Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This report documents the results of therapy in 23 patients treated for malignant thymoma between 1944 and 1979. Of the group, 22 patients had neoplasms which invaded mediastinal structures; six had distant metastases. Four patients had myasthenia gravis and one had erythroid hypoplasia associated with collagen vascular disease. No deaths were associated with primary therapy, which included an operative procedure in all cases. Follow-up ranged from 4 months to 18 years (mean 5.63 +/- 1.03 years, SEM). Fifteen patients died, with postoperative survival times ranging from 4 months to 18 years (mean 3.8 +/- 1.27 years). Five patients were alive without recurrence from 3 to 11 years postoperatively (mean 6.8 +/- 1.36 years), and three patients were alive with recurrence or distant metastases from 4 to 17 years postoperatively (mean 10.75 +/- 2.66 years). Differences in survival on the basis of tumor cell type were not statistically significant. Therapeutic groups were analyzed for 5 year survivors, tumor deaths within 5 years of therapy, deaths due to other causes, deaths due to tumor after 5 years, those presently alive, and longest known survivor. The data suggest that complete surgical excision offers the best chance of long-term survival when compared to partial resection plus irradiation (p less than 0.05). No statistical significance could be demonstrated between the groups who had complete resection with versus without postoperative irradiation. There also was no statistically significant difference between the group of patients receiving irradiation following partial excision of most of their tumor and the group receiving irradiation following only biopsy of the lesion. This observation suggests there is no value in so-called "debulking procedures" and suggests that irradiation may be of value in local control of thymoma. Perpetual surveillance is necessary since late recurrence is common.
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PMID:Management of patients with malignant thymoma. 669 21

Circulating basal levels of prostanoids were measured in non-insulin dependent diabetics (NIDDs) who showed chlorpropamide alcohol flushing (CPAF), with and without diabetic complications, and in non-diabetic controls. Prostanoids were also measured during CPAF in those diabetics in whom CPAF is or is not blocked by indomethacin and also in CPAF-negative patients. There was no significant difference in circulating prostanoids between diabetics with and without severe vascular disease. The level of prostaglandin F, however, was significantly higher in the diabetic than in the non-diabetic subjects (mean +/- SEM PGFM 521 +/- 23 v. 414 +/- 18 pmol/l respectively P less than 0.01). In the group in whom CPAF could be blocked by indomethacin there was a significant rise in thromboxane during CPAF when compared with basal values (mean +/- SEM 905 +/- 48 v. 688 +/- 46 pmol/l respectively P less than 0.01) which was abolished by prior administration of indomethacin. There was no significant rise in prostacyclin or PGF. The group in which CPAF could not be blocked by indomethacin and the CPAF negative group showed no rise in any of the prostanoids measured. These findings support the concept of at least two different groups of CPAF positive NIDDs, one in which prostanoids are involved in CPAF and one in which they are not. It is the group in which prostanoids are involved in CPAF who seem to be highly protected against vascular disease.
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PMID:Circulating prostanoid levels, both basal and during the chlorpropamide alcohol flush, in non-insulin dependent diabetes. 689 21

We reviewed diabetic gangrene in 104 American blacks and found that the clinical features were similar to those reported for the general diabetic population. We observed, however, that there was a significant association of hypertension with above-knee and bilateral amputations in our patients (P less than .001 and .01, respectively), and that the mean blood pressure of the bilateral amputees (124.5 +/- 3.8 mm Hg) (SEM) was significantly higher (P less than .005) than that of the unilateral amputees (114.4 +/- 1.7 mm Hg). There results suggest a strong association of hypertension with far-advanced occlusive vascular disease of the lower limbs. Moderately severe anemia (hematocrit 20% to 30%) was associated significantly with primary above-knee amputation and mortality (P less than .02 and .05, respectively). Mortality resulted mostly from mixed causes (cardiopulmonary failure, uremia, sepsis, diabetic coma). The dead patients had significantly increased prevalence of cardiac disease (P less than .02), higher frequency of above-knee amputation (P less than .01), and a duration of diabetes (17.4 +/- 2.8 years) significantly longer (P less than .025) than that of the surviving patients (12.0 +/- 1.0 years).
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PMID:Diabetic gangrene in black patients. 706 2

