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Biomedical subjects

A Levin

Publications and source records attributed to A Levin.

At least 37 records · Page 2Linked to original sources
PubMed2001

Mutation analysis of the tyrosinase gene in oculocutaneous albinism.

Type I oculocutaneous albinism (OCA) is an autosomal recessive disorder caused by the reduction or the absence of tyrosinase (TYR) activity in melanocytes of the skin, hair and eyes. Here we report an analysis of 45 patients with OCA. We found five novel mutations in the tyrosinase gene involved in the pathogenesis of oculocutaneous albinism type IA or type IB (OCA-1A/B) in five unrelated patients. Three mutations are missense mutations (G109R, P205T and H256Y) and two are nucleotide deletions (336-337delCA and 678-680delAGG). One patient is homozygous for the previously known V275F mutation but has an extremely mild OCA phenotype and has no eye features typical of OCA. In several patients we discovered only one or even no mutation in the coding sequence of the TYR gene. Thus, this disease may also result from mutations in non coding regions of the gene or in another gene involved in the biosynthesis of melanin. Hum Mutat 17:352, 2001.

Albinism↗
PubMed2001

Cardiovascular disease in patients with chronic kidney disease: getting to the heart of the matter.

The high prevalence of cardiovascular disease (CVD) in patients with kidney disease is well described. This Canadian, multicenter, observational cohort study reports the prevalence and risk factors of CVD associated with kidney disease, in a cohort of patients with established chronic kidney disease (CKD), who are followed-up by nephrologists. This analysis sought to answer 2 questions: (1) in patients with established CKD, are the prevalence and progression of CVD accounted for by conventional or uremia-related risk factors, and (2) to what extent can progression to renal replacement therapy (RRT) be explained by CVD versus traditional risk factors for kidney disease? This study population consists of 313 patients (predominantly men) who had a mean age of 56 years and a mean creatinine clearance of 36 mL/min. Thirty percent were diabetic. The overall prevalence of CVD was 46%, and was independent of severity of kidney dysfunction (P = 0.700). The median follow-up time was 23 months, for a total of 462 patient years. We note the overall incidence of CVD events (new CVD or worsening of CVD) was 47/244 (20%). The best predictors of new CVD events among those without preexisting CVD were diabetes (odds ratio [OR] = 5.35, P = 0.018) and age (OR = 1.26, P = 0.08). In those with preexisting CVD, low diastolic pressure (DP) (OR =.72, P = 0.004) and high triglycerides (OR = 1.48, P = 0.019) at baseline were independent predictors of progression of CVD. We could not determine an independent impact of kidney function on CVD in the overall cohort. Furthermore, we determined that the presence of CVD itself confers an increased risk for progression to RRT (relative risk [RR] = 1.58, P = 0.047), adjusted for kidney function. This is the first in-depth analysis of CVD in a cohort of patients with established chronic kidney disease who are not on dialysis. The question regarding the impact of the altered biology of uremia in contributing to CVD progression remains unanswered, and clearly needs further study. However, the findings do raise the issue of whether aggressive treatment of CVD and risk factors might, in fact, reduce progression to RRT. Further large-scale, observational studies as well as interventional studies are needed to more clearly understand the complex biology of cardiovascular and kidney disease progression.

Age Distribution↗
PubMed2001

Intercellular signaling as a cause of cell death in cyclically impacted cartilage explants.

UNLABELLED: Recently, in vitro cartilage studies have shown that impact loading can produce structural damage and osteoarthritis-like changes, including tissue swelling, collagen denaturation, and cell death. OBJECTIVE: This study was to determine whether a signal for cell death moves through the cartilage matrix, resulting in the spread of cell death over time from impacted to unimpacted regions. DESIGN: Cyclic impacts were applied to the 2 mm core of 4 mm cartilage discs. Post-impact culturing extended for 3, 6 or 21 days and occurred in one of two ways. In one, discs were cultured intact. In the second, cores were removed immediately after cessation of impact and cores and rings cultured separately. Cells in apoptosis and later stage necrosis were monitored using the TUNEL assay. RESULTS: The extent of cell death in impacted samples increased with increased duration of post-impact culturing. At the early time, the majority of cell death was located in the regions of direct impact whereas after extended culture, the extent of cell death was similar in the surrounding unimpacted regions and in the impacted core region. However, the physical separation of the impacted core from the surrounding, non-impacted ring regions immediately after impact, and prior to independent culture, kept the level of cell death in the surrounding ring close to control levels, even after 21 days of incubation. DISCUSSION: These findings indicate that soluble intercellular signalling is involved in the spreading of cell death through the cartilage matrix, and that its effects can be prevented by physical isolation of the surrounding ring from the impacted core.

