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Biomedical subjects

T S Jap

Publications and source records attributed to T S Jap.

At least 19 recordsLinked to original sources

Measurement of creatine kinase isoforms by agarose gel electrophoresis in the diagnosis of myocardial infarction.

To evaluate a method to quantitate the isoforms of serum creatine kinase isoenzyme MM (CK-MM) by agarose gel electrophoresis, sera of normal subjects (n = 74) and patients with acute myocardial infarction (n = 21) and other diseases (n = 67) were studied. The within-assay imprecision (CV) for CK-MM1, -MM2, and -MM3 was 1.9%, 0.8%, and 2.2% at the activity of 79, 105, and 64 U/L (30 degrees C, CK-NAC), respectively; while the assay-to-assay imprecision was 4.8%, 3.2% and 3.9%, respectively. The method could detect 5 U/L or more of any CK-MM isoform and was linear with respect to CK activity at values less than 1100 U/L. Sera from healthy subjects (n = 74) contained mainly CK-MM1 (mean = 48.5%), with lesser amounts of CK-MM2 (mean = 30.6%) and CK-MM3 (mean = 20.8%). The central 95-percentile reference range for the ratio of MM3/MM1 was 0.12-1.34 with mean = 0.49. The sensitivity of CK-MM3/MM1 ratio greater than 1.3 in the diagnosis of acute myocardial infarction employing the first available sample was 90% at a specificity of 91%, compared with a sensitivity of 81% and specificity of 87% for the conventional CK-MB assay. At CK-MM3/MM1 ratio of 1.6 or more, the specificity increased to 96% while sensitivity remained unchanged at 90%. This procedure for the quantitation of serum CK-MM isoforms is convenient, practical and suitable for inclusion in the routine panel of cardiac tests.

Adult

Insulin-pen: preliminary report on its use for multiple injection regiment in insulin-dependent diabetic patients.

Insulin pens are pen-like devices for multiple injection of insulin. They can cut down the equipment necessary for a multidose regimen and thus make the therapy more convenient and flexible to help improve daily-life quality. It is of interest for us to known whether the average diabetic patients are motivated to achieve better metabolic control by means of insulin-pens. Seven insulin-dependent diabetic patients (male: 3, female: 4, age: 21-34 years) from the Veterans General Hospital participated in the study. None of them had diabetic proliferative retinopathy or proteinuria. They are initially treated with twice daily injection of mixtures of short- and intermediate-acting insulin (run-in period, 8 weeks). A multi-dose regimen with three premeal injections of short-acting insulin with insulin-pen plus one injection of long-acting insulin at bedtime was then used during the study period (12 weeks). Improved in metabolic control as assessed by HbAlc (7.6 +/- 0.9 vs 6.9 +/- 0.8%) and mean blood glucose (175.2 +/- 34 vs 152.3 +/- 28.1 mg/dl) in all patients was found. The frequency and severity of hypoglycemic episodes were not changed. In addition, all patients chose to continue multiple injection using insulin-pen, indicating a high acceptability of such device.

Adult

Metabolic control and B cell function in patients with diabetes mellitus secondary to chronic pancreatitis.

To investigate the relationship between metabolic control and beta cell functions in chronic pancreatitis, 30 patients were selected for study, including 10 with diabetes mellitus in insulin-dependent state (group 1, Mean age 37.6), 10 with diabetes mellitus in non-insulin-dependent state (group 2, Mean age 47.8), and 10 with normal fasting glucose levels (group 3, Mean age 42.1). Each patient received urine routine, stool fat, renal function, biochemical study such as: serum lipid and glycosylated hemoglobin, eye fundi and X-ray examinations. Beta cell function was measured by C-peptide concentration six minutes after intravenous infusion of 1 mg glucagon. The results showed that the glycosylated hemoglobin concentrations were higher in group 1 than in group 2 or 3 patients (P less than 0.05), and were higher in group 2 than in group 3 patients (P less than 0.001) as well. The cholesterol and triglyceride levels were not significantly different among three groups. Furthermore, eight and two of group 1 and 2 patients manifested pancreatic calcification on abdomen X-ray examination (P less than 0.05). All and eight of group 1 and 2 patients received insulin injection respectively. In addition, group 1 patients were more likely to develop steatorrhea, other associated diseases and uncontrolled plasma glucose levels as compared with group 2 patients. In conclusion, insulin-dependent pancreatic diabetics had more advanced disease process and were therefore more likely to get other associated diseases than noninsulin-dependent pancreatic diabetics.

