serologic studies on a1 H chains with defined amino acid sequence. The amino acid sequences for the VH regions of three homogeneous antibodies elicited by type III pneumococcal vaccine were determined. All three antibodies had the group a allotype a1. Two of the antibody H chains (3372, 3381) had identical amino acid sequences in all framework positions that are considered correlates of the VH allotype, whereas the third H chain (3T72) differed from these at positions 15 and 16. The a1 allotypic specificities of the three homogeneous antibodies were compared by quantitative radiobinding and inhibition assays by using both insolubilized anti-a1 antisera and allotypic antiserum fractions rendered specific for the homogeneous antibody 3374. It was found that antibodies 3374 and 3381 are allotypically indistinguishable and have in common an a1 allotypic specificity that predominates in pooled a1 IgG. The allotypic specificity of the 3T72 antibody, on the other hand, was markedly deficient to those of 3374, 3381, and the a1 IgG pool. This correlation of allotypic difference with amino acid sequence variation at position 15 and 16 of the H chain indicates the involvement of these two residues in a major a1 allotypic determinant.


Murine plasma cells secreting more than one class of immunoglobulin heavy chain. IV. Sequence differences between kappa-chains of SAMM 368 IgG2b and IgA. The amino terminal sequences of the kappa light chains from SAMM 368 IgG2b and IgA have been determined. The two chains belong to different kappa subgroups as indicated by 10 amino acid differences among the first 23 residues. An additional three residue differences were demonstrated in the sequence including the first complementarity region. These results indicate that single cells of SAMM 368 produce two unique kappa-chains.


Circular countercurrent-distribution behavioral genetic maze. An inexpensive, easily constructed apparatus for mass screening of taxes of small animals with a rapid and accurate assignment of individual behavior scores has been described that should be of utility in hastening a behavioral geneticist's chores and allow him to handle more populations with fewer mazes. Also, the apparatus is well suited for use within the constraints of the undergraduate laboratory.


Enzyme-immunoassay in the detection of hepatitis B surface antigen. A new enzyme-immunoassay (EIA, Hepanostika Microelisa System) for the detection of hepatitis B surface antigen was evaluated against other methods, namely complement fixation, Hepanosticon, AusRIA II and Finnish Red Cross Radioimmunoassay (FRC-RIA). EIA detected the greatest number of positive samples in a serum panel consisting of 142 sera from clinical hepatitis patients. FRC-RIA was the most sensitive method for subtype ad, while EIA detected the ay specimen at the highest dilution. None of the test systems gave the 'optimal' result in the screening test, and it is proposed that a separate procedure for each antigen subtype should be carried out to detect the greatest number of positive samples.


Conversion of C5 precipitin line in the serum treated with activating substances of complement system. The hemolytic activity of C5 in the serum treated with zymosan, immune precipitate, or C1s was measured, and the C5 precipitin line on immunoelectrophoresis and the protein concentration of C5 in these serum specimens were also analyzed. A marked decrease in the hemolytic activity of C5 and a complete conversion of C5 precipitin line from beta- to alpha-globulin region were observed in teh serum treated with more than 1 mg/ml of zymosan. The elongation of C5 precipitin line from beta- to alpha-globulin region and the decrease in C5 hemolytic activity were observed in the serum treated with the immune precipitate. But neither  change in C5 precipitin line, nor a decrease in hemolytic activity of C5 was observed in C1s treated serum. C5 protein concentrations in these serum preparations were essentially the same as those of control. From these results, it was concluded that the immunoelectrophoretic change of C5 precipitin line might express the grade of the decrease in C5 hemolytic activity in the serum treated with the activating substances of the complement system.


A solid phase fluorescent immunossay for the quantitation of the C4 component of human complement. A non-competitive method for the determination of the C4 component of human complement in serum is described. This procedure involves use of a specific antibody covalently attached to derivatized polyacrylamide beads and a fluorescently labeled specific antibody. Reproducible results were achieved for C4 in serum in the range of 10 mg/dl to 170 mg/dl within 2 h. C4 levels as low as 150 ng/ml can also be measured. Fluorescent immunoassay and radial immunodiffusion were used to determine C4 levels in healthy adults. Good agreement was found between the two methods.


Inhibition of clone formation as an assay for T cell-mediated cytotoxicity: short-term kinetics and comparison with 51Cr release. The short-term kinetics of T cell-mediated cytotoxicity was investigated using a cloning inhibition assay. Murine cytotoxic thymus-derived lymphocytes (CTL) generated in vitro in mixed leukocyte cultures (MLC), were incubated for various periods of time at 37 degrees C with allogeneic mastocytoma target cells. The mixtures were then plated in soft agar, and mastocytoma clone formation was assessed after 5-7 days incubation. Using this technique, it was demonstrated that events leading to the loss of cloning ability could be detected after 1-3 min incubation at 37 degrees C, and after 20-30 min, 95% of the clone forming cells had been inactivated. When these results were compared directly with those obtained using the conventional 51Cr-release assay, it was found that the events leading to loss of cloning ability occurred more rapidly than indicated by the isotope assay. However, a modification of the 51Cr-release assay involving EDTA addition, gave comparable results to the cloning inhibition assay. These results raise the possibility that the events leading to 51Cr-release of tumor target cells may be related in time to those leading to the loss of cloning ability.


Immunoglobulin gamma chains of a monotreme mammal, the echidna (Tachyglossus aculeatus): amino acid composition and partial amino acid sequence. The echidna represents the lowest stage in phylogeny at which molecules clearly homologous to IgG antibodies appear to occur. We provide evidence that a fraction of gamma chains possess an unblocked N terminal sequence comparable to the VHIII sub-group of human gamma chains and that glycine is the C-terminal residue. Statistical comparison of amino acid composition of the component chains with other immunoglobulin heavy chains suggests that echidna gamma chains are more closely related to eutherian gamma chains than to the 7S Ig heavy chains from amphibia or aves. The results are consistent with our view that true gamma-type heavy chains did not appear in evolution until after the mammalian line diverged from the stem reptiles.


Leukocyte alkaline phosphatase levels in multiple myeloma. Leukocyte alkaline phosphatase levels (LAPL's) were determined in 62 patients with multiple myeloma over a 13-year period. Sixty of the 62 myeloma patients had consistently elevated LAPL's, one patient had normal LAPL, and one patient had an initially normal LAPL which later increased. Elevated LAPL's could not be correlated with age, hemoglobin levels, white blood counts, or elevation of the blood urea nitrogen. LAPL's did not change during objective or subjective responses to chemotherapy or with progression of disease. We suggest that some feature of myeloma may "turn on" an abnormal clone of cells which may be responsible for the elevated LAPL's in patients with multiple myeloma.


Effect of PGE1 on immediate-type immunologic and pharmacologic respiratory responses of the rhesus monkey. The effect of prostaglandin (PG)E1 on the acute, immediate-type airway response to antigen, carbocholine, PGF2alpha, histamine, and physostigmine was studied. In contrast to isoproterenol, which affects all abnormalities of pulmonary function, PGE1 selectively reversed only abnormalities of pulmonary resistance and dynamic compliance. Prior exposure to PGE1 minimally inhibited airway responses but when given simultaneously with antigen, it either selectively inhibited some or dampened all pulmonary function abnormalities. It is suggested that PGE1 acts on receptor sites to produce transient bronchodilation primarily in large central airways in contrast to isoproterenol, which produces bronchodilation in all airways. These results may be consistent with the stimulation of different adenylate cyclase systems in the respiratory tract analogous to those suggested for the gastric mucosa.


Abnormal fibrinogen heterogeneity and fibrinolytic activity in advanced liver disease. The present study demonstrates that the fibrinolytic activity is significantly increased and the level of plasminogen antiactivator diminished in the blood of patients with advanced liver cirrhosis and chronic aggressive hepatitis as compared with the values for healthy subjects. Total fibrinogen concentration was similar in patients and controls. However, electrophoresis of plasma with the use of SDS-polyacrylamide gel (3.5%) showed considerable differences in the composition of fibrinogen fractions. Lower molecular weight (LMW and LMW1) clottable protein was significantly (p less than 0.01) increased in the patients. In two out of 22 patients the higher molecular weight (HMW) fraction was virtually absent. In vitro incubation (37 degrees C for 48 hr) of diluted (1:10) plasma from a patient resulted in extensive degradation of a low-solubility fibrinogen fraction (HMW) previously added to the sample. No degradation was observed in any undiluted plasma samples. It is concluded that the increased concentration of lower-molecular-weight forms of clottable protein in the blood of patients with liver disease is probably related to increased in vivo degradation rather than abnormal synthesis. An association rather than a direct correlation with fibrinolytic activity was found.


Role of gonadotrophin releasing hormones in the reproductive behaviour of female ring doves (Streptopelia risoria). This work was carried out to determine whether gonadotrophin releasing hormone(s) (GnRH) plays a role in the courtship behaviour of female ring doves. In particular, it tests the hypothesis that a high dose of oestrogen suppresses the synergistic action of GnRH with oestrogen which is required to elicit courtship behaviour. The hypothesis was formulated to provide an explanation for a finding in a previous study that ovariectomized ring doves treated with a high dose of oestrogen, paradoxically, failed to show courtship behaviour. In the present study, treatment with synthetic LH releasing hormone (RH) enabled such birds to show typical female behaviour, thus supporting the hypothesis. This LH-RH effect was not apparently mediated by LH or progesterone since treatment with LH or progesterone failed to induce courtship behaviour. In addition, LH-RH can synergise with sub-threshold doses of oestrogen to induce both nest-soliciting and squatting behaviour. This portion of the LH-RH effect complements similar results reported for the rat. Finally, the results of thyrotrophin releasing hormone point to the specificity of LH-RH and the results of an anti-ovulation LH-RH analogue agree with the LH-RH effect.


