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Biomedical subjects

N E Fink

Publications and source records attributed to N E Fink.

At least 19 recordsLinked to original sources

Three single-nucleotide polymorphisms in LPA account for most of the increase in lipoprotein(a) level elevation in African Americans compared with European Americans.

BACKGROUND: The extent which universally common or population-specific alleles can explain between-population variations in phenotypes is unknown. The heritable coronary heart disease risk factor lipoprotein(a) (Lp(a)) level provides a useful case study of between-population variation, as the aetiology of twofold higher Lp(a) levels in African populations compared with non-African populations is unknown. OBJECTIVE: To evaluate the association between LPA sequence variations and Lp(a) in European Americans and African Americans and to determine the extent to which LPA sequence variations can account for between-population variations in Lp(a). METHODS: Serum Lp(a) and isoform measurements were examined in 534 European Americans and 249 African Americans from the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease Study. In addition, 12 LPA variants were genotyped, including 8 previously reported LPA variants with a frequency of >2% in European Americans or African Americans, and four new variants. RESULTS: Isoform-adjusted Lp(a) level was 2.23-fold higher among African Americans. Three single-nucleotide polymorphisms (SNPs) were independently associated with Lp(a) level (p<0.02 in both populations). The Lp(a)-increasing SNP (G-21A, which increases promoter activity) was more common in African Americans, whereas the Lp(a)-lowering SNPs (T3888P and G+1/inKIV-8A, which inhibit Lp(a) assembly) were more common in European Americans, but all had a frequency of <20% in one or both populations. Together, they reduced the isoform-adjusted African American Lp(a) increase from 2.23 to 1.37-fold(a 60% reduction) and the between-population Lp(a) variance from 5.5% to 0.5%. CONCLUSIONS: Multiple low-prevalence alleles in LPA can account for the large between-population difference in serum Lp(a) levels between European Americans and African Americans.

Adolescent↗

Changes in serum calcium, phosphate, and PTH and the risk of death in incident dialysis patients: a longitudinal study.

Elevated bone mineral parameters have been associated with mortality in dialysis patients. There are conflicting data about calcium, parathyroid hormone (PTH), and mortality and few data about changes in bone mineral parameters over time. We conducted a prospective cohort study of 1007 incident hemodialysis and peritoneal dialysis patients. We examined longitudinal changes in bone mineral parameters and whether their associations with mortality were independent of time on dialysis, inflammation, and comorbidity. Serum calcium, phosphate, and calcium-phosphate product (CaP) increased in these patients between baseline and 6 months (P<0.001) and then remained stable. Serum PTH decreased over the first year (P<0.001). In Cox proportional hazards models adjusting for inflammation, comorbidity, and other confounders, the highest quartile of phosphate was associated with a hazard ratio (HR) of 1.57 (1.07-2.30) using both baseline and time-dependent values. The highest quartiles of calcium, CaP, and PTH were associated with mortality in time-dependent models but not in those using baseline values. The lowest quartile of PTH was associated with an HR of 0.65 (0.44-0.98) in the time-dependent model with 6-month lag analysis. We conclude that high levels of phosphate both at baseline and over follow-up are associated with mortality in incident dialysis patients. High levels of calcium, CaP, and PTH are associated with mortality immediately preceding an event. Promising new interventions need to be rigorously tested in clinical trials for their ability to achieve normalization of bone mineral parameters and reduce deaths of dialysis patients.

Adult↗

Undertreatment of hyperlipidemia in a cohort of United States kidney dialysis patients.

