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Biomedical subjects

J Hopper

Publications and source records attributed to J Hopper.

At least 37 records · Page 2Linked to original sources

Simvastatin in the treatment of hypercholesterolaemia in patients with essential hypertension.

Mortality from coronary artery disease is a common problem in treated hypertensive patients, and these people have a high prevalence of elevated cholesterol levels. A study was undertaken to determine whether cholesterol could be lowered effectively without major side effects in patients with treated hypertension. Forty-nine patients (mean age 67.6 years) with cholesterol greater than 5.5 mmol/l were placed on a reduced-fat (less than 30% of calories from fat with a ratio of polyunsaturated to saturated fats of less than 1) diet for 3 months. If the cholesterol was between 5.5 and 7.5 mmol/l and total cholesterol divided by high-density lipoprotein cholesterol was greater than 4.5, the patients were randomly allocated either to the simvastatin (24 patients) or the placebo group (25 patients). Diet and placebo caused minor and insignificant falls in cholesterol and no change in triglycerides or lipids. Treatment with simvastatin reduced cholesterol levels from 6.85 to 4.75 mmol/l (P less than 0.001), triglycerides from 2.7 to 2.1 mmol/l (P less than 0.01), low-density lipoproteins from 4.6 to 2.6 mmol/l (P less than 0.001) and high-density lipoproteins rose from 1.09 to 1.18 mmol/l (P less than 0.01). Total cholesterol divided by high-density lipoprotein cholesterol fell from 6.3 to 4.0 (P less than 0.001). The drug was well tolerated and the side-effect profile did not differ from the placebo in clinical or biochemical events. The active drug was stopped in one patient (abdominal pain, dizziness, headache, tiredness) and in two patients taking the placebo (elevated creatine phosphokinase, cardiovascular collapse). Simvastatin effectively lowered total cholesterol and improved the lipoprotein profile. The dose required in most patients was 40 mg/day. Simvastatin may be an acceptable drug to improve the lipoprotein profile in order to determine whether this improves the prognosis in patients treated for hypertension.

Adult

Prognosis of male patients with treated hypertension followed over 15 years.

1. Male patients aged 50-75 years on treatment for hypertension in 1973 have been followed for 15 years. 2. Overall mortality in the 271 patients was 63% and 41% died of vascular disease. 3. Coronary artery disease or sudden death occurred in 44% of the patients who died and was between 2 and 6 times more common than in the general population. 4. Treatment of hypertension has improved overall prognosis but mortality from coronary artery disease is more common than in the general population.

Aged

The effects of diet differing in fat, carbohydrate, and fiber on carbohydrate and lipid metabolism in type II diabetes.

This study was designed to determine the effects of varying the proportions of carbohydrate, fiber, and fat on metabolic control in Type II diabetes. Ten men, aged 50 to 69 years, with Type II diabetes participated. Four isocaloric diets were consumed for 2 weeks each, with a break of 6 to 14 weeks between diets to ensure no carryover effects. Two of the diets were high in carbohydrate (63% to 65% energy) and low in fat (10% to 12% energy) but differed in their fiber contents (20 vs. 45 gm/day). The other two diets were low in carbohydrate (23% to 27% energy) with either a low or a high fat content (15% vs. 55% energy) and a high or normal protein content (62% vs. 18% energy). The composition of the subjects' usual diets in the week before each of the experimental diets did not vary significantly: carbohydrate 47% to 50% energy, protein 22% to 25% energy, fat 27% to 31% energy, and fiber 24 to 25 gm/day. A 75-gm oral glucose tolerance test and a 12-hour metabolic profile in response to 3 meals typical of the particular diet were conducted before and at the conclusion of each 2-week dietary period. The most significant improvements in metabolic control (as assessed by the effects of the diets on fasting glucose and on lipids, and on the glucose and insulin responses to oral glucose and the mixed meals) were obtained with the high-fiber, high-carbohydrate, low-fat diet and with the low-carbohydrate, high-protein, low-fat diet. Metabolic control was not significantly affected by the low-fiber, high-carbohydrate, low-fat diet, but it deteriorated significantly on the low-carbohydrate, high-fat diet. The results of this study confirmed the importance of high fiber and low fat in improving metabolic control in Type II diabetes. In conclusion, if high-carbohydrate, low-fat diets are to be recommended to patients with diabetes, it is essential that the type of carbohydrate recommended be unrefined and high in fiber.

