Isolated fetal hyperechogenic bowel associated with intra-uterine parvovirus B19 infection

We report a case of fetal hyperechogenic bowel diagnosed at midgestation that was associated with fetal parvovirus B19 infection. Isolated hyperechogenic bowel was detected at 25 weeks. Cystic fibrosis, chromosomal abnormalities and cytomegalovirus infection were excluded, whereas polymerase chain reaction DNA for parvovirus B 19 was found positive on amniotic fluid. The hyperechogenic bowel decreased with complete resolution by 32 weeks of gestation. No other signs of fetal B19 infection were detected prenatally and the baby had normal postnatal outcome. This case provides additional arguments in favor of a possible intestinal tropism of parvovirus B19 during fetal life. Fetal B19 infection should be systematically incorporated in the prenatal evaluation of isolated fetal hyperechogenic bowel.     

Combining immunoreactive trypsinogen and pancreatitis-associated protein assays, a method of newborn screening for cystic fibrosis that avoids DNA analysis

OBJECTIVES: To evaluate the performance of a strategy in which, after immunoreactive trypsinogen (IRT) determination, genetic analysis is replaced by a biological test, the pancreatitis-associated protein (PAP) enzyme-linked immunosorbent assay (ELISA). STUDY DESIGN: The French newborn screening program includes cystic fibrosis (CF) screening by the IRT/CFTR mutation strategy. PAP was assayed on screening cards, in parallel with IRT, in all newborns from 5 French regions (n = 204,749). Analysis of PAP values in CF and non-CF newborns with elevated IRT allowed direct comparison between the current strategy and the proposed IRT/PAP strategy. RESULTS: A protocol in which newborns with IRT >50 ng/mL and PAP >1.8 ng/mL and those with IRT >100 ng/mL and PAP >1.0 ng/mL are directly recalled for sweat testing would have the same performance as the IRT/CFTR mutation strategy. CONCLUSIONS: The IRT/PAP strategy is an alternative for CF newborn screening, which avoids the drawbacks of genetic analysis and is cheaper and easier to implement than the current IRT/CFTR mutation strategy.     

Double-blind randomized evaluation of clinical and biological tolerance of polyethylene glycol 4000 versus lactulose in constipated children

OBJECTIVES: To assess the safety of a polyethylene glycol (PEG) 4000 laxative without additional salts in pediatric patients. STUDY DESIGN: This was a 3-month multicenter, randomized, double-blind, double-dummy, lactulose-controlled, parallel study enrolling 96 ambulatory constipated children aged 6 months to 3 years, treated daily with 4-8 g PEG or 3.33 g-6.66 g lactulose. Total protein, albumin, iron, electrolytes, and vitamins B9 (folates), A and D (25OHD3) were measured in blood before and after treatment (day 84) in a central laboratory. RESULTS: The percentage of children with at least one value out of normal range at day 84 with respect to baseline status (with or without at least one value out of normal range), i.e. the primary endpoint, was 87% and 90% in the PEG and lactulose groups, respectively, without any difference between groups. The whole blood parameters showed no qualitative or quantitative treatment-related changes. Vitamin A values were above normal range in 56% and 41% of children at baseline versus 33% and 36% at day 84 in the PEG and lactulose groups, respectively. Iron values were similarly under normal range in 47% and 51% at baseline versus 42% and 51% at day 84. Clinical tolerance was similar for both treatments except for vomiting and flatulence, which were significantly higher with lactulose. Significantly higher improvements were evidenced with PEG regarding stool consistency, appetite, fecaloma and use of additional laxatives. CONCLUSION: This 3-month study in 96 constipated children aged 6 months to 3 years confirms the long-term tolerance of PEG 4000 in pediatrics and indicates a PEG efficacy similar to or greater than that of lactulose.     

