Accountability and the health reforms.
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Cost Control↗
Biomedical subjects
M G Nicholls
Publications and source records attributed to M G Nicholls.
Comparison of enalapril and nifedipine in treating non-insulin dependent diabetes associated with hypertension: one year analysis.
OBJECTIVES: To compare the efficacy, safety, and tolerance of enalapril and nifedipine in hypertensive patients with non-insulin dependent diabetes. DESIGN: One year double blind follow up of patients randomly allocated to either enalapril or nifedipine with matching placebos for the alternative drug. SETTING: Metabolic Investigation Unit, Hong Kong. SUBJECTS: 102 patients were randomised: 52 to nifedipine and 50 to enalapril. At baseline 44 patients had normoalbuminuria, 36 microalbuminuria, and 22 macroalbuminuria. MAIN OUTCOME MEASURES: Blood pressure, albuminuria, and parameters of renal function and glycaemic control. RESULTS: In patients who completed one year's treatment the median dose required by the nifedipine group (n = 49) was 60 mg/day; seven (14%) required additional diuretics. Of 41 patients given enalapril, 37 required the maximum dose (40 mg/day) and 27 (76%) required diuretics. At one year mean arterial blood pressures were similar in both groups. Albuminuria fell by 54% in the enalapril group and 11% in the nifedipine group (p = 0.006). Fractional albumin clearance ratio fell by 47% in the enalapril group and increased by 3% in the nifedipine group (p = 0.009). Creatinine clearance fell similarly in both groups but plasma creatinine concentration was increased by 20% in the enalapril group versus 8% in the nifedipine group (p = 0.001). CONCLUSION: Patients taking enalapril often required diuretics to control blood pressure. Enalapril reduced proteinuria significantly more than nifedipine in the microalbuminuric and macroalbuminuric patients but increased plasma creatinine concentrations. Longer follow up is required to clarify the importance of enalapril's antiproteinuric effect.
Albuminuria↗
Interaction of natriuretic peptides and cGMP production via the same receptor in mouse astrocytes.
Atrial and brain natriuretic peptides have been found previously to bind to specific receptors on cultured mouse astrocytes and to stimulate cyclic guanosine 5-monophosphate (cGMP) production with similar dose dependency although brain natriuretic peptide (BNP) shows a greater maximal stimulatory effect. The present study provides evidence that both peptides work through the same pathway. No additive or synergistic effect was observed when astrocytes were exposed to both peptides. However, human ANF(99-126) at high concentrations partially inhibited porcine BNP induced cGMP production to the level seen with ANF alone. ANF could be viewed as a partial agonist of pBNP competing for the same effector sites. Differences in structure between human ANF(99-126) and porcine BNP may account for the difference in cGMP response. The interaction between the two peptides and the cGMP response does not reflect receptor binding affinities and is likely to be a post-binding event.
Animals↗
Activation of protein kinase C attenuates the cyclic GMP responses to C-type natriuretic peptide in cultured mouse astrocytes.
C-type natriuretic peptide (CNP), a recently discovered natriuretic peptide, has a potent stimulatory effect on cyclic GMP (cGMP) formation in cultured mouse astrocytes. Pretreatment of astrocytes with phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC), attenuated CNP-induced cGMP responses in a dose-dependent manner, with a half-maximal inhibitory concentration of 6 nM, whereas the inactive phorbol ester analog, 4 alpha-phorbol 12,13-didecanoate, was without effect. In the presence of staurosporine, a PKC inhibitor, the inhibitory effect of PMA on CNP-stimulated cGMP production was reversed. These results suggest that PKC is an inhibitory modulator of CNP-stimulated cGMP responses in astrocytes and that CNP may interact with neuropeptides which stimulate PKC.
Animals↗
The application of nebivolol in essential hypertension: a double-blind, randomized, placebo-controlled study.
