Age-dependent rapid antiinsulin effect of hydrocortisone hemisuccinate during insulin induced hypoglycemia in white rat. The effect of hydrocortisone hemisuccinate upon the intravenous insulin-induced hypoglycemia in various age-groups of white rats was studied. Insulin was injected intravenously in a dose of 10-(2) units per 100 g b.w. in the same age-groups of animals in a basal state, and 2 days later, 15 minutes after the i.p. administration of hydrocortisone hemisuccinate (0.5 mg/100 g b.w.). It has been estabished, that hydrocortisone hemisuccinate had a rapid anti-insulin effect, which is quantitatively different in dependence on the age of animals.


[Proceeding: Production rate, metabolic clearance rate and mean plasma concentration of cortisol in hyperthyroidism (author's transl)]. The adrenocortical function was studied in 23 patients with hyperthyroidism and compared with a group of 15 normal subjects. Parameters of adrenal function were determined with 1,2(3)H-cortisol. The half-life of cortisol is significantly shortened in hyperthyroidism, as compared to normal subjects (49,5 +/- 6,6 min vs 68,3 +/- 10,5 min) and metabolic clearance rate is increased (418,5 +/- 89,5 L/24 h vs 237,5 +/- 48,5 L/24 h, for normal subjects). The production rate of cortisol, calculated from specific and cumulate activities of THE and THF is increased in hyperthyroidism expressed as mg/24 h or mg/m2/24 h (respectively : 26,7 +/- 7,8 mg/24 h vs 15,7 +/- 3 mg/24 h and 16,9 +/- 4,6 mg/m2/24 h vs 9,5 +/- 1,8 mg/m2/24 h). The mean plasma concentration, calculated as the radio (see article) is not statiscally different in hyperthyroid and normal subjects (6,8 +/- 2,1 microg/100 ml vs 7,3 +/- 1,9 microg/100 ml). 7 patients were reinvestigated after treatment of thyrotoxicosis when they were clinically and biologically in euthyroid state. All the values were normalized, without statistically significant difference from control (T 1/2 = 65,4 +/- 18 min, Metb Cl. Rate : 255 +/- 64,5 L/24 h, production rate : 15,6 +/- 1,8 mg/24 h and 9 +/- 1,4 mg/m2/24 h. mean plasma concentration : 6,8 +/- 2,8 microg/100 ml). Shortened cortisol half life, increased metabolic clearance rate and production rate, and normal mean plasma concentration have been reported in hyperthyroidism (Peterson, Copinschi, Gallagher). These changes, secondary to thyroid hormone excess, are the consequences of increased hepatic catabolism of cortisol. The activity of 11 OH steroid deshydrogenase is increased, as demonstrated by increased ratio (see article) in normal subjects (0,001 less than p less than 0,005). There is a high proportion of 17 kéto metabolites (E, DHE, THE) whose feed-back effect is weak as compared to 17 OH metabolites (F, DHF, THF). The hypothalamo-hypophyso-adrenal system is stimulated to maintain a normal plasma concentration. The fact that the mean plasma concentration is normal despite the increased production rate suggest that changes are rather due to increased catabolism than to central effect of thyroid hormones.


[Proceedings: Cortisol-dependent glycogen storage and responses to insulin and glucagon in rat fetal cultured hepatocytes (author's transl)]. It has been shown that in primary cultures of rat fetal hepatocytes cortisol induces the development of glycogen storage ability. Cortisol has also a permissive effect in insulin action on the development of the glycogen synthetic pathway. However the regulation of glycogenolytic pathway by glucagon, which is present before any significant amount of glycogen storage, is not cortisol dependent.


[Annual and circadian rhythms in plasma testosterone of five healthy young male Parisians (author's transl)]. Every other month, during the course of 14 months, the circadian rhythm in plasma testosterone (among others variables) of 5 healthy males (26 to 32 years) was documented. Subjects' synchronization : light-on at 07 +/-  1 hr; light-off at 23hr +/- 1.5 hr all the year long. Blood sampling 4-hourly, at fixed clock hours during 28 hrs, for radioimmunologic testosterone determinations. The cosinor method was used for statistical analyses. An annual rhythm in the testosterone 24-hr mean is detected (p less than 0.025) with a peak in October (from 16 July to 26 December, with 95% confidence limits). Annual mean (+/- 1 SE) - 759 (+/- 26)ng/100 ml. Peak-through difference = 107 ng/100 ml (from 106 to 290 with 95% confidence limits). The timing of the testosterone circadian peak, in the 24 hr-scale varies also in the course of the year. The peak is found around 08(00) in May and around 14(00) in November, this phase-shift being statistically significant (p less than 0.05). The sexual activity (daily self-recording) also has an annual rhythm with a peak in October.


[Proceedings: Sulpiride effects on plasmatic gonadotropins in women (author's transl)]. The study of longitudinal evolution of plasmatic gonadotropins in women receiving sulpirid, a psychotropic drug with a strong anti-ovulatory effect, shows the coexistence of anovulation and the peristance of a physiological pattern of gonadotropins during the first cycle of treatment. It also shows the persistance of LH peaks comparable to preovulatory levels more than one year after the initiation of therapy. However, the basal line became very unsteady. This study suggests the presence of two types of perturbations with sulpirid. A hypothalamic-hypophyseal mild action and, an ovarian resistance to gonadotropins resulting from the hyperprolactinism induced by sulpirid.


[Proceedings: Interrelations between cholinergic and monoaminergic mechanisms in the determinism of spontaneous electrical activity in the central nervous system of scorpion (author's transl)]. Spontaneous electrical activity of the cerebral nervous system of Scorpion is characterized by potentials of 30 muV, and of average frequency varying between 200 et 400 impulses/min. This activity is enhanced by acetylcholine, and inhibited by adrenaline, nor-adrenaline, and serotonine, from a pharmacological study, it is assumed that spontaneous electrical activity of cerebral nervous system is due to cholinergic neurons, and antagonized by a serotoninergic system.


[Proceedings: Plasma renin activity in management of Addison's disease (author's transl)]. 13 patients with Addison's disease, 7 men and 6 women, 19 to 61 years old, were investigated. Plasma Renin Activity (P.R.A.) is measured by radioimmunoassay of Angiotensin I (ng/ml/h) in the supine (S) and the upright (U) position. These patients are studied before treatment and under normal sodium diet in 11 cases: the P.R.A. value is constantly increased [5 men: MS = 10,09 (range: 6,2-12,5) and MU = 23,22 (range : 17,1-31,09), 6 women : MS = 24,48 (range : 3,46-45,04) and MU = 42,23 (range : 42,23 (range 17,37-69,34), to be compared with our normal values (M +/- S.D.) : MS = 1,02 +/- 0,39 and MU = 2,56 +/- 0,99 for men - MS = 0,82 +/- 0,14 and MU = 2,32 +/- 0,93 for women in follicular phase - MS = 1,45 +/- 0,56 and MU = 4,59 +/- 1,63 for women in luteinic phase. After dietary sodium restriction (10 mEq/24 h) in 2 cases, the P.R.A. is significantly increased with respect to the basal value]. Under Hydrocortisone alone (25 to 30 mg/24 h) and normal sodium diet, 4 patients kept significantly increased P.R.A. values. Under Hydrocortisone (20 to 40 mg/24 h) and 9-alpha-fluorohydrocortisone (50 to 100 microgrammes/24 h) for 6 days to 14 months, the P.R.A. value decrease into the normal range [men : MS = 1,02 (range : 0,54-1,92) and MU = 1,68 (RNAGE : 0,81-2,57) - 2 Menopausal women : MS = 1,55 and MU - 1,16. The P.R.A. measurement seems useful in the adaptation of Addision's disease treatment.


[Proceedings: Prolactin adenoma revealed by gemellary? pregnancy after clomiphen therapy. Hypophysectomy during 5 th month of pregnancy (author's transl)]. A 25 year old woman had galactorrhea and secondary amenorrhea since her first pregnancy at 20 years. After several treatments with Clomiphene, menses reappeared for 2 months and she became pregnant. At admission, she was in her 4th pregnancy month and had headaches and bitemporal hemianopsia. Hypophysectomy was performed during 5th pregnancy month. Prolactin adenoma with hemorragic lesions was found. Parturition of normal twins occurred 8th month. Partial hypophyseal recovery took place for the following 2 years, but hyperprolactinemia reappeared too.


[The limits and boundaries of De Morsier's syndrome (based on 33 personal cases) (author's transl)]. If De Morsier's syndrome represents the priviledged anatomo-clinical pattern of olfacto-genital correlations, the deteriorations of the sense of smell are not exclusively due to it. After having studied olfaction very precisely in 101 cases of hypogonadism, the authors report 17 cases of olfacto-genital displasia and bring out a clear hyposmia in other affections: Klinefelter's syndrome (25,7%), congenital anorchidism, puberty delay. A part from th: physio-pathological interpretation of these facts, there arises the problem of the precise nosological limits of De Morsier's syndrome.


[Proceedings: Effect of oestrogens and diet on lipids in the plasma of castrated rats of both sexes (author's transl)]. The hypertriglyceridemia after treatment with oestrogens by the castrated rats is of the same amplitude in both sexes with regimes enriched with saccharose or with beaf fat or with both. The gonosomes not influenced the hypertriglyceridemia after treatment with oestrogens.


[Progesterone administered by percutaneous route: an antiandrogen locally useful (author's transl)]. A skin specimen has been obtained from 5 volunteered men submited to a percutaneous administration of progesterone. Plasma progesterone, testosterone and dihydrotestosterone were evaluated before and after this treatment. Progesterone percutaneously administered does not change plasma testosterone and dihydrotestosterone and only slightly increases plasma progesterone. On the contrary, in the skin samples obtained from subjects percutaneously treated by progesterone, radioactive testosterone was not converted to dihydrotestosterone by skin homogenates. In conclusion, progesterone when percutaneously administered inhibits testosterone 5alpha-reduction and may be considered as an antiandrogen locally useful.


[Proceedings: Study of a new steroid: the 3beta,5alpha-tetrahydro-deoxycorticosterone (3alpha,5beta-tetrahydro-DOC). Its significance during pregnancy (author's transl)]. The physiological significance of a new steroid: the 3beta, 21-dihydroxy-5alpha-pregnan-20-one (3beta,5alpha-tetrahydro-DOC) was studied during human pregnancy. The urinary excretion values in the first and second trimester of pregnancy are 100-400 mug/24 h and in the third trimester the values increase to 240-1080 mug/24 h. This compound is not found in men nor in non-pregnant women but is found in the urine of newborns (2-12 DAYS): 25-80 mug/24 h. After perfusion of the fetus with H-deoxycorticosterone, 3H-3beta, 5alpha-tetrahydro-DOC was found in the fetal liver. These data suggest that this steroid could originate in the fetus: parallel studies of the urinary excretion of the other isomer : 3alpha821 dihydroxy-5beta-pregnan-20-one (3alpha,5beta-tetrahydro-DOC) shows that this compound increases at the end of pregnancy but its excretion rate is 2-3 times less than that of 3beta, 5alpha-tetrahydro-DOC.


