Evaluation of a new antihelminthic for trichuriasis, hookworm, and stronglyloidiasis. Mebendazole was tested in a double-blind trial for its efficacy in the treatment and control of enteric helminths. One hundred and twenty-two children from a community near the Gulf of Carpentaria, and from a community in Cape York Peninsula in northern Queensland were divided into two equal groups to receive a course of either mebendazole or placebo after the identification of one or more intestinal helminths in a single pretreatment specimen of faeces. Between the tenth and twentieth days after a four-day course of treatment, three specimens of faeces were collected from each child. Mebendazole cured trichuriasis in 75% of cases, and over-all egg reduction rate was 96%. The drug also cured hookworm in 13 out of 15 cases and Strongyloides sterocoralis infestation in 14 out of 21 cases. Mebendazole was ineffective against Hymenolepis nana. No cases of Ascaris lumbricoides infestation were present. No side effects or adverse reactions to the drug were noted and patient acceptance was excellent. Mebendazole appears to be a safe drug for use in the treatment of human parasitic intestinal nematode infestations, and should be especially useful in the treatment and control of trichuriasis.


[Diagnostic relevance of thermography in renal transplantation (author's transl)]. During a followup period of 18 months 75 renal transplant recipients were examined by thermography according to Tricoire. Thermography is a not invasive, quickly available and reproduceable method. Because of the high incidence of 85% exact diagnoses this investigation is a helpful additional test in kidney transplantation for evaluation of graft function as well as for diagnosis for evaluation of graft function as well as for diagnosis of pathological intrarenal or perirenal disorders. Thermography is especially recommendable for transplant patients, if postoperative haemodialysis is necessary. In these cases information can easily be obtained whether postoperative olig-anuria is caused by acute tubular necrosis or by primary insufficient vascularisation of the transplant.


[Echinococcosis.--Current problems of diagnosis and epidemiology (author's transl)]. The indirect hemagglutination-test (IHA) and the indirect immunefluorescence-test are two modern methods for the serological diagnosis of an echinococcosis. If both tests are employed, the disease can be diagnosed with great reliability. A titer of 1 : 128 in the IHA makes the diagnosis of an echinococcosis very likely; a titer exceeding 1 : 1000 is significant. Serological tests of 36 patients with E. cysticus and  E. alveolaris are evaluated; the interpretation of the results is discussed. In all patients the diagnosis was established between October 1977 and October 1978. In Germany the complement fixation test is commonly used to diagnose an echinococcosis. This test, however, is unreliable and fails in one third of all cases. It should be--as well as the Casoni skin-test--replaced by more sensitive and specific reactions. If the complement fixation test is positive, it might be used for postoperative controls. Compared to previous years the disease-rate among Germans is rising. The main reason seems to be the increasing tourism to foreign countries. Serological tests in small laboratories are unreliable and make an evaluation difficult. The diagnosis should be established in specialized centres.


A comparative trial of daunorubicin, cytosine arabinoside, and thioguanine, and a combination of the three agents for the treatment of acute myelocytic leukemia. In this study 523 previously untreated patients with acute myelocytic leukemia were randomly allocated to induction therapy with daunorubicin 60 mg/M2 daily X 3, cytosine arabinoside and thioguanine 100 mg/M2 each every 12 hours until marrow hypoplasia was achieved, or a 5-day course of the three drugs with daunorubicin 100 mg/M2 given on dav 1 and cytosine arabinoside plus thioguanine each given at a dose of 100 mg/M2 every 12 hours for five days. All patients received cyclophosphamide 600 mg/M2 followed in 24 hours by hydroxyurea 500 mg/M2 every six hours for four doses monthly for maintenance therapy. Patients were randomized to receive one of three antimetabolite treatments beginning 24 hours after the last dose of hydroxyurea each month for seven days. One such treatment consisted of 6-mercaptopurine 100 mg/M2 daily, another group received 6-thioguanine at the same dose daily, and the third group received 50 mg/M2 of both antimetabolites daily. There were no significant differences in complete response rate, remission duration, or survival among the various treatment groups.


Recent results on how aminoacyl transfer RNA synthetases recognize specific transfer RNAs. Aminoacyl tRNA synthetases discriminate between tRNA species by a highly specific mechanism. Physical and chemical studies indicate that the synthetases bind along and around the inside of the three-dimensional L-shaped tRNA structure. Studies of mutant tRNAs that affect synthetase interaction tend to confirm this conclusion. However, in contrast to proteins that recognize a specific block of contiguous nucleotide units (e.g., repressors, restriction enzymes, etc.), synthetases appear to interact with spatially disperse elements of the structure. Available evidence suggests that tRNA binding clefts on various synthetases may be roughly similar, with specificity being achieved by the choice of amino acid residues in a few critical positions in the tRNA binding clefts. With this idea in mind, it should be possible to introduce amino acid substitutions into the binding clefts and thereby change tRNA recognition specificity. This has been attempted (by genetic manipulations) and a mutant alanine tRNA synthetase with altered tRNA recognition has been isolated. This enzyme can attach alanine to isoleucine specific tRNA. When presented with valine specific tRNA, a tRNA similar in some structural features to the isoleucine specific tRNA, or with the structurally quite different tyrosine specific tRNA, no significant aminoacylation occurs. Thus, a precise specificity alteration can occur through mutation; this result supports the idea of similarities in synthetase binding clefts, with specificity being achieved by the positioning of amino acids at critical positions in these clefts. Finally, further data have been obtained on the issue of possible transient covalent bond formation between synthetases and tRNAs, as a critical part of the interaction.


Mitochondrial glucose-6-phosphate dehydrogenase from Saccharomyces cerevisiae. In Saccharomyces cerevisiae, a small proportion of the glucose-6-P dehydrogenase activity is firmly associated with the mitochondrial fraction and is not removed by repeated washing or density-gradient centrifugation. However, the enzyme is released by sonic disruption. Mitochondrial glucose-6-P dehydrogenase that is released by sonication and partially purified has been found to be similar to cytosol glucose-6-P dehydrogenase with respect to electrophoretic mobility, isoelectric point, pH optimum, molecular size, and apparent KM's for NADP+ and glucose-6-P. These results indicate that a single species of glucose-6-P dehydrogenase is synthesized in S. cerevisiae and that the enzyme has more than one intracellular location. Mitochondrial glucose-6-P dehydrogenase may be a source of intramitochondrial NADPH and may function with hexokinase and transhydrogenase to provide a pathway for glucose oxidation that is coupled to the synthesis of mitochondrial ATP. A constant proportion of total glucose-6-P dehydrogenase activity remains compartmented in the mitochondrial fraction throughout the growth cycle.


[Nature of the heterogeneity of the 30S ribosomal subunits in vitro. II. Two types of inactivation of the 30S subunits of Escherichia coli ribosomes]. The influence of concentration of monovalent cations on the binding constant of Phe-tRNAPhe to 30S.poly(U) complex was studied. Two types of inactivation of the 30S subunits by ammonium ions at the low magnesium concentration (1 mM) were found. The first type of inactivation was observed at high concentrations of NH4+ ions (from 0.5 to 1.5 M) and due to the dissociation of ribosomal proteins from 30S subunits. This inactivation only decreased the binding constant of Phe-tRNAPhe to 30S.poly(U) complex up to 50 times but all 30S subunits were equally achieved in Phe-tRNAPhe binding. This type of inactivation was reversible, addition of S-proteins restored the association constant to the original value. At low concentration of NH4+ ions (below 100 mM) about half of the 30S subunits is irreversibly inactivated (the binding constant of Phe-tRNAPhe decreased below detectable level) probably as a result of conformational changes in ribosomal RNA. Both types of inactivation of the 30S subunits can take place during the preparation of isolated subunits of ribosomes.


[Molecular organization of eukaryotic informational RNA]. The review is devoted to the last achievments in the field of the molecular structure of individual eukaryotic mRNAs. The 3'-terminal poly(A) sequence is described as well as the ways of its posttranscriptional addition and degradation. Various suggestions are made concerning the function of poly(A) in mRNAs. The structure of modified and blocked 5'-terminus of mRNA molecule is described in detail. The chemical reactivity of these modified structures (caps) and their sensitivity to enzymatic degradation are characterized as well as the reaction sequence resulting in cap formation and the possible functions of caps in the control of mRNA translation and life time. The primary structure of the 5'- and 3'-untranslated regions and of translated parts of several individual mRNAs is described.


[Influence of the modification of Phe-tRNA synthetase from Escherichia coli by lysine- and arginine-specific reagent on the ionic interactions of the enzyme with tRNA Phe]. The influence of modification of Phe-RSase from E. coli MRE-600 by lysine- and arginine-specific reagent 2,4-pentandione on the Phe-RSase.tRNAPhe interactions was investigated. It was shown that modification of Phe-RSase with 2,4-pentandion leads to a decrease of the aminoacylation rate without any influence on the value of Km for tRNAPhe in this reaction and only a slight increase of the value of Kdiss for Phe-RSase.tRNAPhe complex. The log Km (Km-1)--ionic strength dependence for native enzyme and log Kdiss (K-1diss) for native enzyme and two forms modified on arginine and lysine residues were investigated. Results were interpreted quantitatively by Debye--Huckel approximation for two spherical macroions and by Daune approximation assuming that the region of tRNA implicated in ionic interactions is locally a cylindrical polyelectrolyte. It was shown that there are 2-4 electrostatic contacts in Phe-RSase.tRNAPhe interactions in limits of both approximations; modification of arginine residues in Phe-RSase doesn't change the number of electrostatic contacts, modification of lysine residues leads to an increase in the number of contacts. It was assumed that there are lysine residues in Phe-RSase essential for the tRNAPhe recognition. The possibility of participation of negative amino acid residues in electrostatic interactions with tRNAPhe is not excluded.


[Physico-chemical characteristics of ribosomal proteins L10 and L11]. The procedure of isolation and purification of ribosomal proteins L10 and L11 from the 50S subparticle of E. coli ribosomes is described. Sedimentation data, spectra of circular dichroism and the results of microcalorimetric studies are given for these proteins. It has been shown that in the range of the concentrations studied protein L11 does not associate in solution. Protein L10 has a tendency to self-association at increased concentrations (over 1.5 mg/ml). Protein L10 also forms a complex with the intact ribosomal protein L7. From the data presented it follows that protein L7 binds to protein L10 in a dimer form and the regions of L7 responsible for its dimerization participate in binding. It has been also shown that the proteins in solution have a rather low thermostability. An assumption is made on the stabilization of proteins within the ribosomes or in the complex with other ribosomal proteins.


