bluuebunny/crossref_metadata_2025 huggingface dataset:
Generation and characterization of functional mutants in the translation initiation factor IF1 of Escherichia coli
Authors: Croitoru Victor , Bucheli‐Witschel Margarete , Hägg Peter , Abdulkarim Farhad , Isaksson Leif A.
Published: December 2004

Three protein factors IF1, IF2 and IF3 are involved in the initiation of translation in prokaryotes. No clear function has been assigned to the smallest of these three factors, IF1. Therefore, to investigate the role of this protein in the initiation process in Escherichia coli we have mutated the corresponding gene infA. Because IF1 is essential for cell viability and no mutant selection has so far been described, the infA gene in a plasmid was mutated by site‐directed mutagenesis in a strain with a chromosomal infA+ gene, followed by deletion of this infA+ gene. Using this approach, the six arginine residues of IF1 were altered to leucine or aspartate. Another set of plasmid‐encoded IF1 mutants with a cold‐sensitive phenotype was collected using localized random mutagenesis. All mutants with a mutated infA gene on a plasmid and a deletion of the chromosomal infA copy were viable, except for an R65D alteration. Differences in growth phenotypes of the mutants were observed in both minimal and rich media. Some of the mutated infA genes were successfully recombined into the chromosome thereby replacing the wild‐type infA+ allele. Several of these recombinants showed reduced growth rate and a partial cold‐sensitive phenotype. This paper presents a collection of IF1 mutants designed for in vivo and in vitro studies on the function of IF1.
Different associational and conformational behaviors between the second and third repeat fragments in the tau microtubule‐binding domain
Authors: Minoura Katsuhiko , Yao Tian‐Ming , Tomoo Koji , Sumida Miho , Sasaki Masahiro , Taniguchi Taizo , Ishida Toshimasa
Published: December 2004

The third repeat fragment (R3) in the four‐repeat microtubule‐binding domain of the water‐soluble tau protein has been considered to play an essential role in the protein's filamentous assembly. To clarify the associational and conformational features that differentiate R3 from the second repeat, R2, the heparin‐induced assembly profiles of these peptide fragments were monitored by the thioflavin fluorescence method and electron microscopy. The trifluoroethanol‐induced reversible conformational change from a random structure to an α‐helical structure, in an aqueous solution, was monitored by CD measurement, and the structure of R2 in trifluoroethanol solution was analyzed by a combination of two‐dimensional 1H‐NMR measurements and molecular modeling calculations to facilitate comparison with the structure of R3. The speed of R3 assembly was remarkably faster than that of R2, in spite of their similar amino acid sequences. The averaged NMR conformers of R2 exhibited the whole‐spanning α‐helical structure. Similar features observed in R2 and R3 conformers in trifluoroethanol were that the Leu10–Leu20/Lys20 sequence takes a helical structure with the amphipathic‐like distribution of the respective side‐chains, whereas the C‐terminal moieties are both flexible. In contrast, a notable difference was observed at the N‐terminal Val1–Lys6 sequence, namely, a helical conformation for R2 and an extended conformation for R3. These conformational behaviors would be associated with the different self‐aggregation speeds and seeding reactions between R2 and R3.
Ontogenic emergence and localization of larval skin antigen molecule recognized by adult T cells of Xenopus laevis: Regulation by thyroid hormone during metamorphosis
Authors: Watanabe Mikihito , Ohshima Madoka , Morohashi Miyuki , Maéno Mitsugu , Izutsu Yumi
Published: December 2004

Results from previous studies using an inbred strain of Xenopus laevis have led to the proposition that metamorphosis includes the events by which the newly differentiating adult immune system, including T lymphocytes, recognizes and eliminates larval skin cells as ‘non‐self’. More recently, a larval antigen targeted by adult T cells was identified as a 59 kDa protein with a specific peptide sequence. Using antisera directed against the larval antigen and the peptide, immunohistochemistry and western blotting were done to examine expression of the 59 kDa larval antigen in the skin during larval and metamorphic periods. There was no expression before Nieuwkoop and Faber stage 53. Expression was first seen at the beginning of metamorphic stage 54, when hind limbs appear, and increased thereafter, in apical and skein cells of both trunk and tail regions. In the trunk region, expression started to decrease at stage 58, until it completely disappeared at stage 62 (metamorphic climax). In the tail skin, however, expression persisted throughout the metamorphic stages. Treatment of larvae with thyroid hormone (TH) resulted in repression of expression of the 59 kDa molecule in a dose‐dependent manner. Downregulation occurred earlier in the trunk than in the tail skin. These results suggest involvement in metamorphic events of an immunological mechanism: differential expression of the larval antigen in the trunk and tail skin cells due to their differing concentration of TH results in the tail, but not the trunk skin, being selectively attacked by the newly differentiating adult‐type immune system.
Visualization of palisade veins in esophageal varices by endoscopic color Doppler ultrasonography
Authors: SATO TAKAHIRO , YAMAZAKI KATSU , TOYOTA JOUJI , KARINO YOSHIYASU , OHMURA TAKUMI , KUWATA YASUAKI , AKAIKE JUN , SUGA TOSHIHIRO
Published: December 2004

Background:  Endoscopic color Doppler ultrasonography (ECDUS) is a useful modality for obtaining color flow images of esophageal varices. Levovist is a microbubble echo‐enhancing agent that improves Doppler ultrasound examination. This study is designed to evaluate the usefulness of ECDUS using Levovist in diagnosing palisade veins of esophageal varices.