The aim of this study was to compare the intensity of typical late complications in diabetic patients (n = 65, 28 type I, 37 type II) who were not on glycoside drugs with low vs. high serum levels of digoxin-like immunoreactive factor (DLIF: group I, n = 42, DLIF < or = the detection limit of 0.2 ng ml-1; and group II, n = 23, mean +/- SEM: 1.17 +/- 0.31 [0.25-4.96] ng ml-1). For detection of nephropathy, urinary albumin excretion (24 h) and creatinine clearance tests were used. For coronary heart disease a questionnaire and standard ECG; for peripheral occlusive vascular disease a questionnaire; for eye disease a fundoscopy; for neuropathy a neurological score system; and for autonomic neuropathy a standardized test battery was employed. Patients with high DLIF levels showed better test results in vibratory perception (95.7 +/- 1.5 vs. 82.8 +/- 3.8%, normal finding = 100%, 2p = 0.016), had better percentile localizations concerning maximal pupillary area in darkness (28.4 +/- 6.6 vs. 8.1 +/- 1.8%, 2p = 0.0004), contraction velocity at 1 s (21.5 +/- 5.8 vs. 8.0 +/- 2.2%, 2p = 0.012), and dilation velocity at 6 s (23.0 +/- 6.8 vs. 10.5 +/- 2.5%, 2p = 0.041), had less retinopathy (with retinopathy: 26.1% vs. 64.3%, 2p = 0.0028), and better percentile localizations in the respiratory sinus arrhythmia test (68.4 +/- 7.3 vs. 44.1 +/- 4.9%, 2p = 0.0064). There was no difference concerning nephropathy, blood pressure, coronary heart disease and peripheral vascular disease. Separate analysis according to the type of diabetes confirmed the results in each group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of digoxin-like immunoreactive factor on late complications in patients with diabetes mellitus. 795 6

Hyperlipidemia is a significant risk factor for atherosclerotic vascular disease. We have shown previously that pancreas transplantation (PTX) improves but does not normalize lipids in most PTX recipients. We studied whether pravastatin was effective in treating 10 patients with elevated low density lipoprotein (LDL)-cholesterol (LDL-C) following PTX. Seven men and 3 women were studied. Six received combined kidney-pancreas transplantations, while 4 received PTX alone. Age at time of PTX was 37.2 +/- 2.2 years (mean +/- SEM), and 4 had established coronary artery disease before PTX. Mean cholesterol (C), LDL-C, triglycerides (TG), and high density lipoprotein (HDL)-cholesterol (HDL-C) were 236 +/- 12, 142 +/- 6, 222 +/- 50, and 49 +/- 4 mg/dl before PTX. The LDL to HDL ratio was 3.0 +/- 0.3. After PTX, excluding the first 45 days, mean C, LDL-C, and HDL-C increased to 278 +/- 10, 178 +/- 7, and 63 +/- 6 mg/dl (all P < or = 0.05), respectively. TG, LDL to HDL ratio, and weight were unchanged. Pravastatin (11.7 +/- 0.8 mg/day, mean +/- SEM) was initiated 250 +/- 53 days after PTX. During therapy, C and LDL-C decreased on average to 231 +/- 10 and 134 +/- 8 mg/dl, respectively (both P < 0.01), while HDL did not change. The decreases in C and LDL-C were unexplained by a decrease in weight, cyclosporine dose or concentration, or increase in serum creatinine. However, prednisone dose decreased over the same interval, so a contribution from this variable cannot be excluded. No evidence of toxicity was identified during therapy. This is one of the first reports demonstrating that pravastatin is a safe and effective treatment for elevated C and LDL-C in patients following PTX. However, pravastatin did not increase HDL or decrease TG, as observed in the nontransplantation setting. Whether pravastatin or any hypolipidemia therapy can prevent cardiovascular events or mortality following PTX remains to be established.
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PMID:Pravastatin reduces serum cholesterol and low density lipoprotein concentrations following pancreas transplantation. 799 64

Hyperinsulinemia has been implicated as a separate risk factor for the development of accelerated cardiovascular disease, but the mechanism is unknown. Recently, we and several other groups have shown that insulin stimulates the production and secretion of the vasoconstrictor peptide endothelin-1 (ET-1) from vascular endothelial cells, and hyperinsulinemia results in increased plasma ET levels in vivo. However, the interactive effects of diabetes, insulin, and glucose on ET target tissues, like those on vascular smooth muscle cells (VSMC), are not well defined. In these studies, we examined the effects of the diabetic factors on ET receptors and [3H]thymidine incorporation into cultured cells prepared from control, streptozocin-diabetic, insulin-treated diabetic, and hyperinsulinemic rats. Scatchard analysis of saturation binding studies revealed a 2-fold increase in ET receptor number in normal VSMC treated in vitro with insulin, whereas glucose had no significant effect. Neither treatment affected receptor affinity. Similarly, aortic smooth muscle cells, brain capillary pericytes, and kidney afferent arteriolar smooth muscle cells from rats made hyperinsulinemic in vivo each showed approximately a 2-fold increase in receptor number. This increase in receptor density probably resulted from the stimulation of receptor protein production, because insulin caused a maximal 2.3 +/- 0.3 (+/- SEM) fold increase in the ETA receptor mRNA expressed in cultured VSMC by 4 h. Both insulin and ET significantly increased thymidine incorporation in aortic VSMC, but ET-1 was much more potent in this regard. However, the combined effects of insulin plus ET-1 resulted in a 10-fold increase in this index of cell proliferation, significantly different from the effects of either peptide alone. We postulate that hyperinsulinemia in vivo may potentiate ET release and receptor-mediated action, thereby contributing to vascular disease in the setting of diabetes.
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PMID:Insulin stimulates endothelin binding and action on cultured vascular smooth muscle cells. 836 55