Aspergillus nidulans as a test organism for assessing radio-induced chromosomal non-disjunction. A genetically marked heterozygous diploid of Aspergillus nidulans was synthesized and the feasibility of using this system for the simultaneous estimation of radio-induced mitotic crossing-over and non-disjunction has been investigated. In the case of the latter, serious experimental problems have been encountered. Nevertheless, induction curves for non-disjunction with 15-MeV electrons, 50-kVp X-rays, beta-particles and alpha-particles are presented showing an increase in non-disjunction with increasing LET.


[Interaction of oligophosphates of pyridoxal with certain enzymes of polynucleotide synthesis]. The interaction of pyridoxal, pyridoxal-5'-mono-, di- and triphosphate with certain enzymes of polynucleotide synthesis (DNA-dependent RNA polymerase, DNA-dependent DNA polymerase I and polynucleotide phosphorylase from Escherichia coli and terminal deoxyribonucleotide transferase from calf thymus) was studied. All compounds tested was found to be reversible and competitive inhibitors of these enzymes. The reduction of the enzyme-inhibitor complex with NaBH4 gives rise to the complete irreversible inhibition of the enzymes under study. The comparison of the inhibition constants for pyridoxal and its phosphorylated derivatives with those for mono-, di- and triphosphates of nucleosides was carried out for the enzymes. The results obtained suggest that the modified epsilon-amino-group of lysine residue should be localized at the catalytic site in the vicinity of the pyrophosphate binding area of an enzyme.


[Transcription of synthetic oligonucleotides]. The decadeoxynucleotides d(pTTC)3 and d(CCATCTTTT) transcription by E. coli RNA-polymerase was studied. The nucleotide composition of d(pTTC)3 transcript was shown to be consistent with that of the template, but RNA-product was several times longer than the template. With nonanucleotide d(CCATCTTTT) the poly(A) synthesis was observed. This fact may be attributed to the reiteration on the TTTT-cluster. When using the oligonucleotide primers d(pGGA) and r(pAAAA) complementary to the templates d(pTTC)3 and d(CCATCTTTT), accordingly, the nucleosidetriphosphates concentration being reduced and the RNA-polymerase "holo" being replaced by "core", the considerable decrease in the unhomogeneity of the transcript length and in the length itself was found. With d(pTTC)3 as a template the length of RNA-product was found to be of 24-25 nucleotides and with d(CCATCTTTT) it was of 18-19 nucleotides. The sequence of RNA transcribed from both templates in the presence of primers was in accordance with the structure of templates.


Radiation-induced mitotic and meiotic aneuploidy in the yeast Saccharomyces cerevisiae. A number of genetic systems are described which in yeast may be used to monitor the induction of chromosome aneuploidy during both mitotic and meiotic cell division. Using these systems we have been able to demonstrate the induction of both monosomic and trisomic cells in mitotically dividing cells and disomic spores in meiotically dividing cells after both UV light and X-ray exposure. The frequency of UV-light-induced monosomic colonies were reduced by post-treatment with photoreactivity light and both UV-light- and X-ray-induced monosomic colonies were reduced by liquid holding post-treatment under non-nutrient conditions. Both responses indicate an involvement of DNA-repair mechanisms in the removal of lesions which may lead to monosomy in yeast. This was further confirmed by the response of an excision-defective yeast strain which showed considerably increased sensitivity to the induction of monosomic colonies by UV-light treatment at low doses. Yeast cultures irradiated at different stages of growth showed variation in their responses to both UV-light and X-rays, cells at the exponential phase of growth show maximum sensitivity to the induction of monosomic colonies at low doses whereas stationary phase cultures showed maximum induction of monosomic colonies at high does. The frequencies of X-ray-induced chromosome aneuploidy during meiosis leading to the production of disomic spores was shown to be dependent upon the stage of meiosis at which the yeast cells were exposed to radiation. Cells which had proceeded beyond the DNA synthetic stage of meiosis were shown to produce disomic spores at considerably lower radiation doses than those cells which had only recently been inoculated into sporulation medium. The results obtained suggest that the yeast sustem may be suitable for the study of sensitivities of the various stages of meiotic cell division to the induction of chromosome aneuploidy after radiation exposure.


[Construction of optimal alignment of two amino acid sequences: a solution of the problem of unnecessary gaps]. A computing method for calculation of total similarity of two amino acid sequences depending on the number of gaps introduced into these sequences has been developed. It was based on Needleman--Wunsch--Sankoff's principles. The application of the method to randomized sequences enables us to select the optimal alignment of real sequences, in which the number of gaps is statistically justified. In this paper an example of the application of this approach is described and the statistically optimal alignment of somatotropin and prolactin amino acid sequences with two gaps is suggested.


The induction of sex-chromosomal nondisjunction and diploid spermatids following x-irradiation of pre-spermatid stages in the northern vole Microtus oeconomus. Chromosome nondisjunction seems to be one of the most important mutagenic effects occurring in man and makes an enormous contribution to human foetal wastage. As yet, little or no information is available on which environmental factors are important in inducing nondisjunction and accordingly we have investigated the effect of X-irradiation on inducing nondisjunction in male germ cells of an experimental mammal, the Northern vole-Microtus oeconomus. Using a staining technique based upon the presence of heterochromatin we have scored the number of sex chromosomes in early spermatids in both irradiated and unirradiated animals. A significant increase in nondisjunction, following treatment, was found with all doses between 25 and 200 R. However, variations in nondisjunction induction at various time intervals following irradiation suggest variations in cell stage sensitivity. More surprising was the large induction of diploid gametes which also demonstrated a significant induction with all irradiation doses. From the distribution of sex chromosomes we conclude that both nondisjunction and diploid gamete induction occur at both meiotic divisions. At present it is not possible to conclude whether the radiation response is linear and to define the cell-stage sensitivity with precision. The reasons for this appear to be variations in sensitivity between animals and also that there is a clear overlap between the duration of the early spermatid stage analyzed (4 days) and the interval between sampling times.


Evaluation of three metabolic activation systems by a forward mutation assay in Salmonella. The strain SV3 of Salmonella typhimurium was used as the indicator bacterium in the intrasanguineous host-mediated mutagenicity assay. Bacterial distribution and spontaneous mutation frequency were determined after intravenous injection of SV3 into CD1 male mice. Bacteria were cleared at an exponential rate from the blood stream and recovered mainly from the liver and in smaller quantities from the lungs and kidneys. No bactericidal effect was observed during incubation within the animal, and bacterial division occurred in the liver and probably in the kidneys. The significance of an increased mutation frequency of bacteria recovered from untreated animals is discussed. Mutation induction was measured in bacteria recovered from liver, lungs and kidneys of CD1 mice and CD rats treated with dimethylnitrosamine (DMN). The sensitivity of the intrasanguineous host-mediated technique was compared with the sensitivity of the assay in vitro with microsomal preparations from each tissue and host. Activation by isolated perfused liver and lungs from CD rats was included for comparison with the results from experiments in vivo and in vitro.


[Oligoadenylate 4-(N-2-chloroethyl-N-methylamino) benzylidene 5'-phosphamides complex formation with DNA by equilibrium dialysis]. Alkylating derivatives of oligoadenylate 5'-phosphamides CIRCH2NH(pA)n n=4-7 attach to complementary regions of denatured E. coli DNA. Apparent binding constants Kapp are evaluated from plots of binding at 0 degrees obtained by equilibrium dialysis. Kapp of CIRCH2NH(pA)7 is shown to be similar to that of (Ap)5ARCl-benzylidene derivatives of hexaadenylate; Kapp both of them differ from Kapp of hexaadenylate only slightly. Under saturation conditions CIRCH2(Ap)7 binds to 24 sites per 10 kilobases of E. coli DNA. Macrostructure of denatured DNA is changed in the course of binding and number of burned complementary sites becomes exposed to following binding with the oligomer.


The micronucleus test: statistical design and analysis. Alternative statistical procedures are discussed which may be employed to compare the incidences among treatment groups of micronucleated polychromatic and normochromatic erythrocytes and their ratios. Comparison of incidences of micronucleated polychromatic erythrocytes using a sequential sampling strategy based on the negative binomial distribution is shown to require fewer animals for the same sensitivity of test than a similar procedure based on the binomial distribution. The sequential test is superior, both in power and number of animals required, to an alternative 1-stage test based on the same distribution. The procedure described permits the investigator to optimize the number of animals in each test group and the number of cells counted per animal to detect a predetermined increase in the incidence of micronucleated cells over that observed in the control population within chosen limits of type I and type II error. An alternative sequential approach based on the binomial distribution is presented, which is applicable when the number of cells analyzed per animal is variable.


Mutagenic activity of propylene oxide in bacterial and mammalian systems. Propylene oxide is used extensively in the chemical and food manufacturing industries, but relatively little is known of its ability to interact with genetic material. Studies were undertaken to investigate its ability to induce gene mutations and primary DNA damage in bacteria and chromosomal damage in mammalian cells. The induction of base-substitution mutations was demonstrated in spot tests with strains of Salmonella typhimurium and Escherichia coli at 700 micrograms/plate of propylene oxide; inclusion of a preparation of rat-liver microsomes and cofactors (S9 mix) was without significant effect on this response. A linear dose--response relationship was recorded in plate tests with S. typhimurium strains TA100 and TA1535 over the range 100--750 micrograms/plate. After addition to dividing lymphocytes in cultures established from human peripheral blood, propylene oxide caused dose-related chromosomal damage, detected at 1.85 and 9.25 micrograms/ml. Oral administration of propylene oxide at 2 x 100, 2 x 250 or 2 x 500 mg/kg to male mice produced no detectable increases in the incidence of micronucleated, polychromatic erythrocytes in bone marrow. A male mouse dominant lethal test employing oral doses of 50 or 250 mg/kg/day for 14 days gave no evidence of mutagenic action on sperm. Intraperitoneal injections of propylene oxide at 2 x 300 mg/kg induced increased numbers of micronucleated erythrocytes in mice, but lower doses given by this route had no such effect. Possible reasons for the contrasting findings in vitro and in vivo are discussed.


