bluuebunny/crossref_metadata_2025 huggingface dataset:
Mapping QTL involved in powdery mildew resistance of the apple clone U 211
Authors: Stankiewicz‐Kosyl M. , Pitera E. , Gawronski S. W.
Published: February 2005

Scab and powdery mildew, caused by Venturia inaequalis (Cke.) Wint. and Podosphaera leucotricha (Ellis et Ev.) Salm. are the most important apple diseases. The apple clone U 211 is resistant to scab and is also highly resistant to powdery mildew under field conditions. The interval mapping method was applied for the identification of genomic regions conferring U 211 resistance to powdery mildew. The genetic maps of the ‘Idared’ and U 211 genome sectors were constructed using amplified fragment lenght polymorphism and simple sequence repeat markers and 98 individuals from the progeny of the cross ‘Idared’× U 211. On the basis of the phenotypic and molecular marker data 10 powdery mildew resistance quantitative trait loci (QTL) were identified in U 211 and ‘Idared’. One of the QTL in the clone U 211 explained 48‐72% of the phenotypic variation and its effect was stable over years.
Mapping of QTL controlling tocopherol content in winter oilseed rape
Authors: Marwede V. , Gul M. K. , Becker H. C. , Ecke W.
Published: February 2005

Tocopherols are natural antioxidants in vegetable oils and are important dietary nutrients. Enhanced tocopherol content has become an important objective in oilseed rape breeding. A segregating DH population was tested for 2 years at two locations in replicated field trials. Genotypic differences occurred for α‐, γ‐ and total tocopherol content as well as α/γ‐tocopherol ratio, but highly significant genotype x environment interactions resulted in low heritabilities. Using a mixed‐model composite interval mapping approach between one and five QTL with additive and/or additive x environment interaction effects could be mapped for α‐, γ‐ and total tocopherol content and α/β‐tocopherol ratio. In addition, one to six locus pairs with epistatic interaction effects were identified, indicating a strong contribution of epistasis to trait variation. In total, the additive and epistatic effects explained between 28% (α‐tocopherol content) and 73% (total tocopherol content) of the genotypic variance in the population, with individual QTL and locus pairs contributing between 7.5 and 29.2% of variance. Considering the low heritabilities of the tocopherol traits, the results of this study indicate that marker‐assisted selection may be an efficient strategy in a breeding program for enhanced tocopherol content in rapeseed.
Conformity and genetic relatedness estimation in crop species having a narrow genetic base: the case of cucumber (Cucumis sativus L.)*
Authors: Staub J. E. , Chung S.‐M. , Fazio G.
Published: February 2005

A set of 155 SSR (107) and SCAR (48) markers were used to evaluate 53 cucumber (Cucumis sativus L.) accessions of diverse origin to characterize genetic relationships and to define a standard marker array that was most effective in detecting genetic differences in this germplasm array. A multivariate marker‐based analysis of diverse germplasm using this standard marker array (17 SSR and 5 SCAR markers) was compared with results from a set of 70 previously reported RAPD markers, and then used to explore the potential value of these genetic markers for plant variety protection (PVP) and the establishment of essential derivation (ED) threshold values in this species using elite lines and hybrids and backcross progeny. Diversity analysis allowed identification of distinctly different lines that were used for the construction of three sets of backcross families (BC1‐BC3). While general genetic relationships among accessions were similar in SSR/SCAR analyses (rs= 0.65) using two genetic distance (GD) estimators, differences in accession relationships were detected between RAPD and SSR/SCAR marker evaluations regardless of the estimator used. The GDs among elite germplasm with known pedigrees were relatively small (0.06‐0.23 for any pairwise comparison). GD values decreased and degree of fixation (at three to seven loci depending on the mating) increased with increased backcrossing such that recurrent parent allelic fixation occurred in least one family of each of the BC3 families. In many instances the degree of fixation of loci was not uniformly achieved in the BC3. Although the level of genetic polymorphisms will likely restrict the use of molecular markers for PVP and the establishment of ED values, the use of single nucleotide differences will likely provide opportunities to define specific functional distances that have potential for PVP in cucumber. Nevertheless, without an expanded, genetically robust standard marker array (e.g. 50 codominant markers), ED threshold values will be difficult to define in this species, and perhaps will require the appraisal of single nucleotide polymorphisms as discriminators of difference in this species.
Histological and inheritance studies of partial resistance in the Brassica napus–Albugo candida host‐pathogen interaction
Authors: Bansal V. K. , Tewari J. P. , Stringam G. R. , Thiagarajah M. R.
Published: February 2005

