Medicine and MBAs.
Explore the source record for details and available documents.
Education, Graduate↗
Biomedical subjects
A Levin
Publications and source records attributed to A Levin.
Mutation analysis of 3 genes in patients with Leber congenital amaurosis.
OBJECTIVE: To assess the frequency of mutations in the CRX, GUCY2D, and RPE65 genes in patients with Leber congenital amaurosis (LCA). PATIENTS: One hundred seventy-six probands with a clinical diagnosis of LCA were from 9 countries, with the largest subgroup being 39 probands from India. METHODS: Samples were screened with single-strand conformation polymorphism analysis followed by DNA sequencing of 3 genes (CRX, GUCY2D, and RPE65) known to be associated with LCA. RESULTS: Of the 176 probands, 28 (15.9%) harbored possible disease-causing mutations. The relative contribution of each gene to the total number of mutations was as follows: CRX, 2.8%; GUCY2D, 6.3%; and RPE65, 6.8%. No patients who harbored mutations in these genes had associated systemic abnormalities. Molecular diagnosis allowed definitive genetic counseling in a family affected with Best disease and LCA. CONCLUSIONS: Molecular diagnosis may be of benefit to patients affected with LCA. The relative paucity of mutations found in this study suggests that more LCA-associated genes remain to be discovered. CLINICAL RELEVANCE: Molecular diagnosis can confirm and clarify the diagnosis of LCA. As genotype data accumulate, clinical phenotypes associated with specific mutations will be established. This will facilitate the counseling of patients on their visual prognosis and the likelihood of associated systemic anomalies.
Adolescent↗
Post-transplant diabetic ketoacidosis--a possible consequence of immunosuppression with calcineurin inhibiting agents: a case series.
Post-transplant diabetes mellitus, a complication due to corticosteroids and the calcineurin inhibitors, cyclosporine and tacrolimus (FK506), is commonly regarded as a form of type-2 (adult-onset) diabetes mellitus. Diabetic ketoacidosis, which requires relative insulin deficiency to impair fatty acid metabolism, is a complication of type-1 diabetes mellitus. We report three patients who presented with diabetic ketoacidosis post-transplant. All three patients presented with severe hyperglycemia, significant ketosis and metabolic acidosis of variable severity. One patient was a renal transplant recipient on a cyclosporine-based regimen. The other two patients were liver transplant recipients receiving either cyclosporine or tacrolimus-based immunosuppression. Both of the liver transplant recipients were found to have moderate to high serum levels of calcineurin inhibitors on presentation. The liver recipient on cyclosporine (Neoral) had a 4 hour post-dose level of 388 ng/ml and the patient on tacrolimus was found to have a trough level of 21.2 ng/ml. Our experience suggests that post-transplant diabetes mellitus, in association with calcineurin inhibition, may result in ketoacidosis either secondary to relative beta cell dysfunction, peripheral insulin resistance, or a combination of the two effects. Post-transplant diabetes mellitus can be an atypical form of adult-onset diabetes with features of both type I and type II diabetes mellitus.
Adult↗
Reliability of measurements of pressures applied on the foot during walking by a computerized insole sensor system.
OBJECTIVE: To evaluate the reliability of measurements of foot pressures while walking using the F-scan computerized system with various insole sensors. DESIGN: Ten healthy subjects were studied. Each used four different pairs of insoles while walking for three 6-second epochs per insole. Peak pressures were recorded at the hindfoot, midfoot, and forefoot and analyzed. Each insole was made of pressure-sensitive 25 mm 2 cells, embedded in protective backing, and scanned electronically every 50 to 100 msec. SETTING AND PARTICIPANTS: Conventional tile floor in a gait laboratory on 10 consecutive normal subjects. RESULTS: The mean +/- standard deviation peak pressure recorded at the hindfoot was 11.1 +/- 2.0 psi; at the midfoot, 3.5 +/- 1.5 psi; and at the forefoot, 11.3 +/- 2.6 psi. The intrasubject mean differences were 0.2 psi at the hindfoot, 0.4 psi at the midfoot, and 0.3 psi at the forefoot. The data suggest that variability between different insoles is not significant. CONCLUSION: The pressure data show these insoles to be sufficiently reliable for use in patients when knowledge of foot pressure distribution is important for the relief of pain, and for designing and assessing appropriate corrective measures to relieve excessive pressure on the foot and to prevent development of pressure ulcers.
