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Biomedical subjects

J A Critchley

Publications and source records attributed to J A Critchley.

At least 19 recordsLinked to original sources
PubMed2000

Pharmacodynamics and pharmacokinetics of intravenous glibenclamide in Caucasian and Chinese patients with type-2 diabetes.

OBJECTIVE: We analysed the kinetics and effects of glibenclamide (Gb) on glucose, insulin and proinsulin secretion in two ethnic groups (10 in each) of type-2 diabetic patients, one of Caucasian, the other of Chinese origin. BACKGROUND: Diabetes mellitus type 2 is a global disease affecting all ethnic groups. There are ethnic differences in both the prevalence and metabolic characteristics of the disease. Important interethnic pharmacodynamic and pharmacokinetic differences have been reported for several drugs. With few exceptions, detailed studies on sulphonylurea are lacking. MATERIAL AND METHODS: The patients were studied on two occasions when either no Gb (control) or 1.25 mg Gb was administered i.v., immediately before the administration of a 75-g oral glucose tolerance test. Concentrations of insulin and proinsulin were determined by means of radioimmunoassay without cross-reactivities. Gb concentration was determined using high-performance liquid chromatography. Pharmacodynamic results were calculated using net areas under the curves, with basal values set as zero. A P value less than 0.05 was considered significant. RESULTS: When glucose was administered orally without Gb, Chinese patients had higher plasma glucose increases at 10 min (7.6 mmol/l x min vs 2.6 mmol/l x min) and higher increases of plasma insulin levels than Caucasians at both 10 min (198 pmol/l x min vs 54 pmol/l x min) and 30 min (2286 pmol/l x min vs 1198 pmol/l x min). When Gb was administered, the plasma glucose increases were reduced, and the increases of serum insulin and proinsulin levels were greater in both ethnic groups. Compared with the basal values (-1 min), proinsulin/insulin ratios (RPI) were lowest at 10-30 min, followed by an increase. Chinese patients had higher increases of serum insulin levels at 10 min (1109 pmol/l x min vs 550 pmol/l x min) and a lower RPI at 30 min (6. 0% vs 7.6%) and 240 min (15.0% vs 21.0%) relative to Caucasians. Serum Gb data were best fitted to a biexponential i.v. model. There were no interethnic differences in any of the pharmacokinetic parameters. CONCLUSION: In summary, following oral glucose administration without Gb, Chinese type-2 diabetic patients had higher plasma insulin levels but also higher plasma glucose levels during the first 10 min, which might reflect reduced insulin sensitivity or more rapid glucose absorption. Gb augmented glucose-induced release of both insulin and proinsulin in both ethnic groups; the effect on insulin secretion was more pronounced. In conclusion, minor pharmacodynamic but no pharmacokinetic differences were found between the two groups. It seems appropriate to employ the same dosage principles when using Gb in Caucasians and Chinese.

Adult↗
PubMed2000

Long-term effects of angiotensin-converting enzyme inhibition and metabolic control in hypertensive type 2 diabetic patients.

