bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of diabetes and/or ischaemic heart disease in classes of increasing carotid artery atherosclerosis: an ultrasonographic study
Authors: Inchiostro S. , Dalfollo M. , Marzano A. , Citroni N. , Peccatori S. , Fait D. , De Venuto G. 
Published: July 2003

AbstractAims To evaluate the prevalence of non‐diabetic subjects and diabetic patients, with or without ischaemic heart disease (IHD), in different classes of increasing carotid atherosclerotic damage.Methods Using high‐resolution B‐mode ultrasound, we studied 598 subjects without known cardiovascular disease (CVD) or diabetes, 74 diabetic patients without CVD, 74 non‐diabetic subjects with IHD and 36 patients with both diabetes and IHD. Carotid atherosclerosis was classified as: normal; thickened intima‐media; non‐stenotic plaque; stenotic plaque.Results Compared with subjects without diabetes or CVD, the frequency of patients with diabetes without known CVD increased significantly from ‘normal’ to ‘stenotic plaque’ (4.1%, 6.4%, 13%, 14.8% for normal, thickened intima‐media, non‐stenotic plaque and stenotic plaque, respectively; P = 0.0057). The same figures were 6%, 7.6%, 10.2%, 23.3% (P = 0.0007) for non‐diabetic subjects with IHD, and 0%, 2%, 5.6%, 15.9% (P < 0.0001) for diabetic patients with IHD. No difference was found comparing subjects with diabetes without CVD with non‐diabetic patients with IHD (P = 0.56). Using polychotomous logistic regression analysis, diabetic patients without CVD and non‐diabetic subjects with IHD showed a similar association with the increasing degree of carotid atherosclerosis (P = 0.59), but significantly stronger compared with subjects without diabetes or CVD (P < 0.03 for both).Conclusions Diabetic patients without known CVD show an advanced degree of carotid atherosclerotic damage similar to non‐diabetic subjects with IHD and significantly higher compared with non‐diabetic subjects without CVD. Our data support the need for an aggressive early prevention of CVD in diabetic subjects.
Angiotensin‐I‐converting enzyme insertion/deletion polymorphism and high urinary albumin concentration in French Type 2 diabetes patients
Authors: Hadjadj S. , Gallois Y. , Alhenc‐Gelas F. , Chatellier G. , Marre M. ,   for the DIABHYCAR Study Group
Published: July 2003

AbstractAims Family‐based studies suggest a genetic basis for nephropathy in Type 2 diabetes. The angiotensin‐I‐converting enzyme (ACE) gene is a candidate gene for Type 1 diabetes nephropathy. We assessed the association between high urinary albumin concentration and ACE insertion/deletion (I/D) polymorphism, in French Type 2 diabetes patients.Methods We studied 3139 micro/macroalbuminuric French patients recruited in the DIABHYCAR Study, an ACE inhibition trial in Type 2 diabetes patients with renal and cardiovascular outcomes. The main inclusion criteria were age ≥ 50 years, urinary albumin concentration ≥ 20 mg/l assessed centrally during two consecutive screening visits, and plasma creatinine concentration ≤ 150 µmol/l. These patients were compared with 605 normoalbuminuric (NA; urinary albumin concentration < 10 mg/l at first screening for the DIABHYCAR Study) French patients. ACE I/D genotype was determined by nested polymerase chain reaction.Results The ACE I/D polymorphism was in Hardy–Weinberg equilibrium. The distribution of genotypes did not differ significantly between micro/macroalbuminuric and NA patients: 552 and 115 II, 1468 and 282 ID, 1119 and 208 DD (P = 0.67). However, the ACE D allele was more frequent among normotensive micro/macroalbuminuric patients than among NA patients (P = 0.039).Conclusions The ACE I/D polymorphism was not associated with high urinary albumin concentration in French Type 2 diabetes patients.
Decreased insulin requirement in relation to GFR in nephropathic Type 1 and insulin‐treated Type 2 diabetic patients
Authors: Biesenbach G. , Raml A. , Schmekal B. , Eichbauer‐Sturm G. 
Published: July 2003