[Proceedings: Iodine metabolism in isolated human thyroid cells (hyperplastic goitre and toxic adenoma) (author's transl)]. We present here data on hormone synthesis and thyroxine secretion by isolated human thyroid cells. Thyroid cells were dispersed by trypsinization. Thyroid tissue was surgically obtained from two euthyroid patients with hyperplastic goitre and from two thyrotoxic patients with toxic adenoma. In 6 hr incubation experiments, we observed that isolated human thyroid cells, i) concentrated iodide, ii) synthetized iodothyronines, iii) released thyroxine in the incubation medium. Each parameters was TSH dependant. That thyroxine release was due to a secretion process is suggested by similar and further documented data obtained with isolated hog thyroid cells. This technique may provide further help for thyroid physiopathology investigation in humans.


Data on the HL-A linkage group.

Data on the HL-A linkage group. Lod scores from a study in 229 families of the linkage relations of HL-A-PGM3 to 19 marker loci and cystic fibrosis are reported. The data exclude that ADA belongs to this linkage group while they give weak support for the inclusion of P. There is weak evidence for linkage of cystic fibrosis to PGM3, but none for linkage to HL-A. No new suggestive linkages appeared.


[Radioautographic study of the action of androgens on the synthesis of nucleic acids in the male genital tract of the white mouse (author's transl)]. A comparison was made, by autoradiographic studies, of the nucleic acids synthesis in the target organs of the male hormone, in normal mice, castrate and castrated mice with an implantation of a testosterone pellet. The results show that the response of each of these organs, to a physiological supply of hormone or to a supraphysiological supply is quite different, both in intensity and in evolution. The differences are still apparent in castrated animals. The transfer of RNA from the nucleus to the cytoplasm seems to be affected by the castration. The signification of these results is discussed.


[Proceedings: Peroxydase activity in benign thyroid diseases and in experimental rat goiters (author's transl)]. Peroxydase activity in various benign thyroid diseases has been investigated. In hyperthyroid patients treated with antithyroid drugs, the observed increase in iodide-peroxydase activity (7 times that of normal tissue) is double than that of the DNA content. In goiter, the activity is 3 times that of normal tissue while the DNA content is unchanged. These results are in agreement with those obtained in rats maintained on a low iodine diet suggesting that high cellular enzymatic activity is due to specific enzyme induction in excess of cell proliferation and protein synthesis.


Genetically determined polymorphism of a form of hexokinase, HK III, found in human leucocytes. 1. A form of hexokinase which appears to correspond to HK III, seen in liver, spleen and lung, has been identified in human polymorphonuclear leucocytes. HK III activity has not been demonstrated in lymphocytes, permanent lymphoblastoid cell lines or in cultured fibroblasts. 2. In fresh leucocyte preparations HK III usually appeared as a single band, but in extracts of post-mortem tissues multibanded patterns were seen. Leucocyte preparations also give multi-banded patterns after storage for more than a few hours. 3. In certain individuals the HK III showed a two-banded pattern even in fresh preparations. Repeat samples and family studies suggested that this pattern was genetically determined and represented a heterozygote for a common allele HK1III and a less common variant HK2III. Out of a total of 330 English people successfully tested 10 probable heterozygotes were found. 4. It is suggested that HK III may be a monomeric enzyme whose genetic determination is independent of that of the other main forms of hexokinase.


[Proceedings: In vitro thyroid hormone formation (author's transl)]. Iodination of a non halogenated goiter thyroglobulin and the resulting thyroxinogenesis was studied in vitro with purified thyroid peroxidase, H2O2 generating system and various concentrations of iodide. The rate of iodination was linear during the first minutes of incubation but thyroxine synthesis only began after a lag period whatever the iodide concentration in the incubation medium was. With high iodide concentrations a highly iodinated thyroglobulin (40-50 iodine atoms) containing no thyroxine was obtained after 3 minutes of incubation. If this highly iodinated goiter thyroglobulin was purified and reincubated with peroxidase and H2O2, thyroxine synthesis was again observed only after a lag period (2-3 min). In the absence of iodide the enzyme to elicit thyroxine synthesis. Depending of its concentration free diiodotyrosine exerts two opposite effects on the reaction catalyzed by thyroid peroxidase : at high concentration (10(-4) M) in inhibition of thyroglobulin iodination, and at low concentration (10(-7), 10(-8) M) a stimulating effect on thyroid hormones biosynthesis.


Premature centromere division: a mechanism of non-disjunction causing X chromosome aneuploidy in somatic cells of man. Apparent acentric fragments which replaced a C-group chromosome in cultured blood lymphocytes from a woman patient were shown by autoradiography, G-banding and C-banding to be complete X chromosomes in which the centromere had divided prematurely in relation to the centromeres of other chromosomes in the same metaphase. Metaphases with multiple 'fragments' suggested that non-disjunction of the 'fragments' had occurred. This anomaly of the X chromosome was associated with increased aneuploidy of a C-group chromosome, presumed to be X. Premature centromere division of the X chromosome (PCD, X) appeared to be a mechanism of non-disjunction which caused significant monosomy and trisomy of the X chromosome in blood cells and skin fibroblasts. The frequency of cells with multiple fragments and the extent of the aneuploidy in 48 hr. blood cultures indicated that this mechanism of non-disjunction operated during mitosis both in vivo and in vitro. Premature centromere division occurred at a lower frequency in normal women donors, and was age-related, being four times more frequent in women 60 years and older than in women under 40. Associated with the higher frequency of PCD, the older women also showed evidence of increased X chromosome aneuploidy. Premature centromere division of the X chromosome is considered to be the mechanism of non-disjunction, causing the well-documented increased number of 45, -C metaphases in ageing women. Premature centromere division was rare in men, but an age effect was again suggested.


Quantitative linkage: a statistical procedure for its detection and estimation. A new approach for detecting and estimating quantitative linkage which uses sibship data is presented. Using a nested analysis of variance design (with marker genotype nested within sibship), it is shown that under the null hypothesis of no linkage, the expected between marker genotype within sibship mean square (EMSbeta) is equal to the expected within marker genotype within sibship mean square (EMSe), while under the alternative hypothesis of linkage, the first is greater than the second. Thus the regular F-ratio, MSbeta/MSe, can be used to test for quantitative linkage. This is true for both backcross and intercross matings and whether or not there is dominance at the marker locus. A second test involving the comparison of the within marker genotype within sibship variances is available for intercross matings. A maximum likelihood procedure for the estimation for the recombination frequency is also presented.


[Proceedings: Kinetics and disposal rate of triiodothyronine in patients with atuonomous hot nodular goiter, with or without thyrotoxicosis (author's transl)]. Eight female patients are studied, four of them without hyperthyroidism. The following were measured before and after surgery = hormonal iodine by column, serum concentrations of T T3, AF T3, TSH, total T3 distribution space, T3 pool size T3 fractional turnover rate. T T3 is measured in the serum of peripheral venous blood, nodular venous blood and of jugular venous blood of the opposite side of the adenoma. Before surgery, the mean of T T3 in patients with hyperthyroidism is increased in serum obtained from brachial and not nodule venous blood. Are also increased AF T3 and T3 production rate. In patients without hyperthyroidism, T T3, AF T3 are increased in two subjects only, but T3 production rate is rised among three of them. After surgery the previous values are not different with normal values. These data are in good agreement with the hypothesis that, in patients without thyrotoxicosis, there is an increase in T3 production from not nodular goiter. There phenomena may explain unresponsiveness to TRH test and inactivity of normal thyroid. Absence of hyperthyroidism may be due to a lack of sensitivity of peripheral tissues to the increase of T3.


A non-parametric test for linkage with a quantitative character. A non-parametric test for the detection of linkage between a quantitative and a mendelian character is described. It can be applied to families of three, two or one generations. The limitations, advantages and disadvantages of this test are discussed.


Phenylketonuria as a balanced polymorphism: the nature of the heterozygote advantage. Mothers of children with phenylketonuria have a significantly lower miscarriage rate than a matched control population in Ireland and west Scotland. This protective effect of the gene against some factor causing foetal death would seem to constitute a heterozygote advantage which might account for the previously observed polymorphism for phenylketonuria. It is suggested that the decrease in foetal mortality is mediated by the higher concentration of phenylalanine in the heterozygous mother's blood, but that this is not a simple nutritional effect of an increased supply of an essential amino acid leading to increased protein deposition.


Linkage data on red cell acid phosphatase from family studies. An analysis of the linkage relationships of red cell acid phosphatase (ACP1) with 36 other loci is presented. Close linkage is excluded for many loci. The hint of loose linkage with MNSs is not statistically significant, nor is it apparently consistent with the assignment of ACP1 and and MNSs to different arms of chromosome 2.


Segregation of ACP1 and MNSs in families with structural rearrangements involving chromosome 2. Data from seven families carrying rearrangements and variants of chromosome 2 have been analysed in relation to the assignment of ACP1 and MNSs. The data are consistent with the regional assignment of ACP1 to 2p23, but not with that of MNSs to band 2q14.


Correlated odour threshold bimodality of two out of three synthetic musks. The odour threshold bimodality for exaltolide described by Whissell-Buechy & Amoore (1973) among American whites is confirmed for a population sample in London. A highly correlated bimodality presumed to be caused by the absence of inactivity of certain receptor sites is shown to exist for another structurally different musk substance, musk ambrette. The thresholds for musk ketone show no bimodality and their correlation with the thresholds for the two other musks is low.


Racial differences in pigmentation and natural selection. The inheritance of skin colour in man is not well understood. A clearer understanding could be obtained by taking into account the biological basis and genetical control of pigmentation in other mammals, particularly the experimental species. In these, most of the loci governing pigmentation are pleiotropic, colour being only one of the traits affected by them. Their products are evidently concerned with other metabolic pathways as well. There is strong evidence for inter-specific homology of pigmentation loci in mammals, and the situation in man may not be radically different. It is therefore possible that racial differences in skin colour may have resulted from the action of natural selection on these other functions of pigmentation genes.


[Comparative immunoelectrophoretic analysis of culture and bloodstream forms of "trypanosoma" (Trypanozoon) brucei gambiense". Demonstration of stage and antigenic type specific antigens (author's transl)]. The comparative immunoelectrophoretic analysis of the antigenic structures of culture and bloodstream forms with cross absorption tests confirm the existence among Trypanosoma gambiense antigens of: --numerous antigenic components common to culture and bloodstream forms;--several antigenic components specific of either culture forms or bloodstream forms. Among the latter, two components are shown to be specific of the antigenic type and appear to support the immunochemical specificity of each variant.


