bluuebunny/crossref_metadata_2025 huggingface dataset:
Skeletal growth and long‐term bone turnover after enterocystoplasty in a chronic rat model
Authors: Gerharz E.W. , Gasser J.A. , Mosekilde L. , Moniz C. , Sitter H. , Barth P.J. , Thomsen J.S. , Ransley P.G. , Riedmiller H. , Woodhouse C.R.J.
Published: July 2003

OBJECTIVE

To investigate skeletal growth and bone metabolism in a chronic animal model of urinary diversion.

MATERIALS AND METHODS

Young male Wistar rats (120) were allocated randomly to four groups undergoing: ileocystoplasty, ileocystoplasty and resection of the ileocaecal segment, colocystoplasty, and controls. All animals received antibiotics for 1 week after surgery; half of each group remained on oral antibiotics. Bone‐related biochemistry was measured in serum and urine. Dual‐energy X‐ray absorptiometry and peripheral quantitative computed tomography (pQCT) were used to determine bone mass ex vivo.

RESULTS

Most (90%) of the rats survived the study period (8 months); six rats died from bowel obstruction at the level of the entero‐anastomosis and four had to be killed because of persistent severe diarrhoea. Vital intestinal mucosa was found in all augmented bladders. There were no differences in bone length and volume. Loss of bone mass was almost exclusively in rats with ileocystoplasty and resection of the ileocaecal segment (−37.5%, pQCT, P < 0.01). There was no hyperchloraemic metabolic acidosis or gross impairment of renal function. Hypomagnesaemia, hypocalcaemia and decreased insulin‐like growth factor‐binding protein 3 were the only significant findings on blood analysis. Deoxypyridinoline crosslinks in urine were higher in rats with an enterocystoplasty than in controls.

CONCLUSIONS

Enterocystoplasty in rats neither impairs skeletal growth nor bone quantity, but leads to significant loss of bone mass when combined with resection of the ileocaecal segment. Rarefaction of the trabecular network is confined to the metabolically highly active cancellous compartment, most likely as a consequence of intestinal malabsorption.
Therapeutic transcatheter arterial embolization in the management of intractable haemorrhage from pelvic urological malignancies: preliminary experience and long‐term follow‐up
Authors: Nabi G. , Sheikh N. , Greene D. , Marsh R.
Published: July 2003

OBJECTIVE

To evaluate the feasibility, efficacy and complications of internal iliac artery embolization as a palliative measure in the control of intractable haemorrhage from advanced pelvic urological malignancies.

PATIENTS AND METHODS

Six patients (mean age 80 years, range 76–87) with advanced pelvic malignancies (three each with bladder carcinoma and prostate carcinoma) underwent embolization between September 1997 and July 2001, using permanent coils in the anterior division of internal iliac artery bilaterally.

RESULTS

All patients had undergone conservative treatment before embolization for a mean of 2 days. The mean requirement for transfusion before embolization was 3.2 units. All patients except one were successfully embolized in a single setting with no complications. Bleeding was successfully controlled in one patient at the second attempt of embolization. There were minor complications, e.g. nausea, vomiting or fever, for a mean of 2 days, responding well to conservative treatment. At a mean follow‐up of 22 months, no patient had a recurrence of bleeding.

CONCLUSION

Internal iliac artery embolization is a feasible, effective and minimally invasive option in managing advanced pelvic urological malignancies presenting with intractable bleeding; it should be bilateral and permanent.
Nerve‐sparing robot‐assisted radical cystoprostatectomy and urinary diversion
Authors: Menon M. , Hemal A.K. , Tewari A. , Shrivastava A. , Shoma A.M. , El‐Tabey N.A. , Shaaban A. , Abol‐Enein H. , Ghoneim M.A.
Published: July 2003

OBJECTIVE

To develop a technique of nerve‐sparing robot‐assisted radical cystoprostatectomy (RRCP) for patients with bladder cancer.

