Early data on long-term efficacy and safety of inotersen in patients with hereditary transthyretin amyloidosis: a 2-year update from the open-label extension of the NEURO-TTR trial.

BACKGROUND AND PURPOSE: Hereditary transthyretin (hATTR) amyloidosis causes progressive polyneuropathy resulting from transthyretin (TTR) amyloid deposition throughout the body, including the peripheral nerves. The efficacy and safety of inotersen, an antisense oligonucleotide inhibitor of TTR protein production, were demonstrated in the pivotal NEURO-TTR study in patients with hATTR polyneuropathy. Here, the long-term efficacy and safety of inotersen are assessed in an ongoing open-label extension (OLE) study. METHODS: Patients who completed NEURO-TTR were eligible to enroll in the OLE (NCT02175004). Efficacy assessments included the modified Neuropathy Impairment Score plus seven neurophysiological tests composite score (mNIS + 7), the Norfolk Quality of Life - Diabetic Neuropathy (Norfolk QOL-DN) questionnaire total score and the Short-Form 36 Health Survey (SF-36) Physical Component Summary (PCS) score. Safety and tolerability were also assessed. RESULTS: Overall, 97% (135/139) of patients who completed NEURO-TTR enrolled in the OLE. Patients who received inotersen for 39 cumulative months in NEURO-TTR and the OLE continued to show benefit; patients who switched from placebo to inotersen in the OLE demonstrated improvement or stabilization of neurological disease progression by mNIS + 7, Norfolk QOL-DN and SF-36 PCS. No new safety concerns were identified. There was no evidence of increased risk for grade 4 thrombocytopenia or severe renal events with increased duration of inotersen exposure. CONCLUSION: Inotersen slowed disease progression and reduced deterioration of quality of life in patients with hATTR polyneuropathy. Early treatment with inotersen resulted in greater long-term disease stabilization than delayed initiation. Routine platelet and renal safety monitoring were effective; no new safety signals were observed.

Inhaled short-acting bronchodilators for managing emergency childhood asthma: an overview of reviews.

International guidelines provide conflicting recommendations on how to use bronchodilators to manage childhood acute wheezing conditions in the emergency department (ED), and there is variation within and among countries in how these conditions are managed. This may be reflective of uncertainty about the evidence. This overview of systematic reviews (SRs) aimed to synthesize, appraise, and present all SR evidence on the efficacy and safety of inhaled short-acting bronchodilators to treat asthma and wheeze exacerbations in children 0-18 years presenting to the ED. Searching, review selection, data extraction and analysis, and quality assessments were conducted using methods recommended by The Cochrane Collaboration. Thirteen SRs containing 56 relevant trials and 5526 patients were included. Results demonstrate the efficacy of short-acting beta-agonist (SABA) delivered by metered-dose inhaler as first-line therapy for younger and older children (hospital admission decreased by 44% in younger children, and ED length of stay decreased by 33 min in older children). Short-acting anticholinergic (SAAC) should be added to SABA for older children in severe cases (hospital admission decreased by 27% and 74% when compared to SABA and SAAC alone, respectively). Continuous nebulization, addition of magnesium sulfate to SABA, and levosalbutamol compared to salbutamol cannot be recommended in routine practice.

Elevated serum measures of lipid peroxidation and abnormal prefrontal white matter in euthymic bipolar adults: toward peripheral biomarkers of bipolar disorder.

