Necrotizing enterocolitis in infants: clinical outcome and influence on growth and neurodevelopment.

BACKGROUND AND PURPOSE: Necrotizing enterocolitis (NEC) is a gastrointestinal emergency in neonates. Whether NEC affects infants' growth and development is controversial. The purpose of this study was to explore the clinical characteristics and outcome and to assess the effect of NEC on growth and neurodevelopment in infants. METHODS: A total of 80 neonates admitted to the neonatal intensive care unit from January 1991 to April 2002 with definite, advanced NEC, including 48 with modified Bell's stage II and 32 with stage III. Sixty six of the patients were premature. Very low birth weight (VLBW) preterm infants without NEC were used as matching controls for the 15 infants with VLBW. The growth and neurodevelopment of patients and controls were assessed using the Bayley Scales of Infant Development-II and compared at 6 and 18 months of corrected age. RESULTS: NEC developed an average of 27.7 days after feeding began. The most common initial signs were abdominal distension, decreased activity, hematochezia, and abdominal tenderness. Thirty four patients (43%) required surgical intervention. Three infants developed short bowel syndrome after surgical resection. The overall mortality was 24% (19/80) and was mostly associated with extensive bowel involvement and NEC-related sepsis or multiple organ failure. Of the surviving 61 infants, 12 (20%) developed intestinal strictures, 2 in the ileum, 6 in the colon, and 4 in both ileum and colon. Compared with controls, the VLBW infants with NEC were shorter and had delayed psychomotor development at 18 months of corrected age. Mental development, however, did not differ significantly. CONCLUSIONS: Intestinal stricture was the most common gastrointestinal complication in this series of infants with NEC. Besides the bowel sequelae, VLBW infants who survive NEC are at risk for impairment of growth and neurodevelopment.     

MR imaging of the major nerves about the elbow: cadaveric study examining the effect of flexion and extension of the elbow and pronation and supination of the forearm

Magnetic resonance (MR) imaging provides useful information in the evaluation of peripheral nerves. Recent advances in MR imaging allow for detailed depiction of the soft tissue structures of the elbow joint. Three major nerves are present about the elbow. Six cadaveric elbows were imaged to depict the normal anatomy of these nerves and to determine the best plane and position of the elbow for optimal visualization of each nerve. Axial images of the elbow in full extension with the forearm in supination allow identification of all major nerves. Axial images with the elbow in full flexion allow accurate assessment of the cubital tunnel and the ulner nerve. Axial images of the elbow in full extension with the forearm in pronation are helpful for assessment of the median and radial nerves in the forearm.     

Risk for osteoporosis in black women

Models of involutional bone loss and strategies for the prevention of osteoporosis have been developed for white women. Black women have higher bone densities than white women, but as the black population ages there will be an increasingly higher population of black women with osteoporosis. Strategies should be developed to reduce the risk of black women for fragility fractures.Dual energy X-ray absorptiometry measurements of the total body, femur, spine, and radius were performed on 503 healthy black and white women aged 20–80 years. Indices of bone turnover, the calcitrophic hormones, and radioisotope calcium absorption efficiency were also measured to compare the mechanisms of bone loss.The black women had higher BMD values at every site tested than the white women throughout the adult life cycle. Black women have a higher peak bone mass and a slightly slower rate of adult bone loss from the femur and spine, which are skeletal sites comprised predominantly of trabecular bone. Indices of bone turnover are lower in black women as are serum calcidiol levels and urinary calcium excretion. Serum calcitriol and parathyroid hormone levels are higher in black women and calcium absorption efficiency is the same in black and white women, but dietary calcium intake is lower in black women.Black and white women have a similar pattern of bone loss, with substantial bone loss from the femur and spine prior to menopause and an accelerated bone loss from the total skeleton and radius after menopause. The higher values for bone density in black women as compared with white women are caused by a higher peak bone mass and a slower rate of loss from skeletal sites comprised predominantly of trabecular bone. Low-risk strategies to enhance peak bone mass and to lower bone loss, such as calcium and vitamin D augmentation of the diet, should be examined for black women. The risk vs. benefits of hormonal replacement therapy should be determined, especially in older women.     

