Search PubMed⌕ Search

Biomedical subjects

K K Pun

Publications and source records attributed to K K Pun.

At least 55 records · Page 3Linked to original sources

Logistic regression model for the assessment of microalbuminuria and microproteinuria in insulin-dependent diabetic patients at risk.

Diabetic microalbuminuria, which predisposes to the irreversible macroproteinuria and terminal renal failure, has been shown to be reversible by stringent metabolic control. In this study, using logistic regression, 23 patients with insulin-dependent diabetes mellitus were evaluated. Basing on the reported biochemical changes in patients with diabetes mellitus, the relationship between microalbuminuria and serum biochemistries was assessed. Four biochemical parameters were shown to be significantly related to the amount of microalbuminuria and microproteinuria. The microalbuminuria as assayed by rocket immunoelectrophoresis is closely correlated with the microproteinuria as measured by the Coomassie dye binding method and both have a significant relationship with plasma creatinine, bicarbonate, albumin and globulin as assessed by the Minitab computer program and the Biomedical Data Package--Logistic Regression computer program. The relationship with bicarbonate and creatinine can be due to a decrease in glomerular filtration rate associated with more advanced microproteinuria. The relationship with albumin and globulin is the result of impaired albumin synthesis by the liver in diabetes mellitus. From these data, two simple equations which can provide a relative risk factor with rough quantitative assessment for microproteinuria and microalbuminuria are derived. Thus, from these four parameters available from relatively simple blood biochemistries, assessment can be made of the severity of coexisting diabetic proteinuria. The measurement of the latter is not readily available and is more costly and tedious. This assessment together with the finding of a decrease in albumin, slight increase in creatinine and decrease in bicarbonate associated with the more severe microalbuminuria can be used to alert the diabetologist in implementing tighter metabolic control and other interventional methods before irreversible macroproteinuria develops.

Adult↗

Elevated atrial natriuretic peptide level in giant right atrium complicating Marfan's syndrome.

We report a rare case of giant right atrial dilatation in a patient with Marfan's syndrome complicated by severe tricuspid regurgitation. Interestingly, the right atrial pressure was normal, but the atrial natriuretic peptide level was markedly elevated. We suggest that the underlying connective tissue abnormality had allowed extensive atrial distension which by causing an increased intramural tension according to Laplace's law stimulated atrial natriuretic peptide secretion.

Adult↗

The importance of parathyroid hormone in inhibition of collagen synthesis and mitogenesis of osteoblastic cell.

Loss of bone substance is a common manifestation of hyperparathyroidism. This suggests that parathyroid hormone (PTH) plays an important role as to bone mass. To investigate the mechanism underlying this change in bone mass, I studied the effects of PTH on collagen synthesis and mitogenesis of UMR-106 rat osteoblastic osteosarcoma cells. PTH inhibits the mitogenesis of UMR-106 rat osteosarcoma cells, the half-maximal concentration being 10(-8) to 10(-7) M, which is similar to the EC50 for cyclic AMP accumulation. Cyclic AMP, whose intracellular concentration was increased by PTH, plays a role in the modulation of mitogenesis, as shown by the comparable inhibitory effects of 8-bromoadenosine-3',5'-cyclic AMP (10(-4) M), forskolin (10(-7) M), and the phosphodiesterase inhibitor, IBMX (10(-5) M). PTH, in a similar concentration range, directly inhibited collagen synthesis. Concurrent with the suppression of collagen synthesis, the amounts of a1(I) and a2(I) collagen mRNA decreased proportionately. The results show that PTH modulates collagen synthesis at the transcriptional level. I concluded that parathyroid hormone inhibits the mitogenesis of osteoblasts as well as collagen synthesis by these cells. The decreases in the number of osteoblasts and the amount of collagen synthesis contribute to the loss of bone substance in hyperparathyroidism.

Animals↗

Thyrotoxicosis.

Explore the source record for details and available documents.

