Gene/Protein Disease Symptom Drug Enzyme Compound
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Recombinant human erythropoietin (Epo) has been used successfully to correct the anemia caused by chronic renal failure in patients undergoing dialysis, as well as the anemia associated with other conditions, including cancer therapy. Despite its benefits, it can be associated with adverse side effects. These include hypertension, headaches, increased seizure activity, clotted vascular access, and occasional thromboembolic events, such as myocardial infarction or stroke. We report a potentially new side effect associated with Epo of a cosmetic nature. Three Southeast Asian women with chronic renal failure developed diffuse, nearly total, hair loss during erythropoietin use. Two cases were strongly associated with Epo use, and a third had other intercurrent illnesses as well. Alopecia may be associated with Epo use in certain ethnic populations.
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PMID:Alopecia in three women of Southeast Asian descent with chronic renal failure: possible association with erythropoietin use. 1113 98

Hemodialysis (HD) causes rapid volume shifts and circulatory changes. In chronic renal failure (CRF) Na+/K+ATP-ase is depressed, whereas endogenous digoxin-like factor (EDLF) is elevated. Our aim was to characterize HD-induced cardiovascular adaptation and its possible links to Na+/K+ATP-ase and EDLF. Eleven children with CRF on HD (aged 14.7 +/- 3.7 years) and 11 healthy children were investigated for basic circulatory parameters. Thoracic impedance (Zo) and circulatory parameters were monitored by impedance cardiography (ICG) during HD. Erythrocyte Na+/K+ATP-ase and EDLF were measured before and after HD. Up to the loss of 6% of total body weight, Zo rose linearly with fluid removal, above this no further increase occurred. Heart rate and mean arterial pressure (MAP) were inversely related (r = -0.97); MAP rose in the first and decreased in the second part of HD. Systemic vascular resistance paralleled MAP, whereas stroke volume rapidly decreased, but stabilized in the second part of HD. The ratio of preejection period/ventricular ejection time (PEP/VET) correlated positively with HD duration (r = 0.92), suggesting diminished cardiac filling. Cardiac index (CI) remained stable. EDLF was high in uremia accompanied by depressed Na+/K+ATP-ase (P < 0.05 and P < 0.01, respectively). Following HD Na+/K+ATP-ase normalized. Correlation between Na+/K+ATP-ase activity and MAP was linear (r = 0.85). In conclusion, ICG during HD provides detailed information concerning circulatory adaptation resulting in stable CI, suggesting that the dialysis-induced hypovolemia is compensated by the centralization of the blood volume. Changes of Na+/K+ATP-ase indicate that dialyzable blood pressure-regulating substance(s) inhibit(s) the pump. However, lack of further correlation between Na+/K+ATP-ase, EDLF, and cardiovascular parameters indicates the complexity of the regulatory processes.
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PMID:Monitoring cardiovascular changes during hemodialysis in children. 1119 97

Hypertension is twice as frequent in diabetic patients than in the general population. Its prevalence is higher in Type 2 than in Type 1 diabetes: in the former, the onset of hypertension often precedes the diagnosis of diabetes, whereas, in the latter it is strictly related to the presence of nephropathy. Sympathetic nerve overactivity is crucial in the pathogenesis of hypertension in diabetes. It can be related to the activation of the renin-angiotensin-aldosterone (RAA) system in Type 1 diabetic patients with chronic renal failure, or to a condition of insulin resistance/hyperinsulinemia in Type 2 patients with the metabolic syndrome. In patients with early autonomic neuropathy, vagal impairment can lead to a relative predominance of sympathetic activity in the sympatho-vagal balance. In these patients, the onset of hypertension is frequently preceded by reduced nocturnal dipping. Sympathetic overactivity stimulates RAA activity, promotes sodium reabsorption, and increases heart rate, stroke volume and peripheral vascular resistance, thus inducing hypertension and increasing cardiovascular risk. A number of drugs acting either directly or indirectly on sympathetic activity are available for the treatment of hypertension in diabetic subjects. Opinions on the potential advantages of the metabolic profile of some of these drugs are as yet conflicting.
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PMID:Sympathetic nervous system, diabetes, and hypertension. 1127 May 88

