bluuebunny/crossref_metadata_2025 huggingface dataset:
The anocutaneous reflex and urinary continence in children with myelomeningocele
Authors: Sanders C. , Driver C.P. , Rickwood A.M.K.
Published: March 2003

Objective To examine the hypothesis that because most patients with myelomeningocele and a positive anocutaneous reflex have a competent sphincteric mechanism they are more likely to be continent on intermittent catheterization than those with a negative reflex, and to become so with less need for adjunctive surgical treatment.

Patients and methods The study included 111 patients with myelomeningocele treated for urinary incontinence; their present means of treatment and the outcome achieved were assessed and related to the presence or absence of an anocutaneous reflex.

Results Among 29 patients with a positive anocutaneous reflex, 26 (90%) are currently dry on a regimen of intermittent catheterization, as opposed 41 (50%) of the 82 with a negative reflex (P < 0.001). Two (7%) of those with a positive and 23 (28%) of those with a negative reflex have undergone adjunctive surgery (P=0.024).

Conclusion These findings are consistent with both aspects of the hypothesis detailed in the Objective.
Severe partial ureteric obstruction in newborn rats can produce renal dysplasia
Authors: Wen J.G. , Frøkiær J. , Zhao J.B. , Ringgaard S. , Jørgensen T.M. , Djurhuus J.C.
Published: March 2003

Objective To investigate whether partial unilateral ureteric obstruction (PUUO produces renal dysplasia in newborn rats.

Materials and methods Left mild (in 31) or severe (in 34) PUUO was induced in 2‐day‐old rats by embedding a quarter or two‐thirds of the ureter into the psoas muscles, respectively. Sham‐operated control rats (36) were assessed in parallel. Kidney morphology, renal parenchymal weight and histology were examined 24 weeks and 30 months afterward.

Results There was significant pelvic dilatation in all obstructed kidneys; four kidneys were dysplastic in those severely obstructed, with a significant decrease in renal volume. There were three dysplastic kidneys after 6 months and one at 30 months. The in vitro dysplastic kidney weight was 36% of the control kidneys. Microscopy showed primitive glomerular and tubular structures, with renal parenchymal developmental disorganization and marked fibrosis. The glomeruli, tubules and collecting ducts were deficient in number and had often undergone cystic changes. Columnar tubular epithelium and peritubular mesenchymal collars were present. There was no renal dysplasia in the mildly obstructed and sham‐operated rats. The parenchymal weight of the kidneys contralateral to the dysplastic kidneys was significantly higher than in the controls (P < 0.001).

Conclusions Severe PUUO can produce renal dysplasia in newborn rats. However, only 12% with severe obstruction had renal dysplasia, indicating that the cause of renal dysplasia might also be related to other factors.
Reliability and validity of the Malay version of the Health‐Related Quality of Life instrument in a Malaysian population
Authors: Quek K.F. , Chua C.B. , Low W.Y. , Razack A.H. , Loh C.S.
Published: March 2003

Objective  To validate the Malay version of the Health‐Related Quality of Life (Mal‐HRQOL‐20) questionnaire in patients with and without urinary symptoms in a Malaysian population.

Patients and methods  The validity and reliability of the Mal‐HRQOL‐20 were assessed in patients with and without lower urinary tract symptoms (LUTS). The reliability was evaluated using the test‐retest method and the internal consistency using Cronbach's α. Sensitivity to change was expressed as the effect size in the score before and after intervention in additional patients with LUTS who underwent transurethral resection of the prostate.

Results

 The internal consistency was excellent; there was a high degree of internal consistency for each of the 20 items and for the overall score (Cronbach's α0.57 and 0.79, respectively) in the population study. The test‐retest correlation coefficient for the 20 item scores was highly significant. The intra‐class correlation coefficient was high ( 0.55). The sensitivity and specificity were high for the effects of treatment. There was a very significant agreement between scores before and after treatment across all domains in the treatment cohort, but not in the control group.

Conclusion  The Mal‐HRQOL‐20 is suitable, reliable, valid and sensitive to clinical change in the Malaysian population.
DNA hypermethylation at the D17S5 locus is not a frequent event in human urothelial cancer
Authors: Bernués M. , Casadevall C. , Caballín M.R. , Egozcue J. , Miró R.
Published: March 2003

Objective To analyse the DNA methylation status and the loss of heterozygosity (LOH) at the D17S5 locus (17p13.3) in urothelial cancer.

Materials and methods DNA methylation was assayed and LOH analysed by Southern blotting in a series of 33 transitional cell carcinomas of the bladder and renal pelvis.

Results DNA hypermethylation and LOH at the D17S5 locus were detected in six (18%) and 17 (52%) of the tumours, respectively. The six cases with DNA hypermethylation were of the papillary type, and four also had LOH at this locus.

Conclusion In contrast to other epithelial tumours, DNA hypermethylation at the D17S5 locus is not a frequent event in human urothelial cancer.
Clinical oncologists favour radical radiotherapy for localized prostate cancer: a questionnaire survey
Authors: Hanna C.L. , Mason M.D. , Donovan J.L. , Barber J.P.
Published: March 2003

Objective  To explore the treatment preferences of clinical oncologists for managing early prostate cancer and to compare the results with the preferences of urologists.

Methods  A postal questionnaire survey was conducted of consultant clinical oncologists in the UK.

Results  Consultant clinical oncologists favour radical radiotherapy in most men aged < 70 years, whereas a previous study showed that consultant urologists had a greater preference for radical surgery.

Conclusion  There is little consensus about which treatment should be used for managing early prostate cancer. There is an urgent need for results from randomized clinical trials to determine the optimum treatment.
Nocturia in relation to sleep, somatic diseases and medical treatment in the elderly
Authors: Asplund R.
Published: March 2003

Objective  To assess the influence of somatic diseases, symptoms and medication on nocturnal micturition in an elderly population.