Evidence suggests that magnesium deficiency may play an important role in cardiovascular disease. In this study, we evaluated the effects of a magnesium infusion and dietary-induced isolated magnesium deficiency on the production of thromboxane and on angiotensin II-mediated aldosterone synthesis in normal human subjects. Because insulin resistance may be associated with altered blood pressure, we also measured insulin sensitivity using an intravenous glucose tolerance test with minimal model analysis in six subjects. The magnesium infusion reduced urinary thromboxane concentration and angiotensin II-induced plasma aldosterone levels. The low magnesium diet reduced both serum magnesium and intracellular free magnesium in red blood cells as determined by nuclear magnetic resonance (186 +/- 10 [SEM] to 127 +/- 9 mM, p < 0.01). Urinary thromboxane concentration measured by radioimmunoassay increased after magnesium deficiency. Similarly, angiotensin II-induced plasma aldosterone concentration increased after magnesium deficiency. Analysis showed that all subjects studied had a decrease in insulin sensitivity after magnesium deficiency (3.69 +/- 0.6 to 2.75 +/- 0.5 min-1 per microunit per milliliter x 10(-4), p < 0.03). We conclude that dietary-induced magnesium deficiency 1) increases thromboxane urinary concentration and 2) enhances angiotensin-induced aldosterone synthesis. These effects are associated with a decrease in insulin action, suggesting that magnesium deficiency may be a common factor associated with insulin resistance and vascular disease.
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PMID:Magnesium deficiency produces insulin resistance and increased thromboxane synthesis. 850 87

Diabetes mellitus may be associated with magnesium depletion, which in turn may contribute to metabolic complications of diabetes including vascular disease and osteoporosis. Intracellular depletion is thought to be due to osmotically induced renal magnesium loss; however, impaired ability of insulin to increase intracellular magnesium during insulin deficiency or insulin resistance could also play a role. Magnesium deficiency per se has also been reported to result in insulin resistance. In order to determine if magnesium transport is altered in non-insulin-dependent diabetes mellitus (NIDDM), we measured intracellular Mg(2+) in circulating lymphocytes obtained from nine normal subjects and seven patients with NIDDM. Ionized intracellular Mg(2+) was determined by fluorescent spectroscopy using Mg-fura-2. A 30 min incubation of insulin with lymphocytes obtained from normal subjects resulted in an increase in Mg(2+) of 8.6 +/- 3.6 percent (mean +/- SEM) at 100 mu U/ml which reached a plateau at approximately 250 mu U/ml (11.0 +/- 1.7 percent). The mean lymphocyte Mg(2+) in the patients (0.198 +/- 0.011 mM) was not significantly lower than normal (0.218 +/- 0.017). Insulin (500 mU/ml) added acutely during the fluorescence reading caused a rapid 31 +/- 3.9 percent rise in intracellular Mg(2+) in the normal subjects, which was significantly greater than the 18 +/- 1.6 percent rise observed in the NIDDM subjects (P < 0.01). The effect of magnesium deficiency was also studied in 3 normal subjects experimentally Mg deficient for 3 weeks. The mean lymphocyte Mg(2+) fell from 0.198 +/- 0.009 mM pre-diet to 0.153 +/- 0.006 mM post-diet. and the insulin-induced rise in Mg(2+) fell from 27.2 percent pre-magnesium depletion to 12.7 percent post-magnesium depletion. These data suggest that insulin resistance and magnesium depletion may result in a vicious cycle of worsening insulin resistance and decrease in intracellular Mg(2+) which may limit the role of magnesium in vital cellular processes.
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PMID:Magnesium transport induced ex vivo by a pharmacological dose of insulin is impaired in non-insulin-dependent diabetes mellitus. 886 Nov 35