Dengue viruses and mononuclear phagocytes. I. Infection enhancement by non-neutralizing antibody. Cultured mononuclear peripheral blood leukocytes (PBL) from nonimmune human beings and monkeys are nonpermissive to dengue 2 virus (D2V) infection at multiplicities of infection of 0.001-0.1, but become permissive when non-neutralizing dengue antibody is added to medium. D2V infection occurred in PBL prepared from anti-coagulated but not from defibrinated plasma. Infection enhancement was produced by multiple lots of heterotypic anti-dengue raised in several mammalian species. Homotypic anti-dengue neutralized D2V at high concentrations but enhanced at low concentrations; enhancement end point in one serum was 1:320,000. The infection-enhancing factor was a noncytophilic antibody of the IgG class. D2V infection occurred in the absence of heat-labile complement components but did not occur when complexes were prepared with anti- dengue F(ab)(2). Treatment of PBL with several proteases increased permissiveness to D2V infection by immune complexes but not by virus alone. Two rhesus monkey serums collected 14 days after D2V infection contained an IgG antibody with high-titered enhancing activity but with no hemagglutination-inhibition or neutralizing activity. Virus-antibody complexes are irreversibly attached to PBL within 15 min and completely internalized in 60 min. There was considerable variation in cellular infection in different experiments, however, maximum virus yields usually exceeded 1,000 plaque-forming units per 1 x 10(6) PBL occurring between 2 and 4 days in culture. In vitro antibody-dependent infection of PBL provides a possible model for study of pathogenetic mechanisms in infants with dengue shock syndrome who passively acquire maternal anti-dengue IgG.


Ly phenotype and mechanism of action of mouse neonatal suppressor T cells. Neonatal suppressor T cells were isolated from the thymuses of 10- to 14-day old BDF mice infected at birth with mouse thymic virus. Such cells were enriched for suppressive activity directed against antibody formation by adult B cells and represented a relatively homogenous population of outer cortical cells. Their surface antigen phenotype was found to be: Ly 1+, Ly 2+, TL+, Thy 1+, and H-2+. The cells were larger and contained more DNA than thymocytes from age-matched controls. These findings identify neonatal suppressor T cells as a unique subpopulation separate from most inducible suppressor cells in the adult mouse. The mechanism of action of neonatal suppressor T cells seems to be a reduction in the number of B cells initially triggered by antigen.


Characterization of an amyloid fibril protein from senile cardiac amyloid. A protein, ASCA, is isolated from amyloid fibrils extracted from heart tissue of five different patients with senile cardiac amyloidosis (SCA). The proteins of all five patients showed immunological identity when reacted with an antiserum raised against one of the proteins. In contrast, no reaction was obtained with antisera against a variety of other amyloid proteins. The antiserum against the subunit protein of senile cardiac amyloid did not react with any other amyloid preparations tested, nor with extracts of normal heart tissue. Thus, the subunit protein appeared to be unique to senile heart amyloid. The protein could form fibrils in vitro, had a mol wt of about 6,000 daltons and the amino acid compositions investigated in two cases showed extensive similarities but were clearly different from that of protein AA of secondary amyloid fibrils.


Phage receptor material in Lactobacillus casei. In Lactobacillus casei S-I, D-galactosamine and L-rhamnose comprised a phage receptor for phage J-I. A mixture of D-galactosamine and L-rhamnose effectively inactivated phage J-I, and a J-I-resistant mutant strain, L. casei S-I/J-I, lacked D-galactosamine in its surface component. The phage-inactivating effects of D-galactosamine and L-rhamnose were strongly dependent on the concentration of each substance and on temperature. It is suggested that the receptor for phage J-I involves both D-galactosamine in the cytoplasmic membrane and L-rhamnose in the wall of the host bacterium L. casei S-I, which lacts teichoic acid in its wall.


Selection from gonococci grown in vitro of a colony type with some virulence properties of organisms adapted in vivo. Gonococci from subcutaneously implanted chambers in guinea pigs produced, on agar, more than 95% small colonies showing a "double highlight" (DH) effect in oblique reflected light combined with transmitted light. Laboratory strains of gonococci produced some DH colonies, but other showed a single highlight (SH) or no highlight (NH). Selection of DH colonies and comparison of their organisms with gonococci grown in vivo and with those from SH colonies, showed that the DH character was associated with high infectivity for guinea-pig chambers, resistance to killing by human phagocytes and heavy pilation. Furthermore, DH colonies were found in the first culture of three fresh samples of urethral pus. Thus, the DH colony characteristic may be a more reliable criterion of pathogenicity of gonococcal isolates than systems used previously. There were, however, some differences between the gonococci grown in vivo and the DH colony types. The gonococci grown in vivo and cultured once on solid medium possessed one or two antigens which differed from those of DH (or SH) colonies. They also formed smooth suspensions (which separated slowly) in saline, compared with the rough suspensions (which separated quickly) formed by gonococci from DH (or SH) colonies. Finally, the organisms grown in vivo were resistant to killing by human serum whereas the DH (and SH) colony types were susceptible; the resistance of the organisms grown in vivo was lost during one subculture on agar suggesting that the property is a phenotypic characteristic. Hence, in addition to selecting DH colony types the conditions in vivo produce organisms which differ, probably phenotypically, from cultured organisms.


Immunization of guinea pigs with Neisseria gonorrhoeae: strain specificity and mechanisms of immunity. Infection of subcutaneusly implanted chambers in guinea pigs conferred immunity against homologous infection of other chambers in the same animals. However, attempts to immunize guinea pigs by subcutaneous injection of filtered fluid from infected chambers, or with small doses of formalin-killed, chamber gonococci were not successful. Thus, neither organisms grown in vivo nor their extracellular products appeared to be exceptionally immunogenic. In immunizing tests with different isolates of gonococci adapted to growth in guinea-pig chambers, cross-immunity to chamber infection with low challenge doses was detected only between two of six isolates. The killing of gonococci in chambers of immunized animals, which occurred only after homologous challenge or with the heterologous strain showing cross-immunity, was not due primarily to humoral factors in the chamber fluid but probably to an enhanced effectiveness of phagocytosis. The serum of immunized animals was bactericidal for homologous strains and for the strain showing cross-immunity but not for strains showing no cross-immunity. Hence, serum bactericidal activity might be a useful indicator for investigating the specificity of immunity produced by different gonococcal strains.


Arginine hydroxamate-resistant mutants of Bacillus subtilis with altered control of arginine metabolism. Arginine hydroxamate inhibits the growth of Bacillus subtilis. From a large number of mutants isolated as resistant to this arginine analogue, 29 were chosen for further investigation. Most of these shared diminished ability to utilize arginine, citrulline and/or ornithine as sole nitrogen source. All 29 had reduced levels of the catabolic enzymes arginase and ornithine aminotransferase under various conditions in which these enzymes are induced in the parent. In some circumstances, five of the mutants also showed elevated levels of the biosynthetic enzyme ornithine carbamoyltransferase. On the basis of these data, the 29 mutants were divided into six phenotypic classes; in four of these, control of ornithine carbamoyltransferase was the same as in the wild type, while in the other two it was altered. It is suggested that the isolates carry regulatory mutations, and that certain of these may affect simultaneously the formation of arginine catabolic and biosynthetic enzymes. The implication of the latter is that in B. subtilis, as in yeast, controls of the catabolic and biosynthetic pathways are connected. Single representatives of five of the phenotypic classes carry mutations conferring arginine hydroxamate resistance linked to cysA by transduction with phage PBSI; this did not appear to be true for a representative of the sixth class.


Transfer and expression of pseudomonas plasmid RP1 in Caulobacter. This study demonstrates that the host range of Pseudomonas plasmid RP1 includes the genus Caulobacter. Caulobacter was shown to acquire three antibiotic resistance markers located in RP1. A fourth plasmid marker, susceptibility to an RNA bacteriophage, was not expressed, but could be transferred from Caulobacter to Escherichia coli. The lack of phenotypic expression of the phage marker was manifested by the inability of the phage to adsorb or to produce plaques on Caulobacter transcipients. Matings of Pseudomonas aeruginosa and Caulobacter vibrioides CV6 were carried out in the presence of bacteriophage phi6, a DNA phage that infects and kills only swarmer cells of Caulobacter. No decrease in plasmid transfer in the presence of phage phi6 was detected, suggesting that stalked cells, and not swarmer cells, serve as recipients. Our evidence suggests that transfer of chromosomal segments from Caulobacter may be mediated by plasmid RP1; such segments are not stably maintained.


The surface of Neisseria gonorrhoeae: isolation of the major components of the outer membrane. Outer membranes were isolated from several strains of Neisseria gonorrhoeae by extraction of whole cells with aqueous lithium acetate. The preparations contained a limited number of components including lipopolysaccharide and two major proteins. One protein was present in all strains examined; the second, which showed anomalous behaviour on sodium dodecyl sulphate-polyacrylamide gel electrophoresis, was absent from some. Fluorescent labelling of intact N. gonorrhoeae showed that the two proteins and pili were the major surface proteins. Each of the three major outer membrane components was isolated in a homogeneous form by selective extraction followed by gel filtration.


Rapid diagnosis of rotavirus infections: comparison of electron microscopy and immunoelectroosmophoresis for the detection of rotavirus in human infantile gastroenteritis. Eighty-seven faecal samples from infants and children suffering from acute gastroenteritis were investigated for the presence of rotavirus by immunoelectroosmophoresis (IEOP) and electron microscopy (EM). Sixty-one % of the samples contained rotavirus antigens when examined by IEOP whereas only 50% were diagnosed as positive EM. However, where it was possible to perform EM within the same day that the sample was received it took 24 h to establish the diagnosis by IEOP. The high sensitivity of the IEOP method was achieved by application of antiserum produced in rabbits to rotavirus immunoprecipitates. The specificity and sensitivity of the diagnostic antiserum produced were tested by application of different immunoelectrophoretic methods.