AbstractAims In the presence of impaired renal function, patients require less insulin mainly because insulin clearance is prolonged. The aim of this study was to evaluate the insulin requirement related to glomerular filtration rate (GFR) in nephropathic Type 1 and Type 2 diabetic patients.Methods In a retrospective study we compared insulin requirement in 20 nephropathic Type 1 diabetic patients and 20 insulin‐treated Type 2 diabetic patients from the onset of overt nephropathy until the final stage of renal disease. All patients had proteinuria > 0.5 g/24 h and creatinine clearance ≥ 80 ml/min per 1.73 m2 at baseline. Creatinine clearance, urinary protein excretion, glycated haemoglobin and the required insulin doses were determined 3‐ to 6‐monthly, basal C‐peptide was measured at the beginning and the end of the observation period. The required insulin doses were evaluated at creatinine clearance rates of 80, 60, 40, 20 and 10 ml/min per 1.73 m2 (or at the initiation of dialysis treatment).Results The insulin requirement of patients with Type 1 diabetes was reduced from 0.72 ± 0.16 IU/kg per day at a creatinine clearance rate of 80 ml/min, to 0.45 ± 0.13 IU/kg per day at a creatinine clearance rate of 10 ml/min (decrement of 38%, P < 0.001). The insulin dose required by Type 2 diabetic patients was reduced from 0.68 ± 0.28 IU/kg per day at a creatinine clearance rate of 80 ml/min to 0.33 ± 0.19 IU/kg per day at a clearance rate of 10 ml/min (decrement 51%, P < 0.001). The fall in GFR, urinary protein excretion and glycated haemoglobin levels was similar in the two groups. In patients with Type 2 diabetes, C‐peptide levels at the beginning and the end of renal function impairment were 2.2 (0.4–7.3) vs. 2.7 (0.1–4.9) ng/ml (NS). The reduction in insulin requirement was approximately the same in patients with an initial C‐peptide level < 1.0 and in those ≥ 1.0 ng/ml (decrement 57% vs. 46%).Conclusions The reduction in insulin requirement in renal insufficiency is similar in Type 1 and insulin‐treated Type 2 diabetic patients. In subjects with Type 2 diabetes, the residual insulin secretion has no impact on the reduction in insulin requirement dependent on the GFR.
Weight gain profiles of new anti‐psychotics: public health consequences
Authors: Tardieu S. , Micallef J. , Gentile S. , Blin O. 
Published: July 2003

SummaryAnti‐psychotic medications are an important therapeutic option for many individuals with schizophrenia. Recently, a growing interest has been observed on weight gain, which is now a well‐known adverse effect of many anti‐psychotics. As obesity is frequently a comorbid condition with schizophrenia, patients with schizophrenia are inherently at increased risk of developing obesity‐related conditions such as cardiovascular disease and type 2 diabetes. The consequences of excessive weight gain (obesity) associated with anti‐psychotic drugs are likely to include adverse effects on health, social burden and poor compliance or even discontinuation of therapy by the patients. In this article, we focus on different aspects of weight gain induced by anti‐psychotics. This review comprises the following sections: (i) the pharmacological basis of anti‐psychotic‐induced weight gain and metabolic effects with a review of all anti‐psychotics that can be used in patients with schizophrenia; (ii) the clinical impact of the body weight gain (morbidity, psychatric consequences, mortality); (iii) the management of obesity (identification of risk factors including pharmacogenetics, diet, behavioural therapies, pharmacological approach). An understanding of these aspects is important for those who prescribe anti‐psychotics in order to provide the patient the best therapeutic management.
Perspectives: molecular genetic research in human obesity
Authors: Hebebrand J. , Friedel S. , Schäuble N. , Geller F. , Hinney A. 
Published: July 2003

SummaryWithin the past decade the molecular basis of single forms of monogenic obesity has been elucidated. With the exception of functionally relevant mutations in the melanocortin‐4 receptor gene, which occur in approximately 2–4% of extremely obese individuals, all other currently known monogenic forms are rare and additionally associated with distinct endocrinological abnormalities. A large number of association studies have been performed in ‘normal’ obesity. Whereas many associations have been reported, it is largely unclear which of these represent true positive findings. Over 20 genome scans pertaining to obesity and related phenotypes have been performed; specific chromosomal peak regions have been identified in different scans. We review the current status and discuss relevant issues related to phenotyping, association and linkage studies. We recommend that the procedure via which a consensus is reached as to what constitutes a true positive association finding requires formalization.
Can obesity be a risk factor in elderly people?
Authors: Inelmen E. M. , Sergi G. , Coin A. , Miotto F. , Peruzza S. , Enzi G. 
Published: July 2003