PATIENTS AND METHODS

Robotic assistance should enhance the ability to preserve the neurovascular bundles during laparoscopic radical cystectomy. Thus we undertook RRCP and urinary diversion using a three‐step technique. First, using a six‐port approach and the da Vinci Surgical System (Intuitive Surgical, Sunnyvale, CA, USA), one surgeon carried out a complete pelvic lymphadenectomy and cystoprostatectomy using a technique developed specifically for robotic surgery. The neurovascular bundles were easily identified and dissected away, the specimen entrapped in a bag and removed through a 5–6 cm suprapubic incision. Second, a different surgical team exteriorized the bowel through this incision and created a neobladder extracorporeally. Third, the neobladder was internalized, the incision closed and the primary surgeon completed the urethro‐neovesical anastomosis with robotic assistance.

RESULTS

RRCP was carried out in 14 men and three women by the primary surgeon (M.M.). The form of urinary reconstruction was ileal conduit in three, a W‐pouch with a serosal‐lined tunnel in 10, a double‐chimney or a T‐pouch with a serosal‐lined tunnel in two each. The mean operative duration for robotic radical cystectomy, ileal conduit and orthotopic neobladder were 140, 120 and 168 min, respectively. The mean blood loss was < 150 mL. The number of lymph nodes removed was 4–27, with one patient having N1 disease. The margins of resection were free of tumour in all patients.

CONCLUSIONS

We developed a technique for nerve‐sparing RRCP using the da Vinci system which allows precise and rapid removal of the bladder with minimal blood loss. The bowel segment can be exteriorized and the most complex form of orthotopic bladder can be created through the incision used to deliver the cystectomy specimen. Performing this part of the operation extracorporeally reduced the operative duration.
Continent urinary tract reconstruction – the Lund experience
Authors: Månsson W. , Davidsson T. , Könyves J. , Liedberg F. , Månsson Å. , Wullt B.
Published: July 2003

The Department of Urology in Lund, Sweden, has a long association with innovations in reconstructive urology. The authors from that department describe their experience over a long period with orthotopic bladder substitution and continent cutaneous urinary diversion. They conclude that continent urinary tract reconstruction is associated with a high incidence of early and late complications. They also found that for storage and emptying, their Lundiana pouch was superior to the Goldwasser neobladder.

OBJECTIVE

To assess the early and late complications and functional results in patients undergoing continent reconstruction of the urinary tract, i.e. orthotopic bladder substitution (OBS) or continent cutaneous diversion (CCD).

PATIENTS AND METHODS

The medical records of all patients undergoing OBS (Goldwasser technique) or CCD (‘Lundiana’ technique) for malignant or benign disease during 1987–1999 and followed to December 2001 were reviewed. There were 67 patients with neobladders, 77 with a Lundiana pouch who had undergone radical cystectomy and 22 with a Lundiana pouch operated for benign disorders.

RESULTS

Early complications requiring reoperation occurred in 12% of the cystectomy group, with no difference with type of reconstruction, and in 10% with benign diseases. Four patients (3%) undergoing radical cystectomy died from early cardiovascular complications, two after surgery for intra‐abdominal complications. Intestinally related complications and wound dehiscence requiring re‐operation occurred in nine and six patients, respectively. The incidence of late complications requiring open surgery was 22% and 23% after cystectomy with OBS and CCD, respectively. The value in patients with benign diseases undergoing CCD was also 23%. Stone formation in the pouch was common, occurring in 12% in patients with OBS and in 10% after CCD. The pouch perforated or ruptured in four patients. The incidence of uretero‐intestinal stricture using the Le Duc technique was 2.4% and renal function was well preserved. The incidence of revisional surgery of the Lundiana pouch outlet for incontinence was low and all patients but four were continent. The functional outcome in patients with OBS was less good; some needed pouch augmentation or an artificial urinary sphincter. Most patients used incontinence products and many needed clean intermittent self‐catheterization.

CONCLUSION

Continent urinary tract reconstruction is associated with a high incidence of early and late complications. For storage and emptying, the CCD Lundiana pouch is superior to the OBS of Goldwasser.
Ex‐vivo comparison of the haemostatic properties of standard transurethral resection and transurethral vaporization resection of the prostate
Authors: Reich O. , Schneede P. , Zaak D. , Siebels M. , Hofstetter A.
Published: July 2003

OBJECTIVE

To compare the haemostatic properties of standard transurethral resection of the prostate (TURP) and transurethral vaporization resection of the prostate (TUVRP), as perioperative bleeding is still regarded as the major complication of prostate resection.