Neonatal treatment with 192 IgG-saporin produces long-term forebrain cholinergic deficits and reduces dendritic branching and spine density of neocortical pyramidal neurons

The role of basal forebrain-derived cholinergic afferents in the development of neocortex was studied in postnatal rats. Newborn rat pups received intraventricular injections of 192 IgG-saporin. Following survival periods ranging from 2 days to 6 months, the brains were processed to document the cholinergic lesion and to examine morphological consequences. Immunocytochemistry for choline acetyltransferase (ChAT) and in situ hybridization for ChAT mRNA demonstrate a loss of approximately 75% of the cholinergic neurons in the medial septum and nucleus of the diagonal band of Broca in the basal forebrain. In situ hybridization for glutamic acid decarboxylase mRNA reveals no loss of basal forebrain GABAergic neurons. Acetylcholinesterase histochemistry demonstrates a marked reduction of the cholinergic axons in neocortex. Cholinergic axons are reduced throughout the cortical layers; this reduction is more marked in medial than in lateral cortical areas. The thickness of neocortex is reduced by approximately 10%. Retrograde labeling of layer V cortico-collicular pyramidal cells reveals a reduction in cell body size and also a reduction in numbers of branches of apical dendrites. Spine densities on apical dendrites are reduced by approximately 20-25% in 192 IgG- saporin-treated cases; no change was detected in number of spines on basal dendrites. These results indicate a developmental or maintenance role for cholinergic afferents to cerebral cortical neurons.      

Inhibition of nitric oxide can ameliorate apoptosis and modulate matrix protein gene expression in bacteria infected chondrocytes in vitro.

Bacterial infection stimulates nitric oxide (NO) production in chondrocytes. However, the role of NO in chondrocyte apoptosis after infection remains unclear. The purpose of the study was to test if inhibition of NO could ameliorate apoptosis and modulate matrix protein gene expression in bacteria-infected chondrocytes. It was shown that pre-treating chondrocytes with L-NAME (1 mM) significantly decreased the release of NO (from 72 to 14 microM) and the extent of apoptosis (from 52.9% to 18.9%). Pre-treatment with L-NAME also counteracted the bacteria-induced downregulation of Type II collagen (from 26% to 79%) and aggrecan (from 63% to 105%) mRNA levels. Inhibition of NO after the induction of infection could not decrease the extent of apoptosis and modulate matrix protein gene expression. The results of this study support the hypothesis that NO has an important role in bacteria-induced chondrocyte apoptosis. Pre-treatment but not post-treatment could ameliorate the extent of apoptosis and reestablish the cartilage matrix protein gene expression. This study suggests that in addition to NO, other mechanisms may be responsible for the sustained destruction of articular cartilage in the post-infectious arthropathy.     

Na+-K+-ATPase pumping activity is not directly linked to myo-inositol levels after sorbinil treatment in lenses of diabetic rats

Changes in tissue levels of sorbitol, myo-inositol, and Na+-K+-ATPase enzyme activity have been implicated in the development of diabetic complications in animal models of the disease and in humans. The ability of the aldose reductase inhibitor sorbinil to reverse the hyperglycemia-induced changes in these lenticular metabolite and enzyme-activity levels in the streptozocin-induced diabetic rat was examined to determine what, if any, relationship exists between these changes. Two weeks of untreated diabetes did not change ouabain-inhibitable ATPase enzyme activity assayed in lens homogenates but did result in a decrease in the Na+-K+-ATPase transport activity as measured by 86Rb uptake in the intact lens. This was accompanied by a 100-fold increase in the levels of sorbitol and significant decreases in the levels of myo-inositol, ATP, and glutathione in the lens. Whereas all of these changes could be reversed by sorbinil treatment, the dose required for restoration of the depleted myo-inositol level (ED50 greater than 20 mg.kg-1.day-1) was much higher than the dose required to reverse the other changes (ED50 range 2-5 mg.kg-1.day-1). These results suggest that the restoration of lenticular Na+ -K+ -ATPase activity is not secondary to a normalization of myo-inositol levels and may provide evidence that the two parameters are not strictly associated in diabetic tissues.     

Comparisons of different animal skins with human skin in drug percutaneous penetration studies.

The in vitro penetration of theophylline, sodium diclofenac and benzoic acid through artificial cellulose membrane and eight animal skins was investigated. The intact animal skins including stratum corneum (SC) and viable epidermis were taken from frog, snake with or without scales, nude mice, Sprague-Dawley rat, porcine and human prepuce and thigh skin. The results indicated that the penetration was fastest through cellulose membrane and frog skin and slowest through human prepuce and thigh skin. The snake skin with scales slowed down the penetration rate more significantly than the scaled skin. Benzoic acid was the fastest penetrant through all animal skins. The permeable behaviors of sodium diclofenac through SC and intact skin of snake, porcine and human were compared. In porcine, sodium diclofenac penetrated through SC at a rate 33 times higher than through intact skin, but in snake and human skin, the rate through SC was only 2.2 and 1.6 times higher than through intact ones. This implies that both viable epidermis and SC were the major rate limiting barriers in drug penetration. DSC thermograms and IR spectra showed that the SC of snake, porcine and human thigh were very similar in structure and components. The study suggests that snake skin, porcine skin and human prepuce skin could replace the human skin in in vitro drug penetration experiments.