Methods:  The study involved 67 patients with esophageal varices using ECDUS. All 67 patients received Levovist intravenously at a concentration of 300 mg/mL. A 7.5‐mL dose of the contrast agent was injected at a slow infusion rate of 1 mL/min. We compared vessel images detected with precontrast with those detected by enhanced ECDUS.

Results:  Color flow images of palisade veins were obtained in 16 (23.9%) of the 67 patients with precontrast ECDUS. Vessel images of palisade veins were detected in 15 of 61 F2 type varices (24.6%) and in one of six F3 varices (16.7%). The color flows of these vessels showed a continuous wave on fast‐Fourier transform analysis. Sixteen palisade veins had velocities in the 3.3 cm/s−11.6 cm/s range. Color flow images of palisade veins were obtained in 27 (40.3%) of the 67 cases by enhanced ECDUS using Levovist. Palisade veins could be delineated after Levovist contrast in 11 patients who could not be detected on precontrast ECDUS. After Levovist contrast, color flow images detected with precontrast ECDUS were enhanced in all patients.

Conclusion:  Endoscopic color Doppler ultrasonography with Levovist contrast can improve the diagnostic quality of the palisade veins in esophageal varices.
Pancreatic stenting for the preservation of pancreatic function in chronic pancreatitis with stricture
Authors: UKITA TAKEO
Published: December 2004

Background:  Although many reports have documented pain relief achieved by pancreatic stenting, the effect of stenting on pancreatic function is less clear. In addition, the effects of stent caliber and patency have not been considered in most previous studies. Pain and pancreatic function after stenting of the main pancreatic duct (MPD) were examined.

Methods:  Records of 24 patients with chronic pancreatitis who had an MPD stricture treated with a 10‐Fr stent from June 1996 to June 2002 were reviewed. The average age was 57.0 ± 1 years, and the male : female ratio was 7 : 1. Eleven patients had diabetes mellitus. Stent patency, pancreatic pain and pancreatic endocrine and exocrine function were examined before stenting and 6 months after stenting. Stenting was continued for 1 year or more, with repeated stent exchange every 3 months.

Results:  The stent became occluded in 29% of cases, migration occurred in 15% of cases, and the 50% patency time was 125 days. Pancreatic pain was relieved by stenting in all cases. The diameter of the MPD, the Bentiromide test value, weight and body mass index were improved.

Conclusion:  Stenting relieves blockage of the main pancreatic duct and provides both pain relief and preservation of residual pancreatic function.
Influence of initial hyperglycaemia, weight and age on the blood glucose lowering efficacy and incidence of hypoglycaemic symptoms with a single‐tablet metformin–glibenclamide therapy (Glucovance®) in type 2 diabetes
Authors: Garber A. , Marre M. , Blonde L. , Allavoine T. , Howlett H. , Lehert P. , Cornes M.
Published: December 2004

Aim:  To evaluate the efficacy and incidence of hypoglycaemic symptoms associated with fixed combinations of metformin and glibenclamide (glyburide in the USA) formulated within a single tablet (tablet strengths 250 mg/1.25 mg, 500 mg/2.5 mg and 500 mg/5 mg), in comparison with metformin 500 mg and glibenclamide 2.5–5 mg monotherapy, in clinically important patient subgroups within the type 2 diabetic population.

Methods:  A total of 1856 patients from three randomized, double‐blind, multicentre, parallel‐group clinical trials were stratified at baseline according to HbA1C (< 8% or ≥ 8%), age (< 65 years or ≥ 65 years) and body mass index (BMI; < 28 kg/m2 or ≥ 28 kg/m2). The effects of study treatments on HbA1C and the incidence of hypoglycaemic symptoms were determined in each subgroup.

Results:  The combination treatments were more effective than either monotherapy irrespective of baseline HbA1C, age or BMI in each trial. Antihyperglycaemic effects were greater in patients with HbA1C ≥ 8% at baseline, especially with the combinations. The majority of hypoglycaemic symptoms with glibenclamide‐containing treatments occurred in patients with HbA1C < 8% at baseline. Neither age nor BMI had a marked effect on the efficacy of the combination treatments, and there was no increase in hypoglycaemic symptoms in older patients.

Conclusions:  Single‐tablet metformin–glibenclamide combination treatment is more effective than metformin or glibenclamide monotherapy, and is well tolerated in patients with hyperglycaemia inadequately controlled by diet and exercise or antidiabetic monotherapy, irrespective of their severity of hyperglycaemia at baseline, age or weight.
Polynesians: prone to obesity and Type 2 diabetes mellitus but not hyperinsulinaemia
Authors: Simmons D. , Thompson C. F. , Volklander D.
Published: December 2004

SUMMARY

Aims  To compare the extent of hyperinsulinaemia among New Zealand Europeans and Polynesians (an ethnic group at high risk of Type 2 diabetes mellitus).

Methods  A cross‐sectional survey from randomly selected households was conducted in inner urban South Auckland.

Subjects  were either European, Maori or Pacific Islands Polynesians aged 40–79 years and were screened for diabetes using a random blood glucose. Those with an elevated result, and 20% randomly selected from those with a normal screening result, were invited to a 75‐g glucose tolerance test. WHO criteria (1998) for diabetes were used

Results  In those aged 40–59 years, total prevalence of diabetes was 7.5 (6.2–9.0)% in Europeans but 21.1 (16.6–25.6)% among Maori and 25.0 (19.8–30.1)% among Pacific peoples; obesity (body mass index ≥ 31.0 kg/m2) was present in 26% Europeans, 63% Maori and 69% Pacific peoples. Non‐diabetic Polynesians were relatively hyperglycaemic and hyperinsulinaemic. After adjusting for the degree of obesity, Polynesians had similar insulin levels to Europeans.