Adult↗
The effect of birth interval on malnutrition in Bangladeshi infants and young children.
This study was undertaken to investigate the independent effect of the length of birth interval on malnutrition in infants, and children aged 6-39 months. Data for this study were drawn from a post-flood survey conducted during October-December 1988 at Sirajganj of the Sirajgani district and at Gopalpur of the Tangail district in Bangladesh. The survey recorded the individual weights of 1887 children. Cross-tabulations and logistic regression procedures were applied to analyse the data. The proportion of children whose weight-for-age was below 70% (moderate-to-severely malnourished) and 60% (severely malnourished) of the NCHS median was tabulated against various durations of previous and subsequent birth intervals. The odds of being moderately or severely malnourished were computed for various birth intervals, controlling for: the number of older surviving siblings; maternal education and age; housing area (a proxy for wealth); age and sex of the index child; and the prevalence of diarrhoea in the previous 2 weeks for the index child. About one-third of infants and young children were moderately malnourished and 15% were severely malnourished. The proportion of children who were under 60% weight-for-age decreased with the increase in the length of the subsequent birth interval, maternal education and housing area. The proportion of malnourished children increased with the number of older surviving children. Children were at higher risk of malnutrition if they were female, their mothers were less educated, they had several siblings, and either previous or subsequent siblings were born within 24 months. This study indicates the potential importance of longer birth intervals in reducing malnutrition in children.
Adult↗
Comparative mortality of hemodialysis and peritoneal dialysis in Canada.
BACKGROUND: Comparisons of mortality rates in patients on hemodialysis versus those on peritoneal dialysis have been inconsistent. We hypothesized that comorbidity has an important effect on differential survival in these two groups of patients. METHODS: Eight hundred twenty-two consecutive patients at 11 Canadian institutions with irreversible renal failure had an extensive assessment of comorbid illness collected prospectively, immediately prior to starting dialysis therapy. The cohort was assembled between March 1993 and November 1994; vital status was ascertained as of January 1, 1998. RESULTS: The mean follow-up was 24 months. Thirty-four percent of patients at baseline, 50% at three months, and 51% at six months used peritoneal dialysis. Values for a previously validated comorbidity score were higher for patients on hemodialysis at baseline (4.0 vs. 3.1, P < 0.001), three months (3.7 vs. 3.2, P = 0.001), and six months (3.6 vs. 3.2, P = 0.005). The overall mortality was 41%. The unadjusted peritoneal dialysis/hemodialysis mortality hazard ratios were 0.65 (95% CI, 0. 51 to 0.83, P = 0.0005), 0.84 (95% CI, 0.66 to 1.06, P = NS), and 0. 83 (95% CI, 0.64 to 1.08, P = NS) based on the modality of dialysis in use at baseline, three months, and six months, respectively. When adjusted for age, sex, diabetes, cardiac failure, myocardial infarction, peripheral vascular disease, malignancy, and acuity of renal failure, the corresponding hazard ratios were 0.79 (95% CI, 0. 62 to 1.01, P = NS), 1.00 (95% CI, 0.78 to 1.28, P = NS), and 0.95 (95% CI, 0.73 to 1.24, P = NS). Adjustment for a previously validated comorbidity score resulted in hazard ratios of 0.74 (95% CI, 0.58 to 0.94, P = 0.01), 0.94 (95% CI, 0.74 to 1.19, P = NS), and 0.88 (95% CI, 0.68 to 1.13, P = NS) at baseline, three months, and six months. There was no survival advantage for either modality in any of the major subgroups defined by age, sex, or diabetic status. CONCLUSIONS: The apparent survival advantage of peritoneal dialysis in Canada is due to lower comorbidity and a lower burden of acute onset end-stage renal disease at the inception of dialysis therapy. Hemodialysis and peritoneal dialysis, as practiced in Canada in the 1990s, are associated with similar overall survival rates.