UNLABELLED: Long-term effects of angiotensin-converting enzyme inhibition and metabolic control in hypertensive type 2 diabetic patients. BACKGROUND: In hypertensive type 2 diabetic patients, treatment with angiotensin-converting enzyme (ACE) inhibitors is associated with a lower incidence of cardiovascular events than those treated with calcium channel-blocking agents. However, the long-term renal effects of ACE inhibitors in these patients remain inconclusive. In 1989, we commenced a placebo-controlled, double-blind, randomized study to examine the anti-albuminuric effects of enalapril versus nifedipine (slow release) in 102 hypertensive, type 2 diabetic patients. These patients have been followed up for a mean trial duration of 5.5 +/- 2.2 years. We examined the determinants, including the effect of ACE inhibition on clinical outcomes in these patients. METHODS: After a six-week placebo-controlled, run-in period, 52 patients were randomized double-blind to receive nifedipine (slow release) and 50 patients to receive enalapril. After the one-year analysis, which confirmed the superior anti-albuminuric effects of enalapril (-54%) over nifedipine (+11%), all patients were continued on their previously assigned treatment with informed consent. They were subdivided into normoalbuminuric (N = 43), microalbuminuric (N = 34), and macroalbuminuric (N = 25) groups based on two of three 24-hour urinary albumin excretion (UAE) measurements during the run-in period. Renal function was shown by the 24-hour UAE, creatinine clearance (CCr), and the regression coefficient of the yearly plasma creatinine reciprocal (beta-1/Cr). Clinical endpoints were defined as death, cardiovascular events, and/or renal events (need for renal replacement therapy or doubling of baseline plasma creatinine). RESULTS: In the whole group, patients treated with enalapril were more likely to revert to being normoalbuminuric (23.8 vs. 15.4%), and fewer of them developed macroalbuminuria (19.1 vs. 30.8%) compared with the nifedipine-treated patients (P < 0.05). In the microalbuminuric group, treatment with enalapril (N = 21) was associated with a 13.0% (P < 0.01) reduction in 24-hour UAE compared with a 17.3% increase in the nifedipine group (N = 13). In the macroalbuminuric patients, enalapril treatment (N = 11) was associated with stabilization compared with a decline in renal function in the nifedipine group, as shown by the beta-1/Cr (0.65 +/- 4.29 vs. -1.93 +/- 2.35 1/micromol x 10-3, P < 0.05) after adjustment for baseline values. Compared with the normoalbuminuric and microalbuminuric patients, those with macroalbuminuria had the lowest mean CCr (75.5 +/- 24.1 vs. 63.5 +/- 21.3 vs. 41.9 +/- 18.5 mL/min, P < 0.001) and the highest frequency of clinical events (4.7 vs. 5.9 vs. 52%, P < 0. 001). On multivariate analysis, beta-1/Cr (R2 = 0.195, P < 0.001) was independently associated with baseline HbA1c (beta = -0.285, P = 0.004), whereas clinical outcomes (R2 = 0.176, P < 0.001) were independently related to the mean low-density lipoprotein cholesterol (beta = 2.426, P = 0.018), high-density lipoprotein cholesterol (beta = -8.797, P = 0.03), baseline UAE (beta = 0.002, P = 0.04), and mean CCr during treatment (beta = -0.211, P = 0.006). CONCLUSION: In this prospective cohort analysis involving 102 hypertensive, type 2 diabetic patients with varying degrees of albuminuria followed up for a mean duration of five years, we observed the importance of good metabolic and blood pressure control on the progression of albuminuria and renal function. Treatment with enalapril was associated with a greater reduction in albuminuria than with nifedipine in the entire patient group, and especially in those with microalbuminuria. In the macroalbuminuric patients, the rate of deterioration in renal function was also attenuated by treatment with enalapril.

Aged↗
PubMed2000

Renin-angiotensin-aldosterone system gene polymorphisms and hypertension in Hong Kong Chinese.

In Chinese populations, hypertension is common and is a major risk factor for cerebrovascular and coronary heart disease. The renin-angiotensin-aldosterone system (RAAS) helps maintain blood pressure and salt homeostasis and appears important in the pathogenesis of hypertension and some forms of vascular disease. We investigated three RAAS gene polymorphisms, the angiotensin-converting enzyme (ACE) insertion/deletion, angiotensinogen (AGT) M235T and angiotensin II type 1 receptor A1166C polymorphisms in 232 hypertensive and 178 normotensive Chinese subjects. The hypertensives were generally more obese and dyslipidaemic. No significant differences in genotype or allele frequencies for any of the polymorphisms were identified between the groups, nor was there any interactive contribution to blood pressure by the ACE and AGT polymorphisms. However, there were large differences in genotype and allele frequencies between the healthy Chinese and published data for equivalent Caucasian populations. These findings suggest these polymorphisms are unlikely to be involved in the pathogenesis of hypertension in Chinese.

Adult↗
PubMed1999

Vitamin D receptor gene polymorphisms and bone mineral density in elderly Chinese men and women in Hong Kong.