Traditional and doubled haploid (DH) genotypes of oilseed Brassica spp. resistant, partially resistant, moderately susceptible, and susceptible to Albugo candida were compared for phenotypic development of host‐pathogen interaction and histology of host‐pathogen interaction. The partially resistant genotype showed pinhead‐size pustules, mainly on the upper surface of cotyledonary leaves. Relatively less mycelium was observed in the partially resistant genotype compared with the susceptible genotype. In resistant B. napus genotypes, there was neither pustule development nor any mycelial growth. In the moderately susceptible genotype, the pustules were similar to those in the partially resistant genotype in being of pinhead‐size and occasionally coalescing. However, ample mycelial growth in the mesophyll tissue in the moderately susceptible genotype was similar to that in the susceptible control B. rapa cv. ‘Torch’. The susceptible genotype B. rapa cv. ‘Torch’ also showed large coalescing pustules. In the non‐host B. juncea cv. ‘Commercial Brown’, no pustules were formed although some mycelial growth was observed beneath the epidermal cell layer and in the mesophyll cell layer of the cotyledonary leaf tissue. For inheritance studies, two partially resistant B. napus genotypes were crossed with a resistant B. napus genotype. Various generations viz., F1, F1(reciprocal), F2, and DHs produced from the crosses were inoculated with a zoospore suspension of race 7v of A. candida. The partially resistant phenotype appeared to be controlled by a single recessive gene designated as wpr with variable expression. The simple inheritance of partial resistance has implications for disease resistance breeding against white rust, as this type of resistance can be easily incorporated into elite breeding lines through conventional and DH breeding methods.
Statin therapy improves brachial artery vasodilator function in patients with Type 1 diabetes and microalbuminuria
Authors: Dogra G. K. , Watts G. F. , Chan D. C. , Stanton K.
Published: February 2005

Aims  Type 1 diabetes mellitus patients with microalbuminuria have endothelial dysfunction associated with the degree of albuminuria but not with LDL‐cholesterol levels. Lipid‐lowering agents such as statins may still be of benefit as they can correct endothelial dysfunction by both lipid and non‐lipid mechanisms. We therefore examined the effects of atorvastatin on brachial artery endothelial dysfunction in these patients.

Methods  In a double‐blind, randomized crossover study, 16 Type 1 diabetes mellitus patients with microalbuminuria received 6 weeks of atorvastatin 40 mg/day or placebo, separated by a 4‐week washout. Brachial artery, endothelium‐dependent, flow‐mediated dilatation (FMD) and endothelium‐independent, glyceryl trinitrate‐mediated dilatation (GTNMD) were measured.

Results  Compared with placebo, atorvastatin produced a significant decrease in apolipoprotein B (34.2%), LDL‐cholesterol (44.1%) (all P < 0.001), and oxidized‐LDL (35.7%, P = 0.03). There was a non‐significant increase in plasma cGMP (P = 0.13) on atorvastatin. FMD and GTNMD increased significantly on atorvastatin (FMD: atorvastatin +1.8 ± 0.4%; placebo +0.2 ± 0.4%, P = 0.007); (GTNMD: atorvastatin +1.3 ± 0.9%; placebo −1.2 ± 0.6%, P = 0.04). An increase in cGMP was independently correlated with an increase in FMD on atorvastatin (adjusted R2 0.41, P = 0.02).

Conclusion  Atorvastatin improves endothelium‐dependent and independent vasodilator function of the brachial artery in Type 1 diabetes mellitus patients with microalbuminuria. This may relate to pleiotropic effects of statins, in particular reduced oxidative stress and increased availability of nitric oxide.
The J‐shape effect of alcohol intake on the risk of developing acute coronary syndromes in diabetic subjects: the CARDIO2000 II Study
Authors: Pitsavos C. , Makrilakis K. , Panagiotakos D. B. , Chrysohoou C. , Ioannidis I. , Dimosthenopoulos C. , Stefanadis C. , Katsilambros N.
Published: February 2005

Aims  To identify the threshold of alcohol consumption above which the balance of risk and benefit becomes adverse in diabetic subjects.

Methods  We studied demographic, lifestyle, dietary and clinical information in 216 hospitalized diabetic patients (171 men, 63 ± 9 years old, 45 women, 67 ± 5 years old) with a first event of an acute coronary syndrome (ACS) and 196 frequency matched (age–sex) diabetic controls, without any clinical evidence of coronary heart disease. Alcohol consumption was quantified and a measure for the comparisons was predetermined to be a wine glass (100 ml of wine, 12 g of ethanol) and its alcohol equivalents.

Results  Alcohol consumption was associated with an age‐adjusted J‐shape relationship with total cholesterol, blood pressure and smoking (all P < 0.001). A J‐shape association was also found between alcohol intake and the risk of ACS (OR = 2.54–2.43 × (alcohol intake) + 0.80 × (alcohol intake)2, R2 = 0.96, P < 0.001), adjusted for several risk factors and interactions between alcohol intake and smoking status, job and familial stress, and low income. In particular, low alcohol consumption (< 12 g/day) was associated with a 47% (OR = 0.53, 95% CI 0.28–0.97) reduction of the prevalence of ACS, while a higher intake (12–24 and > 24 g/day) increased the prevalence by 2.7‐fold (OR = 2.72, 95% CI 1.39–5.38) and 5.4‐fold (OR = 5.44, 95% CI 1.21–24.55), respectively.

Conclusions  Alcohol intake is a significant predictor of coronary events. Low‐to‐moderate intake seems to be associated with a reduction in the prevalence of ACS in diabetes, whereas higher consumption is associated with an increase in lipids and blood pressure levels, and also the risk of developing ACS.
The annual incidence of diabetic complications in a population of patients with Type 1 and Type 2 diabetes
Authors: McAlpine R. R. , Morris A. D. , Emslie‐Smith A. , James P. , Evans J. M. M.
Published: February 2005

Aim  The DARTS diabetes register was used to determine incidence rates of diabetes and related complications in 1997.

Methods  The diabetes register records detailed clinical information for all patients diagnosed with diabetes in Tayside, Scotland. The study population included patients who were alive and registered with a Tayside GP for the duration of 1997 or who died in Tayside during this time. Patients who had diabetes prior to 1997, those who developed diabetes in 1997, and those who developed diabetic complications in 1997, were identified.

