bluuebunny/crossref_metadata_2025 huggingface dataset:
A randomized controlled trial of tolterodine and oxybutynin on tolerability and clinical efficacy for treating Chinese women with an overactive bladder
Authors: Leung H.Y. , Yip S.K. , Cheon C. , Liu Y.S. , Lau J. , Wong H.K. , Chung K.H.
Published: March 2003

Objective To compare the tolerability and clinical efficacy of tolterodine and oxybutynin in the treatment of Hong Kong Chinese women with an overactive bladder.

Patients and methods A randomized controlled trial was conducted at two urogynaecology centres in Hong Kong. In all, 106 women with urodynamically confirmed detrusor instability were recruited. Baseline severity assessments included a visual analogue scale (VAS), urinary diary and urinary pad‐test. The women were randomized to receive either oral tolterodine 2 mg or oxybutynin 5 mg twice daily for 10 weeks. Treatment responses were assessed at 4 and 10 weeks using the VAS and urinary diary. Treatment tolerability was assessed at baseline, 4 and 10 weeks using the Xerostomia Questionnaire. A urinary pad‐test was repeated at 10 weeks.

Results
The perceived change from baseline VAS was better in the tolterodine than the oxybutynin group after 10 weeks of treatment (per‐protocol analysis,
P

 
=
 0.043). The two drugs were effective in reducing the symptoms of frequency (
P

 < 0.001). Tolterodine was significantly better than oxybutynin in reducing urinary leakage (urinary pad‐test; median change − 5.00 g vs 0 g,
P

 
=
 0.019). Both drugs caused a significant worsening of dry mouth (overall dryness,
P

 < 0.005; discomfort,
P

 < 0.005; sleep,
P

 
= 0.021; speaking,
P

 
=
 0.045; swallowing,
P

 
=
 0.004; and liquid consumption,
P   =  0.017).

Conclusions Both oxybutynin and tolterodine were effective in ameliorating the severity of the symptoms of detrusor instability. Tolterodine was better than oxybutynin in both subjective and objective outcome measures, but both drugs caused similar worsening of dry mouth that may limit the tolerability of these medications.
The effect of urinary incontinence and overactive bladder symptoms on quality of life in young women
Authors: Van Der Vaart C.H. , De Leeuw J.R.J. , Roovers J.P.W.R. , Heintz A.P.M.
Published: March 2003

Objective  To assess the consequences that the symptoms of urinary incontinence and an overactive bladder have on the quality of life in young, community‐dwelling women.

Subjects and methods  A population‐based, cross‐sectional cohort study was conducted in women aged 20–45 years. Urogenital symptoms and quality of life were assessed using standardized questionnaires, e.g. the Urogenital Distress Inventory and Incontinence Impact Questionnaire.

Results  The prevalence of symptoms of stress incontinence (39%), urge incontinence (15%) and an overactive bladder (12%) was high in this young population. Compared with urge incontinence, the symptoms of an overactive bladder similarly reduced the quality of life, but stress incontinence did not significantly affect the quality of life. Women with symptoms of an overactive bladder were especially limited in their mobility, whereas urge incontinence was especially associated with feelings of embarrassment. Although many women reported to be bothered by their symptoms, only a minority consulted their physician for them.

Conclusions  The symptoms of urinary incontinence and overactive bladder are common among young adult women and have the same detrimental effect on quality of life as urge incontinence. The reduction in mobility associated with overactive bladder symptoms may be especially distressing for these young and active women.
An audit of urodynamic standardization in the West Midlands, UK
Authors: Sriram R. , Ojha H. , Farrar D.J.
Published: March 2003

Objective  To report a follow‐up postal survey to one conducted in 1998 assessing the feasibility of standardizing urodynamic practice in the West Midlands region.

Methods  From the initial survey there was interest in standardizing the practice of urodynamics and a few simple guidelines were proposed. The postal survey was repeated to identify any changes. The guidelines included zeroing the transducer to atmospheric pressure, a filling rate of 50 mL/min and using the International Continence Society (ICS) definition of detrusor instability, including numerical values and recording any contraction in the presence of urgency. A questionnaire, similar to the initial one, was circulated to all the clinicians who had participated in the initial study, distributed ≈ 8 months after agreed guidelines were issued. Specific questions included details of the filling and voiding cystometrogram, and the basis of diagnosing detrusor instability. They were also asked to comment on whether they would still like the practice to be standardized.

Results  Only 17 of the 23 clinicians who participated in the initial study responded. For zeroing the transducer to atmospheric pressure, eight still zeroed to the patient. Only one unit had changed its practice by zeroing to atmospheric pressure. Varied rates of filling were still used and only eight participants used the ICS criteria to diagnose detrusor instability. Three of the 17 participants did not feel that standardization was achievable.

Conclusions  Obviously there is some apathy amongst clinicians to move towards standardization. No significant changes had been made since standardization guidelines were issued. Although most preferred initially to standardize urodynamic practice, individuals do not seem to have been convinced that they need to change their method to achieve uniformity.
Can the reverse transcriptase‐polymerase chain reaction for prostate specific antigen and prostate specific membrane antigen improve staging and predict biochemical recurrence?
Authors: Adsan Ö. , Cecchini M.G. , Bisoffi M. , Wetterwald A. , Klima I. , Danuser H.‐J. , Studer U.E. , Thalmann G.N.
Published: March 2003

Objective  To evaluate the perioperative gene‐specific primed nested reverse transcription‐polymerase chain reaction (RT‐PCR) for prostate‐specific antigen (PSA) and prostate‐specific membrane antigen (PSMA) for staging patients undergoing radical prostatectomy and predicting biochemical recurrence.

