Effects of in utero arsenic exposure on child immunity and morbidity in rural Bangladesh

Chronic exposure to arsenic, a potent carcinogen and toxicant, via drinking water is a worldwide public health problem. Because little is known about early-life effects of arsenic on immunity, we evaluated the impact of in utero exposure on infant immune parameters and morbidity in a pilot study. Pregnant women were enrolled at 6–10 weeks of gestation in Matlab, a rural area of Bangladesh, extensively affected by arsenic contamination of tubewell water. Women (n = 140) delivering at local clinics were included in the study. Anthropometry and morbidity data of the pregnant women and their children, as well as infant thymic size by sonography were collected. Maternal urine and breast milk were collected for immune marker and arsenic assessment. Maternal urinary arsenic during pregnancy showed significant negative correlation with interleukin-7 (IL-7) and lactoferrin (Ltf) in breast milk and child thymic index (TI). Urinary arsenic was also positively associated with fever and diarrhea during pregnancy and acute respiratory infections (ARI) in the infants. The effect of arsenic exposure on ARI was only evident in male children. The findings suggest that in utero arsenic exposure impaired child thymic development and enhanced morbidity, probably via immunosuppression. The effect seemed to be partially gender dependent. Arsenic exposure also affected breast milk content of trophic factors and maternal morbidity.     

Use of perfusion- and diffusion-weighted imaging in differential diagnosis of acute and chronic ischemic stroke and multiple sclerosis

OBJECTIVE: To investigate differences in lesions and surrounding normal appearing white matter (NAWM) by perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) in patients with acute and chronic ischemic stroke and multiple sclerosis (MS). METHODS: Study subjects included 45 MS patients, 22 patients with acute ischemic stroke and 20 patients with chronic ischemic stroke. All subjects underwent T2-weighted imaging (WI), flair attenuated inversion recovery (FLAIR), DWI and dynamic contrast enhanced PWI. Apparent diffusion coefficient (ADC) and mean transit time (MTT) maps were generated and values were calculated in the acute and chronic ischemic and demyelinating lesions, and in NAWM for distances of 5, 10 and 15 mm. Fifty-three acute ischemic and 33 acute demyelinating lesions, and 775 chronic ischemic and 998 chronic demyelinating lesions, were examined. Univariate, multivariate and data mining analyses were used to examine the feasibility of a prediction model between different lesion types. Correctly and incorrectly classified lesions, true positive (TP), false positive (FP) and precision rates were calculated. RESULTS: Patients with acute ischemic lesions presented more prolonged mean MTT values in lesions (p=0.002) and surrounding NAWM for distances of 5, 10 and 15 mm (all p<0.0001) than those with acute demyelinating lesions. In multinomial logistic regression analysis, 65 of 86 acute lesions were correctly classified (75.6%). The TP rates were 81.1% for acute ischemic lesions and 66.7% for acute demyelinating lesions. The FP rates were 33.3% for acute ischemic and 18.9% for acute demyelinating lesions. The precision was 79.6% for classification of acute ischemic lesions and 68.8% for prediction of acute demyelinating lesions. The logistic model tree decision algorithm revealed that prolonged MTT of surrounding NAWM for a distance of 15 mm (> or =7459.2 ms) was the best classifier of acute ischemic versus acute demyelinating lesions. Patients with chronic ischemic lesions presented higher mean ADC (p<0.0001) and prolonged MTT (p=0.013) in lesions, and in surrounding NAWM for distances of 5, 10 and 15 mm (all p<0.0001), compared to the patients with chronic demyelinating lesions. Data mining analyses did not show reliable predictability for correctly discerning between chronic ischemic and chronic demyelinating lesions. The precision was 56.7% for classification of chronic ischemic and 58.9% for prediction of chronic demyelinating lesions. DISCUSSION: We found prolonged MTT values in lesions and surrounding NAWM of patients with acute and chronic ischemic stroke when compared to MS patients. The use of PWI is a promising tool for differential diagnosis between acute ischemic and acute demyelinating lesions. The results of this study contribute to a better understanding of the extent of hemodynamic abnormalities in lesions and surrounding NAWM in patients with MS.     

Anovestibular fistula with normal anus

Purpose

The purpose of the study was to review a rare anomaly of anorectal malformations in girls, congenital anovestibular fistula (AVF) with normal anus, over a 12-year period.

Materials and Methods

A total of 24 female patients of AVF with normal anus were treated in the Department of Pediatric Surgery, Chittagong Medical College and Hospital, Chittagong, Bangladesh, from January 1994 to June 2006. Clinical features, operative findings, operative procedures, postoperative complications, and outcomes were analyzed.

