bluuebunny/crossref_metadata_2025 huggingface dataset:
Subjective fatigue and subjective sleepiness: two independent consequences of sleep disorders?
Authors: HOSSAIN JAMIL L. , AHMAD PARVEZ , REINISH LAWRENCE W. , KAYUMOV LEONID , HOSSAIN NAHEED K. , SHAPIRO COLIN M.
Published: August 2005

The objective of this investigation was to evaluate subjective fatigue versus subjective sleepiness as independent consequences of sleep disorders. Furthermore, we tried to explore how these symptoms relate to alertness, depressive symptoms and illness intrusiveness. In a prospective observational study, 283 sleep‐disordered patients referred to a hospital‐based sleep laboratory for various indications over a 1‐year period were evaluated vis‐à‐vis fatigue and sleepiness. All patients completed five subjective questionnaires, underwent objective sleep recording and attended a clinical interview with a sleep specialist. The subjective questionnaires included the Epworth Sleepiness Scale, the Fatigue Severity Scale, the Toronto Hospital Alertness Test, the Illness Intrusiveness Rating Scale and the Center for Epidemiologic Studies‐Depression Scale. Only 4% of the total sample was referred to the sleep clinic due to a complaint of excessive fatigue compared with 17% for excessive daytime sleepiness. However, during the assessment, 64% of referred patients reported pathological fatigue without overlap of sleepiness and only 4% reported pathological sleepiness without overlap of fatigue. Pearson's correlation analysis indicated a weak association (r = 0.18) between subjective fatigue and sleepiness in the total sample. Analysis of variance testing showed strong association between those patients with prominent fatigue and depressive symptoms (P < 0.01) and illness intrusiveness (P < 0.001). The findings support the notion that subjective fatigue and sleepiness can be independent manifestations of sleep disorders. Furthermore, predominantly fatigued individuals with sleep disorders seem vulnerable to additional negative consequences due to possible interplay between amplified fatigue and psychological distress.
Improving access to early treatment of malaria: a trial with primary school teachers as care providers
Authors: Afenyadu G. Y. , Agyepong I. A. , Barnish G. , Adjei S.
Published: August 2005

The feasibility of improving access to early case detection and prompt and adequate management of acute episodes of malaria using school teachers was explored through an intervention trial in Ghana. Of all the ‘fevers’ diagnosed as presumptive malaria by the trained teachers, 93% met the case definition. However, a lower proportion (75%) of such correctly diagnosed cases were subsequently treated according to the treatment protocol provided. In a scaled up study, pre‐packaging of the antimalarial drug improved the rate of adequate treatment to 97% of cases correctly diagnosed as presumptive malaria. Pre‐packaging of chloroquine ensured a high level of user compliance (96.6%), even in the face of diminished supervision of the teachers. It is feasible for the health and education sectors to work in partnership to improve access to early case detection and adequate management of acute episodes of malaria.
AIDS‐related Kaposi's sarcoma: epidemiological, diagnostic, treatment and control aspects in sub‐Saharan Africa
Authors: Sissolak Gerhard , Mayaud Philippe
Published: August 2005

Until the 1980s, little attention had been accorded to endemic Kaposi's sarcoma (KS), a neoplasm noted in several parts of Southern Europe and the African continent but with relatively slow progression, except in children and young adults. Furthermore, therapeutic approaches based on surgery, radiation and topical treatment were of limited efficacy, mostly used to overcome the disabling and stigmatizing effects of the disease. With the emergence of the HIV/AIDS epidemic, and the profound impact of KS on AIDS‐related mortality, the pathogenesis of KS has been better studied, and the realisation that a virus (KS‐associated Herpesvirus or Human Herpesvirus 8, or KSHV/HHV‐8), combined with immunosuppression and cytokine‐induced growth, was responsible for the development of this disease has led to novel therapeutic approaches. These are unfortunately still highly toxic, require careful monitoring, and are expensive, thus limiting their use in most parts of Africa. However, the use of highly active antiretroviral therapy (HAART), which has led to a considerable decline in KS incidence in populations of industrialized countries, constitutes the best hope for the control of this stigmatizing and lethal disease in Africa. Trials comparing different regimens of antiretroviral drugs in combination with systemic chemotherapeutic agents are urgently needed.
Spatial autocorrelation of assemblages of benthic invertebrates and its relationship to environmental factors in two upland rivers in southeastern Australia
Authors: Lloyd Natalie J. , Mac Nally Ralph , Lake P. Sam
Published: August 2005

The nature of spatial autocorrelation of biota may reveal much about underlying ecological and biological factors responsible for producing those patterns, especially dispersal processes (drift, adult flight, etc.). We report here on assemblage‐level autocorrelation in the benthic‐invertebrate assemblages (retained in sieves of 300 µm mesh) of riffles in two adjacent, relatively pristine rivers in southeastern Victoria, Australia (40‐km reaches of the Wellington and Wonnangatta Rivers). These are related to patterns of autocorrelation in physical and catchment conditions (‘environmental variables’) in the vicinity of the sampling points. Both the invertebrate assemblages and environmental variables were autocorrelated at small scales (= 8 km) in the Wellington River in one of the sampling years (1996). Dissimilarities of invertebrate assemblages were correlated with dissimilarities of environmental variables in both sampling years (1996 and 1997) in that river. Environmental variables were autocorrelated in the Wonnangatta River, but this was not expressed as autocorrelation in the assemblages of invertebrates, which were not autocorrelated at any scale studied. Individual environmental variables showed different spatial patterns between the two rivers. These results suggest that individual rivers have their own idiosyncratic patterns and one cannot assume that even similar, geographically adjacent rivers will have the same patterns, which is a difficulty for ecological assessment and restoration.
Mapping of an autosomal dominant gene for Dupuytren's contracture to chromosome 16q in a Swedish family
Authors: Hu FZ , Nystrom A , Ahmed A , Palmquist M , Dopico R , Mossberg I , Gladitz J , Rayner M , Post JC , Ehrlich GD , Preston RA
Published: August 2005

