Association of higher rheumatoid arthritis disease activity during pregnancy with lower birth weight: Results of a national prospective study

Objective

To determine the outcome of pregnancy in women with rheumatoid arthritis (RA) in relation to disease activity and medication use during the pregnancy.

Methods

In a prospective study, pregnant women with RA were evaluated before conception (when possible), during each trimester of the pregnancy, and postpartum. Clinical characteristics, disease activity, medication use, and pregnancy outcome were analyzed. To examine the independent influence of prednisone use and disease activity on birth weight, regression analyses were performed, with adjustments for gestational age of the child at delivery, the sex of the newborn, and the mother's smoking status, education level, parity, and use of an assisted reproduction technique. Kaplan‐Meier curve analyses were performed to examine the association between medication use and gestational age at delivery.

Results

Data from 152 Caucasian RA patients with singleton pregnancies were available. Both the mean ± SD birth weight (3,379 ± 564 gm) and the mean ± SD birth weight standard deviation score (SDS; +0.1 ± 1.1), which is the birth weight adjusted for the gestational age and sex of the newborn, were comparable with those in the general population. On multiple linear regression analyses of birth weight and birth weight SDS, both of which were adjusted for covariates, only disease activity was associated with lower birth weight (P = 0.025). The gestational age at delivery was significantly lower in women who were taking prednisone (38.8 versus 39.9 weeks; P = 0.001), and their delivery was more often premature (<37 weeks; P = 0.004).

Conclusion

Pregnancy outcome in women with well‐controlled RA is comparable with that in the general population. The effect of prednisone on birth weight is mediated by a lower gestational age at delivery, whereas a higher level of disease activity independently influences birth weight negatively, suggesting an immune‐mediated mechanism.

     

Co-infection with human immunodeficiency virus and tuberculosis in Asia

Asia has the highest numbers of tuberculosis cases (60% of the global total) and has experienced a marked rise in HIV seroprevalence (22% of the global total) in key subpopulations of these highly populous nations. Thus, co-infected patients are a challenge for practitioners and public health workers alike. The U.S.-Japan Cooperative Medical Science Program is spearheading interdisciplinary collaborations in Asia to address the many outstanding research priorities for HIV-tuberculosis co-infection. There is an urgency to this agenda for many reasons, including the frequency with which tuberculosis accounts for the death of HIV-infected persons in Asia, and the continued rise of multiple drug-resistant Mycobacterium tuberculosis. We review briefly the public health situation in Asia, highlighting research questions from US-Japan-Asian partner joint meetings, and cite salient studies to indicate trends and challenges.     

GABA distribution in lamprey is phylogenetically conserved

The localization of gamma-aminobutyric acid (GABA) has been well described in most classes of vertebrates but not in adult lampreys. The question if the GABA distribution is similar throughout the vertebrate subphylum is therefore still to be addressed. We here investigate two lamprey species, the sea lamprey, Petromyzon marinus, and the river lamprey, Lampetra fluviatilis, and compare the GABA pattern with that of other vertebrates. The present immunohistochemical study provides an anatomical basis for the general distribution and precise localization of GABAergic neurons in the adult lamprey forebrain and brainstem. GABA-immunoreactive cells were organized in a virtually identical manner in the two species. They were found throughout the brain, with the following regions being of particular interest: the granular cell layer of the olfactory bulb, the nucleus of the anterior commissure, the septum, the lateral and medial pallia, the striatum, the nucleus of the postoptic commissure, the thalamus, the hypothalamus, and pretectal areas, the optic tectum, the torus semicircularis, the mesencephalic tegmentum, restricted regions of the rhombencephalic tegmentum, the octavolateral area, and the dorsal column nucleus. The GABA distribution found in cyclostomes is very similar to that of other classes of vertebrates, including mammals. Since the lamprey diverged from the main vertebrate line around 450 million years ago, this implies that already at that time the basic vertebrate plan for the GABA innervation in different parts of the brain had been developed.     

