Attenuation of Corpus Callosum Axon Myelination and Remyelination in the Absence of Circulating Sex Hormones

Sex differences in the structure and organization of the corpus callosum (CC) can be attributed to genetic, hormonal or environmental effects, or a combination of these factors. To address the role of gonadal hormones on axon myelination, functional axon conduction and immunohistochemistry analysis of the CC in intact, gonadectomized and hormone‐replaced gonadectomized animals were used. These groups were subjected to cuprizone diet‐induced demyelination followed by remyelination. The myelinated component of callosal compound action potential was significantly decreased in ovariectomized and castrated animals under normal myelinating condition. Compared to gonadally intact cohorts, both gonadectomized groups displayed more severe demyelination and inhibited remyelination. Castration in males was more deleterious than ovariectomy in females. Callosal conduction in estradiol‐supplemented ovariectomized females was significantly increased during normal myelination, less attenuated during demyelination, and increased beyond placebo‐treated ovariectomized or intact female levels during remyelination. In castrated males, the non‐aromatizing steroid dihydrotestosterone was less efficient than testosterone and estradiol in restoring normal myelination/axon conduction and remyelination to levels of intact males. Furthermore, in both sexes, estradiol supplementation in gonadectomized groups increased the number of oligodendrocytes. These studies suggest an essential role of estradiol to promote efficient CC myelination and axon conduction in both sexes.     

Internal target volume for post-hysterectomy vaginal recurrences of cervical cancers during image-guided radiotherapy

Objective:

The outcome of post-surgical recurrences of cervical cancer may be improved through radiation dose escalation, which hinges on accurate identification and treatment of the target. The present study quantifies target motion during course of image-guided radiotherapy (IGRT) for vault cancers.

Methods:

All patients underwent planning CT simulation after bladder-filling protocol. A daily pre-treatment megavoltage CT was performed. All translations and rotations were recorded. Post-registration displacement of gross tumour volume (GTV) and centre of mass (COM) of GTV was independently recorded by two observers for fractions one to seven. Day 1 image sets served as reference images against which the displacements of COM were measured. We calculated the displacements of common volume (CV) and encompassing volume (EV) of GTV for both the observers.

Results:

A total of 90 image data sets of 15 patients were available for evaluation. Individual patient GTV and average GTV by both the observers were comparable. The average shifts for EV were 2.4 mm [standard deviation (SD) ±1.2] in the mediolateral, 4.2 mm (SD ±2.8) in the anteroposterior and 4.0 mm (SD ±2.1) in superoinferior directions. Similarly, the average shifts for CV were 1.9 mm (SD ±0.6) in the mediolateral, 3.7 mm (SD ±2.7) in the anteroposterior and 4.4 mm (SD ±2.7) in superoinferior directions. Using Stroom''s/van Herk''s formula, the minimum recommended margins would be 4.5/5.2, 8.2/9.4 and 7.3/8.3 mm, respectively, for lateral, anteroposterior and superoinferior directions.

Conclusion:

Differential directional internal margin is recommended in patients undergoing IGRT for post-surgical recurrence of cervical cancers.

Advances in knowledge:

Internal organ motion of vault cancers can be accounted for by a directional margin to the gross tumour.     

Clinical factors predictive of outcome with bortezomib in patients with relapsed, refractory multiple myeloma

Bortezomib, a potent and reversible proteasome inhibitor, affects the myeloma cell and its microenvironment, resulting in down-regulation of growth and survival signaling pathways and durable responses in patients with relapsed and refractory myeloma. Potential associations between baseline parameters and outcomes with bortezomib were explored in 202 patients who received bortezomib 1.3 mg/m2 twice weekly for 2 weeks every 3 weeks for up to 8 cycles in a phase 2 trial. Using European Group for Blood and Marrow Transplantation criteria, the response rate (complete or partial response) to bortezomib alone was 27% and was not associated with sex, race, performance status, isotype, chromosome 13 deletion, number or type of previous therapies, or concentration of hemoglobin or beta2-microglobulin. By multivariate analysis, factors associated with lower response were being age 65 or older versus younger than 65 (19% vs 32%; P < .05) and plasma-cell infiltration in bone marrow greater than 50% versus 50% or less (20% vs 35%; P < .05). Factors that may be indicative of tumor burden (bone marrow plasma-cell infiltration greater than 50%, hypoalbuminemia, thrombocytopenia) were predictive of overall survival. Chromosome 13 deletion and elevated beta2-microglobulin, generally considered poor prognostic factors, were not predictive of poor outcome with bortezomib in this study.     

