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Biomedical subjects

C S Cockram

Publications and source records attributed to C S Cockram.

At least 19 recordsLinked to original sources
PubMed1992

Quantitative determination of glucose in blood plasma and in fruit juices by combined WATR-CPMG 1H NMR spectroscopy.

The quantitative analysis of pure glucose solution < or = 225 mM (< or = 40.8 mg/mL) in 90/10 H2O/D2O was successfully completed in dilute aqueous solution by the WATR-CPMG method whereby the T2 of the water resonance is manipulated by the WATR method followed by elimination of the water peak by the CPMG pulse sequence. The method was applied to the quantitative analysis of total glucose in blood plasma from human subjects undergoing the oral glucose tolerance test in the teaching hospital, and the results were compared to those obtained using a standard glucose oxidase method in a hospital chemical pathology laboratory. The accuracy of the results obtained using the WATR-CPMG method were generally within 5% of the glucose oxidase method. The coefficient of variation was determined to be better than 4% using plasma samples of diabetic subjects. Application to the quantitative analysis of orange and guava juice was also successfully demonstrated.

Beverages↗
PubMed1992

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↗
PubMed1992

The inter-relationships between albuminuria, plasma albumin concentration and indices of glycaemic control in non-insulin-dependent diabetes mellitus.

We studied the relationship between albuminuria (measured as albumin/creatinine ratio (alb/Cr) in a random urine sample) and measures of glycaemic control (fructosamine, HbA1 and glucose) in 470 patients with non-insulin-dependent diabetes mellitus (NIDDM). Albumin excretion was in the microalbuminuric range (alb/Cr ratio > 5.4-40.3) in 112 (23.8%) and in the macroalbuminuric range (alb/Cr ratio > 40.3 mg/mmol) in 89 patients (18.9%). Fourteen percent (n = 67) of patients had a normal plasma HbA1 (< or = 8.5%) while 27% (n = 127) had a normal plasma fructosamine concentration (< or = 2.2 mmol/l). Using stepwise multiple regression analysis, plasma fructosamine concentration was found to be independently and negatively associated with urine albumin/creatinine ratio (B = 0.24, P < 0.006) in the macroalbuminuric group. Further analysis of the relationship between plasma albumin concentration and indices of glycaemic control showed that plasma albumin concentration correlated negatively with random plasma glucose concentration in the normoalbuminuric patients (r = -0.16, P = 0.008) but not in microalbuminuric or macroalbuminuric groups. HbA1 was not correlated with plasma albumin concentration. Our results indicate that albuminuria has an effect on the plasma fructosamine concentration which is independent of plasma albumin concentration.

Adult↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

Effect of insulin on glucose and glycogen metabolism and leucine incorporation into protein in cultured mouse astrocytes.

Insulin, following binding to its receptor, produces a dose- and time-dependent stimulation of entry of 2-deoxy-D-[U-14C] glucose and glycogen synthesis from D-[U-14C] glucose in cultured mouse astrocytes following differentiation. Maximal stimulation of both glucose entry (217% above basal) and of glycogen synthesis (209% above basal) was observed at an insulin concentration of 1.7 x 10(-8) M. Insulin also stimulates the incorporation of leucine into astrocytic proteins with maximal stimulation (156% above basal) at an insulin concentration of 1.7 x 10(-7) M, but no effect on leucine uptake was observed at an insulin concentration of 1.7 x 10(-6) M. These results, together with a previous demonstration that insulin and certain insulin analogues stimulate pyrimidine nucleoside incorporation into nucleic acid, indicate that insulin has diverse actions on biomacromolecular metabolism in cultured mouse astrocytes.

Animals↗
PubMed1992

Microalbuminuria and other cardiovascular risk factors in nondiabetic subjects.