Diethylstilbestrol and 11 derivatives: a mutagenicity study with Salmonella typhimurium. Diethylstilbestrol was tested for mutagenicity with his- S. typhimurium strains under 10 different matabolic situations (no exogenous metabolizing system; S9 mix from liver homogenate of rats induced with Aroclor 1254, with or without inhibition of epoxide hydratase; liver and/or kidney S9 mix from control or hamsters treated with Aroclor 1254; horse-radish peroxidase + H2O2). Under none of these conditions did diethylstilbestrol give any indication of a mutagenic effect. Furthermore, 11 metabolites and other derivatives of diethylstilbestrol, 2 of them potent inducers of sister-chromatid exchange in cultured fibroblasts, were not mutagenic with any of the 4 tester strains (S. typhimurium TA100, TA98, TA1537, TA1535) in the presence or absence of S9 mix from liver homogenate of rats induced with Aroclor 1254. Thus, one of the few known human carcinogens is very resistant to detection by the mammalian enzyme-mediated Salmonella typhimurium mutagenicity test (Ames test). This is especially remarkable since the metabolizing systems used included: (1) some of very high metabolic activity (S9 mix from liver homogenate of rats and hamsters induced with Aroclor 1254); (2) metabolizing systems from organs susceptible to the carcinogenic activity of diethylstilbestrol (hamster kidney); as well as (3) a mixture of (1) and (2) in case both activities are required for the carcinogenic effect in the whole animal.


Mutagenicity of aminophenyl and nitrophenyl ethers, sulfides, and disulfides. The mutagenic activity of several aromatic amines and aromatic nitro compounds related to 4,4'-methylenedianiline towards Salmonella typhymurium tester strains TA100 and TA98 was evaluated. The heteroatomic analogs of 4,4'-methylenedianiline which include aminophenyl and nitrophenyl ethers, sulfides and disulfides were assayed in the presence of rat-liver homogenate. The relative mutagenic response of these analogs indicated the following order of activity, --S-- greater than --O-- greater than --CH2--CH2-- greater than or equal to --S--S--. In both tester strains 4-aminophenylsulfone was inactive with and without microsomal activation. The p-nitrophenyl ethers, sulfides and disulfides were relatively strong mutagens without microsomal activation towards TA100. While 4-nitrophenyldisulfide was found to possess significantly different mutagenic activity than 4-nitrothiophenol in TA98, 4-AMINOPHENYl disulfide has similar mutagenic properties to 4-aminothiophenol in both tester straains TA100 and TA98.


Action of nitrofurans on E. coli: mutation and induction and repair of daughter-strand gaps in DNA. The antibacterial and mutagenic potency of 9 nitrofurans in "treat and plate" experiments varied over almost 5 orders of magnitude. The relative toxicities were as follows: FANFT greater than AF2 greater than ANFT greather than furazolidone greater than furagin greater than nitrofurantoin greater than nitrofurazone greater than methylnitrofuroate greater than nitrofuroic acid. In general, mutagenic activity paralleled toxicity. The compounds at concentrations corresponding to their LD50's, induced mutations at frequencies which ranged from 2.5/10(6) survivors for FANFT to 130/10(6) survivors for furagin (NF416). The observed differences in antibacterial and mutagenic activity are unlikely to be due to lack of activation of the weaker agents since the two most potent agents were reduced somewhat more slowly than many of the less active agents. The relative sensitivities to the antibacterial effects of AF2 of strains WP2, WP2 uvrA, CM561 (lexA) and CM571 (recA) were 1 : 1.6 : 3 : 7 and to nitrofurazone 1 : 1 : 25 : 50. The wvrA strain was 6--7-fold more mutable with both these agents than was WP2. No increase over the spontaneous mutation frequency was observed when recA or lexA strains were exposed to either AF2 or nitrofurazone in these experiments. When wild-type of wvrA bacteria containing nitrofuran-induced lesions replicated their DNA in drug-free medium in the presence of [3H]thymidine for 5 min, the label was found in low molecular weight DNA indicating that daughter-strand gaps were formed. During subsequent incubation in nonradioactive medium the molecular weight of the DNA increased to the control value. A recA strain (which was very sensitive to the lethal effects of AF2 and nitrofurazone) lacked the ability to repair daughter-strand gaps caused by nitrofuran-induced lesions.


The application of mitotic gene conversion in Saccharomyces cerevisiae in a pattern of four assays, in vitro and in vivo, for mutagenicity testing. The induction of mitotic gene conversion of the nitrofuran derivatives nitrofurantoin (N-(5-nitro-2-furfuryliden)-1-aminohydantoin), nifurprazinum (1-(5-nitro-2-furyl)-2-(6-amino-3-pyridazyl)-ethylenehydrochloride) and FANFT (2-formylamino-4-(5-nitro-2-furyl)thiazole) was investigated in the D4-RDII strain of Saccharomyces cerevisiae (heteroallelic at the gene loci ade2 and trp5, respiration-deficient). A battery of tests was applied: direct action of the substance to yeasts, the liver microsome test in vitro, the host-mediated assay and the urinary assay. From the various combinations of positive and negative results, additional pharmacokinetic conclusions were drawn. The three nitrofuran derivatives gave positive results by direct action and in the urine of rats. The additon of liver microsomes of mice in the test in vitro reduced the number of induced convertants. In the first hours, a great deal of nitrofurantoin given orally to rats was excreted in the urine, as shown by a high genetic activity. Nifurprazinum and FANFT were excreted to a lesser extent or more slowly. Addition of glucuronidase/arylsulfatase reduced the genetic activity in the urine in the case of nitrofurantoin, had an increasing effect with nifurprazinum and was without any effect in the case of FANFT. In the host-mediated assay, only nitrofurantoin gave positive results. These results seem to be a consequence of the quick but different excretion of the nitrofuran derivatives.


Cytogenetic effects of diethylstilbestrol-diphosphate (DES-dp) on mouse bone marrow monitored by the micronucleus test. 6 dosages of diethylstilbestrol-diphosphate (DES-dp), ranging from 0.01 to 500 mg per kg of body weight were compared to saline and phosphate buffered saline (negative controls) and two dosages of cyclophosphamide (positive control) in the micronucleus test with 115 ICR mice. DES-dp failed to generate a significant increase in micronucleated polychromatic erythrocytes over negative controls. Cyclophosphamide produced a dose-related increase in micronuclei similar to previously published reports. Iit was therefore determined that the micronucleus test did not detect the types of chromosomal changes known to be generated by DES-dp and DES.


Radionuclide-determined change in pulmonary blood volume with exercise. Improved sensitivity of multigated blood-pool scanning in detecting coronary-artery disease. To assess the clinical usefulness of radionuclide-determined changes in pulmonary blood volume in patients with or without substantial coronary-artery disease, we determined the ratio of pulmonary blood volume at rest as compared with that during exercise. We used multigated blood-pool images obtained at rest and during supine exercise to determine the blood-volume ratio in patients subsequently undergoing coronary arteriography for evaluation of chest pain. Exercise tests were performed by use of a submaximal-workload protocol, although all tests were limited according to each patient's symptoms. The mean exercise/rest pulmonary-blood-volume ratios were lower for persons without coronary-artery disease (0.94 +/- 0.06 [S.D.], 10 patients) and for those with disease confined to the right coronary artery (0.99 +/- 0.12, five patients), as compared with all others with coronary-artery disease (1.14 +/- 0.15, 37 patients) (P less than 0.01). A pulmonary-blood-volume ratio equal to or greater than 1.06 had a sensitivity of 79 per cent. Patients with coronary-artery disease not confined to the right coronary artery usually show an increase in pulmonary blood volume during supine exercise. No such change occurs in persons without coronary-artery disease.


The action of pepsin on the reserve proteins of some leguminous seeds. The action of pepsin on the 11-S and 7-S proteins of vetch, 11-S protein of soybean and 7-S protein of Phaseolus vulgaris was investigated. The first three proteins are hydrolyzed almost completely, the rate of hydrolysis being close to that of hemoglobin, while the hydrolysis of Ph. vulgaris 7-S protein stops after the cleavage of only 2,4% of peptide bonds. The nonhydrolyzable high molecular weight core makes up to 87% of the initial protein and differs from the latter in its electrophoretic mobility and sedimentation coefficient. The action of pepsin does not increase the digestibility of Ph. vulgaris 7-S protein by trypsin. After the consecutive action of these enzymes about two thirds of the protein remain unhydrolyzed. The digestion of Ph. vulgaris 7-S protein by pepsin is completed only after its denaturation by heat treatment or by the action of 6 M guanidine hydrochloride.


Multiple pathways of DNA repair and their possible roles in mutagenesis. In studies on bacteria, the excision repair of UVR-induced DNA base damage has been divided into two major pathways on the basis of physiologic requirements and genetic control. The major pathway requires a functional polA+ gene, does not need complete growth medium, is largely error free, and produces short patches during repair. The second pathway requires complete growth medium and functional recA+, recB+, recC+, lexA+, uvrD+, and polC+ genes, is mutagenic, and produces long patches during repair. A second type of ecision repair exists, in which the modified base is removed by a DNA glycosylase, and the chain is nicked by an apurinic (apyrimidinic) acid endonuclease. Subsequent events are presumed similar to the above excision repair process. The postreplication repair system has been divided into at least four distinct pathways, three of which depend on functional recB+, lexA+, and uvrD+ genes, and are error free. A fourth pathway depends on the above gene products but is blocked by postirradiation treatment with chloramphenicol, and may be the UV-inducible, error-prone, mutagenic pathway of repair ("SOS repair"). A possible fifth pathway is dependent on a functional recF+ gene and is independent of the recB+-dependent pathway. Mutagenesis is the result of error-prone DNA repair, and evidence is growing that carcinogenesis is also the result of error-prone repair. Therefore, a complete understanding of DNA repair is crucial to a complete understanding of the molecular basis of carcinogenesis.


Analysis of base substitutions induced by ultraviolet radiation in Escherichia coli. A system for determining the precise specificity of mutagens operating on Escherichia coli has been described, and the results for UV irradiation have been presented. Attempts to correlate the base pairs preferentially mutated by UV light with pyrimidine-pyrimidine sequences are discussed.


Mutagenesis and cell transformation by ultraviolet irradiation: many hypotheses for few results. UV light-induced mutagenesis in bacteria is a genetically controlled process dependent on induction of some cellular functions, provoked initially by unrepaired photolesions in the DNA. Experiments on the extent and fidelity of in vitro DNA systhesis on UV-irradiated templates by bacterial mammalian DNA polymerases suggest a crucial role for 3' to 5' exonuclease (proofreading) activity in UV light-induced mutagenesis. Two-stage carcinogenesis (initiation and promotion) is discussed in terms of two-stage mutagenesis (mutation fixation in the DNA and mutation expression). A unifying concept for both mutational and viral malignant transformation is proposed.


