Does passive smoking affect the outcome of grommet insertion in children?

Bilateral myringotomy with insertion of ventilation tube (grommet) is the most common surgical procedure done on children under general anaesthetic. A prospective study was conducted on children undergoing grommet insertion to ascertain any relationship between exposures of passive smoking to the outcome of grommet insertion. Six hundred and six children (with 1174 ears) who underwent grommet insertion for recurrent secretory otitis media were followed up till the grommets were extruded. Thirty-three children (65 per cent), whose mothers smoked when they were pregnant, had bilateral narrow external ear canals. The median survival rate of grommet was 59 weeks in children who were exposed to passive smoking as compared to 86 weeks for non-exposed children and the extrusion rate of grommet was 36 per cent higher at the end of one year if both parents smoked compared to the non-smoking group. Post-extrusion myringosclerosis was 64 per cent if both parents smoked and less than 20 per cent if neither parents smoked. It is concluded that post-operative infection rate, attic retraction, post-extrusion myringosclerosis and permanent perforations of tympanic membrane were more common in children exposed to passive smoking. The study provides further support to professional and governmental advice that passive smoking is harmful.     

Bjornstad syndrome

A 9-month-old boy presented with the complaints of loose motion, vomiting and difficulty in breathing. His scalp hairs were thin, brittle, and sparse and were of differing lengths with twisted appearance. Hair shaft microscopy revealed alternate light and dark segments and twisting of the hair shafts by 180 degrees along the axis. Serum copper levels were normal. The audiological testing revealed bilateral sensorineural hearing loss. Child was diagnosed as a case of Bjornstad Syndrome.     

Anatomic analysis of blood vessels in germinal matrix, cerebral cortex, and white matter in developing infants

The germinal matrix (GM) located in the thick subependymal cell layer of the thalamostriate groove is a major site of cerebral hemorrhage in premature infants. Comparing the morphology of vasculature among GM, gray and white matter of the brain may help in understanding the pathogenesis of GM hemorrhage and also of periventricular leukomalacia. The objective of the present study was to determine the morphology of blood vessels in the GM, gray matter, and white matter and to examine maturational changes in the morphology of these vessels as a function of gestational age. We measured vessel density, percentage of blood vessel area, mean surface area, length, breadth, perimeter, radius, and shape of blood vessels in coronal sections of the GM, gray matter, and white matter in postmortem human brain samples for 17 fetuses and premature infants of gestational age 16-40 wk and 2 adults. We performed immunohistochemical staining using anti-laminin primary antibody, confocal microscopy to acquire images, and analysis using Metamorph version 6.1. Vessel density and the percentage of blood vessel area increased as a function of gestational age in the GM, gray matter, and white matter (p < 0.001 each). The blood vessel density and the percentage of blood vessel area were largest in the GM followed by gray matter and then white matter in all of the gestational age categories (p < 0.001 for all comparisons). Increased vascularity of the GM compared with gray and white matter may play a role in GM hemorrhage, whereas a relatively low vascularity of white matter may increase the propensity for the occurrence of periventricular leukomalacia in premature infants     

Endothelial dysfunction as a modifier of angiogenic response in Zucker diabetic fat rat: amelioration with Ebselen

BACKGROUND: Progression of nephropathy in metabolic syndrome is associated with microvasculopathy and vascular dropout. METHODS: Eight- and 22-week-old Zucker diabetic fat (ZDF) and Zucker lean (ZL) rats were studied to characterize the progression of nephropathy, and to test the effect of a peroxynitrite scavenger, Ebselen, on renal microvasculature and angiogenic competence. RESULTS: Capillary density was increased, both in the cortex (P < 0.05) and in the inner medulla (P < 0.001) by the age of 8 weeks, but significantly decreased (P < 0.01 and P < 0.001) by the age of 22 weeks in ZDF compared to ZL rats. Similarly, the angiogenic competence of cortical and medullary renal explants was increased in 8-week-old ZDF (P < 0.01), but decreased at 22 weeks (P < 0.001). Alterations of angiogenic competence in ZDF rats were associated with altered expression of vascular endothelial growth factor (VEGF), reduced expression of Flk-1, and neuropilin. Acetylcholine-induced relaxation of microdissected interlobar arteries from 8-week-old ZDF rats was unimpaired, but significantly attenuated in 22-week-old ZDF rats (P < 0.001). Treatment with Ebselen partially prevented the decrease in capillary density and angiogenic competence of renal explants, and restored acetylcholine-induced vasorelaxation in 22-week-old ZDF rats. CONCLUSION: The progression of nephropathy in ZDF rats is associated with decreased angiogenic competence both ex vivo and in vivo. This is accompanied by a altered expression of VEGF system components and endothelial dysfunction, and scavenging peroxynitrite with Ebselen ameliorates the progression of microvasculopathy and partially restores angiogenesis. These findings reveal the complex mechanism of microvascular dropout in experimental metabolic syndrome.     