Results

Age ranged from 1 day to 7 years (mean, 10.5 months). All 24 female patients presented with passage of stools through 2 perineal openings. In addition, vulvar abscesses were noted in 5 cases. Vestibular opening of the fistula was found behind the vagina in 18 patients, and the anal opening of the fistula was on the anterior anal wall above the dentate line in 20 cases. There were no associated abnormalities. After adequate bowel preparation, 22 patients underwent excision of the fistulous tract with reconstruction of anal wall without a diverting colostomy. All 5 patients with vulvar abscess experienced wound disruption and required reoperation. All 24 girls have normal bowel motions at follow-up.

Conclusions

In the management of AVF with normal anus, primary repair without colostomy is a safe option. In cases of abscess or infection, definitive operation should be deferred until adequate healing is achieved.     

Clinicopathologic Features and Long-Term Outcomes of 293 Phyllodes Tumors of the Breast

BACKGROUND: Phyllodes tumors (PT) are rare fibroepithelial neoplasms of the breast with unpredictable behavior. We reviewed our single institution experience with PT over 51 years to identify factors predictive of local recurrence (LR) and metastasis. METHODS: From 1954 to 2005, a total of 352 cases of PT were identified; 293 had follow-up. All available pathology slides (90%) were rereviewed for margins, borders, fibroproliferation in the surrounding breast tissue, stromal pattern, stromal cellularity, frequency of mitoses, and necrosis. RESULTS: All cases occurred in women, with a median age of 42, with 203 originally categorized as benign and 90 as malignant. Median follow-up was 7.9 years. A total of 35 patients developed LR at a median of 2 years. In univariate analyses, a higher actuarial LR rate was associated with positive margins (P = .04), fibroproliferation (P = .001), and necrosis (P = .006). PT classified as malignant did not have a higher risk of LR (P = .79). Five patients developed distant disease at a median of 1.2 years. These patients constituted 71% of the seven patients who had uniformly aggressive pathologic features, including large tumor size (>or=7.0 cm), infiltrative borders, marked stromal overgrowth, marked stromal cellularity, high mitotic count, and necrosis. CONCLUSIONS: Positive margins, fibroproliferation in the surrounding breast tissue, and necrosis are associated with a marked increase in LR rates. Efforts should be made to achieve negative surgical margins to reduce risk of LR. Death from PT is rare (2%), and only PT that demonstrate uniformly aggressive pathologic features seem to be associated with mortality.     

Environmental cooling of the newborn pig brain during whole‐body cooling

Aim: Therapeutic hypothermia after perinatal asphyxia decreases brain injury in newborns, whereas hyperthermia worsens the brain injury. We examined how different clinical practices influence regional brain temperatures during hypothermia. Methods: Six newborn pigs, which have comparable physiology and brain maturation to human term infants, were maintained at hypothermia (33.5°C) or normothermia with a servo‐controlled whole‐body cooling device that is in clinical use. Pigs were anesthetized and fully instrumented for cardiovascular and temperature (rectal and regional brain) monitoring. Changes in brain temperatures were measured during four different paradigms to mimic different clinical practices. Results: Inserting an insulating pillow between the head and the heated surface reduced cortex temperature by 1 or 2°C during normothermia (core temperature T_core 37°C) or hypothermia, T_core 33.5°C. Reducing ambient temperature from 28°C to 23°C reduced cortex temperature by 3.9 ± 1.9°C. Without a hat and overhead heater at normothermia, cortex and deep brain temperatures were reduced by 1.2 ± 0.8 and 0.7 ± 0.7°C, respectively. Direct overhead heating abolished the normal cortex to deep brain temperature gradient that was maintained if using a head shield. Conclusion: Brain temperature may differ from core temperature during therapeutic hypothermia influenced by different clinical practices.     

Transient heating of expressed breast milk up to 65°C inactivates HIV‐1 in milk: A simple,rapid, and cost‐effective method to prevent postnatal transmission

The postnatal transmission of human immunodeficiency virus (HIV) from mothers to children occurs through breastfeeding. Although heat treatment of expressed breast milk is a promising approach to make breastfeeding safer, it is still not popular, mainly because the recommended procedures are difficult to follow, or time‐consuming, or because mothers do not know which temperature is sufficient to inactivate HIV without destroying the nutritional elements of milk. To overcome these drawbacks, a simple and rapid method of heat treatment that a mother could perform with regular household materials applying her day‐to‐day art of cooking was examined. This structured experiment has demonstrated that both cell‐free and cell‐associated HIV type 1 (HIV‐1) in expressed breast milk could be inactivated once the temperature of milk reached 65°C. Furthermore, a heating method as simple as heating the milk in a pan over a stove to 65°C inhibited HIV‐1 transmission retaining milk's nutritional key elements, for example, total protein, IgG, IgA, and vitamin B₁₂. This study has highlighted a simple, handy, and cost‐effective method of heat treatment of expressed breast milk that mothers infected with HIV could apply easily and with more confidence. J. Med. Virol. 85:187–193, 2013. © 2012 Wiley Periodicals, Inc.     