Adult

The establishment of radioimmunoassay of cyclic AMP.

Succinyl cyclic AMP, coupled with human albumin, was injected into rabbit to elicit antibodies to the cyclic nucleotide hapten. The succinyl cyclic nucleotides were conjugated to human albumin through a carbodiimide coupling procedure. The radioligand was prepared essentially by the modified method of Hunter and Greenwood. The resulting radiolabeled 125-ScAMP-TME was subsequently purified by reverse phase chromatography on Seppak C18 cartridge and used as tracers. Free and bound form of labeled antigens in the assay system were separated according to their differences in adsorption to solid material, i.e., charcoal. The antisera in routine use had 8% cross-reactivity with cyclic GMP, but had no cross-reactivity with ADP, 5'-AMP or ATP. The sensitivity of the assay in standard was around 0.05 pmol/ml. The sequential saturation analysis system was superior to the equilibrium study in terms of its sensitivity in standard curve determination. The media dilution and recovery studies showed good parallelism with the standard curve. The intra-assay and inter-assay coefficient variations were 5% and 7%, respectively. It showed that a significant increase in tracer binding to the antibodies in equilibrium incubating system was obtained when they were incubated at 4 degrees C for up to 72 hours. When the standard curve was derived for Scatchard plot analysis, Kd of the curve decreased inversely with the increase of the antibodies diluted, the total binding capacity of the antibody would not alter. A thyroid-stimulating hormone produced a normal response of cyclic AMP concentrations in FRTL-5 tissue cultures.

Animals

Arginine induced insulin release in patients with newly onset non-insulin-dependent diabetes mellitus.

To examine the release of insulin in response to oral glucose, intravenous glucagon and intravenous arginine, we measured the levels of plasma glucose, immuno-reactive insulin (IRI) and C-peptide levels on fasting and following an oral glucose loading (OGTT), intravenous glucagon (GON) and arginine (ARG) infusion test in nine newly diagnosed non-insulin dependent diabetics. Their ages ranged from 38 to 65. The fasting plasma glucose and hemoglobin A1c levels were 240 +/- 14 mg/dl (Mean +/- SEM) and 10.7 +/- 0.54%, respectively. Mean values of the peak C-peptide/fasting C-peptide ratio and peak IRI/fasting IRI ratio were significantly increased, as compared with the basal level (P < 0.05), but not significantly different from those of the OGTT, GON and ARG test. In conclusion, the effect of arginine-induced insulin secretion in non-insulin dependent diabetes mellitus is as good as those of glucose or glucagon.

Adult

Fibrinolytic activity in Chinese patients with diabetes or hyperlipidemia in comparison with healthy controls.

Plasma tissue-type plasminogen activator (tPA), plasminogen activator inhibitor (PAI) and euglobulin lysis time (ELT) were determined before and after the venous occlusion test (VOT) in 3 groups of patients with mean age about 60 years: 29 diabetic patients (D group), 8 hyperlipidemic patients (H group) and 19 healthy controls (C group). In the D and H groups, the mean of morning tPA was significantly higher than that of the C group, but the means of PAI were not significantly different among the 3 groups. ELT was significantly shortened and tPA was markedly increased after the VOT in all 3 groups whereas PAI had not significantly changed. In conclusion, high tPA activity and good fibrinolytic response without significant change of PAI activity were found in the diabetic and hyperlipidemic patients, and no definite impairment of the fibrinolytic activity could be found in the Chinese patients with diabetes and hyperlipidemia. This might be one of the reasons why the Chinese has low incidence of thromboembolic diseases.

Aged

A twelve month double-blind randomized study of the efficacy and immunogenicity of human and porcine insulins in non-insulin-dependent diabetics.