Patients and methods  In 80 consecutive patients undergoing radical prostatectomy for prostate cancer, blood samples were drawn before, during and 1 and 7 days after removing the prostate. After buffy coat and mRNA extraction, gene‐specific primed nested RT‐PCR was performed for PSA, PSMA and glyceraldehyde‐3‐phosphate dehydrogenase mRNA, and Southern blot analysis of the PCR reaction.

Results
 The sensitivity of gene‐specific RT‐PCR to detect tumour cells was comparable with random primed RT‐PCR. In the 80 patients the stage distribution was pT1 in two (2.5%), pT2 in 30 (37.5%) and ≥ pT3 in 48 (60%); the nodal status was pN0 in 57 (71%), pN1 in 11 (14%) and pN2 in 12 (15%). The gene‐specific RT‐PCR reaction for PSA and PSMA was positive in no patients with pT1, 11 (37%) with pT2 and 23 (48%) with stage ≥ pT3 disease. The result for PSA was positive in 12 (52%) and for PSMA in 11 (48%) of those with positive nodal status. Neither gene‐specific RT‐PCR for PSA or PSMA was able to predict organ‐confined disease (
P  > 0.5). After a median (range) follow‐up of 37 (11–67) months a biochemical recurrence was predicted in 65% of patients by preoperative RT‐PCR for both PSA and PSMA, with a sensitivity, specificity, positive and negative predictive value of 58%, 80%, 87% and 47%, respectively; the assay after surgery predicted a recurrence in 73%, with respective values of 68%, 84%, 84% and 57%.

Conclusions  Gene‐specific primed nested RT‐PCR for PSA and PSMA is a sensitive and simple assay; it might add substantial information for tumour staging in individual patients. RT‐PCR before surgery allows the prediction of recurrence in 65% of cases and after surgery in 73%.
The differences in health outcomes between Web‐based and paper‐based implementation of a clinical pathway for radical nephrectomy
Authors: Chang P.L. , Li Y.C. , Lee S.H.
Published: March 2003

Objective  To evaluate the effects of a web‐based clinical pathway (WCP) for radical nephrectomy on patient care, and to compare the effects with those of a paper‐based clinical pathway (PCP).

Patients and methods  Patients with renal cell carcinoma and who underwent radical nephrectomy were enrolled into the study. The results of using the WCP for radical nephrectomy from July 2000 to August 2001 were compared with those using the PCP between May 1999 and June 2000. The mean hospital stay, average admission charges, six quality indicators, and the advantages of the WCP were determined.

Results
 Using a WCP for radical nephrectomy reduced the hospital stay and admission charges by as much as the PCP. A similar number of patients had variances from the WCP as with the PCP (
P
 = 0.407), but the number of undetected variances and the variance detection time in the WCP were significantly less (
P  = 0.0193 and 0.0162). Implementing a WCP also improved the quality of care by as much as a PCP.

Conclusions  Using a WCP for radical nephrectomy can improve health outcomes by reducing the hospital stay and admission charges, and by improving the quality of care by as much as a PCP. Furthermore, the WCP was more accurate and faster than the PCP in detecting variances.
Vasopressin and hypercalciuria in enuresis: a reappraisal
Authors: Nevéus T. , Hansell P. , Stenberg A.
Published: March 2003

Objective  To test the hypotheses that vasopressin deficiency or hypercalciuria are important in polyuric and non‐polyuric bedwetting, as nocturnal polyuria is a pathogenetic factor in enuresis responsive to antidiuretic therapy with desmopressin.

Subjects and methods  Vasopressin deficiency has been implicated as a cause of nocturnal polyuria, but measurements of vasopressin in plasma have given contradictory results, because the hormone is released in pulses. Urinary levels reflect the secretion over longer periods. Hypercalciuria has also been proposed as a pathogenetic factor. Twenty‐eight enuretic children who responded to desmopressin therapy with or without added anticholinergic agents (diuresis‐dependent enuresis, DE), 15 children with therapy‐resistant enuresis (not diuresis‐dependent, NDE) and 51 continent controls were assessed. Urinary vasopressin, calcium and osmolality were measured in the morning after a 12‐h thirst provocation. Urine production was recorded for 2 days.

Results  Because most data were not normally distributed, the values are expressed as the median (range). There were no differences in urine osmolality; i.e. con‐trols 919 (636–1232), DE 849 (462–1149), NDE 968 (664–1191) mOsml/kg); vasopressin, controls 34 (8–983), DE 26 (9–295), NDE 50 (9–116) pmol/L; or calcium excretion (expressed as the calcium/creatinine ratio), controls 0.16 (0.01–0.71), DE 0.14 (0.04–0.67), and NDE 0.23 (0.03–0.69). The DE group produced more urine, at 18.4 (9.2–52.5) mL/kg/day, than the other groups, i.e. control 12.7 (8.3–42.8) and NDE 12.1 (6.3–36.8) mL/kg/day (P = 0.008).

Conclusion  All enuretic children with nocturnal polyuria do not have vasopressin deficiency. The urinary calcium excretion does not differ between enuretic and dry children.
Vesico‐ureteric reflux in the young infant with follow‐up direct radionuclide cystograms: the medical and surgical outcome at 5 years old
Authors: McLaren C.J. , Simpson E.T.
Published: March 2003

Objective  To compare the 5‐year outcome of 82 infants with vesico‐ureteric reflux (VUR) against the initial (< 1 year) and follow‐up results of the direct radionuclide cystogram (DRC).