Cytopathic effect and plaque formation by arboviruses in a continuous cell line (XTC-2) from the toad Xenopus laevis. Forty-six arboviruses were tested for c.p.e. and/or plaque formation in an amphibian cell line. C.p.e. was observed with a high proportion of the viruses tested. Comparative plaque assay, in the XTC-2 cells at 28 degrees C and Vero cells at 37 degrees C, suggests that these systems are comparable in sensitivity and susceptibility to infection. Practical uses of this cell line are discussed.


End-point dilution and plaque assay methods for titration of cricket paralysis virus in cultured Drosophila cells. Cricket paralysis virus, an insect picorna-like virus, caused a distinct c.p.e. in cultured Drosophila melanogaster cells, allowing the development of titration methods based on end-point dilution or plaque assay methods. The end-point dilution (TCD50) method is more sensitive and economical than plaque assays and is easily scored. The data indicate a minimum infectivity/particle ratio of about 1/2000.


Partial deficiency of long arm of chromosome No. 11. A child is presented with slight psychomotor retardation and few minor anomalies, in whom the cytogenetic analysis revealed a de novo translocation between the long arms of chromosomes 8 and 11, with deficiency of a small distal segment of 11q.


An implant to empty the bladder or close the urethra. An implant has been designed which, in the baboon, will empty the bladder almost completely, or close the urethra so that urine does not leak out despite a contraction of the detrusor muscle. Electrodes on the 1st and 2nd sacral anterior nerve roots (corresponding roughly to the 3rd and 4th sacral in man)  suffice for both actions. Closing the urethra or emptying the bladder artificially in this way seems to cause conscious, neurologically intact, baboons no discomfort. Implants have remained in place for over two years, and have emptied the bladder artificially 12 times a day for many weeks, without deterioration of function.


A prospective study of tracheobronchial bacterial flora in acutely brain-injured patients with and without antibiotic prophylaxis. The authors observed prospectively 28 brain-injured patients, who required respiratory tract intubation, to determine the effect of antibiotic prophylaxis on bacterial flora, the rate of flora change, and the appearance of infection. Antibiotics not only failed to alter the rate of abnormal colonization but were associated with an earlier appearance of Gram-negative bacilli, the organisms that produced the most severe infections. Although more infections occurred in patients initially untreated with antibiotics, these infections were usually mild and caused by organisms susceptible to highly effective and relatively safe drugs. Although highly reproducible as a laboratory determination, the nitroblue tetrazolium dye test score showed no consistent relationship with the presence or absence of bacterial infection. Regular and extensive clinical and laboratory observations, including cultures of the respiratory tract helped to make the antibiotic administration in these patients specific, appropriate, and reasonable. Broad spectrum antibiotic prophylaxis does not prevent and may enhance the development of severe pulmonary infection in these patients.


Urinary riboflavin metabolites in the rat. Male rats were fed a riboflavin-deficient diet for 25 days and then fed [2-14C]riboflavin to replete their riboflavin pool(s). During a second depletion period, urine and feces were collected and 14C excretion monitored. The urine was chromatographed on R-15 resorcinol resin and 14C was measured in all fractions. The 14C compounds in the individual fractions were shown to be different by thin layer chromatography. The amount of 14C recovered as riboflavin increased after acid hydrolysis of the urine indicating the presence of riboflavin in conjugated forms. All R-15 fractions were found to support growth in a microbiological (L. casei) assay for riboflavin. This suggested that other derivatives, in addition to riboflavin and flavin nucleotides, are biologically active. However, the conjugated compounds were apparently less active, since acid hydrolysis of the urine enhanced its growth-promoting ability of L. casei. One 14C metabolite was identified as urea, thus providing evidence for degradation of the riboflavin molecule. This study has shown that the metabolic fates of riboflavin in the rat include conjugation and extensive degradation.


The styloid-stylohyoid syndrome.

The styloid-stylohyoid syndrome. The complexities of the styloid-stylohyoid syndrome are examined from the historical, anatomical, radiographic, clinical and treatment aspects. Although approximately 4% of the population is afflicted with this anomalous growth, the syndrome is not usually seen clinically until after the age of 30. There appears to be little correlation between the size and extent of the anomaly and the predictability of patients having symptoms related to the anomaly. The awareness of the anomaly and the syndrome can lead to a proper diagnosis and the appropriate treatment for the patient who has been labeled by the dental community or medical community, or both, as psychoneurotic.


Endocrine studies in cystinosis: compensated primary hypothyroidism. Children with nephropathic cystinosis exhibit marked growth retardation. Improved medical management and renal transplantation have increased their life expectancy beyond the second decade. We have studied endocrine function in seven patients with cystinosis and reviewed autopsy findings of four patients and medical records of 24 others. One 10-year-old boy was overtly hypothyroid. The six other patients had normal studies of peripheral thyroid function but two had borderline and two had frankly elevated serum TSH levels. Stimulation tests of cortisol and growth hormone secretion and basal levels of serum NSILA-s were normal. Postmortem histology of the thyroid glands revealed extensive destruction and infiltration of the epithelium with cystine crystals. Despite the presence of cystine crystals in other endocrine tissues, there was no destruction of epithelium in glands other than in the thyroid. We conclude that in nephropathic cystinosis "compensated" primary hypothyroidism occurs frequently and early and may be diagnosed by measurement of serum TSH concentrations.


Home total parenteral nutrition: an alternative approach to the management of children with severe chronic small bowel disease. A home program of total parenteral nutrition (HTPN) has been developed for managing patients with severe chronic small bowel disease who would otherwise be unable to leave the hospital. Six such children were treated by this program using a Broviac catheter to shorten hospitalization, to decrease the cost of care, and to normalize their lives as much as possible. They ranged in age from 2 1/4-17 yr and received HTPN for periods of from 1-11 mo. Criteria for instituting this therapy were the inability to maintain fluid and nutritional balance on therapeutic diet or oral formula, or a need for 30 or more days of conventional TPN. The 6 patients had a total of 1139 days on HTPN with 1 episode of catheter sepsis and 1 localized infection at the catheter site. None of the catheters clotted but 1 was accidentally dislodged. Small bowel adaptation occurred in 4 of the 6 patients. This allowed gradual discontinuous of HTPN and reinstitution of total oral alimentation.


Time-dependent kinetics I: Exponential autoinduction of carbamazepine in monkeys. The pharmacokinetics of carbamazepine were studied during a week-long infusion of the drug in 60% polyethylene glycol 400 solution in three rhesus monkeys. Serum concentrations approached steady state within 8-16 hr and then rapidly declined, within 72 hr, to a new asymptotic level approximately 46% of the maximum steady-state concentration. Serum concentrations remained at that level during the rest of the experimental period. The decline from the maximum value to the asymptotic steady state was exponential. It is postulated that the decline in the steady-state concentration is due to autoinduction by carbamazepine of its own metabolism.


Time-dependent kinetics II: Diurnal oscillations in steady-state plasma ethosuximide levels in rhesus monkeys. Morning steady-state (9 am) plasma levels were significantly higher than the corresponding evening (5 pm) plasma levels during a 3-week zero-order infusion of ethosuximide to six monkeys. These differences could not be explained by experimental variables such as GLC assay and infusion pump. Circadian periodicity in steady-state plasma levels was investigated in three monkeys over 4 months under controlled experimental conditions: blood sampling at 2-hr intervals for 26 hr, 1 day/week; fixed lighting, feeding, and noise schedules; and electroencephalogram monitoring. The plasma concentration-time curves showed two minima in the 12 noon-2 pm and 8 pm-12 midnight periods, and the later involved the largest percent change in plasma levels (4-8%). The plasma concentration-time data were subjected to cross-correlation analysis, which indicated a circadian rhythm in steady-state plasma levels with a period of 24-26 hr.


New method for characterizing dissolution properties of drug powders. Various multiparticulate dissolution models that assume a log-normal particle-size distribution are fitted by nonlinear least-squares regression to data from the dissolution of micronized glyburide. Estimates of parameters describing the effective initial particle-size distribution are obtained, together with estimates of the specific dissolution rate parameter. A dissolution equation based on an ideal, untruncated, log-normal distribution, with the single particles dissolving according to the Hixson-Crowell cube root law, is the best model. The dissolution behavior of glyburide can be well described by this model in terms of the specific dissolution rate parameter and one other parameter accounting for the distribution effect. The estimation of these two parameters represents a more exact way of describing the dissolution characteristics of drug powders than previous approaches. The method should be of interest in the quality control of drugs that may cause bioavailability problems because of dissolution rate-limited absorption.


Aldosterone antagonism studies in the rhesus monkey. Renal studies in femal rhesus monkeys indicated that 10 micron g was an optimum i.m. sodium-retaining dose of aldosterone. Aldosterone was injected i.m. at dosages of 2.5, 5, 10 and 20 micron g/animal. The 10-micron g dose induced about a 50% reduction in sodium excretion (from 3.7 to 1.7 mEq/6 hr) and was selected as the standard dose for antagonism studies. K excretion and urine volume remained unchanged. Subsequently, the oral antialdosterone activities of spironolactone and canrenone, a delta6 metabolite, were assessed at dosages of 1, 4 and 8 mg/kg. Dose-related increases in the aldosterone-depressed urinary Na/k ratio occurred primarily as a consequence of enhanced sodium excretion. Canrenone possessed antialdosterone potency equal to that of spironolactone. In the absence of exogenous aldosterone, spironolactone (16 mg/kg) was essentially devoid of diuretic activity whereas hydrochlorothiazide (1 mg/kg) induced marked increases in Na (256%) and K (105%) excretion and urine volume (109%).


Peters-Rieger's syndrome.

Peters-Rieger's syndrome. The joint occurrence of Peter's anomaly, congenital central deep corneal opacity with an enterior cone-shaped polar cataract, and Rieger's anomaly, hypoplasia of iris stroma, dyscoria, and iridocorneal adhesions in the angle of the anterior chamber, is described. The term Peters-Riger's syndrome is proposed for this clinical association. Associated ocular anomalies which apparently have not been previously mentioned in the literature were dysversion of the optic disc, ganglionic neuroretinal hypoplasia (hypoplasia of the optic nerve), and downward ectopia of the macula. Other associated ocular and systemic anomalies of Peters-Rieger's syndrome are also mentioned.