Analysis of Variance↗
PubMed2001

Screening for renal disease using serum creatinine: who are we missing?

BACKGROUND: Appropriate management and timely referral of patients with early renal disease often depend on the identification of renal insufficiency by primary care physicians. Serum creatinine (SCr) levels are frequently used as a screening test for renal dysfunction; however, patients can have significantly decreased glomerular filtration rates (GFR) with normal range SCr values, making the recognition of renal dysfunction more difficult. This study was designed to estimate the prevalence of patients who have significantly reduced GFR as calculated by the Cockcroft-Gault (C-G) formula, but normal-range SCR: METHODS: The study included 2781 outpatients referred by community physicians to an urban laboratory network for SCr measurement. GFR was estimated using the C-G formula. Patients were grouped according to the concordance of SCr level abnormalities (abnormal >130 micromol/l) with significantly abnormal C-G values (abnormal </=50 ml/min). The C-G value of < or =50 ml/min was chosen to reflect substantial renal impairment in all age groups. A further analysis of historical laboratory data was undertaken to determine if there were previously documented changes in renal function parameters in those patients who had overt renal dysfunction during the study period. RESULTS: Of the 2781 outpatients referred, 2543 (91.4%) had normal SCr levels. Of these patients, 387/2543 (15.2%) had C-G calculated GFR < or =50 ml/min, representing substantially impaired renal function. Among patients with normal SCr, abnormal C-G values were identified in 47.3% > or =70 years old, 12.6% 60-69 years old, and 1.2% 40-59 years old. Analysis of historical available laboratory data for patients with abnormal SCr and abnormal C-G values showed that 2 years prior to the study period, 72% of this group had abnormal SCr, while 18% had normal SCr with abnormal C-G values, and 10% had normal SCr with normal C-G values. CONCLUSIONS: This study documents the substantial prevalence of significantly abnormal renal function among patients identified by laboratories as having normal-range SCR: Including calculated estimates of GFR in routine laboratory reporting may help to facilitate the early identification of patients with renal impairment.

Adolescent↗
PubMed2001

Prevalence of cardiovascular damage in early renal disease.

There is a large burden of cardiovascular disease in early renal disease due to multiple risk factors. Although left ventricular hypertrophy (LVH) is prevalent early in the process of progressive renal decline, it is associated with a number of modifiable risk factors (e.g. anaemia and systolic blood pressure (BP)). More importantly, treatment of modifiable risk factors in renal disease can delay progression. It is important to define anaemia physiologically and to remember that it is also associated with a number of cardiovascular risk factors that may/may not be independent of each other. In a recent prospective, multicentre Canadian study of early renal disease patients prior to dialysis (n=446), the baseline prevalence of LVH increased both with decreasing renal function and decreasing haemoglobin (Hb) levels. Notably, Hb levels within current guideline target levels were still associated with a very high degree of LVH. Over a 12-month period, only a decrease in Hb and an increase in systolic BP, and baseline left ventricular mass index (LVMI) predicted left ventricular growth. Patients whose cardiac symptoms progressed over 12 months were those who experienced a significant fall in BP and a significant increase in LVMI during that time. In the future, steps are needed to ensure early identification of both renal disease and specific risk factors. Recognizing modifiable risk factors and addressing them early in the course of renal disease will facilitate the improvement of patient outcomes.

Anemia↗
PubMed2001

Identification of patients and risk factors in chronic kidney disease--evaluating risk factors and therapeutic strategies.

