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Biomedical subjects

J A Colwell

Publications and source records attributed to J A Colwell.

At least 19 recordsLinked to original sources
PubMed1991

Pathophysiology of vascular disease in diabetes: effects of gliclazide.

Diabetes mellitus is a major risk factor for coronary heart disease, peripheral vascular disease, and cardiovascular disease. The prevalence of these complications is increased about two- to four-fold in people with diabetes in the United States, and they contribute substantially to morbidity, mortality, and healthcare costs. The pathogenesis of macrovascular disease in diabetes is multifactorial. Endothelial injury is an early event, followed by macrophage adherence and uptake of lipids to produce a fatty streak. Platelet adherence, aggregation, and release of thromboxane and platelet-derived growth factors may then occur. Quantitative and qualitative alterations of lipoproteins are seen, particularly in uncontrolled insulin-dependent and non-insulin-dependent diabetes. Hyperinsulinemia may be contributory, as may elevated plasma proinsulin levels. Glycation of plasma proteins and of components of the vascular wall occurs, and altered coagulation and/or fibrinolysis may lead to thrombosis. The process is accelerated by hypertension, smoking, and hypercholesterolemia. Gliclazide is an oral sulfonylurea agent that has been reported to have actions on platelet function and fibrinolysis in addition to its effects on glycemia. The evidence for this is reviewed, and recommendations for future studies are made.

Arteriosclerosis↗
PubMed1979

Urinary high density lipoprotein in minimal change glomerular disease and chronic glomerulopathies.

Serum lipids and lipoproteins and urinary apolipoprotein A (Apo A) were determined in two groups of patients. One group consisted of 11 children (ages ranging from 4 to 14 years) with minimal change glomerular disease. The other group consisted of 13 patients, eight less than 19 years old five adults, with different types of chronic glomerulopathy. Elimination of urinary lysozyme was a feature of chronic glomerulopathies, and creatinine clearances were also significantly lower in this group. Patients with chronic glomerulopathies had significantly lower HDL cholesterol and Apo A concentrations in their sera. In contrast, urinary Apo A concentrations were significantly higher in patients with chronic glomerulopathies, who also showed significantly lower urinary protein selectivities. Lipoprotein electrophoresis of urines containing Apo A showed distinct high-density lipoprotein (HDL) fractions, suggesting that HDL is eliminated in the urine as a result of increased glomerular permeability. This is also supported by a correlation coefficient of 0.77 between the selectivity indices and the ratio of urinary Apo A to total proteinuria. The determination of urinary Apo A appears to give valuable diagnostic information in patients with glomerular disease. According to our results the absence of urinary Apo A is very suggestive of minimal change glomerular disease.

Adolescent↗
PubMed1979

Platelet adhesion and aggregation in diabetes mellitus.

Platelets from diabetic patients show both increased platelet adhesiveness and sensitivity to aggregating agents. Plasma levels of the platelet-active von Willebrand Factor and the closely related factor-VIII antigen are significantly elevated, while factor VIII procoagulant activity is not. This may reflect either intravascular coagulation or disproportionate production or degradation. Plasma factors that enhance ADP-induced platelet aggregation are found in 50% of unselected male diabetics. Activity is clearly demonstrated only when plasma is added immediately prior to adding subthreshold doses of ADP to platelet-rich plasma obtained from control subjects. Systematic investigations of the molecular nature of such factors and their interactions with platelets are in progress. In platelets obtained from diabetic subjects, we have previously found increased sensitivity to the aggregating effects of arachidonic acid, and increased synthesis of immunoreactive prostaglandin E-like material. More recent studies have shown that platelets obtained from diabetic subjects are less sensitive to the antiaggregatory effects of imidazole, a thromboxane synthetase inhibitor. These observations suggest that increased synthesis of the labile aggregating substance thromboxane A2 also occurs in platelets obtained from diabetics. Collectively, these platelet and plasma abnormalities may contribute to accelerated vascular disease of diabetes. Prospective studies using antiplatelet agents are presently underway or in the planning stages in diabetics to explore their potential beneficial effects.

Adenosine Diphosphate↗
PubMed1979

Decreased high density lipoprotein cholesterol in hypopituitarism.

Serum triglyceride, cholesterol, and high density lipoprotein cholesterol (HDL-C) levels were measured in 10 men and 3 women with hypopituitarism. The mean total cholesterol and triglyceride levels were significantly increased but were within the range of controls. The mean HDL-C concentration and the HDL-C to total cholesterol ratio were significantly decreased. Similar findings were present in a patient with isolated GH deficiency. Two men with Kallman's syndrome and 3 patients with active acromegaly had values that were either within or just below the normal range. Replacement therapy with thyroid hormone and prednisone resulted in a normalization of HDL-C concentrations in four of the five patients studied. This improvement suggests a role for thyroid hormone and/or glucocorticoids in the maintenance of normal HDL-C concentrations. These observations also suggest that the distribution of plasma lipoprotein fractions is dependent in part, either directly or indirectly, on pituitary hormones.

Adolescent↗
PubMed1978

Rationale for antiplatelet agents in diabetic vascular disease.

Studies summarized in this paper indicate that some diabetics have increased sensitivity to platelet aggregating agents. The problem is in the platelet release reaction and may reflect increased synthesis of prostaglandins or their precursors. An interaction of plasma factor such as von Willebrand factor with platelets may also be involved. Based on these and other considerations, a prospective study on the use of aspirin and dipyridamole on diabetic lower extremity vascular disease is underway as a Veterans Administration Cooperative Study.

