Gene/Protein Disease Symptom Drug Enzyme Compound
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Analgesic abuse is a major public health hazard in Australia, and analgesic nephropathy with consequent terminal renal failure is the underlying cause in 20% of the patients requiring dialysis and transplantation. Analgesics are invariably taken in the form of compounds and mixtures. In the aspirin-phenacetin-caffeine (APC) mixture, aspirin appears to be the major nephrotoxic agent and phenacetin appears to play a secondary and synergistic role. The renal disease associated with abuse of analgesics is characteristic and is part of a much wider clinical syndrome, the analgesic syndrome, which includes peptic ulcer disease (35%), anemia (60 to 90%), hypertension (15 to 70%), ischemic heart disease (35%), psychological and psychiatric manifestations, pigmentation, and possible gonadal- and pregnancy-related effects. The primary lesion in analgesic nephropathy is renal papillary necrosis (RPN), and this is a nephrotoxic effect common to all nonsteroid antiinflammatory agents. The most important factor in the management of patients with analgesic nephropathy is the cessation of analgesic abuse, and this leads to improvement and stabilization of renal function. A small proportion of patients will, however, deteriorate in relation to accelerated hypertension, persistent proteinuria, ischemic heart disease, and complications leading to nephrectomy. Patients with analgesic nephropathy are poor risk patients and have a poor prognosis, even after dialysis and transplantation.
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PMID:Analgesic nephropathy: etiology, clinical syndrome, and clinicopathologic correlations in Australia. 36 34

In a population-based study in Taiwan, 11,478 subjects aged 40 years or older were screened for diabetes in one urban and five rural areas. Among the 715 subjects proven to have diabetes, 527 subjects underwent ophthalmoscopy. Diabetic retinopathy was present in 184 of the 527 subjects (35.0%), including background diabetic retinopathy in 157 subjects (30.0%), preproliferative diabetic retinopathy in 15 subjects (2.8%), and proliferative diabetic retinopathy in 12 subjects (2.2%). Diabetic retinopathy was correlated with the duration of diabetes and age at onset of diabetes, type of diabetes treatment, higher serum creatinine levels, and lower serum cholesterol levels. Several other factors, including gender, age, residential area, family income, educational level, control and family history of diabetes, body mass index, physical activity, exercise, cigarette smoking, stroke, ischemic heart disease, leg vessel disease, hypertension, and proteinuria, had no significant association with retinopathy. By multiple logistic regression analysis, duration of diabetes was the most important risk factor related to retinopathy. Diabetic subjects treated with insulin had a higher risk of developing retinopathy than those treated with dietary control (relative risk, 1.57; .05 < P < .10). The univariate analysis disclosed that proliferative diabetic retinopathy was related to older age at examination, older age at onset of diabetes, type of diabetes treatment, and presence of leg vessel disease. Insulin-treated diabetic subjects also had a higher risk of proliferative diabetic retinopathy than patients in whom diabetes was controlled by diet, with a relative risk of 2.51 (.05 < P < .10) in the multiple logistic regression analysis.
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PMID:Prevalence and risk factors of diabetic retinopathy among noninsulin-dependent diabetic subjects. 146 42