SummaryObesity is increasing in middle‐aged adults and in elderly subjects (over 65 years), owing to the concurrence of different factors: inactivity, wrong nutritional habits, and basal metabolism and nutritional need reduction. This condition is becoming a serious problem because of the increasing numbers of the aged population all over the world. In the past, obesity was considered as a ‘secondary’ pathology of no medical importance in old age; but nowadays, obesity is increasingly being studied in Geriatrics too, because it causes disability and because of its quality‐of‐life impairment consequences. The Euronut‐Seneca study has confirmed the presence of obesity in both men and women in Europe. The definition of obesity, the reference values of body mass index and obesity as a mortality factor in elderly persons are still under discussion. Even when overweight does not represent a serious problem in old age, obese elderly people are certainly at risk of disability, morbidity and mortality. This review focuses on the potential risks of overweight and obesity in the aged population.
Central obesity and breast cancer risk: a systematic review
Authors: Harvie M. , Hooper L. , Howell A.H. 
Published: July 2003

SummaryThe specific effect of central rather than general obesity on breast cancer risk is not clear. This review examines the relationship between waist and waist–hip ratio (WHR) and risk of breast cancer in pre‐ and post‐menopausal women using all available cohort and case‐control data. The databases of the Cochrane Library, Medline, Cancer Lit and Embase were searched until October 2002. Relevant cohort and case‐control studies with separate analyses in pre‐ and/or post‐menopausal women were included. Random effects meta‐analyses were carried out, subgrouped by pre‐ or post‐menopausal status and cohort or case‐control design. Sensitivity analyses were also performed. Five cohort studies with 72 1705 person years of observation (453 pre‐menopausal and 2684 post‐menopausal cases), and three case‐control studies comprising 276 pre‐menopausal cases with 758 pre‐menopausal controls and 390 post‐menopausal cases with 1071 post‐menopausal controls were included. Pooled results from cohort studies using the most adjusted data [but without adjustment for weight or body mass index (BMI)] suggest a 39% lower risk of breast cancer in post‐menopausal women with the smallest waist (compared with the largest) and a 24% lower risk in women with the smallest WHR. In pre‐menopausal women, however, pooled results suggest that measurement of waist or WHR have little effect on risk of breast cancer. Adjustment for BMI abolished the relationship between waist or WHR and risk of post‐menopausal breast cancer, but introduced such a relationship amongst pre‐menopausal women. The relationship between a smaller measurement of waist or WHR and lower risk of post‐menopausal breast cancer appears to result from the associated correlation with BMI. Amongst pre‐menopausal women, central (not general) obesity may be specifically associated with an increased risk of breast cancer.
Modern statistical methods for handling missing repeated measurements in obesity trial data: beyond LOCF
Authors: Gadbury G. L. , Coffey C. S. , Allison D. B. 
Published: July 2003

SummaryThis paper brings together some modern statistical methods to address the problem of missing data in obesity trials with repeated measurements. Such missing data occur when subjects miss one or more follow‐up visits, or drop out early from an obesity trial. A common approach to dealing with missing data because of dropout is ‘last observation carried forward’ (LOCF). This method, although intuitively appealing, requires restrictive assumptions to produce valid statistical conclusions. We review the need for obesity trials, the assumptions that must be made regarding missing data in such trials, and some modern statistical methods for analysing data containing missing repeated measurements. These modern methods have fewer limitations and less restrictive assumptions than required for LOCF. Moreover, their recent introduction into current releases of statistical software and textbooks makes them more readily available to the applied data analyses.
Nanomechanical properties and mineral concentration in articular calcified cartilage and subchondral bone
Authors: Ferguson Virginia L. , Bushby Andrew J. , Boyde Alan 
Published: July 2003