Patients and methods  An initial DRC was taken at a mean age of 0.6 years and the follow‐up study at 1.7 years. VUR was graded using ‘one‐third bladder volume’ grades (BVG) of ‘low’, ‘moderate’, ‘high’ and ‘void’, with ‘low’ considered the most severe. Renal scintigraphy was used to assess renal scarring in 80 of the 82 patients. The outcome at a minimum age of 5 years was defined as resolved reflux, those with corrective surgery or those still being medically followed.

Results  Those being followed comprised 29%, corrective reflux surgery 17% and resolved 54% of the patients. Children with VUR grades of ‘high’ or ‘moderate’ (as the worst grade either side) were more likely to have resolution than those with ‘low’ (by four and two times, respectively). Reflux at ‘low’ bladder volume was 2.6 times more likely to be associated with renal scarring than the other grades combined. ‘Low’ reflux was present in nine of 14 children needing surgery. There was a linear relationship between VUR grade and the scintigraphic findings.

Conclusion  The severity of VUR can be assessed from the bladder‐volume graded DRC. Continuing VUR at ‘low’ BVG is associated with increased renal scarring, resistance to natural resolution and corrective reflux surgery.
Comparison of the cellular molecular stress responses after treatments used in bladder cancer
Authors: Shackley D.C. , Haylett A. , Whitehurst C. , Betts C.D. , O'Flynn K. , Clarke N.W. , Moore J.V.
Published: March 2003

Objective  To investigate the molecular stress responses related to the quality of recovery of normal tissue after various treatments for bladder cancer, i.e. hyperthermia, ionizing radiation, mitomycin‐C and 5‐aminolaevulinic acid photodynamic therapy (ALA‐PDT).

Materials and methods  The study focused particularly on intracellular fibroblast levels of heat‐shock protein‐47 (HSP47) and HSP72, which are associated with collagen metabolism and the development of tolerance to repeated treatment, respectively. Iso‐effective treatment doses (50% clonogenic cell survival) of each method were delivered to a 3T6 murine fibroblast model. Intracellular extracts were analysed at 3, 6, 9, 12 and 24 h after treatment, using Western blot analysis to compare the levels of HSP47 and HSP72. Time‐matched treatment and control groups were quantified by comparison with actin and glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) expression using appropriate software.

Results  There were various changes in levels of HSP expression with treatment method; HSP47 levels were significantly higher after hyperthermia and radiation but not with mitomycin‐C or ALA‐PDT. HSP72 levels were significantly higher with all methods except ALA‐PDT.

Conclusions  Hyperthermia and ionizing radiation are associated with early increases in levels of HSP47 (a marker of collagen metabolism), in contrast to ALA‐PDT and mitomycin‐C. These findings are compatible with clinical findings where fibrosis/scarring is common with the first two but not the last two methods. In addition, all methods except ALA‐PDT are associated with an increase in HSP 72 (a protein associated with cellular tolerance) and this may help to explain, at a cellular level, why resistance to repeated ALA‐PDT treatments does not seem to occur.
Urothelial ingrowth over demucosalized gastrocystoplasty: an experimental study
Authors: Abdel Hay S. , Soliman S.M. , Debeky M.E.
Published: March 2003

Objective  To evaluate histopathologically the ingrowth of urothelium over a demucosalized gastric flap used for augmentation, as such flaps increase the capacity of the bladder if the urothelium can cover the seromuscular patch.

Materials and methods  The study included eight male dogs; the urinary bladder was widely divided at its dome anteroposteriorly to receive a seromuscular gastric flap, sutured to the edges of the urinary bladder. Before and 1 month after surgery the changes in bladder capacity and pressure were recorded, and urothelial ingrowth assessed histopathologically.

Results  Two of the eight dogs died; the increase in mean bladder capacity in the remaining dogs was 20% and the decrease in mean intravesical pressure 34%. Gross pathological examination of the urinary bladder showed good ‘take’ of the gastric flap by the urinary bladder. Histopathologically, there was good healing of the flap, active ingrowth of urothelium, and no mucosal re‐growth.

Conclusion  Bladder augmentation with a demucosalized gastrocystoplasty allows the creation of a large compliant urinary bladder with few complications caused by the incorporation of the enteric or gastric epithelium into the urinary bladder. The stomach has a rich blood supply, allowing the harvesting of a well‐vascularized flap, and urothelial ingrowth over this flap in the present study was significant.
Changes in sodium transport in epithelial cells in a rat ileal‐augmented bladder model
Authors: Fujisawa M. , Sakai Y. , Nakano Y. , Arakawa S. , Kamidono S.
Published: March 2003

Objective  To investigate changes in the morphology and sodium transport ability of intestinal epithelium diverted to the urinary tract, using an in vitro sodium‐binding benzofuran isophthalate (SBFI) technique, as the effects of long‐term urine exposure on the transport of electrolytes through intestine are incompletely understood.

Materials and methods  Ileal augmentation cystoplasty was conducted in female Sprague‐Dawley rats; at 3 and 12 months after surgery the serum concentration of sodium, chloride and potassium were measured. Sodium transport in the ileal epithelial cells diverted to the urinary tract was evaluated using SBFI, as the value of the 340/380 nm excitation ratio measured with fluorescence spectrophotometry. The villous height and the number of villi per ileal length were obtained from haematoxylin and eosin‐stained sections.

