Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Program on the Surgical Control of the Hyperlipidemias (POSCH) was a randomized controlled clinical trial designed to ascertain whether cholesterol lowering induced by the partial ileal bypass operation would favorably affect overall mortality and the mortality and morbidity due to coronary heart disease. The trial results provided strong clinical and coronary arteriographic support for the beneficial effects of lipid modification for the reduction of atherosclerosis progression. At the same time, the surgery-assigned group experienced diarrhea and an increased incidence of kidney stones and gallstones compared to the control-assigned group. Identical quality of life determinations were performed in the POSCH study population shortly before disclosure of the trial results to the patients and shortly thereafter. The purpose of this dual assessment was to evaluate the effect of knowledge of outcomes on the patients' subjective evaluation of quality of life. The primary instrument utilized for analysis of the perception of quality of life in POSCH was the McMasters Health Index Questionnaire (MHIQ). In addition, four study-specific questions were asked of the trial patients. The results for the MHIQ before disclosure of trial results showed a difference (p = 0.07) favoring the control-assigned group (diet-treated), for the social function index of the MHIQ. After disclosure of the trial results, the difference was larger (p < 0.05). For the four study-specific questions, all differences favored the control-assigned group (p < 0.01) before and after disclosure of the trial results, with the exception of satisfaction with randomization allocation in the surgery-assigned group (p = 0.08). The intragroup MHIQ indices before and after disclosure of the trial results showed no suggestive significant differences, except in the surgery-assigned group, in which there was an improvement in the emotional function index after disclosure of the trial results (p = 0.03). The intragroup responses to the study-specific questions before and after disclosure of the trial results again showed no significant differences, except in the surgery-assigned group, in which there was an improvement in patient satisfaction with randomization allocation after disclosure of the trial results (p = 0.04).(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Perception of quality of life before and after disclosure of trial results: a report from the Program on the Surgical Control of the Hyperlipidemias (POSCH). 811 65

Diarrhea is a common problem among the elderly that can have catastrophic results. Atherosclerosis predisposes older adults to morbid sequelae from dehydration resulting from diarrhea. Deaths related to diarrheal illnesses are recognized among older adults living in the community as well as among those confined to nursing homes. Outbreaks have most often been associated with excess deaths from diarrhea among nursing-home patients. Although most cases of dehydration from diarrhea result from gastrointestinal infections, noninfectious causes of diarrhea related to prescription of laxatives, side effects of medications, and use of enteral feedings are common. Clostridium difficile infection is particularly common among older adults in hospitals and nursing homes, and relapsing disease in these groups may be more frequent than among younger adults. The approach to an elderly patient with diarrhea is to ensure proper hydration using available oral rehydration solutions, proceed with diagnostic tests likely to yield a positive result, avoid the use of harmful antiperistaltic drugs, and provide adequate follow-up of the nutritional state.
 ...
PMID:Approach to acute diarrhea in the elderly. 840 28

We describe a 39-year-old woman with an 8-month history of abdominal pain, diarrhea, and weight loss. Clinical and laboratory evaluation indicated the presence of a malabsorption syndrome. Endoscopy revealed multiple gastric ulcerations and an abnormal "picture" of the duodenal mucosa. At duodenal biopsy, necrosis confined to the distal parts of the enteric villi and a polymorphonuclear leukocyte response were found. Further evaluation revealed intestinal ischemia as a result of mesenteric atherosclerosis. After a revascularization procedure was performed, the symptoms disappeared. The macroscopic and microscopic picture of the bowel normalized. In our search for risk factors of atherosclerosis, we found a substantially increased basal plasma homocysteine concentration. This case suggests that hyperhomocysteinemia may have a causal role in the development of symptomatic, premature atherosclerosis of the mesenteric circulation.
 ...
PMID:Malabsorption syndrome associated with ulceration of the stomach and small bowel caused by chronic intestinal ischemia in a patient with hyperhomocysteinemia. 917 39