Electrical responses of rods in the retina of Bufo marinus. 1. Intracellular responses to flashes and steps of light have been recorded from the outer segment and the cell body of rods in the retina of the Bufo marinus. The identification of the origin of recorded responses has been confirmed by intracellular marking.2. Responses to flashes delivered in darkness or superimposed on a background were analysed. Responses recorded from outer segments conform to the principle of ;spectral univariance'. The shape of the response is not affected by enlarging the spot diameter from 150 to 1000 mum.3. The membrane potential measured in darkness at the outer segments varied from -15 to -25 mV. Injection of steady hyperpolarizing currents increases the size of the response to light; depolarizing currents reduce the response. The mean value of the input resistance is 97 +/- 30 MOmega in darkness and increases by 20-30% during illumination.4. The responses obtained from the cell body of rods have the same shape, time course and spectral sensitivity of those recorded at the outer segment. Injection of steady current at the cell body produces different effects than at the outer segment: hyperpolarizing currents reduce the amplitude of the response to light; depolarizing currents increase the response.5. The experimental data are fitted according to a model similar to that used to describe the responses of turtle cones (Baylor & Hodgkin, 1974; Baylor, Hodgkin & Lamb, 1974a, b).6. The model reproduces the electrical responses of the rod outer segment to a variety of stimuli: (a) brief flashes and steps of light in dark adapted conditions; (b) bright flashes superimposed on background illuminations; (c) pairs of flashes delivered at different time intervals. Responses to hyperpolarizing steps of current are also reproduced by the model.


Spectral and orientation specificity of single cells in foveal striate cortex of the vervet monkey, Cercopithecus aethiops. 1. The spectral sensitivity, orientation specificity and inhibitory surround of seventy-three cells were studied in the vervet monkey. The eye was in the dark or illuminated with steady white or spectral light. The cells were in the striate cortex corresponding to the foveal representation. Nearly all the cells gave on- or on/off-responses.2. More than a third of the cells (41%) responded over a narrow spectral band, in the blue, green, yellow or red section. Three quarters of them were orientation specific with flanking inhibitory surround and half of these were of the ;stopped-end' variety as well. The effect of the wave-length of the background indicated that only a half were activated by such excitatory-inhibitory colour pairs as have been described in the geniculate nucleus.3. A third of the cells (36%) responded to most colours but with the greatest response to green, yellow or red. Less than half were orientation specific. Unlike the narrowband cells, the response decreased with the intensity of the light. Two thirds were activated by the excitatory-inhibitory colour pairs that have been described in the geniculate nucleus.4. In both groups of cells the wave-length of the spectral peak could be different when the stimuli were weak compared with when they were strong.5. One quarter of the cells (23%) gave on/off-responses to all spectral flashes; half were not orientation specific. The difference in orientation specificity between narrow- and broadband cells is significant (P < 0.01).


A pure enterococcal abscess after cesarean section. The pathogenic role of the enterococcus in pelvic infections is controversial. This case report of a pure enterococcal abscess developing after cesarean section supports the view that this organism can be a primary pathogen in obstetric and gynecologic infections. Because of its unusual sensitivity pattern, the enterococcus requires specific antibiotic therapy.


Diagnosis and treatment of acute salpingitis. Acute salpingitis is one of the most common acute gynecologic diseases and occurs in approximately 750,000 women each year in the United States. Use of laparoscopy to confirm the diagnosis of acute salpingitis has shown that the signs and symptoms classically ascribed to this disease are not specific to it. Fever, leukocytosis, elevated ESR and adnexal masses or swelling are not necessary to make a diagnosis of acute salpingitis. Lower abdominal pain and adnexal tenderness are the most consistent findings. Microbiologic data obtained by laparoscopy and culdocentesis have raised questions about the role of N. gonorrhoeae in salpingitis and have demonstrated that, as in pelvic infections generally, acute salpingitis is associated with mixed aerobic-anaerobic bacterial flora. Good results in the treatment of acute salpingitis depend upon: (1) early diagnosis, (2) hospitalization and bed rest, (3) the use of antibiotic therapy that takes into account the polymicrobial etiology of acute salpingitis, (4) prevention of recurrent episodes of salpingitis through efforts at patient education and identification and treatment of sexual partners. Most important, we must remember that what is at stake is often the future reproductive potential of a young woman. It must be weighed against both patient and physician convenience and cost. Further investigative efforts are essential to determine the role of IUDs in pelvic infections, discover the true microbiologic etiology of salpingitis and establish appropriate antimicrobial treatment as determined by prospective, microbiologically controlled investigations.


The use of betamethasone and timed delivery in management of premature rupture of the membranes in the preterm pregnancy. Of 43 women admitted with premature rupture of the membranes between 27 and 32 weeks' gestation, 27 received antepartum glucocorticoid with delivery timed to occur approximately 24 hours after the first dose of steriod. Sixteen patients did not receive glucocorticoid and were managed expectantly. Neonatal mortality was significantly less in the steroid group (15% vs. 50%, p less than .01), and this difference was explained by a reduction in deaths from respiratory distress syndrome. Rates of infectious morbidity for both mothers and infants were similar between the steroid-treated group and the group managed expectantly.


An outbreak of caprine listeriosis in the Western Cape. Listerial meningo-encephalitis (circling disease) is reported for the first time in ruminants in South Africa. An account is given of the clinical signs, pathology and bacteriological confirmation of the disease.


[The diagnosis of brucellosis in cattle (author's transl)]. Tests currently in use of the diagnosis of brucellosis and the immune response in cattle following exposure to Brucella antigens are reviewed. The interpretation and evaluation of results obtained by different tests under conditions where S19 vaccine is used, are discussed. Attention is focussed on the possible role of the bull in disseminating Brucella organisms.


The isolation of Brucella abortus biotype I from African buffalo in the Kruger National Park. The isolation of Brucella abortus from free living wild africal buffalo (Syncerus caffer) in the Kruger National Park, South Africa, is described. The four isolates testes proved to be biotype I and it is speculated that the origin of brucellosis in wild animals is from domestic stock.


5-(Tetradecyloxy)-2-furancarboxylic acid and related hypolipidemic fatty acid-like alkyloxyarylcarboxylic acids. 5-(Tetradecyloxy)-2-furancarboxylic acid (91, RMI 14514) was found to lower blood lipids and to inhibit fatty acid synthesis with minimal effects on liver weight and liver fat content. This fatty acid-like compound represents a new class of hypolipidemic agent; it is effective in rats and monkeys. The compound resulted from discovery of hypolipidemic activity in certain beta-keto esters, postulation and confirmation of the corresponding benzoic acids as active metabolites, and systematic exploration of the structure--activity relationships.


Studies on quinoline derivatives and related compounds. 5. Synthesis and antimicrobial activity of novel 1-alkoxy-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids. A series of novel 1-alkoxy-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids was synthesized and screened as antimicrobial agents. The most active compounds in vitro against gram-negative microorganisms and Staphylococcus aureus were 1,4-dihydro-1-methoxy-6,7-methylenedioxy-4-oxo-3-quinolinecarboxylic acid (22), 1,2,6,9-tetrahydro-6-methoxy-9-oxofuro[3,2-f]quinoline-8-carboxylic acid (30, and 2,3,6,9-tetrahydro-6-methoxy-3-methyl -2,9-dioxothiazolo [5,4-f]quinoline-8-carboxylic acid (34). These compounds had antigram-negative activity comparable to that of the corresponding N-ethyl derivatives 1, 2, and 4. Their serum levels and urinary recovery rates in rats, however, were significantly improved relative to the latter compounds (1,2, and 4).


Synthesis and biological activity of some derivatives of thiochroman-4-one and tetrahydrothiapyran-4-one. A small series of pyrazoles and isoxazoles derived from thiochroman-4-one has been synthesized and characterized. The compounds were examined for their in vitro inhibitory activity against Bacillus subtilis and Pseudomonas fluorescens. Among the tested compounds the pyrazole derivative from thiochroman-4-one was found to be the most effective inhibitor of growth of B. subtilis. Extensive H NMR analysis was recorded for all compounds.


Antiprotozoal thiazoles. 2. 2-(5-Nitro-2-furyl-, thiazolyl-, and 1-methylimidazolyl-)thiazoles. Ten 2-substituted 4-thiazolecarboxaldehyde hydrazones bearing 5-nitro-2-furyl, 5-nitro-2-thiazolyl, and 1-methyl-5-nitro-2-imidazolyl functions have been prepared and screened for activity against Trypanosoma cruzi infections in mice. The results permitted the ranking of these substituents in decreasing order of activity: 1-methyl-5-nitro-2-imidazolyl greater than 5-nitro-2-furyl greater than 5-nitro-2-thiazolyl, the last being inactive. Some structural features of the side chain necessary for optimum activity are discussed. The most active compound, 4-[[[2-(1-methyl-5-nitro-2-imidazolyl)-4-thiazolyl]methylene]amino]thiomorpholine 1,1-dioxide, compared favorably with the standard Nifurtimox against three recent clinical isolates of T. cruzi, including one with a high myocardial tissue infiltration.


Synthesis of episilon-rhodomycinone glycosides. Twenty-six episilon-rhodomycinone glycosides have been synthesized. These include the episilon-rhodomycinone glycosides of 2-deoxy-L-fucose, 2-deoxy-L-rhamnose, and 2-deoxy-D-ribose as well as their 2-hydroxyl derivatives. NMR spectroscopy showed that all the glycosides prepared had the saccharide residues linked to position 10 of episilon-rhodomycinone and helped establish the anomeric purity and configuration of several glycosides. Preliminary screening results show that 2-deoxy-di-O-acetyl-D-ribopyranosyl-episilon-rhodomycinone has an activity T/C of 125 on P388 tumors.