MATERIALS AND METHODS

Isolated blood‐perfused porcine kidneys were used to determine the haemostatic efficacy of TURP and TUVRP (using two different electrodes). Bleeding was quantified precisely in relation to tissue ablation for the two techniques, and specimens were evaluated histologically.

RESULTS

Both TUVRP groups had significantly less bleeding (P = 0.005) than the TURP group for a standardized ablation volume of perfused kidney tissue (18.9, 19.5 and 24.1 mL/min, respectively). The different TUVRP electrodes had no significant haemostatic differences. The histology showed significantly (P = 0.03) larger coagulation zones for the TUVRP groups than for standard TURP.

CONCLUSIONS

TUVRP ex‐vivo was associated with significantly better haemostasis than TURP. The haemostatic properties of different active electrodes for TUVRP seem to be equivalent.
Putative protein markers in the sera of men with prostatic neoplasms
Authors: Lehrer S. , Roboz J. , Ding H. , Zhao S. , Diamond E.J. , Holland J.F. , Stone N.N. , Droller M.J. , Stock R.G.
Published: July 2003

OBJECTIVE

To describe the preliminary identification of serum proteins that may be diagnostic markers in prostate cancer.

PATIENTS AND METHODS

The study included 11 men referred for treatment of localized prostate cancer, 12 with benign prostatic hyperplasia (BPH) and 12 disease‐free controls. For serum protein analysis, the protein‐chip array surface‐enhanced laser desorption/ionization (SELDI) technique was used (Ciphergen Biosystems, Fremont, CA). SELDI combines protein‐chip technology with time‐of‐flight mass spectrometry, and offers the advantages of speed, simplicity and sensitivity.

RESULTS

Three protein peaks were identified in the serum of men with prostate cancer and BPH, but not in controls, with relative molecular masses of 15.2, 15.9 and 17.5 kDa. These three proteins were significantly associated with BPH and prostate cancer when compared with controls (P = 0.001, 0.004, and 0.011, respectively, Kruskal–Wallis test). Interestingly, the 17.5 kDa protein was more abundant in five men with stage T1 prostate cancer than in eight with stage T2 (P = 0.016, two tailed Mann–Whitney U‐test corrected for ties).

CONCLUSIONS

These proteins, particularly the 15.9 kDa one, may be used for the diagnosis or monitoring of prostate cancer and differentiation from BPH, and have the potential for antibody‐based chip SELDI‐TOF technology. Identified proteins may be targets for immunotherapy.
Impedance measurements and connexin expression in human detrusor muscle from stable and unstable bladders
Authors: Sui G.P. , Coppen S.R. , Dupont E. , Rothery S. , Gillespie J. , Newgreen D. , Severs N.J. , Fry C.H.
Published: July 2003

Three of this month's Scientific Discovery papers highlight the importance of collaboration in delivering high quality scientific research. As scientific technology increases in power and cost, and specific areas of interest become more specialized, it is becoming more difficult to cover all aspects of a completeresearch story. Collaborating with other experts in the field or other fields, including industry, allows strong scientific proof to be generated for the hypothesis and aims. Building strong collaborative,inter‐disciplinary, multi‐institutional, international groups with academic and industrial partners is the way forward for all discovery. We look forward to publishing more of these collaborative papersin future issues of the BJU International.

OBJECTIVES

To test the hypothesis that intercellular electrical coupling is altered in human detrusor smooth muscle from patients with unstable bladders.

MATERIALS AND METHODS

Human detrusor biopsy samples were obtained from patients with stable and unstable bladders. Intracellular electrical impedance was measured with alternating current (20 Hz−300 kHz) across the ends of detrusor strips in an oil‐gap, after correcting for extracellular space resistance. Gap junctions were identified by localization of connexins (Cx), specifically Cx45, Cx43 and Cx40 transcripts, using immunoconfocal microscopy.

RESULTS

Total intracellular resistivity was greater in strips from unstable than from stable bladders (median 1246 vs 817 Ω.cm). The increase was attributed to an increase in junctional resistance; cytoplasmic resistance was unchanged. Cx43 was localized to a submucosal layer and to connective tissue; Cx40 label was confined to endothelial cells of blood vessels. Cx45 labelling was localized to detrusor bundles and appeared to be less marked in samples from unstable bladders. Semi‐quantitative analysis of Northern blots showed that Cx45 expression in unstable was less than that in stable bladders.

