bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy, dose–response relationship and safety of once‐daily extended‐release metformin (Glucophage® XR) in type 2 diabetic patients with inadequate glycaemic control despite prior treatment with diet and exercise: results from two double‐blind, placebo‐controlled studies
Authors: Fujioka K. , Brazg R. L. , Raz I. , Bruce S. , Joyal S. , Swanink R. , Pans M. 
Published: December 2004

Aim:  The efficacy, dose–response relationships and safety of an extended‐release formulation of metformin (Glucophage® XR) were evaluated in two double‐blind, randomized, placebo‐controlled studies of 24 and 16 weeks' duration, in patients with inadequate glycaemic control despite diet and exercise. Protocol 1 provided an evaluation of metformin XR at a commonly used dosage. Protocol 2 evaluated different dosages of metformin XR.Methods:  In Protocol 1, 240 patients were randomized to receive metformin XR 1000 mg once daily. or placebo in a 2 : 1 ratio for 12 weeks (patients could receive metformin XR 1500 mg during weeks 12–24 if required). In Protocol 2, 742 patients were randomized to receive metformin XR 500 mg once daily, 1000 mg once daily, 1500 mg once daily, 2000 mg once daily, 1000 mg twice daily or placebo for 16 weeks. The primary endpoint in each study was the change from baseline in HbA1C at 12 weeks (Protocol 1) or 16 weeks (Protocol 2).Results:  Metformin XR reduced HbA1C in Protocol 1, with mean treatment differences for 1000 mg once daily vs. placebo of −0.7% at 12 weeks and −0.8% at 24 weeks (p < 0.001 for each). In Protocol 2, a clear dose–response relationship was evident at doses up to 1500 mg, with treatment differences vs. placebo of −0.6% (500 mg once daily), −0.7% (1000 mg once daily), −1.0% (1500 mg once daily) and −1.0% (2000 mg once daily). The efficacy of metformin XR 2000 mg once daily and 1000 mg twice daily were similar (mean treatment differences vs. placebo in HbA1C were −1.0% and −1.2%, respectively). More patients achieved HbA1C < 7.0% with metformin XR vs. placebo in Protocol 1 (29% vs. 14% at 12 weeks) and with once‐daily metformin XR in Protocol 2 (up to 36% vs. 10% at 16 weeks). No significant changes in fasting insulin or body weight occurred. Total and low‐density lipoprotein (LDL)‐cholesterol improved (p < 0.05–p < 0.001) in metformin XR groups in Protocol 2. Metformin XR was well tolerated; gastrointestinal side effects were more common with metformin XR vs. placebo, but few patients withdrew for this reason (1.3% vs. 1.3% in Protocol 1 and 1.6% vs. 0.9% in Protocol 2).Conclusions:  Once‐daily metformin XR presents an effective and well‐tolerated therapeutic option for delivering metformin in a convenient manner, which supports good compliance with therapy.
Combination treatment of vitamin C and desferrioxamine suppresses glomerular superoxide and prostaglandin E2 production in diabetic rats
Authors: Iino K. , Iwase M. , Sonoki K. , Yoshinari M. , Iida M. 
Published: December 2004

Aims:  Increased oxidative stress may contribute to the development of diabetic nephropathy. Conversely, it has been proposed that enhanced glomerular production of prostaglandin E2 (PGE2) may be the cause of glomerular hyperfiltration in streptozotocin (STZ)‐induced diabetic rats. As the role of superoxide anion (O2–) production in early diabetic nephropathy is not fully understood, we investigated the effect of vitamin C and desferrioxamine treatment on glomerular O2– and PGE2 production in diabetic rats.Methods:  STZ‐induced diabetic rats were given drinking water containing 1 g/l of vitamin C and desferrioxamine for 10 days, and glomerular O2– production, glomerular PGE2 synthesis and creatinine clearance were examined.Results:  Glomerular O2– production increased in untreated diabetic rats compared to non‐diabetic controls (142.2 ± 12.4 vs. 65.4 ± 3.6 counts/mg protein/min). Treatment with vitamin C and desferrioxamine significantly decreased glomerular O2– production (93.7 ± 6.7 counts/mg protein/min). Glomerular PGE2 synthesis and creatinine clearance were significantly increased in untreated diabetic rats compared to controls and PGE2 synthesis was reduced and creatinine clearance tended to decrease by the treatment.Conclusions:  Our results demonstrated that vitamin C and desferrioxamine suppressed the enhanced glomerular O2– production with subsequent decrease in PGE2 production. Antioxidant therapy may be beneficial in preventing the development of diabetic nephropathy.
The post‐prandial state in Type 2 diabetes and endothelial dysfunction: effects of insulin aspart
Authors: Ceriello A. , Cavarape A. , Martinelli L. , Da Ros R. , Marra G. , Quagliaro L. , Piconi L. , Assaloni R. , Motz E. 
Published: December 2004