Conclusions  These findings indicate that Polynesians are not intrinsically insulin resistant as a group, a prerequisite found in most other ethnic groups at high risk of Type 2 diabetes mellitus. The high prevalence of Type 2 diabetes in Polynesians could be the result of their high prevalence of obesity.
Association studies of variants in promoter and coding regions of beta‐cell ATP‐sensitive K‐channel genes SUR1 and Kir6.2 with Type 2 diabetes mellitus (UKPDS 53)
Authors: Gloyn A. L. , Hashim Y. , Ashcroft S. J. H. , Ashfield R. , Wiltshire S. , Turner R. C.
Published: December 2004

SUMMARY

Aims  The beta‐cell ATP‐sensitive potassium channel consists of two subunits, SUR1 and Kir6.2. Population association studies have shown that three variants in SUR1 and one in Kir6.2 are associated with Type 2 diabetes. These polymorphisms do not result in a functional change or affect splicing, suggesting that they could be in linkage disequilibrium with a pathogenic mutation. The present study aimed firstly to screen the promoter regions of SUR1 and Kir6.2 to determine whether mutations in linkage disequilibrium with the silent variants lie in regulatory regions, which might lead to changes in gene expression. Secondly, novel and previously described variants associated with Type 2 diabetes (SUR1 exon 16–3t, exon 18 T, and Kir6.2 E23K) were investigated in the UKPDS cohort.

Methods  The promoter sequences of both genes were screened by single‐stranded conformational polymorphism analysis for variants associated with Type 2 diabetes. The previously reported variants were evaluated in 364 Type 2 diabetic and 328 normoglycaemic control subjects.

Results  Two variants were detected in the SUR1 promoter, a three base insertion (caa) at −522 bp and a single base substitution at − 679 bp (c→g). Neither of the variants were associated with diabetes, nor were they in a sequence consensus region for transcription factors. No association with diabetes was observed for either SUR1 variant. However, in contrast, analysis of the Kir6.2 E23K variant showed that the KK homozygosity was more frequent in Type 2 diabetic than control subjects. Variants were not associated with clinical characteristics nor did they affect response to sulphonylurea therapy

Conclusion  There is no support at present for mutations in either Kir6.2 or SUR1 promoter sequences contributing to Type 2 diabetes. However, the minimal promoter region of SUR1 has yet to be investigated. The E23K variant of Kir6.2 is associated with Type 2 diabetes mellitus in the UKPDS cohort.
Use of alternative medicines in diabetes mellitus
Authors: Ryan E. A. , Pick M. E. , Marceau C.
Published: December 2004

Aims  Enormous advances have been made in medical care but more people are still using herbal or alternative remedies. In chronic conditions such as diabetes patients may turn to alternative remedies that have been purported to improve glycaemic control. This study surveyed diabetic and control subjects about their use of all prescribed medication, over‐the‐counter supplements, and alternative medications.

Methods  Subjects were prospectively contacted in person or by telephone. Five hundred and two diabetic subjects and 201 control subjects were asked to provide details about themselves, their diabetes (for the diabetic subjects) and their use of prescribed medication, over‐the‐counter supplements and alternative medications. Subjects were asked to rank their assessment of the effectiveness of each medication. Costs were calculated on a per month basis from average prices obtained from five alternative health stores and five chemist shops.

Results  Of the diabetic subjects, 78% were taking prescribed medication for their diabetes, 44% were taking over‐the‐counter supplements and 31% were taking alternative medications. Of the control subjects, 63% were taking prescribed medication, 51% were taking over‐the‐counter supplements, and 37% were taking alternative medications. Multivitamins, vitamin E, vitamin C, calcium and aspirin were the most commonly used over the counter supplements. Garlic, echinacea, herbal mixtures, glucosamine were the most commonly used alternative medications. Chromium was used only by diabetic subjects and then only rarely. Subjects rated the effectiveness of the alternative medications significantly lower than for prescribed medications but still thought them efficacious. Alternative medications purported to have some hypoglycaemic effect were little used by diabetic subjects. Diabetic subjects spent almost as much money on over‐the‐counter supplements and alternative medications together as they did on their diabetic medications.

Conclusions  One‐third of diabetic patients are taking alternative medications that they consider efficacious but this is no more than in the control group. The money spent on alternative and non‐prescription supplements nearly equals that spent on prescription medications. In view of the money spent in this area the time is past due to evaluate these remedies and to establish what merit they have.
Rosiglitazone in Type 2 diabetes mellitus: an evaluation in British Indo‐Asian patients
Authors: Barnett A. H. , Grant P. J. , Hitman G. A. , Mather H. , Pawa M. , Robertson L. , Trelfa A.
Published: December 2004

Aims To evaluate the effectiveness of rosiglitazone in reducing hyperglycaemia in patients with Type 2 diabetes mellitus (DM) of Indo‐Asian origin taking concurrent sulphonylurea therapy.

Methods A randomized, double‐blind, placebo‐controlled study of 26 weeks’ duration at 31 primary and secondary care centres in areas of the UK with a high Indo‐Asian population, including 177 patients aged 28–78 years. Rosiglitazone 8 mg/day or matching placebo was added to existing sulphonylurea therapy. The primary endpoint was change from baseline in glycosylated haemoglobin A1c (HbA1c) at week 26.