Progression of non-age-related callosal brain atrophy in multiple sclerosis: a 9-year longitudinal MRI study representing four decades of disease development

Background

In multiple sclerosis (MS), multiple periventricular lesions are commonly the first findings on MRI. However, most of these MS lesions are clinically silent. The brain atrophy rate has shown better correlation to physical disability, but it is not clear how atrophy develops over decades. Corpus callosum forms the roof of the third and lateral ventricles. The corpus callosum area (CCA) in a midsagittal image is age independent in a normal adult population up to the seventh decade; therefore it can be used as a marker for non‐age‐related, pathological brain atrophy.

Objectives

To investigate whether and how CCA decreases in size over time in patients with MS.

Methods

In a clinical observational study, 37 patients with MS with a wide range of disease duration at baseline (1–33 years) were followed. Three different MS courses were represented. The mean of individual MRI follow‐up was 9 years. Multiple sclerosis severity score (MSSS) was also applied to evaluate disability at baseline and after 9 years of follow‐up.

Results

A significant decrease in CCA over 9 years (p<0.001) and a persisting association between CCA and the disability status were found. The atrophy rate was similar ever four decades of MS for all MS courses. The mean annual CCA decrease was 9.25 mm² (1.8%). Surprisingly, atrophy rate did not correlate with sex, disease duration, age at MS onset or MS course.

Conclusions

Serial evaluations of CCA might be a robust method in monitoring a non‐age‐related decrease in CCA, reflecting progression of irreversible destructive changes in MS.Multiple sclerosis (MS) is a complex inflammatory disease of the brain and spinal cord,^1,2,3 which leads to a well‐documented early irreversible atrophy.^4,5,6 The main neuroimaging modality used to monitor MS development is MRI, which can visualise both lesions and atrophy. In follow‐up examinations of patients with MS, the correlation between clinical development and extent of MRI findings is generally poor, which is sometimes referred to as “the clinicoradiological paradox”.⁷In contrast with focal MS lesions, atrophy measures of the brain or spinal cord have been regarded as a better predictor of the disability progression in MS.^2,5,8,9,10 However, some reports also show non‐significant correlation between disability and atrophy.^{11,12,13,14,15,16} Focal MS lesions visualised on MRI have a characteristic pattern of oval‐shaped, typically periventricular white matter changes, often located in the corpus callosum. Atrophy of the corpus callosum is common in MS. However, pathological changes in the corpus callosum might develop independently of focal T2‐weighted lesions.¹⁷The corpus callosum, consisting of 2×10⁸ axons in a healthy person, forms the roof of the third and lateral ventricles and has a central role for interhemispheric communication.¹⁸ The corpus callosum area (CCA) is normally resistant to age‐related shrinkage between the third and the seventh decades of life.^19,20 Atrophy of the corpus callosum correlates to other measures of brain atrophy such as widening of third and lateral ventricles.¹ Pelletier et al²¹ reported a persisting association between CCA and disability, as assessed by the Expanded Disability Status Scale (EDSS) in a 5‐year longitudinal study of patients with relapsing–remitting multiple sclerosis (RRMS). Schreiber et al²² reported CCA in patients with MS to be associated with EDSS. In contrast, Barkhof et al²³ reported a lack of correlation between CCA and EDSS. Simon et al¹ found a slight correlation between CCA and EDSS at baseline, but on follow‐up there was no significant correlation between the significant CCA decrease and EDSS change.The corpus callosum atrophy rate has not been reported for different disease durations, sex or types of MS course in longitudinal studies.²¹ The starting point for prospective, longitudinal MRI studies is often close to the time of diagnosis of MS, focusing on the early years of the disease.We followed a patient cohort for 9 years. Disease duration at baseline was widespread (range 1–33 years), giving us the possibility of an overview of disease development over four decades. Our first aim was to study the rate at which the callosal atrophy developed. Second, we wanted to study the correlation between the atrophy rate and disability changes. The third aim was to study the association between CCA and disability at baseline and at the end of the study. The fourth aim was to investigate the association of the atrophy rate to sex, MS course (course at the end of study), disease duration and age at onset.     