Although genetic factors have been strongly implicated in determining bone mineral density (BMD), the role of the vitamin D receptor (VDR) polymorphism remains controversial. An overall consensus is difficult, as the populations studied have been heterogeneous with respect to menopausal status and ethnicity. Moreover, some studies have examined only small populations, and relatively few studies have been conducted in Asian populations. There is mounting evidence that calcium homeostasis in Asian populations differs from that in Caucasians. This difference may be mediated, in part, through VDR effects. In a cross-sectional study we have examined the relationship between the VDR polymorphism and BMD in 272 women (mean age 75 years) and 237 men (mean age 73 years) of Chinese origin from Hong Kong. Consistent with other studies in Asian populations we found higher frequencies of the T, b and a alleles compared with those reported in Caucasian populations. Moreover, no significant difference in BMD was observed when subjects were grouped by a combination of the genotypes (bbAATT, bbAaTT, bbaaTT, BbAaTt, BbAATt). These results suggest that VDR polymorphism is not associated with BMD in elderly Hong Kong Chinese men and women.

Aged↗
PubMed1999

Molecular genetics of diabetes mellitus in Chinese subjects: identification of mutations in glucokinase and hepatocyte nuclear factor-1alpha genes in patients with early-onset type 2 diabetes mellitus/MODY.

AIMS: To examine the prevalence of identified MODY-related genes in Chinese subjects with early onset Type 2 diabetes mellitus and a positive family history of diabetes and to look for possible associations between the gene mutations and the development of diabetes. METHODS: Ninety-two unrelated Chinese subjects with diabetes diagnosed before the age of 40 years who had a positive family history of diabetes were screened for mutations in hepatocyte nuclear factors (HNF-1alpha and HNF-4alpha) and glucokinase genes by direct sequencing. The family members of patients with mutations and 100 healthy controls were also examined. RESULTS: Mutations in the HNF-1alpha and the glucokinase genes were found in 5% and 3% of the diabetic subjects, respectively but no mutations were found in the coding region of the HNF-4alpha gene. Three mutations found in the glucokinase gene were novel missense mutations (I110T, A119D and G385V). The mutations in the HNF-1alpha gene were also new and included four missense mutations (G20R, R203H, S432C, I618M) and one splice acceptor site mutation (IVS2nt-1G-->A). Patients with mutations in these genes were clinically heterogeneous with respect to phenotype and basal pancreatic beta cell function. CONCLUSIONS: Genetic factors such as mutations in the HNF-1alpha and glucokinase genes may be important in the development of diabetes in Chinese people, especially when the disease is of early onset.

Adolescent↗
PubMed1999

A study to determine the optimum dose of metaraminol required to increase blood pressure by 25% during subarachnoid anaesthesia.

We studied dosage optimization for metaraminol when managing hypotension during subarachnoid anaesthesia. Twenty patients aged 53 to 84 years, were recruited. Non-invasive blood pressure (BP) and heart rate were recorded one-minutely. A series of four i.v. metaraminol boluses (0.25 to 1.0 mg per 50 kg adult) were administered. From individual patient time plots of BP predicted dosages for a 25% elevation in BP were estimated. Dose-related elevations in systolic BP [mean (SD)] occurred following dosages of 0.5 mg [25 (11)%] and 1.0 mg [50 (23)%]. Similar elevations occurred in mean and diastolic BP. Overall estimated dosage (median) to produce a 25% elevation in systolic BP was 0.5 mg (per 50 kg adult). However, individual patient responses varied (10-90th centiles = 0.23 to 0.80 mg). Thus, we now recommend a starting dose of 0.25 mg, increasing to 0.5 mg if necessary, to treat hypotension (25% decrease in systolic BP) during subarachnoid anaesthesia.

Aged↗
PubMed1999

Plasma insulin, growth hormone, cortisol, and central obesity among young Chinese type 2 diabetic patients.