Humans↗

Effects of diets with high carbohydrate content on diabetic hyperlipidaemia and microalbuminuria.

Recent dietary recommendations for patients with diabetes mellitus have focussed on the liberalisation of carbohydrate intake to at least 50% of total calories. However, there are reports that this diet may cause adverse metabolic effects as a result of high intake of carbohydrate. Whether this high-carbohydrate diet will exacerbate hypertriglyceridaemia, which increases the risk of atherosclerosis, and diabetic microalbuminuria, which predisposes to progressive renal failure, is unknown. The dietary intake of 28 patients with insulin-dependent diabetes mellitus was assessed by diet histories with both questionnaire surveys and 3-day recall methods. The dietary contents of different constituents were graded according to the type and amount of food typically eaten, and the frequency of their consumption in the past 6 months. Twelve patients were found to have a high dietary intake of carbohydrate and this was confirmed by detailed assessment of food intake records over a 3-day period. The carbohydrate intake of these 12 patients amounted to at least 55% of total calories. Total calorie intake, body weight, mean blood pressure, glycaemic control, and glomerular filtration rate were similar between the 12 patients with high intake of carbohydrate and the other 16 patients with low intake. Urinary protein and albumin appearance as measured by dye binding and immunoassay, fasting cholesterol, triglyceride and high-density lipoprotein cholesterol were also comparable between the two groups. This study provides evidence that a high-carbohydrate diet in the treatment of diabetes mellitus is not associated with significant alterations in the amount of microalbuminuria or in hypertriglyceridaemia.

Adult↗

Parathyroid hormone receptors in human dermal fibroblasts: structural and functional characterization.

Previous studies have established the presence of parathyroid hormone (PTH)-sensitive adenylate cyclase activity in cultured human skin fibroblasts. The present study was undertaken to identify and quantitate PTH receptors directly in such cells. Human dermal fibroblast cell line CRL 1564 was found to possess specific binding sites for [125I]PTH(1-34). These sites bound PTH selectively; bovine and human PTH(1-34) and PTH(1-84) competed for [125I]PTH(1-34) binding sites, whereas the unrelated peptides calcitonin, insulin, AVP, angiotensin II, and ACTH(1-24) were inactive even at micromolar concentrations. Competitive binding experiments demonstrated the presence of binding site heterogeneity. These data fit a "two-site" model (p less than 0.001) in which one binding component has high affinity (Kd = 2.5 ng/ml = 0.6 nM) and low capacity (10(4) sites/cell) while the other has low affinity (Kd = 5.9 micrograms/ml = 1.5 microM) and high capacity (greater than 10(7) sites/cell). Similar high- and low-affinity [125I]bPTH(1-34) binding sites were seen also in CRL 1564 membranes containing a PTH-responsive adenylate cyclase. The Kd of the high-affinity sites was identical to the concentration of unlabeled bPTH(1-34) (4.2 ng/ml = 1.0 nM) required to half-maximally elevated cyclic AMP in CRL 1564 cells. Affinity labeling of specific PTH binding sites revealed the presence of multiple components with Mrs of 85, 70, 40, 33, and 23 kD on SDS-PAGE. Competition experiments did not disclose structurally discrete high- and low-affinity sites. Thus, structurally homologous PTH receptors in human skin fibroblasts apparently can assume two affinity states: (i) a high-affinity state coupled to adenylate cyclase and (ii) a low-affinity state that may represent uncoupled receptors.

Adenylyl Cyclases↗

C-peptide in non-alcoholic cirrhosis and hepatocellular carcinoma.