The mesenteric and intestinal blood flow is organized and regulated to support normal intestinal function, and the regulation of blood flow is, in part, determined by intestinal function itself. In the process of the development and adaptation of the intestinal mucosa for the support of the digestive processes and host defense mechanisms, and the muscle layers for propulsion of foodstuffs, a specialized microvascular architecture has evolved in each tissue layer. Compromised mesenteric and intestinal blood flow, which can be common in the elderly, may lead to devastating clinical consequences. This problem, which can be caused by vasospasm at the microvascular level, can cause intestinal ischaemia to any of the layers of the intestinal wall, and can initiate pathological events which promote significant clinical consequences such as diarrhea, abdominal angina and intestinal infarction. The objective of this review is to provide the reader with some general concepts of the mechanisms by which neurohumoral vasoactive substances influence mesenteric and intestinal arterial blood flow in health and disease with focus on transmural transport processes (absorption and secretion). The complex regulatory mechanisms of extrinsic (sympathetic-parasympathetic and endocrine) and intrinsic (enteric nervous system and humoral endocrine) components are presented. More extensive reviews of platelet function, atherosclerosis, hypertension, diabetes mellitus, the carcinoid syndrome, 5-hydroxytryptamine and nitric oxide regulation of vascular tone are presented in this context. The possible options of pharmacological intervention (e.g. vasodilator agonists and vasoconstrictor antagonists) used for the treatment of abnormal mesenteric and intestinal vascular states are also discussed.
 ...
PMID:Profile of neurohumoral agents on mesenteric and intestinal blood flow in health and disease. 1005 99

Ischemic colitis is one of the most often seen disorders of the large intestine in the elderly. Common predisposing factors are atherosclerosis, shock, and congestive heart failure, but often, elderly patients have no obvious predisposing or precipitating factors. The typical clinical presentation is acute sudden abdominal pain and distention with bloody diarrhea. Common early radiographic signs are bowel-wall thickening with thumbprinting, and later, ulceration and strictures may be found. Endoscopy is valuable in revealing the sharp demarcation between viable and necrotic colonic mucosa that is a strong indicator of ischemia. Within 48 hours, most patients show favorable response to conservative measures consisting of intravenous hydration, bowel rest, antibiotic therapy, and correction of precipitating processes. Vasoconstricting drugs and corticosteroids are contraindicated. When surgical intervention is indicated, it usually consists of resection of the ischemic segment and exteriorization of the remaining ends of the bowel.
 ...
PMID:When to suspect ischemic colitis. Why is this condition so often missed or misdiagnosed? 1022 95

Ischemic stroke, myocardial infarction and peripheral arterial disease are different clinical manifestations commonly due to the same underlying disease, i.e. atherosclerosis with subsequent thrombosis/embolism (atherothrombosis). Many clinical trials of secondary prevention after stroke or TIA have evaluated the benefit of long-term use of antiplatelet drugs in reducing the risk of subsequent vascular events. Aspirin and triclopidine have been shown to be effective in placebo-controlled studies for the composite outcome of stroke, myocardial infarction, or vascular death. Contrasting with these benefits, there were potentially serious, though rare, adverse effects. These considerations certainly justify the development of new antiplatelet agents. Clopidogrel is a new ADP-receptor antagonist, with a greater activity in animal models of thrombosis. CAPRIE (Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events) was a randomized, blinded, international trial designed to assess the relative efficacy of clopidogrel and aspirin in reducing the risk of the outcome cluster of ischemic stroke, myocardial infarction, or vascular death, as well as to assess their relative safety. 19,185 patients were recruited. The intention-to-treat analysis showed that the relative risk reduction was 8.7% (95% CI 0.3-16.5, p = 0.043) in favor of clopidogrel from an overall annual event rate of ischemic stroke, myocardial infarction, or vascular death, ranging from 5.83% in the aspirin group to 5.33% in the clopidogrel group. The percentage of adverse events reported was higher in the aspirin group for all categories except rash, diarrhea, and abnormal liver function. It seems likely that clopidogrel will replace ticlopidine for stroke prevention, because of its better safety profile, and comparable efficacy. Clopidogrel probably will not replace aspirin as the first line therapy for many clinicians because of its higher cost and lack of widespread experience. However, other clinicians have already decided that they will use clopidogrel as first choice, because of the significant advantage over aspirin demonstrated in the CAPRIE study.
 ...
PMID:Clopidogrel for cerebrovascular prevention. 1047 7