Subjects and methods  All 10 216 members of the pensioners’ association in two Swedish counties were asked to participate in a questionnaire survey. The questions concerned their general state of health, occurrence of somatic diseases and symptoms, number of voiding episodes per night, and the use of drugs.

Results

 There were 6143 evaluable questionnaires, of which 39.5% were from men. The mean (
sd ) age of the men and women participating were 73.0 (6.0) and 72.6 (6.7) years, respectively. In a multivariate logistic model, significant independent correlates of having ≥ 3 nocturnal voids (vs ≤ 2 voids) were: being 70–79 years vs < 70 years (odds ratio, OR, 1.7, 95% confidence interval, CI, 1.3–2.2), being ≥ 80 years old vs < 70 years (OR, 1.9, CI, 1.3–2.5) and poor sleep vs good sleep (OR, 2.6, CI, 2.1–3.2), sequelae after stroke (OR, 2.0, CI, 1.1–3.6), irregular heart beats (OR, 1.6, CI, 1.2–2.1) and diabetes (OR, 1.5, CI, 1.1–2.3). Sex, spasmodic chest pain and snoring were all deleted by the logistic model.

Conclusion  Increasing age, poor sleep, irregular heart beats, diabetes and stroke are associated with an increase in nocturnal micturition in the elderly.
Correlation between major histocompatibility complex class I molecules and CD8+ T lymphocytes in prostate, and quantification of CD8 and interferon‐γ mRNA in prostate tissue specimens
Authors: Naoe M. , Marumoto Y. , Ishizaki R. , Ogawa Y. , Nakagami Y. , Yoshida H.
Published: March 2003

Objective  To investigate the immunology of host‐tumour interaction, critical for the development of immunotherapy against cancers, by assessing the major histocompatibility complex (MHC) class I expression in both benign and malignant prostate disease, and the relationship between their expression and degree of tumour‐infiltrating lymphocytes.

Materials and methods  Direct serial analysis of gene expression in tumours is an extremely sensitive and powerful tool for monitoring immunological changes in the immunotherapy of solid tumours. Most previous monitoring protocols rely mainly on the analysis of patient's peripheral blood but in the present study the direct molecular analysis of small tissue samples was used, and its accuracy compared with that of conventional immunohistochemical analysis. Twenty‐four formalin‐fixed, paraffin‐embedded prostate samples (11 benign and 13 carcinoma) were used for the im‐munohistochemical analysis of CD8+ T lymphocytes and MHC class I expression. CD8+ T lymphocytes were counted using an ocular grid and MHC class I measured using digital image‐analysis software. Twenty‐seven frozen prostate tissue samples (12 benign and 15 carcinoma) were used for direct gene measurements of CD8 and interferon‐γ using a quantitative real‐time polymerase chain reaction.

Results  There were significantly fewer CD8+ T lymphocytes in prostate carcinoma nests than in benign prostate. There was a significant correlation between the number of CD8+ T lymphocytes and MHC class I expression in the prostate. There was a strong correlation between the immunohistochemical estimates of CD8+ T lymphocytes and CD8 gene by polymerase chain reaction, but no significant difference between benign prostate and prostate carcinoma tissue in gene measurements.

Conclusion  Down‐regulation of MHC class I expression by prostate cancer cells is associated with fewer CD8+ T lymphocytes and hence might be important in cancer growth. In addition, the measurement of gene expression in small tissue samples might be useful for monitoring the efficacy of treatment throughout cancer therapy.
Penile scintigraphy with 99mTc‐human immunoglobulin G: a novel method for distinguishing the unstable and stable phases of Peyronie's disease
Authors: Erdogru T. , Boz A. , Köksal T. , Usta M.F. , Yildiz A. , Güngör F. , Baykara M.
Published: March 2003

Objective  To investigate the value of penile scintigraphy using 99mTc‐human immunoglobulin G (IgG) to differentiate the unstable (acute) and stable (chronic) phases of Peyronie's disease (PD).

Patients and methods  Thirty‐two consecutive patients (25 with PD and seven without) were evaluated using a detailed sexual history, serum chemistry panel, colour Doppler ultrasonography during simultaneous intracavernosal injection of 50 mg papaverine and stimulation, and 99mTc‐IgG scanning. When indicated, nocturnal penile tumescence monitoring, dynamic infusion cavernosometry, cavernosonography and cavernosal artery systolic occlusion pressure were measured. After administering 370 MBq of 99mTc‐IgG, images were taken at 30 min, 1, 2, 3 and 4 h. The scans were considered positive if there was any focal accumulation of radiopharmaceutical consistent with PD plaque formation.

Results  Eleven of the 25 patients with PD (mean age 56 years, sd 8) were in the unstable phase, the remaining 14 being in the stable phase. There was a localized increase in 99mTc‐IgG activity in 10 patients who had unstable PD. There was complete resolution of increased activity in two patients at 12 and 13 months of follow‐up. Of the 14 patients in the stable phase, 12 (at > 1 year) showed neither increased nor decreased 99mTc‐IgG activity. In the remaining two patients there was increased activity on the plaque side. There was no local increase in activity in the control group.

Conclusion  Inflammatory reactions can develop at various intervals during the unstable phase of PD. Medical methods should be used during the unstable phase and surgery delayed until the stable phase of the disease begins. An objective method of differentiating between the phases is therefore important. Penile 99mTc‐IgG imaging is a new diagnostic approach for confirming the unstable phase of PD.
Progesterone: a novel adjunct to intravesical chemotherapy
Authors: Lewin J. , Cooper A. , Birch B.
Published: March 2003

Objective  To investigate the effect of progesterone on multidrug‐resistant urothelial cell lines, as the failure of intravesical chemotherapeutic drugs is often caused by multidrug resistance (MDR), mediated by the drug efflux pump P‐glycoprotein (PGP), the function of which can be down‐regulated by various compounds including steroid hormones.