Photocarcinogenesis: a review.

Photocarcinogenesis: a review. Clinical observations and epidemiologic studies indicate that the sun is the primary stimus for most human skin can formation. However, investigations directly confirming this association as well as defining the action spectra, time-dose relationships, energy level requirements, etc., have been confined to animal experimentation. Studies in which gross methods are used indicate that the experimental carcinogenic action spectrum falls primarily between 280 and 320 nm. Quantitative studies and tumor promotion investigations indicate that UV-induced cancer formation begins with the initial exposure. Heat, wind, and moisture stimulate UV carcinogenesis. Also, exogenous chemicals may influence carcinogenesis as photosensitizers such as 8-MOP, as additive carcinogens as noted with DMBA, or as promoters as described for Croton oil, retinoic acid, and BCNU. Qualitative studies indicate that progressive alterations occur in the epidermal-dermal basement membrane and dermal conncecive tissue and mucopolysaccharides associated with the progressive development of epidermal cancers. Malignant melanomas have also been induced experimentally in hairless mice with UV energy. Mechanistically, immunologic alterations and effects on DNA have received the most attention. Tumor-specific antigenicity as well as antigen deletion has been demonstrated. Immune suppression by antilymphocyte serum and certain chemicals has led to stimulation of tumor development. Perhaps the most exciting new information relates to the demonstration that chronically UV-irradiated mice have not rejected highly antigenic UV-induced cancers. This indicated that UV irradiation specifically altered the immunologic responses of the animals to these tumors. Within recent years, the influence of DNA injury and repair on cutaneous carcinogenesis has received a great deal of attention. This has been partly due to the demonstration of defective repair of UV-induced DNA damage in patients with XP. The primary photosensitive problem in these patients is an inordinate sensitivity to the carcinogenic effects of sunlight. However, correlation of DNA injury and repair directly with cancer formation has not been accomplished.


A structurally abnormal insulin causing human diabetes. Insulin isolated from the pancreas of a diabetic patient with fasting hyperinsulinaemia showed decreased activity in binding to cell membrane insulin receptors and in stimulating cellular 2-deoxyglucose transport and glucose oxidation. Chemical studies suggest that the isolated hormone is a mixture of normal insulin and an abnormal variant which contains a leucine for phenylalanine substitution at position 24 or 25 of the insulin B-chain.


Fast and slow myosin within single skeletal muscle fibres of adult rabbits. There is good evidence for the coexistence of different myosin types both in developing muscles and in Purkinje cells from adult chicken hearts. In skeletal muscle fibres of adult animals, however, coexistence of fast (FM) and slow (SM) myosin has only been demonstrated after long-term electrical stimulation. The term 'promiscuity' has recently been coined to describe the coexistence of different myosin isoenzymes within a single fibre. Using novel, refined immunological methods we demonstrate here the presence of both FM and SM within single fibres of the musculus tibialis anterior of adult rabbits. Essentially identical results were also obtained with other muscles. Our findings imply that the genes coding for FM and SM can be expressed simultaneously within the same cell throughout an animal's entire life, and not only during development or after artificial electrical stimulation.


Clonal nature of mast-cell clusters formed in W/Wv mice after bone marrow transplantation. We have recently found that the number of mast cells in the skin of adult W/Wv mice is less than 1% of that observed in congeneic +/+ mice, and that no mast cells are detected in other tissues of W/Wv mice. After the transplantation of bone marrow cells from congeneic +/+ mice, the number of mast cells in the skin, stomach, caecum and mesentery of the W/Wv mice increased to levels similar to those of the +/+ mice. Study of the mast-cell number in the W/Wv mice at various times after transplantation suggested to use that mast cells might develop in groups, particularly in the skin and mesentery. In this report, we have attempted to elucidate the possible clonal origin of such mast-cell clusters from a single precursor cell, using giant granules of beige (C57BL/6-bgJ/bgJ, Chediak-Higashi syndrome) mice as a marker to identify the origin of the mast cells (Fig. 1). We found that when WB-W/+xC57BL/6-Wv (WBB6F1)-W/Wv mice were injected with a mixture of bone marrow cells from beige C57BL/6 mice and normal C57BL/6 mice, more than 95% of mast-cell clusters consisted of either beige-type cells alone or normal-type cells alone. We conclude, therefore, that the cluster of mast cells originated from a single precursor cell.


Towards an experimental analysis of molecular self-organization and precellular Darwinian evolution. An experimental system is described, which opens up a novel pathway towards a molecular understanding of the origin of life. The systemic conditions for the evolution of biological macromolecules are investigated in detail.


[Activation, activity and inhibition of bovine trypsin]. Trypsin is a prototype of a large group of enzymes belonging to serine proteinases. The X-ray crystal-structure analyses of its proenzyme trypsinogen, of the active trypsin and of their complexes formed with the pancreatic trypsin inhibitor (PTI) have considerably enhanced our understanding of the mechanisms of activitation, action and inhibition. The trypsinogen is an incompletely folded molecule. Its substrate-binding site becomes only completely fixed upon the enzymatic cleavage of an N-terminal peptide. The contact regions of trypsin and PTI are almost complementary. The complex formed is a (stable) intermediate in the normal tryptic substrate-cleavage reaction.


Advances in chromatin research.

Advances in chromatin research. Recent results in chromatin research are reviewed. The nucleosomal arrangement is described and the roles of DNA, histones and non-histones are discussed in connection with their functions.


The action of the dihydro derivatives of prostacyclin--(6R)-PGI1 and (6S)-PGI1 on the heart and the coronary vasculature. The action of the dihydro prostacyclins, (6R)-PGI1 and (6S)-PGI1, was studied on the isolated guinea pig heart and bovine coronary artery strips. PGE2 and PGI2 were used as standards. In the isolated guinea pig heart (6S)-PGI1 decreased the coronary perfusion pressure (CPP), myocardial force of contraction (MFC) and oxygen consumption (QO2). (6R)-PGI1 did not produce a significant change in these parameters. The ED50 (50% o maximum coronary dilation) was approximately 20 times higher for (6S)-PGI1 than for PGI2 or PGE2. Treatment of the hearts with reserpine + tyramine abolished the (6S)-PGI1-induced decrease in MFC but not the decrease in the CPP. The same pattern of responses was seen with PGE2. Bovine coronary artery strips were contracted by both (6S)-PGI1 and (6R)-PGI1, the ED50 (50% of maximum increase in tension) being 5 and 10 times higher than that for PGE2. The (6S)-PGI1-induced contraction was preceeded by a small relaxation, which, however, was much less than that seen after PGI2. It is concluded that the hydration of the 5,6 double bound in the PGI2 molecule results in an almost complete loss of PGI2-like activity and generates PGE-like activity. The same biological activity of both dihydro prostacyclins in the isolated coronary artery strip but not in the intact coronary vascular bed leads to suggest that the sites of action in these systems are different.


Immunological and bacteriological studies in chronic pyelonephritis associated with kidney stones. Histological and immunofluorescent techniques, urine, stone and renal fragment culture, demonstration of bacteria with fluorescent specific antisera in the renal tissue and determination of circulating antiGBM and antiTBM antibodies in the serum, were studied on the renal biopsies of 46 patients with chronic pyelonephritis (CPN) associated to kidney stones. Results show that the bacteria are often present in renal tissue of CPN with negative urine culture. The presence of C3 and C4 in some cases, and C3 and C3PA in others, at the tubular level associated with bacteria, suggest that the activation of the C system may be through the classic way, i.e., through the bacteriological immune complexes, or the alternate pathway, i.e., through the bacteria or their products. In conclusion, the evolution of the CPN may be related to the activation of the C system and the coagulation mechanism, as shown by frequent fibrinogen deposits.


Renal function during therapy in patients with congestive cardiac failure. Ticrynafen vs. hydrochlorothiazide. 14 patients with congestive heart failure requiring diuretic therapy were randomly assigned to treatment with ticrynafen (TCRN) 250 mg or hydrochlorothiazide (HCTZ) 50 mg once or twice daily. Both diuretics were effective and comparable in effecting a significant weight loss and increase in urinary sodium. The major difference between the two compounds was the marked fall in serum uric acid concentration and the increase in uric acid clearance occurring with ticrynafen. HCTZ caused an increase in serum uric acid and a fall in uric acid clearance. It is concluded that ticrynafen is a useful diuretic in the treatment of congestive heart failure and has the advantage of lowering serum uric acid rather than producing hyperuricemia.


Comparison of ticrynafen and probenecid in patients with elevated uric acid levels. Ticrynafen, 125--250 mg/day was compared with probenecid 0.5--1.0 g/day in patients with elevated serum uric acid values in a randomized, double-blind crossover study. Each treatment period lasted 12 weeks. The mean reduction in serum uric acid from 9.4 +/- 1.2 to 6.22 +/- 1.2 mg/dl (33.8%) during ticrynafen was greater (p less than 0.01) than that from 9.46 +/- 1.1 to 7.0 +/- 1.3 mg/dl (26%) during probenecid treatment. There were slight increases in serum creatinine and BUN and decreases in body weight during ticrynafen treatment. There were no statistically significant changes in serum electrolytes. The hypouricemic effect of ticrynafen was well maintained during its subsequent open-label administration for 18 months without any deterioration of renal function.


Renal function during ticrynafen therapy. 526 patients with essential hypertension or congestive cardiac failure were treated with ticrynafen (250--500 mg/day) or hydrochlorothiazide (50--100 mg/day) for 6 weeks to 6 months. There was no appreciable effect on renal function, as measured by changes in blood urea nitrogen and serum creatinine levels. Both drugs exhibited similar antihypertensive activity and ability to control signs and symptoms of congestive cardiac failure. Side effects were mild and reversible. A notable difference is the marked reduction in serum uric acid in patients treated with ticrynafen, unlike the elevated urate levels occurring after treatment with hydrochlorothiazide.