Laparoscopic left lobe liver resection in a porcine model: a study of the efficacy and safety of different surgical techniques

Introduction  Laparoscopic liver surgery is evolving and the best technique for dividing the liver parenchyma is currently under debate. The aim of this study was to study different techniques during a full laparoscopic lobe resection, and determine the efficacy and risks of bleeding and gas embolism. Methods  Sixteen pigs were randomized to two groups: group US underwent an operation with Ultracision shears (AutoSonix) and ultrasonic dissector (CUSA) and group VS with a vessel sealing system (Ligasure) and ultrasonic dissector. A left lobe resection was performed. Transesophageal endoscopic echocardiography (TEE) was used to detect gas emboli in the right side of the heart and pulmonary artery. The operations and TEE were recorded for later assessment. Results  Compared with group VS, group US exhibited significantly more intraoperative bleeding (p = 0.02), a trend towards a longer operation time (p = 0.08), and a trend towards more embolization for grade I emboli. In total, 10 of 15 animals had emboli during the operation. Conclusions  This study showed that a laparoscopic left lobe resection can be performed with a combination of AutoSonix and CUSA as well as with Ligasure and CUSA instrumentation. In our hands, less bleeding was incurred with Ligasure than with AutoSonix. An erratum to this article can be found at     

Risk factors for deterioration of erectile function: the Krimpen study

This report from the Krimpen study explored the relationship between the determinants for worsening of erectile function in the open population. In Krimpen aan den IJssel (a municipality near Rotterdam), all men aged 50–75 years, without cancer of the prostate or the bladder and without a history of radical prostatectomy or neurogenic bladder disease, were invited to participate in June 1995. The response rate was 50%. The follow-up was until June 2004. At baseline a visit to a health centre for the measurement of urinalysis, height, weight and blood pressure was part of the ongoing study. During baseline and at the first follow-up, second follow-up and third follow-up, a self-administered booklet consisting of a compilation of validated questionnaires including the International Continence Society male sex questionnaire was completed. At the urology outpatient clinic, a urological workup was measured. All participants were asked to keep a frequency–volume chart for 3 days. A multivariate Cox-proportional hazard model was constructed to find the determinants of worsening of erectile function, correcting for age. Total follow-up time was 4948 person years consisting of 975 men. During follow-up, 441 events of worsening of erectile function occurred. Multivariate Cox-proportional hazard ratio analyses showed that body mass index (BMI), irritative lower urinary tract symptoms, diabetes mellitus, chronic obstructive pulmonary disease (COPD) and sexual inactivity were determinants with significant hazard ratios. In addition to age, determinants for a deterioration of erectile function based on multivariate longitudinal analyses are BMI, diabetes mellitus, COPD, sexual inactivity and irritative IPSS. The mechanism of various determinants is discussed.     

Clinical outcome in patients with prostate cancer treated with external beam radiotherapy and high dose-rate iridium 192 brachytherapy boost: a 6-year follow-up

To report the long-term results for treatment of localized carcinoma of the prostate using high dose rate (HDR) brachytherapy, conformal external beam radiotherapy (3D EBRT) and neo-adjuvant hormonal therapy (TAB). From 1998 through 1999, 154 patients with localized prostate cancer were entered in the trial. Biologically no evidence of disease (bNED) was defined at PSA levels < 2 microg/l. In order to compare the results of this treatment with other treatment modalities, the patient's pre-treatment data were used to calculate the estimated 5-year PSA relapse free survival using Kattan's nomograms for radical prostatectomy (RP) and 3D EBRT. After 6 years of follow-up, 129 patients remain alive. The actual 5-year relapse-free survival is 84%. None of the patients demonstrated clinical signs of local recurrence. The median PSA at follow-up among the relapse-free patients was 0.05 microg/l. Among the 80 patients who presented with clinical stage T3 tumours, 55 (68%) were relapse-free. The expected 5-year relapse-free survival using nomograms for RP and 3D EBRT was 54% and 70%, respectively. Late rectal toxicity RTOG grade 3 occurred in 1% of the patients. Late urinary tract toxicity RTOG grade 3 developed in 4% of the patients. Combined treatment, utilizing HDR, 3D EBRT and TAB, produces good clinical results. Rectal toxicity is acceptable. Urinary tract toxicity, most likely can be explained by the fact that during the first years of this treatment, no effort was made to localize the urethra, which was assumed to be in the middle of the prostate.     