Dupuytren's contracture (DC) (OMIM 126900) is the most common connective tissue disease of mankind and has both heritable and sporadic forms. The inherited form is most frequently observed among the xanthochroi peoples of Northern Europe where its most common manifestations are thickening of the palmar fascia and contracture of the fingers. We ascertained a five‐generation Swedish family in which DC is inherited in an autosomal dominant manner with high, but incomplete, penetrance by the end of the fifth decade. Blood was collected from all affected and informative unaffected family members for the performance of a genome‐wide scan at a resolution of approximately 8 cM for all autosomes. Linkage was established to a single 6 cM region between markers D16S419 and D16S3032 on chromosome 16. A maximal two‐point logarithm of odds (LOD) score of 3.18 was achieved at microsatellite marker D16S415 with four other markers in the region producing LODs of >1.5.
A xyloglucan endotransglycosylase/hydrolase1, VrXTH1, is associated with cell elongation in mungbean hypocotyls
Authors: Yun Hye Sup , Kwon Chian , Kang Bin Goo , Lee June Seung , Han Tae‐Jin , Chang Soo Chul , Kim Seong‐Ki
Published: August 2005

Xyloglucan endotransglucosylase/hydrolases (XTHs) are thought to be involved in various aspects of plant development by modifying the structure of xyloglucan cross‐links. To address one of the roles of XTHs in plant growth, we identified an XTH, VrXTH1, in the mungbean through a differential reverse transcriptase‐polymerase chain reaction. The deduced amino acid sequence of VrXTH1 shows high similarity to other XTHs. In addition, a signal peptide consisting of 17 amino acids is found at the N‐terminus. The gene expression of VrXTH1 was differentially regulated in tissues and was higher in hypocotyls and stems than it was in other tissues. The steady state level of VrXTH1 transcripts was closely related to the elongation regions of hypocotyls. Notably, in the elongation region of hypocotyls, most VrXTH1 mRNAs were limited to the epidermis and to some layers of the cortex that act as growth‐limiting tissue. Growth‐promoting hormones, such as auxin and brassinolide, strongly enhanced mRNA accumulation of VrXTH1. However, abscisic acid, a hormone which is antagonistic to auxin, acted as a downregulator. Overall, VrXTH1 seems to play a role in plant growth at the gene level and, thus, by possibly altering cell wall morphogenesis in mungbean hypocotyls.
Biosynthesis profile and endogenous titers of polyamines differ in totipotent and recalcitrant plant protoplasts
Authors: Papadakis Anastasia K. , Paschalidis Konstantinos A. , Roubelakis‐Angelakis Kalliopi A.
Published: August 2005

The expression of totipotency in plant protoplasts is a complex developmental phenomenon and is affected by genetic and physiological factors. Polyamines (PAs) are known to be involved in a variety of growth and developmental processes in higher plants, as well as in adaptation to stresses. In this study, we present the homeostatic characteristics of the endogenous PA putrescine (Put), spermidine (Spd), and spermine (Spm) in totipotent (T) and non‐totipotent (NT) tobacco protoplasts and in recalcitrant (R) grapevine protoplasts. T‐tobacco protoplasts, with high division rates, have the highest level of endogenous PAs. In these protoplasts, the soluble‐hydrolyzed fraction predominates and increases, and the insoluble‐hydrolyzed fraction also increases, whereas soluble (S) PAs decrease rapidly during culture. The isolation process contributes to the increased Put levels, which are higher in freshly isolated NT‐tobacco protoplasts than in T‐protoplasts. During culture, total Put predominates over Spd and Spm, and the highest accumulation is found in T‐protoplasts. Ornithine decarboxylase and arginase activities both increase in T‐protoplasts, whereas arginine decarboxylase activity causes Put accumulation in NT‐tobacco protoplasts. R‐grapevine protoplasts show a different PA profile, mostly due to the lower PA content, the higher S‐fraction, and the higher ratio of Spm to total PAs. The data suggest that the levels and metabolism of the intracellular PAs could be related to the expression of totipotency of plant protoplasts.
Muscle Cellularity at Cranial and Caudal Levels of the Trunk Musculature of Commercial Size Sea Bass,Dicentrarchus labrax(Linnaeus, 1758)
Authors: Abdel I. , López‐Albors O. , Ayala Ma. D. , García‐Alcazar A. , Abellán E. , Latorre R. , Gil F.
Published: August 2005

In eight specimens of Atlantic sea bass of commercial size (≅350 g) muscle cellularity was studied at two selected sampling levels of the trunk axial musculature: caudal (anal opening) and cranial (fourth radius of the dorsal fin). The following parameters were quantified at both sampling levels: white muscle cross‐sectional area, white muscle fibre diameter (900–1200 fibres), muscle fibre number and muscle fibre density. Results showed a higher total cross‐sectional area at cranial than at caudal level (P < 0.05), what is related with their different gross morphology. However, the white muscle fibre size distribution, as well as the muscle fibre number and density did not show significant differences between them. This study contributes to typify muscle fibre sampling in sea bass of commercial size what is of great interest for morphometric studies where white muscle cellularity is commonly correlated with textural or organoleptic parameters.
Schistosomus Reflexus Syndrome: A Heritable Defect in Ruminants
Authors: Laughton K. W. , Fisher K. R. S. , Halina Partlow W. G., G. D.
Published: August 2005