Results  In the Tayside population of 385 774 at the start of 1997, there were 942 and 6632 patients with Type 1 and Type 2 diabetes, with a further 29 and 744 patients diagnosed in 1997. The incidence rates (with 95% confidence intervals) of diabetic complications per 1000 patients with Type 1 and Type 2 diabetes, respectively, were: angina 8.8 (4.5–17.3) and 38.4 (33.4–44.2); myocardial infarction 8.6 (4.4–16.9) and 21.9 (18.4–25.9); cerebrovascular accident 1.1 (0.3–6.0) and 14.2 (11.6–17.5); lower extremity amputation 3.2 (1.2–9.4) and 3.1 (2.1–4.8); peripheral vascular disease 5.5 (2.4–12.8) and 13.6 (11.0–16.8); registered blindness 1.1 (0.3–5.9) and 1.6 (0.9–2.9); end‐stage renal failure 6.4 (3.0–13.8) and 5.0 (3.6–7.0). Mortality was 14.6 per 1000 (9.6–25.7) in Type 1 diabetes and 50.0 per 1000 (45.1–55.3) in Type 2 diabetes.

Conclusion  This study provides baseline figures for rates of diabetic complications for Type 1 and Type 2 diabetes, and confirms the increased burden of macrovascular disease in Type 2 diabetes.
Alcohol consumption and other risk factors for self‐reported diabetes among middle‐aged Japanese: a population‐based prospective study in the JPHC study cohort I
Authors: Waki K. , Noda M. , Sasaki S. , Matsumura Y. , Takahashi Y. , Isogawa A. , Ohashi Y. , Kadowaki T. , Tsugane S. ,   for the JPHC Study Group
Published: February 2005

Aims  Few prospective studies have examined the relationship between lifestyle characteristics and the incidence of diabetes mellitus in an Asian general population. This study was undertaken to evaluate the risk factors for Type 2 diabetes in a population‐based prospective study of middle‐aged Japanese.

Methods  We investigated 12 913 men and 15 980 women, aged 40–59 years at baseline (year 0), who participated in the Japan Public Health Center‐based prospective study on cancer and cardiovascular diseases (JPHC Study) Cohort I. The participants were followed for up to 10 years. Incident cases of diabetes were identified by self‐reporting of a physician's diagnosis on two questionnaires sent to each participant, one at year 5 and the second at year 10.

Results  During the 10‐year follow‐up, 703 men and 482 women reported newly diagnosed diabetes. Age, body mass index (BMI), family history of diabetes and cigarette smoking were independent risk factors in both genders by multivariate analysis. Among men with a BMI ≤ 22 kg/m2, a significant positive association was observed between the diabetes incidence and moderate (23.0 < 46.0 g/day) to high (> 46.0 g/day) alcohol consumption, odds ratio 1.91 (95% CI, 1.05–3.46) and 2.89 (1.63–5.11), respectively. Among men with a BMI > 22 kg/m2, a small non‐significant increase in odds ratio was observed with alcohol consumption.

Conclusions  Established risk factors for diabetes in western populations were also identified as predictors of the disease among Japanese. Moderate to high alcohol consumption was positively associated with the incidence of diabetes in Japanese lean (BMI ≤ 22 kg/m2) men.
Pharmacokinetic profiles of biphasic insulin aspart 30/70 and 70/30 in patients with Type 1 diabetes: a randomized double‐blinded crossover study
Authors: Chen J.‐W. , Lauritzen T. , Christiansen J. J. , Jensen L. H. , Clausen W. H. O. , Christiansen J. S.
Published: February 2005

Aims  To compare pharmacokinetic characteristics of two biphasic insulin aspart (BIAsp) formulations: BIAsp30 and BIAsp70 (30% and 70%, respectively, of fast‐acting insulin aspart) during 15 days of multiple dosing (thrice daily).

Methods  A total of 22 patients with Type 1 diabetes (nine women, 13 men) aged 41.4 ± 9.9 years (mean ± sd) with a diabetes duration of 18.9 (2.3–40.3) years (median and range) completed the randomized, double‐blinded, two‐period crossover study. On day 1 and day 15 of each treatment period, 24‐h serum insulin and glucose profiles were evaluated. Total area under the insulin aspart concentration–time curve (AUC(0−24 h)), AUC after dinner administration stratified into early (AUCdinner(0−6 h)) and intermediate‐phase (AUCdinner(6−14 h)), maximum insulin concentration (Cmax), time to maximum insulin concentration (Tmax) after each meal were recorded.

Results  On day 15 BIAsp70 was associated with a shorter Tmax, and more than 40% elevated Cmax. Comparing with BIAsp30, AUC(0−24 h) and AUCdinner(0−6 h) were increased by 25% and 28%, respectively, but AUCdinner (6−14 h) was markedly lower for BIAsp70 [BIAsp30/BIAsp70: 1.9; 95% CI (1.42, 2.55)]. Similar findings were also observed on day 1. The fasting or pre‐meal serum insulin levels on day 15 tended to be higher with BIAsp30, but the differences were not statistically significant.

