Efficacy and complications of polyethylene glycols for treatment of constipation in children: a meta-analysis.

Constipation is a common childhood complaint. In 90% to 95% of children, constipation is functional, which means that there is no objective evidence of an underlying pathological condition. Polyethylene glycol (PEG or macrogol) solution is an osmotic laxative agent that is absorbed in only trace amounts from the gastrointestinal tract and routinely used to treat chronic constipation in adults. Here, we report the results of a meta-analysis of PEG-based laxatives compared with lactulose, milk of magnesia (magnesium hydroxide), oral liquid paraffin (mineral oil), or acacia fiber, psyllium fiber, and fructose in children. This meta-analysis was conducted in accordance with PRISMA guidelines and involved searches of MEDLINE, Cochrane, EMBASE, and Google Scholar databases up to February 10, 2014, using the keywords (Constipation OR Functional Constipation OR Fecal Impaction) AND (Children) AND (Polyethylene Glycol OR Laxative). Primary efficacy outcomes included a number of stool passages/wk and percentage of patients who reported satisfactory stool consistency. Secondary safety outcomes included diarrhea, abdominal pain, nausea or vomiting, pain or straining at defecation, bloating or flatulence, hard stool consistency, poor palatability, and rectal bleeding. We identified 231 articles, 27 of which were suitable for full-text review and 10 of which were used in the meta-analysis. Patients who were treated with PEG experienced more successful disimpaction compared with those treated with non-PEG laxatives. Treatment-related adverse events were acceptable and generally well tolerated. PEG-based laxatives are effective and safe for chronic constipation and for resolving fecal impaction in children. Children's acceptance of PEG-based laxatives appears to be better than non-PEG laxatives. Optimal dosages, routes of administration, and PEG regimens should be determined in future randomized controlled studies and meta-analyses.

[Impact of clinicopathological features and extent of lymph node dissection on the prognosis in early gastric cancer patients].

OBJECTIVE: To explore the impact of clinicopathological features and extent of lymph node dissection on the prognosis in early gastric cancer (EGC) patients. METHODS: A total of 142 EGC cases screened from database of gastric cancer of Sun Yat-sen University, from Aug. 1994 to Jan. 2010, were included in this study. According to the lymph node metastasis status, they were divided into lymph node negative (n = 116) and lymph node positive (n = 26) groups. The clinicopathological features of the two groups and the impact of extent of lymph node dissection on the prognosis were analyzed. RESULTS: There were no significant differences in age, gender, tumor size and location, Borrmann typing, WHO TNM staging, histological typing, and CEA value between the two groups (P > 0.05). The TNM stages in the lymph node positive group were higher than that in the lymph node negative group (P < 0.001). Between the cases who underwent D1 (n = 21) and D2 (n = 121) dissection, there were no significant differences in postoperative hospital days, blood transfusion volume, and operation time (P > 0.05). The median numbers of LN dissected in D1 and D2 cases were 4 (0 to 16) and 20 (12 to 30), with a significant difference (P = 0.000), but the number of positive LN without significant difference (P = 0.502). The postoperative complication rates were 9.5% in the D1 and 3.3% in the D2 dissection groups, without a significant difference (P = 0.128). The median survival time of the lymph node negative and positive groups was 156 vs. 96 months (P = 0.010). In cases who received D2 and D1 lymph node dissection, the median survival time (MST) was 156 vs. 96 months (P = 0.0022). In the lymph node positive group, D2 dissection prolonged survival time significantly than D1 dissection (96 vs. 27months) (P = 0.001). Cox regression analysis showed that the extent of lymph node dissection and LN metastasis were independent prognostic factors for EGC patients. CONCLUSIONS: It is not able to accurately assess the LN metastasis status preoperatively according to the routine clinicopathological features. For the patients with unknown LN metastasis status, D2 dissection should be the first choice. Comparing with D1 dissection, the morbidity of D2 dissection are not increased, but survival time is prolonged.

Liver-directed neonatal gene therapy prevents cardiac, bone, ear, and eye disease in mucopolysaccharidosis I mice.

Mucopolysaccharidosis I (MPS I) due to deficient alpha-L-iduronidase (IDUA) activity results in accumulation of glycosaminoglycans in many cells. Gene therapy could program liver to secrete enzyme with mannose 6-phosphate (M6P), and enzyme in blood could be taken up by other cells via the M6P receptor. Newborn MPS I mice were injected with 10(9) (high dose) or 10(8) (low dose) transducing units/kg of a retroviral vector (RV) expressing canine IDUA. Most animals achieved stable expression of IDUA in serum at 1240 +/- 147 and 110 +/- 31 units/ml, respectively. At 8 months, untreated MPS I mice had aortic insufficiency, increased bone mineral density (BMD), and reduced responses to sound and light. In contrast, MPS I mice that received high-dose RV had normal echocardiograms, BMD, auditory-evoked brain-stem responses, and electroretinograms. This is the first report of complete correction of these clinical manifestations in any model of mucopolysaccharidosis. Biochemical and pathologic evaluation confirmed that storage was reduced in these organs. Mice that received low-dose RV and achieved 30 units/ml of serum IDUA activity had no or only partial improvement. We conclude that high-dose neonatal gene therapy with an RV reduces some major clinical manifestations of MPS I in mice, but low dose is less effective.