A comparison of 30-, 50-, and 60-mL foley catheter balloon volume and time to achieve cervical ripening for labor induction: A triple-blind randomized controlled trial.

Background: Cervical ripening is one of the most important determinants of the outcome of induction of labor. The findings of studies on the most efficacious inflatable catheter balloon volume for pre-induction cervical ripening have been inconclusive. Aim: To compare the efficacy of the use of different intracervical Foley catheter balloon volumes (30-, 50-, and 60-mL) on cervical ripening. Subjects and Methods: This study was a triple-blind randomized controlled trial. Two hundred and sixteen women with a Bishop score ≤5 at term were randomly assigned into three groups (1:1:1) to receive an intracervical single size eighteen Foley balloon catheter inflated either with 30-mL (control arm) or 50-mL and 60-mL (intervention arm) of sterile saline which was retained for a duration of 12 h. The primary outcome measures were the mean change in Bishop score and achieving a Bishop score of ≥6 at the twelfth-hour post-Foley catheter balloon insertion. Results: In the total study population and among nulliparous women, the 50-mL and 60-mL balloons compared with the 30-mL Foley catheter balloon achieved a statistically significantly greater mean change in Bishop scores at the twelfth hour\post-insertion (P = 0.005 and P = 0.001), while the 60-mL balloon compared with the 30-mL and 50-mL balloons achieved statistically significant higher mean change in Bishop scores among multiparous women (P = 0.047 and P = 0.003) and cervical dilatation irrespective of parity (P = 0.003 and P = 0.002), at the twelfth-hour post-insertion. The larger catheter balloons were also associated with a statistically significant greater chance of having an induction to delivery interval of <12 h in nulliparous women P = 0.003. Conclusion: The findings of this study showed that the larger single Foley catheter balloon volumes (50-mL and 60-mL) aside from being well tolerated and acceptable have the ability to induce faster changes in Bishop score, produce higher cervical dilation, and thus likely reduce significantly the total labor induction process compared to the 30-mL single catheter balloon volume irrespective of parity.

A full genome search in multiple sclerosis.

The aetiology of multiple sclerosis (MS) is uncertain. There is strong circumstantial evidence to indicate it is an autoimmune complex trait. Risks for first degree relatives are increased some 20 fold over the general population. Twin studies have shown monozygotic concordance rates of 25-30% compared to 4% for dizygotic twins and siblings. Studies of adoptees and half sibs show that familial risk is determined by genes, but environmental factors strongly influence observed geographic differences. Studies of candidate genes have been largely unrewarding. We report a genome search using 257 microsatellite markers with average spacing of 15.2 cM in 100 sibling pairs (Table 1, data set 1 - DS1). A locus of lambda>3 was excluded from 88% of the genome. Five loci with maximum lod scores (MLS) of >1 were identified on chromosomes 2, 3, 5, 11 and X. Two additional data sets containing 44 (Table 1, DS2) and 78 sib pairs (Table 1, DS3) respectively, were used to further evaluate the HLA region on 6p21 and a locus on chromosome 5 with an MLS of 4.24. Markers within 6p21 gave MLS of 0.65 (non-significant, NS). However, D6S461, just outside the HLA region, showed significant evidence for linkage disequilibrium by the transmission disequilibrium test (TDT), in all three data sets (for DS1 chi2 = 10.8, adjusted P < 0.01)(DS2 and DS3 chi2 = 10.9, P < 0.0005), suggesting a modest susceptibility locus in this region. On chromosome 5p results from all three data sets (222 sib pairs) yielded a multipoint MLS of 1.6. The results support genetic epidemiological evidence that several genes interact epistatically to determine heritable susceptibility.

Locomotor response of nialamide pretreated old rats to intraaccumbens dopamine.

The objective of this study was to determine the locomotor activity response of young (6 month), mature (15 month), and old (26 month) rats to bilateral intraaccumbens injections of dopamine after pretreatment with nialamide. Young and mature rats responded to dopamine with high rates of activity, while old rats either did not respond at all or responded with a lower intensity of activity. In contrast, the response of old rats to dopamine or ergometrine alone or to dopamine after pargyline pretreatment was not less than that of mature and young rats. These results suggest that the attenuated response of old rats to dopamine after nialamide pretreatment is not due to a decrease in dopamine receptor activity, but appears to be due to some unique property of nialamide in these animals. However, the reduced response of old rats to dopamine was not due to the inability of nialamide to inhibit monoamine oxidase, since nialamide completely inhibited the activity of this enzyme in the nucleus accumbens of old rats.