Materials and methods  Two urothelial cell lines (RT112S and MGH‐U1S) and their MDR sublines (RT112R, to cisplatin; and MGH‐U1R, a cell line expressing PGP) were used to assess the cytotoxic effects of progesterone, epirubicin and their combination. Cytotoxicity was assessed using a tetrazolium‐based assay and in situ confocal microscopy.

Results  Cell lines sensitive to epirubicin (MGH‐U1S, RT112S and RT112R) required a much lower dose of epirubicin to kill half the cells than did the MDR cell line. Progesterone was intrinsically cytotoxic to all cell lines with little difference among them. Combined therapy had no cumulative effect on epirubicin‐sensitive cell lines, but reversed MDR in the MGHU1R cell line, both assessed by confocal microscopy and by the tetrazolium assay.

Conclusions  Progesterone can reverse MDR in urothelial cells in vitro. This, combined with its effects on cell differentiation and apoptosis, together with its safety and tolerability compared to other MDR agents, suggests it may be a valuable adjunct to intravesical chemotherapy.
Predictive factors of radiation therapy for patients with prostate specific antigen recurrence after radical prostatectomy
Authors: De La Taille A. , Flam T.A. , Thiounn N. , Pontvert D. , Saighi D. , Zerbib M. , Debré B.
Published: March 2003

Objective  To assess the efficacy of salvage/adjuvant radiation therapy (RT) for patients with prostate‐specific antigen (PSA) recurrence after radical prostatectomy (RP).

Patients and methods  Between 1997 and 2001, 52 patients were treated in our institution with RT for PSA recurrence after RP. The mean (range) delay between RP and RT was 30.5 (0.16–105.6) months. Eighteen patients received no hormonal therapy before RT. The failure of RT was defined as three consecutive increases in PSA levels with intervals of ≥ 6 weeks.

Results  Within a mean (range) follow‐up of 27.7 (6–69) months, 18 patients presented with biochemical progression. The 3‐year biochemical progression‐free survival was 51%. Using univariate analysis, an age < 65 years (P = 0.0262), a Gleason score on the RP specimen of ≥ 8 (P = 0.0024), stage pT3 (P = 0.02), a detectable nadir PSA after RT (P < 0.001) and the absence of hormonal therapy (P = 0.0359) were associated with a lower biochemical progression‐free survival. However, only the Gleason score (P = 0.0395) and nadir serum PSA after RT (P = 0.028) remained independent predictive factors on multivariate analysis.

Conclusion  Half of the present patients treated with RT for an isolated high serum PSA level after RP were free of biochemical relapse at 3 years of follow‐up. RT may be proposed to selected patients with mild morbidity. However, definitive evidence of the beneficial effect of adjuvant RT for patients with PSA recurrence after RP awaits the conclusion of randomized clinical trials.
Differences between nocturics and non‐nocturics in voiding patterns: an analysis of frequency‐volume charts from community‐dwelling elderly
Authors: Rembratt A. , Norgaard J.P. , Andersson K.‐E.
Published: March 2003

OBJECTIVE

To evaluate differences between elderly people with and without nocturia (waking up in the night to void) in terms of voiding habits, urine production and voided volumes.

SUBJECTS AND METHODS

Nocturics (≥ two voids/night) and non‐nocturics (< one void/night) were recruited from a questionnaire survey. Subjects were asked to complete a 3‐day frequency‐volume chart, including time and volume of each void, and their bedtime and waking time. Diaries from 108 non‐nocturics and 116 nocturics were analysed. The number of voids, urine production, largest and average voided volumes were analysed using repeated‐measures analysis of variance models, controlling for variables such as age, gender, body weight and gender‐diagnosis interaction.

RESULTS

Nocturnal urine volume was higher in nocturics than in non‐nocturics. The difference between the groups was larger among the men (estimated difference 384 mL) than among the women (227 mL), but highly statistically significant (P < 0.001) in both genders. Among the men the diurnal urine and 24‐h urine volumes were significantly higher in nocturics (difference, diurnal 131 mL, 24‐h 462 mL, both P < 0.001). In the women the diurnal urine volume was lower in nocturics than in non‐nocturics (difference 147 mL P = 0.0022) with no difference detected in 24‐h urine volume. The largest voided volume was significantly less in nocturics than in non‐nocturics; the difference was larger in women (128 mL, P < 0.001) than in men (42 mL, P = 0.0027). The average voided volume was 85 mL less (P < 0.001) in nocturics. The overlap between the groups in nocturnal urine and voided volumes was substantial and several significant covariates identified. The ratio between nocturnal urine volume and largest voided volume was the most statistically significant predictor of the number of nocturnal voids.

CONCLUSION

Elderly nocturics had a higher nocturnal urine production and lower volume per void than non‐nocturics. Differences between nocturics and non‐nocturics in urine production and largest voided volume did not follow the same pattern in men and women. Nocturia was a result of a mismatch between nocturnal urine volume and largest voided volume, rather than abnormal values in either. The treatment of nocturia should be directed at one or both of these factors, depending on the findings from the 3‐day frequency‐volume chart of the individual.
Health‐related quality of life in men with metastatic prostate cancer: the misleading effect of lead‐time bias
Authors: Litwin M.S. , Saigal C.S. , Lubeck D.P. , Li Y.‐P. , Henning J.M. , Carroll P.R.
Published: March 2003

OBJECTIVE

To ascertain whether the difference in health‐related quality of life, which appears to be worse in men with metastatic prostate cancer when the metastases are noted at initial diagnosis than during follow‐up after treatment for clinically localized disease, can be attributed to previous local control or to some form of measurement bias.