CONCLUSIONS

These data suggest that intercellular coupling is reduced in detrusor from unstable bladders. Cx45 was localized to the detrusor layer, with Cx 43 more evident in the suburothelial mucosa. Cx45 labelling was less intense in detrusor samples from unstable bladders. These results are consistent with reduced gap junction coupling in detrusor from unstable bladders.
Associations between insulin resistance and thrombotic risk factors in high‐risk South Asian subjects
Authors: Kain K. , Catto A. J. , Grant P. J.
Published: July 2003

Aims There is recognized association of thrombotic factors to insulin resistance in White Europeans. South Asians are more insulin resistant compared with white Europeans and express increased metabolic features of insulin resistance. The aim of the study was to determine whether there was any relationship between insulin resistance and thrombotic risk factors in healthy South Asian subjects.

Methods Healthy South Asians (n = 185) clinically free from ischaemic heart disease, ischaemic stroke or peripheral vascular disease were randomly recruited. Partial correlations of homeostasis model assessment (HOMA) (surrogate of insulin resistance) were analysed with two fibrinolytic and five coagulation factors.

Results Age and gender‐adjusted HOMA was significantly correlated to plasminogen activator inhibitor‐1 (0.51, P = 0.0001), tissue plasminogen activator antigen (r = 0.40, P = 0.0001), fibrinogen (r = 0.28, P = 0.0001), von Willebrand factor (r = 0.17, P = 0.03), factor XIIa (r = 0.22, P = 0.006) factor VII antigen (r = 0.19, P = 0.02) and factor XIII B subunit (r = 0.30, P = 0.001).

Conclusions Insulin resistance significantly clusters with fibrinolytic and coagulation factors in South Asians, which may contribute to high prevalence of vascular disease in this population.
The renin–angiotensin system and the long‐term complications of diabetes: pathophysiological and therapeutic considerations
Authors: Gilbert R. E. , Krum H. , Wilkinson‐Berka J. , Kelly D. J.
Published: July 2003

The relationship between the renin–angiotensin system (RAS) and the progression of diabetic renal disease has been a major focus of investigation over the past 20 years. More recently, experimental and clinical studies have also suggested that the RAS may have a pathogenetic role at other sites of micro‐ and macrovascular injury in diabetes. Complementing major advances into the understanding of the local, as distinct from the systemic RAS, a number of large clinical trials have examined whether blockade of the RAS might provide protection from the long‐term complications of diabetes, beyond that due to blood pressure reduction alone. While some controversy remains, these studies have, in general, suggested that angiotensin converting enzyme (ACE) inhibition and more recently, angiotensin receptor blockade reduce the development and progression of diabetic nephropathy, cardiovascular disease and possibly retinopathy. This review will focus on recent developments in our understanding of the tissue‐based RAS and its role in end‐organ injury in diabetes, the results of recent clinical trials and newer strategies for the pharmacological manipulation of the RAS.
Early detection of emotional and behavioural problems in children with diabetes: the validity of the Child Health Questionnaire as a screening instrument
Authors: Cameron F. J. , Smidts D. , Hesketh K. , Wake M. , Northam E. A.
Published: July 2003

Aims To assess the validity of the Child Health Questionnaire (CHQ) as a screening tool for detecting ‘at risk’ emotional and behavioural maladjustment in children with diabetes, using the Behaviour Assessment System for Children (BASC) as a gold standard measure.

Methods CHQ and BASC were administered to 103 parents of children with Type 1 diabetes, aged 7–12 years. Sub‐scales of the two measures were compared using Pearson's bivariate correlations. CHQ sensitivity and specificity cut‐points were optimized against the BASC borderline category using receiver operating characteristic curves.

Results The BASC Externalizing Problems scale correlated strongly with CHQ Behaviour, Global Behaviour, Mental Health, Family Activities and Family Cohesion scales (r‐values −0.68, −0.54, −0.51, −0.59, and −0.42, respectively). BASC Internalizing Problems scale correlated strongly with CHQ Behaviour, Mental Health and Family Cohesion scales (r‐values −0.40, −0.43 and −0.45, respectively). Using receiver operating characteristic curve analysis, the CHQ Mental Health scale most effectively identified children classified as borderline on the BASC Internalizing Problems scale (sensitivity 87%, specificity 78%), while the CHQ Global Behaviour scale most effectively identified children classified as borderline on the BASC Externalizing Problems scale (sensitivity 73%, specificity 82%).