BACKGROUND: Application of national guidelines regarding cardiovascular disease risk reduction to kidney dialysis patients is complicated by the conflicting observations that dialysis patients have a high risk of atherosclerotic cardiovascular disease (ASCVD), but dialysis patients with higher serum cholesterol have lower mortality rates. Actual treatment patterns of hyperlipidemia are not well studied. METHODS: We assessed the prevalence, treatment and control of hyperlipidemia in this high-risk patient population from 1995 - 1998. We measured low-density lipoprotein cholesterol, treatment with a lipid-lowering agent, and prevalence of hyperlipidemia as defined by the National Cholesterol Education Program (NCEP), Adult Treatment Panel (ATP) II guidelines in 812 incident hemodialysis (HD), and peritoneal dialysis (PD) patients from dialysis clinics in 19 states throughout the United States. RESULTS: Hyperlipidemia was present in 40% of HD and 62% of PD patients. Among subjects with hyperlipidemia, 67% of HD and 63% of PD patients were untreated and only 22% of HD and 14% of PD patients were treated and controlled. Those who entered the study in 1997 or 1998, those with diabetes, males and Caucasians were more likely to be treated and controlled, whereas subjects on PD and those with ASCVD were less likely to be treated and controlled. CONCLUSION: These data suggest that high rates of undertreatment exist in the United States ESRD dialysis population. Whether improved rates of treatment will result in decreased cardiovascular disease events needs to be tested in randomized clinical trials.

Cardiovascular Diseases↗

Blood lead content in a peri-urban population of the South American toad Bufo arenarum.

Blood Pb concentration in a South American toad Bufo arenarum population (n = 152) was determined over 10 samplings carried out between December 1996 and November 1999. The studied population lived in the surroundings of the La Plata City, the largest industrial-urban setting of the Buenos Aires Province, Argentina. The presence of the metal was detected in all the samples tested, the mean concentration range being 1.99-4.66 mg dl(-1). Some preliminary environmental data on soil content of Pb in the sampling area suggest the anthropogenic origin of the metal possibly due to high rate of Pb-containing gasoline utilisation until recently. The reported results may reflect a sequel of a sustained local air-soil-water pollution process.

Animals↗

U.S. nephrologists' attitudes towards renal transplantation: results from a national survey.

BACKGROUND: Renal transplantation is the optimal treatment for persons with end-stage renal disease (ESRD). A shortage of kidneys in the U.S. has focused increasing attention on the process by which kidneys are allocated. A national survey was undertaken to determine the relative importance of both clinical and nonclinical factors in the recommendation for renal transplantation by U.S. nephrologists. METHODS: We conducted a national random survey of 271 U.S. nephrologists using hypothetical patient scenarios to determine their recommendation for renal transplantation based on demographic, clinical, and social factors. Specifically, eight unique patient scenarios were randomly distributed to each survey respondent. RESULTS: According to responding nephrologists (response rate 53%), females were less likely than males to be recommended for renal transplantation [adjusted odds ratio (OR)=0.41; confidence interval (CI) 0.21, 0.79; for whites]. Asian males were less likely than white males to be recommended for transplantation (OR=0.46, CI 0.24, 0.91). Black-white differences in rates of recommendation were not found. Other factors associated with low rates of recommendation for renal transplantation included history of noncompliance (OR=0.17, CI 0.13, 0.23), <25% cardiac ejection fraction (OR=0.15, CI 0.10, 0.21), HIV infection (OR=0.01, CI 0.00, 0.01), and being >200 lbs (OR=0.73, CI 0.56, 0.95). CONCLUSIONS: Female gender, and Asian but not black race, were associated with a decreased likelihood that nephrologists would recommend renal transplantation for patients with end stage renal disease. The well-documented black-white disparities in use of renal transplantation may be due to unaccounted for factors or may arise at a subsequent step in the transplantation process.

Adult↗

Developing a health-related quality-of-life measure for end-stage renal disease: The CHOICE Health Experience Questionnaire.