The intestine synthesizes very low density lipoproteins (VLDL) and chylomicrons (CM) to transport fat and fat-soluble vitamins into the blood. VLDL assembly occurs constitutively whereas CM assembly is a characteristic property of the enterocytes during the postprandial state. The secretion of CM is specifically inhibited by Pluronic L81. CM are very heterogeneously-sized particles that consist of a core of triglycerides (TG) and cholesterol esters and a monolayer of phospholipids (PL), cholesterol and proteins. The fatty acid composition of TG, but not PL, in CM mirrors the fatty acid composition of fat in the diet. CM assembly is deficient in abetalipoproteinemia and CM retention disease. Abetalipoproteinemia results due to mutation in the mttp gene and is characterized by the virtual absence of apoB-containing lipoproteins in the plasma. Patients suffer from neurologic disorders, visual impairment, and exhibit acanthocytosis. CM retention disease, an inherited recessive disorder, is characterized by chronic diarrhea with steatorrhea in infancy, abdominal distention and failure to thrive. It is caused by a specific defect in the secretion of intestinal lipoproteins; secretion of lipoproteins by the liver is not affected. Besides human disorders, mice that do not assemble intestinal lipoproteins have been developed. These mice are normal at birth, but defective in fat and fat-soluble vitamin absorption, and fail to thrive. Thus, fat and fat-soluble vitamin transport by the intestinal lipoproteins is essential for proper growth and development of neonates. Recently, differentiated Caco-2 cells and rabbit primary enterocytes have been described that synthesize and secrete CM. These cells can be valuable in distinguishing between the two different models proposed for the assembly of CM. In the first model, the assembly of VLDL and CM is proposed to occur by two 'independent' pathways. Second, CM assembly is proposed to be a product of 'core expansion' that results in the synthesis of lipoproteins of different sizes. According to this model, intestinal lipoprotein assembly begins with the synthesis of 'primordial' lipoprotein particles and involves release of the nascent apoB with PL derived from the endoplasmic reticulum (ER) membrane. In addition, TG-rich 'lipid droplets' of different sizes are formed independent of apoB synthesis. The fusion of lipid droplets and primordial lipoproteins results in the formation of different size lipoproteins due to the 'core expansion' of the primordial lipoproteins.
Atherosclerosis 2000 Jan
PMID:A proposed model for the assembly of chylomicrons. 1058 Jan 65

The main cause of chronic gastrointestinal ischaemia is atherosclerosis. Stenotic lesions of the mesenteric circulation are relatively common, but lead to chronic ischaemic complaints due to collateral circulation in probably only 2-3 per 100,000 inhabitants per year. The classical presentation (post-prandial abdominal pain, weight loss, upper abdominal souffle) is present in a minority of patients only. Symptoms also occur after exercise. Gastric ulcers and diarrhoea are less frequent. Although patients with 2 and 3 vessel involvement (coeliac artery, superior mesenteric artery and inferior mesenteric artery) usually experience the most severe ischemic complaints, patients with single vessel involvement can also develop symptoms. In the diagnosis of cases with abdominal complaints, factors that aggravate or reduce the complaints anamnestically are the guideline for supplementary diagnostics. The more frequent causes of the symptoms are to be excluded first. Doppler-ultrasonography of the mesenteric vessels can detect most stenotic lesions accurately. To establish the diagnosis visceral angiography is needed. A new method of examination is magnetic resonance angiography (MRA). Another new method is tonometry during exercise: a PCO2 value in the lumen that is higher than that in the blood indicates ischaemia. Non-invasive treatment of chronic gastrointestinal ischaemia is aimed at reduction of the gastrointestinal metabolic workload by smaller meals, at suppression of acid secretion, at inhibition of the secretion of gastric acid and on risk factors for atherosclerosis.
 ...
PMID:[Gastrointestinal surgery and gastroenterology. VIII. Gastroenterologic aspects of chronic gastrointestinal ischemia]. 1080 May 48