Modulation of the immune response to transplantation antigens. IV. Enhanced growth of tumour allografts in mice immunised with papain-solubilised transplantation antigen. C57/Bl mice have been immunised with papain solubilised CBA transplantation antigen and subsequently challenged with a CBA tumour. Variations in antigen dose, immunisation schedules and routes of injection were compared. Two procedures in particular led to enhanced growth of the tumour allograft: (a) a single injection of antigen seven days before graft, and (b) a two-pulse immunisation spaced over 42 days. Mice given the seven-day course showed impaired cell-mediated cytotoxicity and blocking antibody at the time of challenge which was succeeded by blocking antigen in the circulation after challenge. Mice immunised by the two-pulse course developed heightened cell-mediated cytoxicity, but showed a persisting level of blocking antibody in the serum. Thus, although both immunisation regimes enhanced tumour growth, they did so by different mechanisms.


Mineral nutrition of Streptomyces kanamyceticus for kanamycin formation. Kanamycin production by Streptomyces kanamyceticus ATCC 12853 requires magnesium sulfate and potassium phosphate at concentrations of 0.4 and 1.0 g per liter, respectively. The optimal concentrations of Fe and Zn for production of kanamycin are 0.25 and 0.575 mug/ml, respectively, whereas Mo at 0.04 mug/ml allows maximal cellular growth and antibiotic synthesis. Mn and Ca are without any effect. Cu, Co, Ni, and V have inhibitory effect on growth of the organism as well as kanamycin formation.


Regulation of lymphocyte responses in vitro. VI. -Potentiation of the response to phytohemagglutinin by cytochalasin B. Low concentrations of cytochalasin B (CB) potentiated the DNA-synthetic response of rat lymph node cells (LNC) to PHA. Maximal potentiation was observed at suboptimal concentrations of the mitogen, less at optimal and usually none at supraoptimal concentrations. Other metabolic responses (RNA and protein synthesis) as well as the actual number of morphologically transformed lymphocytes were also enhanced. The presence of serum in the culture was an absolute requirement for CB potentiation. A maximal effect was usually obtained when CB was present from the start of the culture. However, addition of CB as late as 46 h after PHA produced a lower but consistent potentiation. The responses to PHA of thymus cells and spleen cells were respectively more and less increased by the drug than that of LNC. These results suggest that CB acts by opposing a serum-dependent cell interaction.


Relationship of early readings of minimal inhibitory concentrations to the results of overnight tests. Broth dilution minimal inhibitory concentration (MIC) readings were compared after different incubation periods and with different inoculum concentrations. The purpose was to determine the best conditions for obtaining early results as close as possible to overnight readings. Initially, 76 antibiotic-organism combinations were tested using the International Collaborative Study technique and inoculum and were read after 3, 8, and 18 h of incubation. Approximately 28% of tests showed fourfold or greater increases in MICs after 18 h of incubation compared with the 3-h readings. No overnight MICs were lower than early readings. MICs of single antibiotics against seven organisms were also read with an automatic particle counter to confirm the validity of the visual readings. Experiments were made to determine whether inoculum manipulation could reconcile the differences between 3- and 18-h MIC results. One hundred and eight organism-antibiotic combinations were tested comparing 3-h MIC readings using an inoculum of 10(7) organisms per ml with overnight readings using 10(5) per ml. In 71 cases, readings with both inocula were within the range tested and 57 (86%) were within +/-1 log(2) of each other and followed an approximately normal distribution. Improved comparability between early read and overnight MICs thus may be achieved by inoculum manipulation, and this may be a suitable approach in the future development of automated procedures.


Simplified method for antimicrobial susceptibility testing of anaerobic bacteria. A simple, abbreviated broth dilution test (tube test) utilizing a commercially available medium and inexpensive disposable materials, and which could be performed entirely in room air, was developed and used to test the susceptibility of 100 strains of anaerobic bacteria to clindamycin, chloramphenicol, ampicillin, and tetracycline. Results are reported in categories of susceptibility: susceptible to concentrations surpassed in vivo with usual dosage, susceptible to concentrations surpassed in vivo with high dosage, and resistant to concentrations achievable in vivo. Results are compared to minimal inhibitory concentrations which were determined simultaneously by using a microdilution method in an anaerobic glove box. Twenty strains of Bacteroides fragilis, 10 strains of Fusobacterium, 20 strains of Clostridium, 10 strains of gram-positive non-sporeforming bacilli, and 30 strains of cocci grew to visible turbidity within 1 day of incubation. Of the 360 antibiotic-organism combinations tested, 98% were in a susceptibility category that corresponded (within one concentration) to the actual minimal inhibitory concentration as determined by the microdilution method. After 2 days of incubation, growth was more abundant, but results often indicated inappropriate degrees of resistance. Variation in inoculum size had little effect on results. Ten strains of B. melaninogenicus did not grow enough for susceptibility to be categorized accurately. The tube test could be used in any clinical microbiology laboratory for a limited number of susceptibility tests on anaerobic bacteria other than B. melaninogenicus without preparation of special media or purchase of special equipment.


Phagocytosis of autologous and heterologous erythrocytes by rat and guinea pig macrophages. Rat and guinea pig peritoneal macrophages are compared in their ability to phagocytose guinea pig, rat and sheep red cells. The ability of the phagocytes to ingest autologous red cells does not seem to be drastically reduced compared to their ability to ingest alien cells.


Comparative in vitro activity and clinical pharmacology of ticarcillin and carbenicillin. The in vitro activity and human pharmacology of ticarcillin, a semisynthetic penicillin more active than carbenicillin against Pseudomonas, were compared. There has been no increase in resistance to ticarcillin of Pseudomonas strains over the past 5 years, but resistance of indole-positive Proteus and Serratia strains has been documented. After intramuscular (i.m.) injection of 1 g of ticarcillin, mean peak levels occurred at 1 h (26.9 mug/ml) with a decline over 6 h (6.8 mug/ml). Serum half-life was 84 min. Dilution of ticarcillin lidocaine reduced pain on i.m. injection but did not alter serum levels. Blood levels after 1 g i.m. are adequate to treat infections produced by Escherichia coli, Proteus mirabilis, and some Enterobacter, but not Pseudomonas. After rapid intravenous infusion of 3 and 5 g, mean peak serum levels of ticarcillin were slightly lower for 1 h than those achieved with carbenicillin. Probenecid administered before infusion produced increases in blood levels, half-lives, and volume of distribution. The biological half-life of ticarcillin was 72 min compared to 66 min with carbenicillin. There was a larger volume of distribution for ticarcillin than carbenicillin (15 liters versus 14 liters). The ticarcillin half-life when administered with probenecid was 108 min. Urinary recovery of ticarcillin was 77% against 95% of carbenicillin. However, approximately 10% of ticarcillin is recovered as penicilloic acid so that 95% of an intravenously administered dose is recovered.


Regulation of lymphocyte responses in vitro. VII. - "Cell contact inhibition", a possible regulatory mechanism for lymphocyte activation. Potentiation by cytochalasin B (CB) of (3H)thymidine incorporation in lymphoid cell suspensions stimulated by phytohemagglutinin (PHA) is counteracted by adherent cells. The drug has no effect on the production of the macrophage product lymphocyte activating factor (LAF) and does not interfere with its potentiating activity. CB appears to inhibit agglutination of lymphocytes. Other factors (absence of serum, macrophages, mechanical disturbance of the cultures) diminishing the size of aggregates increase the response of lymphocytes. Responses to less agglutinating mitogens are less or not enhanced by CB. Factors increasing agglutination or/and cell contacts (high cell density, wheat germ agglutinin) diminish lymphocyte activation and make it susceptible to CB potentiating effect. The results suggest that topoinhibition (cell contact inhibition) is an important mechanism regulating the lymphocyte response to mitogens in culture. Its effect could be modulated by macrophages and certain serum factors, and CB would potentiate these responses by reducing contact inhibition.


Viral keratitis-inhibitory effect of 9-beta-D-arabinofuranosylhypoxanthine 5'-monophosphate. Topical application of 9-beta-d-arabinofuranosylhypoxanthine 5'-monophosphate (ara-HxMP) significantly inhibited the development of keratitis induced by types 1 and 2 herpes simplex virus and vaccinia virus in the eyes of rabbits. Parameters for evaluation of efficacy were infectivity (corneal opacity, lesion size, and type), Draize (erythema, conjunctival swelling, and discharge), and reduction in titer of recoverable virus from the eye. When the relative efficacy of the related compounds 9-beta-d-arabinofuranosyladenine (ara-A), ara-A 5'-monophosphate (ara-AMP), and ara-Hx was determined against type 1 herpes simplex virus in a parallel experiment, the more water-soluble compounds (ara-HxMP, ara-AMP) were the most effective. The relative efficacy of ara-A was also determined against type 2 herpes and vaccinia virus-induced keratitis. Mortality in rabbits due to central nervous system involvement caused by types 1 and 2 herpes simplex virus was inhibited. Ara-HxMP was not discernibly toxic to the eye at concentrations of at least 20%; efficacy was still discernible with a 0.1% solution.


Inhibition of protein synthesis in intact HeLa cells. Polysome analysis has proved to be a sensitive probe for the mode of action of inhibitors of protein synthesis in intact HeLa cells. To classify the active compounds as inhibitors of initiation, elongation, or termination, their effects on the cellular polyribosome pattern were compared under three conditions. These conditions tested (i) their direct effect on the polyribosome profile; (ii) their effect on ribosome run-off produced by hypertonicity; and (iii) their effects on recovery from hypertonicity. Using this technique, diacetoxyscirpenol, 2-(4-methyl-2,6-dinitroanilino)-N-methylpropionamide, and three alkaloids, harringtonine, isoharringtonine, and homoharringtonine, were found to be inhibitors of initiation. Polysome analysis indicated that in HeLa cells 7.8 x 10(-7) M pactamycin, which inhibited protein synthesis 94%, interfered with elongation as well as initiation under these conditions. Emetine, anisomycin, cycloheximide, and trichodermin each gave polysome patterns consistent with inhibition of elongation. Fusidic acid and aurintricarboxylic acid inhibited incorporation of [(14)C]leucine into intact HeLa cells, but polysome analysis did not localize any specific inhibitory effects to the initiation, elongation, or termination steps of protein synthesis. The use of specific inhibitors of initiation of protein synthesis has indicated that most, if not all, mammalian messenger ribonucleic acids contain a single initiation site.