Schistosomus reflexus (SR) is a rare and fatal congenital disorder. Primarily observed in ruminants, its defining features include spinal inversion, exposure of the abdominal viscera because of a fissure of the ventral abdominal wall, limb ankylosis, positioning of the limbs adjacent to the skull and, lung and diaphragm hypoplasia. Variable components of SR include scoliosis, cleft sternum, exposure of thoracic viscera, and abnormalities of the digestive and urogenital systems. This report presents the findings from an anatomical analysis of a female Holstein SR calf with thoracoschisis, scoliosis and anomalies of the appendicular skeleton, cardiovascular, respiratory, digestive and urogenital systems. Many of these malformations have not been previously reported. The reproductive tract of this case is particularly unique, displaying Muellerian duct abnormalities. These abnormalities suggest SR occurs as early as the post‐gastrulation embryo and involves the intermediate mesoderm. Preliminary analysis of associated cases suggests that SR has a genetic aetiology.
A New Stem‐splitting Symptom in Safflower Caused by Macrophomina phaseolina
Authors: Govindappa M. , Lokesh S. , Ravishankar Rai V.
Published: August 2005

Safflower is known to be attacked by several seed‐borne fungi, of which Macrophomina phaseolina is one of the most important pathogens causing serious yield losses. During routine experiments, a new stem‐split symptom was observed in M. phaseolina‐infected plants resulting in poor growth and reduced size of inflorescences. Stem‐split was observed in 30‐day‐old plants as minute cracks approximately 2–3 cm above the soil surface, which over time extended to both upward and downward directions, resulting in the formation of a wider split. The split portion was hollow and brown with a white to grey mycelial mat of the fungus on the inner surface. Such plants became lodged, ultimately resulting in poor seed yield compared with healthy plants. The stem‐split plants showed delayed flowering by 1 week over healthy plants. One of the three M. phaseolina isolates used for inoculation of seeds and plants was more aggressive but all isolates were able to reproduce the stem‐split symptoms found on naturally infected safflower plants in the field.
Influence of N‐fertilization and Fungicide Strategies on Fusarium Head Blight Severity and Mycotoxin Content in Winter Wheat
Authors: Heier T. , Jain S. K. , Kogel K.‐H. , Pons‐Kühnemann J.
Published: August 2005

Nitrogen (N) fertilization and fungicide applications are still subject to discussion concerning the influence on Fusarium head blight (FHB) and related mycotoxin accumulation. Field studies were made in 2000–2001 and 2001–2002 to investigate the effect of two N‐rates and 11 plant protection treatments on FHB severity and the content of FHB‐related mycotoxins, namely deoxynivalenol (DON) and zearalenone (ZEA) under conditions of natural infection. The treatments applied can be summarized as (i) an integrated approach using a decision support system, (ii) the use of two plant strengtheners, Bion® (benzo [1,2,3]thiadiazole‐7‐carbothioic acid S‐methyl‐ester, BTH) and a compound based on the biomass of the cyanobacterium Spirulina platensis, (iii) the use of plant strengtheners in combination with a broad‐spectrum fungicide and (iv) common fungicide strategies against foliar diseases. Fusarium infections as well as the analysed mycotoxins were observed at low levels in both years. Disease severity was significantly increased by conventional N‐fertilization only in 2001. Neither FHB severity nor mycotoxin accumulation was significantly influenced by any of the treatments, although treatments without fungicides appeared to lead to lower disease severities. In 2002, there was a tendency towards higher disease severities when common fungicide strategies were applied. Mycotoxin contamination was found in grain samples from both years. In 2001 DON was mainly traceable, whereas in 2002 ZEA was also detected. Mycotoxin contamination was influenced by N‐fertilization rather than by the treatments. In 2001, the DON content was significantly increased due to the conventional N‐supply. Our results indicate that less intensive fungicide strategies, including plant strengtheners, are no worse than common fungicide strategies under conditions of low FHB severity and mycotoxin accumulation. Immoderate N‐fertilization however, can increase mycotoxin levels significantly even under conditions unfavourable for Fusarium spp.
A systematic review of telemedicine interventions to support blood glucose self‐monitoring in diabetes
Authors: Farmer A. , Gibson O. J. , Tarassenko L. , Neil A.
Published: August 2005

Aims To evaluate evidence for feasibility, acceptability and cost‐effectiveness of diabetes telemedicine applications.

Methods medline,embase,psychinfo,cinahl, Cochrane, andinspecwere searched using the terms diabetes and telemedicine for clinical studies using electronic transfer of blood glucose results in people with diabetes. The technology used, trial design and clinical outcome measures used were extracted for trials and prospective cohort studies. Randomized controlled trials with HbA1cas an outcome were pooled using standard meta‐analytical methods.

Results We identified 539 papers among which 32 papers described 10 prospective cohort studies, 12 parallel group randomized controlled trials (RCT), three crossover trials, and one non‐parallel group trial. Only two studies described full details of randomization, blinding of outcomes and dropouts and withdrawals. Electronic transfer of glucose results appears feasible in a clinical setting. Only two of the RCTs included more than 100 patients, and only three extended to 1 year. Only one study was designed to show that telemedicine interventions might replace clinic interventions without deterioration in HbA1c. Results pooled from the nine RCTs with reported data did not provide evidence that the interventions were effective in reducing HbA1c(−0.1%, 95% CI −0.4% to 0.04%).

Conclusions Telemedicine solutions for diabetes care are feasible and acceptable, but evidence for their effectiveness in improving HbA1cor reducing costs while maintaining HbA1clevels, or improving other aspects of diabetes management is not strong. Further research should seek to understand how telemedicine might enhance educational and self‐management interventions and RCTs are required to examine cost‐effectiveness.
Diabetic ketoacidosis associated with aripiprazole
Authors: Church C. O. , Stevens D. L. , Fugate S. E.
Published: August 2005

Background  Atypical antipsychotics have become the mainstay of management of schizophrenia and other psychotic disorders due to low risk of extrapyramidal symptoms. However, postmarketing data has reported atypical antipsychotic agents being associated with hyperglycaemia and diabetic ketoacidosis (DKA). We believe this to be the first published report of hyperglycaemia and DKA with the newest atypical antipsychotic agent, aripiprazole.