Results  After 3 months the mean (sd) serum sodium concentrations in normal and augmented rats were 140.4 (2.5) and 140.7 (3.5) mmol/L, respectively; the chloride concentration in normal rats was 97.0 (2.9), and in augmented rats at 3 and 12 months it was 102.4 (2.9) and 99.0 (3.7) mmol/L, respectively. At 3 months, chloride concentrations were significantly higher in augmented than in normal rats (P < 0.05). The mean (sd) 340/380 nm ratio increased by 0.85 (0.09) in the normal ileum, and by 0.73 (0.15) and 0.49 (0.23) in the ileum of augmented rats at 3 and 12 months, respectively; the difference between normal and augmented ileum at 12 months was significant (P < 0.05). At 12 months the villous height in the augmented ileum, at 227.6 (16.0) µm, was significantly less than in the normal ileum, at 803.4 (66.2) µm (P < 0.05). However, the number of villi/mm ileum in normal and augmented rats at 12 months was 13.7 (1.5) and 15.0 (0.8), respectively, and not significantly different.

Conclusion  Sodium transport decreased significantly after long‐term exposure to urine; the improvement in metabolic change was probably attributable to alterations of electrolyte transport and atrophic changes of the villus.
Substitution urethroplasty for anterior urethral strictures: a critical appraisal of various techniques
Authors: Dubey D. , Kumar A. , Bansal P. , Srivastava A. , Kapoor R. , Mandhani A. , Bhandari M.
Published: March 2003

OBJECTIVE

To retrospectively compare the outcome of various techniques of substitution urethroplasty.

PATIENTS AND METHODS

Between 1989 and 2000, 109 patients (mean age 39.5 years) underwent substitution urethroplasty for recurrent anterior urethral strictures. Between 1989 and 1995 the procedure was by ventral placement of free grafts (bladder mucosa, buccal mucosa, penile skin) or penile skin flaps. From 1995 onwards the flaps and grafts (buccal mucosa) were applied either ventrally or dorsally. Stricture recurrence and the complications associated with each technique were compared.

RESULTS

Ventral onlay repairs were associated with a higher incidence of complications than dorsal repairs, e.g. postvoid dribbling (39% vs 23%, P = 0.01), ejaculatory dysfunction (20% vs 5%, P = 0.03) and flap/graft pseudo‐diverticulum or out‐pouching (26% vs 2.6%, P = 0.01). Superficial penile skin necrosis was significantly more common with the use of penile skin flaps than with free grafts. There was no significant difference in stricture recurrence, erectile dysfunction and residual penile deformity among the various techniques.

CONCLUSIONS

Dorsal free graft/flap onlay urethroplasty gives better results than ventrally placed free grafts/flaps. Dorsal onlay buccal mucosal urethroplasty is a versatile procedure and associated with fewer complications than other substitution methods.
Day‐case holmium laser enucleation of the prostate for gland volumes of < 60 mL: early experience
Authors: Larner T.R.G. , Agarwal D. , Costello A.J.
Published: March 2003

OBJECTIVE

To examine the safety and effectiveness of holmium laser enucleation of the prostate (HoLEP), as a day‐case procedure for selected patients.

PATIENTS AND METHODS

Thirty‐eight men underwent HoLEP as a day‐case procedure; they were discharged with an indwelling catheter for 48 h with ‘Hospital In The Home’ nursing management. They were evaluated for symptomatic and flow rate improvements after 3 months. Morbidity, length of stay, the duration of catheterization and readmission rates were evaluated.

RESULTS

The objective symptom score and flow‐rate improvements were equivalent to those previously published for transurethral resection of the prostate (TURP). There were five minor complications, three of which required readmission to hospital and one repeat surgery. The mean stay after surgery was 302 min.

CONCLUSIONS

Day‐case HoLEP is a safe and effective treatment for symptomatic benign prostatic hyperplasia. The outcomes are equivalent to those from TURP. Whilst there were three re‐admissions to hospital, two only required an overnight stay and no patient required a blood transfusion.
Intermittent androgen suppression in patients with prostate cancer
Authors: De La Taille A. , Zerbib M. , Conquy S. , Amsellem‐Ouazana D. , Thiounn N. , Flam T.A. , Debré B.
Published: March 2003

OBJECTIVES

To evaluate intermittent androgen suppression (IAS) in patients with prostate cancer and to try to define predictive factors for biochemical progression.

PATIENTS AND METHODS

From 1989 to 2001, 146 patients received IAS as a primary treatment for localized, advanced or metastatic prostate cancer (72 men) or as a treatment for prostate‐specific antigen (PSA) recurrence after radical prostatectomy (RP) and/or radiation therapy (74 men). Androgen‐deprivation treatment (ADT) was continued up to 6 months after PSA became undetectable or a nadir PSA level was reached. ADT was then re‐instituted when the PSA level was> 4 ng/mL for patients who had RP or> 10 ng/mL for the others.

RESULTS

After a mean (range) follow‐up of 45.6 (12–196.9) months, 24 patients had biochemical progression. These patients were younger than those with no biochemical progression (67 vs 72 years, P = 0.004) and had a statistically higher Gleason score (7.21 vs 6.52, P = 0.01) and PSA level (111.1 vs 32.1 ng/mL, P = 0.05), and a shorter first phase without treatment (7.6 vs 11.2 months, P = 0.05). Overall 5‐year metastatic disease free survival of 91.3%. The overall 5‐year biochemical recurrence‐free survival was 68%. Using multivariate analysis, a Gleason score of ≥ 8 (P = 0.021), first‐phase duration with no treatment of < 1 year (P = 0.044), positive lymph nodes or metastatic disease at the time of starting IAS (P = 0.023) and age < 70 years (P = 0.037) were the strongest predictors of biochemical progression.