Conclusions Significant correlations were seen between the CHQ Global Behaviour and Mental Health scales and the BASC Externalizing and Internalizing scales, respectively. Sequential use of the CHQ, as a screening tool, followed by an established mental health measure such as the BASC, may help identify children with diabetes ‘at risk’ for chronic maladjustment and poor health outcomes.
Evaluation of a new non‐mydriatic digital camera for detection of diabetic retinopathy
Authors: Massin P. , Erginay A. , Ben Mehidi A. , Vicaut E. , Quentel G. , Victor Z. , Marre M. , Guillausseau P. J. , Gaudric A.
Published: July 2003

Aims To compare the results of fundus photography using a new non‐mydriatic digital camera with the results of reference standard of Early Treatment Diabetic Retinopathy Study (ETDRS) retinal photographs, for the detection of diabetic retinopathy (DR).

Methods Fundus colour photographs were taken with a Topcon non‐mydriatic camera of 147 eyes of 74 diabetic patients, without pupillary dilation (five overlapping fields of 45°; posterior pole, nasal, temporal, superior and inferior). Three retinal specialists classified the photographs in a masked fashion, as showing no DR or mild non‐proliferative DR (NPDR) not requiring referral, moderate or more severe NPDR and/or macular oedema, or as non‐gradable image requiring referral. ETDRS 35‐mm colour slides served as reference images for DR detection.

Results For moderately severe to severe DR, the sensitivities of detection reported by the three observers were 92, 100 and 92%, respectively, and the specificities, 87, 85, and 88%. For four levels of DR severity (none or mild NPDR, moderate NPDR, severe NPDR and proliferative DR), the percentages of exact agreement between the three observers on the retinopathy grades assigned to the non‐mydriatic photographs and to the ETDRS reference slides were 94.6, 93 and 87.6%, respectively (κ 0.60–0.80). Sixteen eyes of nine patients (11%) were judged ungradable by at least one observer. In a second series of 110 patients, evaluated in the setting of a screening procedure, fewer photographs were ungradable (< 6%).

Conclusion These results suggest that fundus photographs taken by the Topcon TRC‐NW6S non‐mydriatic camera, without pupillary dilation, are suitable for DR screening.
Effectiveness of a new brand of stock ‘diabetic’ shoes to protect against diabetic foot ulcer relapse. A prospective cohort study
Authors: Busch K. , Chantelau E.
Published: July 2003

Aims Diabetic patients with podopathy (diabetic foot syndrome) may need protective footwear, be it customized or industrially produced stock ‘diabetic’ shoes (SDS). The effectiveness of each type of ‘diabetic’ shoe needs to be proven clinically, e.g. in terms of prevention of foot ulceration. The following study assesses a new German SDS, the LucRo® shoe, which consists of rocker‐shaped walking sole, a standardized shock absorption insole, and soft uppers without stiff toe‐caps. The LucRo® SDS has been registered as a Medicinal Product according to the European Community Guideline 93/42/EC.

Patients and methods A total of 92 high‐risk diabetic patients (mean age 63 years, duration of diabetes 13 years) with healed foot ulcer were recruited prospectively over 31 months; 87 patients suffered from polyneuropathy, 24 patients had peripheral ischaemic vessel disease. One group of patients (n = 60) received the LucRo® SDS and wore them, while the remaining patients (n = 32) did not receive the SDS and were forced to use their normal footwear. This allocation reflects the haphazard reimbursement policies of the individual patients’ health insurance, and is in accordance with the current German legislation. The patients were followed up for up to 42 months until the first foot ulcer relapse, or the end of the study.

Results There were no differences between the groups concerning age, sex, type and duration of diabetes, prevalence of polyneuropathy and peripheral ischaemic vessel disease, frequency of foot care and mortality rate. The first year annual rate of foot ulcer relapse was significantly different between the groups: 60% without SDS vs. 15% with SDS. The overall cumulative ulcer‐free survival was significantly greater with SDS (P < 0.0001, log rank test).