Reliability, validity, and responsiveness of Severity of Dyspepsia Assessment (SODA) in a randomized clinical trial of a COX-2-specific inhibitor and traditional NSAID therapy

OBJECTIVES: We aimed to assess the Severity of Dyspepsia Assessment (SODA) scales as measures of change in dyspepsia-related health in a blinded, randomized, controlled trial in arthritis patients treated with nonsteroidal anti-inflammatory drugs. METHODS: Three thousand nine hundred seven arthritis patients completed SODA at baseline and weeks 4, 13, 26, and 52 and/or at early termination. Using baseline and 4-wk data, reliability was evaluated with Cronbach's a and the intraclass correlation coefficient (ICC). Dyspepsia adverse events were defined based on a combined set of World Health Organization Adverse Reaction Terminology terms. The ability of SODA to measure change in dyspepsia-related health was evaluated by comparing SODA change scores by dyspepsia adverse event severity level and withdrawal status. Responsiveness was further evaluated by the area under the curve (AUC) from receiver operating characteristic curves using withdrawal due to dyspepsia as the criterion. RESULTS: The SODA scales--Pain Intensity (alpha = 0.93), Non Pain Symptoms (alpha = 0.82), and Satisfaction (alpha = 0.89)--demonstrated excellent internal consistency reliability using baseline data. Reproducibility was fair to good: Pain Intensity ICC = 0.49, Non Pain Symptoms ICC = 0.61, and Satisfaction ICC = 0.45. SODA change scores (4-wk score - baseline score) increased, or worsened, with increasing dyspepsia severity and differentiated between adjacent levels of dyspepsia severity for eight of nine adjacent comparisons (p < 0.05). SODA change scores also differentiated between those who did and did not withdraw (p < 0.001). Responsiveness was highest with the Pain Intensity scale (AUC = 0.78), followed by the Non Pain Symptoms (AUC = 0.74) and Satisfaction (AUC = 0.75) scales. CONCLUSIONS: SODA is a reliable, valid instrument for use as a measure of dyspepsia tolerability in future clinical trials involving cyclo-oxygenase-2-specific and/or traditional nonsteroidal anti-inflammatory drugs.     

A longitudinal study to determine association of various maternal factors with neonatal birth weight at a tertiary care hospital

Background

Neonatal birth weight is a powerful predictor of infant growth and survival and maternal factors like poor knowledge and insufficient dietary intake are significant risk factors. Other preventable determinants like pre pregnant BMI <18.5, low gestational weight gain (GWG) and anemia are also associated with low birth weight. This study was carried out to identify the impact of these maternal factors with risk of low birth weight (LBW).

Methods

A longitudinal study was carried out on 124 booked antenatal cases at a tertiary care center. A validated protocol containing socio demography, food frequency and anthropometry was administered at the 3rd trimester. Birth weight of the newborn was noted after delivery.

Results

26.28% children had low birth weight (<2500 g), 14.6% mothers were thin (BMI < 18.5), 55.3% mothers had a weight gain of less than 9 kgs and 45.5% were anemic. 81.81% mothers with BMI >18.5 and 28.92% women who were educated till high school had a baby with LBW. Most mothers consumed milk and vegetables daily and a few consumed non vegetarian foods but quality and quantity of food were grossly inadequate. GWG levels and Hb levels were significantly different in different birth weight groups and also were significantly associated with low birth weight.

Conclusion

Quality and quantity of maternal dietary intake during pregnancy, even in normal weight mothers (BMI > 18.5), are important determinants of birth weight. Nutritional counseling for mothers during the antenatal period is the cornerstone for healthy mother and healthy child.     

Infant and young child feeding practices amongst children referred to the paediatric outpatient department

Background

Worldwide, sub-optimal breastfeeding still accounts for deaths of 1.4 million children aged less than five years. Optimal infant and young child feeding (IYCF) practices have been recognised as the most important intervention for improving child survival and development. Causal association has been found between exclusive breastfeeding with infection-specific infant morbidity and mortality.

Methods

A cross sectional study was undertaken to assess the IYCF practices among 100 caregivers of children aged less than five years, using a semi-structured questionnaire, attending the Paediatric OPD.

Results

Children from higher income groups were not given colostrum at birth. 57% mothers started breastfeeding within an hour and 88% of the mothers admitted to have given prelacteal feed. Healthy complementary food was found to be given by most of the mothers. Prevalence of infections was found to be higher (p < 0.05) in children whose birth weight < 2.5 kg and in bottle fed children.

Conclusion

Traditional beliefs and practices, besides lack of knowledge regarding current feeding recommendations, were found to have played an important role in the feeding practices. Creating an enabling environment for comprehensive nutrition education of mothers by health care providers is required.