[Quantitative determination of cells in sterile skin exudate in acute cerebrovascular diseases]. Rebuck's test was done in 126 subjects (40 healthy controls and 86 patients with acute cerebrovascular disease) on both upper extremities. In the control group no statistically significant quantitative difference was found in the number of cells in the exudate on both sides. In the patients, however, the number of cells in the exudate was greater on the paralysed extremity. The reaction dependent on the degree of paralysis, coexistence of sensory and autonomic disturbances, but was independent of the form of acute cerebrovascular disease (haemorrhage, encephalomalacia) and the time after the onset of the disease.


Acute inhibitory effects of antiserum to gonadotropin-releasing hormone in ovariectomized rats. Evidence for pulsatile secretion of gonadotropin-releasing hormone. To evaluate the dependence of pulsatile secretion of luteinizing hormone (LH) on gonadotropin-releasing hormone (GnRH), the acute effects of immunoneutralization of endogenous GnRH on plasma LH were compared in ovariectomized rats with phenobarbital treatment and hypophysectomy. Anti-GnRH produced a rapid dose-dependent decrease in plasma LH and LH pulse amplitude. Pulsatile secretion of LH was eliminated in 6 of 12 rats treated with the highest dose of anti-GnRH, but plasma LH was still 50% of control values 3 h after treatment. Frequency of LH pulses was unchanged in animals which had persistence of pulsatile secretion of LH. Phenobarbital eliminated pulsatile secretion of LH transiently. Hypophysectomized rats displayed a striking decrease in plasma LH which could be resolved into two exponential components with half-lives of 16 and 70 min. The initial half-life of plasma LH from untreated rats determined after LH pulses was also 16 min. These studies support the hypothesis that pulses of GnRH induce the pulsatile pattern of plasma LH and may be responsible for all LH secretion in ovariectomized rats.


Rat gonadotropin release stimulated in vitro by GnRH-depleted rat brain extracts. A study was made to compare the LH and FSH release patterns from isolated adult rat pituitaries in response to exposure to acidic extracts of rat hypothalamus or brain or to acidic extracts of GnRH-depleted hypothalamus, cerebral cortex, or cerebellum of adult (90-100 days old) or young (14 days old) rats of both sexes, using a continuous perifusion system. Hypothalami of adult rats contained 3-5 ng of radioimmunoreactive GnRH, while the corresponding cerebral cortex and cerebellum contained none, or extremely low levels of GnRH. Adult hypothalamic extract (HE) stimulated considerably greater LH and FSH release than was induced by cortical extract (CE) or cerebellar extract (CBE). Removal of assayable GnRH from HE by incubation with anti-GnRH serum reduced, but did not eliminate, release of both LH and FSH, suggesting that GnRH is the principal but not sole agent responsible for both LH and FSH secretions. Adult male HE released slightly more LH and FSH than did female HE due to its greater GnRH content. GnRH-depleted CE or CBE from both sexes induced LH and FSH releases qualitatively and quantitatively similar to those induced by CE, CBE or GnRH-depleted HE. Untreated extracts or GnRH-depleted extracts of all three brain regions from 14-day-old rats of both sexes induced similar LH and FSH releases as those of adult CE or CBE. Hypothalamus of young rats, which contained about 0.5 ng of immunoassayable GnRH did not release more LH and FSH than the corresponding cortex or cerebellum did. The data indicate that all brain regions so far studied, regardless of sex or age, contained presumably nonspecific substance(s), other than GnRH, capable of stimulating minor but significant LH and FSH releases. Their nature or role in physiological regulation of gonadotropin secretion is unknown, but must be considered, since current concepts, in which GnRH is the sole hypothalamic gonadotropin regulator, are not adequate.


Neural control of reproduction.

Neural control of reproduction. The feedback loops involved in the neural control of reproductive cyclicity in primates are reviewed. A combination of morphological, endocrinological, and surgical experimental approaches was used to identify the different mechanisms involved. The main signal for pituitary secretion of gonadotropins is the estrogen secreted by the ovary. Estrogen probably affects the hypothalamic secretion of gonadotropin-releasing hormone (GnRH), which in turn stimulates the pituitary production of gonadotropins. These may in turn, through a short feedback loop, regulate the secretion of GnRH. Evidence for a direct effect of estrogen on the pituitary is presented. Future possible areas of research, including extrahypothalamic influences on reproductive mechanisms, are briefly outlined.


Multiple sclerosis and housedogs: a case-control study. A case-control study was conducted to examine the possible association between ownership of housedogs early in life and later development of multiple sclerosis (MS). Sixty MS patients were compared with 60 neighborhood controls matched for age, sex, and race. There was no significant difference between cases and matched controls in housedog ownership, duration of ownership, or age at first exposure to housedogs over the interval from birth to 19 years of age.


Paraparesis in hereditary multiple exostoses: case report. The authors report a case of hereditary multiple exostoses (HME) with neurologic complications, and review the literature. A 23-year-old man exhibited a worsening spastic paraparesis with sphincter dysfunction. The cranial nerves and the exteroceptive and deep sensations were apparently undamaged. The family history, the physical examination, and the systemic radiologic examination revealed all the characteristics of HME. The neurologic complication was caused by an exostosis, arising from the C2 right hemilamina, compressing the spinal cord. The patient quickly improved after a laminectomy.


The design of clinical studies to assess therapeutic efficacy in multiple sclerosis. Poorly designed trials of therapy for multiple sclerosis (MS) can waste time and money, and may lead either to false hopes or to the overlooking of a potentially effective treatment. A well-designed trial may well develop useful scientific information even if the putative therapy fails to show any therapeutic effect. The diagnosis, clinical course, and definitions of the stages of MS are discussed as they relate to trials of therapy. The goals of such trials include favorable modification of an exacerbation, favorable modification or prevention of future exacerbations, effective treatment of the progressive stage, and improvement of function in the stable-deficit stage. There should be an orderly progression from a small preliminary trial to a modest pilot trial and, when indicated, a full trial. All types of trials require careful organization and management, appropriate selection of patients, and properly planned and recorded observations. The treatment contrast--how the new treatment will be evaluated--provides the essential structure of the trial. The hypothesis being examined, the treatment contrast, and the observations being made in the designed clinical trial will govern the form of the analysis and the nature of the interpretations. Each goal requires that specific strategies and design considerations be applied to preliminary, pilot, and full trials.


From reform to relativism: a history of economists and health care. During the first half of this century economists who studied health care were primarily concerned with reducing the financial burden of illness and making services more accessible. In recent decades, "scholarly research" by professional economists has become characterized by the exchange of social advocacy for scientific neutrality. Historical analysis of the assumptions underlying this shift--assumptions about the worth of resources and alternative ways to allocate resources--shows parallel changes in other social sciences and medicine. As commitment to reform is tempered by relativism, scientific inquiry may benefit at the cost of social justice.


[Comparison between automatic substraction devices and computer subtraction in radioisotope pancreatography]. Reference is made to several indicative cases in a personal series. Their comparative examination with a scanner and a gamma camera computer showed that: a) noticeably different findings were given by the two methods with regard to cystic, neoplastic, and inflammatory lesions of the pancreas, whereas; b) computerised subtraction was much more sensitive in lesions due to cysts and pancreatitis, even though there was no significant difference between the two methods in the case of neoplasia.


[Rupture of the transplanted kidney].

[Rupture of the transplanted kidney]. Five cases of kidney grafts followed by rupture are described. The explanation of the syndrome accompanying such an occurrence is deduced from personal observations as well as from literature data. As a matter of fact, the aetiopathology of this syndrome cannot be with an isolated cause, for several multifactorial immunological and non-immunological components may be involved.


Gentamicin resistance in Christchurch hospitals. Prior to June 1976, the isolation of gentamicin resistant organisms was an infrequent occurrence in North Canterbury Hospital Board institutions. During July 1976, 20 different gentamicin resistant organisms were isolated from patients in Christchurch Hospital. Gentamicin resistant organisms hav e been continually isolated from an increasingly wide area since then. The organisms involved are: providence species; Pseudomonas aeruginosa; Klebsiella species; E coli; Staphyloccus aureus; Proteus mirabilis; Staphylococcus epidermidis; Acinetobacter species; Enterobacter species; Haemophilus influenzae; Pseudomonas maltophilia CDC II F; Citrobacter species; Alcaligenes odorans and Pseudomonas species. The spread of gentamicin resistant organisms has occurred rapidly in the hospital environment. The importance of the urinary tract as a reservoir of microorganisms is indicated in this report.


Diabetes and thyroid disease during pregnancy. In a prospective study of 100 consecutive diabetic pregnancies, 1 was complicated by hyperthyroidism and 4 by hypothyroidism. The association of hypothyroidism with diabetes mellitus merits special attention as this combination of diseases affected 4 of 20 (20%) White's class D and F diabetics. Hydramnios and/or spontaneous premature labor were features of diabetic pregnancies complicated by compensated hypothyroidism. Delayed diagnosis of hypothyroidism may have contributed to the fatal congenital malformations in one of these fetuses, but the remaining infants survived, including 1 infant suffering from severe respiratory distress syndrome (RDS).


Common aspects of immunologic tolerance in pregnancy and malignancy. The fetoplacental allograft and the malignant neoplasm represent the only 2 biologic conditions in which antigenic tissue is tolerated by a seemingly intact immune system. Recent investigations in the fields of tumor and pregnancy immunology have resulted in the recognition of a variety of immunologic mechanisms which are common to both systems. These common denominators are reviewed and a thesis suggesting a common mechanism in the nonrejection of pregnancy and malignancy, based on the presence of embryonic antigens in both systems, is presented.


A new technique for vulvar skin grafting. A new and easy technique for handling and applying a split-thickness skin graft to the vulva is described. The use of petrolatum gauze backing and application with the skin stapler, as well as postoperative management, are discussed.


Pulse granuloma of the alveolar ridge.

Pulse granuloma of the alveolar ridge. Six examples of pulse granulomas of the alveolar ridge are presented. The lesion consists of a foreign-body granuloma containing identifiable particles of leguminous foods. The vegetable matter is introduced through an alveolar defect, usually a postextraction socket. Simple curettage is apparently adequate treatment to effect cure.


Infantile olfactory neuroblastoma. A clinicopathological study with review of the literature. A case of olfactory neuroblastoma occurring in a 3-year-old girl is reported. The rarity of the lesion in early childhood is stressed and discussed with the clinico-pathological characteristics of the tumour, which are apparently more aggressive the younger the patient. Olfactory neuroblastoma should be considered as a possible diagnosis regardless of the age of the patient.


