Intensive gestational glycemic management and childhood obesity: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Hyperglycemia in pregnancy is associated with increased risk of offspring childhood obesity. Treatment reduces macrosomia; however, it is unclear if this effect translates into a reduced risk of childhood obesity. We performed a systematic review and meta-analysis of randomized controlled trials to evaluate the efficacy and safety of intensive glycemic management in pregnancy in preventing childhood obesity. METHODS: We searched MEDLINE, EMBASE, CENTRAL and ClinicalTrials.gov up to February 2016 and conference abstracts from 2010 to 2015. Two reviewers independently identified randomized controlled trials evaluating intensive glycemic management interventions for hyperglycemia in pregnancy and included four of the 383 citations initially identified. Two reviewers independently extracted study data and evaluated internal validity of the studies using the Cochrane Collaboration's Risk of Bias tool. Data were pooled using random-effects models. Statistical heterogeneity was quantified using the I2 test. The primary outcome was age- and sex-adjusted childhood obesity. Secondary outcomes included childhood weight and waist circumference and maternal hypoglycemia during the trial (safety outcome). RESULTS: The four eligible trials (n=767 children) similarly used lifestyle and insulin to manage gestational hyperglycemia, but only two measured offspring obesity and waist circumference and could be pooled for these outcomes. We found no association between intensive gestational glucose management and childhood obesity at 7-10 years of age (relative risk 0.89, 95% confidence interval (CI) 0.65 to 1.22; two trials; n=568 children). Waist circumference also did not differ between treatment and control arms (mean difference, -2.68 cm; 95% CI, -8.17 to 2.81 cm; two trials; n=568 children). CONCLUSIONS: Intensive gestational glycemic management is not associated with reduced childhood obesity in offspring, but randomized data is scarce. Long-term follow-up of trials should be prioritized and comprehensive measures of childhood metabolic risk should be considered as outcomes in future trials.

Pre-symptomatic targeted treatment of patent ductus arteriosus in preterm newborns: A systematic review and meta-analysis.

BACKGROUND: A clinically significant patent ductus arteriosus (PDA) is associated with significant morbidity and mortality in premature newborns. Symptomatic PDAs are often treated with prostaglandin synthesis inhibitors (PSI), but controversy remains if PSIs should also be used to manage early, asymptomatic PDAs. OBJECTIVE: To systematically identify, critically appraise, and evaluate the efficacy and safety of pharmacological management of pre-symptomatic PDA in preterm newborns after confirmed patency by echocardiography. STUDY DESIGN: Systematic review and meta-analysis. SEARCH METHODS: We searched MEDLINE (Ovid), EMBASE (Ovid), Cochrane Central Register of Controlled Trials (Wiley), from date of inception to February 2017. Supplemental searching was performed in Scopus and Web of Science to identify additional relevant citations. We also searched conference proceedings, reference lists of relevant articles and the WHO International Clinical Trials Registry Platform (ICTRP). SELECTION CRITERIA: We included only randomized controlled trials (RCTs) that compared the use of indomethacin or ibuprofen to placebo for treatment of pre-symptomatic PDA in preterm newborns (<32 weeks gestational age and <1500gms). DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials, assessed risk of bias and extracted trial-level data. Outcomes are reported as risk ratios from random-effects models. Absolute risk reduction (ARR) is additionally reported for significant outcomes.We included seven trials (466 newborns). Targeted medical treatment did not significantly reduce mortality rates (RR 0.85, 95% CI 0.50 to 1.43; ARR -2.38%, 95% CI -8.04% to 3.29%; I2 0% 6 studies; 442 newborns), but it did significantly reduce the overall incidence of developing symptomatic PDA (RR 0.39, 95% CI 0.21 to 0.73; ARR -34.3%, 95% CI -50.8% to -17.8%; I2 0%; 3 studies; 97 newborns) compared to placebo. Other efficacy or safety outcomes were not significantly different. CONCLUSIONS: Targeted medical treatment of pre-symptomatic PDA decreases the incidence of developing symptomatic PDA, but not neonatal mortality. Further studies are essential to confirm these results.