Results The mean changes in HbA1c were −1.16% with rosiglitazone (baseline 9.21%) and +0.26% with placebo (baseline 9.06%) (treatment difference P < 0.001; 95% confidence interval (CI) −1.81, −1.08). HbA1c fell below 8% in 55% and 19% of patients, respectively (treatment difference P < 0.001; 95% CI 0.22, 0.51). The greatest improvements occurred in patients whose glycaemic control was initially poor. Improvements in homeostasis model assessment of insulin sensitivity and pancreatic β‐cell function with rosiglitazone were not accompanied by a change in plasma insulin or C‐peptide after 26 weeks. Free fatty acids fell by 0.09 mmol/l with rosiglitazone and increased by 0.03 mmol/l with placebo (treatment difference P < 0.001; 95% CI −0.19, −0.07).

Conclusion Rosiglitazone improved insulin sensitivity, pancreatic β‐cell function, and glycaemic control in Indo‐Asian patients with Type 2 DM who are at greater risk of the complications of Type 2 DM than other ethnic groups.

Diabet. Med. 20, 387–393 (2003)
Proton magnetic resonance spectroscopy study of soleus muscle in non‐obese healthy and Type 2 diabetic Asian Northern Indian males: high intramyocellular lipid content correlates with excess body fat and abdominal obesity
Authors: Misra A. , Sinha S. , Kumar M. , Jagannathan N. R. , Pandey R. M.
Published: December 2004

Aims Intramyocellular lipids (IMCL) appears to be important in the pathogenesis of insulin resistance. Correlation of IMCL content of soleus muscle with insulin sensitivity has been reported in the Caucasian population. In the present study, IMCL content was estimated in the soleus muscle of both non‐obese healthy males and Type 2 diabetic males, and correlated with the anthropometric parameters, blood glucose, plasma lipids, and insulin resistance in Asian Indians from North India.

Methods Twenty males (Type 2 diabetes mellitus 10; healthy controls 10) with body mass index (BMI) ≤ 25 kg/m2 were recruited in the study. In both healthy and diabetic groups, five subjects had percentage body fat (%BF) ≤ 25, and other five subjects had percentage BF > 25. The following were assessed in all subjects: body composition, fasting blood glucose, lipid profile, insulin levels, insulin resistance by homeostasis model assessment, and proton magnetic resonance spectroscopy (1H MRS) study of the soleus muscle.

Results IMCL content was approximately two times higher in Type 2 diabetic males compared with healthy males (P < 0.05). Amongst healthy males, IMCL content was significantly higher (P < 0.05) in subjects with percentage BF > 25 compared with subjects with percentage BF ≤ 25. Similarly, IMCL content was high in subjects with waist–hip ratio (WHR) > 0.95 compared with subjects with WHR ≤ 0.95. In healthy males but not in diabetic males, positive significant correlation of IMCL content of soleus muscle was observed with waist circumference (r = 0.73, P < 0.05) and WHR (r = 0.71, P < 0.05). However, IMCL content did not correlate significantly to insulin resistance in both the groups.

Conclusions 1H MRS study of soleus muscle in a small sample of non‐obese Asian Indians showed higher IMCL content in Type 2 diabetics compared with healthy subjects. Non‐obese healthy male subjects having high percentage BF and WHR also had high IMCL content, and it significantly correlated to waist circumference and WHR. However, lack of relationship of IMCL content with insulin resistance in Asian Indians needs further study.

Diabet. Med. 20, 361–367 (2003)
Classifying diabetic foot surgery: toward a rational definition
Authors: Armstrong D. G. , Frykberg R. G.
Published: December 2004

The purpose of this manuscript was to describe a classification of diabetic foot surgery performed in the absence of critical limb ischaemia. The basis of this classification is centered on three fundamental variables which are present in the assessment of risk and indication: 1) the presence or absence of neuropathy (loss of protective sensation); 2) the presence or absence of an open wound; 3) the presence or absence of acute, limb‐threatening infection. The conceptual framework for this classification is to define distinct classes of surgery in an order of theoretically increasing risk for high‐level amputation. These classes include: Class I: Elective Diabetic Foot Surgery (procedures performed to treat a painful deformity in a patient without loss of protective sensation); Class II: Prophylactic (Procedure performed to reduce risk of ulceration or reulceration in person with loss of protective sensation but without open wound); Class III: Curative (Procedure performed to assist in healing open wound) and Class IV: Emergent (Procedure performed to limit progression of acute infection). The presence of critical ischaemia in any of these classes of surgery should prompt a vascular evaluation to consider a) the urgency of the procedure being considered and b) possible revascularization prior or temporally concomitant with the procedure. It is our hope that this system begins a dialogue amongst physicians and surgeons which can ultimately facilitate communication, enhance perspective, and improve care.
A randomized trial of insulin aspart with intensified basal NPH insulin supplementation in people with Type 1 diabetes
Authors: DeVries J. H. , Lindholm A. , Jacobsen J. L. , Heine R. J. , Home P. D. ,   The Tri‐Continental Insulin Aspart Study Group
Published: December 2004

Aims Insulin aspart has been shown to improve post‐prandial and overall glycaemic control in people with Type 1 diabetes. We hypothesized that insulin aspart with intensified basal NPH insulin supplementation would result in better overall glycaemic control than human regular insulin with standard basal NPH insulin.

