167 results on '"Colwell JA"'
Search Results
52. Oral treatment of diabetes mellitus: the contribution of gliclazide.
- Author
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Colwell JA
- Subjects
- Humans, Diabetes Mellitus, Type 2 drug therapy, Gliclazide therapeutic use
- Published
- 1991
53. Pathophysiology of vascular disease in diabetes: effects of gliclazide.
- Author
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Colwell JA
- Subjects
- Arteriosclerosis etiology, Blood Platelets drug effects, Diabetic Angiopathies drug therapy, Endothelium, Vascular drug effects, Humans, Diabetic Angiopathies etiology, Gliclazide therapeutic use
- Abstract
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.
- Published
- 1991
- Full Text
- View/download PDF
54. Vitamin E and platelet eicosanoids in diabetes mellitus.
- Author
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Gisinger C, Watanabe J, and Colwell JA
- Subjects
- Animals, Blood Platelets metabolism, Humans, Blood Platelets drug effects, Diabetes Mellitus metabolism, Eicosanoids metabolism, Vitamin E pharmacology
- Published
- 1990
- Full Text
- View/download PDF
55. Hemostatic alterations with exercise conditioning in NIDDM.
- Author
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Hornsby WG, Boggess KA, Lyons TJ, Barnwell WH, Lazarchick J, and Colwell JA
- Subjects
- Diabetes Mellitus, Type 2 physiopathology, Enzyme-Linked Immunosorbent Assay, Glucose Tolerance Test, Humans, Male, Middle Aged, Tissue Plasminogen Activator blood, Diabetes Mellitus, Type 2 blood, Fibrinogen analysis, Fibrinolysis, Fibronectins blood, Physical Exertion, Plasminogen analysis
- Abstract
Various parameters of coagulation and fibrinolysis were measured in 13 men (aged 54 +/- 3 yr) with non-insulin-dependent diabetes mellitus (NIDDM) before and after 12-14 wk of exercise training. Subjects exercised for 30 min 3 times/wk at 70% of maximum O2 consumption (VO2max). Training increased VO2max by 12.5% but did not alter body weight, relative body fat, blood pressure, cholesterol, triglycerides, or high-density lipoprotein cholesterol. Slight downward trends were apparent for fasting glucose and insulin, but glycosylated hemoglobin was unchanged. There were no changes in coagulation parameters of plasminogen, hematocrit, or alpha 2-antiplasmin. Plasma fibrinogen (303 +/- 24.2 vs. 256 +/- 12.3 mg/dl) and fibronectin (380 +/- 41.9 vs. 301 +/- 22.2 micrograms/ml) were significantly reduced (P less than 0.02) by exercise conditioning. Three assays of fibrinolytic activity (tissue plasminogen activator, euglobulin lysis time, and an isotopic measure of fibrinolysis) confirmed that neither basal fibrinolysis nor the fibrinolytic responses to venous occlusion and maximal exercise were significantly altered. Exercise conditioning may have antithrombotic effects in NIDDM by reducing plasma fibrinogen and fibronectin. Although the significance of the fall in fibronectin awaits further studies, the reduction in plasma fibrinogen gives a rationale for the use of exercise training in men with NIDDM.
- Published
- 1990
- Full Text
- View/download PDF
56. New concepts about the pathogenesis of atherosclerosis in diabetes mellitus.
- Author
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Colwell JA, Winocour PD, Lopes-Virella M, and Halushka PV
- Subjects
- Animals, Arachidonic Acid, Arachidonic Acids metabolism, Blood Platelets metabolism, Cholesterol metabolism, Cholesterol, HDL, Cholesterol, LDL, Diabetes Mellitus metabolism, Endothelium metabolism, Epoprostenol metabolism, Fibrinolysis, Humans, Lipoproteins metabolism, Lipoproteins, HDL metabolism, Lipoproteins, IDL, Lipoproteins, LDL metabolism, Lipoproteins, VLDL metabolism, Plasminogen Activators metabolism, Platelet Aggregation, von Willebrand Factor analysis, Arteriosclerosis etiology, Diabetic Angiopathies etiology
- Abstract
New concepts about the pathogenesis of atherosclerosis in diabetes mellitus are presented. Emphasis is given to alterations of endothelial function, as indicated by von Willebrand factor activity, prostacyclin release, and fibrinolytic activity in diabetes mellitus. Previous work on platelet aggregation and arachidonic acid metabolism is updated and recent findings are emphasized. The atherogenic mix of elevated low-density lipoprotein cholesterol and low high-density lipoprotein cholesterol levels in uncontrolled diabetes mellitus is noted. The lipid hypothesis is extended by consideration of very low-density lipoprotein and intermediate-density lipoprotein metabolism in diabetes. Lipoprotein-cell interactions that may contribute to atherosclerosis are reviewed and suggestions are made for future research in order to clarify the pathogenesis of atherosclerosis in diabetes mellitus.
- Published
- 1983
- Full Text
- View/download PDF
57. Increased synthesis of prostaglandin-E-like material by platelets from patients with diabetes mellitus.
- Author
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Halushka PV, Lurie D, and Colwell JA
- Subjects
- Adenosine Diphosphate pharmacology, Arachidonic Acids pharmacology, Collagen pharmacology, Epinephrine pharmacology, Female, Humans, Male, Stimulation, Chemical, Blood Platelets metabolism, Diabetes Mellitus blood, Platelet Aggregation drug effects, Prostaglandins E biosynthesis
- Abstract
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.
- Published
- 1977
- Full Text
- View/download PDF
58. Vascular disease in diabetes: pathophysiological mechanisms and therapy.
- Author
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Colwell JA, Halushka PV, Sarji KE, Lopes-Virella MF, and Sagel J
- Subjects
- Arteries metabolism, Arteriosclerosis metabolism, Arteriosclerosis therapy, Capillary Permeability, Diabetic Angiopathies metabolism, Diabetic Angiopathies therapy, Endothelium, Humans, Lipid Metabolism, Platelet Adhesiveness, Platelet Aggregation, Arteriosclerosis physiopathology, Diabetic Angiopathies physiopathology
- Published
- 1979
59. Treatment of diabetes mellitus.
- Author
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Colwell JA
- Subjects
- Diabetes Complications, Diabetes Mellitus physiopathology, Diabetic Ketoacidosis complications, Drug Hypersensitivity, Drug Resistance, Humans, Infections complications, Stress, Physiological, Diabetes Mellitus drug therapy, Insulin therapeutic use
- Published
- 1976
60. Pathogenesis of atherosclerosis in diabetes mellitus.
- Author
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Colwell JA, Lopes-Virella M, and Halushka PV
- Subjects
- Arteriosclerosis physiopathology, Blood Platelets physiology, Diabetic Angiopathies drug therapy, Humans, Insulin therapeutic use, Platelet Aggregation, von Willebrand Factor physiology, Arteriosclerosis etiology, Diabetic Angiopathies physiopathology
- Abstract
Numerous studies have shown that patients with diabetes mellitus have accelerated atherosclerotic vascular disease, and major advances in understanding it pathogenesis have been made. Current suggestions are that endothelial injury may be the initial event in the genesis of atherosclerosis, followed by platelet adhesion and aggregation at the site of injury. In diabetes, evidence of endothelial dysfunction is present. Smooth muscle cell proliferation is an important pathologic finding in atherosclerosis. This process is stimulated by a platelet mitogen, which has been partially characterized. The mitogen has not been studied in diabetes. Lipid accumulation in the area of the atherosclerotic lesion is primarily in the form of intracellular and extracellular esterified cholesterol. In uncontrolled diabetes, elevated plasma low density lipoprotein levels and decreased plasma high density lipoprotein levels favor lipid deposition in large vessels. There is evidence of a thrombotic state in certain diabetic patients. Collectively, these abnormalities of endothelial, platelet, smooth muscle, lipoprotein, and coagulation behavior may be viewed as contributing to the problem of accelerated atherosclerosis in diabetes. A thorough understanding of the pathogenesis of this process aids in designing appropriate preventive therapeutic approaches.