CONCLUSION

IAS appeared to be a feasible treatment; the best candidates being those aged> 70 years with localized prostate cancer and a Gleason score of ≤ 7.
The efficacy of an abbreviated model of the International Prostate Symptom Score in evaluating benign prostatic hyperplasia
Authors: Cam K. , Senel F. , Akman Y. , Erol A.
Published: March 2003

OBJECTIVES

To investigate the acceptability to patients in Turkey of the International Prostate Symptom Score (IPSS) for evaluating benign prostatic hyperplasia (BPH), and to devise a possible abbreviated model, saving time when administered by a physician.

PATIENTS AND METHODS

The IPSS questionnaire was initially self‐administered in 200 consecutive patients aged> 50 years and with lower urinary tract symptoms. Patients were instructed only to mark questions which they clearly understood. The IPSS was then administered to 500 consecutive patients by the same physician. Subsequently, each of the seven questions was separately correlated with the IPSS and quality‐of‐life (QoL) score. The first five questions with the highest correlation coefficient for both the total IPSS and QoL score were identified, and every possible combination of these questions produced and correlated.

RESULTS

In the first group, 29% of the patients did not complete the form and 44% could not mark at least one item; the effect of educational level was significant (P < 0.05). In the second group a combination of the first three items had a Pearson's correlation of 0.90 with the total IPSS; similarly, four questions combined (2, 3, 6 and 7) also correlated well (r = 0.92). Both combinations took significantly less time to administer (P < 0.05).

CONCLUSION

The abbreviated form of the IPSS consisting of three or four items may be used to assess symptoms in patients with BPH, especially in underdeveloped countries.
Renal services for people with diabetes in the UK
Authors: Roderick P. , Armitage A.
Published: March 2003

Diabetic nephropathy is a serious complication of diabetes that can lead to endstage renal failure (ESRF). It is now the most common cause of ESRF in patients accepted onto renal replacement therapy (RRT) programmes in the UK. Rates of diabetic ESRF are more common in ethnic minority populations. The risk of developing diabetic ESRF is higher in Type 1 diabetes but in absolute terms more patients with Type 2 diabetes develop ESRF and are treated. There is still unmet need for RRT amongst patients with diabetes who develop ESRF. The shortage of organ donors, especially amongst ethnic minorities, means that dialysis is the mainstay of treatment in patients with diabetes and ESRF. This is now largely hospital haemodialysis with an increasing proportion being delivered in satellite units. Demand for RRT from patients with diabetes will increase due to demographic change and the increasing prevalence of diabetes, particularly Type 2, in the population. To meet this challenge closer liaison between those primarily caring for patients with diabetes (primary care physicians and diabetologists) and nephrologists is required to ensure effective surveillance of renal function, to increase early referral and to agree protocols of subsequent care. Continued expansion of high‐quality RRT is needed that ensures equity of access with particular targeting in areas with large ethnic minority populations. A national priority must be an increase in the kidney transplant rate.
The projected health care burden of Type 2 diabetes in the UK from 2000 to 2060
Authors: Bagust A. , Hopkinson P. K. , Maslove L. , Currie C. J.
Published: March 2003

Aims/hypothesis To predict the incidence and prevalence of Type 2 diabetes in the UK, the trends in the levels of diabetes‐related complications, and the associated health care costs for the period 2000–60.

Methods An established epidemiological and economic model of the long‐term complications and health care costs of Type 2 diabetes was applied to UK population projections from 2000 to 2060. The model was used to calculate the incidence and prevalence of Type 2 diabetes, the caseloads and population burden for diabetes‐related complications, and annual NHS health care costs for Type 2 diabetes over this time period.

Results The total UK population will not increase by more than 3% at any time in the next 60 years. However, the population over 30 will increase by a maximum of 11% by 2030. Due to population ageing, in 2036 there will be approximately 20% more cases of Type 2 diabetes than in 2000. Cases of diabetes‐related complications will increase rapidly to peak 20−30% above present levels between 2035 and 2045, before showing a modest decline. The cost of health care for patients with Type 2 diabetes rises by up to 25% during this period, but because of reductions in the economically active age groups, the relative economic burden of the disease can be expected to increase by 40−50%.

Conclusion/interpretation In the next 30 years Type 2 diabetes will present a serious clinical and financial challenge to the UK NHS.
Thiazolidinediones: a new class of antidiabetic drugs
Authors: Day C.
Published: March 2003

Thiazolidinediones (TZDs) are a new class of oral antidiabetic agents. They selectively enhance or partially mimic certain actions of insulin, causing a slowly generated antihyperglycaemic effect in Type 2 (noninsulin dependent) diabetic patients. This is often accompanied by a reduction in circulating concentrations of insulin, triglycerides and nonesterified fatty acids. TZDs act additively with other types of oral antidiabetic agents (suphonylureas, metformin and acarbose) and reduce the insulin dosage required in insulin‐treated patients. The glucose‐lowering effect of TZDs is attributed to increased peripheral glucose disposal and decreased hepatic glucose output. This is achieved substantively by the activation of a specific nuclear receptor – the peroxisome proliferator‐activated receptor‐gamma (PPARγ), which increases transcription of certain insulin‐sensitive genes. To date one TZD, troglitazone, has been introduced into clinical use (in Japan, USA and UK in 1997). This was suspended after 2 months in the UK pending further investigation of adverse effects on liver function. TZDs have been shown to improve insulin sensitivity in a range of insulin‐resistant states including obesity, impaired glucose tolerance (IGT) and polycystic ovary syndrome (PCOS). In Type 2 diabetes, the TZDs offer a new type of oral therapy to reduce insulin resistance and assist glycaemic control.