[The cause of a mistake in the determination of the level of serum phosphorous (author's transl)]. The method of Briggs was not suitable for the determination of serum phosphorous levels in the blood of patients treated with blood substitute containing gelatine.


[Bactericidal activity "in vitro" of sulfamethoxazol-tri-methoprime (SMZ-TMP) alone and in combination with various antibiotics on bacterial strains isolated from urinary tract infections (author's transl)]. The authors study "in vitro" effects of sulfamethoxazol-trimethroprime (SMZ-TMP) on 1 078 bacterial strains isolated from urinary-tract infections during january 1974, the second trimester 1974 and january 1975. Study involves two parts : comparison between bacteriostatic activity of SMZ-TMP, ampicillin and nalidixic acid; evaluation of bactericidal activity of antibiotic associations including SMZ-TMP. MIC study included all strains. On Gram- negative bacilli the bacteriostatic activity of SMZ-TMP (74,6 percent of sensitive strains) was comparable with nalidixic acid (79,6 percent of sensitive strains) and better than ampicillin 31,4 percent of sensitive strains). On staphylococcus strains the bacteriostatic activity of SMZ-TMP (84,6 percent of sensitive strains) is better than ampicillin (36,4 percent of sensitive strains); on streptococcus strains the bacteriostatic activity of ampicillin (71 percent of sensitive strains) is better than SMZ-TMP (5l percent of sensitive strains). 473 associations including SMZ-TMP were studied upon 44 strains of Gram- negative bacilli by bactericidal test. ("Cross disposition" method, derive from "cellophane transfer method".


[Evidence for one atypic variant of an alkaline phosphatase from human placenta (author's transl)]. A variant of a partially purified Placental Alkaline Phosphatase, showing a slow electrophoretic mobility but the same kinetic caracteristics as the common type, has been found. This variant also differs from the D type by its insensibility to L-leucine inhibition.


[Hemoglobin oxygen combining capacity power. Reproducibility, variability; the effect of carboxyhemoglobin (author's transl)]. Hemoglobin oxygen combining power (HOCP) was measured in blood samples of 41 non smoking subjects and 36 smokers. The reproductibility and the varibility of this value were established (maximal variability was 2,5% in individual measurement). When the oxygen carrying capacity is reported to total hemoglobin (Hbt.), these two groups are not significantly different (1,344 +/- 0,004 ml O2 g-1 Hbt--n = 77-). However, when oxygen carrying capacity is reported to functional hemoglobin (Hbf = Hbt -- HbCO) there is a significative difference between smokers and non smokers (Student's t test 2 p less than 0,001) (1,404 +/- 0,005 ml O2 Hbf -- n = 77-).


[Serum RIA vasopressin levels in 5 healthy subjects during water loading, before and during treatment by carbamazepine (author's transl)]. Serum vasopressin level has been measured by radioimmunoassay in 5 healthy subjects during water loading, before and during treatment by carbamazepine. Serum vasopressin drops significantly during carbamazepine in spite of antidiuresis. This drop may be explained by an effect of carbamazepine on renal tubular cell.


[Homogeneity of the erythrocyte volume distribution during chronic alcoholism macrocytosis (author's transl)]. The increase in volume of human erythrocytes during chronic alcoholic intoxication and its decrease after alcoholic deprivation was studied with a multichannel analyzer. When fractions of the population of red cells were separated by differential centrifugation the macrocytosis was found to be uniformly distributed. The presence of macrocytes was not related to changes of plasma osmolality or hyperhydration of red cells. A central origin was evoked, however, the role of the folic acid deficiency could not explain the macrocytosis, the mechanism of which remains to be elucidated.


[Compared study of micro-aggregates filters (output, filtration pressure and study of the deposit with scanning electron microscopy) (author's transl)]. Special filters for the elimination of cellular aggregates were conceived especially to prevent pulmonary complications in patients shocked particularly after massive transfusions as well as to prevent cerebral complications after extra-corporeal circulation. The performances and the conditions of use of these filters (perfusion output, change of the filter) were considered. Four filters were carefully studied: the Fenwal filter, the Swank filter, the Biotest filter and the intersep Johnson and Johnson filter. The following studies were carried out for each filter: the perfusion output (of three bottles filtered one after another with or without pressure); the filtration pressure (Swank technique) of the whole blood up-and-down filter; the viscosity and various hematologic parameters (NF, hemoglobin and gobular ATP); finally, the deposit was studied morphologically with scanning electron microscopy. It appeared that a good capacity of aggregates elimination (decrease of the filtration pressure of 95%) was often linked to a feeble output and the necessity of replacing the filter. The efficacy of the Fenwal filter, the Swank filter, the Biotest filter and the intersept filter was practically the same, but the Intersept filter provided the best output with an equal filtration capacity. The other parameters remained about the same. The deposits included fibrinogen, deformed red blood corpuscules (echinocytes), leucocytes and platelets.


[A new case of acute lymphoblastic leukemia with Philadelphia chromosome in the child (author's transl)]. The systematic study of the medullary karyotype in the course of haemopathies has led us to a new case of Philadelphia chromosome in an acute lymphoblastic leukemia. This was a case of a 13 year old child. Is this a particular class of haemopathy? Do such observations put a question on the dual theory of the origins of blood germ cells? The elaborate medullary karyotype in the course of haemopathy may solve this problem. A rigorously nosological classification is essential for appraising the therapeutic plan chosen and making a pronosis.


[About the different steps leading to the quality of medical informations (importance of medical computing (author's transl)]. To draw the best conclusions from a set of medical data, one must first choose correct, valid, representative and well-expressed information. So it's not sufficient to collect data, but we have to valid them before including them in the records. After having put out the general characteristics of any validation and defined the fields where they can be applied we recommend a method over three steps. First, the physician alone, then the physician with an informatician and again the physician seem concerned by the steps of control. It is particularly important to develop the validation of chronology and generally speaking of evolutive data. Of course, the costs of validation with respect to the large groups of data must be taken into account.


[Mini-review on the properties of glial cells of the central nervous system (author's transl)]. During the past 15 years, increasing studies have been devoted to glial cells, i.e. oligodendrocytes, astrocytes and microglial cells of the central nervous system. Although most of their functions remain mysterious, the concept of intracellular interactions between neurons and neuroglia becomes more and more substantiated. This review describes some aspects of phylogeny of glia, recent technical approaches to the study of these cells, their major morphological and biochemical characteristics, their maturation as well as their pathology.


[Semi-automatic assay of post-heparin plasma lipoprotein lipase activity (author's transl)]. A simple method for the assay of post-heparin plasma lipoprotein lipase activity is described. The substrate was a stable intralipid solution. The amount of fatty acids released in the 37 degrees C incubation medium was measured several time during the reaction course, by light absorption on a Technicon auto-analyzer. By plotting these values on a graph paper, the curve of the post-heparin plasma lipoprotein lipase activity was obtained.


[Utilisation of pipemidic acid as antibiotic in patients with renal failure insufficiency. Kinetics of serum and urinary concentrations (author's transl)]. In 23 chronic renal patients serum and urinary concentrations of pipemidic acid were studied, the drug being given orally for 3 to 105 days. In 13 non-dialyzed patients, whose GFR varied from 4.5 to 36 ml/mn the dosage was 11.2 to 30 mg/kg/day. Maximum serum concentrations were comprised between 6 and 29 micrograms/ml. In 2 patients minor clinical side-effects indicated a maximum tolerance level of 25 micrograms/ml. Urinary concentrations remained elevated in spite of severe renal failure. In 10 hemodialyzed patients maximum predialysis levels varied from 5.6 to 28 micrograms/ml. No side-effects were noticed. The dialysance of pipemidic acid was high, due to a low molecular weight and to a binding to proteins which seems to be lower in uremics than in normal subjects. We conclude that pipemidic acid can be utilized in chronic renal patients, in taking advantage of low GFR's for obtaining serum bactericidal concentrations on susceptible organisms.


Systemic air embolism in the respiratory distress syndrome of the newborn. Details of 25 cases of neonatal systemic air embolism, including three of our patients, are reviewed. This rare complication of respiratory distress syndrome (RDS) was observed in 21 premature infants and 4 fullterm newborns, of whom 23 required intermittent positive pressure ventilation (IPPV). In 21 of these patients air embolism was preceded by pulmonary interstitial emphysema, pneumomediastinum, pneumothorax and/or pneumopericardium. Air embolism occurred between 3 and 288 hours after delivery. The outcome was lethal in 24 cases, only one patient survived. Two main pathogenic mechanisms are discussed; entrance of air from ruptured alveoli into the lung capillaries and introduction of air via catheters in umbilical vessels.


Characteristics of impaired chemotactic function in cord blood leukocytes. Mobilities of cord blood granulocytes were studied using the agarose plate method and Boyden's chamber method. In the agarose plate, granulocytes of cord blood were shown to have moderately decreased responses in chemotaxis and chemokinesis induced by Escherichia coli-derived chemotactic factor and/or zymosan-activated serum, whereas they were shown to have a normal capacity of random mobility. Although their distance and index of chemotaxis or chemokinesis in the agarose plate were significantly less than those of adult granulocytes, response rate in both types of mobility were evidently higher compared with those in patients with chemotactic defect. Furthermore, there is a difference between chemotactic responses of cord blood granulocytes to E. coli-derived chemotactic factor and to zymosan-activated serum in the agarose plate method. Using the latter, a more distinguishable difference between chemotactic responses of cord blood granulocytes and adult granulocytes was shown. The Boyden's chamber method tended to show a more significant difference between chemotactic responses of granulocytes of cord blood and adults than in the agarose plate method.


Nosocomial respiratory syncytial virus infections in an intensive care nursery: rapid diagnosis by direct immunofluorescence. A nosocomial outbreak of respiratory syncytial virus infections involved 8 of 17 infants in an Intensive Care Nursery and one additional infant in the adjoining Newborn Nursery. Immunofluorescent staining of nasopharyngeal specimens was positive in six of seven virologically confirmed cases (86%). One additional case with negative viral cultures was also identified by this technique. Viral isolation in tissue cultures required an average of 4.9 days, whereas results of immunofluorescent studies were available in two to four hours. Rapid identification of infected infants by immunofluorescence permitted prompt institution of infection control measures.


The pediatrician and congenital heart disease--1979. Technologic advances in the diagnosis and treatment of children with congenital heart disease have created new, expanded roles for the practicing pediatrician. Early identification of infants with serious lesions continues to be vital, and support of children and their families following surgery is central to the solution of emotional, employment, and childbearing problems these patients may eventually face.