Case report  A 34‐year‐old African‐American female with schizophrenia presented to the emergency department with nausea, vomiting, and malaise for 3–4 days shortly after initiation of aripiprazole therapy. Initial laboratory results revealed significant hyperglycaemia with metabolic acidosis. The patient received treatment for DKA with an intravenous insulin infusion and fluid replacement. Isophane insulin suspension (NPH insulin) was begun immediately following the insulin drip and continued upon discharge from the hospital. Outpatient follow‐up information was not available.

Conclusion  To our knowledge, this is the first case report of aripiprazole associated with hyperglycaemia and DKA. This case is striking in that DKA occurred 4 days following initiation of aripiprazole and the patient had rapid resolution of symptoms and normalization of laboratory values upon discontinuation of aripiprazole. It is important that health‐care providers monitor for hyperglycaemia when prescribing atypical antipsychotics including aripiprazole.
Effects of doxazosin on ambulatory blood pressure and sympathetic nervous activity in hypertensive Type 2 diabetic patients with overt nephropathy
Authors: Yasuda G. , Hasegawa K. , Kuji T. , Ogawa N. , Shimura G. , Umemura S. , Tochikubo O.
Published: August 2005

Aims  Few studies have reported the effect of α1‐adrenergic antagonists on 24‐h blood pressure (BP) and sympathetic nervous activity in hypertensive patients with diabetic nephropathy. We assessed the effects of doxazosin on 24‐h BP and spectral analysis of heart rate variability in hypertensive Type 2 diabetic patients with macroalbuminuria and compared the results with those in hypertensive Type 2 diabetic patients with normoalbuminuria and non‐diabetic patients with essential hypertension.

Methods  Thirty‐three patients in the macroalbuminuric group, 24 patients in the normoalbuminuric group, and 34 patients with essential hypertension underwent ambulatory BP monitoring before and after doxazosin treatment. Spectral analysis was performed to calculate the high‐frequency (HF) components, a marker of parasympathetic nervous activity, and the low‐frequency (LF) components, a marker of sympathetic nervous activity.

Results  Doxazosin decreased waking (from 158 ± 17/88 ± 10 to 148 ± 15/80 ± 7 mmHg, P = 0.001 for systolic and P < 0.001 for diastolic BP) and sleeping BP (146 ± 20/79 ± 10 to 137 ± 17/72 ± 9 mmHg, P < 0.001 and P < 0.001) in the macroalbuminuric group, but only decreased waking BP in the essential hypertension group (157 ± 16/91 ± 9 to 145 ± 15/84 ± 11 mmHg, P < 0.001 and P < 0.001) and normoalbuminuric group (159 ± 15/89 ± 9 to 150 ± 16/82 ± 10 mmHg, P = 0.014 and P < 0.001). Doxazosin decreased waking (from 1.48 ± 0.11 to 1.42 ± 0.12, P = 0.001) and sleeping (1.46 ± 0.11 to 1.40 ± 0.13, P = 0.001) LF components [unit: log(ms2/Hz)] only in the macroalbuminuric group without changing HF components. The normoalbuminuric and essential hypertension groups showed no differences (P = 0.637 and 0.492) in LF components during sleep.

Conclusions  Doxazosin may be an antihypertensive agent that decreases both waking and sleeping BP through inhibiting sympathetic nervous activity in macroalbuminuric diabetes patients.
The impact of diabetes or elevated fasting blood glucose on cardiovascular prognosis in patients with stable angina pectoris
Authors: Held C. , Björkander I. , Forslund L. , Rehnqvist N. , Hjemdahl P.
Published: August 2005

Aims  To examine the influences of diabetes and elevated fasting blood glucose on cardiovascular prognosis in patients with stable angina pectoris.

Methods  In a prospective study of 809 patients with stable angina pectoris randomized to receive metoprolol or verapamil, a subgroup of 69 diabetic patients was compared with non‐diabetic patients with respect to the risk of cardiovascular (CV) death, non‐fatal myocardial infarction (MI) and revascularization. We also analysed a subgroup of 67 patients with fasting blood glucose ≥ 6.1 mmol/l, defined according to the most recent revised guidelines for the diagnosis of diabetes mellitus. Fasting blood glucose was measured in venous whole blood at baseline.

Results  The diabetic patients had a greater risk‐factor burden, with a higher prevalence of hypertension, more likely to be male, a tendency towards a higher prevalence of previous MI, and higher triglyceride and lower high‐density lipoprotein (HDL)‐cholesterol levels. In multivariate analyses, diabetes was an independent risk factor for CV events with a relative risk of 2.64 (CI 1.39–5.00; P < 0.001) for CV death/MI, and 1.79 (CI 1.02–3.15; P < 0.01) for revascularization. Blood glucose ≥ 6.1 mmol/l without a diagnosis of diabetes mellitus was found in 67 patients, and predicted CV death/MI [relative risk 2.76 (CI 1.97–3.84)] in both univariate and multivariate analyses. The prognosis of diabetic or hyperglycaemic patients did not differ significantly with metoprolol compared with verapamil treatment.