Methods The trial was conducted in 43 centres in seven countries. People with Type 1 diabetes were randomized to mealtime insulin aspart with up to four daily NPH doses if meals were > 5 h apart and a 25% increase in bedtime NPH dose (n = 187), or to mealtime human unmodified insulin with once or twice daily basal NPH insulin (n = 181). Efficacy and safety were evaluated at 12 weeks (primary evaluation period) and 64 weeks.

Results At 12 and 64 weeks there was no statistically significant difference in HbA1c between the insulin aspart and regular insulin groups: −0.09 (95% confidence interval (CI) −0.23, +0.05)% and −0.14 (−0.32, +0.04)%. Post‐prandial glucose values were lower and the area under the 24‐h self‐monitored blood glucose curve above 7.0 mmol/l was 28% smaller with insulin aspart (35.2 ± 3.2 vs. 48.9 ± 3.1 mmol/l h, P = 0.0015). No significant differences were found in mild or severe hypoglycaemia, or adverse event rate. At 64 weeks treatment satisfaction was higher in the insulin aspart group (difference 1.57 (95% CI 0.49, 2.64) points, P = 0.004), while quality of life was not different.

Conclusions Improved post‐prandial glycaemic control and treatment satisfaction with insulin aspart were confirmed. Intensifying basal insulin supplementation resulted in a similar HbA1c decrement as previously found with the use of insulin aspart and standard NPH insulin supplementation. This does not support routinely basal NPH insulin intensification when using rapid‐acting insulin analogues in daily practice.
Maternal ante‐natal parameters as predictors of persistent postnatal glucose intolerance: a comparative study between Afro‐Caribbeans, Asians and Caucasians
Authors: Sinha B. , Brydon P. , Taylor R. S. , Hollins A. , Munro A. , Jenkins D. , Dunne F.
Published: December 2004

Aims To measure the prevalence of persistent glucose intolerance at 6–12 weeks postpartum in various ethnic groups to assess the value of targeted postpartum screening.

Methods A retrospective study was performed using computerized databases from two large maternity units within one UK region. Both units used the same screening strategy for gestational diabetes mellitus (GDM) and the same postpartum follow‐up at 6–12 weeks using a 75‐g oral glucose tolerance test (OGTT). A total of 221 women with a diagnosis of GDM/impaired glucose tolerance (IGT) in the index pregnancy in addition to a completed postpartum 75‐g OGTT were studied. Of these, 91 were Caucasian, 89 were of Indo‐Asian (Asian) origin and 41 were of Afro‐Caribbean origin.

Results The study showed that 35% Indo‐Asians had persistent postpartum glucose intolerance compared with 7% Caucasians and 5% Afro‐Caribbeans (P < 0.003). Insulin requirement during pregnancy and a diagnosis of gestational diabetes prior to 20 weeks of pregnancy were predictive for persistent postpartum glucose intolerance amongst Indo‐Asians.

Conclusions The frequency of postpartum glucose intolerance among Indo‐Asian women is significantly greater than among age‐matched Caucasian and Afro‐Caribbean women. We suggest that all Indo‐Asian women with gestational diabetes should undergo postpartum screening for persistent glucose intolerance. However, in non‐Asian women selective screening may be more cost effective.

Diabet. Med. 20, 382–386 (2003)
A lifecourse study of risk for hyperinsulinaemia, dyslipidaemia and obesity (the central metabolic syndrome) at age 49–51 years
Authors: Parker L. , Lamont D. W. , Unwin N. , Pearce M. S. , Bennett S. M. A. , Dickinson H. O. , White M. , Mathers J. C. , Alberti K. G. M. M. , Craft A. W.
Published: December 2004

Aims Suboptimal maternal nutrition and catch‐up growth in early childhood predispose to insulin resistance and other components of metabolic syndrome in later life. A central metabolic syndrome (CMS) has been identified comprising obesity, dyslipidaemia and insulin resistance. This study was designed to investigate determinants of risk for CMS.

Methods Persons born in Newcastle in May and June 1947 (n = 358) were followed to 1996–1998. A lifecourse approach was used to estimate the proportion of variance in a summary measure of CMS at age 49–51 years accounted for by factors operating at different stages of life.

Results After adjustment for other early life variables, childhood catch‐up growth in men accounted for significant variation in the CMS score independent of adult lifestyle. In adulthood, exercise level in men and smoking in both genders were independently associated with CMS. Over two‐thirds of explained variation in the CMS score in women, and almost half in men, was accounted for exclusively by factors measured in adulthood.

Conclusions While risk for CMS in men is compounded by early life disadvantage, promotion of a healthier adult lifestyle and a reduction in the number of people taking up smoking would appear to be the public health interventions most likely to reduce the prevalence of CMS in middle age.

Diabet. Med. 20, 406–415 (2003)
Quality of diabetes management in children and adolescents in Denmark1
Authors: Nordly S. , Jørgensen T. , Andreasen A. H. , Hermann N. , Mortensen H. B.
Published: December 2004

Aim To describe the management of children and adolescents with Type 1 diabetes mellitus in Denmark.

Methods Quality indicators with standards of childhood diabetes management were chosen based on international and national guidelines. Data originated from the nation‐wide Danish Registry for Childhood Diabetes and two questionnaires: one questionnaire was sent to all children with diabetes (response rate 78%, n = 1335) and the other was sent to the 19 centres in Denmark treating these children (response rate 100%). Simultaneously, the children were asked to take a blood sample for central HbA1c‐analysis (normal range 4.3–5.8, mean 5.1%).