Identification of insulin-like peptides in cerebral ganglia neurosecretory cells of the mussel Mytilus edulis.

The immunostaining patterns of cerebral ganglia sections from the mussel Mytilus edulis with monoclonal antibodies raised against cerebral ganglia (CG) extracts were compared to those obtained with various polyclonal anti-insulin-like antibodies. One of the monoclonal antibodies (MAB 46) revealed clusters of positive cells in localization comparable to those revealed by the polyclonal antibodies. The nature of the antigen recognized by MAB 46 and the polyclonal antibodies was compared by gel filtration-HPLC of a cerebral ganglia extract. Similar peaks were revealed by the monoclonal and polyclonal antibodies. MAB 46 significantly inhibited the cerebral ganglia induced stimulation of amino-acid incorporation by mantle edge cell suspensions, suggesting that the antigen recognized by MAB 46 is involved in the control of growth.

Effect of nialamide on the metabolism of dopamine injected into the nucleus accumbens of old rats.

We have reported previously that after nialamide pretreatment there is an age-related difference in the stimulation of locomotor activity produced by the injection of dopamine bilaterally into the nucleus accumbens. Thus, the stimulation of locomotor activity produced by dopamine in old rats was significantly less than that of young and mature rats. The purpose of the present study was to determine whether nialamide was an effective inhibitor of the metabolism of dopamine after dopamine was injected into the nucleus accumbens of old rats. When we measured the concentration of injected dopamine in the limbic forebrain (nucleus accumbens and olfactory tubercle) of young (6 months), mature (15 months) and old (26 months) rats pretreated with nialamide, the amount of dopamine that was present was significantly less in old rats than in young or mature rats. Consistent with this observation, the concentrations of the dopamine metabolites, homovanillic acid and dihydroxyphenylacetic acid were higher in nialamide-pretreated old rats than in young and mature rats, suggesting that there was a smaller inhibition of the metabolism of dopamine in the limbic forebrain of old rats after nialamide pretreatment. In support of this hypothesis, nialamide (25-100 mg/kg i.p.), which inhibited monoamine oxidase activity in limbic forebrain homogenates of old, mature and young rats, was a less effective inhibitor of this enzyme in the old rats. These results suggest that the reduced locomotor activity response of old rats to the intra-accumbens injections of dopamine after nialamide pretreatment may be due to the reduced ability of nialamide to inhibit monoamine oxidase (and dopamine metabolism) in these animals.

Sodium aurothiomalate inhibits T cell responses to interleukin-2.

We studied the effects of the gold compound sodium aurothiomalate (SATM) on the responses of murine CTLL2 cells, and human T cells to Interleukin-2 (IL-2). SATM inhibited tritiated thymidine (3HTdR) incorporation by CTLL2 cells stimulated with human recombinant IL-2. Human T cells were cultured with phytohemagglutinin (PHA) in separate experiments and IL-2 receptor expression measured by using immunofluorescent anti-Tac serum; SATM inhibited IL-2 receptor expression. Furthermore, SATM when added concurrently with PHA, and IL-2 inhibited 3HTdR incorporation by human T cells in 5 day cultures. The kinetics of inhibition were further studied by adding PHA to T cells for 48 hours followed by the addition of SATM and IL-2; SATM inhibited 3HTdR incorporation even though receptor expression had occurred. These results suggest that SATM inhibits the stimulatory effects of IL-2 on T cells partly by interfering with IL-2 receptor expression, and partly by other mechanisms of action. These effects of SATM may explain some of the conflicting data in the literature on T cell responses to IL-2 in rheumatoid arthritis (RA), and suggest a possible mechanism of action for the drug in the treatment of RA.

In vitro effects of two gold compounds, and D-penicillamine on the production of interferon gamma.