Conclusions  The pharmacokinetic properties of BIAsp30 and 70 remain constant during 2 weeks of daily administration in patients with Type 1 diabetes. In comparison with BIAsp30, the administration of BIAsp70 results in a shorter time to and larger maximum insulin aspart concentration. Furthermore, total and early post‐dinner insulin AUC were greater, whereas late‐phase insulin exposure was lower with BIAsp70.
Plasma leptin concentration in patients with Type 2 diabetes: relationship to cardiovascular disease risk factors and insulin resistance
Authors: Abdella N. A. , Mojiminiyi O. A. , Moussa M. A. , Zaki M. , Al Mohammedi H. , Al Ozairi E. S. S. , Al Jebely S.
Published: February 2005

Aims  The aim of this study was to evaluate the relationship of obesity, leptin, insulin resistance and C‐reactive protein (CRP) with coronary heart disease (CHD) risk factors in patients with Type 2 diabetes mellitus (DM) with CHD compared with those with Type 2 DM without CHD.

Methods  Leptin, CRP (high sensitivity assay), fasting plasma insulin, glucose, HbA1c and full lipid profile were determined in 58 Type 2 diabetic patients with CHD and 87 Type 2 DM patients without CHD. Results were compared between those with and without CHD. Univariate correlation as well as logistic regression analyses were used to relate these markers with traditional CHD risk factors.

Results  Leptin showed significant correlations with BMI (r = 0.59; P ≤ 0.0001), waist circumference (r = 0.45; P < 0.0001), CRP (r = 0.36; P < 0.0001), and fasting insulin (r = 0.53; P < 0.0001) as well as with systolic (r = 0.23; P = 0.007) and diastolic (r = 0.23; P = 0.007) blood pressure. However, when those with and without CHD were compared only age (P < 0.0001), duration of diabetes (P < 0.001) and degree of microalbuminuria (P = 0.02) were significantly higher in patients with CHD. Leptin (P = 0.49), CRP (P = 0.19) and lipid parameters were not significantly different between the two groups.

Conclusion  Our study confirms a relationship between leptin and CRP with CHD risk factors. The lack of significant difference when patients with and without CHD are compared may be due to the potential confounding effects of treatment with aspirin and statins.
A comparison of urinary albumin excretion rate and microalbuminuria in various glucose tolerance subjects
Authors: Wang XL. , Lu JM. , Pan CY. , Tian H. , Li CL.
Published: February 2005

Aims  To investigate the difference of urinary albumin excretion rate (UAER) and microalbuminuria (MAU) in various glucose tolerance subjects, especially between isolated‐impaired glucose tolerance subjects and isolated‐impaired fasting glycaemia subjects.

Methods  A total of 2934 subjects were divided into five groups with various glucose tolerances, based on a 75‐g oral glucose tolerance test. Microalbuminuria was defined when urinary albumin excretion rate was between 20 and 200 µg/min.

Results  (i) The UAER in the newly diagnosed Type 2 diabetes mellitus group, impaired glucose tolerance/impaired fasting glycaemia group and isolated‐impaired glucose tolerance group were all higher than that in the isolated‐impaired fasting glycaemia group and normal glucose tolerance group, but it was comparable between isolated‐impaired fasting glycemia group and normal glucose tolerance group. The prevalence of MAU and the odds ratio for MAU with adjustment for age and sex in various glucose tolerance groups showed the same trend as the UAER. (ii) After adjusting for age and sex, there is a significant association between logUAER and independent risk factors (partial correlation coefficients: r = 0.26 for 2‐h post‐challenge blood glucose, r = 0.26 for systolic blood pressure, r = 0.27 for diastolic blood pressure, r = 0.27 for body mass index and r = −0.13 for high density lipoprotein‐cholesterol, all P < 0.001). The risks for MAU were 2‐h post‐challenge blood glucose, body mass index and diastolic blood pressure, while high density lipoprotein‐cholesterol was protective.

Conclusions  The urinary albumin excretion rate and prevalence of microalbuminuria were higher in isolated‐impaired glucose tolerance subjects than those in isolated‐impaired fasting glycaemia subjects. At early abnormal glucose tolerance stage, the increasing post‐challenge glycaemia might be a more important risk factor for urinary albumin excretion rate and microalbuminuria than increasing fasting glycaemia.
Hepatitis C virus infection‐related Type 1 diabetes mellitus
Authors: Chen L.‐K. , Chou Y.‐C. , Tsai S.‐T. , Hwang S.‐J. , Lee S.‐D.
Published: February 2005

Background  Hepatitis C virus (HCV) has been associated with Type 2 diabetes mellitus, and many other viral infections have been associated with Type 1 diabetes mellitus (Type 1 DM). An association between HCV and Type 1 DM, however, has never been reported. We report the case of a 66‐year‐old man who developed Type 1 DM 1 year after a blood transfusion‐related HCV infection. Testing of serum specimens obtained in the weeks following blood transfusion demonstrated evidence of both acute HCV infection and development of Type 1 DM‐related autoantibodies.

Case report  A 66‐year‐old Taiwanese male received blood transfusions during coronary artery bypass surgery in 1987. Serum specimens, obtained as part of a study on post‐transfusion hepatitis, demonstrated that the patient had no evidence of hepatitis C prior to transfusion, but developed acute HCV infection after transfusion. One year later, the patient, who had no personal or family history of diabetes, presented with diabetic ketoacidosis, and tests for C‐peptide confirmed that he had Type 1 DM. Testing of pre‐ and post‐operative serum specimens demonstrated that the patient developed positive tests for islet cell and glutamic acid decarboxylase antibodies 4 weeks after transfusion, concurrent with the development of acute HCV infection.