Fourteen normal controls, eleven patients with non-alcoholic cirrhosis, twenty-nine with hepatocellular carcinoma (HCC) and six with HCC and hypoglycemia were studied. The tests performed include iv glucose tolerance test (25 g) and glucagon challenge test (2 mg). In cirrhosis, glucose intolerance and insulin resistance were demonstrated. The fasting hyperinsulinemia in cirrhosis is the result of decreased degradation as shown by the normal fasting C-peptide. The increased insulin responses to glucose, despite a normal C-peptide response, further supports the importance of impaired degradation in the pathogenesis of hyperinsulinemia after challenge. Despite a strong etiological association between cirrhosis and HCC, patients with HCC do not have significant hyperinsulinemia or glucose intolerance. This provides metabolic evidence to support the clinico-pathological observation that HCC occurred when cirrhosis was not advanced or in a precirrhotic stage. In HCC patients with clinically overt hypoglycemia, the fasting glucose, insulin and C-peptide were very low. The C-peptide responses to glucose and glucagon challenges were suppressed despite pharmacologic stimulation. This can be explained by the suppression of insulin secretion by a circulating substance secreted by hepatoma. The results support the pathogenetic importance of insulin-like activities recently detected in HCC patients with hypoglycemia.

Adult↗

The use of glucagon challenge tests in the diagnostic evaluation of hypoglycemia due to hepatoma and insulinoma.

We previously found that patients with hypoglycemia due to chronic renal and liver disease had anomalous metabolic responses to glucose and glucagon stimulation. In this study we evaluated the use of glucagon (2 mg, iv) tests in the diagnosis of spontaneous hypoglycemia secondary to hepatocellular carcinoma (HCC) and insulinoma. Twenty-one normal subjects, 45 patients with HCC (11 with hypoglycemia), and 14 patients with insulinoma (all with hypoglycemia) were studied. The fasting blood glucose level was low in all patients with hypoglycemia. The fasting plasma insulin and C-peptide concentrations were high in patients with insulinoma and low in patients with HCC and hypoglycemia. The blood glucose responses to glucagon administration were less than normal in patients with HCC and hypoglycemia and within normal limits in patients with insulinoma. The insulinoma patients had increased plasma insulin and C-peptide responses to glucagon despite having low blood glucose levels. Compared with the HCC patients without hypoglycemia, HCC patients with hypoglycemia had impaired plasma insulin and C-peptide responses. The fasting hypoglycemia, hypoinsulinemia, and impaired insulin/C-peptide responses to glucagon in patients with hepatoma and hypoglycemia presumably reflect the production of insulin-like substances by the hepatoma. We conclude that glucagon administration results in characteristic responses in these groups of patients and can be of use in the diagnosis of spontaneous hypoglycemia secondary to hepatoma or insulinoma.

Adenoma, Islet Cell↗

Reduction of serum prolactin after salmon calcitonin infusion in patients with impaired renal function.

The physiological role of calcitonin is still uncertain. Recently human calcitonin gene-related peptide, produced by alternative RNA processing from the calcitonin gene, was shown to have structural homology to salmon calcitonin and probably have a modulator function in the hypothalamus. In this study, salmon calcitonin was infused at a low dose (10 MRC units over 30 min) in seven patients with impaired renal function (51-Cr-EDTA clearance = 34.8 +/- 4.8 ml/min) in order to elucidate its effects on PRL secretion. The results show that salmon calcitonin at a subhypocalcaemic dose significantly suppresses PRL secretion by over 40% (P less than 0.01) and may be of therapeutic use in the treatment of gonadal dysfunction in chronic renal failure.

Adult↗

Effects of selective and non-selective beta-blockers on the alanine and free fatty acid responses to glucagon challenge in hemodialysis patients.

Hypoglycemia is frequently reported in hemodialysis patients on propranolol. The effects of beta-blockers on the glucose, alanine and free fatty acid responses to glucagon challenge (2 mg) in fourteen hemodialysis patients were studied. Patients on propranolol had impaired glycemic response while those on metoprolol had decreased response only before dialysis. There was a significant negative correlation between propranolol level (log-transformed) and glycemic responses, suggesting that propranolol has direct effect on the latter. Hemodialysis patients had fasting alanine levels comparable to those of normal subjects. After glucagon challenge, the decrements in alanine level had no consistent relationship to the impaired glycemic response. Thus suppression of gluconeogenesis is unlikely to be the prime cause of propranolol-induced hypoglycemia. The basal free fatty acid levels were significantly lower among hemodialysis patients on propranolol. This limited availability of free fatty acid as well as the inhibitory effect on hepatic glucagon-stimulated glucose output may contribute to the predisposition to hypoglycemia in dialysis patients given propranolol. The results suggest that metoprolol has less interference on energy substrate supply in hemodialysis patients under fasting conditions.