Patients with the clinical diagnosis of ischemic heart disease who were found to be free of significant coronary artery atherosclerotic disease (n = 150) underwent coronary vasodilator reserve testing, 2-dimensional echocardiography, and dipyridamole limited-stress thallium testing. After exclusions (predominantly for technically poor coronary artery Doppler signals or suboptimal echocardiography), 100 patients formed the study population. The purpose was to characterize typical cardiac and coronary artery findings in hypertensive patients with severe left ventricular (LV) hypertrophy (n = 15) and to investigate the evidence for myocardial ischemia unrelated to coronary atherosclerosis in early and advanced hypertensive heart disease. Normotensive and hypertensive control groups without LV hypertrophy (n = 12 and 34, respectively) were used for comparison. Severe LV hypertrophy was defined as LV mass index greater than or equal to 50% above established gender specific norms using 2-dimensional-directed M-mode echocardiography and the cube equation corrected to agree with necropsy estimates of mass. Clinical characteristics more often associated with severe LV hypertrophy were black race (67%), diabetes mellitus (33%), proteinuria (47%) and elevated creatinine (1.5 +/- 0.9 mg/dl). Baseline electrocardiograms and dipyridamole limited-stress thallium scans were highly likely to be abnormal (94 and 73%, respectively). Both eccentric and concentric cardiac hypertrophies were found in the severe group. Ejection fraction was significantly lower (0.51 vs 0.68, p = 0.002) and basal coronary flow velocity higher (12.0 vs 5.0 cm/s, p = 0.0004) among these patients when compared with normotensive control patients. Coronary flow reserve did not differ between control groups but was significantly depressed in patients with severe LV hypertrophy (2.5 vs 3.9, p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Morphologic, hemodynamic and coronary perfusion characteristics in severe left ventricular hypertrophy secondary to systemic hypertension and evidence for nonatherosclerotic myocardial ischemia. 153 Sep 94

Despite a marked reduction in cardiovascular morbidity and mortality, treated hypertensive patients remain at increased risk of coronary artery disease and its complications compared with untreated normotensive subjects. Mild hypertension is often associated with other, usually chronic, diseases. The failure of first-line antihypertensive therapy to deal adequately with concomitant disease and associated therapy might account for the poor improvement in the cardiovascular prognosis. This possibility has been addressed in an ongoing trial of novel design, the Perindopril Therapeutic Safety Study, a multicenter, double-blind, randomized and placebo-controlled trial to determine the safety, efficacy, and interaction of angiotensin-converting enzyme (ACE) inhibition with eight of the most common concomitant diseases and their therapies. A total of 480 male and female patients (60 per disease group) aged 30-70 years, with a diastolic pressure of 90-104 mm Hg, were included after a 3-week placebo run-in if they satisfied standard criteria for any of the following: hyperlipidemia, type II diabetes, ischemic heart disease, cardiac arrhythmia, peripheral arterial disease, nephropathy with proteinuria, chronic obstructive lung disease, or rheumatoid arthritis. Of these, 460 patients have completed the 6-week double-blind phase (comprising two assessments, at 3 and 6 weeks), and are currently undergoing assessments every 3 months over a 1-year follow-up period. The end points include the incidence of progression or improvement in concomitant disease, the incidence of positive or negative interaction between ACE inhibition and concomitant therapy, change in blood pressure, adverse biochemical and hemodynamic reactions, self-reported side effects, and quality of life indices. Interim results for the 6-week double blind phase will shortly be available. However, the desirability and feasibility of conducting a study according to this novel design have already been proved.
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PMID:Angiotensin-converting enzyme inhibition in mild hypertension with concomitant diseases and therapies: an efficacy, safety, and compatibility study of novel design, the Perindopril Therapeutic Safety Study. 158 Feb 90

In 1974 a cross-sectional study was conducted on 4591 out-patients (2095 males and 2496 females) aged 18-67 years, with diabetes of 1-10 years duration, and cardiovascular fatalities followed for 10 years. A multiple logistic regression was then performed on total cardiovascular deaths, deaths from ischaemic heart disease, and from stroke on selected baseline variables related to the course and control of diabetes, selected symptoms of macroangiopathy, and other risk factors, separately for insulin-treated and non-insulin-treated patients. Hyperglycaemia, proteinuria, arterial hypertension, various symptoms of ischaemic heart disease, age, and current cigarette smoking were found to be important predictors of cardiovascular mortality, more so in non-insulin-treated than in insulin-treated patients. Proteinuria and arterial hypertension carried a greater risk in females than males, but the opposite was true for the signs and symptoms of ischaemic heart disease. Relative body mass was found to correlate inversely with probability of cardiovascular death among insulin-treated males but not in non-insulin-treated males, whereas duration of diabetes was a significant factor only among non-insulin-treated females.
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PMID:Risk factors of cardiovascular death in diabetic patients. 182 45