A myeloliposarcoma in a female Perodicticus potto: mineralogical and elemental chemical analysis. A spherical mass on the medial aspect of the thigh and caudal abdomen of a 15-year-old female Perodicticus potto was surgically removed and shown to be a myeloliposarcoma. Mineralogical examination of these tissues showed them to be amorphous to X-rays. Thirty-two elements were determined by chemical analysis of the tumor.


Correlation of mixed lymphocyte reactivity and skin graft rejection in nonhuman primates. One-way mixed lymphocyte culture (MLC) reactivity and skin graft rejection were investigated to assess immune competence and histocompatibility in the baboon, the cebus monkey, and the cotton-topped marmoset. Adequate and comparable cell-mediated immunity was demonstrated. MLN reactions revealed strong histocompatibility differences among the three primate species and stimulating alloantigens for unrelated individuals of each species. Xenogeneic skin grafts survived nine days and allogeneic grafts, an average of 11 days. These systems appear readily applicable for assessing histocompatibility in nonhuman primates.


Heart rate in caged Macaca fascicularis. Effects of short-term physical exercise. Electrocardiograms were recorded hourly for five days in 16 caged Macaca fascicularis by means of a miniaturized ECG transmitter connected to two chest leads. The lowest heart rates were 135 +/- 35 (mean +/- SD, n= 31) beats/min at 5 a.m., and the highest were 192 +/- 22 (n = 29) beats/min at 3 p.m. Sinus arrhythmia was common. Eight of the animals were trained to exercise in a specially designed enclosed treadmill; their heart rates were recorded daily during two 10-min periods of running at 3.4 km/h. Transfer of the monkeys (n k0) to the treadmill increased heart rate from 186 +/- 24 to 228 +/- 23 beats/min; exercise further increased it to 271 +/- 8 beats/min.


Blood groups of crab-eating macaques (Macaca fascicularis) demonstrated by isoimmune rhesus monkey (Macaca mulatta) sera. Twenty-one isoimmune sera produced in rhesus monkey (Macaca mulatta) containing type-specific antibodies for simian-type red cell antigens were tested for their cross-reactivity with red cells from crab-eating macaques (M. fascicularis). The majority of the antisera gave cross-reactions determining polymorphisms in the red cells of crab-eating macaques, homologous to those of rhesus monkeys. These results attest to the close taxonomic realationship between the two species of macaques, and have the practical implication that isoimmune sera produced for blood typing can also be used for typing red cells from related species, as has been also observed in studies on apes.


Progesterone levels in the Japanese monkey (Macaca fuscata fuscata) during the breeding and nonbreeding season and pregnancy. Progesterone levels were determined in the peripheral blood of the Japanese monkey during the menstrual cycle, breeding season, nonbreeding season, and gestation. Progesterone levels averaged less than 0.3 ng/ml in the earlier follicular phase, rose to maximum values of 3.8 ng/ml approximately eight days before menses, and declined to less than 1.0 ng/ml before menstruation. Progesterone levels during the nonbreeding season were comparable with those during the early follicular phase. In pregnant animals circulating progesterone either continued to rise around day 20, or fell as in the infertile cycle, then rose again. Progesterone levels declined between days 35 and 60 and were variable until about day 130 of gestation.


"Large" and "small" nuclear pore complexes; the influence of glutaraldehyde. Aliquots of lymphocyte cell suspensions were pretreated according to the following three schedules before freeze fracturing: (a) prefixed with 2% glutaraldehyde before infiltration with 25% glycerol in medium RPMI-1640; (b) frozen in medium RPMI-1640 without additional pretreatment; and (c) frozen after pretreatment with 25% glycerol in medium RPMI-1640. The diameters of the fractured nuclear pore complexes of cells prefixed with glutaraldehyde were normally distributed within the range 70-120 nm (median 90 nm). The nuclear envelopes of 66-75% of cells processed through schedules b and c, which omitted glutaraldehyde fixation, had 70-120 nm diameter pores, while the remainder had pores with diameters in the range 120-175 nm. The large pores were structurally similar to the smaller pores except for their dimensions. These results indicate that glutaraldehyde gives rise to shrinkage of the larger pores to the minimum, smaller, diameter. Apparent orifices of at least 30 nm diameter were sometimes observed at the centres of these large pore complexes. We propose that the variation in pore diameters may indicate opening and closure of this orifice, and that the widely reported "central granule" of the nuclear pore complex corresponds with the orifice in a closed configuration.


Oogenesis in the female sterile (1)42 mutant of Drosophila melanogaster. The sex-linked mutation fs(1)42 was induced by ethyl methane sulfonate. It has no effect on either the external morphology or longevity of adult hemizygotes or homozygotes. Heterozygotes and hemizygotes are fertile, but homozygotes are sterile. Egg chamber development proceeds through stages 8, and thereafter chambers degenerate. Dying follicle cells are seen in chambers at all positions in the ovarioles. Profollicle cells also die within germaria, and clusters of sister cystocytes take longer than normal to receive their coverings of follicle cells. Egg chambers in the vitellarium contain only about 60% the normal number of follicle cells, these generally have greater lateral dimensions, and their nuclei and nucleoli are also larger than normal. The follicular envelope of mutant chambers often contains gaps through which cystocytes send cytoplasmic projections. Abnormalities seen in development of the fs(1)42 oocyte are likely to be due to its envelope of defective follicle cells.


Transformation and neoplastic development of hamster chondrocytes after exposure to 4-nitroquinoline-1-oxide and 3-methylcholanthrene in tissue culture. Sternal hyaline cartilages of Syrian hamsters were dissociated with collagenase and culured. Primary monolayer cultures of the dissociated cells were morphologically homogeneous. Secondary cultures of the chondrocytes were treated with 1 x 10(-6) or 2 x 10(-6) M 4-nitroquinoline-1-oxide (4NQO) for 3 hours or with 5 or 10 microgram 3-methylcholanthrene (MCA)/ml for 3 days. Cultured chondrocytes transformed morphologically 29-51 days after 4NQO treatment and 41-61 days after MCA treatment and began to grow continuously in vitro. Cultures of transformed cells, like transformed fibroblasts. Untreated cells and cells treated with dimethyl sulfoxide did not transform within at least 110 days after inoculation. Among the transformed cells, one near-diploid cell line preserved the distinct phenotypic expression of chondrocytes, whereas heteroploid cell lines lost their differentiated features. The near-diploid cell line produced nodules in the cheek pouches of hamsters within a week, by the nodules regressed later. They showed the chondrogenic properties of the original cells and stained metachromatically with toluidine blue. Heteroploid cell lines formed progressive tumors with few chondrogenic features; these tumors were diagnosed as fibrosarcomas.


Sister chromatid exchange and chromosome aberration analysis with the use of several carcinogens and noncarcinogens. Several chemical carcinogens and noncarcinogens were tested for their ability to induce sister chromatid exchanges (SCE) and structural chromosome aberrations in cultured V79-4 Chinese hamster cells. All of the direct-acting carcinogens induced a large increase in SCE frequency. Two chemicals, which are mutagenic in microorganisms but whose carcinogenicity is poorly documented, also increased the frequency of SCE. Carcinogenic polycyclic hydrocarbons caused an increased incidence of SCE only when a metabolizing feeder layer was used, whereas no increase was observed with noncarcinogenic polycyclic hydrocarbons. The other noncarcinogens also did not influence the SCE frequency. Although some chemicals increased the frequency of structural chromosome aberrations, no correlation was found between the frequencies of SCE and aberrations.


Prevention of Rh-hemolytic disease.

Prevention of Rh-hemolytic disease. The results of Anti (D) immunoglobulin (RhoGAM) therapy in 25 Rh-negative women after delivery of Rh-positive babies are presented. None of the patients studied showed evidence of Rh-isoimmunization while two of 51 unprotected patients subsequently had antibodies detected in their serum. The incidence of Rh-negative patients is low in this environment. Because of the potential risk of isoimmunization, RhoGAM prophylaxis is advocated.


Sepsis in the baboon: factors affecting resuscitation and pulmonary edema in animals resuscitated with Ringer's lactate versus Plasmanate. Septic shock and the formation of pulmonary edema were studied in 19 baboons. Four animals served as controls. Four were subjected to deep septic shock by infusion of live E. coli and then deliberately killed while in deep shock. Four were subjected to septic shock, resuscitated with Ringer's lactate (RL), and then killed 11/2 hours after resuscitation was started. Seven were subjected to shock and resuscitation attempted with Plasmanate (PL). Resuscitation with RL was successful for 11/2 hours in all four RL-animals. Resuscitation with PL was successful for 11/2 hours in three of the 7 PL-animals. There was an increased tendency for albumin to extravasate into the interstitium of the lungs after resuscitation. The amount of pulmonary edema, measured by both the thermodye technique and by analysis of post-mortem lung composition, was the same in animals resuscitated with RL and PL. Administration of pure colloid offers no protection to the lungs in resuscitating patients from septic shock.


The effect of sodium salicylate on acute Chagasic myocarditis in C3H mice. In two separate experiments, six months apart, utilizing different controls and different methods, sodium salicylate in anti-inflammatory doses was administered by gavage to mice with acute Chagasic myocarditis (T. cruz) at the onset of parasitemia. Sodium citrate was used as a control. Animals given salicylate showed decreased blood trypanosome counts and myocardial pseudocyst formation, both absolutely and in the rates of formation. Decreased inflammation and necrosis were associated with salicylate therapy. Survival of the animals was not increased by treatment. The effects cannot be explained by sodium ion concentration, the technique of gavage, or any factor except the presence of salicylate ion.


Metabolism of uracil-containing DNA: degradation of bacteriophage PBS2 DNA in Bacillus subtilis. When Bacillus subtilis is infected by the uracil-containing DNA phage PBS2, the parental DNA labeled with radioactive uracil and cytosine remains acid insoluble. If the synthesis of the phage-induced uracil-DNA N-glycosidase inhibitor is prevented, the parental DNA is completely degraded to acid-soluble products beginning at about 6 min after infection. The host N-glycosidase probably initiates the degradation pathway, with nucleases being responsible for the remaining degradation of the DNA.