Nephropathy in Zucker diabetic fat rat is associated with oxidative and nitrosative stress: prevention by chronic therapy with a peroxynitrite scavenger ebselen

Zucker diabetic fat (ZDF) rats with the metabolic syndrome and hyperlipidemia develop focal and segmental sclerosis. The role of oxidative and nitrosative stress in the nephropathy in ZDF was studied. Renal histology, function, and immunohistologic and biochemical parameters of oxidative and nitrosative stress were evaluated at 8 and 22 wk of age in ZDF and Zucker lean (ZL) rats and after chronic treatment with ebselen, an antioxidant and peroxinitrite scavenger. At 8 wk, ZDF rats showed hyperglycemia, no proteinuria or nephropathy, but higher levels of dihydrobiopterin and 3-nitrotyrosine (3-NT)-modified proteins compared with age-matched ZL rats. At 22 wk, ZDF rats developed focal and segmental sclerosis, proteinuria, decreased creatinine clearance, and renal tissue levels of glutathione and tetrahydrobiopterin with further elevation in dihydrobiopterin and 3-NT-modified proteins, in contrast to age-matched ZL rats. Renal immunohistologic expression of lipid peroxidation products and 3-NT-modified proteins also increased in 22-wk-old ZDF but not in ZL rats. Chronic ebselen treatment of ZDF rats restored renal tissue levels of glutathione and tetrahydrobiopterin; prevented significant accumulation of dihydrobiopterin, lipid peroxidation products, and 3-NT-modified proteins; and ameliorated focal and segmental sclerosis, proteinuria, and fall in creatinine clearance without affecting mean BP, body weight, and blood glucose, compared with the untreated ZDF rats. Chronic ebselen therapy also ameliorated vasculopathy with lipid deposits and tubulointerstitial scarring, inflammation, and upregulated alpha-smooth muscle actin expression. These findings suggest that ZDF rats develop a progressive nephropathy with glomerular, vascular, and tubulointerstitial pathology. Oxidative and nitrosative stress predates the nephropathy, which is improved by peroxinitrite scavenger ebselen, and thus considered its cause and not consequence.     

Morphology of and visual performance with posterior subcapsular cataract

PURPOSE: To study the prevalence and clinical profile of etiologically diverse posterior subcapsular cataracts (PSCs) and their effect on visual performance. SETTING: Iladevi Cataract & IOL Research Centre, Ahmedabad, India. METHODS: This prospective observational study comprised 160 eyes of 100 consecutive patients with PSC. Exclusion criteria included cortical opacities, cataract other than PSC, and a nondilating pupil. Lenticular changes such as gross appearance, density of opacity in the central 7.0 mm, and location and approximate area of cataract involvement were noted. The uncorrected distance and near acuities, best corrected visual acuity (BCVA), contrast sensitivity with BCVA, and history of glare were recorded. RESULTS: Sixty patients had bilateral PSC. The most prevalent cataracts were of unknown etiology (32.5%). The most common coexisting disease or factor was atopy (30.6%). Others were myopia, steroid use, diabetes, uveitis, retinitis pigmentosa (RP), glaucoma, and trauma. Most patients (47.0%) were 41 to 50 years old. The PSC was vacuolar in 45.0% of eyes, solid in 15.6%, and mixed in 39.4%. Vacuolar PSC was the most common type in the myopia, diabetes, RP, and trauma groups. Solid PSC was seen with myopia, diabetes, and glaucoma. Mixed PSC was the most common type in the steroid, atopy, uveitis, and idiopathic groups. Eighty-seven percent of patients had reduced visual acuity; 76%, glare; and 46%, decreased contrast sensitivity. More eyes with vacuolar PSC had decreased visual acuity and contrast sensitivity, followed by eyes with solid PSC and eyes with mixed PSC. CONCLUSIONS: Most PSCs were of unknown etiology; a significant number of eyes had more than 1 etiology. Vacuolar PSC was the most common type, with more eyes in this group having significantly reduced visual acuity and contrast sensitivity. Specific morphological patterns occurred with some conditions (eg, RP, myopia, diabetes).     