Diffusion tensor imaging (DTI) studies consistently reported abnormalities in fractional anisotropy (FA) and radial diffusivity (RD), measures of the integrity of white matter (WM), in bipolar disorder (BD), that may reflect underlying pathophysiologic processes. There is, however, a pressing need to identify peripheral measures that are related to these WM measures, to help identify easily obtainable peripheral biomarkers of BD. Given the high lipid content of axonal membranes and myelin sheaths, and that elevated serum levels of lipid peroxidation are reported in BD, these serum measures may be promising peripheral biomarkers of underlying WM abnormalities in BD. We used DTI and probabilistic tractography to compare FA and RD in ten prefrontal-centered WM tracts, 8 of which are consistently shown to have abnormal FA (and/or RD) in BD, and also examined serum lipid peroxidation (lipid hydroperoxides, LPH and 4-hydroxy-2-nonenal, 4-HNE), in 24 currently euthymic BD adults (BDE) and 19 age- and gender-matched healthy adults (CONT). There was a significant effect of group upon FA in these a priori WM tracts (BDECONT: F[1,41]=10.3; P=0.003), and a significant between-group difference in LPH (BDE>CONT: t[40]=2.4; P=0.022), but not in 4-HNE. Multivariate multiple regression analyses revealed that LPH variance explained, respectively, 59 and 51% of the variance of FA and RD across all study participants. This is the first study to examine relationships between measures of WM integrity and peripheral measures of lipid peroxidation. Our findings suggest that serum LPH may be useful in the development of a clinically relevant, yet easily obtainable and inexpensive, peripheral biomarkers of BD.

Do fathead minnows, Pimephales promelas Rafinesque, alter their club cell investment in responses to variable risk of infection from Saprolegnia?

Fish in the Superorder Ostariophysi possess large epidermal club cells that release chemical cues warning nearby conspecifics of danger. Despite the long-held assumption that such club cells evolved under the selective force of predation, recent studies demonstrated that predation has no effect on club cell investment. Rather, club cells have an immune function and cell production may be stimulated by skin-penetrating pathogens and parasites. The current work investigates whether fathead minnows, Pimephales promelas, alter their club cell characteristics based on variation in infection risk. In a 2 × 3 design, we exposed minnows to infective cysts of two oomycete species (Saprolegnia ferax and S. parasitica) at three different concentrations (2, 20 or 200 cysts L(-1)). Club cell characteristics (number and size) were quantified 12 days after exposure. Saprolegnia parasitica is thought to be more pathogenic than S. ferax, hence we predicted greater club cell investment and a larger turnover rate of cells by minnows exposed to S. parasitica than S. ferax. We also predicted that minnows exposed to higher numbers of cysts should invest more in club cells and have a higher turnover rate of cells. We found no difference in club cell density or size between fish exposed to the two Saprolegnia species; however, fish exposed to high concentrations of pathogens had smaller club cells than those exposed to low concentrations, indicating a higher rate of turnover of cells in the epidermis.

Differences in structural geometrical outcomes at the neck of the proximal femur using two-dimensional DXA-derived projection (APEX) and three-dimensional QCT-derived (BIT QCT) techniques.

UNLABELLED: Structural geometric parameters at neck of the proximal femur were obtained using DXA-derived hip structural analysis (APEX 3) and quantitative computed tomography-derived (BIT QCT) techniques in 237 elderly females. Linear correlations for parameters ranged from 0.45 to 0.90. The average value of the subperiosteal width, as determined by the two techniques, was the same; variables dependent on mass measurements were different. INTRODUCTION: There has been increasing interest in using bone structural geometry to assess bone fragility to complement bone mineral mass. The objective of this study is to compare structural geometrical differences between "2D" DXA-derived and "3D" QCT-derived techniques in unselected clinical cases. METHODS: All 237 females had both DXA and QCT assessments of femoral neck structural geometry. Variables compared were areal bone mineral density, cross-sectional area (CSA), cross-sectional moment of inertia (CSMI), section modulus (Z), averaged cortical thickness (Ct), endosteal width (ESW), subperiosteal width (W), and buckling ratio (BR). RESULTS: Correlation of femoral neck variables ranged from 0.45 for ESW to 0.90 for CSA. APEX 3 and BIT QCT-derived femoral neck W values were numerically similar. However CSA, CSMI, Z and Ct values measured by APEX 3 were higher and ESW and BR values were lower than corresponding BIT QCT. CONCLUSIONS: 2D DXA structural analysis of neck of femur is related to but different from same parameters calculated from true 3D images obtained by CT. Femoral neck size values are similar for DXA and QCT, but structural geometrical variables dependent on mass calibration standards, location of neck ROI and mathematical derivation techniques are different.

Introduction of electronic referral from community associated with more timely review by secondary services.