Vitamin D and Dental Caries in Children.

The purpose of this study was to assess the relationship between vitamin D status and dental caries in Canadian school-aged children participating in the Canadian Health Measures Survey (CHMS). The CHMS was a national cross-sectional study involving physical assessments, laboratory analysis, and interviews. Analysis was restricted to data for 1,017 children 6 to 11 y of age. Outcome variables included the presence of caries and overall total caries score (dmft/DMFT index). Levels of 25-hydroxyvitamin D (25(OH)D) were measured from serum samples obtained from participants. Bivariate analysis, logistic regression for the presence of caries, and multiple linear regression for total caries scores were used. Significance was set at P ≤ 0.05. Overall, 56.4% of children experienced caries, and the mean dmft/DMFT score was 2.47 (95% CI 2.09 to 2.84). The unadjusted odds of children with 25(OH)D levels ≥75 nmol/L having experienced caries was 0.57 (95% CI 0.39 to 0.82), while the odds for caries at the ≥50 nmol/L level was 0.56 (95% CI 0.39 to 0.89). After controlling for other covariates, backward logistic regression revealed that the presence of caries was significantly associated with 25(OH) levels <75 nmol/L and <50 nmol/L, lower household education, not brushing twice daily, and yearly visits to the dentist. Similarly, multiple linear regression revealed that total dmft/DMFT caries scores were also associated with 25(OH)D concentrations <75 nmol/L, not brushing twice daily, lower household education, and yearly visits to the dentist. Data from a cross-sectional, nationally representative sample of Canadian children suggest that there is an association between caries and lower serum vitamin D. Improving children's vitamin D status may be an additional preventive consideration to lower the risk for caries.

Sorbitol, myo-inositol, and rod outer segment phagocytosis in cultured hRPE cells exposed to glucose. In vitro model of myo-inositol depletion hypothesis of diabetic complications.

The "myo-inositol depletion hypothesis" remains a leading but still controversial contender among proposed pathogenetic mechanisms for the chronic complications of diabetes. The multifaceted interrelationships among altered tissue myo-inositol content and metabolism and tissue function have been difficult to elucidate in diabetic animal models due in part to the complex, heterogeneous nature of tissues prone to diabetic complications. The retinal pigment epithelium consists of a homogenous cell monolayer that exhibits related alterations in myo-inositol metabolism and function in diabetic animals. Nontransformed human retinal pigment epithelial (hRPE) cells, which retain their general phenotypic and morphological characteristics during monolayer culture in vitro, were examined for parallel alterations in myoinositol metabolism and cell function when grown under carefully controlled conditions in medium containing hyperglycemic concentrations of glucose. Exposure of hRPE cells to 20-40 mM glucose produced time- and dose-dependent increases in sorbitol content and decreases in myo-inositol content that were partially blocked by the aldose reductase inhibitor sorbinil. myo-Inositol was taken up by two Na-dependent transport systems, at least one of which was competitively inhibited by glucose. Exposure to 20 mM glucose impaired the ability of hRPE cells to take up human retinal rod outer segments, an important physiological function of these cells. The impairment of rod outer segment uptake by high glucose levels was prevented by an aldose reductase inhibitor or elevated medium myo-inositol that corrected the fall in myo-inositol content. Thus, hRPE cells provide a new in vitro model in which to examine the biochemical-functional interrelationships of the myo-inositol depletion hypothesis.

Strategies to achieve coronary arterial plaque stabilization.

Acute coronary syndromes result from fissure, erosion or rupture of a vulnerable atherosclerotic plaque. The characteristics of a vulnerable plaque include a large lipid pool, an abundance of inflammatory cells and mediators, a reduced smooth muscle cell and collagen content and a thin overlying fibrous cap. Potential therapeutic strategies at achieving plaque stabilization have targeted these features. Lipid lowering agents, beta-adrenergic blockers, angiotensin converting enzyme inhibitors and antioxidants have been shown to reduce the incidence of acute coronary syndromes, presumably through plaque stabilization. Matrix metalloproteinase inhibitors as well as macrolide antibiotics and gene therapy approaches show promise in achieving plaque stabilization. The evidence supporting plaque stabilization by these agents and the mechanisms by which these agents stabilize plaques are discussed in detail in this review.