Long-term follow-up of children with obstetric brachial plexus palsy II: neurophysiological aspects

The aim of this study was to examine long-term neurophysiological outcomes and sensory function in patients with obstetric brachial plexus palsy (OBPP). The same 70 children/adolescents examined in part I: functional aspects (35 males, 35 females; age range 7-20y, mean 13y 6mo [SD 4y 3mo], median 13y) were examined with neurophysiological methods at 3 to 7 months and at 7 to 20 years of age. Thirteen of the 70 participants underwent nerve reconstruction before 1 year of age. Electromyography (EMG) was performed on deltoid and first interossei muscles; Quantitative Sensory Test was used for C6 and C8 dermatomes. Tests for functional sensibility and 2-point discrimination for C6 and C8 were performed. This study shows that considerable EMG changes can be observed in OBBP, even in those fully recovered. EMG changes in the deltoid were shown to deteriorate over time, and sensibility is considerably less affected than motor function.     

Bone-targeted radium-223 in symptomatic, hormone-refractory prostate cancer: a randomised, multicentre, placebo-controlled phase II study

BACKGROUND: The alpha-emitter radium-223 ((223)Ra) is a bone-seeking radionuclide studied as a new treatment for patients with bone metastases from hormone-refractory prostate cancer. We aimed to study mature outcomes from a randomised, multicentre, phase II study of (223)Ra. METHODS: Patients with hormone-refractory prostate cancer and bone pain needing external-beam radiotherapy were assigned to four intravenous injections of (223)Ra (50 kBq/kg, 33 patients) or placebo (31 patients), given every 4 weeks. Primary endpoints were change in bone-alkaline phosphatase (ALP) concentration and time to skeletal-related events (SREs). Secondary endpoints included toxic effects, time to prostate-specific-antigen (PSA) progression, and overall survival. All tests were done at a 5% significance level, based on intention to treat. FINDINGS: Median relative change in bone-ALP during treatment was -65.6% (95% CI -69.5 to -57.7) and 9.3% (3.8-60.9) in the (223)Ra group and placebo groups, respectively (p<0.0001, Wilcoxon ranked-sums test). Hazard ratio for time to first SRE, adjusted for baseline covariates, was 1.75 (0.96-3.19, p=0.065, Cox regression). Haematological toxic effects did not differ significantly between two groups. No patient discontinued (223)Ra because of treatment toxicity. Median time to PSA progression was 26 weeks (16-39) versus 8 weeks (4-12; p=0.048) for (223)Ra versus placebo, respectively. Median overall survival was 65.3 weeks (48.7-infinity) for (223)Ra and 46.4 weeks (32.1-77.4) for placebo (p=0.066, log rank). The hazard ratio for overall survival, adjusted for baseline covariates was 2.12 (1.13-3.98, p=0.020, Cox regression). INTERPRETATION: (223)Ra was well tolerated with minimum myelotoxicity, and had a significant effect on bone-ALP concentrations. Larger clinical trials are warranted to study (223)Ra on the prevention of SREs and on overall survival in patients with hormone-refractory prostate cancer. Bone-targeting properties of (223)Ra could also potentially be used for treating skeletal metastasis from other primary cancers.