AbstractObjective  Recently, much attention has been focused on the possibility that the post‐prandial state may be a cardiovascular risk factor in diabetes. The aim of the present study was to evaluate whether the post‐prandial state is associated with endothelial dysfunction in patients with diabetes and to explore the effect on this aspect of managing post‐prandial hyperglycaemia by insulin aspart.Research design and methods  Twenty‐three patients with Type 2 diabetes and 10 normal controls were recruited. In the diabetic patients two different tests were performed in each subject: a standard meal preceded by subcutaneous injection of soluble insulin (0.15 U/kg body weight) or of short‐acting insulin aspart (0.15 U/kg body weight). These tests were designed to achieve different levels of post‐prandial hyperglycaemia. Controls received a single standard meal test. Immediately before, and 1, 2, 4 and 6 h after each meal, blood glucose, triglycerides, free fatty acids and flow‐mediated vasodilation were measured.Results  Compared with regular insulin, insulin aspart significantly reduced the area under the curve for post‐prandial hyperglycaemia (58.3 ± 17.6 vs. 68.1 ± 17.7; P < 0.04), and preserved flow‐mediated vasodilation, which was decreased in the post‐prandial state (39.4 ± 2.9 vs. 34.1 ± 2.2; P < 0.01). Triglyceride and free fatty acid levels were not differentially affected by the treatment. In normal controls the meal did not affect flow‐mediated vasodilation.Conclusion  This study shows that the post‐prandial state is accompanied by endothelial dysfunction in Type 2 diabetic patients and that insulin aspart improved endothelial function.Diabet. Med. 21, 171–175 (2004)
Effects of acute hyperglycaemia on anorectal motor and sensory function in diabetes mellitus
Authors: Russo A. , Botten R. , Kong M.‐F. , Chapman I. M. , Fraser R. J. L. , Horowitz M. , Sun W.‐M. 
Published: December 2004

AbstractAims  To determine the effects of acute hyperglycaemia on anorectal motor and sensory function in patients with diabetes mellitus.Methods  In eight patients with Type 1, and 10 patients with Type 2 diabetes anorectal motility and sensation were evaluated on separate days while the blood glucose concentration was stabilized at either 5 mmol/l or 12 mmol/l using a glucose clamp technique. Eight healthy subjects were studied under euglycaemic conditions. Anorectal motor and sensory function was evaluated using a sleeve/sidehole catheter, incorporating a barostat bag.Results  In diabetic subjects hyperglycaemia was associated with reductions in maximal (P < 0.05) and plateau (P < 0.05) anal squeeze pressures and the rectal pressure/volume relationship (compliance) during barostat distension (P < 0.01). Hyperglycaemia had no effect on the perception of rectal distension. Apart from a reduction in rectal compliance (P < 0.01) and a trend (P = 0.06) for an increased number of spontaneous anal sphincter relaxations, there were no differences between the patients studied during euglycaemia when compared with healthy subjects.Conclusions  In patients with diabetes, acute hyperglycaemia inhibits external anal sphincter function and decreases rectal compliance, potentially increasing the risk of faecal incontinence.Diabet. Med. 21, 176–182 (2004)
What does postprandial hyperglycaemia mean?
Authors: Heine R. J. , Balkau B. , Ceriello A. , Del Prato S. , Horton E. S. , Taskinen M‐R. 
Published: December 2004