Canada↗
Comparative hospitalization of hemodialysis and peritoneal dialysis patients in Canada.
BACKGROUND: Most comparisons of hemodialysis (HD) and peritoneal dialysis (PD) have used mortality as an outcome. Relatively few studies have directly compared the hospitalization rates, an outcome of perhaps equal importance, of patients using these different dialysis modalities. METHODS: Eight hundred twenty-two consecutive patients at 11 Canadian institutions with irreversible renal failure had an extensive assessment of comorbid illness and initial mode of dialysis collected prospectively immediately prior to starting dialysis therapy. The cohort was assembled between March 1993 and November 1994. The mean follow-up was 24 months. Admission data were used to compare hospitalization rates in HD and PD. RESULTS: Thirty-four percent of patients at baseline and 50% at three months used PD. Twenty-five percent of HD and 32% of PD patients switched dialysis modality at least once after their first treatment (P = NS). Nine percent of HD patients and 30% of PD patients switched modality after three months (P < 0. 001). Total comorbidity was higher in HD patients at baseline (P < 0. 001) and at three months (P = 0.001). The overall hospitalization rate was 40.2 days per 1000 patient days after baseline and 38.0 days per 1000 patient days after three months. When an adjustment was made for baseline comorbid conditions, patients on PD had a lower rate of hospitalization in intention-to-treat analysis according to the type of dialysis in use at baseline (RR 0.85, 95% CI, 0.82 to 0.87, P < 0.001), but a higher rate according to the type of dialysis in use three months after study entry (RR 1.31, 95% CI, 1.27 to 1.34, P < 0.001). In analyses based on the amount of time actually spent on each treatment modality, PD was associated with a higher rate of hospitalization when analyzed according to the type of dialysis in use at baseline (RR 1.10, 95% CI, 1.07 to 1.13, P < 0.001) and according to the type of dialysis in use three months after study entry (RR 1.26, 95% CI, 1.23 to 1.30, P < 0.001). CONCLUSIONS: Conclusions regarding comparative hospitalization rates are heavily dependent on the analytic starting point and on whether intention-to-treat or treatment-received analyses are used. When early treatment switches are accounted for, HD is associated with a lower rate of hospitalization than PD, but the effect is modest.
Canada↗
Effect of hemoglobin levels in hemodialysis patients with asymptomatic cardiomyopathy.
BACKGROUND: Hemoglobin levels below 10 g/dL lead to left ventricular (LV) hypertrophy, LV dilation, a lower quality of life, higher cardiac morbidity, and a higher mortality rate in end-stage renal disease. The benefits and risks of normalizing hemoglobin levels in hemodialysis patients without symptomatic cardiac disease are unknown. METHODS: One hundred forty-six hemodialysis patients with either concentric LV hypertrophy or LV dilation were randomly assigned to receive doses of epoetin alpha designed to achieve hemoglobin levels of 10 or 13.5 g/dL. The study duration was 48 weeks. The primary outcomes were the change in LV mass index in those with concentric LV hypertrophy and the change in cavity volume index in those with LV dilation. RESULTS: In patients with concentric LV hypertrophy, the changes in LV mass index were similar in the normal and low target hemoglobin groups. The changes in cavity volume index were similar in both targets in the LV dilation group. Treatment-received analysis of the concentric LV hypertrophy group showed no correlation between the change in mass index and a correlation between the change in LV volume index and mean hemoglobin level achieved (8 mL/m2 per 1 g/dL hemoglobin decrement, P = 0.009). Mean hemoglobin levels and the changes in LV mass and cavity volume index were not correlated in patients with LV dilation. Normalization of hemoglobin led to improvements in fatigue (P = 0.009), depression (P = 0.02), and relationships (P = 0.004). CONCLUSIONS: Normalization of hemoglobin does not lead to regression of established concentric LV hypertrophy or LV dilation. It may, however, prevent the development of LV dilation, and it leads to improved quality of life.