Blood Glucose

Enalapril & nifedipine in essential hypertension; synergism of the hypotensive effects in combination.

Twelve male hypertensive patients who had required enalapril and nifedipine to control their blood pressure were entered into a study of modified 2 x 2 factorial design (3 week study periods) to determine the effect of each drug separately and in combination. Factorial analysis indicated that enalapril alone (20 mg/d) lowered supine blood pressure by 10 +/- 2/8 +/- 1 mmHg, nifedipine alone (30 mg/d) lowered supine blood pressure by 11 +/- 2/8 +/- 1 mmHg and there was a positive interactive effect of 10 +/- 3/7 +/- 2 mmHg (P less than 0.001) such that the combination lowered supine blood pressure by 32 +/- 3/24 +/- 2 mmHg. The effects of the individual drugs were both significant (P less than 0.001) but did not differ from each other. Enalapril and nifedipine are both effective antihypertensive drugs and in some hypertensive patients their effects appear to be synergistic.

Aged

The regulatory protein GAL80 is a determinant of the chromatin structure of the yeast GAL1-10 control region.

Chromatin in the regions between the upstream activator sequence and the 5' ends of the yeast GAL1 and GAL10 genes has been analyzed by DNase I chromosomal footprinting and micrococcal nuclease digestion using the indirect end-labeling approach. Comparison of wild type chromatin digests to naked DNA digests shows that there are specific regions of these upstream sequences which are strongly protected in chromatin. Comparison to chromatin digests from cells disrupted for the positive regulatory gene, GAL4, or the negative regulatory gene, GAL80, and thus lacking GAL4 or GAL80 function, shows that these regions of protection in wild type chromatin are GAL80-dependent but not GAL4-dependent. The protected regions include DNA lying on (GAL10) or near (GAL1) the respective TATA boxes. These protections are present in both noninduced and induced cells. Both DNA strands are equally protected. Upstream of GAL1 there is a second protected region. This protection shows considerable expression and strand dependence. These observations provide the first evidence that the GAL80 function influences chromatin structure and suggest possible mechanisms by which GAL80 modulates the GAL1 and 10 promoters in induced cells. Micrococcal nuclease digests also suggest a role for GAL80 in a distinctive higher order organization of the intergenic region, perhaps involving multiprotein complexes.

Chromatin

A comparison of changes seen on radiographs of rheumatoid arthritis patients in Australia and in China.

To test the hypothesis that rheumatoid arthritis in patients in China is milder in severity than that in patients in a western country, a comparison was made of 2 series of consecutive outpatients with definite or classic rheumatoid arthritis who were attending referral centers in Melbourne, Australia and Shanghai, China. This paper reports the findings on radiographs of the wrists and hands. Making allowances for age and duration of disease, changes were more frequent and severe in the Australian patient series, particularly at the metacarpophalangeal joints.

Adult

Fibrillary glomerulonephritis: an entity with unusual immunofluorescence features.