An analysis of "ablation of thyroid remnants" with I-131 in 511 patients from 1947-1984: experience at University of Michigan.

Between January 1947 and June 1983, 511 patients were given treatment doses of I-131 after surgery for thyroid cancer in the presence of I-131 uptake in thyroid remnants. Thirty-four patients were removed from the study leaving 462 patients with a 99% follow-up at 1 or more yr, with a mean follow-up of 15 yr. Of 267 patients with radioiodine uptake confined to the thyroid bed, 233 (87%) had ablation from the first dose of I-131 ranging from 100 to greater than 200 mCi. The higher the percent uptake, the more difficult it was to achieve ablation. In the percentages of successful ablation, there were no significant differences between I-131 doses of: 100-149 mCi, 150-174 mCi, 179-199 mCi, and 200 mCi or more. The 100-149 mCi ablative dose may furnish "adjuvant" therapy for occult metastases.

Time course of thymoxamine reversal of phenylephrine-induced mydriasis.

We conducted a randomized, double-masked, paired comparison of 0.1% thymoxamine vs placebo for the reversal of phenylephrine-induced mydriasis. Mydriasis was induced with 2.5% phenylephrine in each eye of 74 subjects (148 eyes). Each subject then received 0.1% thymoxamine in one eye and placebo in the other eye. Pupillary measurements were obtained at regular intervals during the ensuing 8 hours. At all intervals, a greater percentage of thymoxamine-treated eyes returned to baseline pupillary diameters compared with placebo-treated eyes (P less than or equal to .01). For subjects in whom both pupils returned to baseline, thymoxamine-treated eyes returned to baseline in a mean of 2.2 hours, vs 5.2 hours for placebo (P less than .0001). Among thymoxamine-treated eyes, those with light irides responded more rapidly than those with dark irides, returning to baseline in 1.6 vs 2.8 hours, respectively (P = .0046). After constriction to baseline pupillary diameter had been achieved, no patients experienced a rebound dilation.

Clinical outcomes after successful percutaneous coronary angioplasty of saphenous vein graft disease and the importance of long-term assessment.

We examined the short- and long-term outcome of 327 patients at Mayo Clinic who had undergone coronary angioplasty of saphenous vein graft stenoses to determine whether the traditional 6-month assessment of clinical end points after coronary angioplasty is as useful as it is for patients who have had angioplasty of native vessel disease. Follow-up over 3.3+/-2.7 years was performed. At 6 months, 96+/-1% of the patients were alive, whereas at the 1- and 5-year end points, survival had deteriorated to 92+/-2 and 67+/-3%, respectively. Only 80+/-2% were free of severe angina at 6 months and 62+/-3 and 36+/-3% after 1 and 5 years. Combined event-free rate for death, Q-wave myocardial infarction or repeat coronary artery bypass surgery was 86+/-2% at 6 months, 78+/-2% at 1 year, and 45+/-4% at 5 years. Independent predictors of mortality included advancing age, diabetes mellitus, target vein grafts >5 years old and left ventricular ejection fraction <40%. In conclusion, despite reasonable 6- to 12-month outcomes following vein graft angioplasty, significant attrition in survival and event-free survival was observed. These observations have important implications for the interpretation of results of trials comparing conventional angioplasty and coronary bypass surgery with newer interventional devices if only the traditional 6-month follow-up interval is used.

Effects of pupillary dilation on automated perimetry in normal patients.