PATIENTS AND METHODS

We analysed by univariate and multivariate methods 375 men with metastatic prostate cancer who were enroled in CaPSURE™, a national observational cohort of patients with prostate cancer treated in community and academic settings throughout the USA. In particular, we assessed whether group differences in health‐related quality of life were explained by the timing of metastatic diagnosis in the course of their disease. Health‐related quality of life was measured with the RAND 36‐Item Health Survey (SF‐36).

RESULTS

After controlling for relevant covariates (age, comorbidity and ethnicity), multivariate models suggested that men whose metastases were noted at the time of initial diagnosis scored 5–15 points worse in all eight domains of the SF‐36.

CONCLUSION

Men who are diagnosed with metastatic prostate cancer during the follow‐up after treatment for clinically localized disease report a better quality of life than those who are metastatic at the time of diagnosis, not because the primary treatment confers any benefit but because they are followed more closely over time and diagnosed with metastases earlier in the course of their disease. This apparent difference in quality of life is an effect of lead‐time bias in the diagnosis of metastasis.
Intensive lipid‐lowering strategy in patients with diabetes mellitus
Authors: Kanters S. D. J. M. , Algra A. , De Bruin T. W. A. , Erkelens D. W. , Banga J. ‐D.
Published: March 2003

Aims To assess the feasibility of an intensive lipid‐lowering strategy in diabetic subjects pursuing target plasma lipid levels.

Methods Patients with diabetes mellitus (DM), Type 1 or 2, with plasma lipid levels exceeding target values (LDL‐cholesterol < 2.6 mmol/l, triglycerides < 1.7 mmol/l, HDL‐cholesterol > 0.9 mmol/l for men and > 1.1 mmol/l for women) were eligible. After 6–12 weeks of diet and glycaemic control, lipid‐lowering medication (simvastatin/gemfibrozil/acipimox) was prescribed in steps of incremental dosages and combinations for 30 weeks.

Results Of all eligible clinic patients, 25% initially responded and finally 12% were entered. Thirty‐six patients with Type 1 and 59 with Type 2 DM were studied. Mean baseline lipid levels in Type 1 and Type 2 diabetic subjects were: LDL‐cholesterol 3.6 and 3.7 mmol/l, triglycerides 1.7 and 2.2 mmol/l, HDL‐cholesterol for men 1.1 and 1.0 mmol/l, and for women 1.4 and 1.2 mmol/l, respectively. All three target values were reached in 66% of the patients. LDL‐cholesterol was reduced by 1.2 mmol/l in Type 1 and 1.3 mmol/l in Type 2 diabetic patients and triglycerides by 0.7 mmol/l and 1.1 mmol/l, respectively. HDL‐cholesterol increased by 0.15 mmol/l and 0.34 mmol/l in men and women with Type 1 diabetes mellitus, respectively. The cholesterol–triglyceride ratio decreased significantly in VLDL in Type 1 diabetes and in IDL in Type 2 diabetes and increased significantly in HDL in Type 2 DM.

Conclusions A minority of subjects eligible for intensive lipid lowering agreed to participate in a feasibility study, suggesting a potentially large compliance problem for a general lipid‐lowering programme in a diabetes clinic. Nevertheless, intensive lipid lowering with drug combinations can attain the recommended target lipid levels in 66% of subjects with diabetes. With this strategy the plasma lipoprotein composition shifts towards a less atherogenic profile. Subjects with diabetes should therefore receive lipid‐lowering therapy tailored to reach target levels, rather than standard dosages, in order to reduce atherogenic risk.
Effect of pravastatin on erythrocyte rheological and biochemical properties in poorly controlled Type 2 diabetic patients
Authors: Miossec P. , Zkhiri F. , Pariès J. , David‐Dufilho M. , Devynck M. A. , Valensi P. E.
Published: March 2003

Aims The rheological properties of erythrocytes are impaired in diabetes mellitus, especially because of changes in their membrane lipid composition. In hypercholesterolaemic patients, lowering plasma cholesterol is associated with an improvement of the erythrocyte rheological parameters. The aim of this study was to investigate the relationship between erythrocyte deformability, plasma lipids, lipid membrane composition and cytosolic cations in poorly controlled Type 2 diabetic patients and to test the effects of a cholesterol‐lowering treatment on these parameters.

Methods We compared 37 poorly controlled Type 2 diabetic patients with 26 controls. In 22 of the diabetic patients who showed an impairment in erythrocyte deformability (filtration index > 10.5 on the Hanss’ haemorheometer), a double‐blind randomized trial compared the effect of the inhibitor of HMG CoA reductase pravastatin 20 mg per day for 4 months vs. placebo on the erythrocyte parameters.

Results Compared with controls, diabetic patients had higher filtration index (FI), erythrocyte sodium and calcium contents and lower free cholesterol–phospholipids ratio in erythrocyte membranes. Erythrocyte sodium content correlated positively with the FI and the membrane free cholesterol–phospholipids ratio. In the pravastatin‐treated group (11 patients), fibrinogen decreased significantly, FI reached a normal value (< 10) in six patients. Four of the five other patients who still had abnormal FI after 4 months of treatment had either a high plasma triglycerides (≥ 4.60 mmol/l) or a high plasma fibrinogen (≥ 4 g/l) level at baseline. Only two of the 11 placebo‐treated patients achieved a normal FI.