We describe seven patients with renal biopsy findings of mild glomerular abnormalities on light microscopy but with prominent accumulation of randomly-arranged fibrillar material in the mesangium and capillary walls on electron microscopy. This material differed from amyloid in that fibrils were thicker (diameter range 10 to 19.5 nm) and did not stain with Congo Red. In six of seven cases fluorescence microscopy showed prominent staining for IgG and kappa light chain in mesangium and glomerular capillary walls; in three cases weak lambda chain staining was also present. Stains for IgA, IgM, and lambda chain were otherwise negative. One biopsy showed equal staining for kappa and lambda light chains, but not for heavy chain components. Clinical findings were heterogeneous. Patients presented with features of nephritis and/or nephrotic syndrome. No patient had an associated lymphoplasmacytic disorder, paraproteinemia, or other evidence of systemic disease. On follow-up ranging from five months to 12 years, all patients are still alive; six progressed to end-stage renal disease requiring dialysis. One patient developed recurrent disease in a renal allograft five years after transplantation. Non-amyloidotic fibrillary glomerulonephritis is an ultrastructurally distinct entity of undetermined etiology. The apparent association with monoclonal IgG and kappa light chain deposition observed in this series deserves further study.

Adult

A comparison of rheumatoid arthritis in Australia and China.

A comparison was made of two series of consecutive outpatients with a presumptive diagnosis of rheumatoid arthritis (RA) attending referral centres in Melbourne and Shanghai. No significant differences were observed in disease onset, course, presence of antinuclear antibodies (ANA), or seropositivity. In the Australian series there was a higher frequency of nodules, Raynaud's phenomenon, carpal tunnel syndrome, and 'classical' in comparison with 'definite' disease, and a lower frequency of lymphadenopathy and hepatomegaly. Joint tenderness and soft tissue swelling tended to be more marked in the Chinese series, while deformity and limited range of movement were less severe. Drug therapy was similar overall but influenced by drug availability. Peptic ulceration was recorded in 28% of the Australian series but in only 6% of the Chinese; although 25% of the Chinese were receiving antacids and 6% antiulcerants. X-rays of hands and feet showed more severe disease in the Australian series. The older age group and longer duration of the disease in the Australian patients, who had more chronic and less active disease, may have influenced some of these results.

Anti-Inflammatory Agents

Incremental dynamic computed tomography: practical method of imaging the carotid bifurcation.

A simple, practical method of applying incremental dynamic computed tomography (CT) to the imaging of 20 carotid bifurcations is described. The results are compared with those obtained by conventional carotid angiography and intravenous digital subtraction angiography (DSA). Conventional angiography provided additional information about the carotid bifurcation in only one of 14 cases, while incremental dynamic CT provided information not available from intravenous DSA in two of eight cases. Conventional brain CT is being used increasingly in the workup of patients with transient ischemic symptoms, and dynamic CT scanning at 3-mm increments requires only an extra 5 min of scanner time. The addition of incremental dynamic CT through the carotid bifurcation to the conventional brain CT scan procedure may obviate other screening tests before more definitive angiographic procedures.

Carotid Artery Diseases

Factors that determine the response of people with mild hypertension to a reduced sodium intake.

One hundred and eighty-six males who had had 3 run-in visits entered the study with a supine diastolic BP 95-110 mm Hg. This was followed by 3 pretreatment and 3 post-treatment visits. One hundred and sixty patients were given advice to reduce sodium intake after visit 3, and twenty-six patients served as control. In the control group there were relatively insignificant changes between the pre and post visits. In the diet group blood pressure fell by 13/9 mm Hg; urine sodium from 168 to 85 mmol/day and plasma renin activity rose from .50 to .77 ng AI/ml/h. Regression analysis showed that the only cross-sectional correlations were PRA with age, urine sodium and plasma potassium. There were highly significant correlations between the change in urinary sodium and the change in blood pressure and between the changes in blood pressure and plasma renin activity. Multiple Regression Analysis indicated that the final diastolic blood pressure achieved depended upon the initial diastolic blood pressure, the fall in sodium intake, and was reduced by the rise in plasma renin activity. Patients who responded to sodium restriction had a lower initial renin value than other patients. This study emphasises the importance of the interaction between sodium, potassium and renin in the determination of blood pressure levels.

Adult

Australian National Health and Medical Research Council dietary salt study in mild hypertension.