AbstractWe studied articular calcified cartilage (ACC) and the immediately subchondral bone (SCB) in normal and osteoarthritic human femoral heads. Thick slices of human normal reference post mortem (PM) and osteoarthritic (OA) femoral heads (age 55–89 years) were embedded in PMMA, micromilled, carbon coated and studied using quantitative backscattered electron (qBSE) imaging to determine variations in degree of mineralization. With exact microanatomical location, nanoindentation was performed on the same block faces in representative superior (more highly loaded) and medial regions of the joint surface. Using a partial unloading method, elastic modulus as a function of indenter penetration depth was determined using a spherical tipped diamond indenter. A pointed indenter was used to determine the tissue hardness in selected locations. The relationship between mineralization and indentation modulus was more distinct in ACC than in SCB, the latter having a higher matrix concentration with variable collagen orientation. In OA, the bulk of the measurements were coincident with those in the PM samples, although there was a greater range in the levels of mineralization and modulus in ACC. In OA, extremely hypermineralized ACC was found in ACC proper, especially in superior regions, and translocated into SCB and hyaline cartilage. The very highly mineralized cartilage fragments may function as a hard grinding abrasive, accelerating wear rates whether attached to or fragmented from the eburnated surfaces of OA ACC. Highly mineralized regions would also alter loading patterns and thereby contribute to further destruction of the joint tissues.
Microdamage and mechanical behaviour: predicting failure and remodelling in compact bone
Authors: Taylor D. , Lee T. C. 
Published: July 2003

AbstractThis paper reports on the development of a theoretical model to simulate the growth and repair of microdamage in bone. Unlike previous theories, which use simplified descriptions of damage, this approach models each individual microcrack explicitly, and also models the basic multicellular units (BMUs) that repair cracks. A computer simulation has been developed that is capable of making a variety of predictions. Firstly, we can predict the mechanical behaviour of dead bone in laboratory experiments, including estimates of the number of cycles to failure and the number and length of microcracks during fatigue tests. Secondly, we can predict the results of bone histomorphometry, including such parameters as BMU activation rates and the changing ratio of primary to secondary bone during ageing. Thirdly, we can predict the occurrence of stress fractures in living bone: these occur when the severity of loading is so great that cracks grow faster than they can be repaired. Finally, we can predict the phenomenon of adaptation, in which bone is deposited to increase cortical thickness and thus prevent stress fractures. In all cases results compare favourably with experimental and clinical data.
Age‐related changes in gene expression patterns of matrix metalloproteinases and their collagenous substrates in mandibular condylar cartilage in rats
Authors: Bae Jin‐Wan , Takahashi Ichiro , Sasano Yasuyuki , Onodera Kazuyuki , Mitani Hidetoshi , Kagayama Manabu , Mitani Hideo 
Published: July 2003

AbstractMatrix metalloproteinases (MMPs) have been implicated in physiological cartilage matrix remodelling as well as in pathological and invasive extracellular matrix remodelling of tissue. Age‐related changes in the gene expression patterns of MMPs in mandibular condylar cartilages (MCCs) were analysed. We examined the gene expression patterns of Mmp‐8 and ‐13 and their substrates, Col1a1, Col2a1 and Col10a1, in MCC of growing and ageing rats. Temporomandibular joints of male Wistar rats aged 4, 8, 16 and 32 weeks were subjected to in situ hybridization analysis. Histologically, MMCs showed characteristics of growth plate cartilage at ages 4 and 8 weeks, and more closely resembled articular cartilage thereafter. Mmp‐8 was expressed in the cells in all cartilaginous cell layers at ages 4 and 8 weeks, and then was localized only in the mature cells at ages 16 and 32 weeks. Whereas Mmp‐13 expression was limited to the lowermost hypertrophic chondrocytes in the growth stage, mature chondrocytes instead of hypertrophic chondrocytes expressed Mmp‐13 in adult non‐hypertrophic MCC. Because Mmp‐8 and ‐13 expression overlapped with Col2a1 and Col10a1, chondrocytes could play a pivotal role in degradation as well as production of the cartilaginous matrix in MCC.
Angiogenesis in the distal femoral chondroepiphysis of the rabbit during development of the secondary centre of ossification
Authors: Doschak M. R. , Cooper D. M. L. , Huculak C. N. , Matyas J. R. , Hart D. A. , Hallgrimsson B. , Zernicke R. F. , Bray R. C. 
Published: July 2003