Conclusion These data suggest that in poorly controlled Type 2 diabetic patients there is a link between the chemical composition and the rheological properties of erythrocytes. Erythrocyte deformability may be improved by lowering plasma cholesterol with a statin.
Effects of 3‐week oral treatment with the antioxidant thioctic acid (α‐lipoic acid) in symptomatic diabetic polyneuropathy
Authors: Ruhnau K. ‐J. , Meissner H. P. , Finn J. ‐R. , Reljanovic M. , Lobisch M. , Schütte K. , Nehrdich D. , Tritschler H. J. , Mehnert H. , Ziegler D.
Published: March 2003

Aims To evaluate the efficacy and safety of short‐term oral treatment with the antioxidant thioctic acid (TA) on neuropathic symptoms and deficits in patients with Type 2 diabetes mellitus with symptomatic polyneuropathy.

Methods Patients were randomly assigned to oral treatment with 600 mg of TA t.i.d. (n=  12) or placebo (n=  12) for 3 weeks. Neuropathic symptoms (pain, burning, paraesthesiae, and numbness) in the feet were scored at weekly intervals and summarized as a Total Symptom Score (TSS). The Hamburg Pain Adjective List (HPAL) and the Neuropathy Disability Score (NDS) were assessed at baseline and day 19.

Results At baseline the TSS, HPAL, and NDS were not significantly different between the groups. The TSS in the foot decreased from baseline to day 19 by − 3.75 ± 1.88 points ( −  47%) in the TA group and by − 1.94 ± 1.50 points ( −  24%) in the placebo group (P=  0.021 for TA vs. placebo). The total HPAL score decreased from baseline to day 19 by − 2.20 ± 1.65 points ( − 60%) in the TA group and by − 0.96 ± 1.32 points ( − 29%) in the placebo group (P=  0.072 for TA vs. placebo). The NDS decreased by − 0.27 ± 0.47 points in the TA group, whereas it slightly increased by + 0.18 ± 0.4 points in the placebo group (P=  0.025 for TA vs. placebo). No differences between the groups were noted regarding the rates of adverse events.

Conclusions These preliminary findings indicate that oral treatment with 600 mg of TA t.i.d. for 3 weeks may improve symptoms and deficits resulting from polyneuropathy in Type 2 diabetic patients, without causing significant adverse reactions.
Intra‐individual variability and longitudinal changes in glycaemic control in patients with Type 1 diabetes mellitus
Authors: Jorde R. , Sundsfjord J.
Published: March 2003

Aims Patients with Type 1 diabetes mellitus (DM) appear to have remarkably stable HbA1c levels, regardless of the need for improvement. The purpose of the present study was therefore to study predictors of intra‐individual variability of the HbA1c level together with changes in HbA1c over time.

Methods Hospital records of patients with Type 1 DM seen at our diabetes clinic from February 1992 to May 1997 were reviewed for HbA1c measurements and clinical data. In the main study, 214 patients who had been on insulin for more than 1 year, and in a sub‐study, 14 patients newly started on insulin, were included.

Results The coefficient of variation (CV) of the intra‐individual HbA1c measurements, after at least 1 year of insulin, was 8.8 ± 3.7% (mean ± sd). There was a positive association between the CV and the HbA1c measurement at inclusion in the study (P < 0.05), and also a negative association between the CV and age (P < 0.05). Fifty per cent of the patients had a difference between first and last HbA1c below 1%, and 83.6% had a difference below 2%. In the sub‐study, there was a positive association between the mean HbA1c value the first year on insulin (excluding the first 3 months) and the last HbA1c measurement (P < 0.01).

Conclusions The HbA1c levels in individual patients remain remarkably stable over time. Furthermore, the HbA1c level shortly after starting insulin is a predictor of future glycaemic control.
Influence of a familial history of diabetes on the clinical characteristics of patients with Type 2 diabetes mellitus
Authors: Bo S. , Cavallo‐Perin P. , Gentile L. , Repetti E. , Pagano G.
Published: March 2003

SUMMARY

Aims  To evaluate the roles of maternal and paternal diabetes and diabetes in relatives other than parents on the clinical characteristics in Type 2 diabetes mellitus.

Methods  A total of 2113 Type 2 diabetic patients were recruited, and those with diabetic mothers, diabetic fathers, diabetic relatives other than parents and no known diabetic relatives, were considered separately.

Results  The prevalence of diabetes in the mother, father and other relatives was 25.5, 6.5 and 21.2%, respectively. No difference in the clinical characteristics was found in patients with diabetes in the mother or father. Patients with parental diabetes were significantly younger, with higher LDL‐cholesterol, prevalence of retinopathy and lower age at diabetes diagnosis than those without familial diabetes; on multiple logistic regression, only age (P = 0.0003), age at diabetes diagnosis (P = 0.0014) (inverse association), and LDL‐cholesterol (P = 0.030) remained significantly associated with parental diabetes. Patients with diabetic relatives other than parents displayed significantly higher total and LDL‐cholesterol, prevalence of retinopathy and lower age at diabetes diagnosis that those with no known diabetic relatives; on multiple logistic regression, only age at diabetes diagnosis was inversely associated with diabetes in relatives other than parents (P = 0.013).

Conclusions  The data do not indicate a different influence of maternal and paternal diabetes on the clinical characteristics of Type 2 diabetic patients, while there is evidence that parental diabetes brings to an earlier onset of the disease and higher LDL‐cholesterol values; the presence of diabetes in relatives other than parents constituted a small risk for earlier manifestation of the disease.
Beta blocker prescribing differences in patients with and without diabetes following a first myocardial infarction
Authors: Younis N. , Burnham P. , Patwala A. , Weston P J. , Vora J P.
Published: March 2003

SUMMARY

Aims  To document the prescribed usage of beta blockers in patients with and without diabetes mellitus discharged from hospital following a first myocardial infarction.

Methods  All patients with diabetes and a group of patients matched for age and sex without diabetes, admitted with a documented first myocardial infarction during the period 1995–1999 at the Royal Liverpool University Hospital, Liverpool, UK were audited.