Two-hundred-and-twelve untreated subjects (mean age 52.3 +/- 0.8 years; 181 males and 31 females) with a diastolic blood pressure between 90 and 100 mmHg were recruited to the study. Subjects were seen fortnightly and, after 4 pre-diet visits, were randomized into a normal diet group (A, 55 subjects), a high-potassium diet group (B, 52 subjects receiving greater than 100 mmol K+/day) a reduced-sodium diet group (C, 52 subjects receiving 50-75 mmol Na+/day) or a high-potassium and low-sodium diet group (D, 53 subjects receiving same Na+ and K+ as groups B and C). Two-hundred subjects completed the diet phase of 12 weeks. Urine sodium fell to 86 +/- 7 mmol/day in group C and 73 +/- 6 mmol/day in group D, while daily potassium excretion rose to 96 +/- 5 mmol in group B and 87 +/- 4 mmol in group C. Systolic and diastolic blood pressure fell by 3.8 +/- 1.0 and 1.6 +/- 0.6 mmHg respectively in the normal diet group. The falls in systolic and diastolic blood pressures (mmHg) in the diet phase were 7.7 +/- 1.1 and 4.7 +/- 0.7 (B), 8.9 +/- 1.0 and 5.8 +/- 0.6 (C) and 7.9 +/- 0.9 and 4.2 +/- 0.7 (D). These falls were all greater than those in the control group on an intention-to-treat analysis (P less than 0.005) but did not differ from each other. Factorial analysis confirmed that the falls in pressure attributable to the low-sodium diet and high-potassium diet were not additive.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure

Single light chain subclass (kappa chain) immunoglobulin deposition in glomerulonephritis.

Renal glomerular disease characterized by the deposition of immunoglobulin light chains or monoclonal immunoglobulins was demonstrated by immunofluorescence microscopy in 11 patients. The most common histopathologic findings were those of mesangiocapillary glomerulonephritis, but considerable variability was observed. Lesions resembling diabetic glomerulosclerosis and amyloidosis were seen in some patients. Immunofluorescence findings in seven patients showed concomitant, equally intense staining for kappa light chain and immunoglobulin heavy chain (IgG or IgA), indicative of monoclonal immunoglobulin deposition. Specimens in the remaining cases stained predominantly for kappa light chain alone. In six cases the histologic and ultrastructural pattern was similar to that of type I mesangiocapillary glomerulonephritis. In three cases linear deposits were present, predominantly in subendothelial and inner glomerular basement membranes and, to a lesser degree, in mesangial locations, as in type II mesangiocapillary glomerulonephritis. In one of the latter cases dense deposits were intermixed with aggregates of amorphous fibrillar material indistinguishable from amyloid. In two cases involving IgA kappa chain deposition the histologic and ultrastructural appearance was that of mesangial glomerulonephritis. Considerable heterogeneity was found in the clinical features of the patient population. Specific clinical or serologic parameters for this disease could not be identified. Only one patient had an associated lymphoplasmacytic disorder. After follow-up periods ranging from six months to 17 years, all of the patients were alive, including four who had progressed to end-stage renal disease and required dialysis. Two of the latter patients underwent successful renal transplantation; one had been alive for five years and the other for three months without evidence of recurrence of the renal disease at the last follow-up examination.

Adult

Cure of membranous nephropathy after resection of carcinoma.

Clinical cure was effected in two patients with biopsy-proved membranous nephropathy associated with neoplasms. One had a complete histologic remission as well. The incidence of malignancy in an unselected group of patients with membranous nephropathy in our institution was 9%. Careful workup in all patients over age 40 years with membranous nephropathy should be done to exclude tumor.

Basement Membrane

Light-chain glomerulopathy with amyloid-like deposits.

A 40-year-old man with rapidly progressive renal failure was found to have a lobular glomerulonephritis by renal biopsy. Immunofluorescent microscopy showed prominent glomerular deposition of both kappa and lambda light chains but no significant heavy-chain component. Ultrastructurally, electron-dense deposits in the mesangium and capillary basement membranes had a fibrillar appearance indistinguishable from amyloid. This case illustrates a "light-chain glomerulopathy" distinct from previously reported glomerulopathies associated with the deposition of light chains of a single subclass.