Blood Platelets↗
PubMed1977

Increased synthesis of prostaglandin-E-like material by platelets from patients with diabetes mellitus.

We studied the effects of ADP, epinephrine, collagen and arachidonic acid on platelet production of immunoreactive prostaglandin-E-like material and aggregation in 17 subjects with diabetes mellitus and 21 matched controls. Plateletrich plasma obtained from patients synthesized significantly (P less than 0.05) greater quantities of the prostaglandin-E-like material after exposure to 1 muM ADP, 1, 2 and 5 muM epinephrine and 1 microgram per milliliter of collagen than platelet-rich plasma obtained from controls. That obtained from the diabetic patients was significantly more sensitive (P less than 0.001) to the aggregating effects of the prostaglandin precursor, arachidonic acid, in vitro as compared to controls. Diabetic platelet-rich plasma metabolized arachidonic acid (0.5 mM) to immunoreactive prostaglandin-E-like material at a significantly greater rate (P less than 0.05) and extent (P less than 0.001) than that of controls. Thus, platelets obtained from diabetic patients possess increased activity of the prostaglandin synthetase system, and this characteristic may be related to the increased platelet aggregation associated with the disease.

Adenosine Diphosphate↗
PubMed1977

Serum high density lipoprotein in diabetic patients.

The purpose of the present investigation was the study of HDL lipoprotein changes in patients with diabetes mellitus. The comparison was made between 40 normal and 109 diabetic subjects and the following data was obtained: relative HDL concentration (polyacrylamide gel electrophoresis), HDL-cholesterol and apolipoprotein A concentrations. We found significant decreases in HDL (18-28%) and HDL-cholesterol (31-40 mg/100 ml) in most diabetics except in those with normalized serum levels of glucose and lipids (34% and 50 mg/100 ml respectively). There was a statistically significant difference in HDL and HDL-cholesterol concentrations between patients in the latter group and other diabetic patients. There was a negative correlation between HDL and HDL-cholesterol and serum glucose levels. No statistically significant difference was found when apolipoprotein A was compared in normal and diabetic subjects. Our results suggest that a deficient binding of cholesterol to apoprotein A might be present in diabetes.

Adult↗
PubMed1977

Correlation of platelet aggregation, plasma factor activity, and megathrombocytes in diabetic subjects with an without vascular disease.

Second-phase platelet aggregation induced by adenosine diphosphate (ADP) and epinephrine was measured in fasting platelet-rich plasma in normals, "prediabetics," and diabetics with or without vascular disease. "Plasma factor" potentiation of ADP-induced second-phase platelet aggregation was also estimated, as were megathrombocyte numbers in the same patient groups. There was an increased sensitivity of second-phase platelet aggregation noted with both aggregating agents in all diabetic groups except for the prediabetics. This activity was paralleled by an increase in plasma factor activity. In vivo evidence of an increased turnover of platelets in frank diabetics was suggested by increased numbers of megathrombocytes. These studies demonstrate that platelets from diabetics are sensitive to aggregating agents and that this sensitivity may be related to plasma factor(s) present in diabetics. In vivo platelet aggregation may be present in diabetics. Longitudinal studies will be necessary to establish the relationship of these findings to the genesis of diabetic vascular disease.

Adult↗
PubMed1977

The effect of oral glucose on von Willebrand factor activity in normal and diabetic subjects.

We have previously noted increased platelet aggregation and high von Willebrand factor activity in patients with chemical diabetes. In this paper we have studied platelet aggregation, plasma glucose, insulin, free fatty acids, growth hormone, and von Willebrand factor activity during the glucose tolerance test in six normal and six chemical diabetic subjects. The results suggest that von Willebrand factor activity is suppressed coincident with the rise of glucose and insulin and provide further evidence of hormonal and metabolic control of levels of von Willebrand factor activity.

Aged↗
PubMed1977

Relation between growth hormone levels and Von Willebrand factor activity.

The relationship between growth hormone and von Willebrand factor activity was studied in fasting plasma samples, nocturnal samples, and after intramuscular injection of growth hormone. A significant correlation was seen between the two levels in fasting samples. During sleep, peaks of growth hormone were associated with peaks of von Willebrand factor activity. A subject with isolated growth hormone deficiency had no peaks of either. Intramuscular injection of growth hormone produced a rise of von Willebrand factor activity in all subjects studied. These results indicate that there is a relationship between growth hormone and von Willebrand factor activity.

Adult↗
PubMed1977

Cholesterol determination in high-density lipoproteins separated by three different methods.

We describe a simplified method for measuring high-density lipoprotein cholesterol in serum after very-low- and low-density lipoproteins have been precipitated from the specimen with sodium phosphotungstate and Mg2+. Values so obtained correlate well with values obtained with the heparin-Mn2+ precipitation technique (r = 0.95, CV less than 5% in 66% of the subjects studied and between 5 and 10% in the remaining ones) or by ultracentrifugal separation (r = 0.82, CV less than 5% in 80% of the subjects studied and between 5 and 10% in the remaining ones). Our precipitation technique is more appropriate for routine clinical laboratory use.

Adult↗
PubMed1977

Hypoglycemia.

In the present review, we have tried to briefly define the types of hypoglycemia which may be seen most frequently in medicine. Wherever possible, mechanisms and appropriate diagnostic tests have been described. Treatment of hypoglycemia has been purposely avoided, since therapy should be obvious once diagnosis is made and mechanisms are understood. While it is recognized that this review is not exhaustive, it should cover over 95 per cent of the cases of hypoglycemia encountered by the practicing physician.

Fasting↗