Conclusions  The simultaneous development of HCV infection and diabetes‐related autoantibodies suggest a relationship between HCV and Type 1 DM.
Affective and anxiety disorders in a German sample of diabetic patients: prevalence, comorbidity and risk factors
Authors: Hermanns N. , Kulzer B. , Krichbaum M. , Kubiak T. , Haak T.
Published: February 2005

Aims  The aims of this study were to examine (1) the prevalence of clinical and subclinical anxiety and affective disorders in a sample of diabetic patients attending a secondary care clinic in Germany and (2) risk factors associated with the occurrence of these disorders.

Methods  Four hundred and twenty diabetic patients (36.9% Type 1; 24.7% Type 2; 38.4% Type 2 with insulin) participated in a questionnaire‐based screening survey. Those who screened positive received a diagnostic interview.

Results  Prevalence of clinical affective disorders was 12.6%, with an additional 18.8% of patients reporting depressive symptoms without fulfilling all criteria for a clinical affective disorder. The prevalence of anxiety disorders was 5.9%, with an additional 19.3% of patients reporting some anxiety symptoms. The comorbidity rate of affective and anxiety disorders was 1.8%, whereas 21.4% of the diabetic patients reported elevated affective as well as anxiety symptomatology. Logistic regression established demographic variables such as age, female gender and living alone as well as diabetes‐specific parameters such as insulin treatment in Type 2 diabetes, hypoglycaemia problems and poor glycaemic control as risk factors for affective disorders. For anxiety symptoms female gender, younger age and Type 2 diabetes were significant independent variables.

Conclusion  The prevalence of affective disorders in diabetic patients was twofold higher than in the non‐diabetic population, whereas prevalence for anxiety disorders was not increased. Analysis of risk factors can facilitate the identification of patients who are at a greater risk for these disorders.
Caries risk assessment as a predictor of metabolic control in young Type 1 diabetics
Authors: Twetman S. , Petersson G. H. , Bratthall D.
Published: February 2005

Aims  To investigate the relationship between caries risk and glucosylated haemoglobin and to evaluate the use of a computerized caries risk assessment program as a predictor of metabolic control in schoolchildren with Type 1 diabetes mellitus.

Methods  The material consisted of 64 young Type 1 diabetes mellitus patients (8–16 years) attending an outpatient paediatric clinic. Within 2 weeks after the onset of diabetes, a caries risk assessment was carried out with the aid of a computer‐based program (Cariogram) and data on the level of metabolic control were collected from the medical records at the 3‐year check‐up. Caries increment was registered at recall clinical examinations.

Results  A statistically significant positive relationship between caries risk and metabolic control was found (r = 0.51; P < 0.01), with a sevenfold increased risk of impaired metabolic control after 3 years in those assessed with high caries risk at onset (OR 7.3; P < 0.01). When the Cariogram was used as a predictor for the metabolic state of the disease, the sensitivity and specificity was 75% and 71%, respectively. The negative predictive value was 91%.

Conclusions  Our data suggested that a caries risk assessment at the diagnosis of diabetes mellitus in children may be a good indicator of overall health care that can provide useful prognostic information on the level of metabolic control after 3 years.
An intensified lifestyle intervention programme may be superior to insulin treatment in poorly controlled Type 2 diabetic patients on oral hypoglycaemic agents: results of a feasibility study
Authors: Aas A. M. , Bergstad I. , Thorsby P. M. , Johannesen Ø. , Solberg M. , Birkeland K. I.
Published: February 2005

Aims  The aims of this study were to assess whether, in Type 2 diabetic patients with inadequate glycaemic control on oral hypoglycaemic agents (OHA), a lifestyle intervention programme based on exercise and diet counselling (i) was as effective as insulin treatment in controlling blood glucose, and (ii) could prevent the weight gain usually accompanying the introduction of insulin treatment.

Methods  Thirty‐eight Type 2 diabetic subjects treated with OHA, HbA1c 8–10.5% and body mass index (BMI) 26–40 kg/m2, were randomized to the following treatments: (i) lifestyle intervention (L), (ii) lifestyle intervention + insulin treatment (L+I) and (iii) insulin treatment alone (I).

Results  There was a reduction in HbA1c of −1.2 (interquartile range 1.0), −1.0 (1.7) and −1.5 (2.5)% in group L, L+I and I, respectively, and all treatment groups achieved beneficial changes in blood lipid variables. There was no significant difference between the groups in the change observed in levels of HbA1c between start and 12 months of treatment (P = 0.74). There was a significant difference in weight changes between groups (P < 0.01): group L reduced weight by median −3.0 (4.0) kg, groups L+I and I increased weight by 3.5 (3.4) and 4.9 (6.9) kg, respectively.

Conclusions  Lifestyle intervention was as effective as insulin treatment in improving glycaemic control in poorly controlled subjects with Type 2 diabetes, and resulted in weight loss during the intervention year. However, glycaemic control deteriorated and body weight increased in the lifestyle intervention group 1 year after the intervention stopped.
Low‐dose metformin improves hyperglycaemia related to myotonic dystrophy
Authors: Kouki T. , Takasu N. , Nakachi A. , Tamanaha T. , Komiya I. , Tawata M.
Published: February 2005

Background  One of the clinical features of myotonic dystrophy is insulin resistance with non‐obese diabetes mellitus (DM). Recently, the mechanism of insulin resistance in patients with myotonic dystrophy was revealed. The optimal treatment of DM with myotonic dystrophy has not been established. We report the effect of metformin in a patient with myotonic dystrophy without obesity.

