The aim of this study was to compare the allergy‐preventive effect of a partially hydrolyzed formula with two extensively hydrolyzed formulas, in infants with a high risk for development of allergic ...disease. High‐risk infants from four Danish centres were included in the period from June 1994 to July 1995. Five‐hundred and ninety‐five high‐risk infants were identified. High‐risk infants were defined as having bi‐parental atopy, or a single atopic first‐degree relative combined with cord blood immunoglobulin E (IgE) ≥ 0.3 kU/l. At birth all infants were randomized to one of three different blinded formulas. All mothers had unrestricted diets during pregnancy and lactation and were encouraged to breast‐feed exclusively. If breast‐feeding was insufficient, one of the three formulas, according to randomization, was given during the first 4 months. It was recommended not to introduce cow's milk, cow's milk products, and solid foods until the age of 4 months. After the age of 4 months a normal unrestricted diet and conventional cow's milk‐based formula were given when needed. All infants were followed‐up prospectively with interview and physical examination at the age of 6, 12, and 18 months, and if any possible atopic symptoms were reported. If food allergy was suspected, controlled elimination/challenge procedures were performed in a hospital setting. Of 550 infants included in the study, 514 were seen at all visits and 36 were excluded owing to non‐compliance. Of 478 infants who completed the study, 232 were exclusively breast‐fed, 79 received an extensively hydrolyzed casein formula (Nutramigen), 82 an extensively hydrolyzed whey formula (Profylac), and 85 a partially hydrolyzed whey formula (Nan HA), during the first 4 months of life. These four groups were identical in regard to atopic predisposition, cord blood IgE, birthplace, and gender. Exclusively breast‐fed children were exposed less to tobacco smoke and pets at home and belonged to higher social classes, whereas the three formula groups were identical concerning environmental factors. The frequency of breast‐feeding was high; only eight (2%) children were not breast‐fed at all. The three formula groups were identical in regard to duration of breast‐feeding and age at introduction of formula and solid foods. No significant differences were found in the three groups of infants receiving formula milk regarding the cumulative incidence of atopic dermatitis or respiratory symptoms. The cumulative incidence of parental‐reported cow's milk allergy was significantly higher in children fed partially hydrolyzed formula (Nan HA) compared with extensively hydrolyzed formula (Nutramigen or Profylac) at 12 and 18 months (NanHA, 7.1%; Nutramigen, 2.5%; Profylac, 0%; p = 0.033). The cumulative incidence of confirmed cow's milk allergy was 1.3% (three of 232) in exclusively breast‐fed infants, 0.6% (one of 161) in infants fed extensively hydrolyzed formula (Nutramigen or Profylac), and 4.7% (four of 85) in infants fed partially hydrolyzed formula (Nan HA). Partially hydrolyzed formula was found to be less effective than extensively hydrolyzed formula in preventing cow's milk allergy, 0.6% vs. 4.7% (p = 0.05), but because of the small number of cases the results should be interpreted with caution. Compared with other similar studies the frequency of atopic symptoms was low, even though the dietetic intervention did not include either maternal diet during lactation or dietary restrictions to the children after the age of 4 months.
The effect of detoxification of pertussis toxin (PT) for vaccine usage by either genetic manipulation, hydrogen peroxide or formaldehyde treatment on epitope recognition by a large collection of ...murine monoclonal pertussis toxin antibodies (PT MAbs) was assessed in a solid-phase and a soluble phase enzyme-linked immunosorbent assay (ELISA). The MAb binding patterns were found to be different in the two assays as the immobilization step appeared to cause conformational alterations in the native as well as the toxoided forms of PT. According to the solid-phase ELISA, genetic, hydrogen peroxide and 0.35% formaldehyde detoxification of PT resulted in reduced epitope binding in 2.9, 31.4 and 78.1% of the MAbs, respectively. In the soluble-phase ELISA, in which the MAbs were allowed to react with the toxoids or native toxin in solution, the percentages of MAbs showing decreased binding activity were 9.1, 50.0 and 71.4%, respectively. Stabilization of native PT and the genetically inactivated PT by 0.035% formaldehyde reduced the epitope binding activity in 50.0 and 8.7% of the MAbs, respectively. Increased antibody binding in the soluble-phase ELISA was observed in some of the toxoids: this ranged from 0% in the 0.35% formaldehyde-treated PT to 13.6% in the hydrogen peroxide-treated and 27.3% in the genetically detoxified PT. Regarding the effects of detoxification on epitopes recognized by PT-neutralizing MAbs in the soluble-phase ELISA, we found that treatment of PT with either 0.035%, 0.35% formaldehyde or hydrogen peroxide induced impairment of epitope binding in 72.7, 81.8 and 45.5% of the MAbs, respectively. In the genetically inactivated PT, the epitopes recognized by the neutralizing MAbs either appeared to remain intact or to show increased MAb binding activity. The epitope-binding patterns of several PT MAbs with mouse-protective properties varied considerably and were shown to be dependent on the detoxification procedure employed. The relevance of epitope alterations on PT as a vaccine component is discussed. The results of the present study may have important implications for future quality assessment of PT for use in acellular pertussis vaccines.
