Abstract: To investigate the risk factors for the development of persistent microalbuminuria in insulin dependent diabetic patients.Four year follow up of a cohort of diabetic patients.Outpatient departments of teaching and district general hospitals in England.148 non-microalbuminuric, non-hypertensive insulin dependent diabetic patients.Urinary albumin excretion rate and arterial blood pressure.137 patients completed four year follow up, of whom 11 developed persistent microalbumin-uria (albumin excretion rate > or = 30 micrograms/min on at least two consecutive occasions), giving a cumulative frequency of 8%. 103 remained normoalbuminuric and 23 exhibited intermittent microalbuminuria. At baseline the persistent microalbuminuric group had had significantly raised blood pressure (mean 137.9 (SD 14.9)/82.3 (7.6) v 123.5 (13.2)/72.8 (9.1) mm Hg), glycated haemoglobin concentration 10.4% (2.0%) v 8-9% (2.0%), and albumin excretion rate (median (interquartile range) 17.5 (13.0-22.3) v 4.8 (3.7-6.7) micrograms/min) (p < 0.05 for all) compared with the normo-albuminuric group. Blood pressure and glycated haemoglobin remained significantly higher in the persistent microalbuminuric group throughout the study (p < 0.05). Multiple regression analysis showed initial albumin excretion rate, blood pressure, and smoking to be significant determinants of persistent microalbuminuria (p < 0.02).In insulin dependent diabetic patients with poor glucose control, which may initially increase albumin excretion rate, an early rise of arterial pressure and smoking are implicated in the development of persistent microalbuminuria.

Abstract: We examined the prognostic value of early serum CA125 assay in 58 patients with advanced epithelial ovarian cancer together with residual disease, age, tumour grade, performance status, and the presence of ascites or adhesions at primary surgery. CA125 was a highly significant predictor of both progression free and overall survival after the first cycle and throughout primary chemotherapy. After the first cycle, CA125 was by far the most significant predictor of progression free survival (P < 0.0005). At this time, CA125 was a highly significant predictor of survival (P < 0.005), but did not add to performance status (P < 0.001) in multivariate analysis. We were able to identify three statistically-distinct prognostic groups. Patients in the upper quartile, with CA125 levels greater than 450 U ml-1, had a very poor median survival of 7 months. Patients in the lower quartile, with CA125 levels less than 55 U ml-1 had a good median survival of 23 months. Those in the two interquartile groups, who had CA125 levels ranging from 58-221 U ml-1 and 228-434 U ml-1, had relatively intermediate median survival times of 16 months and 15 months respectively. Although CA125 levels provided significant prognostic information, in the majority of patients CA125 merely confirmed overall clinical impression.

Abstract: summary statistics are thereforepresented as medians and interquartile ranges (IQR).Differences between groups were assessed using theMann-Whitney U test. Correlations between such data were determined with Spearman's rank correlation test. The results of the D-dimer assays were categorical in nature and were therefore analysed with the /test forobserved andexpected observations.PatientsLocalEthicalCommitteeapproval was obtainedtogetherwith informed consent from all patients. The study groups comprised patients presenting with untreated prostate cancer and age matchedcontrols withhistologi-cally proven, benign prostatic hypertrophy (BPH). Nopatient had clinical evidence ofthromboembolic diseaseand none developedhaemorrhagic or thrombotic compli-cations after operation.Assessment ofcoagulopathyActivation ofhaemostasis was assessed by the measure- ment of two markers, D-dimer and Fibrinopeptide A (FpA). D-dimer is produced as a result of cleavage ofcrosslinked fibrin by the fibrinolytic

Abstract: OBJECTIVE To investigate the effects of metformin on glycemic control, insulin resistance, and risk factors for cardiovascular disease in NIDDM subjects from two ethnic groups (Caucasian and Asian) with different risks of cardiovascular disease. RESEARCH DESIGN AND METHODS A total of 27 subjects with NIDDM (17 Caucasian, 10 Asian) were given metformin and placebo each for a 12-wk period in a randomized, double-blind, placebo-controlled crossover study, and the dose was increased after 1 and 6 wk, up to a maximum of 850 mg three times a day. Insulin resistance, glycemic control, and cardiovascular risk factors were assessed before and after each treatment phase. The end of 12 wk of metformin treatment was compared with the end of 12 wk of placebo treatment. RESULTS Metformin treatment was associated with significant improvement in FPG at 6 and 12 wk (mean difference at 12 wk, −3.08 mM, 95% CI −4.12 to −2.04 mM, P −1 · min −1 , interquartile range −0.10 to 1.30 ml · kg −1 · min −1 , P = 0.036). β-cell function calculated by HOMA also improved significantly (median difference 14%, interquartile range 7 to 23%, P P = 0.034), total cholesterol (mean difference −0.52 mM, 95% CI −0.83 to −0.22 mM, P = 0.002), and LDL cholesterol (mean difference −0.40 mM, 95% CI −0.64 to −0.16 mM, P = 0.002) fell significantly on metformin treatment, whereas no significant changes were observed in HDL cholesterol. PAI-1 activity fell significantly (mean difference −5.3 AU/ml, 95% CI −8.2 to −2.4 AU/ml, P = 0.001), but plasma fibrinogen concentrations and platelet function, spontaneous or agonist induced, were unaffected. UAE was lower on metformin treatment (median difference −2.4 μg/min, interquartile range −4.4 to −0.2 μg/min, P = 0.004), but metformin had no significant effect on BP. The effects of metformin on glycemic control and cardiovascular risk factors were generally similar in the two ethnic groups. CONCLUSIONS These findings indicate that metformin treatment improves glycemic control, and lowers insulin resistance and risk factors for cardiovascular disease, including PAI-1, and may therefore be useful in the long-term management of NIDDM subjects who have a high risk of cardiovascular disease.