The insulin gene variable number of tandem repeat: associations and interactions with childhood body fat mass and insulin secretion in normal children

CONTEXT: Polymorphism at the insulin gene (INS) variable number of tandem repeat (VNTR) shows variable associations with childhood body mass index (BMI) in different populations. OBJECTIVE: The objective of this study was to observe INS VNTR associations with body composition and insulin secretion in children. DESIGN: The study was designed as a prospective birth cohort study. PARTICIPANTS: A total of 947 children genotyped for the INS VNTR participated. MAIN OUTCOME MEASURES: Main outcome measures were whole body dual x-ray emission absorptiometry at 9 yr to estimate height-corrected fat mass index (FMI), truncal FMI, and fat-free mass, and insulin secretion after oral glucose at 8 yr. RESULTS: Homozygous III/III children had higher BMI (P = 0.020), FMI (P = 0.015), and truncal FMI (P = 0.022) at 9 yr than class I bearers, but no difference in fat-free mass (P = 0.23). Gain in weight sd score between birth and 3 yr was associated positively with BMI, FMI, and truncal FMI in class I bearers, but not in III/III children (p-interaction with genotype = 0.009-0.066). INS VNTR genotype was not associated overall with insulin secretion at 8 yr (P = 0.64), but class I bearers showed a stronger positive correlation between insulin secretion and BMI at 8 yr (regression coefficient +/- se, 0.26 +/- 0.05; P < 0.0001) than III/III children (-0.10 +/- 0.07; P = 0.48) (p-interaction = 0.003). CONCLUSION: We clarified that the overall association between INS VNTR class III/III genotype and larger BMI in this population relates to fat mass, but not fat-free mass. In contrast, among the subgroup of children who showed rapid infancy weight gain, class I bearers tended to have larger BMI and fat mass than III/III children. This genetic interaction could relate to insulin secretion, which, in class I bearers, increased more rapidly with overweight and obesity.     

Metformin therapy during puberty delays menarche, prolongs pubertal growth, and augments adult height: a randomized study in low-birth-weight girls with early-normal onset of puberty

CONTEXT AND OBJECTIVE: Low-birth-weight (LBW) girls who enter puberty earlier (around 8-9 yr) tend to have earlier menarche, earlier growth arrest, and a shorter adult stature. At present, there is no therapy for most of these girls. In LBW girls with early puberty, hyperinsulinemic insulin resistance could underpin their rapid transit through puberty and their loss of adult stature. We explored the effects of insulin sensitization with metformin during puberty. SETTING, DESIGN, AND PATIENTS: In an open-labeled, prospective study, 22 LBW girls (birth weight < -1.5 sd score for gestational age) with early-normal puberty (stage 2 breast development at age 8-9 yr) were randomized to remain untreated (n = 12) or to receive metformin (850 mg/d; n = 10) for 36 months (mean age at start, 9.0 yr). All girls remained untreated between 36 and 42 months. MAIN OUTCOME MEASURES: Pubertal growth, body composition by absorptiometry, uterine-ovarian size by ultrasound, fasting insulin, glucose, lipids, leptin, IGF-I, and IGF-binding protein-1 were assessed. RESULTS: Metformin treatment resulted in a longer duration from stage 2 breast development to menarche (P < 0.01; median difference, +1.0 yr), taller near-adult height (P < 0.01), and leaner body composition (P < 0.001). Metformin was also associated with lower insulin resistance and leptin and IGF-I levels and higher SHBG and IGF-binding protein-1 levels and with a more favorable lipid profile. Bone mineral density and uterine-ovarian growth were unaffected. CONCLUSION: Metformin treatment for 36 months in LBW girls with early-normal puberty normalized their pubertal progression to menarche and increased height gains up to adult stature. These data support the concept that insulin is a major codeterminant of the pubertal tempo and pubertal height gain in girls.     