Adult↗
Defining a renal anemia management period.
Estimates of the prevalence of anemia during chronic renal insufficiency (CRI) vary depending on how anemia is defined. An analysis of patients beginning dialysis in the United States found that 67% had a hematocrit of less than 30% and 51% had a hematocrit of less than 28%. The anemia of CRI, therefore, appears to be prevalent even as it is underrecognized and undertreated-despite the widespread realization that there is much to be gained by treatment with recombinant human erythropoietin, with little risk of accelerating the progression of kidney disease. It is difficult to separate the effects of anemia in CRI from those of other comorbid conditions, but it is clear that anemia is a strong predictor of mortality and cardiac morbidity. Correction of anemia would be expected to negate the contribution of anemia to the mortality and cardiac morbidity associated with CRI. While this hypothesis is well-validated in hemodialysis patients, data in the population with CRI are preliminary but encouraging. Recent small prospective studies have established that treatment of anemia with recombinant human erythropoietin can reverse some degree of the cardiac morphological changes seen in CRI. While awaiting the results of large long-term clinical trials, the concept of the renal anemia management period (RAMP) draws attention and focus to the need for proactive and aggressive treatment of anemia among patients with CRI. The RAMP is defined as the period of time after the onset of CRI during which anemia develops, requiring diagnosis and treatment. Treatment of anemia during the RAMP has the potential to ameliorate, or even prevent, significant future morbidity in patients with CRI.
Anemia↗
Cardiovascular disease in chronic renal insufficiency.
Cardiovascular illness is an important contributor to the morbidity of kidney disease. The spectrum of cardiovascular disease (CVD) in patients with chronic renal insufficiency (CRI) includes left ventricular hypertrophy (LVH) and dilatation, ischemic heart disease, and peripheral vascular disease. Both "traditional" and "uremia-specific" factors contribute to the occurrence and progression of cardiac disease in renal patients. A growing body of recent evidence indicates that the processes contributing to CVD commence early in CRI, leading to concentric LVH, left ventricular dilatation, congestive heart failure, and ischemic heart disease. Many of the coexisting conditions that have been identified consistently as contributing to the burden of cardiovascular illness in renal populations can be modified through medical interventions. Specific therapies exist for hypertension, anemia, hyperparathyroidism, and dyslipidemia. Studies to date have demonstrated that treatment of many of these factors-such as anemia and hypertension during end-stage renal disease-appear to benefit the cardiovascular system. Earlier intervention may offer the best opportunity to reduce the burden of illness in all groups of CRI patients. Identification of patients at the onset of kidney disease and attention to the known traditional and "uremic" risk factors are emerging as promising strategies. Long-term interventional studies are needed to determine costs, benefits, and risks of such strategies.
Anemia↗
Treatment choices for extremely preterm infants: an international perspective.
OBJECTIVE: To compare treatment choices of neonatal physicians and nurses in 11 European countries for a hypothetical case of extreme prematurity (24 weeks' gestational age, birth weight of 560 g, Apgar score of 1 at 1 minute). STUDY DESIGN: An anonymous, self-administered questionnaire was completed by 1401 physicians (response rate, 89%) and 3425 nurses (response rate, 86%) from a large, representative sample of 143 European neonatal intensive care units. Italy, Spain, France, Germany, the Netherlands, Luxembourg, Great Britain, Sweden, Hungary, Estonia, and Lithuania participated. RESULTS: Most physicians in every country but the Netherlands would resuscitate this baby and start intensive care. On subsequent deterioration of clinical conditions caused by a severe intraventricular hemorrhage, attitudes diverge: most neonatologists in Germany, Italy, Estonia, and Hungary would favor continuation of intensive care, whereas in the other countries some form of limitation of treatment would be the preferred choice. Parental wishes appear to play a role especially in Great Britain and the Netherlands. Nurses are more prone than doctors to withhold resuscitation in the delivery room and to ask parental opinion regarding subsequent treatment choices. CONCLUSION: An extremely premature infant is regarded as viable by most physicians, whereas after deterioration of the clinical conditions decision-making patterns vary according to country. These findings have implications for the ethical debate surrounding treatment of infants of borderline viability and for the interpretation and comparison of international statistics.