BACKGROUND: Electronic referral (eReferral) from community into public secondary healthcare services was introduced to 30 referring general medical practices and 28 hospital based services in late 2007. OBJECTIVES: To measure the extent of uptake of eReferral and its association with changes in referral processing. METHODS: Analysis of transactional data from the eReferral message service and the patient information management system of the affected hospital; interview of clinical, operational and management stakeholders. RESULTS: eReferral use rose steadily to 1000 transactions per month in 2008, thereafter showing moderate growth to 1200 per month in 2010. Rate of eReferral from the community in 2010 is estimated at 56% of total referrals to the hospital from general practice, and as 71% of referrals from those having done at least one referral electronically. Referral latency from letter date to hospital triage improves significantly from 2007 to 2009 (p<0.001), from a paper referral median of 8 days (inter-quartile range, IQR: 4-14) in 2007 to an eReferral median of 5 days (IQR: 2-9) and paper referral median of 6 days (IQR: 2-12) in 2009. Specialists upgrade the referrer-assigned eReferral priority in 19.2% of cases and downgrade it 18.6% of the time. Clinical users appreciate improvement of referral visibility (status and content access); however, both general practitioners and specialists point out system usability issues. DISCUSSION: With eReferrals, a referral's status can be checked, and its content read, by any authorized user at any time. The period of eReferral uptake was associated with significant speed-up in referral processing without changes in staffing levels. The eReferral system provides a foundation for further innovation in the community-secondary interface, such as electronic decision support and shared care planning systems. CONCLUSIONS: We observed substantial rapid voluntary uptake of eReferrals associated with faster, more reliable and more transparent referral processing.

Detection of herpes viruses in respiratory secretions of patients undergoing artificial ventilation.

The significance of detection of herpes viruses in respiratory secretions of critically ill patients is controversial. The study aim was to determine the prevalence of herpes virus DNA in respiratory secretions in patients on artificial ventilation. Respiratory secretions taken thrice weekly from 174 patients in a tertiary center intensive therapy unit (ITU) were tested for herpes simplex virus (HSV) by nested PCR. Samples from 61 patients in ITU for 4 days or more were also tested for Epstein Barr Virus (EBV) and cytomegalovirus (CMV) using real-time PCR. HSV positivity increased with ITU stay with 18.6% admission samples positive, 32.5% day 2-5 samples, and 65.9% day 6-39 samples. Being HSV positive on admission did not influence mortality (9/27, 33.3% vs. 38/118, 32.2%) however, subsequently, mortality of those negative but becoming positive was higher than in those remaining negative (10/35, 29% vs. 5/24 21%). At least one sample was EBV positive in 61% and CMV positive in 19% of patients tested. Of 63 patients tested for all three viruses, 4 were positive for three viruses, 23 patients for two viruses, 24 for one virus and 12 were negative for all the above viruses. Detection of HSV, EBV and CMV is common in ITU patients. Becoming HSV positive while in ITU may increase mortality.

Amygdaloid kindling is anxiogenic but fails to alter object recognition or spatial working memory in rats.

Kindling in rats produces enduring behavioral changes that parallel the psychobehavioral disturbances frequently accompanying temporal lobe epilepsy. Some evidence suggests that the site of kindling is an important determinant of the type of behavioral changes observed following kindling, although this variable has not been systematically investigated. In the present experiments, the effects of amygdaloid kindling were assessed on a battery of behavioral tests we used previously to assess the effects of kindling in dorsal hippocampus or perirhinal cortex. Three generalized seizures were kindled with stimulation in or near the basolateral amygdala. One week later, rats were tested successively on measures of anxiety, activity, object recognition memory, and spatial working memory over a period of 3 weeks. Amygdaloid kindling produced increased anxiety, but spared all other behaviors assessed. This pattern of results is partially distinct from the previously described effects of perirhinal cortical kindling, which increases anxiety but also impairs object recognition memory, and is completely distinct from dorsal hippocampal kindling, which selectively increases activity and impairs spatial working memory. The observations suggest that kindling of distinct highly interconnected temporal lobe sites produces distinct patterns of behavioral comorbidity. The underlying mechanisms are thus most likely localized to intrinsic circuits at the site of seizure origination.