The Choices for Healthy Outcomes in Caring for End-Stage Renal Disease ([ESRD] CHOICE) Study was designed to evaluate the effectiveness of alternative dialysis prescriptions. As part of CHOICE, we developed an instrument for measuring health-related quality of life (HRQOL) for patients with ESRD that would complement the Medical Outcomes Study 36-Item Short-Form Survey (SF-36) and be sensitive to differences in dialysis modality (hemodialysis [HD] and peritoneal dialysis [PD]) and dialysis dose. The selection of HRQOL domains to be included was based on: (1) a structured literature review of 47 articles describing 53 different instruments; (2) content analysis of five focus groups with HD and PD patients, nephrologists, and other providers; (3) a survey of 110 dialysis providers about features of different modalities that affect patient HRQOL; and (4) a semistructured survey of 25 patients with ESRD on the effects of dialysis on functioning and HRQOL. To help prioritize domains and items identified by these methods, a representative sample of 136 dialysis patients rated each item for frequency and bother. A panel of nephrologists provided advice about the salience of items to modality or dose. Items and scales were selected with a preference for existing measures tested in patients with ESRD and were tested for reliability and validity. The first four steps yielded 22 HRQOL domains that included 96 items: 8 generic domains in the SF-36 (health perceptions, physical, social, physical and emotional role function, pain, mental health, and energy); 8 additional generic domains (cognitive functioning, sexual functioning, sleep, work, recreation, travel, finances, and general quality of life); and 6 ESRD-specific domains (diet, freedom, time, body image, dialysis access [catheters and/or vascular], and symptoms). New items were developed or adapted to assess ESRD-specific domains. Scales for these items showed adequate internal consistency (Cronbach's alpha > 0.70, except for time [alpha = 0.57] and quality of life [alpha = 0.68]), as well as convergent and discriminant construct validity in a sample of 928 patients. The final questionnaire included 21 domains (time was deleted) and 83 items. We have designed a patient-centered instrument, the CHOICE Health Experience Questionnaire, that addresses domains that may be sensitive to differences in dialysis modality and dose and shows evidence for reliability and validity as a measure of HRQOL in ESRD.

Adult↗

Timing of nephrologist referral and arteriovenous access use: the CHOICE Study.

Recent clinical practice guidelines recommend the creation of an arteriovenous (AV) vascular access (ie, native fistula or synthetic graft) before the start of chronic hemodialysis therapy to prevent the need for complication-prone dialysis catheters. We report on the association of referral to a nephrologist with duration of dialysis-catheter use and type of vascular access used in the first 6 months of hemodialysis therapy. The study population is a representative cohort of 356 patients with questionnaire, laboratory, and medical record data collected as part of the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease Center Study. Patients who reported being seen by a nephrologist at least 1 month before starting hemodialysis therapy (75%) were more likely than those referred later to use an AV access at initiation (39% versus 10%; P < 0.001) and 6 months after starting hemodialysis therapy (74% versus 56%; P < 0.01). Patients referred within 1 month of initiating hemodialysis therapy used a dialysis catheter for a median of 202 days compared with 64, 67, and 19 days for patients referred 1 to 4, 4 to 12, and greater than 12 months before initiating hemodialysis therapy, respectively (P trend < 0.001). Patients referred at least 4 months before initiating hemodialysis therapy were more likely than patients referred later to use an AV fistula, rather than a synthetic graft, as their first AV access (45% versus 31%; P < 0.01). These associations remained after adjustment for age, sex, race, marital status, education, insurance coverage, comorbid disease status, albumin level, body mass index, and underlying renal diagnosis. These data show that late referral to a nephrologist substantially increases the likelihood of dialysis-catheter use at the initiation of hemodialysis therapy and is associated with prolonged catheter use. Regardless of the time of referral, only a minority of patients used an AV access at the initiation of treatment, and greater than 25% had not used an AV access 6 months after initiation. Thus, further efforts to improve both referral patterns and preparation for dialysis after referral are needed.

Adolescent↗

US nephrologists' recommendation of dialysis modality: results of a national survey.