Results Most children were managed at centres which complied with the standards for the process indicators for good diabetes management, but not with the standards for most structure and outcome indicators. Only one third of the children reached the treatment target for HbA1c. Their mean HbA1c‐level increased gradually from ages 4–14 without significant difference between genders. The youngest children had the lowest HbA1c (mean 8.2%) and the lowest rate of severe hypoglycaemic events (4.6 events per 100 patient years). The subgroup of children without any hypoglycaemic events had the significantly lowest mean HbA1c‐level (8.6%, P = 0.028).

Conclusions The Danish Registry for Childhood Diabetes provided useful data for quality improvement, but had to be supplemented with data from questionnaires on the structure and process indicators. Outcome of paediatric diabetes management in Denmark was unsatisfactory. Centres need feedback on ways to improve care to lower the children's risk of developing severe diabetes complications.

Diabet. Med. 20, 568–574 (2003)
Factors predictive of nephropathy in DCCT Type 1 diabetic patients with good or poor metabolic control
Authors: Zhang L. , Krzentowski G. , Albert A. , Lefèbvre P. J.
Published: December 2004

Aims The study aim was to assess the time‐related risk of developing diabetic nephropathy [albumin excretion rate (AER) ≥ 40 mg/24 h] from baseline covariates in Type 1 diabetic patients with either good or poor metabolic control (MC).

Methods Based on material from the Diabetes Control and Complications Trial study (n = 1441), patients were considered as under good or poor MC if their HbA1c mean level up to last visit fell in the lowest (≤ 6.9%) or highest (≥ 9.5%) quintile of the overall HbA1c distribution, respectively. Prevalence cases of nephropathy were excluded from the study. Survival analysis and Cox regression were applied to the data.

Results Among patients with good MC (n = 277), 15% had developed nephropathy at the end of the study. Conversely, among patients with poor MC (n = 268), the proportion without the complication was 52%. When adjusting for MC, time to diabetic nephropathy was related to age (P < 0.0001), AER (P < 0.001), duration of diabetes (P < 0.005), body mass index (BMI) (P < 0.005), all at baseline, and to gender (P < 0.01). Patients with upper normal range AER levels, longer duration of diabetes and lower BMI were at higher risk, regardless of MC. The adverse effect of younger age on diabetic nephropathy was more marked in good than in poor MC. Although women tended to develop the complication more often under good MC, they appeared to be better protected under poor MC.

Conclusions This study confirms occurrence of diabetic nephropathy under good MC and non‐occurrence of the complication despite poor MC. It also demonstrates that some baseline covariates can affect, in a differential manner, time to diabetic nephropathy depending on MC.

Diabet. Med. 20, 580–585 (2003)
Performance assessment of the Medtronic‐MiniMed Continuous Glucose Monitoring System and its use for measurement of glycaemic control in Type 1 diabetic subjects
Authors: Sachedina N. , Pickup J. C.
Published: December 2004

Aims  To assess the accuracy, reliability and measurement of glycaemic control associated with the Medtronic‐MiniMed Continuous Glucose Monitoring System (CGMS) in comparison with blood glucose self‐monitoring (BGSM) in Type 1 diabetic patients.

Methods  Type 1 diabetic patients (n = 18) underwent glucose monitoring by the CGMS for up to 3 days, when control was also assessed by BGSM performed eight times daily.

Results  Ninety‐five per cent of paired non calibration samples were in the clinically acceptable zones of the Clarke error grid, and 97% in a consensus grid. The median bias was 0.1 mmol/l and relative bias 15%. The failure rate of sensors was 28% of those initially inserted. The CGMS detected significantly more hypoglycaemia and post‐prandial hyperglycaemia, but total duration of hyperglycaemia, blood glucose oscillations and day‐to‐day variability were similarly assessed by CGMS and BGSM.

Conclusions  The CGMS has acceptable clinical accuracy. Detection by the CGMS of more hypoglycaemia and post‐prandial hyperglycaemia than BGSM promises a valuable tool for control assessment and optimization of treatment.
The concentrations of short‐chain fatty acids and other microflora‐associated characteristics in faeces from children with newly diagnosed Type 1 diabetes and control children and their family members
Authors: Samuelsson U. , Ludvigsson J.
Published: December 2004

Aims  The gut flora is quantitatively the most important source of microbial stimulation and may provide a primary signal in the maturation of the immune system. We compared the microflora‐associated characteristics (MACs) in 22 children with newly diagnosed diabetes, 27 healthy controls, and their family members to see if there were differences between the children and if there was a familial pattern.

Methods  The MACs were assessed by determining the concentrations of eight short‐chain fatty acids (SCFA), mucin, urobilin, b‐aspartylglycine, coprastanol and faecal tryptic activity (FTA).

Results  There were no statistically significant differences between the concentrations of SCFA in the diabetes and control children. Members of families with a diabetic child had a higher concentration of acetic acid (P < 0.02) and lower concentrations of several other SCFAs than control families (P < 0.05–0.02). The other MACs showed no differences between the children or between the two family groups.