Fluid and penicillin G dynamics in polyethylene chambers implanted subcutaneously in rabbits. Chemical and cellular characteristics of fluid within subcutaneously implanted polyethylene chambers in rabbits were studied over a 3-month period. The fluid attained a relatively stable protein and cellular composition which was consistent with a mononuclear exudate. After a single dose of intramuscular penicillin G, the antibacterial activity of chamber fluid was found to be dynamic and similar to the serum antibacterial activity. This animal model may be useful for in vivo studies of the interaction of microorganisms with antimicrobial agents.


Response of yeast and mycelial phases of Histoplasma capsulatum to amphotericin B and actinomycin D. The dimorphic fungus Histoplasma capsulatum exists in two phases: a unicellular yeast form at 37 C and a mycelium at 25 C. We have found that these two phases have selective drug susceptibilities. The mycelial form of H. capsulatum was much more susceptible to the polyene antibiotic amphotericin B than the yeast form; in contrast, the yeast form was more susceptible to the antibiotic actinomycin D. The changes in susceptibility occurred early in the transition between the two phases and permitted the transitions to be blocked by sublethal concentrations of the appropriate drugs.


Efficacy of the inactivation of bacterial spores in white petrolatum and a hydrophilic ointment by gamma irradiation. To evaluate the possibilities of using gamma irradiation for the sterilization of ointments, the effect of irradiation on spores of Bacillus pumilus and Bacillus sphaericus in dry material and in two different kinds of ointments was studied. The results indicate that for sterilization purposes irradiation was less effective in white petrolatum as compared to irradiation in the dry state. No such protective effect was found in a hydrophilic ointment. Accordingly, the sterilization dose needed for the sterilization of an ointment can be decided upon only after inactivation experiments with suitable test organisms in the actual preparation.


Toxigenic Aspergillus and Penicillium isolates from weevil-damaged chestnuts. Aspergillus and Penicillium were among the most common genera of fungi isolated on malt-salt agar from weevil-damaged Chinese chestnut kernels (16.8 and 40.7% occurrence, respectively). Chloroform extracts of 21 of 50 Aspergillus isolates and 18 of 50 representative Penicillium isolates, grown for 4 weeks at 21.1 C on artificial medium, were toxic to day-old cockerels. Tweleve of the toxic Aspergillus isolates were identified as A. wentii, eight as A. flavus, and one as A. flavus var. columnaris. Nine of the toxic Penicillium isolates were identified as P. terrestre, three as P. steckii, two each as P. citrinum and P. funiculosum, and one each as P. herquei (Series) and P. roqueforti (Series). Acute diarrhea was associated with the toxicity of A. wentii and muscular tremors with the toxicity of P. terrestre, one isolate of P. steckii, and one of P. funiculosum.


Psychrophilic microorganisms from areas associated with the Viking spacecraft. Microorganisms capable of growth at 7 C were enumerated and isolated from soil samples from the manufacture and assembly areas of the Viking spacecraft. Populations ranging from 4.2 X 10(3) to 7.7 X 10(6)/g of soil were isolated from the 15 soil samples examined. Temperature requirements were determined, and those growing at 3 C, but not at 32 C, were designated as obligate psychrophiles in this investigation. Populations of soil bacteria, including aerobic sporeformers, ranging from 1.5 X 10(2) to 9.8 X 10(5)/g were capable of growth at 3 C, but not at 32 C. Bacterial isolates were identified to major generic groups. No psychrophilic sporeformers were isolated from soil from the manufacture area, but psychrophilic sporeformers ranged from 0 to 6.1 X 10(3)/g from soil from the assembly area.


Methane production in shallow-water, tropical marine sediments. The in situ production of methane was monitored in several types of tropical benthic communities. A bed of Thalassia testudinum located in Caesar Creek (Florida Keys) exhibited the highest methanogenic activity (initial rates = 1.81 to 1.86 mumol CH4/m2 per h) as compared with another seagrass (Syringodium sp., 0.15 to 0.33 mumol/m2 per h) and two coral reef environments (Hydro-Lab, 0.016 to 0.10 mumol/m2 per h; Curacao, 0.14 to 0.47 mumol/m2 per h). The results suggest that a wide variety of benthic metabolic processes (e.g., photosynthetic oxygen production) influences methane production rates.


Effect of microflora on the free amino acid distribution in various regions of the mouse gastrointestinal tract. The distribution of free amino acids in the contents of various regions of the gastrointestinal tract (stomach, upper small intestine, lower small intestine, cecum, upper colon and lower colon) was studied in germfree and conventionalized mice. Particular emphasis was placed on the conversion of tryptophan to indole as a probe for studying intermicrobial interactions and microbe-host interactions in vivo. Great differences were observed in the free amino acid content of the various regions of the digestive tract in each type of mouse and also in any one region between germfree and conventionalized mice. As would be expected, there were fewer differences in amino acid distribution between the types of mice in both regions of the small intestine. This correlates with a much lower population of microorganisms in these regions. The changes in free amino acid content and distribution produced by microflora are great enough to serve as a good probe for studying the interactions of a limited number of species of microbes in gnotobiotic animals and assign possible specific functions to each species.


Heterotrophic activity of deep-sea sediment bacteria. Sediment samples, containing mixed microbial populations that were decompressed during retrieval from 7,750 and 8,130 m in the Puerto Rican Trench, were recompressed and incubated at the approximate in situ temperature (3 C) and pressure (775 or 815 atm) in the presence of 14C-labeled amino acids. Heterotrophic activity (total uptake, CO2 respiration, and cellular assimilation) and cellular-associated "pool" concentrations were measured. Compared with atmospheric controls held at 3 C, the total uptake at elevated pressure at 3 C was reduced, on an average, 55 times, CO2 respiration was reduced 45 times, and cellular assimilation was reduced 69 times. Rate of total uptake at elevated pressure was found to range from 4.0 X 10(-11) mug/cell per h for leucine to 2.61 X 10(-10) mug/cell per h for an amino acid mixture. Also, the percentage of total uptake at elevated pressures, respired as CO2, increased at the expense of cellular assimilation (ca. 22% increase). Two cellular-associated amino acid pools were detected, a large, loosely bound, outer pool and a small, tightly bound internal pool. The loosely bound outer pool was removed by a change in the pH of the incubation medium. Even though heterotrophic uptake and the outer, cellular-associated pool were markedly reduced at an elevated pressure, the percentage of total uptake calculated for the unincorporated, tightly bound, intracellular pool was 2 to 19 times that obtained for cultures held at 1 atm. The results were interpreted as indicating that bacterial metabolism and biosynthesis in the deep sea are markedly reduced, with a greater proportion of metabolic activity devoted to cellular maintenance.


Scanning electron microscope study of bacteria associated with the rumen epithelium of sheep. Examination of the rumen epithelium of sheep by scanning electron microscopy revealed bacteria associated with the epithelial surface. Comparison of epithelial surfaces from 10 sheep revealed areas that were consistently densely covered with bacteria and other areas where the cover was consistently light. The bacterial populations were frequently of mixed morphological types, but areas populated with a single type were also observed. This finding, together with the discovery of bacterial forms not previously described in rumen contents, suggests that a specific flora may exist on the rumen epithelial surface. The functional significance of such a population is discussed.


Specificity of Ustilago maydis killer proteins. Bacteria and fungi were tested for sensitivity to Ustilago maydis killer strains  carrying virus-like particles. Various species taxonomically related to U. maydis were sensitive.


Staphylococcal enterotoxin C: solid-phase radioimmunoassay. A solid-phase radioimmunoassay test employing 125I-labeled enterotoxin C and polystyrene tubes coated with specific antibody was used for the detection and quantitation of entertoxin C in condensed milk, cheddar cheese, custard, and ham salad. The assay was sensitive to 1 to 10 ng of toxin per g of food; nonspecific inhibitions were 16% or less.


Factors affecting the production of sterigmatocystin in semisynthetic media. Production of sterigmatocystin by Aspergillus versicolor was stimulated by inorganic phosphate when used in conjunction with citric acid cycle compounds.


Inhibition of methanogenesis in marine sediments by acetylene and ethylene: validity of the acetylene reduction assay for anaerobic microcosms. Methanogenesis was irreversibly inhibited in sediments by concentrations of acetylene employed in nitrogen fixation assays (1 to 20%, vol/vol). Ethylene, but not ethane, also stopped methane production, and the inhibition was reversed by gassing with hydrogen.


Bactericidal effect of hydrogen peroxide on spacecraft isolates. Solutions of 3, 10, and 15% hydrogen peroxide were found to have pronounced bactericidal effects, as a function of time of exposure, on sporeformers and non-sporeformers isolated from spacecraft.


Diagnostic accuracy in malignant melanoma. The diagnostic accuracy and index of suspicion concerning malignant melanoma were calculated based on review of 5,538 histologically examined lesions (of which 99 were melanomas) that were recorded in the Oncology Section of the Skin and Cancer Unit from 1955 to 1967. The diagnostic accuracy of the physicians in the Section was determined to be 64.4%. Thus, in almost one of every three melanomas an error in clinical diagnosis was made. This "batting average" is, however, better than those of previously published reports. The index of suspicion in relation to malignant melanoma in our series was 96%. Thus, the physicians in the Oncology Section demonstrated an appropriate awareness of this tumor. However, coupled with a diagnostic accuracy of 64%, a problem nevertheless exists in the diagnosis of this serious cutaneous cancer. Our study emphasizes the importance of having histologic verification prior to definitive radical surgery on patients with malignant melanoma.


Effects of topical fluorouracil on normal skin. Daily application of 1% fluorouracil cream to normal white skin results in definite morphologic alterations of the epidermis. Although clinical changes were not present, electron microscopic examination of the tissue demonstrates changes especially pronounced in the epidermal keratinocytes. These changes consist of cytoplasmic vacuoles, alterations in the mitochondria, Golgi complex, and endoplasmic reticulum, as well as widened extracellular spaces.


Metronidazole therapy for cutaneous leishmaniasis. A man acquired cutaneous leishmaniasis in Afghanistan. The disease involved two sites and remained active for seven months. Treatment with metronidazole was followed by resolution of the skin lesions in one month.


Small intestinal biopsy in cows milk protein allergy in infancy. Intestinal biopsies were performed in 31 infants with cow's milk protein intolerance. Mucosal damage was constant, partial villous atrophy being the most usual finding. Though these changes are nonspecific, small intestinal biopsy can be a useful investigation in these patients. With a milk-free diet, recovery of normal mucosal appearence is reached between 3 and 13 months.


Effect of lactose-induced diarrhoea on absorption of nitrogen and fat. The absorption of fat and the absorption and retention of nitrogen were studied in 20 children with kwashiorkor. 13 of the 20 had lactose malabsorption and severe diarrhoea on milk feeds. Fat absorption was not affected by lactose-induced diarrhoea, but nitrogen absorption was impaired. Despite this, nitrogen retention was unaffected and it is concluded that milk and milk products would continue to be used in programmes to eliminate malnutrition.