Results  Data were available on 201 patients with diabetes and 199 patients without diabetes. No significant differences existed between the diabetic and non‐diabetic groups for age and sex. Twenty‐three per cent of patients with diabetes were prescribed a beta blocker compared to 52% of non‐diabetic patients (P < 0.01). Patients with diabetes had a higher frequency of perceived contraindications than patients without diabetes (36 vs. 27%, P < 0.001). Thirty‐five per cent of patients with diabetes and 18% of non‐diabetic patients had no contraindication to the use of beta blocker but were not prescribed one (P < 0.001).

Conclusions  Although beta blockers can provide useful benefits in patients with diabetes following a myocardial infarction, this study suggests that a significant proportion of patients with diabetes and without a contraindication to treatment are still not receiving beta blockers after myocardial infarction.
Short‐term Acipimox decreases the ability of plasma from Type 2 diabetic patients and healthy subjects to stimulate cellular cholesterol efflux: a potentially adverse effect on reverse cholesterol transport
Authors: Dullaart R. P. F. , Van Tol A.
Published: March 2003

Aims  To evaluate the effect of short‐term administration of the anti‐lipolytic agent, Acipimox, on the ability of plasma to stimulate cellular cholesterol removal, which represents one of the first steps in the anti‐atherogenic process of reverse cholesterol transport.

Methods  Eight male Type 2 diabetic patients and eight healthy subjects were studied after a 12‐h fast at baseline, after 24 h of Acipimox administration, 250 mg every 4 h, and again after 1 week (recovery). Plasma lipids, apolipoprotein AI, phospholipid transfer protein (PLTP) activity, pre‐β high‐density lipoproteins (HDL) in incubated plasma and efflux of radiolabelled cholesterol from Fu5AH rat hepatoma cells to plasma were measured at each time point.

Results  Acipimox lowered plasma triglycerides in diabetic patients (P = 0.001) and healthy subjects (P = 0.002), whereas plasma non‐esterified fatty acids were decreased in diabetic patients (P = 0.001) compared with the averaged values at baseline and recovery. Acipimox decreased HDL cholesterol in healthy subjects (P = 0.007) and plasma apolipoprotein AI in both groups (P = 0.001 for diabetic patients; P = 0.008 for healthy subjects). Not only plasma PLTP activity (P = 0.001 for diabetic patients; P = 0.01 for healthy subjects), but also pre‐β HDL in incubated plasma (P = 0.001 for diabetic patients; P = 0.03 for healthy subjects) and cellular cholesterol efflux to plasma (P = 0.04 for diabetic patients; P = 0.005 for healthy subjects) were lowered by Acipimox in both groups.

Conclusions  Short‐term Acipimox administration impairs the ability of plasma from Type 2 diabetic patients and healthy subjects to stimulate cellular cholesterol efflux, in conjunction with alterations in HDL parameters and in PLTP activity. If the impairment of cellular cholesterol efflux to plasma is sustained with long‐term treatment, this potentially adverse effect should be considered when treating diabetic dyslipidaemia with Acipimox.

Diabet. Med. 18, 509–513 (2001)
Obstetric and diabetic care for pregnancy in diabetic women: 10 years outcome analysis, 1985–1995
Authors: Hadden D. R. , Alexander A. , McCance D. R. , Traub A. I.
Published: March 2003

Aim  Ten‐year outcome analysis of all pregnancies in diabetic women in a population of 1.5 million people.

Methods  Ascertainment of patients through the regional obstetrical computer, and by direct contact with each obstetrical unit. Retrospective assessment of early miscarriage of pregnancy from hospital records. Data are presented for the six smallest obstetrical units, the four smaller district hospitals, two larger teaching hospitals and for the regional referral centre.

Results  Nine hundred and eighty‐six fetal outcomes were identified, 753 in mothers treated with insulin before the pregnancy, 131 in mothers in whom insulin was started for the first time during the pregnancy and 102 in mothers treated by diet only. Overall perinatal mortality rates were 35.8 per 1000 for those mothers booked and delivered at a local maternity unit, 28.9 per 1000 for those booked and delivered at the regional centre, but 75.0 per 1000 for those who had booked locally but were transferred to the centre mid‐pregnancy. Information on blood glucose control before and during pregnancy was relatively poorly documented. For the available data at the regional centre, only 160 of the 416 mothers had an identifiable preconception HbA1c measurement (mean 7.9%, range 3.3–16.8%): at booking 360 of these mothers had a mean HbA1c of 7.5% and by the third trimester mean HbA1c was 6.3% (range 3.3–13.2%).

Conclusions  The outcome of pregnancy in a diabetic mother in Northern Ireland remains a higher risk than for the general population. There is evidence that results in the regional centre are better, but problems arise when transfers occur mid‐pregnancy. Measurement and recording of blood glucose control at all stages before and during pregnancy is incomplete.

Diabet. Med. 18, 546–553 (2001)
Acceleration of diabetic retinopathy in pregnancy: a case report
Authors: Joseph S. E. , McHugh D. , Blott M. , Amiel S. A. , Watkins P. J.
Published: March 2003

Aims Diabetic retinopathy can deteriorate during pregnancy. This usually manifests itself as an increase in the number of background retinopathy lesions, notably the appearance of new cotton wool spots, predominantly during the first trimester. The changes are usually attributed to the rapid attainment of tight glycaemic control during pregnancy. We present a case report of catastrophic deterioration in retinopathy during a period of stable glycaemic control.

Results J.P. had normal fundoscopic appearance at booking and during the early part of pregnancy. She experienced rapid deterioration in visual acuity secondary to cystoid macular oedema and vitreous haemorrhage during the third trimester of pregnancy. Her glycaemic control was stable at that stage and had not changed when compared with earlier stages of pregnancy. She required three sessions of intrapartum laser therapy and postpartum vitrectomy.