AbstractAims  The potential importance of postprandial glucose (PPG) control in the development of complications in Type 2 diabetes is much debated. The recent American Diabetes Association (ADA) consensus statement discussed the role of postprandial hyperglycaemia in the pathogenesis of diabetic complications and concluded that the relationship between PPG excursions and the well‐established risk factors for cardiovascular disease (CVD) should be further examined. Using the ADA statement as a starting point and including the more recent American College of Endocrinology guidelines on glycaemic control, a panel of experts in diabetes met to review the role of PPG within the context of the overall metabolic syndrome, in the development of complications in Type 2 diabetes.Results  Post‐prandial hyperglycaemia is a risk indicator for micro‐ and macrovascular complications, not only in patients with Type 2 diabetes but also in those with impaired glucose tolerance. In addition, the metabolic syndrome confers an increased risk of CVD morbidity and mortality. The debate focused on the relative contributions of postprandial hyperglycaemia, the metabolic syndrome and, in particular, raised triglyceride levels in the postprandial state, to the development of cardiovascular complications of diabetes.Conclusions  The panel recommended that in the prevention and management of microvascular complications of Type 2 diabetes, targeting both chronic and acute glucose fluctuations is necessary. Lowering the macrovascular risk also requires control of (postprandial) triglyceride levels and other components of the metabolic syndrome.
Twelve‐month‐olds point to share attention and interest
Authors: Liszkowski Ulf , Carpenter Malinda , Henning Anne , Striano Tricia , Tomasello Michael 
Published: December 2004

Abstract Infants point for various motives. Classically, one such motive is declarative, to share attention and interest with adults to events. Recently, some researchers have questioned whether infants have this motivation. In the current study, an adult reacted to 12‐month‐olds’ pointing in different ways, and infants’ responses were observed. Results showed that when the adult shared attention and interest (i.e. alternated gaze and emoted), infants pointed more frequently across trials and tended to prolong each point – presumably to prolong the satisfying interaction. However, when the adult emoted to the infant alone or looked only to the event, infants pointed less across trials and repeated points more within trials – presumably in an attempt to establish joint attention. Results suggest that 12‐month‐olds point declaratively and understand that others have psychological states that can be directed and shared.
Culture and children's cosmology
Authors: Siegal Michael , Butterworth George , Newcombe Peter A. 
Published: December 2004

Abstract In this investigation, we examined children's knowledge of cosmology in relation to the shape of the earth and the day‐night cycle. Using explicit questioning involving a choice of alternative answers and 3D models, we carried out a comparison of children aged 4–9 years living in Australia and England. Though Australia and England have a close cultural affinity, there are differences in children's early exposure to cosmological concepts. Australian children who have early instruction in this domain were nearly always significantly in advance of their English counterparts. In general, they most often produced responses compatible with a conception of a round earth on which people can live all over without falling off. We consider coherence and fragmentation in children's knowledge in terms of the timing of culturally transmitted information, and in relation to questioning methods used in previous research that may have underestimated children's competence.
Neurophysiological tests and neuroimaging procedures in non‐acute headache: guidelines and recommendations
Authors: Sandrini G. , Friberg L. , Jänig W. , Jensen R. , Russell D. , Sanchez del Rìo M. , Sand T. , Schoenen J. , van Buchem M. , Van Dijk J. G. 
Published: December 2004

The use of instrumental examinations in headache patients varies widely. In order to evaluate their usefulness, the most common instrumental procedures were evaluated, on the basis of evidence from the literature, by an EFNS Task Force (TF) on neurophysiological tests and imaging procedures in non‐acute headache patients. The conclusions of the TF regarding each technique are expressed in the following guidelines for clinical use.

Interictal electroencephalography (EEG) is not routinely indicated in the diagnostic evaluation of headache patients. Interictal EEG is, however, indicated if the clinical history suggests a possible diagnosis of epilepsy (differential diagnosis). Ictal EEG could be useful in certain patients suffering from hemiplegic and basilar migraine.
Recording of evoked potentials is not recommended for the diagnosis of headache disorders.
There is no evidence to justify the recommendation of autonomic tests for the routine clinical examination of headache patients.
Manual palpation of pericranial muscles, with standardized palpation pressure, can be recommended for subdividing patient groups but not for diagnosis. Pressure algometry and electromyography (EMG) cannot be recommended as clinical diagnostic tests.
In adult and paediatric patients with migraine, with no recent change in attack pattern, no history of seizures, and no other focal neurological signs or symptoms, the routine use of neuroimaging is not warranted. In patients with atypical headache patterns, a history of seizures and/or focal neurological signs or symptoms, magnetic resonance imaging (MRI) may be indicated.
If attacks can be fully accounted for by the standard headache classification [International Headache Society (IHS)], a positron emission tomography (PET) or single‐photon emission computerized tomography (SPECT) and scan will generally be of no further diagnostic value.
Nuclear medicine examinations of the cerebral circulation and metabolism can be carried out in subgroups of headache patients for diagnosis and evaluation of complications, when patients experience unusually severe attacks, or when the quality or severity of attacks has changed.
Transcranial Doppler examination is not helpful in headache diagnosis.