Choice of antenatal testing significantly effects a patient's work obligations.

OBJECTIVE: We sought to compare two approaches to antenatal testing for their impact on the workforce. STUDY DESIGN: This is a prospective observational study of women who presented for antenatal testing. All women were given a survey upon presentation. As per hospital protocol, nonstress testing (NST) was performed semiweekly and biophysical profile (BPP) was performed weekly. The choice of testing was determined by the attending physician. chi2- and Student's t-tests were performed where appropriate. A P-value of <0.05 was considered significant. RESULT: A total of 195 women were surveyed. Among them, 94 women had an NST and 101 had a BPP. Overall, 59.2% were multiparous, 33.1% had to arrange for child care and 97.2% felt reassured by the testing. There were no differences in demographic characteristics, education, type of insurance or employment status between the groups. Women who had NSTs were more likely to lose time from work than those who had BPPs (218.4 versus 68.9 min; P<0.001). Of the women who had semiweekly NSTs, 80.6% would have preferred weekly testing. If the 94 women who received semiweekly testing had weekly testing, a total of 534.4 h would have been available for the workforce. CONCLUSION: Twice-weekly NST results in a significant increase in time lost from the workforce compared with weekly BPP.

Anterior perirhinal cortex kindling produces long-lasting effects on anxiety and object recognition memory.

Temporal lobe epilepsy (TLE) is frequently accompanied by memory impairments and, although their bases are unknown, most research has focused on the hippocampus. The present study investigated the importance of another medial temporal lobe structure, the perirhinal cortex (Prh), in changes in memory in TLE using kindling as a model. Rats were kindled twice daily with anterior Prh stimulation until three fully generalized seizures were evoked. Beginning 7 days later and on successive days, rats were tested in an elevated plus maze, a large circular open field, an open field object exploration task and a delayed-match-to-place task in a water maze in order to assess anxiety-related and exploratory behaviour, object recognition memory and spatial cognition. Kindling increased anxiety-related behaviour in both the elevated plus and open field mazes and disrupted spontaneous object recognition but spared all other behaviours tested. These results are consistent with other findings indicating a greater role for the Prh in object memory and emotional behaviour than in spatial memory and contrast with the selective disruption of spatial memory produced by dorsal hippocampal kindling. The site-selectivity of the behavioural disruptions produced by kindling indicates that such effects are probably mediated by changes particular to the site of seizure initiation rather than to changes in the characteristic circuitry activated by limbic seizure generalization. Further investigation of the behavioural effects of Prh kindling may be useful for studying the mechanisms of mnemonic and affective dysfunction associated with TLE and offer insights into bases for variability in such dysfunction across patients.

The relation between extent of dorsal hippocampal kindling and delayed-match-to-place performance in the Morris water maze.

Dorsal hippocampal kindling impairs subsequent performance on spatial tasks. The relation between this effect and the extent of kindling achieved prior to testing has not been clearly established. Thus, the present study investigated the effects of dorsal hippocampal kindling on performance of a delayed-match-to-place (DMTP) task in the Morris water maze by assessing performance after each of series of different points in the kindling process including 1, 6, 11, and 16 afterdischarges, 1 stage 1 seizure, and 1 stage 5 seizure. We found that kindling produced a deficit that was apparent very early into kindling in terms of both direct swim (by 1 AD) and escape distance (by 6 ADs) measures but that did not clearly change in severity with further kindling. These results illustrate that kindling of even a few localized hippocampal seizures can disrupt spatial cognition and suggest that the mechanisms mediating memory disruption either do not change substantially as kindling progresses or that compensatory processes are engaged across training that mitigate any further kindling-related deteriorations in performance.

Comparison of total, complexed and free prostate-specific antigens and their ratios in the detection of prostate cancer in a non-screened population.