Adult↗
Consequences of late referral on patient outcomes.
There is growing awareness of a need not only to identify patients with chronic renal failure (CRF) at an earlier stage in the disease process, but also to initiate treatment strategies earlier, in order to delay both progression of CRF and co-morbid diseases and to define the optimal time required to prepare CRF patients for renal replacement therapy (RRT). These three strategies are linked, and rely on appropriate identification of patients at risk of renal disease. The challenge currently facing nephrologists is both how to minimize the consequences of late referral and how to improve the timeliness of referral. Published studies support the notion that outcomes are poor in patients who access specialized nephrology care late in the course of their renal disease (just prior to the need for dialysis). A National Institute of Health consensus publication recommends early referral to a multidisciplinary renal care team, and the recent Canadian Society of Nephrology guidelines recommend that at least 12 months are needed prior to initiation of dialysis for adequate medical and psychological preparation for RRT. Despite these recommendations, a substantial proportion (20-50%) of patients starts dialysis without prior exposure to nephrologists. Limited data exist on current referral patterns to nephrologists. Diabetes and/or hypertension cause renal disease in up to 40% of patients requiring dialysis. These patients are presumably being monitored by internists, endocrinologists or cardiologists, and many referrals come from these physicians; other patients may be referred by general practitioners. Data regarding disease status at the time of referral are also limited. Substantial cardiovascular disease and risk factors are evident at the time of referral. Most of the literature describes data for those starting dialysis (i.e. late referral) rather than a broader spectrum of all patients with renal insufficiency referred to nephrologists. Reasons for late referral include insensitivity of current screening tools. Serum creatinine is well known to be an inaccurate marker of renal dysfunction, and too insensitive to identify patients with very early stages of disease, thus contributing to the prevalence of late referrals. Physician and patient attitudes are other barriers to early referral and need to be studied more fully. The consequences of late referrals include increased morbidity, mortality, and resource utilization. There is also an impact on patients' quality of life and missed opportunities for pre-emptive transplantation. Late referral also limits therapeutic options, and these limitations have consequences on long-term outcomes once patients are on dialysis. It is clear that late referral of patients with CRF obviates the opportunity for significant delay of disease progression and institution of proactive strategies to reduce the overall burden of illness in the population. There is ample evidence that strategies to delay progression of renal disease are effective, as are strategies to reduce cardiovascular disease. Anaemia and a fall in haemoglobin concentration have been associated with left ventricular hypertrophy and with growth of the left ventricle. A combined approach is necessary for best nephrological clinical practice, with a clear definition of early renal insufficiency; this will involve the development of tools to permit early identification of patients with early renal insufficiency, and the implementation of strategies to optimize treatments aimed at both delaying progression and preparing patients for RRT.
Family Practice↗
Seroprevalence of hepatitis C virus in the general population of northwest Tanzania.
Sera from 516 participants enrolled in a population-based cross-sectional study in northwest Tanzania were tested for antibodies to hepatitis C virus (HCV). The mean age of study subjects was 29 years (range = 16-49 years); 43% were men, 6% reported a history of blood transfusion, and 4% were infected with human immunodeficiency virus-1 (HIV-1). Although 53 of 516 sera (10.3%, 95% confidence interval [CI] = 7.8-13.2%) were repeatedly reactive by a third-generation enzyme immunoassay (EIA-3), only 6 of the 53 were positive when tested with a third-generation recombinant immunoblot assay (confirmed HCV seroprevalence = 1.2%, 95% CI = 0.4-2.5%). The positive predictive value of the HCV EIA-3 in this population was 18.8% (95% CI = 7.0-36.4%). False positivity was not correlated with EIA-3 optical density values, age, sex, infection with HIV-1, or a history of blood transfusion, but it was marginally associated with increased serum IgG levels. We conclude that the prevalence of HCV is low in this region and that the HCV EIA-3 has a higher false-positivity rate in this population than has been reported among U.S. blood donors.