Selection of a dialysis modality for persons with end-stage renal disease (ESRD) has important lifestyle and occupational implications. The factors affecting modality choice remain unclear, resulting in a low rate of peritoneal dialysis (PD) in the United States compared with other countries. A national survey of 271 US nephrologists was conducted from June 1997 to June 1998 to assess the relative importance of nonclinical and clinical factors related to dialysis modality selection for patients with ESRD. Hypothetical patient scenarios were randomly assigned to nephrologists to determine their recommendation for dialytic therapy based on patient demographic, clinical, and social factors. US nephrologists were more likely to recommend PD for men with ESRD compared with women (39% versus 33%; P: < 0.05; adjusted odds ratio, 1.44; 95% confidence interval, 1.15 to 1.80), as well as for patients with good compliance (adjusted odds ratio, 11.80; 95% confidence interval, 9.29 to 15.01), weight less than 200 lb (adjusted odds ratio, 2.3; 95% confidence interval, 1.8 to 2.9), residual renal function (adjusted odds ratio, 2.14; 95% confidence interval, 1.71 to 2.70), absence of diabetes (adjusted odds ratio, 2.0; 95% confidence interval, 1.6 to 2.5), and living with family (adjusted odds ratio, 1.7; 95% confidence interval, 1.4 to 2.1). Nephrologists in practice for 11 or more years were less likely to recommend PD. The association of male sex with PD therapy suggests a potential bias or sensitivity to women's perception of body image. Race was not associated with PD recommendations after controlling for other demographic and clinical characteristics. Because the incident US ESRD population is increasingly characterized by factors associated with not selecting PD (diabetes, obesity, malnourishment, living alone, and substance abuse problems), our results suggest that PD use may decrease over time.

Adult↗

Formal literature review of quality-of-life instruments used in end-stage renal disease.

Although quality-of-life assessment is an important complement to conventional clinical evaluation, there are limited opportunities for researchers in end-stage renal disease (ESRD) to examine evidence for a range of quality-of-life measures. To better understand how quality of life has been conceptualized, measured, and evaluated for ESRD, we conducted a structured literature review. Eligible articles were identified from a MEDLINE search, expert input, and review of references from eligible articles. A standardized instrument was created for article review and included type of measure, instrument development process, study sample characteristics, quality-of-life domains, and reliability and validity testing. From 436 citations, 78 articles were eligible for final review, and of those, 47 articles contained evidence of reliability or validity testing. Within this set, there were 113 uses of 53 different instruments: 82% were generic and 18% were disease specific. Only 32% defined quality of life. The most frequently assessed domains were depression (41%), social functioning (32%), positive affect (30%), and role functioning (27%). Testing was completed for test-retest reliability (20%), interrater reliability (13%), internal consistency (22%), content validity (24%), construct validity (41%), criterion validity (55%), and responsiveness (59%). Few articles measuring quality of life in ESRD defined quality-of-life domains or adequately described instrument development and testing. Generic measures, such as the Sickness Impact Profile, and disease-specific measures, such as the Kidney Disease Questionnaire, had been tested more thoroughly than others. Standardized reporting and more rigorous testing could help researchers make informed choices about instruments that would best serve their own and their patients' needs.

Humans↗

Blood lead concentration and delta-aminolevulinic acid dehydratase activity in adult Bufo arenarum.

The effects of sublethal doses of lead (as acetate) on blood parameters of adult male Bufo arenarum were studied. Toads received one single injection with 10, 25, 50 or 100 mg/kg of body weight, equivalent to approximately 1/90-1/10 of the 120 h-LD50; seven days after the injections, the hematocrit and the blood delta-aminolevulinic acid dehydratase (ALAD) activity were measured. Hematocrit of lead-injected animals did not exhibit significant changes respective to controls that received sodium acetate (range 29.8-38.8%). Blood lead concentrations were positively and significantly correlated with the injected metal doses. Blood ALAD activity declined proportionately to the doses of the metal as well as to its whole blood concentration. Because of its sensitivity and specificity, it was concluded that the activity of delta-ALAD may be adopted as a reliable biomarker of Bufo arenarum experimental lead intoxication.

Animals↗

Red blood cell osmotic fragility confidence intervals: a definition by application of a mathematical model.

