A randomized intervention since infancy to reduce intake of saturated fat: calorie (energy) and nutrient intakes up to the age of 10 years in the Special Turku Coronary Risk Factor Intervention Project

OBJECTIVE: To evaluate the longitudinal impact of dietary counseling on children's nutrient intake. DESIGN: A prospective, randomized, clinical trial. PARTICIPANTS: Children were recruited to the study between December 1, 1989, and May 30, 1992. At the age of 7 months, children were randomized to the intervention group (n = 540) or the control group (n = 522) and were followed up until the age of 10 years.Intervention Families in the intervention group have, since randomization, received regularly individualized counseling about how to modify the quality and quantity of fat in the child's diet, the goal being an unsaturated-saturated fat ratio of 2:1. MAIN OUTCOME MEASURES: Nutrient intakes between the ages of 4 and 10 years based on annual 4-day food records. RESULTS: The fat intake of the intervention children was constantly around 30% of the calorie (energy) intake, while that of the control children was 2 to 3 calorie percentage units higher (P<.001). The intervention children received 2 to 3 calorie percentage units less saturated fats and 0.5 to 1.0 calorie percentage unit more polyunsaturated fats than the control children (P<.001 for both). However, neither group reached the 2:1 goal set for the unsaturated-saturated fatty acid ratio. The vitamin and mineral intakes of the intervention and control children closely resembled each other despite the marked differences in fat intake. CONCLUSION: Individualized, biannually given, fat intake-focused dietary counseling that began at the child's age of 8 months continued to influence favorably the diet of 4- to 10-year-old intervention children without disadvantageous dietary effects, but the 2:1 goal for unsaturated-saturated fat ratio was not reached.     

Haplotype structure and genotype-phenotype correlations of the sulfonylurea receptor and the islet ATP-sensitive potassium channel gene region

The genes for the sulfonylurea receptor (SUR1; encoded by ABCC8) and its associated islet ATP-sensitive potassium channel (Kir6.2; encoded by KCNJ11) are adjacent to one another on human chromosome 11. Multiple studies have reported association of the E23K variant of Kir6.2 with risk of type 2 diabetes. Whether and how E23K itself-or other variant(s) in either of these two closely linked genes-influences type 2 diabetes remains to be fully determined. To better understand genotype-phenotype correlation at this important candidate gene locus, we 1) characterized haplotype structures across the gene region by typing 77 working, high-frequency markers spanning 207 kb and both genes; 2) performed association studies of E23K and nearby markers in >3,400 patients (type 2 diabetes and control) not previously reported in the literature; and 3) analyzed the resulting data for measures of insulin secretion. These data independently replicate the association of E23K with type 2 diabetes with an odds ratio (OR) in the new data of 1.17 (P = 0.003) as compared with an OR of 1.14 provided by meta-analysis of previously published, nonoverlapping data (P = 0.0002). We find that the E23K variant in Kir6.2 demonstrates very strong allelic association with a coding variant (A1369S) in the neighboring SUR1 gene (r(2) > 0.9) across a range of population samples, making it difficult to distinguish which gene and polymorphism in this region are most likely responsible for the reported association. We show that E23K is also associated with decreased insulin secretion in glucose-tolerant control subjects, supporting a mechanism whereby beta-cell dysfunction contributes to the common form of type 2 diabetes. Like peroxisome proliferator-activated receptor gamma, the SUR1/Kir6.2 gene region both contributes to the inherited risk of type 2 diabetes and encodes proteins that are targets for hypoglycemic medications, providing an intriguing link between the underlying mechanism of disease and validated targets for pharmacological treatment.     

A genome-wide scan in families with maturity-onset diabetes of the young: evidence for further genetic heterogeneity

Maturity-onset diabetes of the young (MODY) is a heterogeneous single gene disorder characterized by non-insulin-dependent diabetes, an early onset and autosomal dominant inheritance. Mutations in six genes have been shown to cause MODY. Approximately 15-20% of families fitting MODY criteria do not have mutations in any of the known genes. These families provide a rich resource for the identification of new MODY genes. This will potentially enable further dissection of clinical heterogeneity and bring new insights into mechanisms of beta-cell dysfunction. To facilitate the identification of novel MODY loci, we combined the results from three genome-wide scans on a total of 23 families fitting MODY criteria. We used both a strict parametric model of inheritance with heterogeneity and a model-free analysis. We did not identify any single novel locus but provided putative evidence for linkage to chromosomes 6 (nonparametric linkage [NPL]score 2.12 at 71 cM) and 10 (NPL score 1.88 at 169-175 cM), and to chromosomes 3 (heterogeneity LOD [HLOD] score 1.27 at 124 cM) and 5 (HLOD score 1.22 at 175 cM) in 14 more strictly defined families. Our results provide evidence for further heterogeneity in MODY.     