BACKGROUND: The role of prostate-specific antigen (PSA) isoforms in the detection of prostate cancer in a non-screened population in the UK remains to be determined. METHODS: Consecutive patients undergoing diagnostic transrectal ultrasound-guided biopsy of the prostate were studied. Prior to biopsy, a blood sample was obtained and total, complexed and free PSA concentrations measured. RESULTS: Of the 171 patients included in the study, 103 were found to have prostate cancer. There were significant differences in total and complexed PSA concentrations and in the ratio of free-to-total PSA (all P <0.001) between patients with prostate cancer and those with benign disease. Receiver operating characteristics (ROC) curve analysis showed that the corresponding areas under the curves were similar. Restricting the analysis to the 77 patients who had total PSA concentrations between 2 and 10 micro g/L, ROC curve analysis showed that total and complexed PSA concentrations failed to discriminate between benign and malignant disease. In contrast, the areas under the ROC curve were greater for the free-to-total ratio (P = 0.033). CONCLUSION: These results show that in patients with total PSA concentrations between 2 and 10 micro g/L, the free-to-total PSA ratio was superior to total PSA concentration in discriminating between patients with benign and malignant disease.

Generalized equations for predicting body density of men. 1978.

1. Skinfold thickness, body circumferences and body density were measured in samples of 308 and ninety-five adult men ranging in age from 18 to 61 years. 2. Using the sample of 308 men, multiple regression equations were calculated to estimate body density using either the quadratic or log form of the sum of skinfolds, in combination with age, waist and forearm circumference. 3. The multiple correlations for the equations exceeded 0.90 with standard errors of approximately +/-0.0073 g/ml. 4. The regression equations were cross validated on the second sample of ninety-five men. The correlations between predicted and laboratory-determined body density exceeded 0.90 with standard errors of approximately 0.0077 g/ml. 5. The regression equations were shown to be valid for adult men varying in age and fatness.

[Relationship between learning ability and memory and free radical in hippocampus of old rats].

OBJECTIVE: To study the relationship between the amount of free radical in hippocampus and the learning ability and memory in old rats. METHODS: Morris water maze was used for 10 days to examine the learning scores, latency scores, and the loci of movement in the maze among 46 old rats (aged 20 months), 36 young rats (aged 6 months), and 34 adult rats (aged 12 months). Salicylate was injected intraperitoneally and hippocampus dialysis was performed. Chromatography was used to measure the basic values of 2,3DHBA and 2,5DHBA in dialysis fluid chemiluminometry was used to measure the superoxide dismutrase (SOD) in the sample. The rats were killed and their brains were taken out. Histological examination was conducted to calculate the number of neurons in CA1, CA4, and PM regions in hippocampus. RESULTS: The learning scores on the first, fifth, and tenth days were 36.5 +/- 5.9 sec, 38.6 +/- 5.9 sec, and 39.4 +/- 6.9 sec (P > 0.05) in the old rats; 60.2 +/- 5.4 sec, 156.8 +/- 5.8 sec, and 165.1 +/- 6.8 sec in the young rats; and 61.7 +/- 5.8 sec, 152.3 +/- 6.9 sec, and 168.7 +/- 6.5 sec in adult rats. The learning scores at any time point of old rats were significantly lower than those of the young and adults rats (all P < 0.01). The latency scores of the first, fifth, and tenth days were 25.7 +/- 1.2 sec, 27.5 +/- 1.9 sec, and 27.7 +/- 1.9 sec in the old rats without significant difference between any two of these values (P > 0.05), however, the 3 latency scores of the old rats were all significantly larger than those of the young and adult rats (21.8 +/- 1.7 sec, 5.9 +/- 1.0 sec, and 3.6 +/- 0.6 sec, and 21.8 +/- 1.6 sec, 5.0 +/- 0.9 sec, and 4.8 +/- 0.7 sec respectively, all P < 0.01). The basic value of 2,3DHBA after intraperitoneal injection of salicylate was 20.7 +/- 0.3 pmol/ml in the old rats, 5 times that of the young rats and 6 times that of the adult rats (P < 0.01). The basic value of 2,5DHBA after intraperitoneal injection of salicylate was 60.12 pmol/ml in the old rats, 6 times that of the young rats and 5.8 times that of the adult rats (P < 0.01). The SOD activity was 410 U x g(-1) x min(-1) +/- 50 U x g(-1) x min(-1), significantly lower than those in the young and adult rats (880 U x g(-1) x min(-1) +/- 62 U x g(-1) x min(-1) and 860 U x g(-1) x min(-1) +/- 60 U x g(-1) x min(-1) (both P < 0.01). The values of neuron density in CA1, CA4, and PM regions of the old rats were all significantly lower than those of the young and adult rats (all P < 0.01). CONCLUSION: The decrease of learning ability in old rat is positively correlated with the increase of free radicals and loss of neurons in hippocampus.