Diabet. Med. 16, 179–192 (1999)
Natural course of kidney function in Type 2 diabetic patients with diabetic nephropathy
Authors: Christensen P. K. , Rossing P. , Nielsen F. S. , Parving H. ‐H.
Published: March 2003

Aims To determine the natural course of kidney function and to evaluate the impact of putative progression promoters in Caucasian Type 2 diabetes mellitus (DM) patients with diabetic nephropathy who had never received any antihypertensive treatment.

Methods A long‐term observational study of 13 normotensive to borderline hypertensive Type 2 DM patients with diabetic nephropathy. Glomerular filtration rate (GFR) was measured approximately every year (51Cr‐EDTA plasma clearance technique). Albuminuria, blood pressure (BP) and haemoglobin A1c (HbA1c) was determined 2–4 times per year and serum cholesterol every second year.

Results The patients (12 males/one female), age 56 ± 9 (mean ±sd) years, with a known duration of diabetes of 10 ± 6 years, were followed for 55 (24–105) (median (range)) months. GFR decreased from 104 (50–126) to 80 (39–112) ml.min–1.1.73 m–2 (P = 0.002) with a median rate of decline of 4.5 (– 0.4 to 12) ml.min–1.year–1. During follow‐up, albuminuria rose from 494 (301–1868) to 908 (108–2169) mg/24 h (P = 0.25), while BP, HbA1c and serum cholesterol remained essentially unchanged. In univariate analysis the rate of decline in GFR did not correlate significantly with neither baseline nor mean values during follow‐up of BP, albuminuria, HbA1c and serum cholesterol.

Conclusions Our study suggests that normotensive to borderline hypertensive Type 2 DM patients with diabetic nephropathy have a rather slow decline in kidney function, but we did not unravel the putative progression promoters responsible for the variation in rate of decline in GFR.

Diabet. Med. 16, 388–394 (1999)
The British Diabetic Association Cohort Study, II: cause‐specific mortality in patients with insulin‐treated diabetes mellitus
Authors: Laing S. P. , Swerdlow A. J. , Slater S. D. , Botha J. L. , Burden A. C. , Waugh N. R. , Smith A. W. M. , Hill R. D. , Bingley P. J. , Patterson C. C. , Qiao Z. , Keen H.
Published: March 2003

Aims To measure cause‐specific mortality, by age, in patients with insulin‐treated diabetes incident at a young age.

Methods A cohort of 23 752 patients with insulin‐treated diabetes diagnosed under the age of 30 years, from throughout the United Kingdom, was identified during 1972–93 and followed to February 1997. Death certificates have been obtained for deaths during the follow‐up period and cause‐specific mortality rates and standardized mortality ratios by age and sex are reported.

Results During the follow‐up period 949 deaths occurred and at all ages mortality rates were considerably higher than in the general population. Acute metabolic complications of diabetes were the greatest single cause of excess death under the age of 30 years. Cardiovascular disease was responsible for the greatest proportion of the deaths from the age of 30 years onwards.

Conclusions Deaths in patients with diabetes diagnosed under the age of 30 have been reported and comparisons drawn with mortality in the general population. To reduce these deaths attention must be paid both to the prevention of acute metabolic deaths and the early detection and treatment of cardiovascular disease and associated risk factors.
Pakistani moslems with Type 2 diabetes mellitus: effect of sex, literacy skills, known diabetic complications and place of care on diabetic knowledge, reported self‐monitoring management and glycaemic control
Authors: Hawthorne K. , Tomlinson S.
Published: March 2003

Aims To study factors such as sex, educational status and place of care, which might influence knowledge and self‐management of diabetes, and glycaemic control in a Pakistani moslem diabetic population attending primary care general practices (GP) and secondary care clinics at the Manchester Diabetes Centre (MDC).

Methods Patients with Type 2 diabetes mellitus took part in a one‐to‐one semi‐structured interview and gave blood for haemoglobin A1c levels.

Results Two hundred and one patients entered the study. Knowledge about diabetic diets was good (average scores 72%), and patients claimed to perform regular glucose measurements (66%), but they were not good at applying their knowledge to problems in daily life. Only 24% knew how to manage persistent hyperglycaemia. Women were worse than men at this (19 vs. 31% (χ2 = 3.8, P = 0.05)), were less likely to understand why glucose levels should be monitored, and had poorer glycaemic control overall (HbA1c 8.8 vs. 8.1%, P = 0.04). Fifty‐four patients were completely illiterate. They had similar knowledge scores to readers but were less able to handle problem scenarios. Forty‐five of these patients were women, and multiple regression analysis showed they were more likely to have the poorest glycaemic control. No major differences were found between general practioner and hospital attenders, or between patients with and without known complications, except that hospital attenders were more likely to have complications and poorer control.

Conclusions Women who cannot read in this population are likely to have poorer glycaemic control and may be finding it more difficult to learn how to apply their knowledge to daily life. This subgroup may need more intensive, culturally appropriate, health education and support.
Oral candidal carriage and infection in insulin‐treated diabetic patients
Authors: Willis A. M. , Coulter W. A. , Fulton C. R. , Hayes J. R. , Bell P. M. , Lamey P. ‐J.
Published: March 2003

Aim To evaluate candidal load and carriage of candidal species in 414 insulin‐treated diabetes mellitus patients with and without clinical signs of infection. Host factors that could influence candidal load in diabetic patients with oral candidosis were also investigated.