Although many of the examinations described are of little or no value in the clinical setting, most of the tools have a vast potential for further exploring the pathophysiology of headaches and the effects of pharmacological treatment.
Zolmitriptan Nasal Spray Exhibits Good Long‐Term Safety and Tolerability in Migraine: Results of the INDEX Trial
Authors: Dowson Andrew J. , Charlesworth Bruce R. , Green Judy , Färkkilä Markus , Diener Hans‐Christoph , Boes Hansen Steen , Gawel Marek ,   INDEX Study Group
Published: December 2004

Background.—Previous studies have shown that zolmitriptan 5 mg nasal spray has a fast onset of action, high efficacy, and good tolerability in the acute treatment of migraine.Objective.—This open‐label, noncomparative, multicenter, multinational phase III study was designed to further evaluate the long‐term safety and tolerability of zolmitriptan 5 mg nasal spray in a population of migraineurs largely naïve to triptan nasal sprays who treated multiple migraine attacks over a 1‐year period.Methods.—Patients were required to have an established diagnosis of migraine with or without aura (based on International Headache Society criteria), a high frequency of migraine attacks, and were allowed to treat migraine with any baseline headache intensity. A secondary objective of the study was to assess the long‐term efficacy of zolmitriptan nasal spray. A subgroup analysis aimed to determine whether rhinitis had any influence on outcomes of treatment.Results.—The safety population consisted of 538 patients who treated 20 717 migraine attacks with zolmitriptan 5 mg nasal spray. Overall, adverse events occurred in 32.8% of attacks, and led to treatment withdrawal in 4.5% of patients. The most common adverse events were unusual taste (19.0%) and paresthesia (6.8%). Adverse events were generally of mild intensity, transient, and well tolerated, showing a decline in incidence over time. Serious adverse events were rare. The presence of rhinitis and use of a second dose of trial medication had no effect on the incidence of adverse events. At 2 hours, 53.8% of attacks treated with zolmitriptan nasal spray 5 mg were rendered pain free. The highest 2‐hour pain free rates were seen for headaches of mild baseline intensity (83.3%), followed by headaches of moderate (56.5%), and severe (32.2%) baseline intensity. The 2‐hour pain‐free rate remained consistent throughout the study period. The presence of rhinitis had no effect on efficacy.Conclusions.—Zolmitriptan 5 mg nasal spray demonstrated a well‐tolerated and efficacious profile in the acute treatment of multiple migraine attacks over a 1‐year period.
Chronic Post‐Traumatic Neck and Head Pain
Authors: Solomon Seymour 
Published: December 2004

Objective.—This is a review of current concepts of chronic post‐traumatic neck and head pain. In this article, I will emphasize the physiological and sociological aspects of these disorders.Background.—The pathophysiology of chronic post‐traumatic neck and head pain has not been well understood. Some have emphasized the organic factors and others the psychogenic aspects of these conditions. Only in recent years have this dichotomy been integrated with sociocultural concepts.Methods.—The history of chronic post‐traumatic head and neck pain is reviewed. Paradoxes are discussed, ie, the great differences in prevalence around the world, the inconsistent relationship of symptoms to degree of trauma, the curious phenomena of structural disease without symptoms, and symptoms without structural disease. The organic and pathophysiologic factors are reviewed, then those factors that modulate pain in these conditions are discussed.Conclusion.—Chronic post‐traumatic neck and head pain is rarely either organic or psychogenic. Rather physiological, social, and cultural factors play major roles in modulating pain and either perpetuate or ameliorate these chronic pain conditions.
Functional‐Task Exercise Versus Resistance Strength Exercise to Improve Daily Function in Older Women: A Randomized, Controlled Trial
Authors: De Vreede Paul L. , Samson Monique M. , Van Meeteren Nico L. U. , Duursma Sijmen A. , Verhaar Harald J. J. 
Published: December 2004