One hundred and eighty-eight known Type 2 diabetic patients aged over 60 years identified by a geographically based survey of a population of 40,076 were followed for a median of 6 years to determine the incidence of various complications. There were 63 deaths and two patients were lost to follow-up. The presence of complications was determined using a structured questionnaire and clinical examination. Incidence rates of ischaemic heart disease, stroke, and peripheral vascular disease (PVD) were 56 (95% CI 41-75), 22 (13-35), and 146 (117-174) 1000-person-years-1 of follow-up, respectively. Rates of stroke and PVD rose significantly with age. Retinopathy occurred at a rate of 60 (42-83) 1000-person-years-1 and cataract at 29 (17-46) 1000-person-years-1 although visual acuity in survivors did not deteriorate overall, probably reflecting the high mortality associated with cataract. The rate of proteinuria (albumin concentration greater than 300 mg l-1) was 19 (9-34) 1000-person-years-1. Incidence rates were unrelated to sex or duration of diabetes. Diabetes is associated with a continuing incidence of complications into old age. Adequate facilities are required to assess and treat the resulting morbidity in a population with an increasing proportion of elderly people.
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PMID:A population-based study of the incidence of complications associated with type 2 diabetes in the elderly. 183 44

We have examined the relationship between baseline variables and the incidence of new macrovascular complications amongst the 497 members of the London cohort of the WHO Multinational Study of Vascular Disease in Diabetics over a mean 8.33-year follow-up. In univariate logistic regression analysis the incidence of new ischaemic electrocardiographic abnormality was significantly associated with systolic and diastolic blood pressure, diabetes duration and hypertension in patients with insulin-dependent diabetes, and with smoking in patients with non-insulin-dependent diabetes. New myocardial infarction was associated with systolic blood pressure, plasma cholesterol, proteinuria and smoking in patient with non-insulin-dependent diabetes; there were no significant associations among patients with insulin-dependent diabetes. All new ischaemic heart disease was associated with hypertension in patients with insulin-dependent diabetes, and plasma cholesterol and smoking in patients with non-insulin-dependent diabetes. New cerebrovascular disease was associated with systolic and diastolic blood pressure, ECG abnormality and hypertension. New peripheral vascular disease was associated with smoking. Multivariate analysis showed the following significant associations 1) in patients with insulin-dependent diabetes: ECG abnormality; hypertension, myocardial infarction; smoking, ischaemic heart disease; hypertension, diabetes duration and smoking, 2) in patients with non-insulin-dependent diabetes: ECG abnormality; smoking, myocardial infarction; serum cholesterol, proteinuria and smoking ischaemic heart disease; smoking. For new cerebrovascular disease, proteinuria and ECG abnormality were significant predictors in multivariate analysis. Patients with diabetes share many of the established risk factors for nondiabetic subjects, in addition proteinuria may be of significance in the prediction of macrovascular disease in diabetes.
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PMID:Risk factors for macrovascular disease in diabetes mellitus: the London follow-up to the WHO Multinational Study of Vascular Disease in Diabetics. 193 63

The incidence of some risk factors of ischaemic heart disease (IHD) was investigated in a group of 91 type 2 diabetics. A group of 57 patients who had a myocardial infarction was compared with a control group of 34 diabetics without clinical and electrocardiographic signs of IHD. In the group of diabetics with IHD there was a significantly higher proportion of hypertonic patients (70%), as compared with the control group (47%). The diabetics with an infraction in the case-history had a significantly higher mean age and a longer mean duration of diabetes. There was not a significant difference between the two groups as regards mean values of cholesterol, triacylglycerols, blood sugar, urea, creatinine, proteinuria and cerebrovascular attacks. As to metabolic factors, there were significantly higher mean uric acid values in the whole group with a myocardial infarction in the case-history, whereby this increase was more marked in men with IHD. Regression analysis did not reveal a significant correlation between uric acid values and the serum cholesterol or triacylglycerol levels or the incidence of hypertension. A significant biserial correlation between the presence of myocardial infarction and uric acid serum levels persisted also after elimination of the effect of age and creatinine serum levels. Based on these results and analyses of data in the literature, the authors favour the view that uric acid is rather a marker than true risk factor of atherosclerosis in type 2 diabetics.
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PMID:[Uric acid--a risk factor or atherosclerosis marker in type 2 diabetes?]. 213 61