The association between urinary albumin:creatinine ratio and other cardiovascular risk factors such as age, blood pressure, obesity, glycemic indices, insulin and lipid profile was examined in a population in a Chinese community consisting of 795 men (mean age 35.8 +/- 8.8 yr) and 538 women (mean age 37.9 +/- 8.9 yr) with a normal glucose tolerance defined by WHO criteria. Men with a urinary albumin:creatinine ratio above the 90th percentile had higher systolic and diastolic blood pressures, fasting plasma glucose, 2-h glucose after a 75 g oral glucose load, and fasting serum insulin. Women with high urinary albumin:creatinine values had higher systolic and diastolic blood pressures, body mass index, waist-hip ratio, fasting insulin and triglycerides. Multivariate analysis showed that only systolic blood pressure and fasting glucose in men, and diastolic blood pressure and fasting insulin in women, independently contributed to urinary albumin:creatinine. When the effect of blood pressure was eliminated by excluding subjects with systolic blood pressure > 140 and diastolic > 90 mm Hg, only fasting insulin was associated with urinary albumin:creatinine in women. No associations were found for men. We conclude that microalbuminuria may be a marker for cardiovascular disease only because of its association with blood pressure in men, while in women, there is an additional independent association with fasting serum insulin.

Adult↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

Susceptibility to IDDM in a Chinese population. Role of HLA class II alleles.

MHC associations with IDDM in a Chinese population were studied to investigate genetic susceptibility to the disorder. The frequency of HLA-DR3 was significantly higher in the diabetic patients (19/49 [38.7%] vs. control subjects, 11/105 [10.5%], Pc less than 1.3 x 10(-3), RR = 5.3 [CI 2.3-12.1]), whereas DR4 was not (11/49 [22.4%] vs. 28/105 [26.7%], NS). The frequency of DR3/4 heterozygosity was higher in the diabetic patients (6/49 [12.2%] vs. control subjects, 0/105 [0%], P = 1.7 x 10(-3), RR = 31.5 [CI 3.8-263.6]). The frequency of DR3/9 heterozygosity also was higher in the diabetic patients (6/49 [12.2%] vs. control subjects, 2/105 [1.9%], P = 0.03, RR = 6.2 [CI 3.0-12.7]). No significant associations were noted between DQB1 alleles and IDDM. Among DR4-positive subjects, the frequency of DQB1 allele DQB1*0302 was higher in the diabetic patients (10/11 [90.0%] vs. control subjects, 12/24 [50%], Pc less than 0.05, RR = 7.0 [CI 1.3-38.0]), and the frequency of DQB1*0401 was significantly lower in the diabetic patients (2/11 [18.2%] vs. control subjects, 16/24 [66.7%], Pc = 0.04, RR = 0.1 [CI 0.02-0.46]). No DR4 subtype was associated significantly with IDDM. The frequency of DQA1*0501, a DQA1 allele, was higher in diabetic patients (22/41 [53.7%] vs. control subjects, 20/95 [21.1%], Pc less than 3 x 10(-3), RR = 4.3 [CI 2.0-9.3]). The frequency of DQA1*0301, which has been associated consistently with IDDM in other ethnic groups, was not significantly higher in the diabetic patients in this study (27/41 [65.9%] vs. control subjects, 53/95 [55.8%], NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1992

Assessment of glucose tolerance test criteria for diagnosis of diabetes in Chinese subjects.

OBJECTIVE: To examine and compare WHO diagnostic criteria for diabetes mellitus. RESEARCH DESIGN AND METHOD: The relationship between FPG and 2-h glucose are examined in 680 OGTTs with a quadratic regression model and ROC analysis. Simultaneous measurements of HbA1 and fructosamine are also compared with multiple linear regression. RESULTS: Two hundred eighteen subjects (32%) had 2-h glucose greater than or equal to 11.1 mM, of which only 86 had FPG greater than or equal to 7.8 mM. Only 2 subjects had FPG greater than 7.8 mM and 2-h glucose less than 7.8 mM. Of subjects with 2-h glucose less than 7.8 mM (n = 332), only 9 had FPG greater than 6.0 mM. From the quadratic model, the predicted FPG corresponding to 2-h glucose = 11.1 mM was 5.7 mM, whereas the predicted 2-h glucose corresponding to FPG = 7.8 mM was 15.2 mM. ROC analysis showed that, with 2-h glucose greater than or equal to 11.1 mM as indicating diabetes, an FPG of 5.6 mM gave an intersect for sensitivity and specificity of 87%. HbA1 and fructosamine correlated more closely with 2-h glucose and area under the OGTT curve than with FPG. CONCLUSIONS: Given that a 2-h glucose cutoff of 11.1 mM can be justified from other studies, our results suggest that the FPG cutoff of 7.8 mM when used for screening purposes should be reduced. At a suggested value of 7.0 mM, specificity remains 98.5%, whereas sensitivity increases to 57%.