Intravenous linoleic acid supplementation in children with cystic fibrosis. Ten children with CF in matched pairs were infused with either Intralipid or with 10% glucose on a double blind basis every other week for one year. Although statistically there was significantly greater gain in height and weight in the study year compared to the previous year only for the test group, both groups improved more than expected. Cumulative data analysis showed greater improvement for the Intralipid group (23 of a possible 45 points) compared to the glucose group (-2 points; P less than .02). This study indicates the need to better define the role of nutrition in the pathophysiology of CF. Meanwhile, it is recommended that all children with CF have plasma linoleic acid levels measured at least once yearly, and if levels are low, appropriate supplements should be given.


Clostridium botulinum in fish.

Clostridium botulinum in fish. 1407 fish caught in Scandinavian waters, the North Sea and the North Atlantic have been examined for the presence of Cl. botulinum. The incidence in gut samples expressed as percentage of fish tested was generally highest in fish from Scandinavian coastal waters and the Baltic Sea (4--43%), decreasing in fish from the North Sea (0--8%), and the organism was practically absent in fish from the North Atlantic. When gut samples were examined, the incidence was highest in demersal fish (cod and flatfish) as compared with pelagic fish (herring). The latter fish species were mainly contaminated on outer surfaces and gills. Only type E was detected in this survey, and Cl. botulinum was not detected in any wild fresh water fish. It is suggested that type E spores may originate in the sea bed and that they be spread by fish and water currents.


[Nerve "mixed" suture. A new technique (author's transl)]. A critical evaluation of the various methods of nerve suture, followed by the description of a new personal method of "mixed suture" taking up the neurolemma and the perineurium in the same stitch. It may be used under emergency conditions or not, at all levels of nerve trunk interruption (and in particular in the region of the plexi) without the need for costly optical equipment. The technique is simple and may be used under all circumstances, even by the non-specialised surgeon. Results obtained over more than 10 years, involving the treatment of 109 nerve lesions confirm the value of this type of suture.


[Alternative complement pathway (author's transl)]. The dual role of the alternative complement pathway in recognition of foreign substances by a non-immune host and in the intrinsic regulation of the complement sequence is now well recognized. Activation of this pathway occurs through escape from its regulatory mechanisms induced by the activating principle; its functional expression depends on the respective levels of the component proteins C3, factor B, factor D and properdin, and on the control proteins beta 1H and C3bINA. This article presents recently acquired knowlege on the molecular mechanisms of activation, regulation and behaviour under pathological conditions of the alternative complement pathway.


Antiplatelet drugs in thromboembolism.

Antiplatelet drugs in thromboembolism. Evidence is mounting that three drugs that inhibit platelet function--aspirin, dipyridamole, and sulfinpyrazine--have an antithrombotic effect in humans. Particularly in men, aspirin is beneficial in controlling transient ischemic attacks and stroke, and there is evidence that it may be effective in preventing thrombotic and embolic complication of hip surgery. It abolishes symptoms in peripheral ischemia associated with thrombocytosis and spontaneous platelet aggregation and may prove effective in coronary artery disease. When combined with oral anticoagulants, aspirin is more effective than oral anticoagulants alone in preventing systemic embolism in patients with prosthetic heart valves. Dipyridamole in combination with oral anticoagulants reduces the incidence of systemic embolism after prosthetic heart valve replacement. Sulfinpyrazone reduces the incidence of sudden death in the first year after myocardial infarction, decreases the incidence of arteriovenous shunt thrombosis in patients undergoing chronic hemodialysis, and when combined with anticoagulants, may be effective in reducing the frequency of episodes in recurrent venous thrombosis.


Ascorbic acid and the common cold: reviewing the evidence. Large-scale clinical trials of the effect of vitamin C on the common cold conducted since Pauling's pronouncement on its efficacy in 1970 have produced conflicting results. Benefits shown have been modest, and positive findings have not been reproducible. Reported benefits probably are due to statistical artifact, minor vitamin-induced physiologic changes, the placebo effect, or a combination of these.


Effects of intravenous and oral domperidone on the motor function of the stomach and small intestine. One hundred and fifty-six patients referred for barium meal with follow-up examination, participated in a placebo-controlled blind assessment of the effects of domperidone against placebo, on gastric motility and emptying. None of the patients had organic obstruction, had undergone previous gastrointestinal surgery or were currently taking anticholinergic drugs. In one study, patients were randomly given either 10 mg, 20 mg or 50 mg of domperidone or placebo suspension orally 30 minutes prior to barium meal to simulate therapeutic conditions. In a separate study conducted under identical conditions, either 8 mg domperidone or placebo was given intravenously. Domperidone (8 mg i.v. or 20 and 50 mg orally) significantly promoted antral peristalsis and gastric emptying compared to placebo. The results suggest that domperidone improves motor function in the proximal part of the gastrointestinal tract and synchronizes motor function due to its protracted activity.


A double-blind study of domperidone in the symptomatic treatment of chronic post-prandial upper gastrointestinal distress. Oral domperidone (30 mg/day) or placebo tablets were given to 41 patients presenting with symptoms of chronic post-prandial dyspepsia, in a double blind study. The tablets were taken three times a day before meals. The first part of the study lasted four weeks and was followed by a second four week period in which domperidone was given on an open basis to all subjects. At the end of the double-blind phase all indices but one (bitter regurgitation) as well as the gastro-oesophageal reflux cluster had significantly improved on domperidone treatment while none had done so on placebo. During the subsequent open four weeks of domperidone all items improved in both study groups. No side effects were seen in any of the participants in the study.


A double-blind crossover trial of domperidone in chronic postprandial dyspepsia. A doubld-blind crossover study of oral domperidone (10 mg t.d.s.) involving 48 patients suffering from chronic postprandial dyspepsia, showed a significant relief of symptoms on active treatment compared to placebo. The trial lasted eight weeks, the crossover in medication taking place at four weeks. Side effects were rare and mild and it is concluded that domperidone could be a very useful drug for the symptomatic treatment of upper gastrointestinal distress.


Domperidone in the treatment of functional dyspepsia in patients with delayed gastric emptying. Forty patients who were suffering from chronic dyspepsia, diagnosed clinically and radiologically as being related to delayed gastric emptying, were treated with either domperidone or placebo in a double-blind trial. The trial lasted four weeks and the dose of domperidone was 10 mg orally t.d.s. before meals. The results showed that the drug markedly improved symptoms and that side effects were few, being recorded in one patient only, on active treatment. It is concluded that domperidone is a useful agent for the treatment of dyspepsia with retarded gastric emptying.


Domperidone for the symptomatic treatment of chronic post-prandial nausea and vomiting. Forty patients with postprandial nausea and vomiting from a variety of underlying causes, were given either domperidone 20 mg t.d.s. or placebo in a double-blind study lasting two weeks. The tablets were taken before meals and no other anti-emetics were used. Nausea and vomiting were reduced in those patients given the active therapy, the results being recorded as excellent in 62% in the domperidone group and 18% of controls.


A double-blind comparison of domperidone and metoclopramide suppositories in the treatment of nausea and vomiting in children. In a double-blind trial in 60 children suffering from gastroenteritis complicated by vomiting, it was found that suppositories of domperidone (30 mg) were more effective than either metoclopramide (10 mg) or placebo in reducing the severity of vomiting, nausea and other symptomatic parameters. No side effects were reported throughout the 24 hour period of the trial and the results suggest that domperidone suppositories may well prove to be the drug of choice in such cases of paediatric vomiting.


Domperidone drops in the symptomatic treatment of chronic paediatric vomiting and regurgitation. A comparison with metoclopramide. Forty-seven infants and children suffering from chronic vomiting or regurgitation, participated in a two-week double-blind trial comparing 1% drops of domperidone, 1% metoclopramide drops or placebo. The dose was 0.3 mg/kg given t.d.s. before meals. Both active medicaments were significantly more effective than placebo in controlling the symptoms and domperidone was also significantly superior to metoclopramide. It is concluded, in view of the good safety margin with domperidone, that this drug could become the treatment of choice in such cases.


A multicentre pilot study of parenteral and rectal administration of domperidone in the treatment of severe vomiting in children. A small scale pilot study among 41 children with severe vomiting, showed that a single administration of domperidone either intravenously, intramuscularly or rectally, effectively controlled the symptom within 3 hours in 36 (88%) patients. The excellent results together with the safety of this new drug indicate its potential value in these patients.


Domperidone in the prevention of post-operative nausea and vomiting. In a series of open pilot studies, intravenous domperidone was given to three groups of post-operative patients, at doses ranging from 10 mg to 60 mg. As a  result of these studies, it was decided that a regime of 20 mg initially, followed by maintenance doses of 10 mg at 6 hourly intervals was highly effective in preventing post-operative nausea and vomiting. Consequently this regime was chosen to evaluate domperidone against placebo in a double-blind study involving 106 patients. The results showed that only three out of 53 patients (5.7%) on active treatment were having nausea and vomiting compared with 16 of 53 patients (30.2%) on placebo. It is concluded that this regime is effective in preventing post-operative nausea and vomiting.


Evaluation of the effect of domperidone on human oesophageal and gastroduodenal motility by intraluminal manometry. Intraluminal manometry has been used in a series of five studies on healthy volunteers and patients, to examine the action of domperidone on lower oesophageal sphincter pressure (LOSP), on peristaltic contraction, amplitudes and on antral, pyloric and duodenal motility. Furthermore, the effect on gastric acid secretion, pH, secretory volume and serum gastrin levels was studied. It was found that domperidone increased LOSP significantly but was less effective in patients with symptomatic gastro-oesophageal reflux than in normal volunteers. The drug also increased the amplitude of oesophageal and duodenal peristalsis but had no effect on endogenous gastrin release or on gastric acid secretion. The results suggest that this drug may be useful in the treatment of gastro-oesophageal and gastroduodenal reflux. This potential benefit is enhanced by the absence of side effects even when given in high doses.


Nutrition and lactation.

Nutrition and lactation. Recommended dietary allowances for women during pregnancy are discussed in the light of actual intakes both in the developing and industrialized countries. The difference between total energy intakes in the industrialized countries (around 2900 kcal) and in the developing countries (around 1600 kcal) is emphasized. Data are provided from The Gambia which demonstrate the effect of seasonal changes in maternal dietary intake on the quantity of breast milk produced and on its quality. The relationship between breast-milk supply and infant growth is also demonstrated.