This study aims to compare the effectiveness and immunogenicity of semisynthetic human insulin (NOVO) and highly purified (monocomponent) porcine insulin over a 12 month period in 16 non-insulin-dependent diabetic subjects not previously exposed to insulin. Sixteen patients were randomly allocated for treatment with either human (n = 9) or monocomponent porcine (n = 7) insulin in a double-blind trial. Both groups were identical with respect to age, sex and measures of metabolic control. Significant insulin antibody was detected in seven of the nine patients (78%) 3 months after the commencement of human insulin therapy whereas it was detected in all patients (100%) in the group treated with monocomponent porcine insulin as early as 2 months after insulin therapy. Besides the delayed rise of insulin antibodies during the first 3 months of human insulin therapy, it tended to have a lower mean insulin antibody titer, though statistically insignificant, at the end of the study. No adverse reaction to either type of insulins was noted. It is concluded that both semisynthetic human and monocomponent porcine insulin were safe and effective. Although human insulin showed a slightly lower immunogenicity than monocomponent porcine insulin of the same formulation and purities, it was not non-immunogenic. Hence, there is no reason to treat all insulin-requiring diabetic subjects with human insulin except those who have developed insulin allergy or those at risk or with a history of allergy.

Adult

Insulin treatment improved glucose-induced insulin release in elderly non-insulin-dependent diabetes mellitus, secondary failure to oral hypoglycemic agents.

In order to observe whether the improvement of diabetic control would promote insulin release of elder non-insulin-dependent diabetics, we performed oral glucose tolerance test and glucagon infusion in eight patients before and after fasting plasma glucose normalized with insulin therapy for three weeks. The levels of plasma glucose and C-peptide both on fasting and following intravenous glucagon infusion and oral glucose loading were measured. Their ages ranged from 60 to 72 years old. The initial fasting plasma glucose levels were 261 +/- 18 mg/dl (Mean +/- SEM). After insulin therapy for three weeks, the fasting plasma glucose levels dropped to 130 +/- 8 mg/dl (Mean +/- SEM, P less than 0.001). The fasting C-peptide/glucose ratio showed no difference before and after therapy. On the other hand, the C-peptidogenic index was markedly improved following insulin therapy, as compared with the value before therapy (P less than 0.05). These results suggested that greater C-peptide response was found in non-insulin dependent elderly diabetics following oral glucose after plasma glucose normalized with insulin therapy.

Administration, Oral

Changes of insulin receptor in aortic endothelial cells from diabetic rats.

Endothelial cells are likely to play an important role in the development of diabetic vascular diseases since they are exposed directly to the abnormal circulating metabolites of diabetes and may be easily damaged early in the natural course of vascular complications. Recently, we have demonstrated a decrease of insulin binding and autophosphorylation of the insulin receptor in cultured capillary endothelial cells of diabetic rats. In this study, similar defects in insulin receptor of aortic endothelial cells cultured from diabetic BB rats were found. The specific insulin binding was 45% lower in cells from diabetic than from non-diabetic rats (3.9 +/- 1.3 vs 7.3 +/- 1.2% per mg protein, p less than 0.05), which was due to a decrease of cell surface binding sites. In contrast to the decrease in insulin binding, insulin-like growth factor-I binding was higher in cells of diabetic than control rats (20.6 +/- 5.6 vs 13.7 +/- 4.6% per mg protein). The decrease in insulin binding could not be induced by the two-week treatment of endothelial cells from non-diabetic rats with medium containing high concentration of glucose (400 mg/dl). Insulin-induced tyrosine kinase activity of partially purified insulin receptor measured using poly-glutyr as substrate was also lower in cells from diabetic rats (normal:1.4 +/- 0.6-fold; diabetic 0.5 +/- 0.3-fold above baseline; (p less than 0.05). These data suggest that the diabetic milieu in vivo can induce persistent defects in insulin receptor of aortic endothelial cells. Further studies are warranted to understand the potential pathophysiological role of these defects.

Animals

Fanconi syndrome: report of a case.