OBJECTIVE: To examine the relationships between central obesity, insulin resistance index, plasma insulin, growth hormone (GH), and cortisol concentrations in 90 young Chinese type 2 diabetic patients (aged 33+/-5 years) and 104 age- and sex-matched control subjects (aged 32+/-9 years). RESEARCH DESIGN AND METHODS: Young Chinese diabetic patients (aged <40 years) were recruited from the Prince of Wales Hospital. Blood pressure, height, weight, and waist and hip circumferences were determined. Venous blood was sampled for measurements of fasting plasma glucose, HbA1c, lipids, creatinine, insulin, GH, and cortisol. A 24-h urine was assayed for urinary albumin excretion (UAE). General and central obesity was represented by BMI and waist circumference, respectively. Insulin resistance index was estimated as a product of fasting plasma insulin and glucose concentrations. RESULTS: Compared with control subjects, diabetic patients were more obese, hyperglycemic, and had worse lipid profile, higher blood pressures, UAE, insulin resistance index, plasma insulin, and cortisol concentrations (all P < 0.001) but lower GH concentrations (P < 0.05). When analyzed as a whole group (n = 194), increasing quartiles of waist circumference were associated with increasing trends of insulin resistance index, plasma insulin, and cortisol concentrations (all P < 0.01) but a decreasing trend of plasma GH concentration (P < 0.05). Using stepwise multiple regression analysis, waist circumference was only associated with sex variable (being higher in men) in the control subjects. In the diabetic group, 51% of waist circumference was independently related to male sex and increased plasma insulin and cortisol concentrations as well as reduced plasma GH levels. CONCLUSIONS: In young Chinese type 2 diabetic patients, hyperinsulinemia, hypercortisolemia, and reduced plasma GH levels were closely associated with central obesity. Based on these findings, we postulate that maladaptive hormonal responses to rapid changes in lifestyle may have led to obesity and type 2 diabetes in these young patients. Alternatively, lifestyle-related obesity may have given rise to these hormonal changes. More studies are required to delineate the nature of these relationships.

Adolescent↗
PubMed1999

A sibling-pair analysis of fasting lipids and anthropometric measurements and their relationship to hypertension.

Fifty non-diabetic, young Chinese hypertensives were compared to their normotensive siblings with respect to body fat distribution and fasting lipid and glucose (FPG) profiles. Sitting BP in hypertensives met conventional hypertension criteria after a 4-week washout period on placebo. Hypertensives had greater body mass index (BMI), subscapular skin-fold thickness (SFT), waist circumference (W), waist-to-height (WHtR) and waist-to-hip ratio (WHR), p<0.0001 for all. Higher triglycerides (p=0.004) and lower HDL-cholesterol (p=0.015) concentrations were also observed. Weight, W, WHtR and BMI were higher in hypertensives in both male (n=9) and female gender-concordant sibling pairs (n=21). Higher WHR, hip circumference and subscapular SFT were only seen in the male hypertensives. Hypertension is associated with central adiposity and adverse lipid profiles in this group of young hypertensives, supporting the hypothesis that obesity, particularly central, is closely associated with hypertension in Chinese as in other ethnic groups.

Adult↗
PubMed1998

Simultaneous measurement of catecholamines and kallikrein in urine using boric acid preservative.

Catecholamines, dopamine and the renal kallikrein-kinin system may participate in the pathogenesis of hypertension. In the past these systems have been studied independently in isolation. Attempts to study the systems together have been hampered by incompatibility of the current urine preservatives for the two assays involved. In order to measure acid-stable catecholamines and acid-labile kallikrein enzyme together, we have established boric acid solution as a preservative by comparing the stability of urinary catecholamines stored in it with the commonly employed preservative, hydrochloric acid (HCl) as well as the stability of urinary kallikrein in untreated urine with and without boric acid at ambient temperatures for 24 and 48 h, and at -20 degrees C for 2 weeks and 1, 2 and 3 months. The stability of other common urine parameters including cortisol, electrolytes, creatinine and protein, was also investigated after storage with boric acid at ambient temperature for 24 h. Our results showed that there was a good agreement between the measurements of urinary catecholamines stored in both HCl and boric acid and that the latter did not interfere with measurements of urinary kallikrein or other common urine parameters.

Albuminuria↗
PubMed1998

Lung fluid and impedance cardiography.

Serial thermodilution and impedance cardiac output measurements in two critically ill patients are presented. Impedance cardiography failed to detect changes in cardiac output and provided values lower than those derived from thermodilution. Chest X-ray examination and changes in thoracic impedance suggested that these two patients had significantly increased extravascular lung water. This failure of impedance cardiography is attributed to aberrant electrical conduction though the lungs as a result of increased lung fluid that alters the impedance waveform. Although reliable when used in normal subjects, impedance cardiography appears not to provide accurate measurements in critically ill patients.