There are contradictory reports on Interferon Gamma (IFN gamma) production by peripheral blood mononuclear cells (PBMC) in rheumatoid arthritis (RA). Since many patients previously studied were on Gold Sodium Thiomalate (GST), Auranofin (Auf), or D-Penicillamine (D-Pen) we have investigated the effects of these drugs on IFN gamma production using PBMC from normal controls (NC), and RA patients off GST, Auf, and D-Pen. Auf in low concentrations enhanced IFN gamma production by PBMC from NC but not RA; GST, and D-Pen had no effect. In other experiments PBMC were stimulated with concanavalin A (CONA A), or phytohemagglutinin (PHA). Auf, and GST inhibited IFN gamma production by CON A - stimulated NC and RA cells; D-Pen had no effect. Auf in low concentrations enhanced IFN gamma production by PHA - stimulated NC cells, but this effect was not seen with RA cells; GST inhibited both RA and NC cell production of IFN gamma, and D-Pen had no effect. Auf has a biphasic effect on IFN gamma production by NC cells with low concentrations being stimulatory or co-stimulatory, possibly by acting on T helper cells. Higher concentrations of Auf and GST, equivalent to those achieved in vivo in the course of therapy, inhibit IFN gamma production. These results suggest that gold therapy may affect IFN gamma production in RA, and could explain discrepancies noted in previous studies.

The modulation of interleukin 1 production by interferon gamma, and the inhibitory effects of gold compounds.

We have studied the in vitro effects of gold sodium thiomalate (GST) and auranofin (Auf) on the production of interleukin 1 (IL1) expressed as thymocyte co-stimulatory activity (TCSA), and interleukin 1 beta (IL1 beta) as modulated by interferon gamma (IFN gamma). Adherent cells (ADC), of which 80% were monocytes, were obtained from human peripheral blood, and stimulated with lipoprotein polysaccharide (LPS) for 24-48 h. TCSA and IL1 beta production by fresh ADC (0-24 h) was significantly higher than that of aged ADC (24-48 h). The addition of IFN gamma to ADC cultures, however, maintained the capacity of aging ADC to respond optimally to LPS. The addition of GST or Auf inhibited this modulatory effect of IFN gamma, resulting in a marked reduction of TCSA and IL1 beta production. The effects of IFN gamma on the production of IL1 may be important in the pathogenesis of rheumatoid arthritis (RA). The inhibition by GST and Auf of IFN gamma modulation may contribute to the therapeutic efficacy of these drugs in RA.

Cytokine production and lymphocyte transformation during stress.

The production of interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN gamma) and blast transformation in peripheral blood mononuclear cells were assessed in medical students writing an academic examination. Blood samples were obtained on three occasions: (1) 1 month prior to the examination during a period of relatively low academic demand; (2) immediately after the examination; and (3) 10 days later. Results indicated that immune responses were significantly different immediately after the examination compared with the baseline and postexam measures. Lymphocyte responsiveness to both concanavalin A and pokeweed mitogen was decreased, as was the production of IFN gamma, supporting earlier reports of immunosuppression after relatively commonplace stressors. In contrast to predictions, IL-1 beta production was significantly elevated after the examination. Cortisol levels were also measured, but did not change across the three sample points. Our finding of an increase in IL-1 beta production suggests that stress may have different effects on different cell populations by enhancing the responses of monocytes and depressing those of lymphocytes.

Coverage and overlaps in bibliographic databases relevant to forensic medicine: a comparative analysis of MEDLINE.

This study was designed to make a comparative evaluation of the performance of MEDLINE in covering serial literature. Forensic medicine was chosen because it is an interdisciplinary subject area that would test MEDLARS at the periphery of the system. The evaluation of database coverage was based upon articles included in the bibliographies of scholars in the field of forensic medicine. This method was considered appropriate for characterizing work used by researchers in this field. The results of comparing MEDLINE to other databases evoked some concerns about the selective indexing policy of MEDLINE in serving the interests of those working in forensic medicine.

Use of monoclonal antibodies for identification of growth-controlling neuropeptides in the mussel Mytilus edulis (Mollusca:Bivalvia).

Monoclonal antibodies were developed against cerebral ganglia (CG) of the mussel Mytilus edulis by the immunization of mice with unpurified homogenates of these organs. The screening protocol of hybridoma was based upon immunohistological observations of cytocentrifugated ganglia cells. A panel of 29 monoclonal antibodies (MABs) specific of CG epitopes was harvested and subsequently used for the immunocytochemical study of CG cells. Several subpopulations of ganglia cells were specifically revealed by MABs. Identification of epitopes involved in growth control was approached via the application of a bioassay allowing the assessment of protein synthesis stimulation. MAB 42 and 46 affected amino acid incorporation induced by CG extract. These results lead to the conclusion that the epitopes recognised by these antibodies are involved in growth control. An immunoenzymatic assay was performed with CG extracts for quantitative analyses of epitopes.