Clinical and biologic factors related to oral implant failure: a 2-year follow-up study

The purpose of this study is to evaluate urinary biomarkers of bone formation and resorption as predictive factors for oral implant failure, and to contribute to the knowledge of factors related to oral implant failure. A total of 93 patients between 18 and 85 years old, with an indication of oral implant, were eligible in this 2-year prospective, open, and nonrandomized study. Patients who had bone graft before implantation or presented with prosthetic difficulties (implant-to-crown ratio < 1, and/or unfavorable intermaxillary space) were excluded. All patients received either Frialit-2 (Friadent, Mannheim, Germany), cylinder, or screwed implants or IMZ Twin Plus (Friadent), cylinder implants, with FRIOS (Friadent) titanium coating. Serum osteocalcin, and urinary pyridinoline and deoxypyridinoline were measured, together with bone density at implant location. The primary endpoint (implant failure) was the implant removal (radiographic evidence of peri-implant bone loss and/or pockets). Factors related to implant failure were analyzed using multilevel logistic regression models to consider within-patient effects. Of the 93 patients included, 61% were female, and 16% were current smokers. A total of 266 oral implants were placed and analyzed, with a mean number of 3.1 implants by patient. Eleven and 15% of bone locations scored at D1 and D4, respectively, for the Misch bone density scoring. The majority of implants (72%) were placed more than 3 months after tooth extraction, using a Frialit-2 system in 73% of cases. The mean of osteocalcin was 17.3 (+/-9.4) ng/L; those of pyridinoline and deoxypyridinoline were 33.2 (+/-15.8) and 10.2 (+/-11.9) mmol per creatinine mmol, respectively. At one-year, 95.5% (95% confidence interval 92.5-97.5) of implants have not been removed. One year later, no further implant failed. In both univariate and multivariate analysis, osteocalcin, pyridinoline, and deoxypyridinoline were not significant predictive factors of oral implant failure. In multilevel logistic regression analysis, only tobacco consumption and single-tooth replacement or removable prosthesis were independent and significant predictive factors of oral implant failure. Serum osteocalcin, and urinary pyridinoline and deoxypyridinoline were not predictive of oral implant failure in this study. These results suggest that oral implants are more likely to fail for posterior single-tooth replacements and removable prostheses rather than for complete edentulous fixed bridgeworks or overdentures. Tobacco smoking has been identified as a major risk factor of oral implant failure.     

Is there a difference in the reliable measurement of temporomandibular disorder signs between experienced and inexperienced examiners?

AIMS: To determine whether there is a difference in terms of reliability between experienced examiners and inexperienced examiners in the measurement of signs of temporomandibular disorders (TMD). METHODS: A total of 27 patients seen for treatment of TMD were rated blindly and in random sequence by 2 experienced and 2 inexperienced examiners. The examiners participated in a 4-hour calibration session on the day preceding the reliability study. Both experienced and inexperienced examiners participated in the calibration session to reduce the effect of examiner subjectivity and allow the study focus to be on the effect of experience. The rating followed the Research Diagnostic Criteria for Temporomandibular Disorders and included mandibular movements, joint sounds, and digital palpation of muscles and joints. Intraclass correlation coefficients and kappa statistics were calculated to estimate interrater reliability. The Wilcoxon signed rank test was performed to test for differences between experienced and inexperienced examiners' results, and the Friedman test was used for differences between all 6 examiner combinations. RESULTS: Excellent overall reliability was found for vertical mandibular motions, acceptable reliability was found for the summed muscle palpation pain sites, and moderate to poor reliability was found for excursive movements, joint sounds, and single muscle palpation pain sites. No significant differences in the measurement results could be found between the experienced examiners and the inexperienced examiners. CONCLUSION: Examiner calibration rather than professional experience seems to be the most important factor for reliable measurement of TMD symptoms.     

Development of the ICH guidelines for immunotoxicology evaluation of pharmaceuticals using a survey of industry practices