Conclusions  Diabetes mellitus is an independent risk factor for CV death/MI and for revascularization in patients with stable angina pectoris. Elevated fasting blood glucose was seen in 9% of patients without known diabetes and was an equally strong and independent risk factor for CV death/MI as diagnosed and treated diabetes.
Five‐year risk of developing clinical diabetes after first myocardial infarction; the FINAMI study
Authors: Pajunen P. , Koukkunen H. , Ketonen M. , Jerkkola T. , Immonen‐Räihä P. , Kärjä‐Koskenkari P. , Mähönen M. , Niemelä M. , Kuulasmaa K. , Palomäki P. , Mustonen J. , Lehtonen A. , Arstila M. , Vuorenmaa T. , Lehto S. , Miettinen H. , Juolevi A. , Torppa J. , Tuomilehto J. , Kesäniemi Y. A. , Pyörälä K. , Salomaa V.
Published: August 2005

Aim  To investigate the incidence of clinical diabetes as determined by the incidence of diabetes drug reimbursements within a 5‐year period after the first myocardial infarction (MI) in patients who were non‐diabetic at the time of their first MI.

Research design and methods  A population‐based MI register, FINMONICA/FINAMI, recorded all coronary events in persons of 35–64 years of age between 1988 and 2002 in four study areas in Finland. These records were used to identify subjects sustaining their first MI (n = 2632). Participants of the population‐based risk factor survey FINRISK (surveys 1987, 1992, 1997 and 2002), who did not have diabetes or a history of MI, served as the control group (n = 7774). The FINMONICA/FINAMI study records were linked with the National Social Security Institute's drug reimbursement records, which include diabetes medications, using personal identification codes. The records were used to identify subjects who developed diabetes during the 5‐year follow‐up period (n = 98 in the MI group and n = 79 in the control group).

Results  Sixteen per cent of men and 20% of women sustaining their first MI were known to have diabetes and thus were excluded from this analysis. Non‐diabetic men having a first MI were at more than twofold {hazard ratio (HR) 2.3 [95% confidence interval (CI) 1.6–3.4]}, and women fourfold [HR 4.3 (95% CI 2.4–7.5)], risk of developing diabetes mellitus during the next 5 years compared with the control population without MI.

Conclusions  Many patients who do not have diabetes at the time of their first MI develop diabetes in the following 5 years.
Repaglinide treatment amplifies first‐phase insulin secretion and high‐frequency pulsatile insulin release in Type 2 diabetes
Authors: Hollingdal M. , Sturis J. , Gall M.‐A. , Damsbo P. , Pincus S. , Veldhuis J. D. , Pørksen N. , Schmitz O. , Juhl C. B.
Published: August 2005

Aims/hypothesis  First‐phase insulin release and coordinated insulin pulsatility are disturbed in Type 2 diabetes. The present study was undertaken to explore a possible influence of the oral prandial glucose regulator, repaglinide, on first‐phase insulin secretion and high‐frequency insulin pulsatility in Type 2 diabetes.

Methods  We examined 10 patients with Type 2 diabetes in a double‐blind placebo‐controlled, cross‐over design. The participants were treated for 6 weeks with either repaglinide [2–9 mg/day (average 5.9 mg)] or placebo in random order. At the end of each treatment period, first‐phase insulin secretion was measured. Entrainment of insulin secretion was assessed utilizing 1‐min glucose bolus exposure (6 mg/kg body weight every 10 min) for 60 min during (A) baseline conditions, i.e. 12 h after the last repaglinide/placebo administration, and (B) 30 min after an oral dose of 0.5 mg repaglinide/placebo with subsequent application of time‐series analyses.

Results  Postprandial (2‐h) blood glucose was significantly reduced by repaglinide after 5 weeks of treatment (P < 0.001). The fall in HbA1c did not reach statistical significance (P = 0.07). AUCins,0−12 min during the first‐phase insulin secretion test was enhanced (P < 0.05). In addition, glucose entrained insulin secretory burst mass and amplitude increased markedly (burst mass: repaglinide, 44.4 ± 6.0 pmol/l/pulse vs. placebo, 31.4 ± 3.3 pmol/l/pulse, P < 0.05; burst amplitude: repaglinide, 17.7 ± 2.4 pmol/l/min vs. placebo, 12.6 ± 1.3 pmol/l/min, P < 0.05) while basal insulin (non‐pulsatile) secretion was unaltered. After acute repaglinide exposure (0.5 mg) basal insulin secretion increased significantly (P < 0.05). Neither acute nor chronic repaglinide administration influenced frequency or regularity of insulin pulses during entrainment.

Conclusion/interpretation  Repaglinide augments first‐phase insulin secretion as well as high‐frequency insulin secretory burst mass and amplitude during glucose entrainment in patients with Type 2 diabetes, while regularity of the insulin release process was unaltered.

Diabet. Med. (2005)
Evaluation of the association between the EQ‐5Dindex (health‐related utility) and body mass index (obesity) in hospital‐treated people with Type 1 diabetes, Type 2 diabetes and with no diagnosed diabetes
Authors: Lee A. J. , Morgan C. Ll. , Morrissey M. , Wittrup‐Jensen K. U. , Kennedy‐Martin T. , Currie C. J.
Published: August 2005

Aims  The purpose of this study was to characterize the impact of body mass index (BMI) on health‐related utility for patients with Type 1 and Type 2 diabetes and those without diabetes.

Methods  The study was conducted in Cardiff and the Vale of Glamorgan, Wales, UK. Health‐related utility was measured using the EQ‐5Dindex. Patients from the Health Outcomes Data Repository (HODaR) were surveyed by postal questionnaire either 6 weeks post discharge for in‐patients or at out‐patient clinics between January 2002 and July 2003. BMI was calculated from self‐reported data within the survey. Patients with diabetes were identified by a previous history of an in‐patient admission with diabetes or as an out‐patient with diabetes recorded as a coexisting diagnosis.