Adolescent↗
A randomized placebo-controlled double-blind trial of lipid-lowering strategies in patients with renal insufficiency: diet modification with or without fenofibrate.
BACKGROUND: Renal insufficiency is characterized by lipoprotein abnormalities including elevated triglyceride levels. PATIENTS AND METHODS: The safety and efficacy of micronized fenofibrate as a treatment for dyslipidemia in patients with progressive renal insufficiency was evaluated in a randomized, placebo-controlled double-blind study comparing fenofibrate and dietary modification to dietary modification alone. Patients were evaluated following a 3-month pre-randomization period of dietary counseling. Twenty-eight patients with moderate renal insufficiency and triglyceride levels 2.3 mmol/l or LDL/HDL ratio 5 were randomized to placebo (n = 12) or fenofibrate (n = 16) therapy. Treatment and dietary counseling continued for 6 months. RESULTS: Ten of 16 patients (63%) treated with fenofibrate achieved a 30% reduction in triglyceride levels or LDL/HDL ratio reduction < 5 compared to 2 of 17% in the placebo group (p = 0.015). Triglyceride levels were significantly reduced in the fenofibrate group (-31%) versus placebo (+1.3%, p = 0.003). In compliant patients (n = 25) there was also a significantly greater increase in HDL cholesterol levels in the fenofibrate group (+19.9%) compared to placebo (-4.7%, p = 0.001). Changes in measured creatinine clearance were not significantly different between the groups and there were no serious adverse effects of treatment. CONCLUSION: Fenofibrate therapy combined with dietary modification effectively reduced triglyceride levels in renal insufficiency patients without serious adverse effects.
Adult↗
Elevated levels of serum creatinine: recommendations for management and referral.
BACKGROUND: The potential benefits of earlier referral to a nephrologist of patients with elevated levels of serum creatinine include identifying and treating reversible causes of renal failure, slowing the rate of decline associated with progressive renal insufficiency, managing the coexisting conditions associated with chronic renal failure and facilitating efficient entry into dialysis programs for all patients who might benefit. METHODS: A subcommittee of the Canadian Society of Nephrology, which included representatives from family practice and internal medicine, conducted a MEDLINE search for the period 1966 to 1998 using the key words referral and consultation, dialysis, hemodialysis, peritoneal dialysis, renal replacement therapy and kidney diseases. Where published evidence was lacking, conclusions were reached by consensus. GUIDELINES: Earlier referral to nephrologists of patients with elevated creatinine levels is expected to lead to better health care outcomes and lower costs for both the patients and the health care system. All patients with newly discovered renal insufficiency (as evidenced by serum creatinine elevated to a level above the upper limit of the normal range of that laboratory, adjusted for age and height in children) must undergo investigations to determine the potential reversibility of disease, to evaluate the prognosis and to optimize planning of care. All patients with an established, progressive increase in serum creatinine level should be followed with a nephrologist. Adequate preparation for dialysis or transplantation (or both) requires at least 12 months of relatively frequent contact with a renal care team. Nephrologists should provide consultation in a timely manner for any patient with an elevated serum creatinine level. In addition, they should provide advice about what aspects of the condition require particularly urgent or emergency assessment. SPONSORS: This clinical practice guideline has been endorsed by the Canadian Society of Nephrology and the College of Family Physicians of Canada. Meeting, teleconference and travel expenses of the Referral Guideline Subcommittee were covered by The Momentum Program, a collaboration between Baxter Corp. and Janssen-Ortho Inc. However, the authors are solely responsible for the editorial content of this article.
Clinical Protocols↗
Nutrition and policy. 5: Who should teach patients about nutrition?
Explore the source record for details and available documents.
Curriculum↗
Nutrition and policy. 4: Dietary supplements.
Explore the source record for details and available documents.
Advertising↗
Nutrition and policy. 3: Food industry response to nutritional standards.
Explore the source record for details and available documents.
Advertising↗