Amyloid

Crescentic glomerulonephritis associated with nonrenal malignancies.

A review of 80 patients with the renal biopsy diagnosis of idiopathic glomerulonephritis with extracapillary proliferation (crescentic GN) disclosed 7 cases with a coexistent nonrenal malignancy; 6 carcinomas and 1 lymphoma. In a control group of 80 patients with the renal biopsy diagnosis of minimal change or focal segmental glomerulosclerosis, only 1 case of coexistent malignancy was found (chi-square = 4.74, p less than 0.05). All of the malignancies occurred in patients older than 40 years of age and the prevalence of malignancy in patients with crescentic GN over the age of 40 was 20%. Light microscopy, immunofluorescence, and electron microscopy revealed fibrin deposition in all cases and no evidence of anti-GBM or immune complex disease. 3 patients experienced a rapidly progressive course while renal function improved in 4 patients following treatment of the underlying malignancy. The pathogenic mechanisms leading to crescentic GN in patients with malignancy are unknown; however, the high prevalence of malignancy in crescentic GN patients older than 40 along with the improvement during the treatment of the underlying malignancy suggests an etiological relationship.

Adolescent

Membranous nephropathy: predictors of terminal renal failure.

By univariate analysis of patients with membraneous nephropathy, terminal renal failure was associated with male sex, a large amount of proteinuria, low serum albumin concentration, low creatinine clearance rate, high serum creatinine concentration, and high systolic blood pressure, but was not associated with age or prednisone treatment. In a multivariate life table analysis that controlled for all these factors simultaneously, the risk of developing terminal renal failure was significantly independently associated only with sex, serum albumin concentration, and prednisone treatment, being higher in men, lower in those treated with prednisone, and inversely related to serum albumin. Except for the minimal electron-dense deposition, the electron microscopic findings had no predictive value.

Adolescent

Late development of systemic lupus erythematosus in patients with glomerular "fingerprint" deposits.

Two patients presenting with nephrotic syndrome but without evidence of collagen vascular disease had organized glomerular immune deposits with a "fingerprint" pattern. This finding has been previously associated with lupus nephritis and, in our institution, has been seen in 6% of the biopsy specimens from patients with lupus nephritis. Clinical signs and symptoms of systemic lupus erythematosus in these two patients did not develop until 2 and 5 years later, respectively. The cases of these patients suggest that glomerular deposits with a fingerprint pattern may be a specific marker for lupus erythematosus even when overt clinical features of this disease are lacking. Patients with this finding on renal biopsy should have an extended follow-up for possible development of lupus erythematosus.

Adult

Failure of sodium aurothiomalate and triethyl phosphine gold to cause renal tubular injury in rheumatoid arthritis: implications for the aetiology of gold-related nephropathy.

The urinary excretion of two proteins, B-2-microglobulin (beta 2M) and N-acetyl-B-D-glucosaminidase (NAG) was measured in 25 patients with rheumatoid arthritis (RA) on nonsteroidal anti-inflammatory drugs (NSAID). Although beta 2M excretion was normal NAG excretion was raised. As NAG excretion by a group of osteoarthritis patients receiving similar doses of NSAIDs was normal, it is concluded that rheumatoid disease per se may be associated with mild renal tubular dysfunction. Twelve of the above 25 patients were then given oral triethylphosphine-gold (auranofin) 6 mg daily and urinary beta 2M and NAG were measured after 6 months' treatment. Urinary excretion of beta 2M and NAG was also measured in 13 patients with RA established on intramuscular sodium aurothiomalate (MGST) and NSAIDs. Neither auranofin nor myocrisin were found to further significantly increase beta 2M and NAG excretion. These results suggest that gold compounds are not toxic to renal tubular epithelium.

Acetylglucosaminidase