The effects of pupillary dilation (tropicamide 1%) on automated static threshold perimetry were studied in 18 normal subjects using the Humphrey field analyzer 30-2 and STATPAC programs. The mean defect worsened by 0.83 decibels (standard deviation, 0.92 decibels) in dilated fields as compared with baseline visual fields (P = 0.001). These findings indicate that pupillary dilation in healthy subjects who are not receiving ocular medications produces statistically significant declines in threshold sensitivities. Valid comparison of results from serial visual field testing, therefore, depends on control of or adjustment for the effect of pupillary dilation.

The effects of exercise on intraocular pressure in pigmentary glaucoma patients.

Previous studies of normal volunteers and open-angle glaucoma patients have shown that exercise temporarily lowers intraocular pressure. However, two case reports have described pigmentary dispersion syndrome patients who developed symptomatic increased intraocular pressure after exercise. We evaluated the intraocular pressure response to exercise in ten pigmentary glaucoma patients. An exercise protocol was designed to increase the likelihood of lens zonule-iris pigment epithelium contact. Intraocular pressure measurements during the first two hours after exercise showed no statistically significant elevation of mean intraocular pressure. The pressure rose 6 mm Hg and 7 mm Hg respectively at 15 minutes in two eyes, but returned to baseline by 30 minutes. Our results suggest that exercise may not significantly increase the clinical intraocular pressure in pigmentary glaucoma patients.

Effects of pupillary constriction on automated perimetry in normal eyes.

The authors studied the effects of pupillary constriction (pilocarpine 2%) on automated static threshold perimetry in 20 normal subjects using the Humphrey Field Analyzer 30-2 and STATPAC programs. The mean defect (MD) worsened by an average of 0.67 decibels (dB) (standard deviation, 0.67 dB) in constricted fields compared with baseline visual fields (P less than or equal to 0.001). Independent comparisons of the unweighted means of threshold values for the central 30 degrees, 24 degrees, and 10 degrees were also done and showed significant reductions in sensitivity after constriction (P less than or equal to 0.001). These findings indicate that changes in pupillary diameter may produce significant declines in threshold sensitivities and support the importance of consistent pupillary diameters on serial automated visual field examinations.

Bone metastases in pheochromocytoma: comparative studies of efficacy of imaging.

Bone is the most common site of metastasis from pheochromocytoma. Now that the effects of hypercatecholaminemia can be adequately controlled with adrenergic blockade, pathologic fractures are becoming an increasingly significant cause of morbidity in patients with metastatic pheochromocytoma. Bone metastases from pheochromocytoma have not been extensively reevaluated since the advent of computed tomography (CT), high-resolution bone scintigraphy, and iodine 131 MIBG scintigraphy. Plain radiographs, CT scans, bone scans, and I-131 MIBG scans of 38 patients with pheochromocytoma bone metastasis were reviewed. The axial skeleton was the most common site of metastasis. Metastases typically appeared expansile and mixed lytic-sclerotic on radiographs. Bone scintigraphy was the most sensitive modality for detecting bone metastasis, with 74% of all alleged lesions being identified. In screening for bone metastasis from pheochromocytoma, bone scanning in conjunction with I-131 MIBG scanning is recommended, followed by scan- and symptom-directed radiography and - where a question still exists - CT.

The effects of glaucoma medications on Tenon's capsule and conjunctiva in the rabbit.

Glaucoma filtering surgery fails most frequently due to fibrosis at the episcleral-conjunctival/Tenon's capsule interface. Sherwood et al have suggested that chronic topical antiglaucoma medications increase conjunctival inflammatory cells, which could increase the likelihood of fibrosis and subsequent bleb failure. In a pilot study in a rabbit model, we placed timolol, pilocarpine, and epinephrine, or a combination of all three, in one eye of 24 animals twice daily for 7 months. The fellow eye received distilled water. Microscopic examination revealed no statistically significant change in the number of acute or chronic inflammatory cells, fibroblasts, or goblet cells in the treated as compared with the control eyes. A longer duration of drug administration, or drug administration followed by surgical intervention, may be required to produce an effect on the conjunctiva and Tenon's capsule, if such an effect exists.