Case report  A 58‐year‐old woman (BMI = 22.1 kg/m2) with myotonic dystrophy and DM was followed at our clinic. She had been treated with glimepiride for DM for the last 6 months, without achieving good control (HbA1c 9.3%). She was admitted with congestive heart failure and cholecystitis. She was treated with diuretics, antibiotics and insulin. As her blood glucose fell, we discontinued insulin and started glimepiride, but her glycaemic control had worsened. We started metformin instead of glimepiride. After 4 weeks of metformin, HbA1c was decreased to 7.4%, while HOMA‐IR during glimepiride treatment was 4.9, and 3.7 with metformin. Three months later, HbA1c was maintained (7.5%).

Conclusion  It is important to choose the optimal treatment for DM in myotonic dystrophy, because the patients have hyperinsulinemia caused by specific mechanism and could not reduce the insulin resistance. Metformin improved hyperglycemia through increased insulin‐independent glucose uptake in peripheral muscle. We believe metformin is the optimal agent for these patients.
Salt – its role in meat products and the industry's action plan to reduce it
Authors: Matthews K. , Strong M.
Published: February 2005

Summary  The food industry is currently under pressure from the Food Standards Agency (FSA) to deliver reductions in the salt intake of the population through the introduction of lower salt levels in processed foods (Gilbert & Heisler 2004 in same issue). Government research indicates that meat and meat products as a category are the second largest contributor to dietary salt after cereal products. This use of a combined category of ‘meat and meat products’ is misleading, as carcase meat is naturally low in sodium and therefore salt. Salt is added to meat products for a variety of technical reasons, including microbiological safety. There is evidence that consumers are confused about the difference between the terms ‘sodium’ and ‘salt’. Analysis of products for labelling purposes therefore requires careful consideration to ensure that misleading information is not presented. While the debate about the role of salt in blood pressure control will no doubt continue, the British meat industry has committed to reducing the salt, or more specifically sodium, content of its products. To this end an action plan for sodium reduction in meat products has been developed which focuses on those products with the highest sodium contents and encourages producers to seek opportunities to reduce the sodium content of all meat products.
A review of the Food Standards Agency's Optimal Nutrition Research Programme (N05)
Authors: Ashwell M.
Published: February 2005

Summary  The Food Standards Agency's Optimal Nutrition Research Programme (N05) has been in existence since 1993 and a review was undertaken of its achievements over the last 5 years in order to determine its future direction. An independent panel of experts agreed that the Programme as a whole represented a sustained effort and has resulted in an excellent body of nutrition research within the UK. The Programme is large and mainly covers work on micronutrient status (i.e. markers of exposure to dietary intake and functional markers) and bioavailability of micronutrients. It also covers projects on the effect of several nutrients on bone health, cognitive function and life‐course events. With respect to these health outcomes, the Programme has expanded beyond its original remit for research on micronutrients. It now covers aspects of bioavailability and function of macronutrients and other bioactive dietary factors, such as n‐3 fatty acids. However, the experts agreed there is no advantage to be gained in re‐focusing onto micronutrients or for splitting the Programme into smaller units. Priorities were re‐confirmed and suggestions were made for future directions of the Programme.
Dyslexia and oral reading errors
Authors: Singleton Chris
Published: February 2005

Thomson was the first of very few researchers to have studied oral reading errors as a means of addressing the question: Are dyslexic readers different to other readers? Using theNeale Analysis of Reading Abilityand Goodman's taxonomy of oral reading errors, Thomson concluded that dyslexic readersaredifferent, but he found that they do not resemble beginning readers. Thomson's study and his use of miscue analysis is re‐evaluated, both in relation to the educational and political climate of the time – which was hostile to the concept of dyslexia – and in the light of research and social developments since then. The study of oral reading still has value today, both for the teacher and the researcher, provided its limitations as a technique are fully appreciated.
Picture naming and developmental reading disorders
Authors: Nation Kate
Published: February 2005

One of the most frequently cited papers from the twenty‐five years of the Journal of Research in Reading is ‘Object‐naming deficits in developmental dyslexia’ by Maggie Snowling, Bente van Wagtendonk and Carolyn Stafford, published in 1988. Looking back at the paper some sixteen years after its publication, it is striking to note how topical some of the issues discussed by Snowling and colleagues remain. This commentary revisits some of these issues and examines how subsequent research has consolidated and extended Snowling et al.'s findings and conclusions.
The epidemiology of preterm labour
Authors: Steer Philip
Published: February 2005

Although the definition of preterm birth is birth before 37 completed weeks, the major transition in terms of needing special care occurs between 34 and 37 weeks. The Homo sapiens neonate is born much more immature than other anthropoid species, perhaps because earlier birth has evolved to avoid the large head of the human fetus becoming impacted in the small pelvis of the mother, who has become adapted to a bipedal gait. The main burden of preterm birth exists in developing countries. There are no accurate recent worldwide data, but estimates of preterm birth rates range from 5% in developed countries to 25% in developing countries. The preterm delivery rate has been relatively stable at 5–10% in developed countries for many years. The North Thames database of 517,381 pregnancies demonstrates significant ethnic variation in preterm birth rates, with higher rates in black women. This is associated with an accelerated rate of maturity in the black fetus and neonate, with correspondingly lower gestation‐specific neonatal mortality rates below 38 weeks, and higher at 38 weeks of gestation and beyond. Ethnic differences can explain only a very small proportion of global preterm births. The greatest aetiological factor worldwide is infection, mainly due to malaria and HIV. In developed countries, iatrogenic delivery is responsible for almost half of the births between 28 and 35 weeks; hypertension and pre‐eclampsia are the major pathologies. Other factors include multiple pregnancy, intrauterine growth restriction, maternal stress and heavy physical work.
The economic consequences of preterm birth duringthe first 10 years of life
Authors: Petrou Stavros
Published: February 2005

Objective  To examine the association between gestational age at the time of birth and long‐term use and cost of hospital inpatient services.