This pharmacogenetics substudy from the Losartan Intervention for Endpoint reduction in Hypertension study in patients with hypertension and left ventricular hypertrophy (LVH) treated with the ...angiotensin receptor blocker losartan versus the beta-blocker atenolol for 4.8 years tested whether the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene and 12 other previously well-characterized polymorphisms of hypertension susceptibility genes affected blood pressure reduction, heart rate reduction, cardiovascular events, and/or response to treatment. These polymorphisms were chosen because they could affect blood pressure control or the pharmacological action of losartan or atenolol.
We genotyped 3503 patients, 1774 on losartan and 1729 on atenolol.
ACE and the 12 other genotypes did not affect the reduction in systolic blood pressure, diastolic blood pressure, pulse pressure, mean arterial pressure, or heart rate, or treatment differences between losartan and atenolol on these endpoints, as assessed by general linear models. Also, ACE and the 12 other genotypes did not affect risk of the primary composite endpoint or its components stroke, myocardial infarction, and cardiovascular death, or treatment differences between losartan and atenolol on these endpoints, as assessed by Cox proportional hazards models including baseline Framingham risk score and LVH.
ACE insertion/deletion and 12 other polymorphisms of hypertension susceptibility genes did not affect blood pressure reduction, heart rate reduction, or cardiovascular events in patients with hypertension and LVH, or treatment differences between losartan and atenolol on these endpoints. These results suggest that the observed effects of losartan versus atenolol in the Losartan Intervention for Endpoint reduction in hypertension study do not depend on ACE and 12 other polymorphisms of hypertension susceptibility genes.
We performed a genome-wide association analysis of 1,897,764 SNPs in 1,043 German ulcerative colitis (UC) cases and 1,703 controls. We discovered new associations at chromosome 7q22 (rs7809799) and ...at chromosome 22q13 in IL17REL (rs5771069) and confirmed these associations in six replication panels (2,539 UC cases and 5,428 controls) from different regions of Europe (overall study sample Prs7809799 = 8.81 × 10−11 and Prs5771069 = 4.21 × 10−8, respectively).
Objective
To evaluate the reduction of surgical site infections by prophylactic incisional negative pressure wound therapy compared with standard postoperative dressings in obese women giving birth ...by caesarean section.
Design
Multicentre randomised controlled trial.
Setting
Five hospitals in Denmark.
Population
Obese women (prepregnancy body mass index (BMI) ≥30 kg/m2) undergoing elective or emergency caesarean section.
Method
The participants were randomly assigned to incisional negative pressure wound therapy or a standard dressing after caesarean section and analysed by intention‐to‐treat. Blinding was not possible due to the nature of the intervention.
Main outcome measures
The primary outcome was surgical site infection requiring antibiotic treatment within the first 30 days after surgery. Secondary outcomes included wound exudate, dehiscence and health‐related quality of life.
Results
Incisional negative pressure wound therapy was applied to 432 women and 444 women had a standard dressing. Demographics were similar between groups. Surgical site infection occurred in 20 (4.6%) women treated with incisional negative pressure wound therapy and in 41 (9.2%) women treated with a standard dressing (relative risk 0.50, 95% CI 0.30–0.84; number needed to treat 22; P = 0.007). The effect remained statistically significant when adjusted for BMI and other potential risk factors. Incisional negative pressure wound therapy significantly reduced wound exudate whereas no difference was found for dehiscence and quality of life between the two groups.
Conclusion
Prophylactic use of incisional negative pressure wound therapy reduced the risk of surgical site infection in obese women giving birth by caesarean section.
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RCT: prophylactic incisional NPWT versus standard dressings postcaesarean in 876 women significantly reduces the risk of SSI.
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RCT: prophylactic incisional NPWT versus standard dressings postcaesarean in 876 women significantly reduces the risk of SSI.
TGR5, the G protein-coupled bile acid receptor 1 (GPBAR1), has been linked to inflammatory pathways as well as bile homeostasis, and could therefore be involved in primary sclerosing cholangitis ...(PSC) a chronic inflammatory bile duct disease. We aimed to extensively investigate TGR5 sequence variation in PSC, as well as functionally characterize detected variants.
Complete resequencing of TGR5 was performed in 267 PSC patients and 274 healthy controls. Six nonsynonymous mutations were identified in addition to 16 other novel single-nucleotide polymorphisms. To investigate the impact from the nonsynonymous variants on TGR5, we created a receptor model, and introduced mutated TGR5 constructs into human epithelial cell lines. By using confocal microscopy, flow cytometry and a cAMP-sensitive luciferase assay, five of the nonsynonymous mutations (W83R, V178M, A217P, S272G and Q296X) were found to reduce or abolish TGR5 function. Fine-mapping of the previously reported PSC and UC associated locus at chromosome 2q35 in large patient panels revealed an overall association between the TGR5 single-nucleotide polymorphism rs11554825 and PSC (odds ratio = 1.14, 95% confidence interval: 1.03-1.26, p = 0.010) and UC (odds ratio = 1.19, 95% confidence interval 1.11-1.27, p = 8.5 x 10(-7)), but strong linkage disequilibrium precluded demarcation of TGR5 from neighboring genes.
Resequencing of TGR5 along with functional investigations of novel variants provided unique insight into an important candidate gene for several inflammatory and metabolic conditions. While significant TGR5 associations were detected in both UC and PSC, further studies are needed to conclusively define the role of TGR5 variation in these diseases.
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