- Published
- 1981
- Full Text
- View/download PDF
61. Surface binding, internalization and degradation by cultured human fibroblasts of low density lipoproteins isolated from type 1 (insulin-dependent) diabetic patients: changes with metabolic control.
- Author
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Lopes-Virella MF, Sherer GK, Lees AM, Wohltmann H, Mayfield R, Sagel J, LeRoy EC, and Colwell JA
- Subjects
- Adolescent, Adult, Blood Glucose analysis, Cells, Cultured, Child, Diabetes Mellitus blood, Diabetes Mellitus drug therapy, Diabetes Mellitus, Type 1 blood, Diabetes Mellitus, Type 1 drug therapy, Female, Humans, Lipids blood, Male, Diabetes Mellitus metabolism, Diabetes Mellitus, Type 1 metabolism, Fibroblasts metabolism, Insulin therapeutic use, Lipoproteins, LDL metabolism
- Abstract
A previous study of low density lipoprotein metabolism by cultured cells focused on the metabolism of normal lipoproteins in vitro by fibroblasts isolated from diabetic patients. No abnormalities were found. We have followed the opposite approach. Using normal human fibroblasts as test cells we compared the metabolism in vitro of low density lipoproteins isolated from diabetic patients before and after metabolic control. We found a significant decrease (p less than 0.02) in internalization and degradation of low density lipoproteins isolated from diabetic patients before metabolic control when compared with those isolated from normal control subjects or from the same patients after metabolic control. The observed changes were mainly apparent in intracellular degradation. To evaluate whether the observed differences in low density lipoprotein behaviour were correlated with lipid or apolipoprotein composition, we measured cholesterol, triglyceride, apolipoprotein B and total protein levels in the low density lipoproteins tested. A significant decrease (p less than 0.05) of the triglyceride/protein ratio was found in post-control low density lipoproteins suggesting that a high triglyceride content may interfere with low density lipoprotein metabolism. The present study represents the first observation that metabolic control in diabetes mellitus can alter low density lipoprotein-cell interaction and suggests a possible mechanism for the enhanced incidence of atherosclerosis in diabetic patients.
- Published
- 1982
- Full Text
- View/download PDF
62. Elevated glucose concentrations increase factor VIIIR:Ag levels in human umbilical vein endothelial cells.
- Author
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Mordes DB, Lazarchick J, Colwell JA, and Sens DA
- Subjects
- Cells, Cultured, Endothelium cytology, Factor VIII metabolism, Humans, Umbilical Veins cytology, von Willebrand Factor, Antigens metabolism, Factor VIII immunology, Glucose metabolism, Umbilical Veins metabolism
- Abstract
To determine if endothelial cell metabolism is affected by the elevated glucose concentrations known to occur in diabetes mellitus, we measured cellular Factor VIIIR:Ag in endothelial cells grown under conditions of increased glucose concentration. The results of this study illustrate that, under cell culture conditions, an increase in glucose concentration results in increased cellular levels of Factor VIIIR:Ag. Specifically, a glucose concentration of 300 mg/dl resulted in a 23% increase in Factor VIIIR:Ag levels while a glucose concentration of 600 mg/dl resulted in a 54% increase in Factor VIIIR:Ag levels. These in vitro findings may relate to the increase in plasma Factor VIIIR:Ag levels known to occur in diabetic patients.
- Published
- 1983
- Full Text
- View/download PDF
63. Time course of changes in in vitro platelet function and plasma von willebrand factor activity (VIIIR:WF) and factor VIII-related antigen (VIIIR:Ag) in the diabetic rat.
- Author
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Winocour PD, Lopes-Virella M, Laimins M, and Colwell JA
- Subjects
- Adenosine Diphosphate pharmacology, Animals, Blood Glucose analysis, Cholesterol blood, Diabetes Mellitus, Experimental physiopathology, Factor VIII analysis, Male, Platelet Aggregation, Platelet Function Tests, Rats, Rats, Inbred Strains, Thrombin pharmacology, Time Factors, Antigens analysis, Blood Coagulation Factors analysis, Diabetes Mellitus, Experimental blood, Factor VIII immunology, von Willebrand Factor analysis
- Abstract
The relationship between platelet abnormalities and vessel wall changes in diabetes is not known. We have examined the time course of alterations in in vitro platelet function and endothelial damage, as assessed by measurement of plasma levels of von Willebrand factor (VIIIR:WF) and factor VIII-related antigen (VIIIR:Ag), in streptozotocin-induced diabetic rats. Platelet aggregation and the platelet release reaction in response to ADP, thrombin, and collagen were measured in suspensions of washed platelets prepared from rats 3, 7, 14, or 28 days after induction of diabetes and in control animals. Platelets from diabetic animals showed enhanced aggregation response to ADP as early as 3 days after induction of diabetes and became hyperresponsive to thrombin after 7 days, compared to control platelets. Thrombin-induced release of serotonin was greater in platelets from diabetic animals at 14 days. Collagen-induced responses were not different at any time studied. VIIIR:WF was determined by ristocetin-induced platelet agglutination time in gel-filtered platelets, and VIIIR:Ag was determined by immunoelectrophoretic technique. VIIIR:WF and VIIIR:Ag were significantly enhanced in plasma from rats at 28 days after induction of diabetes and VIIIR:Ag was enhanced in plasma from rats at 14 days after induction of diabetes, but at the earlier times studied, neither were different from values in plasma from control-treated rats. Changes in VIIIR:WF and VIIIR:Ag therefore occurred later than the changes in platelet function. Plasma cholesterol concentrations were not significantly different at any of the times studied, but plasma triglyceride concentrations were significantly increased at 3 days and remained increased with further durations of diabetes. This may have contributed to the observed platelet and vessel wall changes. If these in vitro alterations reflect in vivo behavior, then platelet alterations occur before vessel wall changes and therefore do not appear to be a consequence of such changes in experimental diabetes mellitus.
- Published
- 1983
64. Veterans Administration Cooperative Study on antiplatelet agents in diabetic patients after amputation for gangrene: II. Effects of aspirin and dipyridamole on atherosclerotic vascular disease rates.