Conclusions  The case highlights the importance of regular retinal surveillance in a diabetic pregnancy, even in the absence of sudden improvements in glycaemic control.

Diabet. Med. 18, 675–678 (2001)
Beta‐cell function evaluated by HOMA as a predictor of secondary sulphonylurea failure in Type 2 diabetes
Authors: Taverna M. J , Pacher N. , Bruzzo F. , Slama G. , Selam J. L.
Published: March 2003

Background and aims  Secondary failure to oral hypoglycaemic agents, a common evolution of long‐standing Type 2 diabetes, is usually assessed by non‐standardized indices requiring fine clinical assessment, including hyperglycaemia resistant to maximum doses of sulphonylureas despite appropriate diet and follow‐up. The goal of this study was to evaluate if HOMA, a modelized plasma insulin/glucose ratio allowing simple evaluation of residual insulin secretion and sensitivity, is a better predictor of the insulin requiring stage than clinical indices.

Materials and methods  HOMA was measured in 84 Type 2 diabetic patients aged 58 ± sd 6 years, with diabetes duration 11 ± 4 years, hospitalized because of hyperglycaemia resistant to maximal doses of sulphonylureas (e.g. glibenclamide ≥ 15 mg/day), with no apparent external reason for hyperglycaemia. Despite reinforced appropriate diet recommendations, 62 of these patients remained hyperglycaemic (insulin‐requiring group).

Results  Age, duration of diabetes, body mass index (BMI) and HOMA value for insulin sensitivity (71 ± 6% vs. 76 ± 7%, normal values 59–161%) were comparable in the two groups. HbA1c was higher (10.0 ± 0.2% vs. 8.3 ± 0.3%, P < 0.001) and HOMA insulin secretion values lower (25 ± 2% vs. 43 ± 6%, normal values 70–150%, P < 0.01) in the insulin‐requiring group. Of the following potential predictors: HbA1c > 8%, duration of diabetes ≥ 10 years, HbA1c combined with diabetes duration, insulin sensitivity ≤ 40%, insulin secretion ≤ 20%, the latter showed the best positive predictivity (86% patients with low insulin secretion were insulin‐requiring).

Conclusions  (i) HOMA is a simple and good predictor of the insulin‐requiring stage in Type 2 diabetes mellitus; (ii) this stage of diabetes is characterized by a further decline of insulin secretion rather than of insulin sensitivity.

Diabet. Med. 18, 584–588 (2001)
Glucose counterregulation in Type 2 diabetes mellitus
Authors: De Galan B. E. , Hoekstra J. B. L.
Published: March 2003

Glucose counterregulatory failure and hypoglycaemia unawareness frequently complicate treatment of Type 1 diabetes mellitus, especially when aiming for intensive metabolic control. Since tight metabolic control reduces microvascular long‐term complications in Type 2 diabetes mellitus, the integrity of glucose counterregulation in Type 2 diabetic patients is important. Using a Medline search, we identified 12 studies in which counterregulatory responses to insulin‐induced hypoglycaemia were compared between Type 2 diabetic patients and appropriate controls. A review of these studies showed that some patients with Type 2 diabetes mellitus develop mild counterregulatory dysfunction and reduced awareness of insulin‐induced hypoglycaemia. Some studies suggested an association between counterregulatory impairment and intensity of metabolic control. We speculate that the relatively low frequency of (severe) hypoglycaemic events in Type 2 diabetes may explain why glucose counterregulation remains unaffected in most patients. We hypothesize that residual β‐cell reserve and insulin resistance provide protection against severe hypoglycaemia and limit impaired counterregulation.

Diabet. Med. 18, 519–527 (2001)
Insulin‐treated diabetes and driving in the UK
Authors: Gill G. , Durston J. , Johnston R. , MacLeod K. , Watkins P.
Published: March 2003

Diabetes, and particularly insulin‐treated diabetes, has important implications for motor vehicle driving, largely because of its association with potential hypoglycaemia. For this reason, most countries operate some driving restrictions on insulin‐treated diabetic patients, as well as systems of intermittent reassessment of hypoglycaemic risk. In the UK, regulations are operated by the Driver and Vehicle Licensing Agency (DVLA), which is an agency of the Department of the Environment, Transport and the Regions (DETR). They are supported by an Expert Panel which advises the Secretary of State on diabetes‐related issues relating to fitness to drive. The patient organization Diabetes UK is also concerned with diabetes and driving issues, largely from a position of lobbying policy‐influencers and supporting individual cases. All parties involved with diabetes and driving issues recognize the need for more research on the subject, as the current literature is flawed in design, though no convincing excess of accidents amongst diabetic drivers has been conclusively demonstrated. Currently in the UK, Class 2 vehicles (large trucks and passenger vehicles) are barred to diabetic drivers on insulin. European law has recently extended this to so‐called C1 (large vans and small lorries) and D1 (minibuses) vehicles, though the law has recently been revised to allow individual consideration for potential diabetic C1 drivers on insulin treatment. Diabetes and insulin‐treated diabetes is an emotive and difficult issue, for which a stronger evidence base is urgently needed.
Retinopathy in latent autoimmune diabetes of adults: the Fremantle Diabetes Study
Authors: Balme M. , McAllister I. , Davis W. A. , Davis T. M. E.
Published: March 2003

Aims To determine the prevalence of retinopathy and its associations in patients diagnosed clinically with Type 2 diabetes and serum antibodies to glutamic acid decarboxylase (GADA) from a community‐based sample.

Methods In a case‐control design, 24 GADA‐positive Type 2 patients from the Fremantle Diabetes Study (FDS) cohort were recruited and matched as closely as possible for age, sex and diabetes duration with 72 GADA‐negative Type 2 patients from the FDS. Each patient had a detailed clinical and biochemical assessment including slit lamp biomicroscopy and colour fundus photography with Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) grading.