Circadian clock resetting by arousal in Syrian hamsters: the role of stress and activity.

Circadian rhythms in the Syrian hamster can be markedly phase shifted by 3 h of wheel running or arousal stimulation during their usual daily rest period ("subjective day"). Continuous wheel running is predictive but not necessary for phase shifts of this "nonphotic" type; hamsters aroused by gentle handling without running can also show maximal shifts. By contrast, physical restraint, a standard stress procedure and thus presumably arousing, is ineffective. To resolve this apparent paradox, phase-shifting effects of 3-h sessions of restraint or other stress procedures were assessed. In a preliminary study, phase shifts to arousal by gentle handling were significantly potentiated by the cortisol synthesis inhibitor metyrapone, suggesting that stress-related cortisol release may inhibit phase shifts to arousal. Next, it was confirmed that restraint in the subjective day does not induce phase shifts, but behavioral observations revealed that it also does not sustain arousal. Restraint combined with noxious compressed air blasts did sustain arousal and induced a significant cortisol response compared with arousal by gentle handling but did not induce shifts. Restraint combined with continuous horizontal rotation was also ineffective, as was EEG-validated arousal via confinement to a pedestal over water. However, 3 h of resident-intruder interactions (an intense psychosocial stress) or exposure to an open field (a mild stress) did induce large shifts that were positively correlated with indexes of forward locomotion. The results indicate that large phase shifts associated with arousal in the usual sleep period are neither induced nor prevented by stress per se, but are dependent on the expression of at least low levels of locomotor activity. Sustained arousal alone is not sufficient.

The cell morphogenesis gene ANGUSTIFOLIA encodes a CtBP/BARS-like protein and is involved in the control of the microtubule cytoskeleton.

The ANGUSTIFOLIA (AN) gene is required for leaf hair (trichome) branching and is also involved in polarized expansion underlying organ shape. Here we show that the AN gene encodes a C-terminal binding proteins/brefeldin A ADP-ribosylated substrates (CtBP/BARS) related protein. AN is expressed at low levels in all organs and the AN protein is localized in the cytoplasm. In an mutant trichomes, the organization of the actin cytoskeleton is normal but the distribution of microtubules is aberrant. A role of AN in the control of the microtubule cytoskeleton is further supported by the finding that AN genetically and physically interacts with ZWICHEL, a kinesin motor molecule involved in trichome branching. Our data suggest that CtBP/BARS-like protein function in plants is directly associated with the microtubule cytoskeleton.

Mast cells differentially express and release active high molecular weight neurotrophins.

Nerve growth factor (NGF), a target-derived factor for survival and maintenance of peripheral and central neurons, has been implicated in inflammatory processes. Mast cells are the principal effector cells in IgE-dependent hypersensitivity reactions, and also play a role in diseases characterised by inflammation, including those of the nervous system like multiple sclerosis. Mast cells are capable of synthesising and responding to NGF, although the occurrence of other members of the NGF family of neurotrophins and their protein forms have not been described. Immunoblot analysis with highly selective neurotrophin antibodies has now been used to show that rat peritoneal mast cells express a higher molecular weight form (73 kDa) of NGF, but not the monomeric (13 kDa) NGF polypeptide. Mast cells also expressed 73 kDa forms of neurotrophin-4 and neurotrophin-3; brain-derived neurotrophic factor was not detected. Medium conditioned by degranulating peritoneal mast cells contained similar high molecular weight forms of NGF and neurotrophin-4 on Western blots, but no neurotrophin-3. Mast cell-derived neurotrophin immunoreactivities were inhibited by the respective peptide antigen, further demonstrating the specificity of the mast cell-derived neurotrophic protein. Mast cell-released proteins supported the survival of cultured chicken embryonic neural crest- and placode-derived sensory neurons; neurotrophic activities were inhibited by neutralising antibodies for NGF and neurotrophin-4, respectively. High molecular isoforms of neurotrophins have been reported to occur in experimental colitis and in the inflamed gut of patients with Crohn's disease and ulcerative colitis, tissue sites rich in mast cells. The data suggest an important role for neurotrophins in the pathophysiology of inflammatory disease.