This randomized, double-blind, placebo-controlled study investigated the effects of nebivolol on blood pressure, plasma renin and vasoactive hormones (aldosterone and atrial natriuretic peptide) and the heart (arrhythmias, left ventricular mass and ejection fraction) in 32 hypertensive Chinese patients aged 25-65 years. Patients received either placebo (3 men, 11 women) or nebivolol 5 mg (5 men, 13 women) once daily for 4 weeks. In the nebivolol group, a significant decrease in blood pressures (P less than 0.001) and heart rate (P less than 0.01) was seen. Nebivolol therapy also suppressed plasma renin and aldosterone concentration (P less than 0.02) but increased plasma atrial natriuretic peptide levels (P less than 0.03). No significant changes in routine blood biochemistry were demonstrated in either group. There was a tendency for left ventricular mass to decline, and left ventricular ejection fraction to rise during nebivolol therapy, but these changes did not reach statistical significance. There was no significant change in ectopic activity. None of the 32 subjects had adverse experiences requiring cessation of therapy. In conclusion, nebivolol in a dose of 5 mg daily is effective and well tolerated in patients with essential hypertension. It suppresses plasma renin and aldosterone and stimulates plasma atrial natriuretic peptide.
Adrenergic beta-Antagonists↗
Atrial natriuretic peptide and urinary dopamine output in non-insulin-dependent diabetes mellitus.
1. Disturbances of sodium and water homoeostasis may contribute to the close association between diabetes, hypertension and proteinuria. We therefore studied the patterns of two natriuretic hormones, plasma atrial natriuretic peptide and urinary dopamine, in 165 Chinese patients with non-insulin-dependent diabetes mellitus controlled by diet or oral hypoglycaemic agents on two occasions over a 6-week period. Patients were divided into three groups based on the mean value of two 24h urinary albumin excretion measurements. In group 1, 88 patients had normoalbuminuria (urinary albumin excretion < or = 30 mg/day), in group 2, 48 patients had microalbuminuria (urinary albumin excretion between 30 and 300 mg/day), and in group 3, 29 patients had macroalbuminuria (urinary albumin excretion > or = 300 mg/day). 2. The supine systolic blood pressure (mean +/- SD) was higher in patients with abnormal albuminuria (group 1: 140.9 +/- 27.4 mmHg; group 2: 158.1 +/- 26.4 mmHg; group 3: 166.7 +/- 23.9 mmHg; F = 13.1, P < 0.001, analysis of variance). Urinary sodium output was similar in these three groups of patients. The geometric means (anti-logarithm of 95% confidence interval logarithm) of plasma atrial natriuretic peptide concentrations increased with increasing proteinuria [group 1: 33.3 (29.9-37.1) pg/ml; group 2: 39.1 (34.2-44.6) pg/ml; group 3: 50 (38.6-54.7) pg/ml; F = 4.24, P < 0.01; analysis of variance], whereas those of urinary dopamine output were related inversely to proteinuria [group 1: 1291.7 (1167.2-1437.0) nmol/day; group 2: 1142.3 (975.9-1337.2) nmol/day; group 3: 982.7 (775.7-1245) nmol/day; F = 3.10, P < 0.05, analysis of variance].(ABSTRACT TRUNCATED AT 250 WORDS)
Atrial Natriuretic Factor↗
Lack of efficacy of octreotide in the long term treatment of orthostatic hypotension.
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Humans↗
C-type natriuretic peptide is a potent stimulator of cyclic GMP production in cultured mouse astrocytes.
The effect of C-type natriuretic peptide (CNP), a novel member of the natriuretic peptide family, on cyclic GMP (cGMP) generation was studied in primary cultures of mouse astrocytes. CNP stimulated cGMP production by mouse astrocytes in a dose-dependent fashion, with an EC50 of 32 nM and a maximal stimulatory concentration of greater than 1 microM, which induced a rise of cGMP level from a baseline of 1.0 +/- 0.1 pmol/mg of protein to 196.2 +/- 22.0 pmol/mg of protein. Compared with our previously reported atrial and brain natriuretic peptide-induced cGMP responses, CNP had a lower EC50 and was 10-20 times more efficacious in its maximal effect on cGMP stimulation. These data lend support to the concept of a significant role of CNP in neuromodulation/neurotransmission.
Animals↗
Factors influencing long-term survival and disability among three-month stroke survivors.