Conclusion  In this pilot study we saw no differences in the MACs between children with diabetes and their controls. There were, however, some differences between the family members of diabetic children and controls that may indicate a familial pattern regarding the production of SCFAs by the gut flora. The role of the gut flora in relation to the risk of developing Type 1 diabetes needs to be analysed in larger and/or prospective studies.
Gestational diabetes affects platelet behaviour through modified oxidative radical metabolism
Authors: Mazzanti L. , Nanetti L. , Vignini A. , Rabini R. A. , Grechi G. , Cester N. , Curzi C. M. , Tranquilli A. L.
Published: December 2004

Aims  Patients with Type 1 and Type 2 diabetes mellitus show altered platelet function including decreased nitric oxide synthase (NOS) activity and increased peroxynitrite production. Gestational diabetes mellitus (GDM) is a clinical condition which is ideal for evaluating short‐term effects of impaired glucose metabolism, ruling out the possibility that the platelet abnormalities are a consequence of diabetic complications. The aim of the present work was to study NO metabolism in platelets from pregnant women with GDM. The production of peroxides was also studied as it is strongly involved in peroxynitrite formation.

Methods  Platelet NOS activity and peroxynitrite production, levels of hydroperoxides and thiobarbituric acid reactive substances (TBARS) in platelet membranes in the basal state and after in vitro peroxidative stress with phenylhydrazine were determined in 40 pregnant women with GDM, 40 healthy pregnant women (pregnant controls) of comparable age and gestational age, and 15 healthy non‐pregnant women (controls).

Results  NOS activity was significantly increased in both groups of pregnant women compared with non‐pregnant ones, and in GDM women compared with pregnant controls. Production of peroxynitrite was higher in GDM women than in pregnant controls, who also had significantly reduced production compared with non‐pregnant women. Basal levels of peroxidation of the platelet membranes evaluated either by hydroperoxide content and TBARS levels or the susceptibility to peroxidation were increased in GDM patients in comparison with both control groups.

Conclusions  We have shown a modification in platelet NO and peroxynitrite production and an increase in platelet indicators of oxidative stress in GDM women compared with healthy pregnant women which might be at the basis of a cellular dysfunction.
Comparison of a high‐carbohydrate and a high‐monounsaturated fat, olive oil‐rich diet on the susceptibility of LDL to oxidative modification in subjects with Type 2 diabetes mellitus
Authors: Rodríguez‐Villar C. , Pérez‐Heras A. , Mercadé I. , Casals E. , Ros E.
Published: December 2004

Aims  To compare the effects of a high‐carbohydrate (CHO) diet and a high‐monounsaturated fatty acid (MUFA) diet on LDL oxidative resistance in free‐living individuals with Type 2 diabetes mellitus.

Methods  Twenty‐two men and women out‐patients with Type 2 diabetes, with mean age 61 years and in fair metabolic control (HbA1c < 8.0%), were enrolled at a university hospital lipid clinic in a randomized, crossover feeding trial comparing two isocaloric diets for 6 weeks each: CHO (fat, 28% energy) and MUFA (fat, 40% energy) based on virgin olive oil. Outcome measurements were changes in LDL susceptibility to oxidation, body weight, glycaemic control, and lipoprotein profiles.

Results  Planned and observed diets were well matched. Participants preferred the MUFA diet over the CHO diet. The lag time of conjugated diene formation during Cu2+‐induced LDL oxidation was similar after the CHO and MUFA diets (36.4 ± 12.2 min and 36.0 ± 13.7 min, respectively). Body weight, glycaemic control, total triglycerides, and total, LDL‐ and HDL‐cholesterol levels also were similar after the two diets. Compared with the CHO diet, the MUFA diet lowered VLDL‐cholesterol by 35% (P = 0.023) and VLDL triglyceride by 16% (P = 0.016).

Conclusions  Natural food‐based high‐CHO and high‐MUFA diets have similar effects on LDL oxidative resistance and metabolic control in subjects with Type 2 diabetes. A MUFA diet is a good alternative to high‐CHO diets for nutrition therapy of diabetes because it also has a beneficial effect on the lipid profile and superior patient acceptance.
Direction of movements in Hungarian Barn Owls (Tyto alba): gene flow and barriers
Authors: Mátics Róbert
Published: December 2004

Abstract.An analysis of dispersal directions of the barn owl showed that all individuals immigrating to Hungary came from W‐NW‐N. It was shown that immigrating owls breed in Hungary. There is no prevailing direction in emigration from Hungary. The time of fledging does not influence the direction of movement and there is no difference between sexes concerning dispersal direction. The percentages of emigrating owls is greater than that of immigrating ones. These percentages did not differ in relation to most of the analysed countries (Germany, Italy, Switzerland, Poland and countries of the former Yugoslavia and Czechoslovakia) but it differed in relation to Austria. The degree and direction of introgression into and from the transition zone and the recent distribution of the phenotypes are discussed based on the comparative analysis of published European data. These suggest that the subspeciesTyto alba albaandTyto alba guttatadisappear by introgression, to form a phenotypically very variable species.
Landscape characteristics, spatial extent, and breeding bird diversity in Ohio, USA
Authors: Mayer Audrey L. , Cameron Guy N.
Published: December 2004