- Author
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Colwell JA, Bingham SF, Abraira C, Anderson JW, Comstock JP, Kwaan HC, and Nuttall F
- Subjects
- Clinical Trials as Topic, Double-Blind Method, Gangrene etiology, Humans, Male, Middle Aged, Random Allocation, United States, United States Department of Veterans Affairs, Amputation, Surgical, Arteriosclerosis prevention & control, Aspirin therapeutic use, Blood Platelets drug effects, Diabetes Mellitus, Type 2 complications, Diabetic Angiopathies prevention & control, Dipyridamole therapeutic use, Gangrene surgery
- Abstract
We report the results of a randomized multicenter clinical trial on the effects of aspirin plus dipyridamole versus placebo on major vascular end points in 231 non-insulin-dependent diabetic men with either a recent amputation for gangrene or active gangrene. Primary end points were death from atherosclerotic vascular disease plus amputation of the opposite extremity for gangrene. There were 24 atherosclerotic deaths in the drug treatment group (21.8%) and 23 in the placebo group (19.0%). There were 22 patients in the drug treatment group (20.0%) and 29 patients in the placebo group (24.0%) with opposite-side amputations. Survival curve analyses revealed little difference between these groups for major vascular end points, total mortality, all amputations, or myocardial infarctions. The most noteworthy group difference was observed for cerebrovascular end points (strokes and transient ischemic attacks), with an incidence of 8.2% (9 patients) in the drug treatment group and 19.0% (23 patients) in the placebo group. We conclude from this study that antiplatelet agents have no effect on the primary vascular end points, vascular deaths and/or amputation of the opposite extremity, in this population. Similarly, no effects were seen on secondary vascular end points, except for a suggestion of protection versus strokes and transient ischemic attacks. However, this finding must be interpreted with caution, since it is a secondary end point and was found only after multiple analyses of the data.
- Published
- 1986
- Full Text
- View/download PDF
65. Urinary high density lipoprotein in minimal change glomerular disease and chronic glomerulopathies.
- Author
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Lopes-Virella M, Virella G, Debeukelaer M, Owens CJ, and Colwell JA
- Subjects
- Adolescent, Adult, Apolipoproteins blood, Apolipoproteins urine, Child, Child, Preschool, Cholesterol blood, Creatinine metabolism, Female, Glomerulonephritis blood, Humans, Lipoproteins, HDL blood, Male, Muramidase urine, Nephrosis, Lipoid blood, Triglycerides urine, Glomerulonephritis urine, Lipoproteins, HDL urine, Nephrosis, Lipoid urine
- Abstract
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.
- Published
- 1979
- Full Text
- View/download PDF
66. Increased platelet thromboxane synthesis in diabetes mellitus.
- Author
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Halushka PV, Rogers RC, Loadholt CB, and Colwell JA
- Subjects
- Adult, Female, Humans, Imidazoles pharmacology, Male, Platelet Aggregation drug effects, Prostanoic Acids pharmacology, Thromboxane A2 biosynthesis, Thromboxane B2 biosynthesis, Blood Platelets metabolism, Diabetes Mellitus blood, Thromboxanes blood
- Abstract
Platelets obtained from some diabetic patients show enhanced in vitro platelet aggregation. This study sought to determine whether platelets obtained from diabetic subjects synthesize increased quantities of the labile aggregating substance. TXA2, and whether it may play a role in the enhanced platelet aggregation. Arachidonic acid (1 mM)-stimulated TXA2 synthesis, as determined via radioimmunoassay of its stable metabolite TXB2, was significantly greater (p < 0.01, n = 12) in platelet-rich plasma obtained from diabetic patients than in matched controls. Arachidonic acid-stimulated TXB2 synthesis in the diabetic platelet-rich plasma was positively correlated with the ambient fasting plasma glucose (r = 0.61, p < 0.02, n = 15). Platelet aggregation induced by arachidonic acid (0.4 to 0.8 mM) was inhibited significantly less than in matched controls by imidazole, a thromboxane synthetase inhibitor (p < 0.01, n = 11), and 13-azaprostanoic acid, an antagonist of the actions of PGH2 or TXA2 on platelets (p < 0.04, n = 14). We conclude that platelets obtained from some diabetic subjects manifest increased synthesis of TXA2, which may contribute to the enhanced platelet aggregation.
- Published
- 1981
67. Platelet adhesion and aggregation in diabetes mellitus.
- Author
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Colwell JA, Nair RM, Halushka PV, Rogers C, Whetsell A, and Sagel J
- Subjects
- Adenosine Diphosphate pharmacology, Adult, Arachidonic Acid, Arachidonic Acids pharmacology, Blood Coagulation Factors metabolism, Blood Platelets metabolism, Factor VIII metabolism, Humans, Imidazoles pharmacology, Insulin blood, Male, von Willebrand Factor physiology, Diabetes Mellitus blood, Platelet Activating Factor, Platelet Adhesiveness, Platelet Aggregation drug effects
- Abstract
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.
- Published
- 1979
- Full Text
- View/download PDF
68. Platelets, prostaglandins, and coagulation in diabetes mellitus.
- Author
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Colwell JA and Halushka PV
- Subjects
- Arachidonic Acid, Arachidonic Acids metabolism, Humans, Blood Coagulation, Blood Platelets, Diabetic Angiopathies blood, Prostaglandins blood
- Published
- 1982
69. Altered platelet function in diabetes mellitus.
- Author
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Colwell JA, Halushka PV, Sarji K, Levine J, Sagel J, and Nair RM
- Subjects
- Adenosine Diphosphate pharmacology, Adult, Arachidonic Acids pharmacology, Aspirin pharmacology, Collagen pharmacology, Cyclooxygenase Inhibitors, Diabetic Angiopathies blood, Diabetic Nephropathies blood, Diabetic Retinopathy blood, Epinephrine pharmacology, Female, Humans, Male, Middle Aged, Prostaglandin-Endoperoxide Synthases blood, Prostaglandins biosynthesis, von Willebrand Factor physiology, Blood Platelets physiology, Diabetes Mellitus blood, Platelet Aggregation drug effects
- Abstract
An increased sensitivity of platelets to aggregation from ADP and epinephrine is described in diabetics with or without vascular disease. This sensitivity correlates with elevated levels on von Willebrand factor (vWF), which, in turn appears to be influenced by growth hormone. VWF activity correlates with previously described "plasma factor" activity. Platelets from diabetic subjects are more sensitive than platelets from normal subjects to arachidonic acid-induced aggregation. This sensitivity is abolished by aspirin, which is a prostaglandin synthetase (cyclo-oxygenase) inhibitor. Platelets from diabetc subjects synthesize increased amounts of PGE2-like material (iPGE) in response to ADP, epinephrine, collagen, and arachidonic acid. The latter finding suggests that a fundamental mechanism for increased platelet aggregation in diabetes is increased prostaglandin synthetase activity. Therapeutic endeavors that would lower growth hormone levels, vWF activity, and/or prostaglandin synthetase activity may be of benefit in the prophylaxis of diabetic vascular disease. Prospective studies are needed to explore these hypothesis, as are more studies on the precise mechanisms and platelet aggregation in diabetes mellitus.
