Epidemiological and family studies imply that genetic factors are important in the etiology of diabetic nephropathy in subjects with IDDM (1,2). Vascular disease is characteristic of nephropathy, and lipoproteins are important determinants of atherosclerosis. Apolipoprotein E (apoE) is a major protein constituent of lipoproteins, mediating hepatic lipoprotein uptake and reverse cholesterol transport. ApoE occurs as three isoproteins: E3 with normal function, E2 with reduced affinity, and E4 with increased affinity for the apoE receptor. These are encoded by three codominant alleles e2, E3, and e4. This polymorphism has an influence on lipid levels, the E2 isoform being associated with lower cholesterol but higher triglyceride levels compared with the E3 isoform, and the E4 isoform being associated with higher cholesterol but lower triglyceride levels (3). There is also an association with vascular disease in diabetic and nondiabetic populations (3,4). Preliminary data suggest that this triallelic polymorphism may be associated with genetic susceptibility to diabetic nephropathy (5). The aim of this study was thus to determine the role of the apoE gene polymorphism in a large cohort of IDDM patients with and without diabetic nephropathy.Four patient cohorts were examined: IDDM patients with diabetic nephropathy (nephropathy group, n = 252), IDDM patients with long duration of disease and no nephropathy (long-duration non-nephropathy group [LDNN], n = 197), a Received for publication 7 April 1997 and accepted in revised form 22 October 1997. apoE, apolipoprotein E; LDNN, long-duration non-nephropathy; UA/UC, urinary albumin/creatinine. background population of recently diagnosed patients with IDDM (sporadic diabetic group, n = 270), and nondiabetic control patients (nondiabetic group, n = 346). The criteria used to classify patients has been described previously in detail (6). Presence of hypertension, and retinopathy were inclusion criteria in the nephropathy cohort. DNA was extracted from peripheral blood leukocytes by the Nucleon method (Scotlab, Paisley, Scotland, U.K.). ApoE genotyping was performed by the method of Crook et al. (7).The distribution of alleles and genotypes were compared between the groups by x 2 analysis. A probability of <1 in 20 (P < 0.05) was taken to be significant. Odds ratios were determined by the logit method (Woolfs analysis). Statistical analysis was performed using the statistical package SPSS.No significant difference was seen between the nephropathy and LDNN groups in age at diagnosis of diabetes, duration of diabetes, mean HbA lc , and serum cholesterol at time of venesection. The nephropathy group had a significantly higher proportion of men (P < 0.01), systolic and diastolic blood pressure (P < 0.001), proportion on antihypertensive therapy (P < 0.01), and serum creatinine (P < 0.001). Allele frequencies between the nondiabetic group and the sporadic group (Table 1) were almost identical (x 2 = 0.886, P = 0.642). There was, however, significant heterogeneity in allele frequen...

Premature cardiovascular disease is common in insulin-dependent diabetic (IDDM) patients who develop diabetic nephropathy. Genetic polymorphism within the renin-angiotensin system has been implicated in the aetiology of a number of cardiovascular disorders; these loci are therefore candidate genes for susceptibility to diabetic renal disease. We have examined the angiotensin converting enzyme insertion/deletion polymorphism and angiotensinogen methionine 235 threonine polymorphism in a large cohort of Caucasian patients with IDDM and diabetic nephropathy. Patients were classified as having nephropathy by the presence of persistent dipstick positive proteinuria (in the absence of other causes), retinopathy and hypertension (n = 242). Three groups were examined for comparison: ethnically matched non-diabetic subjects (n = 187); a geographically defined cohort of newly diagnosed diabetic patients (n = 341); and IDDM patients with long duration of disease (> 15 years) and no evidence of overt nephropathy (n = 166). No significant difference was seen in distribution of angiotensin converting enzyme or angiotensinogen genotypes between IDDM patients with nephropathy and recently diagnosed diabetic subjects (p = 0.282 and 0.584, respectively), nor the long-duration non-nephropathy diabetic subjects (p = 0.701 and 0.190, respectively). We conclude that these genetic loci are unlikely to influence susceptibility to diabetic nephropathy in IDDM in the United Kingdom.

Over a five-year period 64 Quinton Permcaths were inserted into 51 dialysis patients (age range 17-72 years, mean 52.1 SD 12.83). The duration of catheter use ranged from 5 to 1479 days, mean 315.7 SD 337. The actuarial catheter survival rate at 1 year was 74%, at 2 years 43%, at 3 years 25% and at 4 years 12%. The indications for use were: exhausted peripheral access; CAPD contraindicated; abrupt failure or lack of an arteriovenous fistula; acute renal failure; limited life expectancy; patient insistence; conventional access contraindicated. Only minor complications occurred during insertion: haemorrhage requiring exploration in three patients and a temporary left recurrent laryngeal nerve palsy in one patient. The exit site infection and septicaemia rates were 4.95 and 3.36 per 1000 catheter days respectively. Eighteen catheters failed due to infection (range of use 72-1479 days, mean 559 SD 388). Inadequate initial blood flow (less than 150 ml/min) occurred in 10% of dialyses but only six catheters failed due to intractable flow difficulties (range of use 5-49 days, mean 22 SD 17.5). Catheter sepsis was implicated in the death of two patients. One subclavan/innominate vein thrombosis occurred. The Quinton Permcath represents a significant advance providing immediate, durable, and relatively safe access in a variety of difficult circumstances.

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The development of a new polarographic sensor for measuring simultaneously both N2O and O2, in either gas or blood, is described. The cathode is made of silver, and it is shown that silver deposition on normal platinum or gold cathode electrodes can result in an enhancement of a PO2 signal, when measured in the presence of nitrous oxide. Silver can be deposited on the cathode by means of Ag+ ions diffusing through the electrolyte from an Ag/AgCl reference electrode. The use of an Ag cathode enables both O2 and N2O signals to be measured.