The respiratory response to pregnancy.

The respiratory response to pregnancy. The respiratory response to pregnancy appears to be largely mediated by the action of progesterone and, perhaps to a lesser extent, oestrogens, at least in the first and second trimesters. The mechanical effects of the gravid uterus cause relatively little change in pulmonary mechanics, although finer changes in airways function require further investigation. Dyspnoea during pregnancy is also probably hormone-mediated but the exact temporal relationship between hormone status, functional change and the development of symptoms is not yet clearly defined.


Respiratory disease in pregnancy.

Respiratory disease in pregnancy. Respiratory disorders seem to be better tolerated during pregnancy than disorders of the cardiovascular system. Pregnancy seems to have a variable effect on bronchial asthma although respiratory function in general shows little change. Similarly patients with bronchiectasis do not tend to show functional deterioration. Fetal growth, however, may be adversely affected in these conditions if arterial hypoxaemia is present. The problems of drug treatment of respiratory disorders in pregnancy, particularly asthma and tuberculosis, are discussed.


Renal physiology in pregnancy.

Renal physiology in pregnancy. The changes which occur in renal excretory function during pregnancy are discussed. The relationship between glomerular filtration rate and effective renal plasma flow is examined in the light of new serial data obtained under conditions of saline diuresis. Changes in the renal handling of nutrients and in the excretion of waste products during pregnancy are reviewed.


Renal disease in pregnancy.

Renal disease in pregnancy. In this review the need for early antenatal assessment of renal disease is stressed as is the need to follow-up all patients in the puerperium in whom renal dysfunction has been suspected during pregnancy. A variety of renal disorders and their effect on the outcome of pregnancy are discussed.


The physiology of thyroid function in pregnancy. Pregnancy has a variety of effects on maternal thyroid function. Thyroid gland enlargement is common particularly in areas of relative iodine deficiency. The renal clearance of iodine is increased in pregnancy and together with an increased volume of iodine distribution, leads to a low plasma inorganic iodine and thus increases the thyroidal iodine clearance. However, the absolute iodine uptake and hormone production rate remain unchanged. There is an increase in the serum thyroxine (T4)and triiodothyronine (T3) concentration largely due to an increase in thyroid hormone-binding proteins. Free thyroxine and free T3 remain unchanged in pregnancy as does the Free Thyroxine Index, which gives the single most accurate measure of thyroid function. The placenta secretes a number of thyroid stimulators including human chorionic gonadotrophin and possibly chorionic thyrotrophin and molar thyrotrophin whose physiological role is to date poorly understood. The fetal thyroid develops independently, and although fetal T4 CONCENTRATION RISES PROGRESSIVELY To maternal by term, the T3 concentration is markedly reduced owing to preferential formation of inactive reverse T3.


Liver and gastrointestinal function in pregnancy. Difficulties arise in the interpretation of liver tests in the pregnant subject, since some values increase (alkaline phosphatase) whilst others remain unchanged (transaminases) or fall during pregnancy. The diagnosis and management of some causes of jaundice in pregnancy, such as viral hepatitis, gall stones, benign intrahepatic cholestasis and acute fatty liver of pregnancy are discussed. Little is known about the commonest symptoms of pregnancy (nausea, vomiting and constipation) other than that they might be due to hormonally induced alteration of sphincter tone. However, pre-existing bowel disease has a greater effect on pregnancy. Fertility is reduced in poor nutritional states (e.g. coeliac and Crohn's diseases) and an increased occurrence of spontaneous abortion has been noted. For inflammatory bowel diseases, the time of onset is important in determining the outcome of pregnancy. Relapse in the disease is commonest in the first trimester and in the puerperium. Treatment of these conditions is essentially as in the non-pregnant subject. The controversial subject of sulphasalazine and steroid usage in pregnancy is discussed.


Metabolic changes in pregnancy relevant to diabetes mellitus. The alterations in carbohydrate metabolism during pregnancy are discussed and possible mechanisms for these changes are put forward. It is stressed that the raised levels of plasma glucose, the enhanced response to insulin and the decreased tissue sensitivity to insulin are all features of normal pregnancy. It may be difficult to distinguish this from very early forms of diabetes mellitus during pregnancy, the detection of which is briefly considered.


Blood clotting and fibrinolysis in pregnancy. During normal pregnancy, the concentrations of many of the clotting factors rise, thereby increasing the potential to generate fibrin. There is also evidence of increased thrombin activity during normal pregnancy which sharply increases during placental separation. Antithrombin III, the main inhibitor of thrombin and activated factor X, shows no compensatory rise during pregnancy but increases during the puerperium. Plasminogen and antiplasmin concentrations rise during pregnancy but systemic fibrinolytic activity, as measured by the euglobulin lysis time, is markedly depressed during pregnancy; the reduced fibrinolytic activity returns to non-pregnant values very soon after delivery. The loss of fibrinolytic  activity is presumed to be loss of plasminogen activator, because when this is added in excess in the urokinase sensitivity test, the fibrinolytic response is normal. The capacity for localized fibrinolytic activity is not lost, however, because fibrinolytic degradation products are slightly raised during pregnancy. The overall pattern is one of increased coagulant and reduced fibrinolytic capacity during pregnancy which may protect the pregnant woman against the haemostatic challenge of placental separation.


Coagulation problems in human pregnancy. Coagulation problems in pregnancy are primarily associated with overactivity of the intrinsic clotting system. This accounts for the increased incidence of thrombo-embolism during pregnancy. Where specific obstetric complications cause clotting problems the common underlying feature is usually placental pathology as in abruptio placentae, pre-eclampsia or hydatidiform mole. Abnormal activation of the clotting system is an early, and occasionally the first detectable feature of pre-eclampsia, but there is no evidence that this is a primary change. Therefore the role of anticoagulant treatment in the management of pre-eclampsia remains questionable. A new test for estimating factor VIII consumption is proving to be a sensitive index of early activation of the clotting system and can be used for the diagnosis of early pre-eclampsia.


Comparative susceptibility and effect of mild Aspergillus fumigatus infection on three strains of chickens. A single Comb White Leghorn strain (Dryden X Auburn = DAX) was more susceptible to Aspergillus fumigatus infection and suffered significantly greater mortality than the Athens-Canadian or a Vantress X Arbor-Acres cross exposed soon after hatching. The unexposed controls of the three types weighed significantly more than the corresponding exposed survivors at 5 weeks of age.


Medial plantar sensory flap for coverage of heel defects. A sensory flap, based on the medial plantar artery and incorporating the cutaneous branches of the medial plantar nerve, is described for the coverage of heel defects.


The free latissimus dorsi myocutaneous flap. The general anatomy and the detailed vascular anatomy of the latissimus dorsi myocutaneous flap is described, and its use as a free flap is illustrated. The speed and ease with which it can be raised, its long vascular pedicle, the large diameter of the donor vessels, and the potentially large size of the flap are emphasized.


Construction of natural appearing female genitalia in the male transsexual. A surgical technique is presented which gives an excellent appearance and functional result in male-to-female transsexual conversion of genitalia. The complications have been few, and the conversion is done in one operation.


The relationship between the number of sutures and the strength of microvascular anastomoses. The relative strengths of microvascular anastomoses in rat femoral arteries were measured, comparing controls (no anastomosis) to those with 4, 6, 8, 10, 12, and 14 stitches. The ones in which 8 sutures were used most closely paralleled the control state, whereas those with 4 or 6 sutures were clearly inferior. With a greater number of sutures the vessel behaves as a "shorter" vessel, with the anastomosis becoming the weakest part of the vessel.


Use of submandibular flap to close pharyngostomes and other defects of lower anterior neck region. We describe the use of a suprahyoid flap for reconstruction in the lower anterior neck. It has been most useful for immediately closing pharyngostomes and for resurfacing defects from the excision of squamous cell carcinoma of the larynx or other neoplasms involving the skin. This flap provides a good deal of viable tissue, it can easily be rotated without a delay procedure, and the donor area is closed by direct suture. We present our experience with 22 cases.


Bone scintigraphy of experimental composite bone grafts revascularized by microvascular anastomoses. In these experiments the reliability of bone scintigraphy with 99mTc diphosphonate, to assess anastomotic patency and the viability of revascularized composite fibular grafts, was studied. It was shown that bone scintigraphy is very useful for the diagnosis of anastomotic patency, but only in the first postoperative weeks. Bone scintigraphy gives no information on the viability of bone grafts.


Bone formation by revascularized periosteal and bone grafts, compared with traditional bone grafts. Three groups of dogs were studied to compare the bone formation obtained with traditional bone grafting techniques, and that obtained with revascularized periosteum or revascularized bone grafts--all in unstressed bone. Revascularized periosteum did not produce a significant amount of bone in this unstressed model. At 4 months the revascularized rib grafts had a slightly greater tolerance to stress at the callus site than traditional bone grafts, but the incidence of non-union was the same. We conclude that the use of revascularized bone grafts should be reserved for situations in which traditional bone grafting techniques are unlikely to be successful.


Beneficial effect of staged division of pedicle in experimental axial-pattern flaps. Using an experimental model, the effect of a staged division of the pedicle of a flap on vascularization from its bed was studied. This delay procedure seemed to stimulate the ingrowth of a greater number and larger size of vessels--to enhance the blood flow from the bed with significantly greater tissue survival in the flap after complete division of the pedicle.


Nutrient blood flow in delayed axial pattern skin flaps in pigs. Blood flow was investigated in 112 skin flaps (84 delayed and 28 undelayed) in 28 pigs. The flow was significantly (P less than 0.001) increased over the control flow with increasing delay intervals, reaching the greatest flow at one week after the delay (paralleling the increase in tissue survival). This increased blood flow persisted after definitive flap raising. The circulatory adjustments within the first week of the delay constitute the delay phenomenon, and they determine the ultimate viability of the skin flap in this model.


The seventeenth-century transformation of the hysteric affection, and Sydenham's Baconian medicine. Before 1600 the 'hysteric affection' was a paroxysmal ailment of women explained as primarily due to the condition or malposition of the womb. During the seventeenth century attention shifted from the womb to the brain. Then Thomas Sydenham's clinical method yielded a view of hysteria which comprehended a wide range of illness with a mental component, and which was related to the whole person. In the course of this paper the relation of the hysteric affection to witchcraft, demonic possession, St Vitus' dance (chorea), hypochondria and melancholy is also noted.