Prophage F116: evidence for extrachromosomal location in Pseudomonas aeruginosa strain PAO. F116 is a temperate-generalized transducing phage of Pseudomonas aeruginosa. Genetic evidence leads to the conclusion that F116 prophage DNA is maintained extrachromosomally as a plasmid. Preliminary physical evidence is presented to support this hypothesis.


Successful management of ileal conduit-enteric fistula: the case against loopograms. The second reported case of ileal conduit-enteric fistula successfully managed with long-tube decompression and intravenous hyperalimentation is presented. Loopograms are not indicated unless excretory urography is contraindicated or intraperitoneal leakage is suspected.


Computerized cranial tomography. Effect on diagnostic and therapeutic plans. The effect of computerized cranial tomography (CCT) on physicians' diagnostic and therapeutic plans in 194 patients scanned consecutively during a 17-day period at the Massachusetts General Hospital was studied. Use of CCT substantially decreased the perceived need for other neurodiagnostic tests in this patient population. There was a reduction of a least 41% in radionuclide scans, 52% angiograms, and 73% in pneumoencephalograms compared to the needs projected had CCT not been available. Therapy was altered after 37 scans in 36 patients (19% of those examined): new treatment was begun after 15 scans, previously planned therapy became more precise after 9 scans, treatment was found to be unnecessary after 7 scans, and treatment was abandoned as worthless after 6 scans.


Tissue persistence of gentamicin in man. A two-compartment pharmcokinetic model was used to caracterize serum concentrations and to predict tissue accumulation of gentamicin in 47 treated patients. Postmortem tissues were obtained in six cases; in each instance, tissues yielded the predicted amount of drug. Slow release of tissue-bound gentamicin accounts for its prolonged retention in the body. The two-compartment model adequately predicts gentamicin accumulation from serum concentrations and explains why this antibiotic persists in serum and urine.


Problem-oriented approach to practice. I. Economic impact. The problem-oriented system provides a unique management tool for medical practice. It follows basic management principles for any complex human endeavor (ie, define goals, set standards, audit performance to those standards, and assess results). The basic tool is the problem-oriented record, which demands that statements of medical action be explicit to permit audit. This concept can be extended to provide and assess care for an entire practice. Five years of cumulative data were assessed. The following changes were noted: (1) The ratio of patients to physicians doubled. (2) The total hospitalization rate fell by more than 20% and general medical portion by 60%. (3) Ambulatory use and cost decreased by approximately 20%. (4) Expenditures for services fell by 22%, while national expenditures for physician services increased by 28%.


Immunogenetic studies on the rhesus monkey (Macaca mulatta): XI use of blood groups in problems of parentage. A battery of 21 alloimmune blood typing reagents was developed and used for resolving cases of disputed parentage in the rhesus monkey (Macaca mulatta). Using these reagents, the breeding records of a large colony of rhesus monkeys were monitored. Among 1263 complete families typed, 46 (3.6%) disputed parentage cases were discovered by excluding an assigned parent. Of these disputed parentage cases, 76% were resolved and the most probable parents assigned. In addition, the paternity of 63% of the infants born into a man-made troop which included several unrelated adult males was determined. The probability of excluding an incorrectly assigned (randomly chosen) male as a father was calculated as 73% when all 21 reagents are employed.


Correlation of perineal detumescence and ovulation in the pigtail macaque (Macaca nemestrina). A study was made of the relationship between ovulation and perineal detumescence in the pigtail macaque (Macaca nemestrina). Daily laparoscopic examation of both ovaries was made beginning on the 9th day of the menstrual cycle. The appearance of the ovaries was recorded and photographs were taken of the perineum and ovaries. This procedure was repeated daily until the 5th day after ovulation or until the 20th day of the menstrual cycle for presumed anovulatory cycles. The time at which ovulation occurred was correlated with first signs of detumescence, both events occurring within a 24-hour period.


Accidental methyl methacrylate inhalation toxicity in a rhesus monkey (Macaca mulatta). A rhesus monkey (Macaca mulatta), accidentally exposed to vapors of methyl methacrylate for 22 hours was found in a comatose condition. Attempts to revive the animal were unsuccessful. Necropsy revealed a diffusely mottled liver, pulmonary edema, and atelectasis. The thoracic cavities each contained 30 ml of clear yellow fluid. Histopathologic review of the tissues showed central lobular liver necrosis, pulmonary edema, pulmonary emphysema, and atelectasis. Analysis of a blood sample obtained from the monkey 1.5 hours prior to death showed a normal hemogram, but elevated values for serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, lactate dehydrogenase, phosphohexose isomerase, blood urea nitrogen, and serum sodium. The pathologic findings, laboratory results, and clinical history suggested a diagnosis of methyl methacrylate poisoning.


Mode of payment and length of stay in the hospital: more work for PSROs? The Professional Standards Review Organizations (PSROs) mandated by the Social Security Act aim to monitor and control hospital utilization by publicly funded patients, particularly those whose care is paid for by Medicare and Medicaid. One question to ask is, if PSROs prove successful in reducing suspected overutilization by public patients, would the principal private third parties, Blue Cross and commericial insurance plans, benefit by applying those techniques to their patients, as well. Data are presented from the Chicago Hospital Discharge Study, which was conducted in February, 1970, before PSRO activities were undertaken. They show that average length of stay for Medicaid patients is not consistently different from that for patients who pay by other means. Therefore, it is argued that, if it proves successful as applied to Medicaid patients, private third parties might benefit by using the PSRO mechanism to try to monitor and control the stays of their patients, as well.


Distribution of indigenous Lactobacilli in the digestive tract of conventional and gnotobiotic rats. Distribution of indigenous lactobacilli in the gastrointestinal tracts of rats was investigated at the species level. The indigenous lactobacilli isolated from conventional rats were divided into three groups, Lactobacillus acidophilus and its related strains, L. fermentum, and L. murini. Localization of the Lactobacillus groups in the gastrointestinal tracts could be distinguished clearly based on arabinose and glucose fermentation reaction of isolates from each part of the gastrointestinal tract. Group I (L. acidophilus and the related strains) and Group II (L. fermentum) were the major populations of lactobacilli on the walls of the non-glandular part and in the contents of the stomachs of both conventional and gnotobiotic rats. Group I predominated in all the parts of the digestive tract of conventional rats, whereas Group II was in the minority in the lower part of the gastrointestinal tracts of both groups of rats. Group III (L. murini) was the predominant population of Lactobacillus in the lower part of small intestine of conventional rats and in all parts of the gastrointestinal tracts of gnotobiotic rats except for the wall of the non-glandular part of the stomach.


Neonatal necrotizing enterocolitis: 2. Perinatal risk factors. Forty-four infants were diagnosed as having necrotizing enterocolitis (NEC) during a 33 months' period; these represented 4% of all neonatal admissions. An increase in incidence was observed during this period, particularly in low-birth-weight infants weighing under 1,500 g. Perinatal risk factors occurring in infants preceding their onset of NEC are found also to be significantly more common in infants under 1,500 g compared with those between 1,500 and 2,499 g. When the incidence of these clinically associated conditions in infants with NEC are compared with the incidence in infants who did not have NEC in the same birth weight category, a difference can be demonstrated only in 4 out of the 23 analysed: prolonged rupture of membranes with amnionitis; birth asphyxia; hypertonic milk feeds; exchange transfusion. As NEC is possibly a disease of multifactorial aetiology, a multivariant analysis of the data is indicated to define the role of combined perinatal risk factors in the pathogenesis of this disease.


Triplet pregnancy and Rhesus isoimmunization. A case of Rh isoimmunization complicating triplet pregnancy is reported and the rarity of the combination is noted. The management of Rh immunized pregnancy is review with particular reference to problems associated with plural pregnancy. The findings confirm earlier reports that fetal or placental influences as well as antibody titres determine the severity of erythroblastosis.


Heterochromatin of the Drosophila melanogaster Y chromosome as modifier of position effect variegation: the time of its action. Addition of heterochromatin suppresses while subtraction enhances position effect variegation. The heterochromatin-sensitive period has been determined in white/white-apricot variegated eyes of YSWa/Wa; Dp (1,3)W264-58 flies. When such larvae, carrying a Y-short (YS) arm at the distal end of one X chromosome, are X-rayed, mitotic recombination leads to one daughter cell with two YS arms and an adjacent daughter cell with no YS arm. When induced after clonal initiation, the frequency of dark clones developing from daughter cells with two YS arms is significantly higher than the frequency of dark clones in the rest of the eye; and this frequency is even higher when induced before clonal initiation. The modifying action of the Y-heterochromatin is exerted, therefore, during and after clonal initiation. Surprisingly, the frequency of dark clones developing from cells with no YS arm is not lower than the frequency of dark clones in the rest of the eye.


Biogenesis of mitochondria 48: mikamycin resistance in Saccharomyces cerevisiae--a mitochondrial mutation conferring resistance to an antimycin A-like contaminant in mikamycin. Commercial preparations of mikamycin have been shown to act as both inhibitors of mitochondrial protein synthesis and respiration. These preparations are shown to consist of two major streptogramin components (mikamycin A and mikamycin B) and a number of minor components. The major streptogramin components which inhibit mitochondrial protein synthesis in vitro are without effect in vivo due to whole cell impermeability to these compounds. A minor antimycin A-like component is the active compound in mikamycin preparations which inhibits growth of yeast cells on ethanol. The site of this inhibition is at the level of respiratory Comples III. The mitochondrial [mik 1-r] mutation confers resistance to this minor growth inhibitory component and cross resistance to antimycin A. For clarity the designation mik 1 has therefore been renamed ana 1 to denote the mitochondrial determinant conferring resistance to antimycin A. Genetic and physical mapping studies localise the ana 1 determinant in the region of mitochondrial DNA specifying cytochrome b. It is proposed that the ana 1 locus is part of a gene specifying a membrane component of Complex III.