Three strategies can help delay chronic kidney disease (CKD) progression: early identification of patients, modification of risk factors, and implementation of the best interventions. Early identification of patients requires accurate screening tools. As serum creatinine is an unreliable marker of kidney dysfunction, clinicians should focus on the glomerular filtration rate or other markers of true kidney function. Clinicians should also be aware of other indicators of abnormal kidney function, such as anaemia, acidosis, and increases in parathyroid hormone level. Additionally, both clinicians and patients should be aware of the "non-modifiable" and "modifiable" risk factors for CKD. Non-modifiable risk factors include age, gender, race, diabetes, and genetic make-up, while modifiable risk factors include elevated blood pressure and blood glucose, proteinuria, anaemia, metabolic disturbances, and dyslipidaemia. Patients should be particularly aware of the risk factors common to both cardiac and kidney disease, such as hypertension, proteinuria, anaemia, and (possibly) dyslipidaemia and diabetes. A single centre study demonstrated that inclusion in a multidisciplinary CKD clinic programme produced the greatest increases in time to renal replacement therapy, haemoglobin levels, and epoetin treatment usage at initiation of dialysis in comparison with standard nephrology care or no care. Two years after starting dialysis, the number of deaths was lowest, and the number of patients who had received a transplant or were still on dialysis was highest, in the CKD clinic-treated group. These results confirm those of previous studies, which showed that timely referral to a multidisciplinary team for management prior to dialysis decreases the risk of adverse patient outcomes. This suggests that a multidisciplinary, collaborative, proactive approach increases the likelihood of early identification of CKD patients and risk factor modification. However, further evidence-based demonstrations of success are required, showing benefit to both patients and health care systems.

Humans↗
PubMed2001

Chronic kidney disease: why is current management uncoordinated and suboptimal?

Morbidity and mortality associated with chronic kidney disease (CKD) is higher than that of the normal population, and the incidence of end-stage renal disease (ESRD) continues to increase. Several factors contribute to the uncoordinated and suboptimal management of CKD, including the attitude and behaviour of nephrologists, referring physicians and patients, and economic constraints on healthcare systems. Late referral of at-risk patients to specialist care is an area of particular concern, as this denies nephrologists adequate opportunity to prevent progression of CKD and associated complications such as anaemia. Due to the ageing population and advances in technology, the costs of treating CKD and ESRD continue to escalate and represent another barrier to the delivery of optimal care. Optimizing the care provided to CKD patients requires a coordinated approach to the management of the condition. Closer collaboration and improved communication across specialities is important for the timely referral of patients and for efficient utilization of available resources. A multidisciplinary approach may facilitate patient identification and improve the management of CKD.

Anemia↗
PubMed2001

Obstacles to residents' conducting research and predictors of publication.

Internal medicine residents at one school identified barriers to and predictors of publishing their research. Insufficient time was the key obstacle to completing research. Residents with previous research experience, senior residents, and men were more likely to publish.

Attitude of Health Personnel↗
PubMed2001

Diagnosis of babesiosis using an immunoblot serologic test.

Although the current indirect immunofluorescent assay (IFA) diagnostic antibody test for human babesiosis is sensitive and specific, an immunoblot antibody test may be easier to standardize and to perform. Our objective, therefore, was to determine the efficacy of and develop interpretive criteria for an immunoblot antibody test for diagnosing acute human babesiosis using a Babesia microti whole-cell lysate as the antigen. We compared the reactivity of sera to a B. microti immunoblot assay in 24 human subjects experiencing symptoms and expressing laboratory evidence of babesiosis, 28 subjects who experienced Lyme disease, 12 subjects who experienced human granulocytic ehrlichiosis, and 51 subjects who reported no history of any of these diseases and whose sera did not react against B. microti antigen in an IFA test. Immunoblot strips were impregnated with proteins derived from the GI strain of B. microti that had been electrophoresed in an acrylamide sodium dodecyl sulfate gel, followed by electroblotting onto nitrocellulose membranes. The sera of all subjects who experienced babesiosis reacted against the B. microti antigen in the IFA and against at least one of nine immunoblot protein bands specific to B. microti. In contrast, none of the sera from people who appeared not to have experienced this infection reacted against the B. microti antigen in the IFA (compared to 4% in the immunoblot assay). When two reactive bands were considered as definitive, immunoblot test sensitivity was 96%, while specificity was 99% and predictive positivity and predictive negativity were 96 and 99%, respectively. Our B. microti immunoblot procedure shows promise as a sensitive, specific, and reproducible assay for routine clinical diagnosis of acute babesiosis.

Antibodies, Protozoan↗
PubMed2001

Cardiac risk factors and the use of cardioprotective medications in patients with chronic renal insufficiency.