A 59-year-old female patient was admitted because of muscle weakness in all four limbs for a period of 5 days. She had been found to have Graves' disease 4 years ago previous to this, and had received a subtotal thyroidectomy 1 year later. Hypothyroidism supervened and she had been receiving levothyroxine replacement in recent years. She also had non-insulin-dependent diabetes, which was controlled with diet only. During the 5 days prior to admission, she developed muscle weakness which finally worsened to complete paralysis of all four limbs. Physical examination showed tenderness and weakness of the extremity muscles. Abnormal laboratory data included serum K, 1.6 mEq/L; P, 1.2 mg/dl; uric acid, 1.6 mg/dl; fasting glucose, 267 mg/dl; T3, 36.65 ng/dl; T4, 4.0 micrograms/dl; TSH, 5.35 mu u/ml; free T4, 0.57 ng/dl; and metabolic acidosis with pH, 7.298; PCO2, 27.0 mmHg; and HCO3, 12.8 mEq/L. An EKG showed a prominent U wave, and urinalysis revealed renal glucosuria and massive aminoaciduria. An oral sodium bicarbonate loading test showed an increasing loss of bicarbonate through the urine, while the plasma bicarbonate level was elevated. Clinical manifestations improved after the administration of sodium bicarbonate, potassium chloride and neutral phosphate.

Autoimmune Diseases

Intractable diabetic ketoacidosis due to insulin antibody--response to steroid therapy.

To examine the effect of steroid therapy on insulin antibody titer in insulin-dependent diabetes mellitus, we studied a 58 year-old gentleman with recurrent diabetic ketoacidosis. No any overt precipitating factors could be accounted for, except limited pancreatic beta cell reserve and high titers of anti insulin antibodies. Despite the persistence of high titers of plasma antiinsulin antibodies, the clinical manifestations of diabetic ketoacidosis improved greatly by the administration of steroid. Nevertheless, the patient still showed the great excursion of plasma glucose concentration.

Diabetes Mellitus, Type 1

Thyrotropin-and prolactin--secreting pituitary tumor dissociated hormonal response to bromocriptine.

A 41-year-old male with recurrent hyperthyroidism resulting from pituitary tumor was studied. Because of recurrent hyperthyroidism, he had been treated with propylthiouracil for four years and had been operated. At the time of high serum thyroid hormone (T4: 20 micrograms/dl; T3:502 ng/dl), there was also elevated basal serum TSH level (55 microU/ml) which could not be suppressed by exogenous thyroid hormone administration. In addition, the serum TSH showed blunt response to intravenous TRH infusion. An elevated serum prolactin level was also observed (111 ng/ml). After bromocriptine administration (2.5 mg daily), the suppressibility of serum TSH level was found better than that of prolactin level. The existence of a TSH- and PRL-secreting pituitary tumor in this patient exhibited a dissociated hormonal response to low doses of dopaminergic agents.

Adult

Comparison of insulin secretion and insulin sensitivity between normal and impaired glucose tolerance subjects with normal fasting plasma glucose.

To examine glucose-stimulated insulin secretion and insulin sensitivity in the normal subjects and patients with impaired glucose tolerance, we performed the oral glucose tolerance test (OGTT) and modified insulin suppression test in 34 non-obese subjects. The plasma glucose and insulin concentrations were measured during fasting and every 30 min up to 120 min following 75 g of oral glucose loading. Ten subjects were classified as impaired glucose tolerance (IGT), and 24 subjects were as having normal glucose tolerance. In addition, the insulin-stimulated glucose uptake was estimated in all subjects by measuring the final 30 min steady-state plasma glucose (SSPG) of a continuous infusion of somatostatin, insulin and glucose for 4 hours (modified insulin suppression test). The mean plasma glucose concentrations of fasting and 60, 90, 120 min during OGTT study were significantly higher in the IGT subjects than in the normals. In addition, the mean incremental glucose areas under the curve during OGTT study were also greater in the IGT subjects than in the normals. The mean serum insulin concentrations were significantly higher at 90 and 120 minutes in the IGT patients than in the normals. During the modified insulin suppression test, the mean SSPG concentrations were significantly higher in the IGT patients than in the normals under the similar steady-state plasma insulin in both groups. There was a good correlation between the incremental insulin areas under the curve (OGTT) and the SSPG in the normal subjects (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Coexisting hyperthyroidism and hyperparathyroidism: two cases report.