[Importance of the use of the Betatron in combination with other procedures in the treatment of retinoblastoma]. High energy (Betatron) improves the results of retinoblastoma therapy. Among its advantages we should like to mention the following: high doses at the tumour may be reached within a few days; the exact position of the tumour may be determined without half-light; the duration of irradiation is short which permits to keep the patients-mostly children-immoble more easily, and the good general and local tolerance of the irradiation.


Peripheral uveitis in the owl monkey. Experimental model. Primary intravitreous HA injections cause a great variation in ocular inflammatory response, ranging from slight Tyndall effect (LI-HA) to severe inflammation (HI-HA). Both slight and severe inflammation are transient and subside completely within 10-30 days (early inflammatory response), whereas multiple injections ( greater than 3 times) cause a peripheral uveitis, which can be of interest as an experimental model. Control experiments with endotoxin (endotoxin uveitis) fail to produce the same or similar pathological alterations.


[Diabetes and estrogens-gestagens (author's transl)]. The glucose tolerance of the normal woman is not disturbed by oral contraceptives, or only slightly so. In women with a hereditary diabetic taint or diabetic complications during pregnancy, however, the diabetogenic effect is intensified. Estrogens/gestagens (OE-P) are contraindicated in patients with latent diabetes because they may develop an irreversible manifest diabetes. OE-P may be given in manifest diabetes with careful supervision of the blood sugar, lipid levels and the vascular condition. The doses of insulin or oral antidiabetics must often be raised. If the diabetes is not adequately stabilized, the OE-P must be discontinued. Young diabetic women should have their children before the onset of vascular complications. If a diabetic has two living children, surgical sterilization must be given serious consideration.


[Essential labile diabetes (author's transl)]. "Essential labile diabetes" is an insulin-dependent diabetes, in the course of which irregular and unpredictable hyperglycemias, frequently with ketosis, and sometimes serious hypoglycemias alternate. In spite of careful treatment with insulin, diet and suitable hygienic measures, this form of diabetes cannot be influenced. Fortunately, it seldom occurs, not more frequently than in 1 to 2% of diabetics. Various attempts have been made to explain the pathogenesis of this form of the disease. The most probable explanation is that there is an almost complete exhaustion of insulin secretion. This hypothesis is based on the extremely low level of the C peptide below 0.60 ng/ml, whereas in non-labile insulin-dependent diabetics the C peptide amounts to more than 2.2 ng/ml


[Funnel chest and pigeon breast (author's transl)]. The dominant heredity of funnel chest formation is considered proved. The incidence of funnel chest is about 0.05% of the population, with the emphasis on boys. In very many cases deformities of the anterior chest wall are associated with other deformities. All patients with pigeon breast or funnel chest suffer considerably psychically under their deformity. This is the main indication for operation. The best age for operation is from the 2nd to 6th years of life. Conservative methods of treatment are never successful. Of the present day operative techniques, the stabilizing--by implantation of metal clips--are opposed to the nonstabilizing operative procedures. Both achieve equally good and completely satisfactory results in 85% of cases.


[Traffic accidents in childhood--an analysis of 4100 cases (author's transl)]. Every hour a child dies as a result of an accident. Most accidents to children occur between 10.00 and 12.00 in the morning and between 15.00 and 17.00 in the afternoon. 2-6 year-old children are particularly liable to accidents. They make up 50% of all accidents to children. 20% of all accidents occur in traffic; in this group especially, the most deaths and multiple injuries are to be seen. An inquiry among 1000 children revealed that their knowledge of traffic behavior is particularly poor; according to the school standards of assessment, one third of all children would not reach the level of the class in this special field. 52% of all children in cars and 36% of all children on bicycles are in danger of their lives.


[The postcholecystectomy syndrome. Prophylaxis and therapy (author's transl)]. The postcholecystectomy syndrome is no inevitable sequel to operation on the biliary tract. The conditions for the postcholecystectomy syndrome are only created if the patients do not come for operation early, i.e. in good time, because the gall bladder disease has by then become a disease of the biliary tract and consequently the technique of the operation and prognosis have assumed considerably more serious characteristics. The postcholecystectomy syndrome is an internal medical, surgical and general medical problem which is preprogramed by procrastinators.


[Operation for draining the stomach by subtotal pyloro-myectomy with and without dilatation of the mucous membrane (author's transl)]. According to our experiences a pyloroplasty adequate in shape and function can be formed by a separate plastic surgical treatment of the serosa muscularis and mucosa, which can not only be carried out in a very simple way, but if strict attention is paid to its indications and the technical details are adhered to exactly, it also guarantees a complete normalization of evacuation of the stomach without dumping syndrome and duodenal reflux with satisfactory reliability. The necessary intervention consists essentially of a subtotal pyloro-myectomy which is combined with distention of the canal mucous membrane if it is too narrow.


[Surgical treatment of cerebral ischemia. Indications for surgery in carotid artery stenosis (author's transl)]. Reconstruction of carotid arteries should preferably be a prophylactic measure and only in exceptional cases a therapeutic procedure. The best results are seen in stage I (asymptomatic) or in stage II (transient ischemic attacks). Surgical intervention in acute cerebral vascular insufficiency is indicated only with a conscious patient with a negative brain scan and without progressing symptoms (stage III a). In stage IIIb (progressive stroke) and stage IVa (acute completed stroke) operative treatment is contraindicated because of a high mortality rate. In accidents with persisting neurologic symptoms (completed stroke more than 2 weeks old) necessary reconstruction of the contralateral vessel is indicated.


[Covering defects by free grafting of skin and soft tissue with microvascular anastomoses (author's transl)]. The technique of free tissue transplantation with microvascular anastomoses in 3 patients is presented. Transplants consisting of skin and subcutaneous tissue from the groin with the superficial circumflex iliac artery and the superficial epigastric artery were used to cover defects over the calcaneum and to treat a scalping wound of the head, and a transplant from the dorsum of the foot with the A. dorsalis pedis and accompanying sensory nerves to the palmar surface of a hand following a third degree burn. Eight of a total of 13 transplants with microvascular connections healed completely. Partial necrosis occurred three times and total necrosis twice.


[Therapy of malignant tumors of the thyroid]. Early detection is still the most urgent concern for the successful treatment of carcinoma of the thyroid. A considerable obstruction to early tumor recognition in Germany is the still much too frequently recorded "endemic goiter". A consistent general goiter prophylaxis by iodization of the domestic salt may also have a favorable influence on tumor diagnosis. The basis for an exhaustively planned treatment of "struma maligna" is the histomorphological classification of tumors. By radical surgical intervention and the selective application of isotope and megavolt irradiation and obligatory prescription of thyroid hormone the treatment results, especially in the differentiated thyroid carcinomata, can be improved to 10-year survival rates of more than 85%.


[Treatment of breast cancer (author's transl)]. Controlled trials and long term studies in patients with breast cancer of stage I and II have shown, that this disease in the majority of cases is no longer localized when first noticed clinically. Surgical therapy is therefore only a part of the complete management of these patients and must be thought over concerning its radicality. In England several controlled studies are under way for that reason. They are conducted and continuously evaluated by multidisciplinary teams of which the surgeon is an important member.


[Changed aspects of gastric cancer (author's transl)]. In our western countries gastric cancer is no longer a local disease when first diagnosed in more than 55% of patients. Fairly extensive experience with extended radical procedures has failed to demonstrate any significant improvement in the 5-year survival rate. Moreover, increased operative morbidity and mortality have even aggravated our results. Subtotal gastrectomy (Billroth II) is therefore recommended for the carcinoma of the antrum, total gastrectomy (with interposition of jejunum) for carcinoma of the cardia and selected cases. Our current goal should be greater efforts towards early diagnosis to reach the results of Japanese surgeons with "early superficial cancer" of the stomach.


[New thoughts on diabetes mellitus (author's transl)]. The significance of genetic factors in the origination of a diabetes mellitus is generally recognized. Besides this, the possibility of a virus etiology and an autoimmune etiology is discussed. The numerous very complex actions of insulin on the cells of liver, muscle and other organs take place with the assistance of special receptors, the number of available receptors probably being important. A great advance in therapy is the development of the monocomponent insulins. They are primarily indicated in the labile forms, especially in infantile and juvenile diabetes, in insulin resistance, for high antiinsulin titiers, insulin allergy, lipoatrophy and microangiopathy. We must wait and see how far transplantation of a pancreas or Langerhans islet cells or the "artificial" pancreas can be used in future treatment.


[Diabetic angiopathy. A new concept of pathogenesis (author's transl)]. In juvenile diabetes there is a renal hypertrophy: glomerular volume and capillary lumen of the individual glomeruli are about twice the size of healthy ones. The hypertrophy is associated with a hyperfunction (increased glomerular filtration and tubular reabsorption). If the diabetes is strictly controlled these changes may regress, which suggests a metabolically induced hypertrophy. Long-standing diabetes is characterized by a phase of intermittent proteinuria which gradually becomes permanent. Diabetic angiopathy is the result of many years of abnormal metabolism, presumably with involvement of the growth hormone and glucose. Whereas microangiopathy is considered specific for diabetes, it is still a matter for discussion whether a diabetic macroangiopathy exists. The results of numerous investigations suggest that it does.


[Hyperosmolar coma in diabetes (author's transl)]. Diabetic hyperosmolar coma is characterized by the appearance of a diabetic metabolic state in middle age, lack of ketosis, osmolarity of the plasma greater than 350 milliosmoles, psychic and neurological disturbances, increased occurrence of secondary diseases, arterial thromboses, azotemia. The mortality is 30-60%. The pathogenesis is still uncertain in many respects, consequently the suggestions for therapy are varied. The authors have found the following procedure useful: rapid compensation of sodium deficit, restoration of water balance, normalization of the composition of body fluids by reference to continuous laboratory investigation.