216 survivors of acute stroke were studied 3 months postictus to determine predictors of long-term survival and disability 20 months after the initial stroke. Factors predicting mortality were, in order of importance, old age, a history of ischaemic heart disease, low mental-test score, low serum cholesterol concentration, low Glasgow Coma Score on admission, and the presence of left ventricular hypertrophy. 73% of subjects were correctly classified by discriminant function analysis using these variables. Factors predicting poor functional outcome (Barthel Index 15) were a low Barthel Index at 3 months, old age, low mental-test score at 3 months and a low Glasgow Coma Score on admission. 70% of subjects were correctly classified into 3 functional-outcome groups using these variables. Stroke subtype and size, position, and the territory of the lesion on brain CT did not influence long-term outcome. We conclude that factors affecting long-term survival and disability are different from those affecting outcome immediately after stroke.
Aged↗
Stroke subtypes among Chinese living in Hong Kong: the Shatin Stroke Registry.
The Shatin Stroke Registry is a prospective study of all patients admitted with acute stroke to a general hospital in Hong Kong where the population is predominantly Chinese. Each patient was examined by a neurologist and 95.5% of the patients had a brain CT. Of 777 patients included in the study, 44.0% had a cortical/subcortical infarct, 18.5% a supratentorial lacunar infarct, 24.2% a supratentorial intracerebral hemorrhage, 5.8% brainstem/cerebellar infarct, 2.9% a brainstem/cerebellar hemorrhage, and 4.5% an uncertain diagnosis. The overall 30-day case fatality rate was 25.4%. Comparison with five stroke registries from the West suggests that intracerebral hemorrhage occurs between two and three times more frequently in the Chinese than in Westerners. Whether there is any difference in the relative frequencies for lacunar infarction remains unclear.
Adult↗
Binding of brain and atrial natriuretic peptides to cultured mouse astrocytes and effect on cyclic GMP.
125I-Porcine brain natriuretic peptide (125I-pBNP) bound to mouse astrocytes in primary culture in a time-dependent manner (t1/2 = 4.5 min), similar to 125I-human atrial natriuretic peptide (125I-hANP) (t1/2 = 5 min). Binding was saturable and reached equilibrium after 90 min at 22 degrees C for both radioligands. Scatchard analysis suggested a single class of binding sites for pBNP with a binding affinity and capacity (KD = 0.08 nM; Bmax = 78.3 fmol/mg of protein) similar to those of hANP1-28 (KD = 0.1 nM; Bmax = 90.3 fmol/mg of protein). In competition binding studies, pBNP or human/rat atrial natriuretic peptide (ANP) analogues [hANP1-28, rat ANP1-28 (rANP1-28), and rANP5-28] displaced 125I-hANP, 125I-pBNP, and 125I-rANP1-28 completely, all with IC50 values of less than nM (0.14-0.83 nM). All four peptides maximally stimulated cyclic GMP (cGMP) production by 10 min at 22 degrees C at concentrations of 1 microM with EC50 values ranging from 50 to 100 nM. However, maximal cGMP induction by brain natriuretic peptide (BNP) (25.9 +/- 2.1 pmol/mg of protein) was significantly greater than that by hANP1-28 (11.5 +/- 2.2 pmol/mg of protein), rANP1-28 (16.5 +/- 2.0 pmol/mg of protein), and rANP5-28 (15.8 +/- 2.2 pmol/mg of protein). These studies indicate that BNP and ANPs act on the same binding sites and with similar affinities in cultured mouse astrocytes. BNP, however, exerts a greater effect on cGMP production. The difference in both affinity and selectivity between binding and cGMP production may indicate the existence of receptor subtypes that respond differentially to natriuretic peptides despite similar binding characteristics.
Animals↗
Environmental temperature and stroke in a subtropical climate.
The effect of environmental temperature on stroke occurrence in a subtropical climate was studied over a 1-year period by documenting the number of strokes (subdivided into cerebral infarct and intracerebral hemorrhage) admitted into a district hospital in Hong Kong at different temperatures. There was no significant correlation between the number of strokes (or its subtypes) per day per temperature category and the environmental minimum or maximum temperature. However, an association was present between the occurrence of cerebral infarcts and maximum temperature on the day of onset in elderly patients aged 70 years and above. Environmental temperature is not a strong risk factor for the occurrence of stroke in a subtropical climate.
Age Factors↗
Atrial natriuretic peptide in the central nervous system.