Caregiver distress in parkinsonism

This study examined the frequency and degree of caregiver burden in persons with parkinsonism, a group of disorders with four primary symptoms that include tremor, rigidity, postural instability, and bradykinesia. We assessed associations between perceived caregiver burden and physical, cognitive, and functional impairments using well-established tools for persons with parkinsonism. The 49 individuals with parkinsonism ranged in age from 61 to 87 (mean = 75), while their caregivers (N = 49) ranged in age from 48 to 83 (mean = 70). The caregivers were predominantly either wives (82%) or daughters (6%), with other family members, friends, and/or neighbors (12%) making up the rest. The caregivers reported a relatively high ability for coping (mean scores = 4.6/6). Caregiver burden was significantly negatively associated with activities of daily living and motoric difficulties as measured on the Unified Parkinson's Disease Rating Scale (UPDRS). Likewise, caregiver burden was negatively associated with caregiver self-reported sleep and coping ability. Results did not demonstrate an association on the UPDRS among mentation, behavior, and mood. We found a significant negative correlation for mentation between the Folstein Mini-Mental Status Examination and caregiver burden measures; however, we did not find this association with the Dementia Rating Scale-2. Patient's self-reported pain and caregiver burden were not associated.     

Drug-related problems on hospital admission: relationship to medication information transfer

BACKGROUND: Patients with end-stage renal disease (ESRD) are at risk for drug-related problems (DRPs), especially on hospital admission. OBJECTIVE: To identify and characterize the DRPs experienced by patients with ESRD on admission and investigate how these DRPs could be related to gaps in medication information transfer. METHODS: Patients with ESRD admitted to the hospital were prospectively identified and clinically assessed by a pharmacist to identify and categorize DRPs on admission. Each DRP was evaluated to determine whether it could have been caused by a gap in medication information transfer. For DRPs caused in this manner, the interface in the information transfer process where the gap may have occurred was determined. RESULTS: A total of 199 DRPs were identified in 47 patients with ESRD over a 12 week period. Ninety-two percent of patients had at least one DRP on admission, with an average of 4.2 +/- 2.2 DRPs per patient. The most common DRP identified was indication for drug therapy--patient requires drug but is not receiving it (51.3%). Of the total DRPs, 130 (65%) were related to gaps in medication information transfer, with 21.5% occurring between the inpatient hospital and the ambulatory clinic pharmacists and 17.7% between the admitting physician and the patient. CONCLUSIONS: Results of this study demonstrate that, in patients with ESRD, DRPs on admission are frequently related to gaps in medication information transfer between healthcare professionals and also between healthcare providers and patients. Improved communication is required at medication information transfer interfaces to prevent these DRPs.     

Real-time PCR detection of male-specific coliphages

Male-specific coliphages are often used as indicators of contamination by enteric viruses. These phages can be detected in water samples by plaque assays and by polymerase chain reaction. In this study, the M13 coliphage was used to develop a real-time PCR assay for the detection of male-specific DNA coliphages. The real-time PCR was found to have a reaction efficiency of 1.45 and detection limit of 10(-3) plaque forming units per reaction mix. Repeated amplification and melting curve analyses demonstrated high specificity and reproducibility of the real-time assay. Quantitative detection with the real-time PCR should allow rapid assessment of the level of viral contamination in water.     

Modern microbiology – a quiet revolution with many benefits

In the clinical microbiology laboratory, classical culture and identification methods are rapidly giving way to molecular techniques with many benefits for clinicians and patients. Building on the discovery of the structure of DNA and the genetic code, four main scientific advances have been made which underpin these techniques (hybridisation probes, polymerase chain reaction, the observation that the microbial species signature can be read in the ribosomal genes and also in the proteins). Early discoveries have paved the way for new diagnostic methods, which are rapid, highly sensitive and specific. Automation has provided high throughput for large numbers of clinical specimens combined with reasonable cost. The benefits for the clinician and patient include confirmation of clinical diagnoses and information about antimicrobial susceptibility within hours compared to days for conventional methods. In resource-poor settings, molecular techniques and automated systems may seem unaffordable but new public-private partnerships, initiatives by the World Health Organization and new, innovative laboratory methods offer the promise of benefit for all.     

Germline <Emphasis Type="Italic">MUTYH</Emphasis> gene mutations are not frequently found in unselected patients with papillary breast carcinoma

MUTYH- associated polyposis (MAP) is an autosomal recessive disease, which predisposes to polyposis and colorectal cancer. There is a trend towards an increased risk of breast cancer in MAP patients, with a remarkable proportion of papillary breast cancers. To determine whether MUTYH mutations are associated with this specific and rare type of breast cancer, 53 unselected patients with papillary breast cancer were analyzed for founder mutations in the MUTYH gene. No germline mutations were identified, indicating that biallelic MUTYH mutations are not a frequent underlying cause for the development of papillary carcinomas of the breast.