China↗
PubMed1992

Association between insulin and blood pressure in a community population with normal glucose tolerance.

The purpose of this study was to examine the relationship between insulin and BP in patients with normal glucose tolerance. The associations between systolic and diastolic BP, age, body mass index, waist/hip ratio, fasting glucose, insulin, fructosamine, glycosylated haemoglobin, lipid profile, and glucose and insulin two hours after 75 g oral glucose were examined in 1,520 employees of a public utility company and non-medical staff of a district hospital. Patients with impaired glucose tolerance or diabetes mellitus (using WHO criteria) were excluded. In men (mean age 35.6 +/- 8.7 years, n = 769), both systolic and diastolic BP were positively associated with age, body mass index, waist/hip ratio, fasting and 2h glucose and insulin, triglycerides and apolipoprotein B, and were negatively associated with glucose/insulin ration, and high density lipoprotein and cholesterol and its subfractions. However, in multivariate analysis only body mass index, age, fasting glucose and insulin were independent predictors of systolic BP, while only body mass index and age predicted diastolic BP. In women, age, glycosylated haemoglobin, 2h glucose/insulin ratio, 2h glucose, fructosamine and triglycerides were predictors of systolic BP. Fasting or 2h insulin, and glucose/insulin ratios did not predict diastolic BP. The results are compatible with the hypothesis that systolic hypertension may reflect a hyper-insulinaemic state even in those with normal glucose tolerance, independent of age and obesity. The association between plasma lipids and blood pressure is probably mediated by insulin and obesity.

Adult↗
PubMed1991

In vivo and in vitro sodium pump activity in subjects with thyrotoxic periodic paralysis.

OBJECTIVE: To examine whether sodium pump activity plays a part in the pathogenesis of thyrotoxic periodic paralysis. DESIGN: Measurement of platelet sodium-potassium ATPase and in vivo sodium pump activities in healthy subjects and thyrotoxic subjects with and without paralysis. SETTING: University hospital in Hong Kong. SUBJECTS: 21 healthy subjects, 23 untreated thyrotoxic subjects, 13 untreated men with periodic paralysis, seven treated thyrotoxic subjects, and six treated men with periodic paralysis. MAIN OUTCOME MEASURES: Platelet Na+, K(+)-ATPase activity and plasma rubidium concentration after oral loading. RESULTS: Median (range) platelet Na+, K(+)-ATPase activity in thyrotoxic subjects was 253 (169-821) mumol inorganic phosphate/h/g protein--significantly higher than that in healthy subjects (134 (81-180) mumol/h/g protein; p less than 0.001). Na+, K(+)-ATPase activity in those with periodic paralysis was 374 (195-1196) mumol/h/g protein, again significantly higher than that in healthy subjects (p less than 0.001) and that in other thyrotoxic subjects (p less than 0.01) despite similar degrees of hyperthyroidism. Activities in treated thyrotoxic subjects with and without periodic paralysis were 148 (110-234) and 131 (86-173) mumol/h/g protein respectively. Mean (95% confidence interval) plasma rubidium concentration five hours after oral administration in thyrotoxic subjects (7.0 (6.6 to 7.5) mumol/l) was significantly lower than in healthy subjects (10.2 (9.5 to 10.9) mumol/l; p less than 0.001) and higher than in those with periodic paralysis (6.0 (5.7 to 6.3) mumol/l; p less than 0.01). CONCLUSIONS: Sodium pump activity in untreated subjects with periodic paralysis is higher than in other thyrotoxic subjects, and this may be responsible for the hypokalaemia.

Adult↗
PubMed1991

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↗
PubMed1991

Histiocytosis X involving the thyroid and hypothalamus.

A case of histiocytosis X involving the thyroid and hypothalamus is reported. A 16 year old female presented with amenorrhoea and diabetes insipidus. She subsequently developed a painful goitre with biochemical hypothyroidism, and stridor. The stridor and goitre responded to cyclophosphamide. Previous publications on the use of cytotoxics in histiocytosis X involving the thyroid are reviewed. We describe for the first time both the ultrasound appearances of the thyroid in this condition and the use of serial volumetric measurements to monitor therapy.

Adolescent↗
PubMed1991

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↗