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We have previously demonstrated that a plasma natriuretic factor is present in Alzheimer's disease (AD), but not in multi-infarct dementia (MID) or normal controls (C). We postulated that the natriuretic factor might induce the increased cytosolic calcium reported in AD by inhibiting the sodium-calcium antiporter, thereby activating the apoptotic pathway. To test for a factor in AD plasma that induces apoptosis, we exposed nonconfluent cultured LLC-PK(1) cells to plasma from AD, MID, and C for 2 h and performed a terminal transferase-dUTP-nick-end labeling (TUNEL) assay. The plasma from AD increased apoptosis nearly fourfold compared with MID and C. The effect was dose dependent and the peak effect was attained after a 2-h exposure. Additionally, apoptotic morphology was detected by electron microscopy, and internucleosomal DNA cleavage was found. We inhibited apoptosis by removing calcium from the medium, inhibiting protein synthesis with cycloheximide, alternately boiling or freezing and thawing the plasma, and digesting a partially purified fraction with trypsin. Heating AD plasma to 56 degrees C did not deactivate the apoptotic factor. These results demonstrate the presence of an apoptotic factor in the plasma of patients with AD.
Background: Accurate information on prevalence and status of blood pressure (BP) control in hemodialysis patients is lacking. Our Hemodialysis Quality Improvement Program, sought to determine: 1) The extent and control of hypertension (HTN), 2) whether Erythropoietin (EPO) dose or intradialytic fluid loss had any effect on BP and 3) a means to follow the severity of HTN. Patients and methods: The pre/post mid-week dialysis BP readings of 190 patients (64 +/- 14.1 years, 53% males, 77% whites) were evaluated over a 3 month period. HTN was defined as BP > 150/90. Hypertension was further characterized according to whether the patients had normal or elevated pre-dialysis systolic, pre-dialysis diastolic, post-dialysis systolic or post-diastolic BP readings on more than 6 of the possible 13 recordings. The average EPO dose and weight loss during dialysis was correlated with BP. To better understand the extent of HTN, systolic and diastolic pressures were separately graded from 0 to 3 and a number designated as hypertension sensitivity index (HSI) was assigned to each patient. Results: Of the 190 patients, 146 (76.8%) were hypertensive. 117 out of 146 hypertensive patients (80.1%) had persistent elevation of BP despite being on one or more antihypertensive medications. Most patients were on calcium channel blockers (39%) with 27% being on beta-blockers and 14% on Angiotensin converting enzyme inhibitors. There was no correlation between the number of medications used and the control of HTN. The dose of EPO also had no effect on the degree of HTN. 69.8% of all HTN was systolic. Of this, 64.7% was pre-dialysis and 35.3% post-dialysis. Multiple regression analysis demonstrated a significant correlation with loss of weight during dialysis and lowering of systolic BP (r = 0.33, p = 0.0001). The mean HSI for this population was 2.3 +/- 1.8. Conclusion: HTN was a frequent finding in our hemodialysis population and it was controlled in only 19.9% of hypertensive patients. Most of this HTN was pre-dialysis systolic. There was a significant correlation between fluid loss during dialysis and lowering of blood pressure. The use of the HSI has proven to be helpful in differentiating type and severity of HTN.
Uric acid metabolism is reviewed as it relates mainly to kidney and electrolyte disorders, with emphasis on the difficulties in understanding urate transport because of its bidirectional transport and the species differences in which animal data may not have relevance to the human condition. A critical review of the effects of pyrazinamide and extracellular volume expansion on urate transport raises questions about the current popular teachings that pyrazinamide exclusively blocks tubule urate secretion and extracellular volume expansion has a major role in controlling urate excretion. There appears to be a renal salt-wasting syndrome with overlapping clinical features that make it indistinguishable from the syndrome of Inappropriate secretion of antidiuretic hormone (SIADH), except possibly for extracellular Volume depletion. Hypouricemia and the elevation in the fractional excretion of urate (%E/F-urate) are extensively reviewed with a proposal to use the persistence of hypouricemia and elevated %E/F-urate after the correction of hyponatremia to differentiate these patients from those with SIADH. An algorithm is proposed to differentiate one group from the other. A plasma natriuretic factor has been shown in some with probable renal salt wasting, which includes patients with AIDS, cancer, and pulmonary and intracranial diseases. The natriuretic factor may have etiologic implications and diagnostic and therapeutic applications. (C) 1998 by the National Kidney Foundation, Inc.