Hydroxychloroquine enhances the endocrine secretion of adenovirus-directed growth hormone from rat submandibular glands in vivo.

Use of gene transfer technology for treating single protein deficiency disorders requires delivery of therapeutic levels of the transgene product. We have suggested that salivary glands may provide a potentially valuable target site for certain systemic applications of gene therapeutics (He et al., Gene Ther. 1998;5:537-541). However, the ability of salivary glands to deliver therapeutic proteins to either the upper gastrointestinal tract via saliva or to the bloodstream, as required, must be carefully evaluated. In the anterior pituitary gland, human growth hormone (hGH) is secreted into the bloodstream via the regulated secretory pathway. However, when expressed from an adenoviral vector delivered to salivary glands, most hGH follows the regulated, tissue-specific, exocrine secretory pathway into saliva, where it is not therapeutically useful. We tested the hypothesis that the commonly used, FDA-approved drug hydroxychloroquine (HCQ) can divert adenovirus-directed hGH from this regulated secretory pathway in rat submandibular glands and enhance delivery into the bloodstream. In untreated rats, there was approximately 20-fold more vector-directed hGH in saliva than in serum. Administration of HCQ led to a shift of hGH secretion into the bloodstream. When delivered at doses of 1 or 10 mg/kg body weight, via intraperitoneal injection plus intraductal infusion, the saliva:serum hGH ratio was approximately 2:1. Such HCQ delivery did not significantly alter the total amount of hGH measured, but increased the serum level of hGH 5- to 6-fold. Also, HCQ had no significant effects on serum chemistries or hematological parameters. We conclude that HCQ is able to significantly enhance hGH secretion from salivary glands into the bloodstream and may be useful to facilitate clinical applications of gene therapeutics via salivary glands.     

神经外科中高渗盐注射液应用研究进展

控制脑水肿和颅内压(ICP)升高是神经外科围手术期治疗的重要组成部分.颅脑创伤、动脉梗塞、静脉高压/梗塞、大脑内出血、蛛网膜下腔出血、肿瘤和术后脑组织水肿的治疗过程中ICP的控制都是决定患者预后的关键因素.虽然利用渗透压脱水药物是控制ICP的最基础的工具,但却缺乏前瞻性研究以指导其运用,高渗盐被认为是甘露醇的替代物,早期的数据表明每种药的用药指征最终取决于ICP的病因.在这篇综述中,我们总结了有关高渗盐(HS)治疗颅内高压的相关数据,以及这些数据和我们有关HS的经验是如何指导目前的ICP治疗的.     

Hybrid braided 3-D scaffold for bioartificial liver assist devices

Three-dimensional ex vivo hepatocyte culture is a tissue-engineering approach to improve the treatment of liver disease. The extracorporeal bioartificial liver (BAL) assists devices that are used in patients until they either recover or receive a liver transplant. The 3-D scaffold plays a key role in the design of bioreactor that is the most important component of the BAL. Presently available 3-D scaffolds used in BAL have shown good performance. However, existing scaffolds are considered to be less than ideal in terms of high-density cultures of hepatocytes maintaining long-term metabolic functions. This study aims to develop a 3-D hybrid scaffold for a BAL support system that would facilitate high-density hepatocyte anchorage with long-term metabolic functions. The scaffolds were fabricated by interlacing polyethylene terephthalate (PET) fibers onto the polysulfone hollow fibers utilizing a modern microbraiding technique. Scaffolds with various pore sizes and porosities were developed by varying braiding angle which was controlled by the gear ratio of the microbraiding machine. The morphological characteristics (pore size and porosity) of the scaffolds were found to be regulated by the gear ratio. Smaller braiding angle yields larger pore and higher porosity. On the other hand, a larger braiding angle causes smaller pore and lower porosity. In hepatocyte culture it was investigated how the morphological characteristics (pore size and porosity) of scaffolds influenced the cell anchorage and metabolic functions. Scaffolds with larger pores and higher porosity resulted in more cell anchorage and higher cellular functions, like albumin and urea secretion, compared to that of smaller pores and lower porosity.