Conclusion The LucRo® stock ‘diabetic’ shoe appears effective in the prevention of foot re‐ulceration in high‐risk patients with diabetic podopathy.
From minimal background diabetic retinopathy to profuse sight threatening vitreoretinal haemorrhage: management issues in a case of pregestational diabetes and pregnancy
Authors: Chatterjee S. , Tsaloumas M. D. , Gee H. , Lipkin G. , Dunne F. P.
Published: July 2003

Deterioration of retinopathy is a recognized complication of pregnancy in Type 1 diabetes. We discuss management issues relating to a case of rapid sight‐threatening progression of retinopathy in pregnancy complicated by pregestational diabetes.
Effect of the rapid‐acting insulin analogue insulin aspart on quality of life and treatment satisfaction in patients with Type 1 diabetes
Authors: Bott U. , Ebrahim S. , Hirschberger S. , Skovlund S. E.
Published: July 2003

Aims To compare quality of life (QoL) and treatment satisfaction in patients with Type 1 diabetes receiving the rapid‐acting insulin analogue, insulin aspart (IAsp), with that in patients receiving soluble human insulin (HI).

Methods In this 6‐month, multinational, randomized, open‐label trial, 424 patients from German‐speaking countries were subjected to psychometric assessment before and after randomization (ratio 2 : 1) to basal‐bolus treatment with either IAsp (n = 283) or HI (n = 141). Patients on HI were advised to keep an injection–meal interval of 30 min, whereas patients on IAsp were advised to inject immediately before meals. Treatment satisfaction and diabetes‐related QoL were assessed using validated instruments to measure the domains of patients’ individual treatment goals, physical complaints, worries about the future, social relations, leisure time flexibility, daily hassles, diet restrictions, burdens and fear of hypoglycaemia, blood glucose fluctuations, self‐efficacy, and fear of insulin analogues.

Results After 6 months, IAsp was associated with significantly greater improvement in treatment satisfaction than HI in two different scales (P < 0.01), and in QoL with respect to diet restrictions (P < 0.01). Improved satisfaction was mainly due to increased dietary and leisure time flexibility (P < 0.0001). Twenty‐three percent of the IAsp group vs. 14% of the HI group achieved small but important improvements of total QoL (between‐group difference, P < 0.06). The number needed to treat (NNT) with IAsp for an important increase in QoL was calculated to be 10. Regression analyses of potential predictors of improvement in QoL highlighted patients intensely striving for physical strength (P < 0.01; NNT = 7) and patients feeling less protected against hypoglycaemia (P < 0.005; NNT = 8) as being the most likely to benefit from IAsp.

Conclusions Under these study conditions, IAsp improved treatment satisfaction and quality of life regarding diet restrictions when compared with human insulin. The ‘numbers needed to treat’ for important quality of life benefits indicate that the effect of IAsp in this regard is not trivial.
The effects of applied felted foam on wound healing and healing times in the therapy of neuropathic diabetic foot ulcers
Authors: Zimny S. , Schatz H. , Pfohl U.
Published: July 2003

Aims The application of felted foam is a promising method for plantar pressure reduction in the ulcer region of diabetic foot ulcers, but knowledge of its effects on wound healing is sparse. The objective of this study was to evaluate the effects of felted foam on wound healing in diabetic foot ulcers compared with a standard method of plantar pressure relief.

Materials and methods A total of 54 Type 1 or Type 2 diabetic patients with neuropathic diabetic foot ulcers were evaluated in this prospective randomized controlled study. Ulcer healing was assessed by planimetric measurement of the wound area at beginning of the study and after 10 weeks and at least until wound healing. The patients were consecutively enrolled in the study; 24 patients were randomized to the felted foam therapy, and 30 patients were randomized to conventional therapy.

Results In the felted foam group, the initial average wound area was 102.3 ± 45.3 mm2 (mean ± sd), and 5.4 ± 3.1 mm2 after 10 weeks with an average healing time of 75 days [95% confidence interval (CI) 67–84]. In the conventional therapy group, the initial average wound area was 112.5 ± 50.8 mm2, and 10.6 ± 4.2 mm2 after 10 weeks with an average healing time of 85 days (95% CI 79–92) (P = 0.03). The mean wound radius decreased by 0.48 mm (95% CI 0.42–0.56) per week in the felted foam group and by 0.39 mm (95% CI 0.35–0.42) per week in the conventional group (P = 0.005).