Co-treatment with riluzole and GDNF is necessary for functional recovery after ventral root avulsion injury

Unilateral avulsion of lumbar ventral roots kills approximately 50% of injured motoneurons within 2 weeks of surgery. Immediate treatment involving surgical reimplantation of the ventral root (VRI) or intrathecal glial cell line-derived neurotrophic factor (GDNF) delivery or intraperitoneal injection of riluzole for 2 weeks ameliorates motoneuron death to 80% of control but combining the different treatment paradigms did not further enhance survival except when GDNF was combined with VRI. At 3 months, all combined treatments provided a neuroprotective effect compared to avulsion only, but the neuroprotective effect of surgical reimplantation alone was not maintained unless combined with riluzole and GDNF treatment. Analysis of regenerating motoneurons using retrograde labelling techniques showed that riluzole, but not GDNF, increased the number of dendrites per labelled motoneuron. However, when functional motor recovery was assessed using the BBB locomotor score and rotarod tests, only VRI animals treated with riluzole and GDNF application showed significantly improved locomotor function in both tests. Our results show that functional recovery appears related to a combination of enhanced dendrite formation, increased motoneuron survival and the neurotrophic actions of GDNF. Thus, combination treatment may offer a new therapeutic strategy for treating patients with avulsion injury.     

Development and validation of an HPLC method for AG331 bulk drug substance and lyophilized powder for injection

AG331 is a water soluble glucuronate salt of a novel antitumor compound synthesized by protein structure based drug design. A lyophilized powder for injection was developed for clinical studies. During HPLC assay development, AG331 showed an inherent tailing problem due to an amino group in the structure. An optimized reverse-phase gradient HPLC method was developed to minimize the tailing and separate AG331 from its synthetic intermediates (I-1, I-2, I-3, I-4, I-5, I-6, I-8), other impurities and degradation compounds. The method was shown to be linear, precise, accurate, rugged and stability-indicating.     

The impact of visual impairment on functional vision of children in rural South India: the Kariapatti Pediatric Eye Evaluation Project

PURPOSE: To determine the impact of visual impairment on functional vision of children in a rural population of south India. METHODS: A visual function questionnaire (LVP-VFQ) was administered to 1194 children aged 7 to 15 years identified through a systematic random sampling technique from 144 hamlets of Kariapatti in rural south India as part of a larger population-based project. Visual acuity estimations and clinical examinations for morbidity were performed in these 1194 children. A Rasch analysis was performed to validate the use of the instrument in this population. Bootstrap estimates (95% confidence intervals) of the regression coefficients were used to compare visual function scores between children with normal sight and children with uncorrected monocular and binocular visual impairment. RESULTS: The mean age of children was 10.3 +/- 2.1 years. The reliability estimates were 0.82 for person ability and 0.88 for item difficulty parameters, according to the Rasch analysis. A separation index of 2.15 was obtained for person measures and 2.74 for item measures, and the mean square infit and outfit statistics were 1.03 (Z(STD) 0.1) and 0.99 (Z(STD) -0.1), respectively. Children with monocular visual impairment (bootstrap estimate [95%CI] -0.05 [-0.08 to -0.01]) and binocular visual impairment (bootstrap estimate [95%CI] -0.09 [-0.11 to -0.07]) were more likely to have functional visual deficits than were normally sighted peers. CONCLUSIONS: Monocular or binocular visual impairment impacts on the functional vision of children in this rural population. Further studies are needed to determine the impact of treatment of visual impairment on functional vision in children of this population.