AbstractIn the developing chondroepiphyses of long bones, the avascular cartilaginous anlage is invaded by numerous blood vessels, through the process of angiogenesis. The objective of this study was to investigate the chronology of this vascular invasion with the spontaneous calcification of the cartilaginous epiphysis during development of the secondary ossification centre in the rabbit distal femur. The time‐course of chondroepiphyseal vascular invasion was determined histologically and standardized for eight gestational and four postnatal intervals by plotting kit body mass against crown–rump length. Similarly, microcomputed tomography (µ‐CT) helped to visualize calcification at those same gestational and postnatal intervals. To confirm the angiogenic nature of the avascular chondroepiphysis, such samples were assayed on the chick chorio‐allantoic membrane (CAM). Neovascular outgrowths from the CAM were apparent 48 h following introduction of an 18‐day (gestational) chondroepiphyseal sample. Chondroepiphyseal samples were assayed for the potent developmental angiogenic factors bFGF and VEGF, with the mRNA expression for both these mediators being confirmed using RT‐PCR. As angiogenesis and calcification during chondroepiphyseal development occur in a defined tissue environment initially devoid of blood vessels and mineral, those processes provided a unique opportunity to study their progression without complication of injury‐related inflammation or extant vasculature and mineral. Furthermore, the discovery of angiogenic, angiostatic or mineral‐regulating mediators specific to developing connective tissue may prove useful for analysing the regulation of vascular and mineral pathogenesis in articular tissues.
The histological structure of the malleolar groove of the fibula in man: its direct bearing on the displacement of peroneal tendons and their surgical repair
Authors: Kumai T. , Benjamin M. 
Published: July 2003

AbstractThe peroneal (fibularis) tendons are held in place within the malleolar groove by the superior peroneal retinaculum. If this is torn, the tendons can subluxate or dislocate. Understanding the anatomy of the region is important for treating these injuries when it becomes necessary to reconstruct the malleolar groove surgically. Serial transverse sections of the groove were cut from 10 dissecting room cadavers after routine histology processing. The structure of the malleolar groove differed significantly in its proximal and distal parts. Distally, the bone is convex and the shape of the groove is determined by a thick periosteal cushion of fibrocartilage that covers the bone surface. Proximally, the groove shape is determined by the bone itself, and the periosteum is thin and fibrous. The restriction of a periosteal fibrocartilage to the distal end suggests that it serves to adapt the shape of the malleolar groove to that of the tendons within it and thus promotes stress dissipation. Paradoxically, however, it increases the risk of damage to subluxated tendons, because these can be sliced longitudinally by a sharp ridge created from periosteal fibrocartilage when the retinaculum is torn. Our results suggest that if bone‐block surgical procedures are used to reconstruct the malleolar groove, they are best restricted to its proximal part.
The growth and morphogenesis of the early mouse mandible: a quantitative analysis
Authors: Ramaesh Thaya , Bard Jonathan B. L. 
Published: July 2003

AbstractThree‐dimensional reconstruction and BrdU incorporation have been used to quantify the development and growth of the mouse mandible and to analyse its relationship to Meckel's cartilage and the molar teeth. The mandible anlage is first histologically detectable at E13.5 as paired plates of osteoid tissue within condensed mesenchyme (∼0.9 mm long and ∼0.36 mm deep) that are lateral to the two arms of Meckel's cartilage. Over the next 3 days, each plate lengthens to ∼3.6 mm, and extends medially at its superior and inferior edges, folding over to enclose the alveolar nerve and Meckel's cartilage and producing additional processes that form the molar tooth sockets (E15.5). At around E15.5, the first molar tooth socket forms from two processes that extend from the medial and distal parts of the mandible to surround the tooth. By E16.5, this process is complete in the distal region where Meckel's cartilage is beginning to degenerate. Mandible ossification begins at E14 with proliferation restricted to the outer surface. BrdU incorporation rates are particularly high at the proximal and distal ends where lengthening occurs, and at the superior and inferior edges as they extend medially to surround Meckel's cartilage. Incorporation rates slow at the distal ends of each mandible at E16.5 as they approach each other at the symphysis. The results indicate that the mandible mainly grows at its periphery, and the pattern of mandibular growth and morphogenesis suggests that these processes are mainly directed and constrained by paracrine signalling from Meckel's cartilage and the tooth buds.