The red blood cell osmotic fragility test is based on the measure of the resistance of red blood cells to lysis as a function of decreasing NaCl concentration. Up to now, several methods have been used for recording these data, but for the first time, the human red blood cell osmotic fragility confidence interval using the Orcutt mathematical model was determined. The absorbance of the hemoglobin measured at 540 nm, released by the red blood cells of 40 healthy adult individuals, was fitted to the equation Absorbance=p3 erfc ([NaCl] - p1/p2); p3 measures one half the absorbance produced by maximum red blood cell hemolysis, p1 is the [NaCl] producing 50% red blood cell hemolysis, and p2 is the dispersion in [NaCl] producing red blood cell hemolysis. Confidence intervals (mean+/-SD) for the three parameters were as follows: p1=4.2718+/-0.1848; p2=0.1947+/-0.0391, and p3=0.5568+0.0426. The usefulness of this osmotic fragility data analysis method using two pathological samples (beta-thalassemia minor and hereditary spherocytosis) was demonstrated. Parameters of the fitted data were compared with those obtained by the conventional recording method of Beutler.

Adult↗

Immunohistochemical localisation of a galectin from Bufo arenarum ovary.

Galectins are a group of soluble animal lectins that exhibit specificity for beta-galactosides and conserve sequence homology in the carbohydrate-recognition domain. The galectin from Bufo arenarum ovary showed a strong cross-reaction with the lectin of 14.5 kDa purified from embryos at early blastula stage. In this paper, we studied the immunohistochemical localisation of the galectin of 14.5 kDa from ovary of the toad B. arenarum in adult ovary sections. We also analysed the immunohistochemical localisation of the embryonic lectin during early development using the antiserum anti-ovary galectin. In the ovary, oocytes in the previtellogenic stage showed strong reactivity in the nucleus and the cortex but not in the cytoplasm. Oocytes in the stage of primary vitellogenesis exhibited a similar pattern in the nuclear and cortical areas but showed immunostaining in the cytoplasm. Intense nuclear staining was detected in oocytes in the stage of late vitellogenesis and in mature oocytes, which also presented strong reactions in the yolk platelets that completely covered the cytoplasm. In blastula embryos the staining was found in the blastomeres, the yolk platelets and the blastocoele. Each lectin localisation is discussed in relation to potential biological roles in the corresponding tissues.

Animals↗

Red blood cell osmotic fragility in Bufo arenarum exposed to lead.

The effects on red blood cells of a single sublethal dose of Pb of 100 mg kg-1 administrated to adult Bufo arenarum were studied. The blood d-aminolevulinic acid dehydratase (d-ALAD) activity, the red blood cell (RBC) osmotic fragility (OF), and the hematocrit (Hct) were measured in control and lead poisoned toad. The enzyme d-ALAD is considered as a specific biomarker for human and animals lead exposure. In Bufo, lead also provoked a significant decrease in the d-ALAD activity without changes in the Hct. OF test was used to compare the impact of Pb on the extent of the RBC hemolysis produced by osmotic stress. Experimental data (absorbance of solubilized hemoglobin and [NaCl]) were fitted to the Orcutt et al. equation (1995) that allows a precise characterization of the parameters involved in OF. In blood from injected toads, the OF resulted significantly reduced. These changes were interpreted as a consequence of alterations in the composition and conformation of the RBC membrane due to Pb, as it was described for human erythrocytes.

Animals↗

Evaluation and additional recommendations for preparing a whole blood control material.

OBJECTIVE: The assessment of an easy to prepare and low cost control material for Hematology, available for manual and automated methods. MATERIAL AND METHOD: Aliquots of stabilized whole blood were prepared by partial fixation with aldehydes; the stability at different temperatures (4.20 and 37 degrees C) during periods of up to 8-9 weeks and aliquot variability with both methods were controlled. RESULTS: Aliquot variability with automated methods at day 1, expressed as CV% (coefficient of variation) was: white blood cells (WBC) 2.7, red blood cells (RBC) 0.7, hemoglobin (Hb) 0.6, hematocrit (Hct) 0.7, mean cell volume (MCV) 0.3, mean cell hemoglobin (MCH) 0.6, mean cell hemoglobin concentration (MCHC) 0.7, and platelets (PLT) 4.6. The CV (coefficient of variation) percentages obtained with manual methods in one of the batches were: WBC 23, Hct 2.8, Hb 4.5, MCHC 5.9, PLT 41. Samples stored at 4 degrees C and 20 degrees C showed stability, only a very low initial hemolysis being observed, whereas those stored at 37 degrees C deteriobed a rapidly (metahemoglobin formation, aggregation of WBC and platelets, as well as alteration of erythrocyte indexes). CONCLUSIONS: It was confirmed that, as long as there is no exposure to high temperatures during distribution, this material is stable, allowing assessment, both external and internal, for control purposes, with acceptable reproductivity, both for manual and automatic methods.