Conclusions The felted foam technique appears to be at least as effective as conventional plantar ulcer treatment. It may be a useful alternative in treating neuropathic foot ulceration, especially in patients who are not able to avoid weight‐bearing reliably.
Therapeutic effect of recombinant human erythropoietin on anaemia with erythropoietin deficiency in diabetic patients
Authors: Kim D. J. , Kim Y. M. , Yun Y. S. , Ahn C. W. , Cha B. S. , Song Y. D. , Lim S. K. , Kim K. R. , Hahn J. S. , Huh K. B. , Lee H. C.
Published: July 2003

Aims The aim of this study was to investigate the therapeutic effect of recombinant human erythropoietin (rHuEpo) on anaemia with erythropoietin deficiency in diabetic patients.

Methods Twenty diabetic patients with anaemia and Epo deficiency were enrolled. All patients were treated with rHuEpo (Epokine®; 4000 U/day s.c., three times a week) for 8 weeks.

Results The responder group (n = 14) had significant increments in haemoglobin compared with the non‐responder group (n = 6) (P < 0.05). No significant differences were found between the responder and non‐responder groups in terms of duration of diabetes mellitus, serum creatinine level, 24‐h urine albumin excretion rates, frequency of diabetic microangiopathy, or HbA1c. There was no difference between the two groups in terms of serum iron and total iron‐binding capacity (TIBC). Serum ferritin level was significantly higher in the responder group than in the non‐responder group (240.3 ± 108.4, 25.8 ± 3.0 µg/l, P < 0.05), as was transferrin saturation (32.7 ± 7.9%, 21.2 ± 5.3%, P < 0.05).

Conclusions rHuEpo could be useful in the treatment of anaemia with erythropoietin deficiency in diabetic patients, and the degree of iron storage and functional iron deficiency might be the main cause of hyporesponsiveness to rHuEpo.
Insulin lispro: a potential role in preventing nocturnal hypoglycaemia in young children with diabetes mellitus
Authors: Ford‐Adams M. E. , Murphy N. P. , Moore E. J. , Edge J. A. , Ong K. L. , Watts A. P. , Acerini C. L. , Dunger D. B.
Published: July 2003

Aims The long duration of action of soluble insulin given in the evening could contribute to the high prevalence of nocturnal hypoglycaemia seen in young children with Type 1 diabetes mellitus (T1DM). We examined whether replacing soluble insulin with insulin lispro reduced this risk in children on a three times daily insulin regimen.

Methods Open crossover study comparing insulin lispro vs. soluble insulin in 23 (16 boys) prepubertal children (age 7–11 years) with T1DM on three injections/day; long‐acting isophane insulin remained identical. At the end of each 4‐month treatment arm, an overnight 15‐min venous sampled blood glucose profile was performed.

Results Despite similar blood glucose levels pre‐evening meal (lispro vs. soluble: mean ± se 6.5 ± 1.0 vs. 7.1 ± 1.1 mmol/l, P = 0.5), post‐meal (18.00–22.00 h) blood glucose levels were lower on insulin lispro (area under curve 138 ± 12 vs. 170 ± 13 mmol min−1 l−1, P = 0.03). In contrast, in the early night (22.00–04.00 h) the prevalence of low blood glucose levels (< 3.5 mmol/l) was lower on lispro (8% of blood glucose levels) than on soluble insulin (13%, P = 0.01). In the early morning (04.00–07.00 h) mean blood glucose and prevalence of low levels were no different between the two treatment groups, and fasting (07.00 h) blood glucose levels were similar (6.1 ± 0.8 vs. 6.3 ± 0.9 mmol/l, P = 0.8). At the end of each treatment arm there were no differences in HbA1c (lispro vs. soluble 8.6% vs. 8.4%, P = 0.3), or in insulin doses (mean, range 0.97, 0.68–1.26 vs. 0.96, 0.53–1.22 U/kg per day, P = 0.2).

Conclusions The shorter duration of action of insulin lispro given before the evening meal may reduce the prevalence of early nocturnal hypoglycaemia without compromising HbA1c in young children with T1DM.
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

Aims 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

Aims 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

Aims 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

Anti‐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

Within 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

Obesity 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

The 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

This 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

We 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

This 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.