The role of specific risk factors in the development of diabetic nephropathy was examined among noninsulin-dependent diabetic subjects attending the Diabetes Clinic of Christian Medical College Hospital, Vellore during 1986-87. Seventy-three subjects with normal protein excretion (less than 150 mg/24 hr) were compared with 66 microproteinuric (150-500 mg/24 hr) and 61 macroproteinuric subjects (greater than 500 mg/24 hr). The risk factors included family history of diabetes, tobacco use, dietary habits and metabolic control; the latter was assessed from an average of 5 clinic blood sugar determinations done annually per patient. Patients who had developed proteinuria were characterized as mostly men, with increased tobacco consumption and early onset of proteinuria in relation to duration of diabetes. The mean blood sugar value was significantly high in both the proteinuric groups compared to the group with no proteinuria (p less than 0.01). There was a striking increase in the prevalence of ischemic heart disease, hypertension and retinopathy in the macroproteinuric group compared to the other two groups (p less than 0.01). It is concluded that the risk of developing nephropathy was significantly higher in men, in smokers and in those with poor metabolic control (mean postprandial blood sugar more than 200 mg/dL). Furthermore, it was clearly evident from our study that the diabetic subjects with nephropathy had a higher incidence of hypertension, retinopathy, hyperlipidemia and ischemic heart diseases.
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PMID:Nephropathy in noninsulin-dependent diabetes mellitus: comparative study with normoproteinuric and microproteinuric subjects. 214 34

Patients with insulin dependent diabetes mellitus who develop proteinuria may die prematurely, whereas those who do not develop this complication have a comparatively normal life span. The excess mortality in diabetics with proteinuria is from cardiovascular as well as renal disease, but the reason is unclear. Risk factors for vascular disease were therefore assessed in 22 insulin dependent diabetics with proteinuria, but not renal failure, who were matched for sex, age, duration of diabetes, and glycated haemoglobin (HbA1) values with a similar number who had normal urinary albumin excretion rates. Macrovascular disease (ischaemic heart disease and peripheral vascular disease) was present in 10 patients with proteinuria but in only three with normal albumin excretion rates, and proliferative retinopathy was detected in 11 and four patients in the two groups. There was no significant excess of smokers in the group with proteinuria. Blood pressure was, however, higher in the patients with proteinuria--mean systolic pressure 161 (SD 18) mm Hg compared with 135 (19) mm Hg (95% confidence interval of difference between means 15 to 38 mm Hg); mean diastolic pressure 90 (SD 12) mm Hg compared with 79 (15) mm Hg (confidence interval 3 to 19 mm Hg). The concentration of serum high density lipoprotein (HDL) cholesterol isolated by precipitation was lower in the patients with proteinuria (confidence interval 0.02 to 0.41 mmol/l). Their concentration of HDL2 cholesterol isolated by ultracentrifugation was also decreased (confidence interval 0.02 to 0.40 mmol/l), whereas HDL3 cholesterol tended to be increased (confidence interval -0.01 to 0.23 mmol/l). There was also a trend for serum cholesterol concentrations to be higher in the presence of proteinuria (confidence interval -0.39 to 1.20 mmol/l). The aggregation of risk factors for atherosclerosis in insulin dependent diabetes mellitus complicated by proteinuria helps to explain the increased prevalence of ischaemic heart disease and peripheral vascular disease reported in these patients. Early renal disease in insulin dependent diabetes may have an important role in hypertension and altered lipoprotein metabolism.
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PMID:Influence of proteinuria on vascular disease, blood pressure, and lipoproteins in insulin dependent diabetes mellitus. 311 68


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