Transcervical Foley catheter for preinduction cervical ripening in an outpatient versus inpatient setting.

OBJECTIVE: To compare use of the Foley catheter for preinduction cervical ripening in an inpatient versus outpatient setting. METHODS: A randomized trial was conducted from May 1998 to December 1999. Women with a term gestation in the vertex presentation, a reactive nonstress test, an amniotic fluid index above the fifth percentile, and a Bishop score of no more than 5 were included. The primary outcome variable was a change in Bishop score. A Foley catheter with a 30-mL balloon was placed through the cervix on gentle traction in each group. The outpatient group was then discharged home with written instructions and returned in the morning for induction. The inpatient group was admitted to labor and delivery, with induction started upon extrusion of the Foley. RESULTS: Sixty-one women were randomized into the outpatient group, and 50 women into the inpatient group. Maternal age, gravidity, previous cesarean delivery, and gestational age did not differ between the groups. The median Bishop score at entry was 3.0 for each group (P =.97). The mean change in Bishop scores after catheter placement was not different between the inpatient and outpatient groups (3.0 versus 3.0; P =.74). The maximum dose of oxytocin, time of oxytocin, epidural rate, induction time, 1-minute and 5-minute Apgar scores, and cord pH were not significantly different. The outpatient group on average avoided 9.6 hours of hospitalization. There were no adverse events or maternal morbidity in either group. CONCLUSIONS: The Foley bulb is as effective in the outpatient as the inpatient setting for preinduction cervical ripening.

Thyroxine treatment in patients with symptoms of hypothyroidism but thyroid function tests within the reference range: randomised double blind placebo controlled crossover trial.

OBJECTIVES: To determine whether thyroxine treatment is effective in patients with symptoms of hypothyroidism but with thyroid function tests within the reference range, and to investigate the effect of thyroxine treatment on psychological and physical wellbeing in healthy participants. DESIGN: Randomised double blind placebo controlled crossover trial. SETTING: Outpatient clinic in a general hospital. PARTICIPANTS: 25 patients with symptoms of hypothyroidism who had thyroid function tests within the reference range, and 19 controls. METHODS: PARTICIPANTS were given thyroxine 100 microgram or placebo to take once a day for 12 weeks. Washout period was six weeks. They were then given the other to take once a day for 12 weeks. All participants were assessed physiologically and psychologically at baseline and on completion of each phase. MAIN OUTCOME MEASURES: Thyroid function tests, measures of cognitive function and of psychological and physical wellbeing. RESULTS: 22 patients and 19 healthy controls completed the study. At baseline, patients' scores on 9 out of 15 psychological measures were impaired when compared with controls. Patients showed a significantly greater response to placebo than controls in 3 out of 15 psychological measures. Healthy participants had significantly lower scores for vitality when taking thyroxine compared to placebo (mean (SD) 60 (17) v 73 (16), P<0.01). However, patients' scores from psychological tests when taking thyroxine were no different from those when taking placebo except for a poorer performance on one visual reproduction test when taking thyroxine. Serum concentrations of free thyroxine increased and those of thyroid stimulating hormone decreased in patients and controls while they were taking thyroxine, confirming compliance with treatment. Although serum concentrations of free triiodothyronine increased in patients and controls taking thyroxine, the difference between the response to placebo and to thyroxine was significant only in the controls. CONCLUSIONS: Thyroxine was no more effective than placebo in improving cognitive function and psychological wellbeing in patients with symptoms of hypothyroidism but thyroid function tests within the reference range. Thyroxine did not improve cognitive function and psychological wellbeing in healthy participants.