Adult↗
PubMed1998

Evaluation of drug usage and expenditure in a hospital diabetes clinic.

BACKGROUND: Diabetes mellitus is a major public health problem and often coexists with hypertension and dyslipidaemia. A prescription-based survey was conducted to examine the use of antidiabetic, antihypertensive and lipid lowering drugs in a hospital diabetes clinic. The expenditure incurred was also evaluated. METHOD: Prescriptions issued from the diabetes clinic were collected for 4 consecutive weeks. Drugs were categorized into three main classes--antidiabetic, antihypertensive and lipid-lowering drugs. The unit cost of each drug and the total amount prescribed were used to estimate the total drug costs. RESULTS: During the 4-week study period, 534 prescriptions were collected, of which 520 contained antidiabetic drugs. Oral hypoglycaemic agents were prescribed in 379 patients (72.9%). Sulphonylurea was used as a single agent in 119 (22.9%) patients, in combination with metformin in 219 (42%) patients and with insulin in 17 patients (3.3%). Among patients treated with sulphonylureas (n=342), glibenclamide (47.7%) and gliclazide (30.7%) were the main drugs prescribed. Metformin monotherapy was prescribed in only 31 patients (6%). Insulin treatment was prescribed in 141 (27%) patients and in combination with oral drugs in 23 patients (4.5%). Of the 534 prescriptions, 225 (42%) contained antihypertensive drugs. Calcium channel blocking agents and angiotensin converting enzyme inhibitors were the most commonly prescribed drugs in both monotherapy (n=155) and combination therapy (n=70). The antidiabetic and antihypertensive drugs accounted for 45% and 39% of the total drug expenditure, respectively. Lipid-lowering drugs were prescribed in 8% of the diabetic patients. Simvastatin and gemfibrozil were the most common drugs prescribed and accounted for 12% of the total drug expenditure. CONCLUSION: The use of antidiabetic drugs represents a major burden on the health care system. The high proportions of patients requiring antihypertensive drugs and lipid lowering drugs further increase drug expenditure. Most of these treatments have been shown to improve clinical outcomes and quality of life, if used appropriately. The impacts of these long-term medications on health care financing require careful evaluation to assess their cost-effectiveness.

Adult↗
PubMed1998

Drug utilization in a hospital general medical outpatient clinic with particular reference to antihypertensive and antidiabetic drugs.

OBJECTIVES: To examine the prescribing patterns, particularly antihypertensive and antidiabetic drugs, in a hospital outpatient clinic and to evaluate the expenditure incurred. METHODS: Prescriptions from a general medical outpatient clinic in a teaching hospital were collected for 4 weeks. Drug expenditures were calculated. RESULTS: A total of 622 prescriptions containing 1903 items were collected. Antihypertensive and antidiabetic drugs accounted for 25.9 and 9.1% usage, respectively. Calcium channel blocking agents, angiotensin converting enzyme inhibitors and beta-blocking agents were the most popular antihypertensive drugs used. Sulphonylureas were the most frequently prescribed antidiabetic agents. Amlodipine, doxazosin and sotalol accounted for 4.5% of all prescription items but 27.8% of the total drug expenditure. CONCLUSION: The use of antihypertensive and antidiabetic drugs accounted for most of the drug usage in this study. Use of newer and more expensive agents has further increased drug expenditure. Monitoring drug usage and their correlations with clinical outcomes are warranted.

Aged↗
PubMed1998

Use of indapamide in hospital and community clinics and its effect on plasma potassium in Chinese patients.