Cardiovascular disease (CVD) is a major cause of morbidity and mortality among patients with chronic renal insufficiency (CRI). beta-Adrenergic blockers, acetylsalicylic acid (ASA), angiotensin-converting enzyme (ACE) inhibitors, and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) all reduce CVD mortality, but little is known about the extent to which these medications are used in patients with CRI. This study, a prospective cross-sectional study of consecutive patients seen by nephrologists in four Canadian centers for follow-up of progressive CRI in 1999, was performed to investigate the prevalence of coronary risk factors and use of cardioprotective medications among patients with CRI. Patients had creatinine clearances of 75 mL/min or less but were not on dialysis therapy. Three hundred four consecutive patients meeting the inclusion criteria were enrolled. Mean age was 60.8 +/- 15.7 years, mean creatinine clearance was 30.3 +/- 18 mL/min, and the case mix of kidney diseases was similar to that in the Canadian Organ Replacement Registry data. One hundred seventeen of 304 patients (38.5%) had a history of previous CVD, and the prevalence of CVD was greater in patients with more severe CRI. Two hundred forty-three patients (79.9%) had a history of hypertension, 132 patients (43.4%) had hyperlipidemia, 114 patients (37.5%) had diabetes mellitus, and 71 patients (27.3%) were smokers. Thirty-five percent of the patients with CVD had blood pressures greater than 140/90 mm Hg; 103 patients (33.9%) were administered beta-blockers; 196 patients (64.5%), ACE inhibitors or angiotensin-receptor blockers; 83 patients (27.3%), ASA; and 56 patients (18.4%), statins. Patients with diabetes were not more likely than those without diabetes to be prescribed cardioprotective medications. CVD is common in the predialysis population, and its prevalence increases with more severe kidney failure. Despite this, the use of cardioprotective medications is relatively low, and many patients had suboptimal blood pressure control. Given the high burden of disease in these patients, beta-blockers and ACE inhibitors should be used to control hypertension and/or for cardioprotection, and the increased use of ASA and statins should be considered.

Adult↗
PubMed2001

An analysis of allelic variation in the ABCA4 gene.

PURPOSE: To assess the allelic variation of the ATP-binding transporter protein (ABCA4). METHODS: A combination of single-strand conformation polymorphism (SSCP) and automated DNA sequencing was used to systematically screen this gene for sequence variations in 374 unrelated probands with a clinical diagnosis of Stargardt disease, 182 patients with age-related macular degeneration (AMD), and 96 normal subjects. RESULTS: There was no significant difference in the proportion of any single variant or class of variant between the control and AMD groups. In contrast, truncating variants, amino acid substitutions, synonymous codon changes, and intronic variants were significantly enriched in patients with Stargardt disease when compared with their presence in subjects without Stargardt disease (Kruskal-Wallis P < 0.0001 for each variant group). Overall, there were 2480 instances of 213 different variants in the ABCA4 gene, including 589 instances of 97 amino acid substitutions, and 45 instances of 33 truncating variants. CONCLUSIONS: Of the 97 amino acid substitutions, 11 occurred at a frequency that made them unlikely to be high-penetrance recessive disease-causing variants (HPRDCV). After accounting for variants in cis, one or more changes that were compatible with HPRDCV were found on 35% of all Stargardt-associated alleles overall. The nucleotide diversity of the ABCA4 coding region, a collective measure of the number and prevalence of polymorphic sites in a region of DNA, was found to be 1.28, a value that is 9 to 400 times greater than that of two other macular disease genes that were examined in a similar fashion (VMD2 and EFEMP1).

ATP-Binding Cassette Transporters↗
PubMed2001

Identifying and slowing progressive chronic renal failure.

OBJECTIVE: To help inform primary care physicians about how to identify and slow progressive chronic renal failure. QUALITY OF EVIDENCE: The National Library of Medicine (1996 to 2000) was searched using PubMed with search terms pertinent to studies on identification, course, and management of chronic renal failure. References in retrieved papers and older literature known to the authors supplemented the searches. In general, sufficient high-quality studies, systematic reviews, or guidelines based on such evidence were available to support our main points. MAIN MESSAGE: End-stage renal disease (ESRD) poses a large and growing morbidity, mortality, and financial burden. Almost all patients reach ESRD as a result of chronic progressive conditions, particularly diabetic nephropathy, hypertensive-vascular renal disease, and glomerular disorders. Patients at risk merit regular renal assessment with serum creatinine tests and urinalysis. Persistent high blood pressure and heavy proteinuria are the strongest predictors of progression of chronic renal failure. Patients with renal disease should be examined and treated for vascular disease and vice versa. Blood pressure lowering, ACE inhibition, and avoidance of further renal insults (such as use of nephrotoxins) can slow the decline of renal function. Restricting dietary protein has a weak effect on slowing renal failure and is not easy to apply in primary care. Timely involvement of specialized nephrology teams is important. CONCLUSION: Family physicians play an important role in recognizing patients with potential for renal failure, in demonstrating progressive chronic renal failure, and in initiating therapy early to improve outcomes.