Results  Questionnaires were returned from 27 924 patients of whom 2575 had diabetes. Increasing BMI was found to reduce utility in all three groups. BMI was significantly greater for those with Type 2 diabetes compared with those with Type 1, and those without diabetes (P < 0.001). Multiple regression analysis demonstrated that both BMI and diabetes status had a significant effect on utility. However, the rate of change of utility attributable to BMI was not found to be significantly different between the various groups.

Conclusions  Obesity negatively impacts upon health‐related utility and thus quality of life for all patient groups. There was no significant difference in the effect of obesity on utility between those with and without diabetes.
Prevalence of Type 2 diabetes in urban and rural Chinese populations in Qingdao, China
Authors: Dong Y. , Gao W. , Nan H. , Yu H. , Li F. , Duan W. , Wang Y. , Sun Bin , Qian R. , Tuomilehto J. , Qiao Q.
Published: August 2005

Aims  To determine the prevalence of diabetes in the Chinese adult population in rural and urban areas of Qingdao city.

Methods  A population‐based cross‐sectional study of diabetes was performed in 12 436 (5346 men) Chinese adults (20–74 years old) from 2001 to 2002. Fasting capillary whole blood glucose test (FCG) was performed in all participants and a 2‐h 75‐g oral glucose tolerance test in those with FCG ≥ 6.1 mmol/l following initial screening. The 1999 World Health Organization diagnostic criteria for diabetes were used.

Results  The age‐standardized prevalence of diabetes was 6.1% (4.1% for undiagnosed and 2.1% for previously known diabetes) in adults aged 20–74 years. Diabetes prevalence increased with age up to the oldest age group (70–74); in subjects over 50 years of age, the prevalence reached 10%. Men tended to have a higher prevalence of known diabetes than women, whereas the prevalence of undiagnosed diabetes was lower in men than in women (4.6% vs. 3.3%, d.f. = 1, P = 0.001). Diabetes was more prevalent in the urban than in the rural population (6.9% vs. 5.6%, d.f. = 1, P < 0.001). However, the proportion of undiagnosed diabetes was higher in the rural than in the urban areas (70.5% vs. 58.0%, d.f. = 1, P < 0.001).

Conclusions  The prevalence of Type 2 diabetes in Qingdao city is moderately high, but much higher than reported in 1996. The large proportion of undiagnosed cases of diabetes indicates the lack of public awareness of diabetes and shortage of medical facilities. In view of the huge population in China, the results of this study emphasize the need to improve the early detection and prevention of diabetes in China to prevent the emerging diabetes epidemic.
The perils of procrastination: effects of early vs. delayed detection and treatment of incipient Charcot fracture
Authors: Chantelau E.
Published: August 2005

Background  At the onset of acute diabetic Charcot foot, therapeutic intervention may be delayed because plain X‐rays may not show fractures.

Aim of the study  To assess the clinical course of acute Charcot foot in 24 patients without evidence of definite fractures on the first X‐ray after onset of symptoms, who were referred to the foot clinic for diagnosis and treatment either early or delayed, i.e. before or after definite fractures were detectable on repeat X‐rays.

Patients and methods  Eleven patients were referred early (incipient Charcot foot, case group), and 13 patients were referred delayed (overt Charcot foot, control group). In the foot clinic, both groups were immediately treated with off‐loading and total contact casting. After the healing process of the Charcot foot was complete, the extent of fractures and subsequent deformities were evaluated.

Results  Based on X‐rays at the onset of symptoms, in 19 of the 24 patients the condition had been misdiagnosed prior to referral (in 11 patients as sprain injury). Additional imaging techniques (MRI, CT scan or bone scintigraphy) had been performed in 10 patients prior to referral. While these techniques had been used more frequently in the cases vs. the controls (P = 0.012), misdiagnosis was less frequent in the cases vs. the controls (P = 0.013). Only one out of 11 case patients developed extended foot fractures and severe deformity, vs. 12 out of 13 control patients (P < 0.001).

Conclusion  Early detection of incipient Charcot foot is facilitated by imaging techniques other than plain X‐rays. Immediate off‐loading of incipient Charcot foot appears to minimize fractures and incapacitating deformities.
Interventions to promote optimal health outcomes in children with Type 1 diabetes—are they effective?
Authors: Northam E. A. , Todd S. , Cameron F. J.
Published: August 2005

The incidence of Type 1 diabetes is increasing worldwide, imposing enormous public health costs, as well as profoundly affecting individual quality of life. There is evidence that psychological problems are increased in children with diabetes and this morbidity is often associated with poor metabolic control. Specific risk factors for this dual morbidity are emerging from empirical studies. The next challenge is to identify effective interventions for use with children at risk for adverse mental and physical health outcomes. The intervention literature is reviewed. It is noted that most studies have used diabetes‐specific, unstandardized interventions in groups of adolescents, with few interventions trialled with younger children. No study has targeted a specific psychological disorder such as behaviour problems or depression, both of which are known to be increased in children with diabetes and for which effective standardized interventions are available. Attention is drawn to methodological limitations in many of the studies conducted to date and suggestions made to reduce these in future interventions attempting to reduce the burden of illness in children with diabetes.
Novel polymorphisms in the GCKR gene and their influence on glucose and insulin levels in a Danish twin population
Authors: Køster B. , Fenger M. , Poulsen P. , Vaag A. , Bentzen J.
Published: August 2005

Aim  The glucokinase regulatory protein gene is a candidate gene for Type 2 diabetes. This study reveals three new polymorphisms and examines the impact of one new and one known polymorphism on insulin secretion and parameters associated with the insulin resistance syndrome in Danish twins with different degrees of glucose tolerance.

Methods  Single nucleotide polymorphism detection was performed in 20 healthy subjects and in 20 subjects with Type 2 diabetes. The effect of the polymorphisms on lipid, glucose and insulin measures was studied in 566 same‐sex twins aged 55–74 years.