OBJECTIVES: To investigate the usage pattern of indapamide and other antihypertensive drugs in patients attending a community-based government outpatient clinic (GOPC) or a hospital-based specialist clinic (SC). The plasma potassium concentrations of patients receiving indapamide and other diuretics were also examined. METHOD: Prescriptions from the SC and the GOPC were reviewed and collected during January 1998. Patients' plasma potassium concentrations and the date of initiation of each medication were retrieved from the hospital computer databases at SC. An age- and sex-matched control group of patients on non-diuretic antihypertensive drugs was identified. RESULTS: A total of 1648 and 773 prescriptions were collected from the SC during a 1-week period and GOPC during a 1-month period, respectively. Approximately half (45%) of the patients received antihypertensive treatment. Indapamide was five times more frequently prescribed in GOPC than SC (84.7 vs. 17.7%, P<0.001). Calcium channel blocking agents were the commonest antihypertensive drugs used in both clinics. The mean plasma potassium concentration of patients taking indapamide was lower than that of the control group (P = 0.037). Multiple linear regression analysis showed that consumption of indapamide (P =0.002) and duration of diuretic therapy (P = 0.023) were significantly related to changes in plasma potassium concentrations [multiple regression equation for potassium level = 4.09-0.145 (thiazide = 1)-0.377 (indapamide = 1) -0.00468 (duration of diuretic therapy in months)]. CONCLUSION: Indapamide was used extensively in the community clinic and less in the hospital-based outpatient clinic. Patients receiving indapamide had a significantly lower plasma potassium concentration as compared to other diuretics or antihypertensive groups and this was predicted by a multiple linear regression model. Monitoring plasma electrolytes before initiation of indapamide treatment and at regular intervals thereafter is essential for detecting the hypokalaemia that may occur in Chinese patients.

Aged↗
PubMed1998

Angiotensinogen T235 and ACE insertion/deletion polymorphisms associated with albuminuria in Chinese type 2 diabetic patients.

OBJECTIVE: Genetic polymorphisms of the renin-angiotensin system (RAS) have been implicated in the pathogenesis of diabetic proteinuria. Ethnic differences in the frequencies of these genotypes have also been reported. To date, most of these studies have been performed in white and Japanese populations. In this study, we examined the associations between albuminuria and RAS genetic polymorphisms in Chinese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: In a case-control study, the ACE insertion/deletion (I/D) gene, the angiotensinogen (AGT) gene (M235T), and the angiotensin II (AII) type 1 receptor gene (AT1 A1166C) were examined in 110 Chinese type 2 diabetic patients. Increased urinary albumin excretion (UAE) was defined as > or = 30 mg/day on at least two occasions during a 6-week study period. RESULTS: Compared with whites, there were high frequencies of the AGT TT genotype in Chinese control subjects (120/183 = 70%) and type 2 diabetic patients (74/110 = 67%). The frequencies of the MM genotype were 5 and 3%, respectively, and those of the ACE DD genotype were 13 and 10%, respectively. Although 9% of subjects carried the C allele, the AT1 CC genotype was not found in either group. Chinese type 2 diabetic patients with increased albuminuria (n = 56) had higher systolic blood pressure (160 +/- 26 mmHg vs 145 +/- 27 mmHg, P < 0.001) than the normoalbuminuric patients (n = 54). Both the AGT TT genotype (78.6% [44/56] vs. 55.6% [30/54], odds ratio [OR]: 3.0 [1.3-6.8]) and the T allele (88% [99/112] vs. 77% [83/108], OR: 2.5 [1.3-5.4]) were associated with an increased risk of albuminuria. Patients with the AGT TT genotype (n = 74) had higher 24-h UAE than those with the MT or MM genotypes (n = 36) (median: 37.8 mg/day vs. 17.8 mg/day, P < 0.01). This association remained significant in patients with normotension (56 mg/day [n = 19] for patients with the TT genotype vs. 22 mg/day [n = 14] for those with the MT/MM genotype, P = 0.03). The D allele carriers (DD or DI, n = 61) had higher serum ACE activities (75.5 +/- 29 U/l vs. 60.5 +/- 36.3 U/l, P < 0.01) than the noncarriers (II genotype). The median 24-h UAE also tended to be higher in the D allele carriers (38.9 mg/day vs. 21.4 mg/day, P = 0.07). The lowest UAE was observed in patients with the MM/MT/II genotype (16.3 mg/day [n = 18]) and the highest, in patients with the TT/DD/DI genotype (52.3 mg/day [n = 43]). No association was found between the TT genotype or D allele and hypertension. CONCLUSIONS: The high frequencies of the TT genotype and T allele in Chinese populations may contribute to the high prevalence of albuminuria in patients with type 2 diabetes. The possibility of synergism between the AGT TT genotype and the ACE D allele should also be explored.

Adult↗
PubMed1997

Non-invasive continuous arterial pressure, heart rate and stroke volume measurements during graded head-up tilt in normal man.