Adrenergic beta-Antagonists↗

Anomalous adenosine cyclic 3':5'-monophosphate responses to glucagon in patients with hepatocellular carcinoma.

Glucagon resistance has been reported in rat hepatoma models. We studied the responses to glucagon challenge in 35 patients with hepato-cellular carcinoma. They have increased cyclic AMP and decreased glucose responses to glucagon (2 mg) challenge when compared with normal controls. Possible explanations for increased cyclic AMP responses include special membrane properties of hepatoma cells and increased adrenergic stimulation of adenylate cyclase during hypoglycemia. Decreased glucose responses are most apparent in patients with overt hypoglycemia. This may be related to a number of postulates, including depleted glycogen store of liver, impaired glycogenolysis, fatty metamorphosis, or insulin-like activities secreted by hepatoma. In this study, the increased cyclic AMP responses do not support the postulation that glucagon receptors are damaged in hepatocellular carcinoma.

Aged↗

Evaluation of Coomassie dye binding method for microprotein assay in diabetic proteinuria.

A simple and relatively cheap method for quantitating diabetic microproteinuria with Coomassie brilliant blue dye binding method was evaluated. It provides a proportional reactivity to urinary albumin as measured by the more expensive immunoassay. The significant correlation between haemoglobin A1 and microproteinuria shows that the quantity of urinary protein is affected by metabolic control of diabetes.

Adult↗

Hypoglycaemia and insulin resistance in uraemia associated with insulin fragments.

The pathogenetic role of insulin fragments in spontaneous hypoglycaemia and insulin resistance in chronic renal failure is discussed. Four different evidences are presented. In our studies, a dialysable 'toxin' with insulin-like actions was found in uraemia. Indeed small polypeptide fragments of hormones with potent activities have been recently identified in uraemic plasma. The varying bioactivities of different insulin fragments can explain the coexistence of insulin resistance and hypoglycaemia in these patients. As shown by our studies, removal of these fragments by haemodialysis results in normalisation of metabolic disturbances. However actual proof is difficult with the present technological problems.

Carcinoma, Hepatocellular↗

Rapid diagnosis of trichinosis by percutaneous muscle biopsy.

A new rapid diagnostic procedure for trichinosis is described. Percutaneous needle biopsy of the medial gastrocnemius muscle was used to obtain tissue for examination by a compression method. This procedure may facilitate early diagnosis and treatment of symptomatic trichinosis.

Adult↗

Effects of nadolol and propranolol on renal function in hypertensive patients with moderately impaired renal function.

Effects of oral administration of equipotent antihypertensive doses of propranolol and nadolol on renal function were examined in 20 hypertensive patients with moderately impaired renal function. Creatinine clearance increased, and serum beta 2-microglobulin concentrations decreased, when patients were switched from propranolol to nadolol therapy (creatinine clearance = 46.7 +/- 4.9 ml min-1 on propranolol and 52.7 +/- 5.9 on nadolol; beta 2-microglobulin = 6.14 +/- 0.66 mg l-1 on propranolol and 5.62 +/- 0.62 on nadolol). When patients were put back on propranolol, their creatinine clearances (45.9 +/- 5.0 ml min-1) and serum beta 2-microglobulin concentrations (6.51 +/- 0.67 mg l-1) returned to values comparable to those obtained before the change to nadolol was made. Serum beta 2-microglobulin concentrations correlated significantly with creatinine clearance (r = -0.819, P less than 0.001).

Adult↗