Objectives: To determine whether a functional‐task exercise program and a resistance exercise program have different effects on the ability of community‐living older people to perform daily tasks.Design: A randomized, controlled, single‐blind trial.Setting: Community leisure center in Utrecht, the Netherlands.Participants: Ninety‐eight healthy women aged 70 and older were randomly assigned to the functional‐task exercise program (function group, n=33), a resistance exercise program (resistance group, n=34), or a control group (n=31). Participants attended exercise classes three times a week for 12 weeks.Measurements: Functional task performance (Assessment of Daily Activity Performance (ADAP)), isometric knee extensor strength (IKES), handgrip strength, isometric elbow flexor strength (IEFS), and leg extension power were measured at baseline, at the end of training (at 3 months), and 6 months after the end of training (at 9 months).Results: The ADAP total score of the function group (mean change 6.8, 95% confidence interval (CI)=5.2–8.4) increased significantly more than that of the resistance group (3.2, 95% CI=1.3–5.0; P=.007) or the control group (0.3, 95% CI=−1.3–1.9; P<.001). Moreover, the ADAP total score of the resistance group did not change significantly compared with that of the control group. In contrast, IKES and IEFS increased significantly in the resistance group (12.5%, 95% CI=3.8–21.3 and 8.6%, 95% CI=3.1–14.1, respectively) compared with the function group (−2.1%, 95% CI=−5.4–1.3; P=.003 and 0.3%, 95% CI=−3.6–4.2; P=.03, respectively) and the control group (−2.7%, 95% CI=−8.6–3.2, P=.003 and 0.6%, 95% CI=−3.4–4.6; P=.04, respectively). Six months after the end of training, the increase in ADAP scores was sustained in the function group (P=.002).Conclusion: Functional‐task exercises are more effective than resistance exercises at improving functional task performance in healthy elderly women and may have an important role in helping them maintain an independent lifestyle.
Effects of a Nap on Nighttime Sleep and Waking Function in Older Subjects
Authors: Campbell Scott S. , Murphy Patricia J. , Stauble Thomas N. 
Published: December 2004

Objectives: To examine, in older subjects, the effect on waking function of increasing 24‐hour sleep amounts by providing a nap opportunity; to assess what effects an afternoon nap may have on subsequent nighttime sleep quality and composition.Design: Two‐session, within‐subject laboratory design.Setting: The study was conducted in the Laboratory of Human Chronobiology at Weill Cornell Medical College.Participants: Thirty‐two healthy men and women aged 55 to 85.Measurements: Polysomnography (sleep electroencephalogram), cognitive and psychomotor performance, body core temperature.Results: Napping had little effect on subsequent nighttime sleep quality or duration, resulting in a significant increase in 24‐hour sleep amounts. Such increased sleep resulted in enhanced cognitive and psychomotor performance immediately after the nap and throughout the next day.Conclusion: A behavioral approach that adds daytime sleep to the 24‐hour sleep quota seems worthy of consideration when presented with a situation in which physiological changes associated with aging may limit the duration of nighttime sleep.
Genetic Variant of Lactase‐Persistent C/T‐13910 Is Associated with Bone Fractures in Very Old Age
Authors: Enattah Nabil S. , Sulkava Raimo , Halonen Pirjo , Kontula Kimmo , Järvelä Irma 
Published: December 2004

Objectives: To determine the relation between the C/T‐13910 single‐nucleotide polymorphism residing 13,910 base pairs from the 5′ end of the lactase gene associated with lactase persistence and the occurrence of bone fractures in elderly people.Design: Population‐based study.Setting: Vantaa 85+ population‐based study, including all 601 subjects born before April 1, 1906, who were living in the city of Vantaa, Finland, on April 1, 1991.Participants: Four hundred eighty‐three people aged 85 and older (106 men and 377 women).Measurements: Genotype determination was made using a polymerase chain reaction minisequencing technique.Results: The frequency of the genotype C/C‐13910 associated with adult‐type hypolactasia (low lactase enzyme activity or primary lactose malabsorption (LM)) was significantly greater in individuals with hip fractures, with an adjusted odds ratio (OR) of 3.7 (95% confidence interval (CI)=1.8–7.8), wrist fractures with an adjusted OR of 2.5 (95% CI=1.2–5.2), and hip and wrist fractures combined with an adjusted OR of 4.1 (95% CI=2.0–8.3).Conclusion: The C/C‐13910 genotype associated with primary LM could represent a genetic risk factor for bone fractures for elderly people.