Results  The new nucleotide (nt) 363 polymorphism was found only in subjects with impaired glucose tolerance and Type 2 diabetes. The nt 11216 polymorphism influenced insulin measured at 120 min during an oral glucose tolerance test (OGTT). Subjects with genotype C11216C/T11216C had 21% higher insulin values (P < 0.05) than subjects with genotype T11216T. In twins discordant for this genotype, the C‐allele was associated with significantly higher plasma insulin levels at all time points during the OGTT, higher β‐cell function and lower plasma glucose levels during the OGTT.

Conclusion  The C‐allele of nt 11216 polymorphism was associated with increased insulin secretion, and may therefore exert a potentially protective effect against Type 2 diabetes. This remains to be shown in a larger study population.
Common promoter polymorphism in monocyte differentiation antigen CD14 is associated with serum triglyceride levels and body mass index in non‐diabetic individuals
Authors: Shin H. D. , Park K. S. , Park B. L. , Cheong H. S. , Cho Y. M. , Lee H. K. , Lee J.‐Y. , Lee J.‐K. , Kim H. T. , Han B. G. , Kim J. W. , Koh I. , Kim Y. J. , Oh B. , Kimm K. , Park C.
Published: August 2005

Aims  Growing evidence supports the hypothesis that chronic low‐grade inflammation related to innate immunity may play an important role in the pathophysiology of Type 2 diabetes mellitus (T2DM). The monocyte differentiation antigen CD14 gene (CD14) acts as the receptor for lipopolysaccharide (LPS) and augments monocyte/macrophage inflammatory responses.

Methods  We have sequenced the gene, including all exons, exon/intron boundaries, and the −1.5 kb of the 5′ flanking region. Two common loci (minor allele frequency > 0.05) were genotyped in 775 T2DM patients and 316 control subjects recruited in the Korean T2DM Study.

Results  Eight polymorphisms, including four non‐synonymous forms, were identified in CD14. No polymorphisms were found in association with T2DM. However, one common promoter SNP (−260T>C) was significantly associated with both the serum triglyceride level (TG) and body mass index (BMI) in non‐diabetic control subjects. Individuals who carried the minor allele (C) had higher TG levels (1.65 ± 0.81 vs. 1.46 ± 0.80 mmol/l; P = 0.0007) and BMI (23.96 ± 3.00 vs. 23.28 ± 3.22 kg/m2; P = 0.04) as compared with subjects carrying T/T genotypes.

Conclusion  Our data suggest that lipid metabolism and obesity, important pathophysiological elements of T2DM and the metabolic syndrome, are regulated by complex mechanisms that include the CD14 gene polymorphism‐mediated genetic propensity to non‐specific inflammatory responses.
Alcohol is a potent stimulant of immature neuronal networks: implications for fetal alcohol spectrum disorder
Authors: Galindo Rafael , Zamudio Paula A. , Valenzuela C. Fernando
Published: August 2005

Ethanol consumption during development affects the maturation of hippocampal circuits by mechanisms that are not fully understood. Ethanol acts as a depressant in the mature CNS and it has been assumed that this also applies to immature neurons. We investigated whether ethanol targets the neuronal network activity that is involved in the refinement of developing hippocampal synapses. This activity appears during the growth spurt period in the form of giant depolarizing potentials (GDPs). GDPs are generated by the excitatory actions of GABA and glutamate via a positive feedback circuit involving pyramidal neurons and interneurons. We found that ethanol potently increases GDP frequency in the CA3 hippocampal region of slices from neonatal rats. It also increased the frequency of GDP‐driven Ca2+ transients in pyramidal neurons and increased the frequency of GABAA receptor‐mediated spontaneous postsynaptic currents in CA3 pyramidal cells and interneurons. The ethanol‐induced potentiation of GABAergic activity is probably the result of increased quantal GABA release at interneuronal synapses but not enhanced neuronal excitability. These findings demonstrate that ethanol is a potent stimulant of developing neuronal circuits, which might contribute to the abnormal hippocampal development associated with fetal alcohol syndrome and alcohol‐related neurodevelopmental disorders.
ATP‐sensitive potassium channel opener iptakalim protected against the cytotoxicity of MPP+ on SH‐SY5Y cells by decreasing extracellular glutamate level
Authors: Hu Li‐Fang , Wang Sen , Shi Xue‐Ru , Yao Hong‐Hong , Sun Ye‐Hong , Ding Jian‐Hua , Liu Shu‐Yi , Hu Gang
Published: August 2005

Mounting evidence reveals that ATP‐sensitive potassium (KATP) channel openers (KCOs) exert significant neuroprotection in vivo and in vitro in several models of Parkinson's disease (PD). However, the mechanisms are not well understood. In this study, we demonstrated that SH‐SY5Y cells expressed mRNA and proteins for Kir6.1, Kir6.2, SUR1 and SUR2 subunits of KATP channels. Moreover, our results showed that 1‐methyl‐4‐phenyl‐pyridinium ion (MPP+) induced up‐regulation of mRNA for the Kir6.2 subunit and down‐regulation of SUR1. It was further found that pretreatment with iptakalim, a novel KATP channel opener, could attenuate increased extracellular glutamate level and decreased cell survival in SH‐SY5Y cell culture after exposure to MPP+. Trans‐pyrrolidine‐2, 4‐dicarboxylic acid (t‐PDC), a glutamate transporter inhibitor, partially blocked the effect of iptakalim decreasing extracellular glutamate level. Additionally, iptakalim prevented MPP+‐induced inhibition of glutamate uptake in primary cultured astrocytes. The beneficial effects of iptakalim on glutamate uptake of astrocytes were abolished by selective mitochondrial KATP (mitoKATP) channel blocker 5‐HD. These results suggest (i) KATP channel dysfunction may be involved in the mechanisms of MPP+‐induced cytotoxicity and (ii) iptakalim may modulate glutamate transporters and subsequently alleviate the increase of extracellular glutamate levels induced by MPP+ through opening mitoKATP channels, thereby protecting SH‐SY5Y cells against MPP+‐induced cytotoxicity.
Netrin induces down‐regulation of its receptor, Deleted in Colorectal Cancer, through the ubiquitin–proteasome pathway in the embryonic cortical neuron
Authors: Kim Tae‐Hong , Lee Hyun Kyoung , Seo In Ae , Bae Hae Rahn , Suh Duk Joon , Wu Jane , Rao Yi , Hwang Kyu‐Geun , Park Hwan Tae
Published: August 2005