The haemodynamic effects of head-up tilt (HUT) at different tilt angles were investigated non-invasively in eight normal male subjects. Mean arterial pressure (MAP; by Ohmeda Finapres 2300), stroke volume (SV) and heart rate (HR; by BoMed NCCOM3-R7S) were continuously recorded whilst performing a series of HUTs (55 degrees, 10 degrees, 20 degrees, 30 degrees and 55 degrees) lasting 3 min each. The response to HUT was proportional to the sinc of the tilt angle. The magnitude of the response varied between subjects. HUT to 55 degrees resulted in mean (95% confidence limits) increases in MAP by 16 (+/-16)% and HR by 11 (+/-24)% and a decrease in SV by -25 (+/-22)%. These results were repeatable after 30 min. At small tilt angles, i.e. < or = 20 degrees, MAP did not change and HR decreased by -3 (+/-4)%. A detailed analysis revealed immediate dynamic (0-30 s), late dynamic (30-90 s) and plateau (after 90 s) phases in the response to HUT. In conclusion, HUT produces reproducible haemodynamic effects, although differences exist among subjects. A detailed analysis of these effects can be successfully performed using non-invasive methods.

Adult↗
PubMed1997

Single-dose pharmacokinetics of paracetamol and its conjugates in Chinese non-insulin-dependent diabetic patients with renal impairment.

OBJECTIVE: A single oral dose of paracetamol (20 mg.kg-1) was given to 38 Chinese patients with non-insulin-dependent diabetes mellitus (NIDDM) who had either normal renal function or varying degrees of renal impairment, with creatinine clearances ranging from 4 to 123 ml.min-1.1.73 m-2. The plasma and urinary concentrations of paracetamol and its major metabolites were measured by high-performance liquid chromatography (HPLC). RESULTS: The absorption and elimination of paracetamol were unaffected by renal impairment. However, the area under the plasma concentration time curve and the elimination half-life of paracetamol metabolites increased significantly with worsening renal insufficiency. Mean renal clearances of paracetamol and its conjugates were significantly reduced in these subjects. There was no evidence of altered metabolic activation with renal impairment. CONCLUSION: The results demonstrate that paracetamol disposition is minimally affected by diabetic nephropathy; however, extensive accumulation of conjugates may occur.

Acetaminophen↗
PubMed1997

A prescription survey in a hospital hypertension outpatient clinic.

AIMS: The objective of this study was to investigate drug utilization in the management of hypertension in Hong Kong. METHODS: We conducted a prescription survey to examine the use of antihypertensive drugs in a hypertension clinic in a regional hospital and the resulting expenditure incurred. The use of concurrent medications such as antidiabetic drugs and lipid-lowering agents was also examined. RESULTS: During a 7-week study period, 530 prescriptions were collected. All except 14 patients received antihypertensive drugs with 262 (50.8%) on monotherapy and 254 (49.2%) on combination therapy. Calcium channel blocking agents and beta-adrenoceptor blocking agents were the two most popular antihypertensive drugs used in both monotherapy (38% and 31%, respectively) and combination therapy (27% and 33%, respectively). Forty-nine patients (19%) received three antihypertensive drugs or more. The number of antihypertensive drugs showed a significant positive correlation with the duration of attendance at the clinic (r=0.88, P < 0.001). Of the total 530 prescriptions, 5.6% and 10% contained antidiabetic drugs and lipid-lowering agents, respectively. Calcium channel blocking agents, angiotensin converting enzyme (ACE) inhibitors and lipid lowering agents, accounted for 82% (HK$211,654; pounds sterling 1 approximately HK$12) of the total drug expenditure (HK$258,115). Seventy-nine percent of the lipid lowering agents prescribed were hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors. Amlodipine accounted for 26% of usage but contributed to 41% of the overall costs of calcium channel blocking agents. Alpha1-adrenoceptor blocking agents were only used infrequently and were the most expensive class of drugs, due to the preferred use of doxazosin rather than prazosin which is far cheaper than the former. CONCLUSIONS: In view of the use of these often costly drugs for long-term therapy, monitoring of their use and its correlation with clinical outcomes and quality of life is essential to ensure the optimal use of health care resources.

Antihypertensive Agents↗