Abstract. Avian communities are often used by ecologists as indicators of environmental decline over large spatial areas, because of the ease with which birds can be monitored by nonprofessionals and the availability of continent‐wide breeding bird data. The influence of scale on the relationship between bird diversity and the characteristics of the landscape, which can serve as proxies for decline, is receiving greater attention but is still not well understood. We combined data from the Breeding Bird Survey with landscape characteristics derived from the National Land Classification Data for Ohio, USA, to determine the effects of landscape extent on relationships between birds and landscape characteristics. These relationships were determined through previous work to be correlated with avian richness and diversity. We created areas of varying sizes using buffers around each of 58 routes, and calculated diversity for several groups of birds: all birds, five habitat guilds, and three migration guilds. The landscape extent over which landscape characteristics were considered affected the relationship between these characteristics and bird richness and diversity overall, as well as richness and diversity for several of the habitat and migratory guilds. Diversity of woodland birds, Neotropical migrants, and richness of short‐distance migrants were best explained by the landscape characteristics examined here, possibly due to a less homogeneous collection of species in the other guild groups. These results suggest that more attention is required in selecting the appropriate scale when using landscape characteristics to predict or manage avian communities, as some characteristics may be more useful for management activities over small areas versus efforts over larger areas.
Effect of acute carbon monoxide exposure on heart rate variability in patients with coronary artery disease*
Authors: Tarkiainen Tuula H. , Timonen Kirsi L. , Vanninen Esko J. , Alm Sari , Hartikainen Juha E. K. , Pekkanen Juha
Published: December 2004

Epidemiological studies have shown that air pollution is associated with increased cardiovascular mortality. Although the pathophysiological mechanisms behind this association have remained largely unknown, it has been suggested that changes in cardiac autonomic function may play a role. In this study, we investigated the association between acute carbon monoxide (CO) exposure and cardiac autonomic function as measured by heart rate variability (HRV) in subjects with stable coronary artery disease. Twenty‐four hour ambulatory electrocardiographic recording with simultaneous continuous personal CO concentration monitoring was performed in six male patients with angiographically verified coronary artery disease three times with 1‐week intervals. Time domain measures of HRV were calculated for 5‐min segments before and during the CO exposure periods. For further analysis CO exposures were divided into low (≤2·7 p.p.m.) and high (>2·7 p.p.m.) CO exposure periods. The mean of maximum CO levels during 61 CO exposure periods was 4·6 p.p.m. (SD 5·0 p.p.m.). High CO exposure was associated with an increase in the square root of the mean of the sum of the squares of differences between adjacent RR intervals (r‐MSSD) (P = 0·034). Heart rate remained unchanged during the CO exposure. In conclusion, acute CO exposure which represented most likely exposure derived from traffic seems to modify cardiac autonomic control in patients with stable coronary artery disease.
The single breath transfer factor (Tl,co) and the transfer coefficient (Kco): a window onto the pulmonary microcirculation
Authors: Hughes J.M.B.
Published: December 2004

The transfer factor, Tl,co (with the transfer coefficient, Kco, also known as the transfer factor per unit alveolar volume, [Tl/Va]), is one of the most useful clinical tests of pulmonary function, the only one which specifically focuses on pulmonary microcirculation. It was originally devised in 1909 as a physiological tool to assess the diffusive capacity of the lung as a gas exchanger. It was subsequently developed as a clinical tool, but cumbersome analytical techniques delayed its introduction into clinical medicine until 1950s. The physiology of the carbon monoxide transfer factor (also called the diffusing capacity Dl,co) is based on the Roughton–Forster equation which partitions Dl,co, a conductance, into membrane (Dm) and red cell (θVc) diffusion conductances. Recent work (1987–2001) suggests that 70–80% of the resistance to CO (and O2) diffusion may reside in the red cell fraction. The clinical implication is that Tl,co and Kco are ‘windows’ onto the pulmonary microcirculation. As regards reference values for clinical use, Tl,co depends on age, height and gender. Kco, which is actually a rate constant, is independent of gender, and is affected principally by age. A schema is presented for the clinical interpretation of Tl,co. As Tl,co is derived from the product of Kco and the accessible alveolar volume (Va), examination of these two components (Kco and Va) will usually suggest a specific pathophysiological mechanism as the explanation for a reduction in Tl,co.
Relationship between exercise performance and water distribution measured by new bioelectrical impedance analysis in patients with chronic obstructive pulmonary disease
Authors: Mamoto Takashi , Fujiwara Hiroshi , Toyama Yoshiki , Hirata Kazuto , Yoshikawa Junichi , Fujimoto Shigeo
Published: December 2004

Body composition analysis is useful for objective evaluation of malnutrition in patients with chronic obstructive pulmonary disease (COPD). The purpose of this study was to evaluate the influence of body composition on exercise performance by patients with COPD using a new method of bioelectrical impedance analysis. Twenty patients with COPD performed incremental exercise ramp tests to the symptom‐limited maximum and constant work rate tests for 10 min. Their body compositions were measured by bioelectrical impedance analysis with eight electrodes and four frequencies, which could estimate the amount of intra‐ and extracellular water (ICW, ECW) and water distribution of the extremities separately. Some pulmonary function parameters of airflow limitation or hyperinflation and body composition parameters were significantly correlated with . Stepwise multiple regression analysis revealed that independent predictors of included ECW/ICW ratio, lower extremity water and FEV1·0 (P<0·0001, R = 0·892), which explained 27, 31 and 21% of , respectively. Furthermore, there was a significant correlation between ECW/ICW ratio and time constant of oxygen consumption in constant work rate tests. These findings indicate that increased ECW/ICW ratio and lower extremity water correlated with exercise intolerance independent of pulmonary function, and that changes in cellular hydration state might affect oxygen utilization of skeletal muscle in patients with COPD. In conclusion, the BIA used in our study, which can easily and simultaneously evaluate the water distribution of the extremities and cellular hydration state, is useful for the evaluation of exercise performance in COPD patients.