Poststreptococcal nephritis--a rare disease?. Forty-three children presenting with acute nephritis were studied for evidence of preceeding steptococcal infection. They were compared with a group of control children of similar age. Two-thirds of those with nephritis gave a history of a preceeding respiratory infection (compared with one-third of the controls). A significant rise of antistreptolysin O tire occurred in only 16 children with nephritis and within this minority several did not show a fall of serum C3 level. It is probable that only one-third of the children with acute nephritis had poststreptoccoccal glomerulonephritis. Poststreptococcal glomerulo-nephritis is no longer the main cause of childhood acute nephritis in the Leeds area. There may be many different aetiological factors and this diversity calls for more rigorous investigations and a more guarded prognosis.


Hypertension, oedema, and suppressed renin aldosterone system due to unsupervised salt administration. This paper describes an infant with gastroenteritis, who developed hypertension and oedema after administration of inaccurately prepared oral glucose salt solution. The renin aldosterone system was suppressed in this child and it was suggested that this may be a factor in the development of hypernatraemia when abnormal water losses occur in infants fed on hyperosmolar feeds. Unless salt can be given accurately in small amounts it may be safer to advise feeds of glucose only in infants with mild diarrhoea.


Thymic dysplasia, persistence of measles virus, and unexpected infant death. A case of sudden infant death in an 18-month female infant is described which occurred 3 weeks after clinical recovery from a typical attack of measles. At post-mortem examination no obvious cause of death could be found apart from some terminal aspiration of vomit. Histologically, the thymus showed selective absence of Hassall's corpuscles with a normal number of cortical lymphocytes. There were many atypical lymphocytoid cells in the lymph nodes, spleen, and portal tracts, and measles virus was subsequently isolated from the lung and tonsil. There was a raised titre of complement fixing measles antibody (1/256).


Clinical significance of catecholamine excretion levels in diagnosis and treatment of neuroblastoma. Bond, J.V. (1975). Archives of Disease in Childhood, 50, 691. Clinical significance of catecholamine excretion levels in diagnosis and treatment of neuroblastoma. The pattern of urinary excretion of vanillylmandelic acid (VMA) was studied in 50 children with neuroblastoma. There were 10 disease-free survivors, and 4 children who survive for 3 or more years with residual nonmetastatic disease, 36 children died with widespread metastic disease. The urinary VMA level was raised at diagnosis in 8 of the 10 disease-free survivors but rapidly returned to normal after treatment. In 3 out of 4 children with residual tumour, VMA remains persistently raised. In 28 of the 36 children who died VMA was raised at diagnosis and remained so throughout the course of their disease. In the majority of the children with metastatic disease the finding of a raised VMA revealed the nature of the primary tumour. Measurement of urinary VMA is a simple diagnostic test which confirms the presence of neurblastoma and avoids the need for more complex investigations. The prompt return to normal levels in the disease-free survivors confirms the importance of serial VMA estimations in assessing response to treatment and ultimate prognosis. The other good prognostic features in the surviving patients were young age at diagnosis, primary tumour in the thorax, and histologically well-differentiated tumours which had not metastasized.


Perinatal cardiac arrest. Quality of the survivors. Steiner, H., and Neligan, G. (1975). Archives of Disease in Childhood, 50, 696. Perinatal cardiac arrest: quality of the survivors. Twenty-two consecutive survivors of perinatal cardiac arrest have been followed to a mean age of 4 1/4 years, using methods of neurological and developmental assessment appropriate to their ages. 4 showed evidence of gross, diffuse brain-damage (2 of these died before the age of 3 years). These were the only 4 survivors of the first month of life who took more than 30 minutes to establish regular, active respiration after their heartbeat had been restored. The arrest in these cases had occurred during or within 15 minutes of delivery, and followed antepartum haemorrhage, breech delivery, or prolapsed cord. The remaining 18 were free of any evidence of brain damage. In the majority of these the arrest had occurred during shoulder dystocia or exchange transfusion, or was unexplained; the heartbeat had been restored within 5 minutes in most cases, and regular, active respiration had been established within 30 minutes thereafter in all cases.


Familial insulin-resistant diabetes, multiple somatic anomalies, and pineal hyperplasia. West, R. J., Lloyd, J. K., and Turner, W. M. L. (1975). Archives of Disease in Childhood, 50, 703. Familial insulin-resistant diabetes, multiple somatic anomalies, and pineal hyperplasia. A syndrome comprising unusual facies, dry skin, acanthosis nigricans, thickened nails, hirsutism, dental precocity and dysplasia, abdominal protuberance, and phallic enlargement is described in 2 sibs. Both have developed diabetic ketoacidosis with insulin resistance. The elder child, a girl, had recurrent septic episodes and died at the age of 7-8 years. At necropsy the pineal gland was hyperplastic, weighing 900 mg. Investigation of the younger sib over a 4-year period has shown decreasing glucose tolerance, and he was frankly diabetic with ketoacidosis by the age of 6-8 years. Serum insulin concentrations have always been grossly raised. Though the mechanism for insulin resistance has not been definitely established, a functional abnormality of the hypothalamus or pituitary is postulated to explain the many endocrine features of the syndrome.


Effect of bronchodilators on respiratory resistance in infants and young children with bronchiolitis and wheezy bronchitis. Rutter, N., Milner, A. D., and Hiller, E. J. (1975). Archives of Disease in Childhood, 50, 719. Effect of bronchodilators on respiratory resistance in infants and young children with bronchiolitis and wheezy bronchitis. Respiratory resistance was measured using a forced oscillation technique in 16 infants and young children with bronchiolitis and wheezy bronchitis. Measurements were made before and after administration of nebulized salbutamol or isoprenaline. No significant change in resistance was found.


Familial non-cystic fibrosis mucus inspissation of respiratory tract. Perlman, M., Williams, J., Hirsch, M., and Bar-Ziv, J. (1975). Archives of Disease in Childhood, 50, 727. Familial non-cystic fibrosis mucus inspissation of respiratory tract. Two sibs, whose parents are first cousins, have had chronic obstructive airways disease from birth with recurrent otitis media, sinusitis, and mastoiditis. The disease, associated with clinically abnormal mucus, differs from other familial obstructive airways diseases and probably constitutes a new entity.


Plasma osmolality, sodium, and urea in healthy breast-fed and bottle-fed infants in Newcastle upon Tyne. Dale, G., Goldfinch, M. E., Sibert, J. R., and Webb, J. K. G. (1975). Archives of Disease in childhood, 50, 731. Plasma osmolality, sodium, and urea in healthy breast-fed and bottle-fed infants in Newcastle upon Tyne. Plasma osmolality, sodium, and urea were measured on samples from 50 healthy infants, aged between 18 and 125 days, attending child health clinics in Newcastle upon Tyne. 3 infants had osmolalities greater than 300 mOsm/kg, a lower incidence of hyperosmolality than that previously reported. There was a difference (P less than 0-001) between the plasma urea levels of breast-fed and bottle-fed infants, but not between the osmolalities of these groups. The mean plasma urea of bottle-fed babies was 53 mg/100 ml (SD 12-47), 50-1 mg/100 ml (SD 10-9) if additional solids were being given, and 18-4 mg/100 ml (SD 7-81) for breast-fed babies. There was little difference between the plasma sodium levels of each group. The mean plasma sodium for all groups combined was 135-2 mmol/1 (SD 2-3); no plasma sodium exceeded 140 mmol/1.


Further in vitro studies on the biochemistry of the inhibition of nucleic acid and protein synthesis induced by arsenic. Human lymphocytes, stimulated by PHA, and exposed to increasing Na2HAsO4 concentrations, show an identical incorporation rate for 14C thymidine and 14C-TTP into the DNA. 14C uridine is incorporated 3--4 per cent less at an As concentration of 1.0 mug/ml medium, above this however approximately 15 per cent less into the RNA as compared to 14C-UTP. In free pyrimidine bases, the incorporation of labelled triphosphates into the DNA and RNA is significantly reduced above 1 mug and 10 mug Na2HAsO4. Corresponding to its approximately uniform distribution into DNA and RNA, the incorporation rate of 14C-ATP above 10 mug Na2HAsO4/ml culture medium lies between that of 14C-UTP and 14C-TTP. The incorporation of 14C alanine and 14C leucine into cellular protein is not reduced below 10 mug Na2HAsO4/ml. The incorporation rate is 41 per cent at a concentration of 100 mug Na2HAsO4/ml medium.  Compared to 14C-UTP, 14C-ATP and 14C-TTP it is increased by the factor of 1.8; 2.5 and 6.8 respectively. The inhibition of enzymes of the dark repair mechanisms and the synthesis of biopolymers together with their altered sequence and the involvement of long-lived messenger RNA serve as an explanation of the observed alterations of the lymphocyte metabolism, caused by arsenic.


[Desmosomal structures in the cytoplasm of normal and abnormal keratinocytes (author's transl)]. The occurrence of intracytoplasmic desmosomes in normal, hyperplastic, and hyperkeratotic epithelia, in carcinoma-in-situ and in invasive carcinoma of the human oral cavity is demonstrated by electron microscopy. The mechanism for formation of these structures by invagination, separation and by intracytoplasmic incorporation of plasma membrane-desmosome-complexes are described in various oral epithelia, and other possible mechanisms are discussed. Intracytoplasmic desmosomes may occur in normal and pathological keratinocytes of all layers of the oral epithelium. Their ultrastructure in the peripheral cytoplasm is similar to that of the regular desmosomes on the cell surface. However, as they migrate centripetally, they show signs of degeneration, suggesting dissolution by lysosomal enzyme systems. Various surface membrane alterations involved in the formation of intracytoplasmic desmosomes may lead to a reduction of plasma membrane material and of desmosome structures and to defective intercellular adhesion. The intracytoplasmic incorporation of desmosome structures is a ubiquitous phenomenon exhibited by epithelial keratinocytes under certain physiological or pathological conditions.


Photodermatoses induced by oral contraceptives. The pathogenetic role of liver damage in photodermatoses induced by oral contraceptives was investigated. From among 121 cases with photodermatosis, it was in 4 cases of polymorphic light eruption-like dermatosis and in 2 cases of porphyria cutanea  tarda that a longterm use of antibaby pills preceded the development of skin disease. Physical and biochemical studies of the liver of the patients suggested that the hepatotoxicity of the estrogen component of oral contraceptives can play a role not only in the pathomechanism of porphyric cases, but also in that of cases occurring with the clinical picture of polymorphic light eruption.