The assessment of iron status for hemodialysis patients has been hindered by the inaccuracy of commonly used diagnostic tests. A novel assay, the reticulocyte hemoglobin content (CHr), has recently been found to sensitively detect functional iron deficiency among nonuremic patients treated with recombinant erythropoietin (rHuEPO). The purpose of this study was to evaluate the CHr far the assessment of iron status in hemodialysis patients. One hundred sixty-four stable hemodialysis patients had a mean CHr of 27.5 +/- 2.8 pg with a normal distribution of values. The mean CH (mature red cell hemoglobin content) was 26.4 +/- 2.4 pg. There was a close correlation between CHr and CH (r = 0.86, P < 0.0001). A significant subgroup of patients (12.2%) had CHr values < CH. These patients had recent increases in rHuEPO dose, and a lower mean transferrin saturation and hematocrit, suggesting the recent onset of functional iron deficiency due to the increase in rHuEPO dose. In the second phase of the study, 32 patients were randomly selected to receive treatment with a single dose infusion of 1,000 mg of intravenous iron dextran (IVFe). Patients were classified as iron deficient (N = 7) if they responded with a significant reticulocytosis (sustained 1 basis point increase in corrected reticulocyte index within 2 weeks). All other patients were classified as iron replete (N = 25). A CHr < 26 pg at baseline predicted iron deficiency with a sensitivity of 100%, specificity of 80%. The serum ferritin, transferrin saturation and percentage of hypochromic red blood cells all were less accurate. The time to correction of iron deficiency at the level of the reticulocyte was found to be within 48 hours as measured by correction of the mean CHr to > 26 pg, and by the shift of the vast majority of the reticulocyte population to CHr > 26 pg within this time span. We conclude that CHr < 26 pg is an accurate measure of iron status in hemodialysis patients, that a CHr value < CH indicates the acute onset of iron deficiency, and that a single dose infusion of intravenous iron results in correction of iron deficiency at the level of the reticulocyte within 48 hours.
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Total Results:
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Cerebral salt-wasting syndrome: does it exist?
Cerebral salt-wasting syndrome (CSWS) has been regarded as a misnomer of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). We take the position that CSWS does exist and might be more common than SIADH. Differentiation between groups has been difficult because of overlapping signs, symptoms, and associated diseases. Euvolemia in SIADH and hypovolemia in CSWS may be the only contrasting variables. However, clinical assessment of extracellular volume is accurate in about 50% of these patients. Determination of serum urate and fractional excretion rates of urate can differentiate one group from the other. In both groups, hyponatremia coexists with hypouricemia and increased fractional excretion of urate. When the hyponatremia is corrected by water restriction, hypouricemia and elevated FEurate correct in SIADH but persist in CSWS. Persistent hypouricemia and elevated FEurate were commonly noted with pulmonary and/or intracranial diseases. The absence of intracranial diseases in some patients suggests that renal salt wasting might be a more appropriate term than CSWS. A review of renal/CSWS reveals three studies involving hyponatremic neurosurgical patients who had decreased blood volume, decreased central venous pressure, and inappropriately high urinary sodium concentrations in the majority of them, suggesting that CSWS was more common than SIADH in neurosurgical patients. Evidence for the presence of a plasma natriuretic factor in CSWS is presented.
PMID: 10364700
ISSN: 1660-8151
CID: 3885392
Partial characterization of apoptotic factor in Alzheimer plasma
ISI:000079665500004
ISSN: 1931-857x
CID: 3464772
Beneficial effects of iron therapy in renal failure patients on hemodialysis
Iron deficiency is a common problem in patients treated with hemodialysis. If not detected and treated appropriately, the effectiveness of recombinant human erythropoietin therapy is compromised. Much has been learned in recent years with respect to iron therapy for hemodialysis patients. A series of studies have clearly defined the efficacy of intravenous iron compounds, and recently released clinical practice guidelines have set the appropriate clinical context for the use of these agents. The purpose of this article is to examine the beneficial effects of iron replacement therapy for hemodialysis patients.
PMID: 10084289
ISSN: 0098-6577
CID: 3885262
Prevalence of hypertension in a hemodialysis population [Meeting Abstract]
ISI:000078661300003
ISSN: 0301-0430
CID: 3464752
Regulation of renal urate excretion: A critical review [Review]
ISI:000077383900003
ISSN: 0272-6386
CID: 3464742
Utilizing continuous quality improvement techniques in dialysis: Application to anemia management
ISI:000071538500013
ISSN: 0894-0959
CID: 3464732
Nutritional supplementation during the hemodialysis treatment in malnourished hemodialysis patients. [Meeting Abstract]
ISI:A1997XY10301193
ISSN: 1046-6673
CID: 3465592
Hematocrit cycling in hemodialysis patients. [Meeting Abstract]
ISI:A1997XY10301082
ISSN: 1046-6673
CID: 3465572
The effect of a multidisciplinary intervention on the admission rate and length of stay of dialysis patients with peripheral vascular disease. [Meeting Abstract]
ISI:A1997XY10301115
ISSN: 1046-6673
CID: 3465582
Reticulocyte hemoglobin content in the evaluation of iron status of hemodialysis patients [Meeting Abstract]
ISI:A1997XG72300027
ISSN: 0085-2538
CID: 3465562