Results The GADA‐positive patients had a significantly higher HbA1c (median (interquartile range); 8.4 (7.3, 9.6)%) than those who were GADA‐negative (7.2 (6.5, 8.1)%: P = 0.002). The overall prevalence of retinopathy amongst the 96 subjects was 26.0%. The majority (92%) of the retinopathy detected was mild and non‐proliferative. GADA‐positive patients had double the retinopathy prevalence of the GADA‐negative group (41.7% vs. 20.8%; P = 0.044). In a logistic regression model, diabetes duration, HbA1c, systolic blood pressure and current smoking were each significantly and independently predictive of retinopathy (P < 0.025), but GADA status was not.

Conclusions These data show that GADA‐positive patients have an increased prevalence of retinopathy compared with GADA‐negative controls with Type 2 diabetes from an urban Australian community. This increased prevalence is due mainly to relatively poor glycaemic control in the GADA‐positive group.
Diminution of early insulin response to glucose in subjects with normal but minimally elevated fasting plasma glucose. Evidence for early β‐cell dysfunction
Authors: Sato Y. , Komatsu M. , Katakura M. , Ohfusa H. , Yamada S. , Yamauchi K. , Hiramatsu K. , Ichikawa K. , Aizawa T. , Hashizume K.
Published: March 2003

Aim Systematic analysis of β‐cell function in Japanese health examinees.

Methods In 938 Japanese health examinees (627 men and 311 women, mean age and body mass index, 54.0 years and 23.6 kg/m2, respectively), plasma specific insulin was measured at fasting and during a 75‐g oral glucose tolerance test. The subjects were stratified into six groups based on fasting plasma glucose ≤ 5.1 mmol/l, 5.2–6.0 mmol/l, 6.1–6.9 mmol/l, 7.0–7.8 mmol/l, 7.9–8.7 mmol/l, and ≥ 8.8 mmol/l as the 1st, 2nd, 3rd, 4th, 5th and 6th groups, respectively.

Results Distribution of fasting insulin showed a very modest ‘inverted U’ shape, with the peak in the 5th group. Progressive increase from the 1st toward the 5th group was significant. In contrast, the ratio of change in insulin to change in glucose from 0 to 30 min during the glucose tolerance test was greatest in the 1st group and progressively declined in the groups with higher fasting glycaemia. Difference in the ratio was most striking and highly significant between the 1st and 2nd groups. Distribution of the insulin to glucose ratio of subjects with normal glucose tolerance significantly overlapped with that of untreated patients with diabetes.

Conclusions In a Japanese population, (i) β‐cell starts to deteriorate during normoglycaemia with a minimal elevation of fasting plasma glucose, and (ii) there are glucose‐tolerant subjects with β‐cell dysfunction.
Space–time clustering of childhood Type 1 diabetes in Devon and Cornwall, England
Authors: Zhao H. X. , Moyeed R. A. , Stenhouse E. A. , Demaine A. G. , Millward B. A.
Published: March 2003

Aims Several studies on space–time clustering have been reported in childhood diabetes, but the findings are conflicting. The present study was undertaken to examine whether such clustering could be detected at either birth or the time of diagnosis in the far South‐west of England.

Methods A cohort of 518 children aged 0–15 years and diagnosed with Type 1 diabetes from 1975 to 1996 contained in the population‐based Cornwall and Plymouth Children's Diabetes Register (CPCDR) were included in the analyses. The case ascertainment for this register is estimated to be 94.4% complete. Mantel's modification of Knox's method was employed. A method based on K‐function was also used, for the first time, to investigate the space–time clustering of diabetes.

Results Significant space–time clustering at diagnosis was found by the Knox's test in the following combinations of critical cut‐off thresholds: 25, 35 and 50 km and 90, 270 and 360 days (all P < 0.05), with the highest significance found at 35 km and 360 days (P = 0.0011). K‐function analysis also confirmed the overall clustering (P = 0.013).

Conclusions There is strong evidence of space–time clustering in the onset of childhood Type 1 diabetes in Devon and Cornwall, England. These results lend some support to the hypothesis that viral infections and some unknown localized environmental factors play a role in the development of childhood Type 1 diabetes.

Diabet. Med. 19, 667–672 (2002)
Type 2 diabetes, obesity, and the renal response to blocking the renin system with irbesartan
Authors: Price D. A. , Lansang M. C. , Osei S. Y. , Fisher N. D. L. , Laffel L. M. B. , Hollenberg N. K.
Published: March 2003

Aim Our recent studies revealed a striking but variable enhancement of renal vasodilator responses to blockers of the renin‐angiotensin system in subjects with diabetes mellitus, possibly reflecting the level of intrarenal activation of the renin‐angiotensin system, and thus a risk of nephropathy. As obesity is a common finding in diabetic individuals, and obesity has been linked to an increase in plasma angiotensinogen levels, we enrolled diabetic subjects with a wide range of body mass index (BMI) for this study.

Methods Twelve Type 2 diabetic subjects in balance on a low sodium diet participated after baseline renal plasma flow and glomerular filtration measurements were made. Each subject then received 150 mg irbesartan, and renal function was measured every 45 min for 4 h.

Results The average vasodilator response to irbesartan was 174 ± 33 ml/min. No correlation was found between renal plasma flow response to irbesartan and duration of diabetes, baseline glucose, or HbA1c level. BMI, our measure of obesity, was highly correlated to the renal response to irbesartan (r
 
=
 0.7; P   =  0.01).

Conclusions Our findings suggest an important role for obesity in activating the intrarenal renin system, perhaps via production of angiotensinogen. BMI may be an indicator of risk of nephropathy.