Hematology↗

Delta-aminolevulinic acid dehydratase (ALAD) activity in blood of Bufo arenarum (Anura).

The aim of the present investigation was to standardize a method for measuring delta-aminolevulinic acid dehydratase (ALAD) activity in circulating red blood cells of adult Bufo arenarum kept in controlled environmental conditions, and to obtain reference basal values suitable for environmental monitoring of lead exposure. The normal ALAD activity for B. arenarum was 131.86 +/- 14.47 U per liter of red blood cells (n = 38, mean +/- SEM; interval 72.98-236.33). In animals exposed to lead, ALAD activity decreased as lead dose increased.

Animals↗

Hematological parameters in Bufo arenarum injected with sublethal dose of lead acetate.

Lead has been recognized as a high risk toxic for most organisms including human. The effects of Pb in non-mammalian vertebrates are poorly known, particularly in anuran amphibians. The purpose of this study was to determine the effect of this metal on some hematological parameters of adult Bufo arenarum. It was found that all parameters remained unaltered within normal ranges, with the exception of reticulocyte counts which was significantly increased compared to the in controls (3.7% vs. 0.2%). It is suggested that the selective change found in reticulocyte count might be considered as an early response of a biomarker to sublethal exposition of Bufo arenarum to lead.

Animals↗

Patient's view of dialysis care: development of a taxonomy and rating of importance of different aspects of care. CHOICE study. Choices for Healthy Outcomes in Caring for ESRD.

Quality assessment efforts to enhance public accountability in dialysis care and to support provider efforts to improve care have lacked patient input. To develop brief patient evaluation or satisfaction surveys suitable for busy clinical settings, knowing patients' priorities can be helpful in deciding which aspects of care should be tracked. We conducted a study to identify salient attributes of dialysis care and to rank the importance of these attributes from the perspective of dialysis patients. We analyzed the content of patient focus group transcripts to characterize dialysis care from the patients' perspective. We then surveyed 86 patients to determine how patients would rank the importance of each aspect to quality of dialysis care. The 18 broad aspects of care identified in the focus group included: (1) care provided by nephrologists, (2) care provided by other physicians (nonnephrologists), (3) care provided by dialysis center nurses, (4) care provided by social workers and psychologists, (5) care provided by dieticians, (6) clergy, (7) care provided by technicians and physician assistants/nurse practitioners, (8) care provided by dialysis center staff in general, (9) supplies, (10) treatment choice and effectiveness, (11) patient education and training, (12) self-care, (13) dialysis machines, (14) unit environment and policies, (15) cost containment, (16) billing, (17) cost of care, and (18) health outcomes. Items ranked in the top 10 by both groups of patients included issues related to nephrologists, other doctors, nurses, and patient education and training. Compared with hemodialysis patients, peritoneal dialysis patients gave higher ratings to hospital doctors' and nurses' attention to cleanliness when working with access sites, how correct the nephrologist's instructions to patients are, whether emergency room doctors check with nephrologists, the amount of information patients get about their diet, and how well nurses answer patients' questions. Patients value certain aspects of dialysis care highly, and these aspects differed in some respects for the relatively small number of hemodialysis and peritoneal dialysis patients studied. Construction of brief questionnaires for quality assessment and assurance requires thoughtful consideration of what questions to include. Knowing patients' priorities regarding the most important aspects of care that have high potential for dissatisfaction may be helpful to continuous quality improvement of end-stage renal disease care.

Adult↗