[Diabetes and pregnancy (author's transl)]. The metabolic and hormonal adaptation of the maternal organism in pregnancy, the glucose dependency of the fetus, the adaptation of the fetus to the pregnancy and the clinical consequences of the adaptation are important aspects of pregnancy in diabetics. Hyperglycemia in the mother possibly leads to a fetal anoxia by reducing the oxygen in the maternal hemoglobin and at the same time to a hyperglycemia of the fetus which causes hyperinsulinism. The consequences of hyperinsulinism are, inter alia, adiposity and respiratory insufficiency in the child due to hyaline membranes. Insulin treatment of the mother before and during pregnancy in order to normalize the blood sugar level is consequently absolutely essential to prevent such complications.


[The hemophiliac as a surgical patient (author's transl)]. In the Surgical Clinic of the University of Munich, 23 surgical interventions were performed on 20 hemophiliac patients between 1967 and 1976. There were 13 emergency and 10 elective operations. The spectrum ranged from removal of atheroma to subtotal gastric resection. For adequate substitution of factors a comprehensive preoperative "hemostasis profile", selection of a suitable preparation and postoperative supervision with coagulation analysis are necessary. Despite a normalization of the hemostasis, atraumatic surgical technique is particularly important. Risks of substitution therapy are primarily hepatitis, allergic reactions and the appearance of inhibitors. Whereas, especially using low-fibrogenic substrates, the operative risk is not essentially increased, in our experience the patients seem to be endangered particularly by infection and septic complications.


[TSH state after thyroid hormone deprivation in athyrotic thyroid cancer patients (author's transl)]. The duration of thyroid hormone deprivation necessary on the one hand to achieve a sufficiently high endogenous TSH level for the identification of 131I-storing metastases or local relapses, and on the other hand to keep the consequences of thyroid hormone deprivation as low as possible, was determined in 111 athyrotic patients with thyroid carcinoma by means of the basal TSH level or a TRH stimulation test. From the first follow-up examination, a T3 deprivation of 8 days is to be recommended. Low basal TSH levels and marked stimulation in the TRH test should be sufficient cause to prolong the T3 deprivation to 10 days with further examinations. After a longterm suppression of athyrotic patients with thyroid hormone, a decrease in the TSH rise was observed in the course of 2 years, after appropriate interruption of the substitution.


[Neurological complications after influenza vaccination (author's transl)]. The clinical aspects and differential diagnosis of 11 neural complications following influenza vaccination (Guillain-Barré syndrome, serogenetic polyneuritis, encephalomyelitis) are discussed. Etiopathogenetically a hypersensitivity to components in the serum must be taken into consideration, as a case with anaphylactoid reaction shows. The incubation period of the remaining cases (beginning only after the 4th day post vaccination) is on the other hand consistent with the assumption of a pathomechanism rather like that of serum sickness. The number of influenza vaccinations previously administered in the individual case bears no relation to the neurological disturbances described. Vaccines of different manufacture can, in the same way, provoke these rare inoculation complications (frequency: 1 case per 0.7-1.3 mio vaccinations). The indication for influenza vaccinations is not limited by these occurrences.


Mutagenicities of N-nitrosamines on Salmonella. The mutagenic activities of 11 N-nitrosamines were tested using Salmonella typhimurium TA100 and TA98. All the carcinogenic N-nitrosamines were mutagenic on TA100 with a drug-activating system from the rat liver, whereas N,N-diphenylnitrosamine, a non-carcinogen, was not mutagenic. None of the N-nitrosamines was mutagenic on TA98, except N,N-diethylnitrosamine which was weakly mutagenic. To detect the mutagenicity of N,N-dimethylnitrosamine, the pre-incubation of bacteria and N,N-dimethylnitrosamine with S-9 Mix before if was poured onto plates was obligatorily required. Dimethyl sulfoxide inhibited the mutagenic effect of N,N-dimethylnitrosamine.


Mutagenicity of four hair dyes in Drosophila melanogaster. The hair dye constituents p-phenylenediamine, 2,4-diaminoanisole sulfate, 2,4-diaminotoluene and 4-nitro-0-phenylenediamine were tested for mutagenicity in Drosophila melanogaster. The compounds were given orally to adult males. The induction of sex-linked recessive lethal mutation was used as a measure of mutagenicity. All four of the dyes tested were mutagenic with a peak mutagenic activity in metabolically active germ cells (spermatids and spermatocytes).


Mutagen screening by a simplified bacterial fluctuation test: use of microsomal preparations and whole liver cells for metabolic activation. We describe the use of a simplified bacterial fluctuation test to detect induced mutation, either incorporating liver microsomal or whole liver cell preparations. We have evaluated both types of test using three agents. The fluctuation assay seems somewhat slower, simpler and more sensitive than a conventional plating test with microsomes. A whole cell preparation appears marginally more effective than a microsomal fraction for metabolic activation of 9,10-dimethyl-1,2-benzanthracene, but rather less effective for benz(a)pyrene and 2-acetamidofluorene. Ultimately the usefulness of activation by whole cells may depend upon whether the method can give a correlation with carcinogenicity that is more quantitative than microsome methods and better reflects organ and species specificity.


Vinyl chloride mutagenesis in Drosophila melanogaster. In inhalation experiments, Drosophila males were exposed to vinyl chloride at concentrations of 200, 850, 10,000 30,000 or 50,000 ppm for 2 days, and to 30 or 850 ppm for 17 days. VCM was mutagenic in the recessive-lethal test both after short-term and long-term exposures. The lowest effective concentration (LEC) was 850 ppm after 2 day exposure, and this value could be lowered to 30 ppm by prolonging the exposure time to 17 days. With the concentration levels tested, the mutation frequency increased with concentrations and reached a plateau at 10,000 ppm. This indicates a substrate saturation effect. In contrast with the recessive lethal assay, negative results were obtained when tests on dominant lethals, translocations, entire and partial sex-chromosome loss were carried out with VCM at 30,000 ppm for 2 days. This finding of a false negative seems a logical consequence of the observed saturation effect, and strengthens the concept that there exist two effective concentrations for point mutations vs the induction of chromosome breakage events. Vinyl chloride monomer provides another example to support our view that chromosome breakage is not a reliable measure of mutagenic activity.


Acute leukemia after alkylating-agent therapy of ovarian cancer. To estimate the leukemogenic potential of alkylating agents, we surveyed 70 institutions using these drugs for the frequency of second cancers in patients with advanced ovarian cancer. Thirteen cases of acute nonlymphocytic leukemia occurred among 5455 patients, as compared to 0.62 cases expected (relative risk = 21.0). All 13 had received alkylating agents. Nine also received radiotherapy. The relative risk for patients given chemotherapy was 36.1 and rose to 171.4 for those surviving for two years (rate = 13.75 per 1000 patients per year). To evaluate the role of therapy versus underlying disease, a historical control of 13,309 patients with ovarian cancer in the National Cancer Institute's End Results Program was analyzed. No excess of leukemia was noted in this group, even among 6596 women receiving radiation. The excess of acute nonlymphocytic leukemia, therefore, appears attribute to alkylating agents, although the effect may be enhanced by exposure to radiation, as previously suggested for Hodgkin's disease.


Diabetic ketoacidosis: low-dose insulin therapy by various routes. Since in normal persons the hypoglycemic effect of low-dose intramuscular exceeds that of subcutaneous insulin we studied the effect of routes of insulin therapy in diabetic ketoacidosis. Forty-five patients with diabetic ketoacidosis entered a randomized prospective protocol with insulin administered either intravenously, subcutaneously or intramuscularly. Initial priming dose of insulin had to be repeated in two of 15, three of 15 and six of 15 of the intravenous, subcutaneous and intramuscular groups respectively. The intravenous group had a more rapid fall in plasma glucose (P less than 0.01) and ketone bodies (P less than 0.05) during the first two hours. Thereafter, there were no significant differences in the rate of decline of plasma glucose or ketones nor in the time required for glucose to reach 250 mg per deciliter or for complete recovery from diabetic ketoacidosis. The data confirm the efficacy of low-dose insulin therapy for diabetic ketoacidosis and indicate that the optimal route of insulin administration is by initial intravenous combined with subcutaneous or intramuscular.


[Radiometric determination of 11 carbamate pesticides in the nanogram and subnanongram ranges by means of cholinesterase inhibition]. This method for determining carbamates is based on the inhibiting action of these substances on acetylcholinesterase activity. The use of radioactively labelled acetylcholine as a substrate, the ensuing extractive separation of the radioactive acetic acid (formed by hydrolysis) and its radiometric determination permit to detect very small amounts of carbamates. The limit of detection for aldicarb, baygon, benomyl, bux, carbaryl, CIPC, matacil, phenmedipham and promecarb lies in the picogram range; that for barban and methomyl, in the nanogram range. The lower, linear parts of the curves for the different carbamates fall within the range 0.001-10 ng. The sensitivity (expressed as delta% inhibition/delta lg ng carbamate) ranges from 1.0 to 9.7.


Proposals for national health insurance in the USA: origins and evolution, and some perceptions for the future. Reliance upon private and voluntary efforts in health insurance has proved to be inadequate as the promise of medical science has become socially more complex, expensive, and elusive. The real, even if discontinuous, movement toward public and compulsory approaches to national health insurance is accelerating. Any program with reasonable promise of success must achieve both cost controls and systems improvements. Of the proposals before Congress, only one offers assurance that the good in the present system of care will not continue to be an enemy of the better system for the future.


[Long-term clinical study of a new molecule (nifedipine) in ischemic cardiopathy]. Results with a new anti-angina molecule (nifedipine: Adalat) in the long-term management of 28 patients with ischaemic heart disease are presented. The effectiveness of the drug was judged outstanding on the strength of its reduction of angina outstanding on the strength of its reduction of angina crises and consumption of NTG beads. Non side-effects were noted.