Atrial natriuretic peptide (ANP), first isolated from rat atrial cardiocytes, is a potent natriuretic, diuretic and vasorelaxant hormone when given intravenously. In keeping with increasing evidence that many bioactive peptides that were first discovered in peripheral organs, are often present in the central nervous system, ANP and its binding sites have been localized on neurons in different regions of the brain. Further, ANP binding sites have been found on primary astrocyte and glial cell lines and ligand binding results in cyclic GMP production. In this review, we shall discuss the possible role of ANP as a neuromodulator and its effects on astrocytes, the most numerous cell type in mammalian brain.
Animals↗
Effect of subcutaneous and intraperitoneal administration of recombinant human erythropoietin on blood pressure and vasoactive hormones in patients on continuous ambulatory peritoneal dialysis.
The effect of subcutaneous and intraperitoneal administration of recombinant human erythropoietin (rHuEPO) on blood pressure was evaluated in 20 patients with renal failure on continuous ambulatory peritoneal dialysis. The two groups of patients were commenced on a 16-week course of twice weekly rHuEPO by either the subcutaneous (10 patients) or the intraperitoneal route (10 patients). One patient in the latter group was subsequently excluded because of operation and transfusion. The hemoglobulin increased significantly from 6.9 +/- 0.3 g/dl to 9.8 +/- 0.6 g/dl after subcutaneous rHuEPO treatment (p less than 0.01) at an average dose of 84 +/- 9 U/kg body weight/week. For the intraperitoneal group, despite a higher average rHuEPO dosage (133 +/- 7 U/kg body weight/week), the hemoglobin level was not significantly altered (7.0 +/- 0.4 g/dl to 8.0 +/- 0.4 g/dl, p less than 0.05). During the 16-week period of rHuEPO therapy, an increase in antihypertensive therapy was required more frequently in patients in the intraperitoneal group but the difference between groups failed to reach statistical significance. There was no conclusive evidence that the rise in hematocrit was an independent precipitant of hypertension. Patients who were hypertensive prior to rHuEPO therapy appeared most susceptible to the pressor effects in that 8 of 11 treated hypertensive patients required more intensive antihypertensive treatment during EPO administration whereas none of the untreated patients developed hypertension during the study (Fisher's exact test, p = 0.007). Plasma levels of the vasoactive hormones, atrial natriuretic peptide (ANP), plasma renin activity (PRA), and endothelin (ET) remained unchanged during both subcutaneous and intraperitoneal rHuEPO therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Hypertension, lipoprotein(a), and apolipoprotein A-I as risk factors for stroke in the Chinese.
We analyzed the serum concentrations of lipids and lipoproteins and the prevalence of other risk factors in a case-control study of 304 consecutive Chinese patients with acute stroke (classified as cerebral infarction, lacunar infarction, or intracerebral hemorrhage) and 304 age- and sex-matched controls. For all strokes we identified the following risk factors: a history of ischemic heart disease, diabetes mellitus, or hypertension; the presence of atrial fibrillation or left ventricular hypertrophy; a glycosylated hemoglobin A1 concentration of greater than 9.1%; a fasting plasma glucose concentration 3 months after stroke of greater than 6.0 mmol/l; a serum triglyceride concentration 3 months after stroke of greater than 2.1 mmol/l; and a serum lipoprotein(a) concentration of greater than 29.2 mg/dl. We found the following protective factors: a serum high density lipoprotein-cholesterol concentration of greater than 1.59 mmol/l and a serum apolipoprotein A-I concentration of greater than or equal to 106 mg/dl. The patterns of risk factors differed among the three stroke subtypes. When significant risk factors were entered into a multiple logistic regression model, we found a history of hypertension, a high serum lipoprotein(a) concentration, and a low apolipoprotein A-I concentration to be independent risk factors for all strokes. The attributable risk for hypertension was estimated to be 24% in patients aged greater than or equal to 60 years. In this population, in which cerebrovascular diseases are the third commonest cause of mortality, identification of risk factors will allow further studies in risk factor modification for the prevention of stroke.
Apolipoprotein A-I↗
The radiological (CT) and clinical sequelae of primary intracerebral haemorrhage.