In vitro evaluation of methotrexate and azathioprine for antipsoriatic activity. The effects of methotrexate and azathioprine, two drugs used in antipsoriatic therapy, on oxygen consumption of surviving human skin and on enzymatic activities of human skin homogenates were investigated. In concentrations of 1 mM/1, both substances provoked a significant decrease in oxygen consumption of human skin; in this respect, there was practically no difference between methotrexate and azathioprine. In the enzyme assays, however, azathioprine was, by far, less effective than methotrexate. After an incubation of 120 min azathioprine (1mM/1) inhibited lactate and glucose-6-phosphate dehydrogenase activities by about 10 per cent only, whereas the corresponding values with methotrexate amounted to 80 and 70 per cent, respectively. Methotrexate revealed an immediate inhibitory effect on pure glucose-6-phosphate dehydrogenase whereas azathioprine produced no changes in this mode. Furthermore, only methotrexate inhibited "acid" phosphatase activity of human skin homogenates.--These data sustain the theory that the better clinical efficacy of methotrexate in patients with psoriasis might be due to the more pronounced inhibition of important enzymes such as the enzymes of the pentose phosphate shunt.


[Ultrastructure of nuclear bodies in connective tissue cells of psoriatic lesions (author's transl)]. Electron microscopic observations were made in 6 psoriatic lesions of the skin. All specimens showed an increased number of nuclear bodies containing glycogen and lipids in the nuclear plasma of connective tissue cells. The results indicate an activation of connective tissue cell metabolism. They are discussed in connection with previously described signs of the participation of mesenchymal tissue in the psoriatic skin reaction. The increased metabolism could be part of a "nonspecific mesenchymal tissue reaction".


[Mitogenic activity of melanoma extracts in leucocyte cultures (author's transl)]. From a mixed cell suspension of five primary melanomas an aqueous sterile extract was made and added to homologue leucocyte cultures of eight melanoma patients and seven controls. The extract had a blastogenic and mitogenic effect in all cultures. There was no significant difference between the responses of patients and controls. In experiments with an equally prepared extract of normal skin, added to homologue leucocyte cultures of nine persons, none but one had a positive reaction. This indicates, that the motigenic principle of the melanoma extract is not related to the histocompatibility antigen nor caused by chemical or bacterial contamination of the primary cell suspensions. It seems to be derived from the cytoplasmic fraction of melanoma cells. Other experiments to solve the problem were impossible because of lack of material. There are several reports in the literature which by using different methods indicate, that there might be an immunological reaction to melanoma associated principles in healthy persons, too.


[Lamelate corpuscles in lymph nodes and their significance for metastasizing melanoma (author's transl)]. For the first time the occurrence of corpuscles of Vater-Pacini lacated in the hili of lymph nodes in patients with melanoma is described. As these corpuscles are pressure sensitive they participate in the regulation of blood and lymph flow inside the lymph node. By these means they may influence secondary deposition of melanoma cells.


[Fluorescence histochemical and microfluorometrical investigations of pigmentary tumors of the skin (author's transl)]. Junction nevus, dermal nevus, melanosis circumscripta praecancerosa Dubreuilh, superficial spreading melanoma, and nodular melanoma were investigated and characterized by use of the formalin induced fluorescence method (FIF). In the vicinity of junctional nevus cell clusters and near tumor cells of the superficial spreading melanoma increased numbers of melanocytes are found. These show different types of dendritic branching. Spherical nevus cells however are completely devoid of dendritic processes. On the other hand, the atypical pigment cells in melanosis circumscripta praecancerosa Dubreuilh exhibit a shape similar to that of melanocytes, whereas the globular cells of superficial spreading melanoma have the appearance of nevus cells. The arrangement of nodular melanoma cells resembles that observed in dermal nevus. However the characteristic decrease in fluorescence intensity from epidermal junction to deeper dermis as observed in the dermal nevus was missed in nodular melanomas. Dendritic pigment cells displaying formalin induced fluorescence (FIF) could be demonstrated in all types of malignant melanomas investigated in the present study. The fluorophores of the pigment lesions are characterized microspectrofluorimetrically by (1) ill-defined emission maxima between 470 and 490 nm and (2) a clear-cut excitation maximum at 430 nm accompanied by a lower one at 320 nm. Hydrochloric acid vapor induces a hyposochromic shift of the 430 nm excitation maximum to 370-380 nm and a marked elevation of the 320 nm maximum. These results indicate fluorophores of DOPA and its derivatives; in this respect there are no marked differences between melanocytes, nevus cells and the cells of malignant melanoma.


Biochemical and physiological particularities on the skin surface of diabetics. Biochemical and physiological examinations were carried out on the skin surface of the following groups: on 16 newly diagnosed diabetics; on 26 diabetics receiving treatment; and on 2 control groups of 16 and 26 healthy persons respectively of corresponding age and sex. The tests on the surface of the skin of the newly diagnosed diabetics when compared with the corresponding control group show the following significant results: 1. An increase in the percentage of free cholesterol in the lipids of the skin's surface possibly as a result of an increased cell turnover in the epidermis. 2. An increase in the free fatty acid concentration to the disadvantage of the triglycerides in the lipids of the skin's surface as an expression of an improved bacterial lipolysis. 3. A decrease in the reducing substances as confirmed by the phenol-sulfuric acid method in the so called water solubles. 4. An increase in the amino acids as confirmed by the ninhydrin method in the so called water solubles. All the above mentioned changes were more pronounced in the newly diagnosed diabetics than in those already receiving treatment; it can be seen that these changes can partly be normalised under diabetic therapy.


The measurement of corticosteroid induced dermal atrophy by a radiological method. Dermal atrophy due to the application of Clobetasolpropionate has been detected and measured by an X-ray method after four weeks topical application to the forearm. This effect was found to have recovered when the subjects were re X-rayed eight weeks after they had stopped using the steroid preparation.


Exposure of apple thinners to parathion residues. In studies of potential exposure of a volunteer working under controlled conditions during apple hand-thinning operations at 1, 24, 48, 72, 96, 168, and 240 hr after application of conventional 0.03% parathion spray, both dermal and respiratory exposure values were greater where water-wettable powder formulations were used than where emulsifiables were used. Residue levels of parathion on leaves from the two types of applications were about the same. Only trace amounts of paraoxon could be detected at one and seven days after application. Highest exposure values (14.2 mg/hr dermally and 0.15 mg/hr respiratorily) were obtained within 24 hr of application. Exposure was considerably less after residues were 72 hr old. Greatest exposure was on the forearms and hands. Urinary p-nitrophenol excretion indicated slightly more absorption following exposure in water-wettable powder experimental plots. Potential exposure values indicate that absorption could reach hazardous levels after one or two hr of work, even at the 96-hr residue period, if all the pesticide were absorbed. Considering that only a small fraction of the total amount would be absorbed, it is calculated that at 75-hr residue period poisoning should not occur. There was no significant change in blood cholinesterase activity of the volunteer worker. Variation in spray deposit within an orchard due to poor tank mixing did not appear to be great enough to be considered an important factor affecting exposure.


Metabolism of terbacil in orange seedlings. Orange seedlings were cultured in aqueous solutions of 3-tert-butyl-5-chloro-6-methyluracil (terbacil and terbacil-2-14C). Radioactivity was distributed throughout the plant with the largest amount in the roots and the smallest amount in the leaves. Terbacil was metabolized to form 3-tert-butyl-5-chloro-6-hydroxymethyl uracil, which was conjugated to form a beta-glucoside as the conjugate was hydrolyzed by beta-glucosidase. Identification of the metabolite was made by infrared and mass spectrometry after isolation and purification by column and thin layer chromatography. An additional unidentified water-soluble material was accumulated in the plant. 5-chloro-uracil was not detected as a metabolite of terbacil.


Concentration of mercury in animal products and soils of North Dakota. Total mercury (Hg) was determined in milk, eggs, beef, pork, human head hair, soil and water obtained from four geographical areas of North Dakota. The sampling areas were selected on the basis of differences in prevalent agricultural practices, climate and topography. Statewide average Hg concentrations in ppb were milk, 0.8; eggs, 12; beef muscle, 5; beef liver, 10; pork muscle, 11; pork liver, 15; head hair, 1708; soil, 30; rainwater and well water, less than one. There were no significant differences observed among areas in Hg content of any substance sampled except beef muscle. Beef muscle obtained from areas 2 and 4 contained significantly (P less than or equal to 0.05) higher levels of Hg than beef muscle from the other two areas. However, the magnitudes of differences were small (4 to 6 ppb). Considerable variation among individual beef and swine were noted but only six beef of 453 sampled and three swine of 156 sampled had tissue Hg exceeding 50 ppb. Appreciable variation was observed in Hg in eggs with respect to farms within an area, eggs from the same farm, and sampling times within a year. Few eggs sampled contained more than 50 ppb. Significantly (P less than or equal to 0.01) higher levels of Hg were found in head hair of women as compared with men and relatively large differences among individuals were observed. Average Hg in hair was generally low irrespective of sex of donor or area of the state as compared with data given in the literature. Soil Hg levels were consistently low in all areas of the state, and no relationship between cropping practices and soil Hg was detected.


Establishment of reentry intervals for organophosphate-treated cotton fields based on human data: III. 12 To 72 hours post-treatment exposure to monocrotophos, ethyl- and methyl parathion. Five human volunteers entered methyl parathion, ethyl parathion, or monocrotophos treated cotton fields for five-hr exposure periods when the residues of the respective pesticides had aged 12 hr, 24 and 48 hr and 72 hr. Foliage residues of methyl parathion disappeared fastest, those of monocrotophos slowest. Personal exposure to pesticide was evaluated from contamination of skin, clothing, and ambient air, while actual absorption of chemical was assessed from pesticide concentration in blood, urinary metabolite excretion, and effects on blood cholinesterase activities. There was good correspondence between magnitudes of foliar residue, estimates of personal contamination, and measures of chemical absorption. Field exposures caused no symptoms or clinical signs of organophosphate poisoning and depressed averaged blood cholinesterase activities by no more than 14% of pre-exposure levels.


The distribution of tracer doses of cadmium in the normal rat. The distribution and excretion of a single tracer dose of cadmium-109 given intravenously to rats were studied in a 60-day time course experiment. The organs that accumulated the most cadmium were the liver, kidneys, and pancreas. Initial high plasma levels decreased rapidly, and most of the cadmium that remained in the blood after 24 hr was found in the red cells. In most organs and tissues a level was reached within 24 hr at which the cadmium concentration remained relatively stable. Kidney was a marked exception because the amount of cadmium found in that organ increased progressively. Excretion of cadmium was found to be predominantly via the feces. Twenty-five to 28% of the dose was excreted by that route in 60 days, the most rapid phase occurring during the first three days. Less than 0.15% of the dose was excreted via the urine.