Aspirin inhibits platelet activation by irreversibly inhibiting platelet cyclooxygenase and thromboxane production, and reduces the odds of serious vascular events (stroke, myocardial infarction or vascular death) by about one quarter in a range of patients with symptomatic atherosclerosis at high risk of a subsequent event. The adenosine diphosphate (ADP) receptor antagonists clopidogrel and ticlopidine are significantly more effective than aspirin in high-risk vascular patients, further reducing the odds of serious vascular events by about 10% (95% CI 2-19%) over the benefit provided by aspirin. The ADP receptor antagonists are also associated with a significant 30% reduction in the odds of gastrointestinal haemorrhage (odds ratio 0.71, 95% CI 0.59-0.86). Ticlopidine increases the odds of skin rash and of diarrhoea by more than twofold compared with aspirin, whereas clopidogrel is associated with a one-third increase in the odds of rash and of diarrhoea. Only ticlopidine increases the odds of neutropenia compared with aspirin. There is no clear evidence as yet for the benefit of dipyridamole or an oral GP IIb/IIIa receptor antagonist as single antiplatelet agents in atherothrombotic patients. Amongst high vascular risk patients, the combination of low-dose aspirin and high-dose dipyridamole is associated with about a 10% (95% CI 0-20%) reduction in the odds of a serious vascular event. Most of this reduction is due to a 23% reduction in non-fatal stroke. The size of this estimate continues to be investigated in an ongoing study of patients with transient ischaemic attack and stroke. The combined use of aspirin and ticlopidine is markedly superior to heparin, warfarin and aspirin for reducing thrombotic complications after coronary artery stenting. Clopidogrel plus aspirin has been shown to be safer than aspirin and ticlopidine in coronary stenting, and is now under long-term evaluation in unstable angina, and other conditions in which patients are at high risk of atherothrombotic events.
 ...
PMID:Current oral antiplatelet agents to prevent atherothrombosis. 1131 17

Cilostazol (Pletal), a quinolinone derivative, has been approved in the U.S. for the treatment of symptoms of intermittent claudication (IC) since 1999 and for related indications since 1988 in Japan and other Asian countries. The vasodilatory and antiplatelet actions of cilostazol are due mainly to the inhibition of phosphodiesterase 3 (PDE3) and subsequent elevation of intracellular cAMP levels. Recent preclinical studies have demonstrated that cilostazol also possesses the ability to inhibit adenosine uptake, a property that may distinguish it from other PDE3 inhibitors, such as milrinone. Elevation of interstitial and circulating adenosine levels by cilostazol has been found to potentiate the cAMP-elevating effect of PDE3 inhibition in platelets and smooth muscle, thereby augmenting antiplatelet and vasodilatory effects of the drug. In contrast, elevation of interstitial adenosine by cilostazol in the heart has been shown to reduce increases in cAMP caused by the PDE3-inhibitory action of cilostazol, thus attenuating the cardiotonic effects. Cilostazol has also been reported to inhibit smooth muscle cell proliferation in vitro and has been demonstrated in a clinical study to favorably alter plasma lipids: to decrease triglyceride and to increase HDL-cholesterol levels. One, or a combination of several of these effects may contribute to the clinical benefits and safety of this drug in IC and other disease conditions secondary to atherosclerosis. In eight double-blind randomized placebo-controlled trials, cilostazol significantly increased maximal walking distance, or absolute claudication distance on a treadmill. In addition, cilostazol improved quality of life indices as assessed by patient questionnaire. One large randomized, double-blinded, placebo-controlled, multicenter competitor trial demonstrated the superiority of cilostazol over pentoxifylline, the only other drug approved for IC. Cilostazol has been generally well-tolerated, with the most common adverse events being headache, diarrhea, abnormal stools and dizziness. Studies involving off-label use of cilostazol for prevention of coronary thrombosis/restenosis and stroke recurrence have also recently been reported.
 ...
PMID:Cilostazol (pletal): a dual inhibitor of cyclic nucleotide phosphodiesterase type 3 and adenosine uptake. 1183 Jul 53


<< Previous 1 2 3 4 5 Next >>