Design  Multi‐level modelling of the hospital service utilisation and cost profile of each child born in hospital during 1978–1988 in two areas covered by the Oxford Record Linkage Study.

Setting  Oxfordshire and West Berkshire.

Population  117,212 children divided into four subgroups by gestational age at birth: <28 weeks, 28–31 weeks, 32–36 weeks, 37 weeks or greater.

Main outcome measures  Number and duration of hospital admissions during the first 10 years of life. Costs, expressed in £ sterling and valued at 1998–1999 prices, of hospital inpatient services.

Results  The cumulative cost of hospital inpatient admissions incurred during the first 10 years of life, including the initial birth admission, averaged £17,819.94 [£22,322.87] for children born at <28 weeks gestation, £17,751.00 [£19,055.53] for children born at 28–31 weeks gestation, £5,376.39 [£7,393.78] for children born at 32–36 weeks gestation, and £1,658.63 [£3,409.14] for children born at 37 weeks gestation or greater. The adjusted number of hospital inpatient admissions, inpatient days and costs, respectively, over the first 10 years of life was 130%, 77% and 443% higher for children born at <28 weeks gestation than for children born at term.

Conclusion  The adverse sequelae of preterm birth are likely to have considerable long‐term economic consequences for the health services and for society as a whole.
Role of matrix metalloproteinases in preterm labour
Authors: Vadillo‐Ortega Felipe , Estrada‐Gutiérrez Guadalupe
Published: February 2005

Extracellular matrix homeostasis is a key process in the maintenance of the tensile strength of the amniochorion. This tensile strength guarantees the role of the membranes as a physical and functional boundary for the fetus during human pregnancy. Pathological rupture of these structures before 37 completed weeks of gestation is known as preterm prelabour rupture of the membranes (PPROM) and it is a major cause of spontaneous preterm labour and preterm birth. A mechanism involving the activation of matrix metalloproteinases (MMP)‐9, a 92‐kDa type IV collagenase, as an essential mediator of tissue damage is under investigation. The proposed mechanism involves the abnormal expression and activity of MMP‐9 with subsequent connective tissue degradation taking place at a time that does not synchronise with other events of labour. The local physiological signal by amniochorion cells to induce MMP‐9 expression is not known, but bacterial products and/or the proinflammatory cytokines, IL‐1β and TNF‐α, as paracrine or autocrine signals may trigger these processes in pregnancies complicated with intra‐amniotic infection. These signalling pathways indicate complex cooperative and bidirectional communications between amnion and choriodecidua in response to bacterial products, which include intermembranous cytokine traffic and signalling between tissues. Products secreted in culture by amniochorion and choriodecidual leucocytes, obtained from women who delivered following normal labour in the absence of infection, condition a specific microenvironment that induces collagen degradation in fetal membranes. Further characterisation of the role of choriodecidual leucocytes in the control of extracellular matrix degradation in amniochorion is currently under way.
Changes in the cervical competence in preterm labour
Authors: Facchinetti Fabio , Venturini Paolo , Blasi Immacolata , Giannella Luca
Published: February 2005

Cervical competence is a key function in normal and abnormal labour. Remodelling of the cervical structure, by reorientation and changes in the integrity of collagen fibres by an alteration in the content of water, proteoglycans and hyaluronic acid, takes place before parturition. Such morphological changes have been associated with the activation of several biochemical pathways, sharing those of an apyretic, proinflammatory reaction, including the inducible isoform of the nitric oxide synthase (NOS). Nitric oxide (NO) is believed to be the final mediator in the mechanisms that allow ripening of the cervix. A reduction of NO activity in the uterus, together with its activation in the cervix, is hypothesised to be a facilitating factor in human parturition. The local application of NO donors in both animals and humans induces ultrastructural changes similar to those occurring during physiological cervical maturation. NO donors have proven to be clinically effective in facilitating first trimester dilation and curettage. Preliminary data also suggest that in women presenting with threatening preterm labour, there is increased activity of NO in the cervix, which is associated with shortening. A complex interaction between cytokines, prostaglandins (PGs) and NO is the key biochemical pathway accounting for the preterm ripening of the cervix.
Primary predictors of preterm labour
Authors: Goffinet François
Published: February 2005

Spontaneous preterm birth accounts for 60% of all preterm births in developed countries. With the increase in multiple pregnancies, induced preterm birth and the progress in neonatal care for extremely preterm neonates, spontaneous preterm birth for singleton pregnancies in developed countries has probably decreased over the past 30 years. This decrease is likely to be related to better prenatal care for all pregnant women because the recognition of primary risk factors in early or late pregnancy remains a basic part of prenatal care. The failure to distinguish between induced and spontaneous preterm labour in most population‐based studies makes it difficult to interpret results with respect to the primary predictors of preterm labour. Many such primary predictors of preterm labour have been used over the past 20–30 years. These include individual factors, socio‐economic factors, working conditions and obstetric and gynaecological history. Risk scores have been proposed in order to produce these data. Unfortunately, the predictive value of these scores, especially their specificity, is poor, mainly because all of these factors are indirect. We still cannot identify the mechanisms that lead to preterm labour and birth. New markers more directly related to preterm labour have recently been proposed, some of which relate to direct causes of preterm labour such as cervical ultrasound measurement, fetal fibronectin (FFN), salivary estriol, serum CRH and bacterial vaginosis. Several of these have predictive values, which are potentially useful for clinical practice. Nonetheless, pregnant women in developed countries are already closely monitored throughout pregnancy. Before proposing new screening tests to be applied systematically to all pregnant women, their advantages and drawbacks must be fully evaluated.
Nifedipine trials: effectiveness and safety aspects
Authors: van Geijn Herman P. , Lenglet Joris E. , Bolte Annemieke C.
Published: February 2005