An investigation of the safety of cotton reentry after organophosphate application. Twelve cotton insect scouts were monitored during an entire pesticide application season by weekly determinations of para-nitrophenol excretion and biweekly cholinesterase measurements. These data were compared to weekly reentry intervals and pesticide application rates to study the validity of a 48-hr minimum reentry interval for methyl parathion-treated cotton. Methyl parathion represented 54.2% of the total amount of pesticide used with toxaphene 35.3%, ethyl parathion 4.1%, and other 6.4%. A significant decrease in erythrocyte and plasma cholinesterase was observed during initial exposure but during peak exposure the cholinesterase levels had returned to normal. The maximum mean amount of methyl and ethyl parathion absorbed by calculation from PNP excretion was 0.95 mg/24hr (n = 12). Twelve percent of all reentries were within two days and during one week 48% occurred during the first two days after pesticide application.


Dislodgeable azinphosmethyl residues from air blast spraying of apple foliage in Ohio. The distribution and decay rates of dislodgeable residues of azinphosmethyl applied by two types of air blast sprayers on apple foliage in Ohio were investigated. Leaf discs were taken from nine sites located on the periphery of Cortland apple trees at five dates after spraying. The sprayer delivering the higher airflow rate, but lower velocity, deposited the pesticide much more uniformly over the trees and applied more in the top of the tree. The other sprayer deposited the greatest proportion of pesticide on the site nearest the sprayer. The residue decreased at all sites and ranged from 42 to near 100% decrease at 14 days after spraying.


Influence of humidity and rain on uptake and metabolism of 14C-azinphos-methyl in bean plants. In several experiments the influence of relative humidity and rain on uptake and metabolism of carbonyl-14C-azinphos-methyl was examined in bean plants under the following environmental conditions: Growth room with 35/80%, 65/85% and 95/95% (day/night) relative humidity and open field with and without rain. Increasing relative humidity had an enhancing effect on the rate of uptake and metabolism. A higher portion of water-soluble compounds was found in the bean tissue, although the azinphos-methyl itself is relatively non-polar. Low relative humidity and possible dry periods in summer will reduce the uptake and will leave the azinphos-methyl relatively persistent on the leaf surface. Rain or spray irrigation easily removed azinphos-methyl from the leaves. The rate of this removal seemed to depend on the intensity and time of rainfall after application. However, repeated wettings by rain may simultaneously stimulate uptake and metabolism of azinphos-methyl by the leaves.


Seasonal effects of leached mirex on selected estuarine animals. Four 28-day seasonal experiments were conducted using selected estuarine animals in outdoor tanks that received continuous flow of mirex-laden water. Mirex (dodecachlorooctahydro-1,3,4-metheno-2H-cyclobuta [cd] pentalene) leached from fire ant bait (0.3% mirex) by fresh water and then mixed with salt water was toxic to blue crabs (Callinectes sapidus), pink shrimp (Penaeus duorarum), and grass shrimp (Palaemonetes pugio) but not to sheepshead minnows (Cyprinodon variegatus), at concentrations less than 0.53 mug/L in water. The amount of leaching was greatest in summer and least in spring. Greatest mortality occurred in summer at the highest water temperature and concentration of mirex; least mortality occurred in spring at the next to the lowest temperature and at the lowest concentration. Earliest deaths of blue crabs occurred after six days of exposure and shrimps after two days. Small juvenile crabs were more sensitive to leached mirex than were large juveniles. Mirex did not appear to affect growth or frequency of molting in crabs. All exposed animals concentrated mirex. Among animals that survived for 28 days, sheepshead minnows concentrated mirex 40,800X above the concentration in the water, blue crabs 2,300X, pink shrimp 10,000X, and grass shrimp 10,800X. Sand substrata contained mirex up to 770X that in the water. Most control and exposed animals in samples examined histologically had normal tissues, but alteration in gills of some exposed fish and natural pathogens in some exposed and control crabs and shrimp were observed. The experiments demonstrated that mirex can be leached from bait by fresh water, concentrated by estuarine organisms, and can be toxic to crabs and shrimps.


Some new evidence on human joint lubrication. Theoretical consideration has been given to the use of pendulum machines which are used to examine the frictional properties of human joints by incorporating them as fulcra. As a result, a new type of pendulum machine has been built which incorporates the facility to apply sudden loads to the joint on starting the swinging motion, and also the ability to measure directly the frictional torque experienced by the joint. The results obtained from natural hip joints indicate the presence of squeeze film lubrication under conditions of sudden loading of a joint. In addition, a self-generated fluid film process was observed at low loads while at higher loads boundary lubrication appeared to be important. These results have been used to describe the lubrication regimens occurring in a normal activity such as walking. A single experiment carried out on a hip from a patient suffering from severe rheumatoid arthritis has also been reported and the frictional resistance was seen to be increased fifteenfold compared to a normal hip.


Quantitative study of stiffness in the knee joint. Data from a knee arthrograph, which imparts a passive sinusoidal motion to the joint and measures the resistive torque and displacement, have been shown to be reproducible. Tests carried out on joints (from 49 males, 21 females) showed that the energy loss per cycle of the joint increased with age for both sexes but the peak to peak torque (elastic stiffness) did not vary with age. Muscle bulk had a large influence on the stiffness (both dissipative and elastic) of the knee as did the size of the joint itself. Women's knee joints exhibited lower values of dissipative energy loss and peak to peak torque than men's for all ages and sizes of joints.


The foot in chronic rheumatoid arthritis. The feet of 200 consecutive admissions with classical or definite rheumatoid arthritis were studied. 104 were found to have pain or deformity. Clinical involvement of the joints was seen more often than radiological joint damage in the ankle, but the reverse was the case in the midtarsal joints. The metatarsophalangeal joints were involved most frequently both clinically and radiologically. Sixty per cent of the patients required modified shoes but only a third of these had received them. The need for more shoes is clear, and although this is a highly selected group of patients they were all under specialist care. The increased expenditure on special footwear would benefit the patient, firstly by improving ambulation, and secondly perhaps by reducing the number of operations necessary. Hallux valgus was very common and occurred with similar frequency to disease in the other metatarsophalangeal joints. Although not exclusive to rheumatoid arthritis, hallux valgus must have been caused for the most part by the rheumatoid arthritis and if so, then it is suggested that the provision of suitable shoes for patients may be less costly than subsequent surgical treatment.


Attempt to classify patients with arthritis of the hip suitable for prosthetic replacement, and their femoral heads. Using clinical, radiological, and morbid anatomical data about patients with arthritis of the hip and their femoral heads resected during total hip replacement, an attempt has been made first, to classify patients and femoral heads by a cluster analysis technique, and secondly and more realistically, to use existing clinical and radiological classification as a basis for seeking discriminating features in the data from the femoral head. Both types of analysis failed to give results, and led to a conclusion that arthritis of the hip is a spectrum of disease. This may not pose problems to the clinician, but it does to the investigator studying the pathogenesis of osteoarthrosis. This problem is briefly discussed.


Aortic valve incompetence and replacement in rheumatoid arthritis. Five cases of aortic incompetence and nodular seropositive rheumatoid arthritis are presented. Four cases underwent aortic valve replacement. Two of these had granulomatous involvement of the aortic cusps similar to subcutaneous rheumatoid nodules, and another showed a nonspecific fibrosis. One case had definite coincidental rheumatic aortic and mitral heart disease. Two patients had undergone pericardectomy previously for constrictive pericarditis. Good results were obtained in all four operated cases and cardiac surgery enabled continuation of rehabilitation for the rheumatoid arthritis, including major orthopaedic procedures. A review of 22 cases from the literature with rheumatoid granulomata within the aortic valve shows that they are associated with mitral valve granulomata in 63-6%. Congestive cardiac failure was found in 75%. Macroscopical evidence of aortic incompetence was seen in 36-8% and of aortic stenosis in 15-8%. Associated pericarditis occurred in 59-1%, which was severe or complicated in 13.6%. The associated arthritis was severe in 77-8% with subcutaneous nodules (71-5%), rheumatoid factor (83-6%), and episcleritis (66-6%). From these cases and a review of the literature the following points are emphasized. (1) Both the granulomatous and nonspecific aortic valvulitis of rheumatoid arthritis may result in significant haemodynamic abnormality. (2) The valve lesions found are often clinically and macroscopically indistinguishable from rheumatic valve lesions. (3) Granulomata, when present, are usually found in the valve cusp or ring and only occasionally in the aortic wall. (4) Associated joint disease, although usually severe, may be mild. (5) The valve lesion may be accompanied by a severe pericardial involvement--either tamponade or constriction. (6) Aortic valve replacement for aortic incompetence in rheumatoid arthritis is both feasible and worthwile, despite severe joint disease.


Cardiac valvular disease in chronic inflammatory disorders of connective tissue. Factors influencing survival after surgery. Three cases of cardiac valvular disease complicating chronic inflammatory disorders of connective tissue are described. Each underwent surgical valve replacement. The outcome in the first case, a patient with aortitis complicating Reiter's syndrome and in good health otherwise, has been excellent. The other two patients, one with rheumatoid arthritis and vasculitis, the other with systemic lupus erythematosus and nephritis, died after operation as the result of their systemic disease. The importance of systemic features in assessing this type of patient is emphasized.


Urinary copper excretion in rheumatoid arthritis. The pattern of urinary copper excretion in relation to urine osmolality (as shown by series of aliquots of urine) was studied in rheumatoid patients and in control groups. Rheumatoid patients showed an abnormal copper excretion pattern compared with nonrheumatoid subjects. This was not a direct function of the raised serum copper in rheumatoid disease. Measurements based on 24-hour series of aliquots of urine (as distinct from total pooled 24-hour collections) have been shown to be a useful and sensitive method for studying copper excretion patterns.


Protein sulphydryl depression during adjuvant arthritis. The changes in plasma protein sulphydryl level were measured during the course of adjuvant-induced arthritis in rats. Major depressions in the plasma sulphydryl level occurred at the onset of adjuvant disease, and the extent of the depression was related to the severity of the disease. Plasma sulphydryl levels remain unchanged when the systemic arthritis is suppressed by inclusion of a competing antigen in the adjuvant. Changes in sulphydryl content of the plasma were shown not to be due to weight loss or decrease in plasma protein level.


Uric acid, joint morbidity, and streptococcal antibodies in Maori and European teenagers. Rotorua Lakes study 3. Two hundred and ninety-four New Zealand secondary school students were examined by questionnaire, and physical and biochemical methods. The sample contained almost equal numbers of Maoris and Europeans. The findings related to joint conditions are presented. Past injury and rheumatic disease accounted for some of the reported morbidity, but no important sex or race differences in these factors emerged. There were, however, significant differences in serum uric acid levels with the Maori having higher levels than the Europeans. A significant correlation with body mass was present in both race and sex groups but a correlation with haemoglobin was present only in the European females. While hyperuricaemia was not associated with morbidity in this young sample, ethnic differences anticipated the higher prevalence of gout already observed in Maori men.