Antihypertensive Agents↗
PubMed2001

What is the "payback" for early intervention in CRI?

The Renal Agency in B.C. is an example of the successes that can be achieved by the collaboration of physicians and other medical professionals with government-funding and health care agencies. Through clear definition of goals and proposed outcomes, based on clinical evidence, well-research business plans, and rational discussion, we have achieved an improvement in the cohesive approach to patients with kidney disease. The Renal Agency has succeeded in redefining the scope of kidney disease services to include services prior to dialysis. The recognition of kidney disease as a chronic identifiable condition, amenable to cost effective interventions early in its course, will undoubtedly lead to improved patient outcomes. With the ongoing cohesiveness of the renal community, the existence of the Renal Agency, and the use of the information system PROMIS, we will be able to demonstrate these successes to government bodies over the coming years.

Canada↗
PubMed2000

Neonatal end-of-life decision making: Physicians' attitudes and relationship with self-reported practices in 10 European countries.

CONTEXT: The ethical issues surrounding end-of-life decision making for infants with adverse prognoses are controversial. Little empirical evidence is available on the attitudes and values that underlie such decisions in different countries and cultures. OBJECTIVE: To explore the variability of neonatal physicians' attitudes among 10 European countries and the relationship between such attitudes and self-reported practice of end-of-life decisions. DESIGN AND SETTING: Survey conducted during 1996-1997 in 10 European countries (France, Germany, Italy, the Netherlands, Spain, Sweden, the United Kingdom, Estonia, Hungary, and Lithuania). PARTICIPANTS: A total of 1391 physicians (response rate, 89%) regularly employed in 142 neonatal intensive care units (NICUs). MAIN OUTCOME MEASURES: Scores on an attitude scale, which measured views regarding absolute value of life (score of 0) vs value of quality of life (score of 10); self-report of having ever set limits to intensive neonatal interventions in cases of poor neurological prognosis. RESULTS: Physicians more likely to agree with statements consistent with preserving life at any cost were from Hungary (mean attitude scores, 5.2 [95% confidence interval ¿CI¿, 4.9-5.5]), Estonia (4.9 [95% CI, 4.3-5.5]), Lithuania (5.5 [95% CI, 4.8-6.1]), and Italy (5.7 [95% CI, 5.3-6.0]), while physicians more likely to agree with the idea that quality of life must be taken into account were from the United Kingdom (attitude scores, 7.4 [95% CI, 7.1-7.7]), the Netherlands (7. 3 [95% CI, 7.1-7.5]), and Sweden (6.8 [95% CI, 6.4-7.3]). Other factors associated with having a pro-quality-of-life view were being female, having had no children, being Protestant or having no religious background, considering religion as not important, and working in an NICU with a high number of very low-birth-weight newborns. Physicians with scores reflecting a more quality-of-life view were more likely to report that in their practice, they had set limits to intensive interventions in cases of poor neurological prognosis, with an adjusted odds ratio of 1.5 (95% CI, 1.3-1.7) per unit change in attitude score. CONCLUSIONS: In our study, physicians' likelihood of reporting setting limits to intensive neonatal interventions in cases of poor neurological prognosis is related to their attitudes. After adjusting for potential confounders, country remained the most important predictor of physicians' attitudes and practices. JAMA. 2000;284:2451-2459.

Adult↗
PubMed2000

Vaccines today.

Explore the source record for details and available documents.

Adult↗
PubMed2000

Imaging the electron wave function in self-assembled quantum dots.

Magnetotunneling spectroscopy is used as a noninvasive and nondestructive probe to produce two-dimensional spatial images of the probability density of an electron confined in a self-assembled semiconductor quantum dot. The technique exploits the effect of the classical Lorentz force on the motion of a tunneling electron and can be regarded as the momentum (k) space analog of scanning tunneling microscopy imaging. The images reveal the elliptical symmetry of the ground state and the characteristic lobes of the higher energy states.

Journal Article↗