- Published
- 1976
70. Dangers of intravenous ritodrine in diabetic patients.
- Author
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Mordes D, Kreutner K, Metzger W, and Colwell JA
- Subjects
- Adult, Blood Glucose analysis, Female, Humans, Insulin therapeutic use, Pregnancy, Pregnancy in Diabetics drug therapy, Ritodrine administration & dosage, Diabetic Ketoacidosis chemically induced, Obstetric Labor, Premature prevention & control, Pregnancy in Diabetics physiopathology, Propanolamines adverse effects, Ritodrine adverse effects
- Published
- 1982
71. Increased platelet prostaglandin and thromboxane synthesis in diabetes mellitus.
- Author
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Halushka PV, Rogers RC, Loadholt CB, Wohltman H, Mayfield R, McCoy S, and Colwell JA
- Subjects
- Arachidonic Acids pharmacology, Humans, Insulin therapeutic use, Platelet Aggregation drug effects, Prostaglandins blood, Thromboxanes blood, Blood Platelets metabolism, Diabetes Mellitus blood, Prostaglandins biosynthesis, Thromboxanes biosynthesis
- Abstract
Platelets obtained from some diabetic patients show enhanced in vitro platelet aggregation. These studies were designed to determine if platelets obtained from diabetic subjects manifest increased metabolism of arachidonic acid to labile aggregating substances, such as thromboxane A2 (TXA2), and if they play a role in the enhanced platelet aggregation. Arachidonic acid stimulated TXA2 synthesis, as determined via radioimmunoassay of its stable metabolite TXB2, was significantly greater (p less than 0.01, n = 12) in platelet-rich plasma obtained from diabetic compared to matched controls. Arachidonic acid stimulated TXB2 synthesis in the diabetic platelet-rich plasma was positively correlated with the ambient fasting plasma glucose (r = 0.61, p less than 0.02, n = 15). Platelet aggregation induced by arachidonic acid (0.4-0.8 mM) was inhibited significantly less by 13-azaprostanoic acid (p less than 0.04, n = 14), an antagonist of the actions of prostaglandin H2 or TXA2 on platelets, compared to matched controls. We conclude that platelets obtained from some diabetic subjects manifest increased metabolism of arachidonic acid to labile aggregating substances which may contribute to the enhanced platelet aggregation.
- Published
- 1981
72. Increased platelet arachidonic acid metabolism in diabetes mellitus.
- Author
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Halushka PV, Mayfield R, Wohltmann HJ, Rogers RC, Goldberg AK, McCoy SA, Loadholt CB, and Colwell JA
- Subjects
- Arachidonic Acid, Arachidonic Acids pharmacology, Blood Glucose metabolism, Blood Platelets drug effects, Epinephrine pharmacology, Humans, Kinetics, Platelet Aggregation drug effects, Prostanoic Acids pharmacology, Thromboxane B2 biosynthesis, Thromboxane B2 blood, Arachidonic Acids blood, Blood Platelets metabolism, Diabetes Mellitus blood
- Abstract
Platelets obtained from some diabetic patients show enhanced in vitro platelet aggregation. This study sought to determine if platelet obtained from insulin-dependent diabetic subjects synthesize increased quantities of the labile aggregating substance, thromboxane A2 (TXA2), and if it may play a role in the enhanced platelet aggregation. Arachidonic acid (1 mM)-stimulated TXA2 synthesis, as determined via radioimmunoassay of its stable metabolite TXB2, was significantly greater (P less than 0.01, N = 12) in platelet-rich plasma obtained from diabetics compared with matched controls. Arachidonic acid-stimulated TXB2 synthesis in the diabetic platelet-rich plasma was positively correlated with the ambient fasting plasma glucose (r = 0.61, P less than 0.02, N = 15). Platelet aggregation induced by arachidonic acid (0.4-0.8 mM) was inhibited significantly less by 13-azaprostanoic acid (P less than 0.04, N = 14), a competitive antagonist of the actions of prostaglandin H2 or TXA2 on platelets, compared with matched controls. The results support the notion that platelets obtained from some insulin-dependent diabetic subjects manifest increased synthesis of TXA2, which may contribute to the enhanced platelet aggregation.
- Published
- 1981
- Full Text
- View/download PDF
73. Diabetic lipoprotein deficient serum: its effect in low density lipoprotein (LDL) uptake and degradation by fibroblasts.
- Author
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Lopes-Virella MF, Sherer G, Wohltmann H, Sens D, and Colwell JA
- Subjects
- Adolescent, Adult, Apolipoproteins A metabolism, Cells, Cultured, Child, Culture Media, Fatty Acids, Nonesterified metabolism, Female, Fibroblasts metabolism, Humans, Insulin metabolism, Male, Phosphatidylcholines metabolism, Phosphatidylethanolamines metabolism, Receptors, Cell Surface metabolism, Receptors, Lipoprotein, Diabetes Mellitus, Type 1 blood, Lipoproteins, LDL metabolism
- Abstract
Low density lipoproteins (LDL) isolated from poorly controlled diabetic patients are known to be taken up and degraded by fibroblasts at a lower rate than LDL isolated from normal subjects. This aberrant metabolic behavior has been attributed to a diabetic-related abnormality in LDL composition yet to be characterized. The studies reported in this article show that the decrease in uptake and intracellular degradation of LDL from diabetic patients is further enhanced when the cells are exposed to lipoprotein deficient serum (LPDS) isolated from the same poorly controlled diabetic patients. Comparative studies of the composition of LPDS obtained from normal donors and poorly controlled diabetic patients showed an increase in saturated and total unesterified fatty acids (UFA), lecithin, apolipoprotein A1, and immunoreactive insulin in the LPDS from diabetic patients. We postulate that exposure of cells to LPDS obtained from poorly controlled diabetic patients may induce changes in the composition of the fibroblast membrane and alter its fluidity, leading to further decrease in the uptake and degradation of LDL. During poor diabetic control, cell membrane changes, and modification of LDL composition are likely to act either additively or synergistically to induce an abnormal LDL-cell interaction. This abnormal interaction may be a relevant factor to explain the greater incidence of arteriosclerosis in diabetes mellitus.
- Published
- 1985
- Full Text
- View/download PDF
74. Platelet survival in streptozotocin-induced diabetic rats.
- Author
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Winocour PD, Laimins M, and Colwell JA
- Subjects
- Animals, Blood Glucose analysis, Blood Platelets cytology, Cell Survival, Male, Platelet Count, Rats, Rats, Inbred Strains, Time Factors, Blood Platelets physiology, Diabetes Mellitus, Experimental physiopathology
- Abstract
Platelet survival in diabetes mellitus may be decreased or normal, and it is not clear whether altered platelet survival is due to a platelet or to a non-platelet defect. Therefore, platelet survival studies were performed at intervals up to 28 days in streptozotocin-induced diabetic and normal rats, using washed platelets from diabetic or normal animals. When compared to platelets from control rats, there was a significant decrease in platelet survival when platelets from 7 and 14 day diabetic rats were injected into normal controls or into diabetic rats. After 28 days of diabetes, platelet survival in diabetic rats was significantly lengthened, whether the platelets came from control or diabetic rats. Conclusions. Shortened platelet survival in the diabetic rat is caused initially by a platelet defect. Later, non-platelet factors become dominant. These findings may help explain reported discrepancies in results of platelet survival in diabetes mellitus.