Tenecteplase: stability and bioactivity of thawed or diluted solutions used in peripheral thrombolysis

PURPOSE: Tenecteplase (TNK; TNKase) is a third-generation plasminogen activator approved for acute myocardial infarction with an enhanced safety profile compared to alteplase. The stability and bioactivity of reconstituted frozen/thawed and diluted tenecteplase solutions used in noncoronary peripheral thrombolysis was determined. MATERIALS AND METHODS: Lyophilized TNK was freshly reconstituted in sterile water (5 mg/mL) and used as control. In freeze/thaw studies, reconstituted TNK aliquots were stored frozen for 4 weeks at -20 degrees C, thawed at ambient temperature, and assayed with and without an additional freeze/thaw cycle. Additional freshly reconstituted TNK aliquots were assayed after six freeze/thaw cycles when frozen at two separate temperatures (-20 degrees and -70 degrees C) and thawed at 2-8 degrees C or ambient temperature. In dilution studies, reconstituted TNK was diluted in 500-mL commercially available normal saline solution bags to concentrations of 0.01, 0.02, and 0.05 mg/mL. Samples were assayed after 0, 8, and 24 hours at ambient temperature. Optical clarity, pH, protein concentration, particle counts, and in-vitro clot-lysis assays were performed. Protein monomer (%), single-chain protein (%), and particle counts were performed in freeze/thaw studies. RESULTS: Frozen/thawed TNK aliquots met all specifications as freshly reconstituted product. For dilution studies (0.01, 0.02, and 0.05 mg/mL), the recovered protein retained 83%-100% bioactivity after 24 hours. The recovered protein rates over the course of 24 hours (relative to target concentration) were 70%-75%, 80%-85%, and 94%-95% at 0.01, 0.02, and 0.05 mg/mL, respectively. Assayed solutions were clear/colorless at all concentrations and time points. CONCLUSION: TNK is fully active after reconstitution and freezing/thawing. TNK dilutions used in clinical practice (0.01-0.05 mg/mL) demonstrated retention of biologic activity at 24 hours without precipitates.     

Normative values for tympanometry in 4-5-year-old children

The objective of this study was to determine normative values for tympanometric variables for 4-5-year-old children. Tympanometry was performed at a pre-scheduled visit at the age of 49-68 months on children recruited to a follow-up visit in a vaccine efficacy trial (n=756 children). Tympanograms obtained successfully from healthy ears were analysed. At the time of the visit, mean static acoustical admittance (SAA) was 0.52 cm3, mean tympanometric peak pressure (TPP) was -48 daPa, and mean tympanometric width (TW) was 101. Compared to results obtained for the same study population at 24 months of age, the SAA had increased significantly with age, while the values for TPP and TW had decreased with age. A history of previous tympanostomy tubes increased the admittance of the tympanic membrane by producing atrophic scars. Thus, the tympanograms obtained from ears with previous tubes were considerably higher and narrower (high SAA and low TW). In conclusion, this study further emphasizes the need for age-specific normative values for interpretation of SAA and TW.     

Occupational asthma due to manual metal-arc welding of special stainless steels.

Occupational asthma (OA) can be induced by fumes of manual metal-arc welding on stainless steel. In recent years, the use of special stainless steels (SSS) with high chromium content has increased. This study presents two cases of OA caused by manual metal-arc welding on SSS. In both cases, the diagnosis of OA was based on respiratory symptoms, occupational exposure and positive findings in the specific challenge tests. In the first case, a 46-yr-old welder had experienced severe dyspnoea while welding SSS (SMO steel), but not in other situations. Challenge tests with both mild steel and stainless steel using a common electrode were negative. Welding SSS with a special electrode caused a delayed 37% drop in forced expiratory volume in one second (FEV1). In the second case, a 34-yr-old male had started to experience dyspnoea during the past few years, while welding especially SSS (Duplex steel). The workplace peak expiratory flow monitoring was suggestive of OA. Challenge tests with both mild steel and stainless steel using a common electrode did not cause bronchial obstruction. Welding SSS with a special electrode caused a delayed 31% drop in FEV1. In conclusion, exposure to manual metal-arc welding fumes of special stainless steel should be considered as a new cause of occupational asthma.     

Occurrence of symptomatic knee osteoarthrosis in rural Finland: a prospective follow up study.

All visits to physicians in the Orivesi Region Federation of Municipalities for Public Health Work in Finland paid due to symptomatic osteoarthrosis of the knee joint were prospectively recorded over a period of one year. Two hundred and thirty four visits were made, accounting for 0.63% of all visits. The prevalence of knee osteoarthrosis was 1.11% (men 0.45%, women 1.72%), and the incidence was 0.60%. The disease occurred almost twice as often in the right knee than in the left. The study provides basic information about patients needing medical help because of symptomatic knee osteoarthrosis. The results can be used as an aid to the planning of examination and treatment resources and in assessment of the need for such services.