Nifedipine (Adalat) is marketed as an anti‐hypertensive agent. Nifedipine inhibits voltage‐dependent L‐type calcium channels, which leads to vascular (and other) smooth muscle relaxation and negative inotropic and chronotropic effects on the heart. Vasodilation, followed by a baroreceptor‐mediated increase in sympathetic tone then results in indirect cardiostimulation. Nifedipine was introduced as a tocolytic agent at a time when β‐agonists and magnesium sulphate dominated the arena for the prevention of preterm birth. The oral administration route, the availability of immediate and slow‐release preparations, the low incidence of (mild) side effects, and its limited costs explain the attraction to this medication from the obstetric field and its rapid and widespread distribution. Currently, over 40 studies have been published on nifedipine's tocolytic effectiveness, including seven meta‐analyses. The quality of the studies suffers particularly from performance bias because the majority of them failed to ensure adequate blinding to treatment both for providers and patients. Concerns about other methodological flaws include measurements, outcome assessment and attrition bias. In particular, the safety aspects of nifedipine for tocolysis have been underassessed. Conclusions from the meta‐analyses, favouring the use of nifedipine as a tocolytic agent, are not supported by close examination of the data. The tocolytic effectiveness and ‘safety’ of nifedipine has been studied primarily in normal pregnancies. Based on its pharmacological properties, one should be cautious to administer nifedipine when the maternal cardiovascular condition is compromised, such as with intrauterine infection, twin pregnancy, maternal hypertension, cardiac disease, etc. Life‐threatening pulmonary oedema and/or cardiac failure are definite risks and have been reported. Under such circumstances, the baroreceptor‐mediated increase in sympathetic tone may not balance the cardiac‐depressant activity of nifedipine.
Frequently asked questions on tocolytics
Authors: Helmer Hanns
Published: February 2005

The majority of drugs that are used today for tocolysis have been developed for clinical conditions other than preterm labour. Obstetricians started to use these drugs as tocolytics because of their additional influence on uterine smooth muscle relaxation, accepting their cardiovascular (side) effects. Because the majority of these drugs are used off label, today's strict criteria to evaluate drugs for their predominant use in pregnancy have not been applied; therefore, we also lack sufficient peri‐ and neonatal follow up data for these drugs. This problem is compounded as our understanding of the regulation of myometrial smooth muscle contraction and relaxation is still incomplete.
Genetic factors in preterm birth—the future
Authors: Esplin M. Sean , Varner Michael W.
Published: February 2005

The genetic regulation of common biological functions has redundant control mechanisms, and it is unlikely that a single marker will ever be identified that will be both highly sensitive and specific. It is more likely that combinations of gene and/or protein markers, perhaps also combined with obstetric family histories, will be required to achieve the goal of a truly sensitive and specific screening profile for spontaneous preterm labour and preterm birth. The rapidly evolving disciplines of genomics and proteomics are now beginning to be applied to the study of spontaneous preterm labour and preterm birth. These techniques are able to measure multiple markers (in the thousands) in a biological sample and, given the likely presence of biological changes that precede by weeks or even months the clinical manifestations of the disease, are ideally suited to the evaluation of spontaneous preterm labour and preterm birth. Over the next few years, these technologies will hasten a deeper understanding of the pathophysiology of spontaneous preterm labour, discover novel target molecules and diagnostic biomarkers and ultimately aid in formulating more effective interventions to prevent preterm birth. Pharmacogenomics is another rapidly evolving discipline that holds great promise for the treatment and prevention of spontaneous preterm labour and preterm birth. Because spontaneous preterm labour is a final common pathway for multiple aetiologies, there remains no reason why any single therapy will work optimally for all women. As patient‐specific pharmacogenomic profiles are developed, it will be possible to develop patient‐specific treatment regimens. Beyond that, it may become possible to identify those women who are, or are not, destined to labour spontaneously and give birth remote from term and to institute patient‐specific preventive measures. Spontaneous preterm labour and preterm birth remains a syndrome, with a final common pathway for multiple aetiologies. As a result, no single explanation, marker or treatment is likely to be 100% sensitive, specific or successful. It is also clear, however, that there is a genetic predisposition in many cases of spontaneous preterm labour. Over the next few years, several recently developed diagnostic mechanisms, and others that have yet to evolve, will hold a greater potential than ever before to unlock the secrets of the genetic predisposition to spontaneous preterm labour and its underlying causes. An improved understanding of these mechanisms will allow clinicians to employ therapies that will be optimally effective for individual women and their unborn babies. Eventually, these advances could be applied to the presymptomatic prevention of spontaneous preterm labour. It is the intent of this manuscript to review the current status of these new technologies and disciplines and to speculate on their applications in the intermediate future.