- Published
- 1984
75. Effect of metabolic control on lipid, lipoprotein, and apolipoprotein levels in 55 insulin-dependent diabetic patients. A longitudinal study.
- Author
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Lopes-Virella MF, Wohltmann HJ, Mayfield RK, Loadholt CB, and Colwell JA
- Subjects
- Adolescent, Adult, Apolipoproteins A, Apolipoproteins B, Child, Child, Preschool, Cholesterol blood, Humans, Lipoproteins, HDL blood, Lipoproteins, VLDL blood, Longitudinal Studies, Male, Middle Aged, Sex Factors, Triglycerides blood, Apolipoproteins blood, Diabetes Mellitus drug therapy, Insulin therapeutic use, Lipids blood, Lipoproteins blood, Lipoproteins, LDL blood
- Published
- 1983
- Full Text
- View/download PDF
76. Effect of parathyroidectomy on hypercalcemic hypersecretory peptic ulcer disease.
- Author
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McGuigan JE, Colwell JA, and Franklin J
- Subjects
- Calcium blood, Humans, Hypercalcemia therapy, Hyperparathyroidism therapy, Male, Middle Aged, Parathyroid Glands surgery, Peptic Ulcer therapy, Gastric Juice, Gastrins blood, Hypercalcemia complications, Hyperparathyroidism complications, Peptic Ulcer complications
- Published
- 1974
77. Decreased platelet vitamin C in diabetes mellitus: possible role in hyperaggregation.
- Author
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Sarji KE, Kleinfelder J, Brewington P, Gonzalez J, Hempling H, and Colwell JA
- Subjects
- Arachidonic Acids pharmacology, Ascorbic Acid pharmacology, Cyclic AMP metabolism, Humans, Insulin metabolism, Male, Prostaglandins biosynthesis, Tongue, Ascorbic Acid blood, Blood Platelets metabolism, Diabetes Mellitus blood, Platelet Aggregation drug effects
- Published
- 1979
- Full Text
- View/download PDF
78. The effects of dopamine on human platelet aggregation, in vitro.
- Author
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Braunstein KM, Sarji KE, Kleinfelder J, Schraibman HB, Colwell JA, and Eurenius K
- Subjects
- Adenosine Diphosphate pharmacology, Aspirin pharmacology, Collagen antagonists & inhibitors, Dopamine Antagonists, Drug Interactions, Epinephrine antagonists & inhibitors, Haloperidol pharmacology, Humans, In Vitro Techniques, Male, Metaraminol pharmacology, Phentolamine pharmacology, Propranolol pharmacology, Time Factors, Dopamine pharmacology, Platelet Aggregation drug effects
- Abstract
An unexpected inhibition of human platelet aggregation by dopamine -- the precursor of epinephrine and norepinephrine -- is presented. Human platelet-rich plasma was incubated in an aggregometer for 120 seconds at 37 degrees C, with either dopamine or saline control. Adenosine diphosphate, epinephrine or collagen was added as the aggregating agent. Dopamine inhibits induction of platelet aggregation by all three agents and causes platelet disaggregation. At low doses (400 mug/ml or less), dopamine induces platelet aggregation and enhances ADP-induced aggregation. In addition, a concentration of dopamine of 40 mug/ml induces aggregation, enhances ADP-induced aggregation and inhibits epinephrine aggregation. Phentolamine is able to block dopamine enhancement of ADP aggregation, but propranolol and haloperidol fail to prevent dopamine inhibition of epinephrine aggregation. These observations are explained neither by the currently known intracellular actions of dopamine which involve competition with serotonin nor by a single mediator such as cyclic adenosine 3':5'-monophosphate. It appears that dopamine may exert its effects via the platelet membrane.
- Published
- 1977
79. Correlation of platelet aggregation, plasma factor activity, and megathrombocytes in diabetic subjects with an without vascular disease.
- Author
-
Colwell JA, Sagel J, Crook L, Chambers A, and Laimins M
- Subjects
- Adult, Blood Cell Count, Clinical Trials as Topic, Diabetes Complications, Diabetic Nephropathies blood, Diabetic Retinopathy blood, Humans, Male, Middle Aged, Prediabetic State blood, Vascular Diseases etiology, Blood Coagulation Factors analysis, Blood Platelets metabolism, Diabetes Mellitus blood, Platelet Aggregation
- Abstract
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.
- Published
- 1977
- Full Text
- View/download PDF
80. Insulin and arachidonic acid metabolism in diabetes mellitus.
- Author
-
Halushka PV, Mayfield R, and Colwell JA
- Subjects
- Animals, Arachidonic Acid, Arthritis, Rheumatoid complications, Aspirin pharmacology, Blood Platelets metabolism, Epoprostenol biosynthesis, Humans, Platelet Aggregation, Thromboxane A2 metabolism, Thromboxane B2 metabolism, Arachidonic Acids metabolism, Diabetes Mellitus metabolism, Insulin metabolism
- Abstract
The alterations in the metabolism of arachidonic acid to prostaglandin I2 (prostacyclin), a vasodilator antiaggregatory substance, and thromboxane A2, a vasoconstrictor proaggregatory substance, in diabetes mellitus are reviewed in this article. When tested in vitro, platelet aggregation is enhanced in some patients with diabetes mellitus. The synthesis of thromboxane B2, the stable metabolite of thromboxane A2, by platelets is increased in patients with diabetes mellitus compared with control subjects. This increased synthesis appears to play a role in the enhanced platelet aggregation since the latter can be reversed by aspirin treatment and in vitro by the thromboxane receptor-antagonist 13-azaprostanoic acid. Vascular prostacyclin synthesis is decreased in both patients and experimental animals with diabetes mellitus. Treatment of experimental animals with insulin reverses the decreased synthesis of prostacyclin. The etiology of the altered arachidonic acid metabolism remains uncertain but appears to be multifactorial and includes alterations in metabolic control and circulating immune complexes. The increased ratio of thromboxane A2 to prostacyclin, which favors an enhanced thrombotic state, may play a role in the accelerated vascular disease of diabetes mellitus.
- Published
- 1985
- Full Text
- View/download PDF
81. Hypoglycemia.
- Author
-
Colwell JA
- Subjects
- Fasting, Humans, Hypoglycemia classification, Hypoglycemia physiopathology, Liver physiopathology, Pancreas physiopathology, Hypoglycemia diagnosis
- Abstract
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.
- Published
- 1977
82. Antiplatelet agents and diabetic vascular disease.
- Author
-
Colwell JA
- Subjects
- Humans, Aspirin therapeutic use, Blood Platelets physiology, Diabetic Angiopathies drug therapy, Dipyridamole therapeutic use
- Published
- 1987
83. VA cooperative study on antiplatelet agents in diabetic patients after amputation for gangrene. IV. Issues in design, interpretation, and analysis.