Failure to show mycoplasmas and cytopathogenic virus in rheumatoid arthritis. Synovial needle biopsies, joint aspirates, and joint tissue obtained at open operation from 41 cases of rheumatoid arthritis were inoculated onto PPLO media, L-form medium, and cell cultures for the isolation of mycoplasmas, L-form bacteria, and viruses. Medium suitable for the isolation of 'T' strain mycoplasmas was not employed. No mycoplasmas, L-form bacteria, or cytopathogenic viruses were shown. Similar specimens from nine patients diagnosed as having Reiter's disease were examined in a like manner and yielded only one Mycoplasma hominis type 1 isolate from a knee joint biopsy. It is concluded that known strains of mycoplasma and bacterial L-forms do not play a direct role in early and established cases of rheumatoid arthritis. Some of the cell cultures used in this study contained mycoplasma contaminants. Bacterial contaminants were also encountered in occasional batches of L-form medium.


Clinical echinococcosis.

Clinical echinococcosis. In 221 patients (0.48% of hospital admissions) with hydatid disease (122 female and 99 males), 81% had single and 19% multiple organs involved. Lungs, liver and spleen as single sites of echinococcosis together represented 83.24% of cases and the liver alone represented 95.24% of instances with multiple organ involvement. One hundred seventy-nine single and 74 multiple cysts (ratio of 2.42/1) represented a total of 363 cysts (1.64 cysts/patient). The incidence of intact cysts was 51.52% and 48.48% had ruptured. Ruptures numbered highest in the lungs (73.44%) and greater in multiple (79.66%) than in single cysts (68.12%). In the liver, 27.14% of single and 54.55% of multiple cysts (40.44% of all liver cysts) had ruptured. Cysts varied in size from 0.8 to 35 cm diameter. Single cysts averaged significantly higher (14.16 cm) and multiple ones lower (5.71 cm) as did intact (6.75 cm) versus reptured cysts (4.33 cm). Except for 10 silent and 15 symptomatic cysts treated medically, all the rest were treated surgically by removal of the endocyst or resection of both endo and exocysts including 205 first, 31 second and 5 third procedures (1.75% of all major operations). Complications occurred in 28.57%. Surgical mortality (3.57%) was markedly lower than with conservative treatment (60%) and significantly less than that of the whole group (14.48%).


Total esophageal reconstruction after extraction of the esophagus. During the period between 1971 and 1974, 25 cases of carcinoma of the hypopharynx and cervical esophagus underwent esophageal extraction and total esophageal reconstruction without operative mortality. The operative methods used for this series were blunt dissection, or everting stripping of the thoracic esophagus without thoractomy followed by pharyngogastro or -colostomy as a one stage procedure via a posterior mediastinal route created by esophageal extraction. The operative technique of esophageal extraction without thoracotomy is described. It is obvious that mediastinal tunnel is the shortest route through which to put the chosen organ for esophageal substitution. This operation is to be recommended for lesion of the hypopharynx and cervical esophagus as well as some esophageal stricture because of its operative simplicity, ease, safety and rare postoperative complications.


Intragastric microbial colonization in common disease states of the stomach and duodenum. Forty-nine patients undergoing elective or emergent gastric surgery have been included in this study. Gastric needle aspiration was performed at the time of surgery in each case, followed by qualitative aerobic and anaerobic bacteriologic analysis. In 18 patients undergoing elective operation for chronic nonobstructing duodenal ulcer a gastric microflora was present in only three patients and no postoperative wound infections were observed. In 29 of 31 patients, in the other groups of patients with bleeding or obstructing duodenal ulcer or in those with gastric ulcer or malignancy, intragastric micro-organisms were present. Six of the 7 postoperative wound infections which developed in these groups of patients were due  to one of the same bacteria isolated at the time of original needle aspiration. It appears that the endogenous intragastric microflora is a significant factor in the development of postoperative wound sepsis following gastric resection, in those groups of patients with a compromise of their normal gastric antibacterial inhibitory mechanisms.


Studies in burns: XIV, Heling in burn wounds treated with Ethyl Linoleate alone or in combination with selected topical antibacterial agents. Studies of the efficacy, in terms of burned wound healing, of a mixture of Ethyl Linoleate (ethyl 9-12 (cis, cis) octadecadienoate) with alpha-1-histidine, alpha-tocopherol, and TBHQ (hELate) was undertaken in 12 swine. The species was selected so as to study an animal with skin anatomy similar to the human. Statistically significantly greater healing occurred in 730 C/7sec contact burns (20% BSA) treated with hELate than in untreated burns in pigs. Further, there was no contracture noted in the hELate treated lesions, while marked contracture occurred in the untreated burns. Additionally, we noted that there was a proportional increase in weight gain amongst swine studied as their burn lesions epithelialized. In order to evaluate the compatibility of hELate with selected, currently-used topical antibacterial agents, 154 rabbits with 20% 730 C/7 sec contact burns were studied. The lipid was applied (0.01 ml/cm2 burn) at 1 hour postburning; the topical agent was applied at 2 hours post-burn and every 24-hours. All animals were washed once daily. hELate was applied only once. We found no statistical difference in the number of subjects healed or in the mortality between animals treated with hELate alone and those treated with the agent plus Gentamycin cream, Neosporin cream, and silver sulfadiazine 1% in Unibase USP (compounded at Medical College of Georgia specifically and only for this study.) We suggest that Ethyl Linoleate agent (hELate) may be used safely in combination with selected antibacterial substances. Further, these selected combinations seem to be non-toxic and appear to allow the calorie-saving and healing effects of the lipid to proceed unimpeded.


Tumor thickness, level of invasion and node dissection in stage I cutaneous melanoma. From a retrospective study of 97 and a prospective study of 41 Stage I cutaneous melanomas, it was found that tumor thickness is a better measure of prognosis than is the level of invasion of the tumor. The chance of developing recurrent disease appears to be directly proportional to tumor thickness. Prophylactic lymph node dissection doubled the rate of survival for patients with lesions greater than 1.50 mm thick but had no effect on those with thinner lesions. Thirty-nine per cent of the patients had lesions less than 0.76 mm thick and all survived free of disease for 5 or more years. Six per cent of the tumors that recurred or metastasized were in an intermediate range of 0.76-1.50 mm thick, and no discriminant could be found to separate these 9 lesions with a bad prognosis from the remaining 18 in this group.


Operative management of pancreatic pseudocysts in infants and children: a review of 75 cases. This report combines the findings and treatment in 15 infants and children with pancreatic pseudocysts with 60 additional cases from a literature review. The mean age at diagnosis was 7.5 years with pseudocyst being more common in boys (44:31). Sixty per cent were due to trauma, while in 32% the cause was unknown. Abdominal pain (68%), a mass (64%), and vomiting (52%) were the most frequent findings. The serum amylase was elevated and the upper gastrointestinal contrast study consistent with a mass in 88% of cases. Operative treatment included external drainage in 25 children (33%), cystgastrostomy or cyst-jejunostomy in 34 (45%), excision in 10 (13%) and miscellaneous procedures in 6 (8%). Complications were relatively few and there were no deaths recorded. Recurrence rate for cyst-gastrostomy was 4.7%, cyst-jejunostomy 7.6%, external drainage 8% and cyst-duodenostomy 50%. External drainage operations had prolonged cutaneous drainage. These observations suggest the appropriate operation is determined by the location and duration of pseudocyst. Internal drainage is preferred and avoids complications seen following resection and external drainage. Cyst-gastrostomy is effective when the pseudocyst is retrogastric and adherent to the stomach wall. Cyst-jejunostomy is most useful in instances in which the pseudocyst in not adherent to the stomach wall. Low recurrence rates and a zero mortality rate makes operative treatment highly acceptable therapy. Low recurrence rates are expected in childhood cases, (particularly related to trauma) due to an absence of underlying pancreatic disease and ductal obstruction.


Surgical treatment of 297 soft tissue sarcomas of the lower extremity. The results of surgical treatment of 297 soft tissue sarcomas arising in the lower extremity were critically examined. En bloc wide soft part resection (158 cases) yielded five and ten year survival rates of 63% and 50%. Amputation or major disarticulation (139 cases) gave corresponding survival rates of 45% and 29%. The most frequent cause of treatment failure was distant metastases, commonly in the lungs. The tissue type of sarcoma, histologic grade of malignancy, and tumor size appear to be important determinants of survival irrespective of the type of surgical treatment. Local recurrence of sarcoma occurred in 18% of the cases, more commonly after soft part resections than amputations. The proximity of a sarcoma to major vessels, bone or joint tends to compromise the margins of a wide soft part resection, thus increasing the risk of local recurrence. In appropriate cases, the scope of soft part resection can be extended by en bloc excision of the femoral vessels, with the hope of improving local control of sarcoma. Amputation should br resorted to if an adequate margin of resection cannot otherwise be obtained. This decision must be weighted against the high frequency of distant metastases in this disease. Postoperative adjuvant chemotherapy and immunotherapy offer prospects of prevention of this tragic outcome.


Distal antrectomy with vagectomy for duodenal ulcer: results in 611 cases. Distal antrectomy (25% or less) resection of the distal stomach with bilateral vagectomy, Billroth II, antecolic, Polya or Hofmeister gastrojejunostomy, continues to be our operation of choice for chronic duodenal ulcer. This is based upon our experience in 611 operations and as a result of careful complete repeat in-patient followup studies conducted since our original operation which was devised and performed in July 1953. This procedure controls or eliminates the two major gastric acid stimulatory phases responsible in the pathogenesis and chronicity of a duodenal ulcer: neurogenic (cephalic phase) via the vagel gastric pathways, and the humoral (gastrin) phase via antral stimulation. Even though part of the antrum may remain in the gastric remnant in some patients, antral control is maintained because the antrum remains in the gastric acid stream, there is no stasis, and it is vagectomized. The ulcer diathesis is controlled with a minimal disturbance in gastric physiology, in function, and in gastric reservoir capacity; the procedure will almost eliminate all of the undesirable postoperative gastrointestinal sequelase associated with other operations for duodenal ulcer. It insures the least chance for marginal, gastric, or recurrent ulcer formation, and a low morbidity rate.


Principles in the management of arterial injuries associated with fracture/dislocations. Ten out of 355 patients admitted with fracture and/or dislocations of long bones secondary to blunt trauma had associated vascular injuries. The clinical recognition of the associated vascular injury and its vertification of arteriography, Doppler study or surgical exploration resulted in early vascular repair and limb salvage. The controversial aspects of bone stabilization followed by vascular repair versus primary vascular repari, skeletal traction and delayed internal fixation together with fasciotomy-fibulectomy are discussed. Our results with the injuries seen justify the principle of bone stabilization followed by vascular repair, particularly since a team effort resulted in little time lost prior to circulatory restoration. The problems following vascular repair-namely anterior compartment snydrome, acute renal failure and cardiac arrest are present with their principles of management.