Hypopituitary patients, particularly women, have excess mortality, mostly due to vascular disease. We have studied circulating lipid and lipoprotein concentrations, fasting and over 24 h, in hypopituitary women and men and in matched controls. Firstly, 67 hypopituitary patients (36 women) and 87 normal controls (54 women) were studied after an overnight fast. Secondly, 12 patients (6 women) and 14 matched controls (7 women) were studied over 24 h of normal meals and activity. The patients were all GH deficient and were replaced with cortisol, T4, and sex hormones where appropriate, but not with GH. In the first study, circulating triglycerides, total cholesterol, high density lipoprotein (HDL) cholesterol, and low density lipoprotein (LDL) cholesterol were measured after an overnight fast. In the second study, fasting levels of apolipoprotein B, apolipoprotein A1, and lipoprotein(a) were also measured, and then circulating triglyceride and total cholesterol concentrations were measured over 24 h. Fasting concentrations of triglyceride (mean +/- SEM, 1.73 +/- 0.22 vs. 1.11 +/- 0.09 mmol/L; P = 0.0025), total cholesterol (6.45 +/- 0.25 vs. 5.59 +/- 0.21 mmol/L; P = 0.002), LDL cholesterol (4.58 +/- 0.24 vs. 3.80 +/- 0.19 mmol/L; P = 0.007), and apolipoprotein B (135 +/- 10 vs. 111 +/- 9 mg/dL; P = 0.048) were elevated in hypopituitary compared to control women. The lipid alterations were observed in older and younger women and occurred independently of sex hormone or glucocorticoid replacement. Fasting values were not significantly different in hypopituitary and control men. Patients and controls (women and men) had similar fasting HDL cholesterol, apolipoprotein A1, and lipoprotein(a) concentrations. Although the differences that existed in fasting lipid values were most marked in women, the men were also abnormal in this respect, in that a higher proportion of hypopituitary than control men had total and LDL cholesterol above recommended values (> or = 6.2 and > or = 4.1 mmol/L, respectively). In the postprandial period (0730-2030 h), the areas under the curve (AUC) for circulating triglyceride and total cholesterol were significantly higher in hypopituitary than control women (P = 0.0089 and P = 0.0016, respectively). The AUC for triglyceride and total cholesterol over 24 h were also significantly increased (P = 0.009 and P = 0.0004, respectively). No significant differences were observed for postprandial and 24-h AUC for triglyceride and total cholesterol concentrations in men. We conclude that hypopituitarism with conventional replacement therapy is associated with unfavorable fasting and postprandial lipid and lipoprotein concentrations, particularly in women. The changes may contribute to the observed increased vascular morbidity and mortality.
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PMID:Fasting and postprandial lipid abnormalities in hypopituitary women receiving conventional replacement therapy. 925 49

Premature atherosclerosis is a major cause of morbidity and mortality in chronic renal failure (CRF). Endothelial dysfunction is a key early event in atherogenesis. The aim of this study was to assess the effect of CRF on endothelial function using physiological and biochemical measures. To focus on the effect of CRF itself, 23 children (matched with 23 controls for age and vessel diameter) were selected because they were normotensive, had normal total cholesterol (TC) levels, and were not on vasoactive drugs. Their mean (range) age was 12.0 (7.8 to 17.0) years; GFR 17.5 (8.8 to 34.5) ml/min/1.73 m2. The physiology of endothelial function in the brachial artery was assessed using high resolution ultrasound by measuring its diameter at rest, during reactive hyperemia (endothelium dependent dilation) and after sublingual glyceryl trinitrate (GTN; endothelium independent dilation). Nitric oxide (NO) metabolites and endogenous NO synthetase (eNOS) inhibitors were measured as an assessment of endothelial metabolism. Brachial artery dilation to flow [FMD, mean (SEM)%] was reduced in CRF to 4.9 (0.6) and controls 8.6 (0.6), P < 0.0001. In contrast, the response to GTN was similar in both groups: CRF 25.1 (1.6), controls 23.3 (1.2), P = 0.31. There was no difference in TC, low density lipoprotein (LDL) or high density lipoprotein (HDL) between the patients and the controls. Triglycerides (TG) were higher in the patients but within the normal range. Antibodies against oxidized LDL (ox-LDL) were high in CRF. Endogenous NOS inhibitors were high in CRF, and intermediate NO metabolites were low. There was no correlation between FMD of the brachial artery and lipid subfractions, or with NO metabolites or eNOS inhibitors. Endothelium dependent dilation of the brachial artery is impaired in children with CRF who do not have co-existing risk factors for atherosclerosis. This may represent early evidence of atherogenic vascular disease.
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PMID:Physiology and biochemistry of endothelial function in children with chronic renal failure. 926 3


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