To examine the biochemical changes in coexisting hyperthyroidism and hyperparathyroidism, we have studied two female cases in our medical center. Both patients received biochemistry study, thyroid function test, thyroid autoantibody determination, parathyroid function tests and thyroid scan. They all had increased thyroid function. The concentration of parathyroid hormone was found to elevate in both cases. After thyroid function turned normal, hypercalcemia was still present. Both patients underwent neck operation. Parathyroid adenoma was found in both cases. The pictures of thyroid pathology showed diffuse hyperplasia in one case and lymphocytic thyroiditis in the other case.

Adenoma

Severe rhabdomyolysis induced acute renal failure, caused by diabetic ketoacidosis.

A 23 year-old obese Chinese gentleman was admitted to our hospital with the main problem of conscious disturbance for one day. The physical examination and laboratory data confirmed that this is a case of diabetic ketoacidosis complicated with rhabdomyolysis resulting in acute renal failure three days after admission, and regained his renal function after intensive hemodialysis and other conservative treatment.

Acute Kidney Injury

Insulin secretion and sensitivity in acromegaly.

To examine the effect of excess growth hormones on carbohydrate metabolism, we studied glucose-stimulated insulin secretion and glucose utilization in 6 patients with acromegaly and 6 age-, sex- and weight-matched normal subjects. The levels of plasma glucose and serum insulin were determined during fasting and every 30 min up to 180 min after 75 g of oral glucose loading. In addition, plasma glucose, serum insulin and serum C-peptide were measured during euglycemic glucose clamp with insulin infusion of 40 mU/m2,min-1. The acromegalic patients had significantly higher mean levels of fasting plasma glucose (p less than 0.05) and insulin (p less than 0.01). After glucose loading for 3 h, the acromegalic patients also had a higher incremental area under the curve of plasma glucose (p less than 0.05) and serum insulin (p less than 0.05). However, no significant difference in the fasting molar ratio of C-peptide/IRI was noted between these two groups. During euglycemic clamp studies, the steady-state serum insulin levels were identical between the two groups. The glucose disposal rate was lower in acromegalics than in normal subjects (p less than 0.01). The results demonstrated that glucose intolerance, hyperinsulinemia and insulin resistance are present in acromegalic patients.

Acromegaly

Hyperparathyroidism presenting as a large bone tumour. A case report.

A 59-year-old man, who presented to hospital with a large expansile bone tumour over the left elbow and a mass in the right side of the neck, was eventually found to have parathyroid adenoma manifesting clinically as severe hypercalcaemia. Histological examination of a section of the neck mass showed parathyroid adenoma and the bone biopsy specimen revealed a 'brown tumour', consistent with hyperparathyroid bone disease.

Adenoma

Insulin secretion and sensitivity in hyperthyroidism.

To examine the effect of hyperthyroidism on carbohydrate metabolism, we studied glucose-stimulated insulin secretion and glucose utilization in 8 subjects with Graves' disease before and after treatment for hyperthyroidism and 8 age-, sex- and weight-matched normal subjects. Subjects with Graves' disease had significant elevated serum levels of thyroxine (24.81 +/- 2.44 micrograms/dl, mean +/- SEM) and triiodothyronine (459 +/- 5.5 ng/dl, mean +/- SEM). Simultaneous measurement of plasma glucose, serum insulin and C-peptide levels during fasting and every 30 minutes up to 180 minutes after 75 g oral glucose loading was determined. In addition, plasma glucose, serum insulin and serum C-peptide were measured during euglycemic glucose clamp with insulin infusion of 40 mU/m2 min-1. Mean fasting plasma glucose (P less than 0.05, serum insulin (P less than 0.005) and serum C-peptide (P less than 0.005) levels were significantly higher in the hyperthyroid patients. After glucose loading, the plasma glucose (P less than 0.05), serum insulin (P less than 0.05) and C-peptide (P less than 0.05) responses were significantly higher in hyperthyroid patients at all times up to 180 minutes. During euglycemic clamp studies, the steady-state serum insulin levels were identical in the two groups. The glucose disposal rate was lower in hyperthyroid patients before treatment (P less than 0.01) than in normal subjects. After thyroid function had been normalized for 2 to 4 weeks, the glucose disposal rate increased significantly (P less than 0.05), but was still significantly lower than those of normal subjects (P less than 0.05). Our data show that patients with Graves' hyperthyroidism manifest glucose intolerance, hyperinsulinemia and insulin resistance.

Administration, Oral