The number of patients who needs for dialysis therapy is increasing rapidly among the older population. Although control of hypertension can delay or arrest the progression of renal failure, there are lacking of studies about antihypertensive treatment of chronic renal failure in the elderly. We have studied the effects of treating hypertension with a calcium antagonist, benidipine, on renal function and blood pressure in 58 patients (mean age: 71 +/- 9) with hypertension and chronic renal insufficiency (the levels of creatinine ranging from 1.5 to 4.0 mg/dl). The underlying disease included glomerulopathies (in 33), diabetic nephropathy (in 15), and other causes (in 10). Forty two patients who had been treated with other antihypertensive drugs other than angiotensin converting enzyme (ACE) inhibitors, antihypertensive drugs were withdrawn 2 weeks before the entry. At the entry, patients should have sitting systolic blood pressure (SBP) of above 160 mmHg and diastolic blood pressure (DBP) of above 90 mmHg. In total, both SBP and DBP decreased from 169/95+/-12.5/8.9 to 148/81+/-16.1/8.0 mmHg (p<0.001) with remaining the serum creatinine levels from 2.2+/-0.8 vs 2.4+/-1.3 mg/dl (P>0.05). Retrospective analysis revealed that in 4 of 4 patients treated with benidipine and 2 of 3 patients with benidipine and ACE inhibitors with systolic blood pressure more than 160 mmHg at the end of the study, the levels of serum creatinine increased from 2.5+/-0.3 to 2.8+/-0.4 with significance (P<0.05). If systolic blood pressure was reduced less than 159 mmHg, 38 of 48 patients did not show any deterioration of renal function. Compared to the significance of SBP in preserving renal function, DBP did not associate with the changes in renal function. No patients died during the study. One patient had transient ischemic attack and one patient had stroke in benidipine treated group. One patient had angina pectoris in benidipine-ACE inhibitors treated group. The results of our trial seem to give some support for the idea that long-acting calcium antagonists such as benidipine are renoprotective through reduction of SBP in the elderly people with hypertension and chronic renal insufficiency. However, if systolic blood pressure was not reduced below 160 mmHg throughout a year, the substantial declines in renal function would be expected.
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PMID:Effects of calcium antagonist, benidipine, on the progression of chronic renal failure in the elderly: a 1-year follow-up. 1133 86

Protein-energy malnutrition (PEM) is common in connection with chronic disease and is associated with increased morbidity and mortality. Because the risk of PEM is related to the degree of illness, the causal connections between malnutrition and a poorer prognosis are complex. It cannot automatically be inferred that nutritional support will improve the clinical course of patients with wasting disorders. We reviewed studies of the treatment of PEM in cases of chronic obstructive pulmonary disease, chronic heart failure, stroke, dementia, rehabilitation after hip fracture, chronic renal failure, rheumatoid arthritis, and multiple disorders in the elderly. Several methodologic problems are associated with nutrition treatment studies in chronically ill patients. These problems include no generally accepted definition of PEM, uncertain patient compliance with supplementation, and a wide range of outcome variables. Avail-able treatment studies indicate that dietary supplements, either alone or in combination with hormonal treatment, may have positive effects when given to patients with manifest PEM or to patients at risk of developing PEM. In chronic obstructive pulmonary disease, nutritional treatment may improve respiratory function. Nutritional therapy of elderly women after hip fractures may speed up the rehabilitation process. When administered to elderly patients with multiple disorders, diet therapy may improve functional capacity. The data regarding nutritional treatment of the conditions mentioned above is still inconclusive. There is still a great need for randomized controlled long-term studies of the effects of defined nutritional intervention programs in chronically ill and frail elderly with a focus on determining clinically relevant outcomes.
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PMID:Treatment of protein-energy malnutrition in chronic nonmalignant disorders. 1272 Jun 5

To determine the nature of neurologic dysfunction after deep hypothermic circulatory arrest during aortic arch surgery, we reconsidered the cases of 154 patients who had undergone aortic arch surgery (either of the ascending or transverse aorta, or both) between November 1993 and July 1999. Temporary postoperative neurologic dysfunction was seen in 9 patients (5.8%), and another 3 patients (1.9%) experienced stroke. Patients with temporary neurologic dysfunction had no new infarct and were discharged home with no residual symptoms. Computed tomographic scans revealed that 2 patients with stroke had multiple infarcts in the brainstem, and the 3rd had bilateral border-zone infarcts. The patients with brainstem infarcts died on postoperative days 7 and 15, and the patient with border-zone infarct was discharged home with no symptoms 3 months after surgery. Univariate analysis revealed that patients with neurologic deficits had significantly higher rates of history of hypertension, concomitant coronary artery bypass grafting, cardiac ischemia times longer than 90 minutes, and chronic renal failure. A multivariate logistic regression analysis revealed that the significant preoperative variables associated with neurologic deficits were a history of hypertension and a cardiac ischemia time longer than 90 minutes. Deep hypothermic circulatory arrest is a safe and useful technique for protection of the brain during surgery for complex aortic problems. In future, some patients at extreme risk for perioperative neurologic complications might be offered novel neuroprotective agents, in combination with deep hypothermia.
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PMID:Neurologic complications after deep hypothermic circulatory arrest: types, predictors, and timing. 1145 37

Moderate hyperhomocysteinemia and endothelial dysfunction are consistent findings in uremic patients. Although an exceedingly high incidence of cardiovascular disease and stroke has been shown in dialysis patients, several traditional risk factors are relatively limited predictors. Hyperhomocysteinemia could be a principal candidate for endothelial dysfunction. Recent findings suggest that hyperhomocysteinemia may impair endothelial function by the generation of oxygen species and decreased nitric oxide (NO) bioavailability. However, the precise mechanisms underlying the link between hyperhomocysteinemia and impaired endothelial function in chronic renal failure remain unclear. Endothelial function was evaluated by the response to reactive hyperemia and donor of NO. We observed impairment in both endothelium-dependent and endothelium-independent vasodilation in dialysis patients. These data suggest that patients with chronic renal failure may have defective NO-mediated function in the endothelium and smooth muscle of vessels. Most reports have shown only impairment of endothelium-dependent vasodilation, whereas another report observed impaired smooth muscle function and intact endothelial function. Only a few previous observations included a full set of vascular function data, such as baseline vessel diameter, reactive hyperemia, and responses of endothelium to hyperemia and NO donor, although all these observations could be essential for comparison with other reports. Treatment with folic acid was reported to reduce plasma homocysteine levels, but not to normal levels, and failed to improve impaired endothelial function in patients in a predialysis phase and on maintenance dialysis therapy. Another investigation, directed at reducing homocysteine levels in earlier stages of renal failure, may be necessary to clarify the link between hyperhomocysteinemia and endothelial function.
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PMID:Association of endothelial dysfunction with sulfur amino acid metabolism in chronic renal failure. 1157 31