To determine the radiological and clinical outcome of primary intracerebral haemorrhage, a prospective study was carried out involving computed tomography (CT) of 388 consecutive Chinese patients admitted with acute stroke to a large public hospital in Hong Kong. Further CT and functional assessment were performed 3 months later in 71% of survivors. The patients were admitted over a 6 month period. 120 (31%) were found to have had presumed primary intracerebral haemorrhage. Of these, 64 patients (53%) died within 3 months. From 40 of the 56 survivors who returned for a follow-up study at 3 months, 30 were functionally independent and five mildly disabled; only five were significantly disabled. Follow-up CT showed no residual lesion in 27%, low attenuation areas in 37%, slit-like lesions in 25% and calcification in 10% of patients. The size of residual lesions correlated statistically with the degree of residual disability, although the association was not close. It is concluded that primary intracerebral haemorrhage accounts for a high percentage of strokes among Hong Kong Chinese with more than half of the patients dying within 3 months. Many survivors, in whom follow-up CT appearances are variable, show good functional recovery.
Activities of Daily Living↗
Large-volume paracentesis versus dialytic ultrafiltration in the treatment of cirrhotic ascites.
We compared the clinical efficacy and safety of large-volume paracentesis and dialytic ultrafiltration in the treatment of refractory ascites in cirrhotic patients. A group of cirrhotic subjects (age 49-80 years) were randomly allocated to either continuous paracentesis (1-1.5 l/hour) or dialytic ultrafiltration until disappearance of ascites. Each patient was maintained on bed rest, fluid restriction (1 l/day) and a low (25 mmol/day) sodium diet for 14 days. Five patients (three in the paracentesis group and two in dialytic ultrafiltration group) developed massive ascites 3-5 months later, and received the crossover treatment. The average volume of fluid removed was similar in the two groups (4.70 +/- 1.47 l for dialytic ultrafiltration versus 4.69 +/- 1.84 l for paracentesis), but the treatment period was significantly shorter with dialytic ultrafiltration. The plasma creatinine significantly increased three days after paracentesis but did not increase in patients treated with dialytic ultrafiltration. There was an initial fall in mean arterial pressure during the first two hours of either treatment; a further fall in blood pressure was observed with paracentesis but not with dialytic ultrafiltration. Pretreatment plasma renin activity was elevated, but was not altered by either treatment. Plasma atrial natriuretic peptide levels were in the high-normal range before treatment. Paracentesis was associated with a delayed fall in plasma atrial natriuretic peptide, while dialytic ultrafiltration induced a modest but significant rise. No complication was experienced with dialytic ultrafiltration in the two weeks following treatment, but four of the eight patients who underwent paracentesis had developed severe complications.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Vasoactive hormones in uremic patients on continuous ambulatory peritoneal dialysis.
Plasma levels of atrial natriuretic peptide (ANP), renin activity (PRA), and endothelin (ET) are often elevated in uremic patients on hemodialysis treatment. The profile of these vasoactive hormones and their relationships with hemodynamic indices in patients on continuous ambulatory peritoneal dialysis (CAPD), however, are not clear. We therefore measured plasma concentrations of ANP, PRA, ET, together with parathyroid hormone (PTH) in 17 patients (mean age 38.5 years) on maintenance CAPD over a period of 12 weeks. Baseline ANP, PRA, and ET levels were significantly higher than those of healthy subjects, and no significant changes in these indices were observed over the 12 week period. There was a significant positive correlation between levels of plasma ANP and PRA [rank correlation coefficient, R(s) = 0.496, p less than 0.05] as has been reported in cardiac failure. Despite the absence of clinically overt heart failure, a significant proportion (approximately 50%) of our patients demonstrated evidence of myocardial dysfunction on echocardiography. Furthermore, a significant positive correlation was demonstrated between plasma ANP and left atrial size [R(s) = 0.61, p less than 0.01] and an inverse correlation existed between plasma ANP and the left ventricular ejection fraction [R(s) = 0.51, p less than 0.05]. Twelve patients (71%) had biochemical evidence of hyperparathyroidism with raised levels of serum PTH. Our study demonstrates increased levels of plasma ANP, PRA, and ET in uremic patients on long-term CAPD. A positive correlation exists between plasma ANP and PRA suggesting their myocardial function may be compromised and this was confirmed on echocardiography. The possibility that high circulating PTH concentrations contribute to impaired cardiac function in such patients, deserves further study.
Adult↗