- Author
-
Colwell JA and Bingham SF
- Subjects
- Aspirin therapeutic use, Cerebrovascular Disorders diagnosis, Cerebrovascular Disorders drug therapy, Clinical Trials as Topic, Diabetes Mellitus blood, Diabetes Mellitus drug therapy, Diabetes Mellitus mortality, Dipyridamole therapeutic use, Gangrene surgery, Humans, Male, Myocardial Infarction diagnosis, Amputation, Surgical, Blood Platelets drug effects, Diabetes Complications, Gangrene etiology, Hospitals, Veterans
- Abstract
This paper review some of the issues faced by the investigators involved in a VA Cooperative Study on Antiplatelet Agents in Diabetic Patients after Amputation for Gangrene. The study was a negative one, and some of the reasons for this are considered. In addition, suggestive results in two subgroups, cerebrovascular disease and unexpected, sudden, or unobserved deaths, were found. The implications and interpretation of these findings are discussed.
- Published
- 1986
- Full Text
- View/download PDF
84. Do platelets have anything to do with diabetic microvascular disease?
- Author
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Colwell JA, Winocour PD, and Halushka PV
- Subjects
- Animals, Arachidonic Acid, Arachidonic Acids blood, Diabetes Mellitus, Type 1 blood, Diabetic Angiopathies drug therapy, Endothelium, Vascular physiopathology, Fibrinolysis, Humans, Platelet Aggregation, Platelet Aggregation Inhibitors therapeutic use, beta-Thromboglobulin metabolism, von Willebrand Factor metabolism, Blood Platelets physiology, Diabetic Angiopathies blood
- Abstract
It has been postulated that abnormal platelet and endothelial function may contribute to microangiopathy in diabetes mellitus. If this proposal is correct, alterations in platelet and endothelial function should be found before the appearance of vascular disease in insulin-dependent patients and in animal models of diabetes mellitus. This appears to be the case for the following: platelet aggregation, increased platelet production of the proaggregatory prostaglandin metabolite thromboxane, decreased endothelial production of the antiaggregatory prostaglandin prostacyclin, and decreased platelet survival. Insulin therapy will return some of these findings to normal. Platelet-plasma interactions that promote platelet aggregation and increased plasma levels of the platelet-specific protein beta-thromboglobulin have been reported in insulin-dependent diabetic patients who have not manifested vascular complications as well as in those with vascular complications. It has now been demonstrated in animal models that platelet microthrombi are found in small retinal vessels after months of experimental diabetes. Collectively, these findings demonstrate that alterations in platelet and endothelial function that favor thrombosis occur early in the diabetic state and may contribute to microvascular disease. There are several ongoing studies of antiplatelet agents in diabetic vascular disease that will provide clinical evidence bearing on the major postulate. Until these and other studies are completed, the platelet-endothelial story remains an attractive hypothesis in the genesis of diabetic microvascular disease.
- Published
- 1983
- Full Text
- View/download PDF
85. Shock during oral glucose tolerance testing.
- Author
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Sagel J and Colwell JA
- Subjects
- Adenoma, Acidophil surgery, Administration, Oral, Dumping Syndrome complications, Dumping Syndrome etiology, Exudates and Transudates, Glucose administration & dosage, Glucose adverse effects, Humans, Hypertonic Solutions, Hypopituitarism diagnosis, Hypotension diagnosis, Jejunum drug effects, Male, Middle Aged, Pituitary Neoplasms surgery, Time Factors, Vision Disorders diagnosis, Glucose Tolerance Test adverse effects, Shock etiology
- Published
- 1973
86. Glucose and insulin responses in sheep subjected to a second episode of hemorrhagic shock.
- Author
-
Fritz SD, Fitts CT, and Colwell JA
- Subjects
- Animals, Hematocrit, Hydrogen-Ion Concentration, Lactates blood, Potassium blood, Sheep, Blood Glucose analysis, Insulin blood, Shock, Hemorrhagic blood
- Abstract
These studies indicated that the responses of the sheep beta cell parallel mnay of those seen in man. Regulation by pH, potassium, and epinephrine and suggested, as is the existence of a two-pool system for insulin synthesis and release which is responsive to glucose. Differences in glucose and insulin responses following a second episode of shock are noted. It is shown that the addition of hypertonic glucose to a resuscitation regimen is associated with a response to a second episode of shock that is more nearly like that to a first episode of shock.
- Published
- 1976
87. Platelet function during continuous insulin infusion treatment in insulin-dependent diabetic patients.
- Author
-
Mayfield RK, Halushka PV, Wohltmann HJ, Lopes-Virella M, Chambers JK, Loadholt CB, and Colwell JA
- Subjects
- Adenosine Diphosphate pharmacology, Adolescent, Adult, Arachidonic Acid, Arachidonic Acids pharmacology, Blood Glucose analysis, Blood Platelets physiology, Diabetes Mellitus, Type 1 drug therapy, Diabetic Angiopathies blood, Female, Humans, Insulin pharmacology, Lipoproteins blood, Male, Middle Aged, Platelet Aggregation drug effects, Thromboxane A2 biosynthesis, Thromboxane B2 blood, Blood Platelets drug effects, Diabetes Mellitus, Type 1 blood, Insulin Infusion Systems
- Abstract
Patients with diabetes mellitus manifest increased in vitro platelet aggregation and increased synthesis of the proaggregant and vasoconstrictor, thromboxane A2 (TXA2). We studied the effects of continuous insulin infusion treatment on platelet aggregation and arachidonic acid (AA)-stimulated platelet TXA2 synthesis (15 and 30 s post-AA, 1 mM) in 16 type I diabetic patients. Strict glycemic control was induced with the Biostator for 2 days and maintained for 12-14 days with continuous subcutaneous insulin infusion (CSII). The average premeal plasma glucose level (4/day) fell from 184 +/- 15, before treatment, to 107 +/- 6 mg/dl on the final day (P less than 0.001). After control, platelet synthesis of TXA2, measured by radioimmunoassay of its stable metabolite, immunoreactive TXB2 (iTXB2), decreased in all patients (30 s: 276 +/- 31 versus 199 +/- 28 ng iTXB2/ml/5 X 10(5) platelets; P less than 0.05). The reduction in platelet iTXB2 synthesis (15 and 30 s) was greater in poorly controlled patients (HbA1c greater than 12%; N = 8), and for all patients the decrease in iTXB2 (15 and 30 s) was correlated with the prestudy HbA1c level (15 s: r = 0.6; P less than 0.01). In contrast, platelet aggregation responses did not improve during intensive insulin treatment. The ED50 for AA (dose producing 50% maximum aggregation at 1 min) was unchanged after 2 wk of treatment and the ED50 for aggregation induced by ADP fell significantly in patients with HbA1c greater than 12% (2.8 +/- 1.3 versus 1.2 +/- 0.6 microM; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1985
- Full Text
- View/download PDF
88. Primary hyperparathyroidism and salt-wasting nephropathy.
- Author
-
Bell NH, Del Greco F, and Colwell JA
- Subjects
- Absorption, Adult, Calcium metabolism, Humans, Intestinal Absorption, Kidney Tubules metabolism, Male, Nephrocalcinosis complications, Osteitis Fibrosa Cystica complications, Phosphorus blood, Potassium metabolism, Hyperparathyroidism complications, Kidney Diseases complications, Sodium metabolism
- Published
- 1975
- Full Text
- View/download PDF
89. V.A. Cooperative Study on antiplatelet agents in diabetic patients after amputation for gangrene: I. Design, methods, and baseline characteristics.