An anonymous survey of pharmaceutical industry practices for immunotoxicology evaluation was conducted. This was in support of the development of the guideline on the preclinical evaluation of unintended modulation of the immune system for the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. The survey was conducted in two phases in 2003 and 2004. A total of 64 responses were received of which 45 were included in the formal evaluation. The remaining compounds were excluded because they were cytotoxic anti-neoplastic drugs (N = 7), or due to insufficient information (N = 12). The purpose of the survey was to gather data on the correlation between routine toxicology studies (RTS) and additional immunotoxicological studies (AIS). The results of the survey were evaluated by the Expert Working Group (EWG) and classified as to positive or negative findings in RTS and AIS. The results of the survey showed that for 27 of 45 compounds (60%), the RTS and AIS endpoints were in agreement. In 12 of 45 cases (27%), the RTS endpoints showed immune modulation not observed in the AIS assays. Finally for 6 of 45 drugs (13%) a response was seen with the AIS methods where no significant effect was observed in the RTS endpoints. Length of dosing and the number of tests evaluated were similar in all groups. The groups where RTS detected signs of immunosuppression were more likely to have been dosed at or above MTD. This data contributed to the consensus in the EWG that routine immune function testing as an initial screen for all new drugs is not required. Instead, a weight-of-evidence approach including RTS and other causes for concern is recommended to identify the need for additional immunotoxicity studies.     

Reflux, dysphagia, and gas bloat after laparoscopic fundoplication in patients with incidentally discovered hiatal hernia and in a control group

BACKGROUND: Laparoscopic fundoplication effectively controls reflux symptoms in patients with gastroesophageal reflux disease (GERD). However, symptom relapse and side effects, including dysphagia and gas bloat, may develop after surgery. The aim of the study was to assess these symptoms in patients who underwent laparoscopic fundoplication, as well as in control subjects and patients with hiatal hernia. METHODS: A standardized, validated questionnaire on reflux, dysphagia, and gas bloat was filled out by 115 patients with a follow-up of 1 to 7 years after laparoscopic fundoplication, as well as by 105 subjects with an incidentally discovered hiatal hernia and 238 control subjects. RESULTS: Patients who underwent fundoplication had better reflux scores than patients with hiatal hernia ( P = .0001) and similar scores to control subjects ( P = .11). They also had significantly more dysphagia and gas bloat than patients with hiatal hernia and controls ( P < .005 for all comparisons). Gas bloat and dysphagia were more severe in hiatal hernia patients than in controls ( P < 0.005). After fundoplication, the 25% of the patients with the shortest follow-up (1.5 +/- 0.2 years) and the 25% patients with the longest follow-up (5.8 +/- 0.6 years) had similar reflux, dysphagia, and gas bloat scores ( P = .43, .82, and .85, respectively). CONCLUSION: In patients with severe GERD, laparoscopic fundoplication decreases reflux symptoms to levels found in control subjects. These results appear to be stable over time. However, patients who underwent fundoplication experience more dysphagia and gas bloat than controls and patients with hiatal hernia-symptoms that should be seen as a side effect of the procedure and of GERD itself.     

Effect of fructose overfeeding and fish oil administration on hepatic de novo lipogenesis and insulin sensitivity in healthy men

High-fructose diet stimulates hepatic de novo lipogenesis (DNL) and causes hypertriglyceridemia and insulin resistance in rodents. Fructose-induced insulin resistance may be secondary to alterations of lipid metabolism. In contrast, fish oil supplementation decreases triglycerides and may improve insulin resistance. Therefore, we studied the effect of high-fructose diet and fish oil on DNL and VLDL triglycerides and their impact on insulin resistance. Seven normal men were studied on four occasions: after fish oil (7.2 g/day) for 28 days; a 6-day high-fructose diet (corresponding to an extra 25% of total calories); fish oil plus high-fructose diet; and control conditions. Following each condition, fasting fractional DNL and endogenous glucose production (EGP) were evaluated using [1-13C]sodium acetate and 6,6-2H2 glucose and a two-step hyperinsulinemic-euglycemic clamp was performed to assess insulin sensitivity. High-fructose diet significantly increased fasting glycemia (7 +/- 2%), triglycerides (79 +/- 22%), fractional DNL (sixfold), and EGP (14 +/- 3%, all P < 0.05). It also impaired insulin-induced suppression of adipose tissue lipolysis and EGP (P < 0.05) but had no effect on whole- body insulin-mediated glucose disposal. Fish oil significantly decreased triglycerides (37%, P < 0.05) after high-fructose diet compared with high-fructose diet without fish oil and tended to reduce DNL but had no other significant effect. In conclusion, high-fructose diet induced dyslipidemia and hepatic and adipose tissue insulin resistance. Fish oil reversed dyslipidemia but not insulin resistance.