Methods Candidal species were recovered from 414 insulin‐treated diabetes mellitus patients attending two hospital diabetic clinics, using an oral rinse technique.

Results Seventy‐seven per cent of diabetic patients carried Candida species in their oral cavity, with C. albicans being the species most frequently isolated. C. dubliniensis was found for the first time in this patient group. Forty per cent of patients colonized with candidal species had no clinical signs of oral candidosis. Where oral candidosis was present, erythematous candidosis was the most common clinical presentation. Candidal load was not associated with age, sex or glycaemic control. However, it was significantly increased in those patients who were tobacco smokers, and non‐significantly increased in those patients who wore dentures, or who had clinical signs of oral candidosis.

Conclusion The epidemiology of oral candidal carriage and infections in diabetic patients is complex and includes species which have not been previously reported in this group of patients. The development of oral candidosis in insulin‐treated diabetes mellitus patients is not the result of a single entity, but rather, a combination of risk factors.
Poorly controlled elderly Type 2 diabetic patients: the effects of increasing sulphonylurea dosages or adding metformin
Authors: Gregorio F. , Ambrosi F. , Manfrini S. , Velussi M. , Carle F. , Testa R. , Merante D. , Filipponi P.
Published: March 2003

Aims To assess the effects and safety of increasing sulphonylurea dosages or adding metformin in poorly controlled elderly Type 2 diabetic patients.

Methods A 18‐month multicentre clinical study was performed on sulphonylurea‐treated diabetic patients over 70 years of age with well‐preserved renal function, steady fasting blood glucose ≥  200 mg/dl and HbA1c≥  9%. Patients were randomly assigned to sulphonylurea increased up to its maximum dosage (1st group) or to addition of metformin (2nd group). Glycaemic control, lipid pattern, haemostatic status and safety were monitored during run‐in, at baseline and at scheduled intervals for 18 months. Results[85 patients in the 1st group and 89 patients in the 2nd with complete data.

Results Similar improvements in glycaemic levels were observed with both treatments within the first month and a similar decrease in HbA1c within the third month. No further changes occurred in glycaemic control. In the 1st group, fasting glucose (mmol/l, mean ± se) decreased from 14.21 ± 0.49 to 9.88 ± 0.21, average day‐long glucose from 14.87 ± 0.27 to 10.69 ± 0.19 and HbA1c (%) from 10.32 ± 0.13 to 8.66 ± 0.13. In the 2nd treatment group fasting glucose decreased from 14.59 ± 0.61 to 9.05 ± 37.28, average day‐long glucose from 15.09 ± 0.29 to 10.32 ± 0.21 and HbA1c from 10.33 ± 0.13 to 8.77 ± 0.12 (for all P <  0.0005). In this 2nd group, a decrease in LDL‐cholesterol (P <  0.05) and an increase in HDL‐cholesterol levels (P <  0.02) were also observed. In the 1st group, anthrombin III activity increased significantly (P <  0.01). In the 2nd group, significant reductions in markers of platelet function (FP4 and βTG, P <  0.01), thrombin generation (FPA, F1 +  2 and D‐D, P <  0.01), and fibrinolysis inhibition (PAI‐1 activity, PAI‐1 antigen, P <  0.001) were observed. Increases in some fibrinolytic activation markers (t‐PA activity, and AT‐III activity, P <  0.01) occurred. Fasting lactate concentrations were unchanged in the metformin‐treated group. No serious adverse effects were observed in either group.

Conclusions These results suggest that either high sulphonylurea dosages or a therapy combining lower sulphonylurea dosages with metformin are effective and safe in an aged but healthy population. Metformin provides additional benefits counteracting several cardiovascular risk factors but must be administered with caution, bearing in mind the general contra‐indications for the drug but not age alone.
Correlations between insulin sensitivity and bone mineral density in non‐diabetic men
Authors: Abrahamsen B. , Rohold A. , Henriksen J. E. , Beck‐Nielsen H.
Published: March 2003

Aims To investigate relationships between bone mineral density (BMD), insulin secretion and insulin sensitivity, controlling for body composition, in view of data suggesting that hypoglycaemia leads to decreased osteoblast proliferation and a negative calcium balance and that insulin stimulates osteoblast differentiation and collagen synthesis, with no clear evidence if this response in impaired in insulin resistance.

Methods Femur and whole body (WB) BMD was measured in 55 male patients with ischaemic heart disease and 40 healthy men, using a Hologic QDR‐2000 densitometer. Insulin sensitivity (Si) was estimated as the rate of glucose disappearance divided by the area under the insulin curve during an intravenous glucose tolerance test.

Results Insulin and C‐peptide levels were not correlated with BMD, but Si was a significant predictor of femur (log, r = 0.35) and WB BMD (log r = 0.29, both P < 0.01), even after controlling for weight and age. Fat mass (FM) was a predictor of BMD (femur: r = 0.33 P < 0.01, WB: r = 0.43 P < 0.001). In the femur the association with FM disappeared when log(Si) was entered in the regression. Lean body mass (LBM) contributed significantly to BMD (r = 0.50 and r = 0.66, both P < 0.001).