- Author
-
Colwell JA, Bingham SF, Abraira C, Anderson JW, and Kwaan HC
- Subjects
- Aspirin therapeutic use, Diabetic Angiopathies complications, Dipyridamole therapeutic use, Epoprostenol therapeutic use, Gangrene etiology, Humans, Male, Middle Aged, Random Allocation, Research Design, Amputation, Surgical, Clinical Trials as Topic methods, Diabetic Angiopathies drug therapy, Gangrene surgery, Platelet Aggregation drug effects
- Abstract
This report describes the experimental design, methods, and baseline characteristics of patients enrolled in a Veterans Administration Cooperative Study on the effect of aspirin (325 mg t.i.d.) and dipyridamole (75 mg t.i.d.) (110 patients), or placebo (121 patients) on major vascular outcome variables in noninsulin-dependent diabetic patients with either a recent amputation for gangrene (n = 207) or active gangrene (n = 24). It also describes the baseline characteristics of the patients. A total of 231 patients of 563 screened (41%) were enrolled at 11 participating V.A. Medical Centers during a 39 month period. The median age at entry was 60 years, the median duration of diabetes was 10 years, and weight was 110% of desirable. All patients were men. Sixty-eight percent were treated with insulin and 32% with diet alone. Only 42% were smokers at entry, 40% had retinopathy, 61% sensory neuropathy, 42% hypertension, and 29% had a history of myocardial infarction, angina, and/or congestive heart failure. Thirteen percent had a history of cerebrovascular disease. Despite randomization, the treatment group had an increased frequency of a history of cerebrovascular disease (p = 0.01), diagnosed as stroke (p = 0.03), a finding suggesting that the treatment group was at a slightly increased risk for vascular disease upon enrollment in the study. Other baseline variables did not differ significantly between the two groups. This study should provide definitive data on the efficacy of these doses of antiplatelet agents in preventing further vascular disease in diabetic men with gangrene or recent amputation for gangrene, using death due to vascular disease and subsequent amputation of the opposite extremity for gangrene as major outcome variables. It should also give useful information on the effect of antiplatelet therapy on vascular outcome variables such as same side amputations, myocardial infarction, stroke, transient ischemic attack, retinopathy, and renal failure. Finally, the study should provide useful data on the natural history and significance of risk factors in this patient population.
- Published
- 1984
- Full Text
- View/download PDF
90. Effects of exercise on platelet function, coagulation, and fibrinolysis.
- Author
-
Colwell JA
- Subjects
- Endothelium physiology, Fibrinolysin metabolism, Humans, Male, Plasminogen metabolism, Platelet Factor 4 metabolism, beta-Thromboglobulin metabolism, Blood Coagulation, Blood Platelets physiology, Fibrinolysis, Physical Exertion
- Abstract
Exercise and physical conditioning may reduce the subsequent risk of major vascular thrombotic events. In view of this, it may be important to examine the effects of exercise on the blood coagulation system. The present paper reviews the effects of physical exercise and conditioning on blood coagulation, platelet function, and fibrinolytic activity. A hypothetical scheme is developed, in which increased blood coagulability and activated platelet function is counterbalanced by increased fibrinolytic activity and endothelial prostacyclin release. Some consideration is given to how this sequence of events may be altered in vascular disease states.
- Published
- 1986
- Full Text
- View/download PDF
91. Serum-high-density-lipoprotein in diabetic patients.
- Author
-
Lopes-Virella MF and Colwell JA
- Subjects
- Humans, Hypolipoproteinemias, Diabetes Mellitus blood, Lipoproteins, HDL blood
- Published
- 1976
- Full Text
- View/download PDF
92. Effect of metabolic control with insulin on plasma von Willebrand factor activity (VIIIR:WF) in diabetes mellitus.
- Author
-
Gonzalez J, Colwell JA, Sarji KE, Nair RM, and Sagel J
- Subjects
- Blood Glucose metabolism, Growth Hormone, Humans, Male, Middle Aged, Night Care, Sleep, Blood Coagulation Factors metabolism, Diabetes Mellitus metabolism, Insulin metabolism, von Willebrand Factor metabolism
- Published
- 1980
- Full Text
- View/download PDF
93. Cholesterol determination in high-density lipoproteins separated by three different methods.
- Author
-
Lopes-Virella MF, Stone P, Ellis S, and Colwell JA
- Subjects
- Adult, Chemical Precipitation, Heparin, Humans, Lipoproteins, HDL isolation & purification, Magnesium, Manganese, Methods, Phosphotungstic Acid, Triglycerides blood, Ultracentrifugation, Cholesterol blood, Lipoproteins, HDL blood
- Abstract
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.
- Published
- 1977
94. Platelet lipoproteins. A comparative study with serum lipoproteins.
- Author
-
Lopes-Virella MF, Sarji K, Virella G, and Colwell JA
- Subjects
- Electrophoresis, Polyacrylamide Gel, Humans, Immunodiffusion, Lipoproteins, HDL blood, Lipoproteins, LDL blood, Lipoproteins, VLDL blood, Molecular Weight, Solubility, Blood Platelets analysis, Lipoproteins blood
- Abstract
The nature of human platelet lipoproteins was studied in two series of experiments. In the first series, whole platelets were utilized for extraction of lipoproteins by three different methods: chloroform/methanol/phenol; saline; or sucrose-gradient ultracentrifugation of platelet homogenates. By polyacrylamide gel electrophoresis we were able to demonstrate the existence of lipoprotein in the extracts obtained by the last two methods. These lipoproteins were found not to share antigenic determinants with alpha and beta serum lipoproteins. The second series of experiments utilized platelets solubilized either in sodium deoxycholate or sodium dodecyl sulfate. The solubilized product was characterized by double immunodiffusion and polyacrylamide gel electrophoresis. The nonidentity between plasma and platelet lipoproteins previously demonstrated in the first series of experiments was confirmed. This nonidentity was also supported by a comparison between the apoproteins of purified serum lipoproteins and platelet proteins released after solubilization with sodium dodecyl sulfate. No identical protein fractions were found. Our results suggest that, unlike erythrocyte membrane lipoproteins, the platelet lipoproteins are structurally different from plasma lipoproteins.
- Published
- 1976
- Full Text
- View/download PDF
95. President's address.
- Author
-
Colwell JA
- Subjects
- Education, Medical, Fund Raising, History, 20th Century, Humans, Research Support as Topic, United States, Diabetes Mellitus, Voluntary Health Agencies history, Voluntary Health Agencies organization & administration
- Published
- 1988
- Full Text
- View/download PDF
96. Glycosylation of low density lipoprotein in patients with type 1 (insulin-dependent) diabetes: correlations with other parameters of glycaemic control.