To elucidate brain oxygen metabolism in uremic patients, regional cerebral blood flow (rCBF), oxygen extraction (rOEF), and oxygen metabolism (rCMRO(2)) were measured by positron emission tomography (PET) in 10 hemodialysis (HD) patients and 13 predialysis patients with chronic renal failure (CRF). Data were compared with 20 nonuremic patients (controls) without neurological abnormalities, congestive heart failure, history of cerebrovascular accident, diabetes mellitus, or symptomatic brain lesion on magnetic resonance imaging. In the hemisphere, rCMRO(2) in both HD (1.82 +/- 0.10 mL/min/100 g) and CRF patients (1.95 +/- 0.09 mL/min/100 g) showed significantly lower values compared with controls (2.23 +/- 0.05 mL/min/100 g; P < 0.01). Hemispheric rCBF in HD (35.6 +/- 2.1 mL/100 g/min) and CRF patients (36.1 +/- 2.1 mL/100 g/min) was not different from controls (31.8 +/- 1.4 mL/100 g/min). Hemispheric rOEF in CRF patients (45.7% +/- 1.6%) was significantly greater than that in controls (40.5% +/- 1.2%; P < 0.02), but rOEF in HD patients (43.7% +/- 1.9%) did not increase significantly. These tendencies were similar in all regions of interest, especially cerebral cortices. All PET parameters in frontal cortices tended to show the lowest values in patients with renal failure. For all HD patients, rCBF in both the frontal cortex and white matter correlated inversely with HD therapy duration (P < 0.05). In conclusion, brain oxygen metabolism is depressed in patients with renal failure on or before the start of HD therapy. The cause for depressed brain oxygen metabolism is considered to be either dysregulation of cerebral circulation or lower brain cell activity.
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PMID:Depressed cerebral oxygen metabolism in patients with chronic renal failure: a positron emission tomography study. 1157 38

In the early stage of hypertension, diastolic blood pressure has greater prognostic importance, but in the elderly, systolic blood pressure is the most important marker of cardiovascular complications. Therefore, the need for more strict control of this component of blood pressure must be reconsidered. The benefit obtained in different studies in the elderly suggests that the treatment of isolated systolic hypertension is associated with a reduction in overall cardiovascular mortality of 22%, in coronary heart disease mortality of 26%, and in stroke mortality of 33%. However, a higher percentage of patients (73%) attain the diastolic goal of <90 mm Hg, while only 34% have systolic pressure reduced to <140 mm Hg. In a review of randomized trials comparing at least four different antihypertensive drugs, significant differences in systolic blood pressure reduction have not been demonstrated, except in black populations, in whom calcium channel blockers and diuretics seem to be more effective. In patients with isolated systolic hypertension, data are inconclusive, but calcium channel blockers and diuretics appear to lower blood pressure to a greater degree than do other antihypertensive drugs. Two main predictors of difficulty in controlling systolic blood pressure are the baseline blood pressure and the presence of diabetes. Other predictors are the duration of arterial hypertension, older age, the presence of target organ damage and associated clinical conditions (myocardial infarction, stroke, chronic renal failure), and an elevated serum uric acid level. It appears that the profile of patients with a poorer therapeutic response includes a greater severity of hypertension and/or the presence of cardiovascular disease.
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PMID:Factors influencing the systolic blood pressure response to drug therapy. 1182 35

Patients with atherosclerotic renal artery stenosis may develop hypertension, recurrent pulmonary edema and chronic renal failure, but have a much higher risk of dying from stroke or myocardial infarction than of progressing to end-stage renal disease. Indeed, atherosclerotic renal artery stenosis typically occurs in high risk patients with coexistent vascular disease elsewhere. Recent controlled trials comparing medication to revascularization have shown that only a minority of such patients can expect hypertension cure, whereas the results of trials designed to document the ability of revascularization to prevent progressive renal failure are not yet available. Revascularization should be undertaken in patients with atherosclerotic renal artery stenosis and resistant hypertension or heart failure, and probably in those with rapidly deteriorating renal function or with an increase in plasma creatinine levels during angiotensin-converting enzyme inhibition, especially if their renal resistance--index before revascularization is less than 80. With or without revascularization, medical therapy using antihypertensive agents, statins and aspirin is necessary in almost all cases.
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PMID:[Management of atherosclerotic renal artery stenoses]. 1207 Aug 43


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