Conclusions These results are compatible with a direct influence of lean body mass on bone, while the impact of fat mass may consist of insulin resistance with increased insulin exposure of bone. It is hypothesized that patients with insulin resistance in the metabolic pathway do not exhibit resistance to the skeletal actions of insulin.
Relation between insulin resistance and carotid intima‐media thickness and stenosis in non‐diabetic subjects. Results from a cross‐sectional study in Malmö, Sweden
Authors: Hedblad B. , Nilsson P. , Janzon L. , Berglund G.
Published: March 2003

Aims To assess whether there is an association between insulin resistance and carotid intima‐media thickness and stenosis in non‐diabetic subjects free from symptomatic cardiovascular disease.

Methods A cross‐sectional population‐based study in Malmö, Sweden, of 4816 (40% men) subjects, born 1926–1945. The prevalence of insulin resistance was established by the homeostasis model assessment (HOMA) and defined as values above the 75th percentile. Criteria issued by the European Group for the Study of Insulin Resistance (EGIR) were used for the definition of the insulin resistance syndrome. Common carotid artery intima‐media thickness (IMT) and carotid stenosis (> 15%) were measured by B‐mode ultrasonography.

Results Age and sex‐adjusted common carotid IMT among subjects with the insulin resistance syndrome (12.7%) and controls was 0.812 mm, respectively, 0.778 mm (P < 0.001). The prevalence of stenosis in the two groups was 22.9 and 19.2% (P = 0.040). Insulin resistance per se was after adjustment for age and sex associated with increased IMT (0.780 mm vs. 0.754 mm, P < 0.001). This association disappeared, however, when other factors included in the insulin resistance syndrome were taken into account.

Conclusions Fasting serum insulin covaries with a number of factors and conditions known to influence the development of atherosclerosis. It is concluded that the association between insulin resistance, as assessed by the HOMA method in non‐diabetic subjects, and atherosclerosis is explained by its covariance with established risk factors for cardiovascular disease of which hypertension seems to be the most significant.
Altered heel‐pad mechanical properties in patients with Type 2 diabetes mellitus
Authors: Hsu T. ‐C. , Wang C. ‐L. , Shau Y. ‐W. , Tang F. ‐T. , Li K. ‐L. , Chen C. ‐Y.
Published: March 2003

SUMMARY

Aims  To compare the heel‐pad mechanical properties in patients with Type 2 diabetes mellitus with forefoot ulceration, without forefoot ulceration and age‐matched healthy subjects.

Methods  Heel‐pad mechanical properties in 40 heels of 20 healthy subjects (group I) age‐matched with the other groups, 42 heels of 21 diabetic patients without forefoot ulceration (group II), and 14 heels of 12 diabetic patients with active forefoot ulceration (group III) were assessed using a self‐constructed loading–unloading device and a 10‐MHz linear‐array ultrasound transducer.

Results  There were no differences in the unloaded heel‐pad thickness, compressibility index and elastic modulus between the three groups. When compared with group I subjects (mean ± sd, 27.9 ± 6.1%), a significant increase (P < 0.001) was found in both group II (36.1 ± 8.7%) and group III patients (43.2 ± 6.6%) for the energy dissipation ratio. This ratio was also significantly different (P = 0.003) between groups II and III.

Conclusions  The higher impact energy dissipated in the heel‐pad may put patients with Type 2 diabetes at higher risk for developing foot ulceration.
When and how to start insulin treatment in gestational diabetes: a UK perspective
Authors: Hadden D. R.
Published: March 2003

Gestational diabetes mellitus, however currently defined, is relatively rare in a UK Caucasian population, but is much more common in other ethnic groups. There is likely soon to be better agreement on diagnostic levels of hyperglycaemia in pregnancy, but there is still considerable reluctance to start insulin therapy. There is now good evidence that insulin administered twice daily during the third trimester to mothers who have even a mild degree of hyperglycaemia will reduce fetal size, and in particular fetal adiposity. In relation to recent concepts of the transgenerational passage of Type 2 diabetes and obesity, further epidemiological investigation is required. Insulin treatment in pregnancy may also prove to have a role in prevention of Type 2 diabetes in the next generation.

Diabet. Med. 18, 960–964 (2001)
The Utrecht Diabetes Project: telemedicine support improves GP care in Type 2 diabetes
Authors: Rutten G. E. H. M. , Maaijen J. , Valkenburg A. C. H. , Blankestijn J. G. , De Valk H. W.
Published: March 2003

Introduction The Utrecht Diabetes Project (UDP) is a shared‐care project providing remote diabetologist support for 85 GPs. In the UDP all examinations, performed by the GP, follow standardized procedures, results being sent to the diabetologist. Laboratory results are sent automatically to both GP and diabetologist.

Aims To study the composition of the UDP population; completeness of data recording; changes in biochemical variables of UDP patients; and GPs' motives for enrolling them.

Methods Data were extracted from the records of 19 GPs and a questionnaire was sent to all UDP GPs.

Results Of 770 patients with Type 2 diabetes, 44% were treated with UDP support, 29% by their GPs alone, and 27% at out‐patient clinics. The 336 UDP patients were representative of all UDP patients. Patients older than 75 years were the greater part of those treated by GPs alone; out‐patient clinics had more patients with diabetes > 10 years or with complications. UDP patients' records were the most complete. Diabetes regulation, lipid levels and diastolic blood pressure in the UDP patients improved significantly after inclusion in the UDP. GPs tend to seek UDP aid especially for patients who are young, or of recent onset, at risk of macrovascular complications, or needing insulin.

Conclusions Standardized data transfer between GP, diabetologist and laboratory might establish an effective infrastructure for shared diabetes care.

Diabet. Med. 18, 459–463 (2001)