- Author
-
Lyons TJ, Baynes JW, Patrick JS, Colwell JA, and Lopes-Virella MF
- Subjects
- Adult, Blood Glucose analysis, Blood Proteins analysis, Cholesterol blood, Female, Glycation End Products, Advanced, Humans, Lipoproteins, LDL isolation & purification, Male, Middle Aged, Patient Compliance, Reference Values, Triglycerides blood, Diabetes Mellitus, Type 1 blood, Lipoproteins, LDL blood
- Abstract
Glycosylation of low density lipoproteins obtained from 16 patients with Type 1 (insulin-dependent) diabetes and from 16 age-, sex-, and race-matched controls, was determined. The diabetic patients were normolipaemic and were in good or fair glycaemic control. Eleven patients performed home blood glucose monitoring. Glycosylation of low density lipoproteins in the diabetic patients was significantly higher (p less than 0.001) than in the control subjects, and was significantly correlated with haemoglobin A1c, (p less than 0.01), glycosylation of plasma proteins, (p less than 0.001), and mean home blood glucose, (p less than 0.01). This study confirms that, in diabetic patients, increased glycosylation of low density lipoprotein occurs to an extent which correlates closely with other commonly used indices of glycaemic control.
- Published
- 1986
- Full Text
- View/download PDF
97. The effect of oral glucose on von Willebrand factor activity in normal and diabetic subjects.
- Author
-
Graves JM, Colwell JA, Nair RM, and Sarji KE
- Subjects
- Aged, Blood Glucose, Female, Glucose Tolerance Test, Growth Hormone blood, Humans, Insulin blood, Male, Middle Aged, Platelet Aggregation, Blood Coagulation Factors analysis, Diabetes Mellitus blood, Glucose pharmacology, von Willebrand Factor analysis
- Abstract
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.
- Published
- 1977
- Full Text
- View/download PDF
98. Predicting insulin requirements for a portable insulin pump using the Biostator. Evidence for reversible insulin resistance in poorly controlled type I diabetics.
- Author
-
Mayfield RK, Sullivan FM, Colwell JA, and Wohltmann HJ
- Subjects
- Adolescent, Adult, Blood Glucose, Child, Female, Humans, Insulin Resistance, Male, Middle Aged, Diabetes Mellitus, Type 1 drug therapy, Insulin administration & dosage, Insulin Infusion Systems
- Abstract
Glycemic control was achieved in 14 patients with insulin-dependent diabetes mellitus (IDDM) by 36-48-h treatment with a recently marketed clinical model, Biostator glucose controller (Life Science Instruments, Miles Laboratories, Elkhart, Indiana). Control was maintained by continuous subcutaneous insulin infusion with a portable pump, programmed using infusion profiles from the Biostator. Control of glycemic excursion with the Biostator was variable among patients. This control, reflected by the M-value or a blood glucose index (mean of pre-, peak, and 2-h postmeal levels for four meals) of each patient, correlated directly with their prior glycemic control, as assessed by hemoglobin A1c (HbA1c) level (r = 0.66, P less than 0.01 and r = 0.82, P less than 0.005, for M-value and blood glucose index, respectively). Total insulin infused by the Biostator/24 h overpredicted the subcutaneous infusion dose required on day 2 of pump treatment (183 +/- 11%, P less 0.001). Therefore, these data were not used to program the portable pump. Instead, total insulin dose was estimated using a dietary glucose/insulin (G/I) ratio. This ratio, derived from dietary total available glucose, urine glucose, and insulin dose/24 h during depot insulin treatment, accurately estimated total insulin for pump infusion (97 +/- 4%). The basal infusion rate of the Biostator between 2400 and 0600 h also exceeded the subcutaneous infusion requirement and was reduced to 40% for the initial pump basal rate. The remainder of the insulin (total minus basal) was distributed as premeal boluses according to the Biostator infusion profile for meals.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1983
- Full Text
- View/download PDF
99. V.A. Cooperative Study of antiplatelet agents in diabetic patients after amputation for gangrene: unobserved, sudden, and unexpected deaths.
- Author
-
Colwell JA, Bingham SF, Abraira C, Anderson JW, Comstock JP, Kwaan HC, and Nuttall F
- Subjects
- Aspirin therapeutic use, Dipyridamole therapeutic use, Drug Therapy, Combination, Hospitals, Veterans, Humans, Male, Middle Aged, Multicenter Studies as Topic, Myocardial Infarction chemically induced, Myocardial Infarction mortality, Random Allocation, Risk Factors, South Carolina, Amputation, Surgical, Aspirin adverse effects, Death, Sudden, Diabetes Mellitus, Type 2 drug therapy, Dipyridamole adverse effects, Gangrene surgery
- Abstract
We report on unobserved, sudden, and unexpected deaths that occurred in a randomized multicenter trial. The long-term effects of aspirin plus dipyridamole on major vascular outcome variables were studied in 231 non insulin-dependent diabetic men with either a recent amputation for gangrene or active gangrene. Depending upon the definition of sudden death used, there were 14, 22, or 17 deaths in the drug group versus 6, 6, or 3 deaths in the placebo group (p = 0.04, 0.001, or 0.001, respectively). Total deaths from atherosclerotic vascular disease or deaths from all causes did not differ in the two treatment groups. Since this finding of a secondary end point is found only after multiple analyses of the data, it must be interpreted with caution. However, it is suggested that further studies on effects of antiplatelet agents on sudden deaths should be performed.
- Published
- 1989
- Full Text
- View/download PDF
100. Reduced platelet-mediated and enhanced leukocyte-mediated fibrinolysis in experimentally induced diabetes in rats.
- Author
-
Winocour PD and Colwell JA
- Subjects
- Animals, Blood Glucose analysis, Diabetes Mellitus, Experimental blood, Fibrin metabolism, Iodine Radioisotopes, Leukocyte Count, Leukocytes physiology, Male, Rats, Rats, Inbred Strains, Time Factors, Diabetes Mellitus, Experimental physiopathology, Fibrinolysis
- Abstract
Studies of fibrinolytic activity in diabetes mellitus have produced conflicting results. This may be a result of methodologic insensitivity or of variable contributions of the different blood components to whole blood fibrinolysis. To explore these two possibilities, we used a sensitive solid-phase radiometric assay to examine the fibrinolytic activity of whole blood, platelet-rich plasma, leukocytes, and platelet- and leukocyte-poor plasma prepared from control rats and rats with streptozocin-induced diabetes at various times after induction of diabetes. Fibrinolytic activity of whole blood from diabetic rats after 7 days was significantly reduced, and remained reduced after longer durations of diabetes up to 28 days. Platelet-rich plasma from diabetic rats had decreased fibrinolytic activity, which followed the same time course of changes as in whole blood. The platelet contribution to whole blood fibrinolysis was further reduced in vivo after 14 days of diabetes by a reduced whole blood platelet count. In contrast, fibrinolytic activity of leukocytes from diabetic rats became enhanced after 7 days of diabetes. After 49 days of diabetes, the whole blood leukocyte count was reduced, and in vivo would offset the enhanced activity. Plasma fibrinolytic activity was small compared with that of whole blood and was unaltered in diabetic rats. We conclude that altered platelet function contributes to decreased fibrinolytic activity of whole blood in diabetic rats, and that this may be partially offset by enhanced leukocyte-mediated fibrinolysis.
- Published
- 1985
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