The proper regulation of temporal and spatial expression of the axon guidance cues and their receptors is critical for the normal wiring of nervous system during development. Netrins, a family of secreted guidance cues, are involved in the midline crossing of spinal commissural axons and in the guidance of cortical efferents. Axons normally lose the responsiveness to their attractants when they arrive at their targets, where the attractant is produced. However the molecular mechanism is still unknown. We investigated the molecular mechanism of down‐regulation of netrin‐1 signaling in the embryonic cortical neurons. Netrin‐1 induced the ubiquitination and proteolytic cleavage of Deleted in Colorectal Cancer (DCC), a transmembrane receptor for netrin, in dissociated cortical neurons. A dramatic decrease of DCC level particularly on the cell surface was also observed after netrin‐1 stimulation. Specific ubiquitin–proteasome inhibitors prevented the netrin‐induced DCC cleavage and decrease of cell surface DCC. We suggest that the ligand‐mediated down‐regulation of DCC might participate in the loss of netrin‐responsiveness in the developing nervous system.
Androgens activate mitogen‐activated protein kinase signaling: Role in neuroprotection
Authors: Nguyen Thuy‐Vi V. , Yao Mingzhong , Pike Christian J.
Published: August 2005

Recent evidence indicates that testosterone is neuroprotective, however, the underlying mechanism(s) remains to be elucidated. In this study, we investigated the hypothesis that androgens induce mitogen‐activated protein kinase (MAPK) signaling in neurons, which subsequently drives neuroprotection. We observed that testosterone and its non‐aromatizable metabolite dihydrotestosterone (DHT) rapidly and transiently activate MAPK in cultured hippocampal neurons, as evidenced by phosphorylation of extracellular signal‐regulated kinase (ERK)‐1 and ERK‐2. Importantly, pharmacological suppression of MAPK/ERK signaling blocked androgen‐mediated neuroprotection against β‐amyloid toxicity. Androgen activation of MAPK/ERK and neuroprotection also was observed in PC12 cells stably transfected with androgen receptor (AR), but in neither wild‐type nor empty vector‐transfected PC12 cells. Downstream of ERK phosphorylation, we observed that DHT sequentially increases p90 kDa ribosomal S6 kinase (Rsk) phosphorylation and phosphorylation‐dependent inactivation of Bcl‐2‐associated death protein (Bad). Prevention of androgen‐induced phosphorylation of Rsk and Bad blocked androgen neuroprotection. These findings demonstrate AR‐dependent androgen activation of MAPK/ERK signaling in neurons, and specifically identify a neuroprotective pathway involving downstream activation of Rsk and inactivation of Bad. Elucidation of androgen‐mediated neural signaling cascades will provide important insights into the mechanisms of androgen action in brain, and may present a framework for therapeutic intervention of age‐related neurodegenerative disorders.
Two types of detergent‐insoluble, glycosphingolipid/cholesterol‐rich membrane domains from isolated myelin
Authors: Arvanitis Dina N. , Min Weixian , Gong Yanping , Heng Yew M. , Boggs Joan M.
Published: August 2005

Two different types of low‐density detergent‐insoluble glycosphingolipid‐enriched membrane domain (DIG) fractions were isolated from myelin by extraction with Triton X‐100 (TX‐100) in 50 mM sodium phosphate buffer at room temperature (20°C) (procedure 1), in contrast to a single low‐density fraction obtained by extraction with TX‐100 in Tris buffer containing 150 mM NaCl and 5 mM EDTA at 4°C (procedure 2). Procedure 1 has been used in the past by others for myelin extraction to preserve the cytoskeleton and/or radial component of oligodendrocytes and myelin, whereas procedure 2 is now more commonly used to isolate myelin DIG fractions. The two DIG fractions obtained by procedure 1 gave opaque bands, B1 and B2, at somewhat lower and higher sucrose density respectively than myelin itself. The single DIG fraction obtained by procedure 2 gave a single opaque band at a similar sucrose density to B1. Both B1 and B2 had characteristics of lipid rafts, i.e. high galactosylceramide and cholesterol content and enrichment in GPI‐linked 120‐kDa neural cell adhesion molecule (NCAM)120, as found by others for the single low‐density DIG fraction obtained by procedure 2. However, B2 had most of the myelin GM1 and more of the sulfatide than B1, and they differed significantly in their protein composition. B2 contained 41% of the actin, 100% of the tubulin, and most of the flotillin‐1 and caveolin in myelin, whereas B1 contained more NCAM120 and other proteins than B2. The single low‐density DIG fraction obtained by procedure 2 contained only low amounts of actin and tubulin. B1 and B2 also had size‐isoform selectivity for some proteins, suggesting specific interactions and different functions of the two membrane domains. We propose that B1 may come from non‐caveolar raft domains whereas B2 may derive from caveolin‐containing raft domains associated with cytoskeletal proteins. Some kinases present were active on myelin basic protein suggesting that the DIGs may come from signaling domains.