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Biomedical subjects

L Feldman

Publications and source records attributed to L Feldman.

At least 19 recordsLinked to original sources
PubMed2006

The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes.

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, starting in early childhood and persisting into adulthood in the majority of cases. Family and twin studies have demonstrated the importance of genetic factors and candidate gene association studies have identified several loci that exert small but significant effects on ADHD. To provide further clarification of reported associations and identify novel associated genes, we examined 1,038 single-nucleotide polymorphisms (SNPs) spanning 51 candidate genes involved in the regulation of neurotransmitter pathways, particularly dopamine, norepinephrine and serotonin pathways, in addition to circadian rhythm genes. Analysis used within family tests of association in a sample of 776 DSM-IV ADHD combined type cases ascertained for the International Multi-centre ADHD Gene project. We found nominal significance with one or more SNPs in 18 genes, including the two most replicated findings in the literature: DRD4 and DAT1. Gene-wide tests, adjusted for the number of SNPs analysed in each gene, identified associations with TPH2, ARRB2, SYP, DAT1, ADRB2, HES1, MAOA and PNMT. Further studies will be needed to confirm or refute the observed associations and their generalisability to other samples.

Adolescent↗
PubMed2005

Preoperative evaluation of laparoscopic living renal donors with computerized tomography and its effect on donor morbidity and graft function.

OBJECTIVE: To assess the efficacy of CT angiography (CTA) in evaluating the renovascular anatomy in 50 patients who underwent laparoscopic donor nephrectomy, and to correlate results with donor morbidity and recipient outcome. METHODS: Forty-eight patients were evaluated by CTA prior to laparoscopy. Donors with aberrant renovasculature and their respective recipients were divided into: 1) accurate preoperative CTA ("predictive group", PG), 2) inaccurate CTA ("non-predictive group", NPG). Warm ischemia times (WIT), estimated blood loss (EBL), operative time (OT), and the open conversion rate were compared. Recipient creatinine values on post-operative day 1 and 3 months were recorded with the rate of delayed graft function (DGF) and ureteral complication. Statistical significance was calculated using the student's T-test. RESULTS: Among patients with aberrant vasculature (48%, 23/48) at laparoscopy, 14 were accurately predicted by CT angiography (11 arterial, 3 venous). NPG consisted of 5 duplicated arteries, 1 early arterial branching, and 3 anomalous veins. CT accuracy was 85%. The sensitivity and specificity of the arterial imaging were 65% and 100% respectively, while those of venous imaging were 50% and 100%. EBL, WIT, OT, number of open conversions, and ureteral complications were statistically insignificant between groups (p= 0.05, 95% C.I.). The mean decreases in creatinine between NPG and PG on post-operative day 1 and at 3 months were 45.4% and 54.8%, and 71.5% and 79.1% respectively, both statistically insignificant. Two of 8 in the NPG experienced DGF as compared to 1/8 in the PG. CONCLUSIONS: Despite the lower sensitivity of this study, the discordance between imaging and laparoscopy did not augment donor morbidity or increase adverse recipient outcomes. This may indicate that regardless of the shortcomings of 2-D CTA for living donors, it represents a safe and effective imaging modality when coupled with meticulous laparoscopic dissection and central intraoperative involvement of the transplant surgeon.

Angiography↗
PubMed2004

The effect of sildenafil on gastric emptying in patients with end-stage renal failure and symptoms of gastroparesis.

BACKGROUND: Delayed gastric emptying is a common disorder among patients with end-stage renal failure (ESRF). Pyloric relaxation, a major determinant of gastric emptying, is a nitric oxide (NO)-mediated process. NO-induced smooth muscle relaxation is mediated through its second messenger cyclic guanosine monophosphate, which is broken by tissue phosphodiesterases (PDEs). Thus the inhibition of cyclic guanosine monophosphate breakdown by PDE inhibitors can potentiate NO-mediated responses and facilitate pyloric relaxation. In an animal model of diabetes mellitus, treatment with sildenafil (a PDE-5 inhibitor) restored NO-mediated pyloric relaxation and improved gastric emptying. The aim of our study was to examine the hypothesis that sildenafil may improve gastric emptying in patients with ESRF and symptoms of gastric paresis. METHODS: We studied 12 patients with ESRF (6 men; age range, 54-80 years; 5 with diabetic nephropathy; 4 +/- 1 years receiving long-term renal replacement therapy) after either placebo or a 25-mg tablet of sildenafil (Viagra; Pfizer Inc). Gastric emptying of a solid meal (one medium-sized fried egg mixed with 37 MBq [1 mCi] technetium Tc 99m phytate plus 1 slice of bread and 150 mL of water at the end of the meal) was assessed 1 hour after dosing by use of a single-headed camera. Images were acquired every 30 seconds for 90 minutes immediately after patients ate. RESULTS: The gastric emptying rate was decreased at baseline (after placebo), to 33% +/- 6% (normal, > or =50%). Treatment with sildenafil had no effect on gastric emptying rates after 90 minutes (from 33% +/- 6% after placebo to 30% +/- 6% after sildenafil, P =.9). CONCLUSIONS: Sildenafil did not improve gastric emptying in patients with ESRF and gastric paresis. Sildenafil may have opposing effects on gastric peristalsis (causing gastric relaxation) compared with its effects on pyloric relaxation. Studies combining sildenafil with prokinetic drugs are of interest.

Aged↗
PubMed2003

Hantavirus infection in people inhabiting a highly endemic region of the Gran Chaco territory, Paraguay: association with Trypanosoma cruzi infection, epidemiological features and haematological characteristics.

The seroprevalences of anti-hantavirus antibodies were determined in 712 individuals (551 Indians, 140 Mennonites of German ancestry, and 21 Paraguayans of Spanish ancestry) inhabiting a region of western Paraguay in the Gran Chaco territory of South America. The overall seroprevalence of hantavirus infection among the 712 subjects, who were aged 2-80 years, was 42.7% (45.2% in the Indians and 34.2% in the non-Indians). Of the 672 subjects also checked for antibodies against Trypanosoma cruzi, 226 (33.6%) were seropositive for this protozoan parasite. The results of a multivariate regression analysis indicated that, after adjusting for age, sex, setting of residence (rural/urban) and infection with the human T-cell leukaemia/lymphoma virus type II (HTLV-II), a T. cruzi-seropositive individual was 1.73 times more likely to be hantavirus seropositive than a T. cruzi-seronegative individual. Living in a rural setting increased the risk of being hantavirus seropositive 2.17-fold. In both the Indians and non-Indian subpopulations, hantavirus seroprevalence increased with age in both sexes, but only in the non-Indian supopulation was this increase significantly greater in males than in females. Hantavirus seropositivity was significantly associated with thrombocytosis, even after adjusting for the relevant confounders.

Adolescent↗
PubMed2002

[Myocardial revascularization at the acute phase of myocardial infarction in the octogenarian].

Elderly patients are at high risk of complications in acute myocardial infarction (AMI). In this population, myocardial reperfusion at the acute phase improves the prognostic. The mortality rate is above 50% in the absence of reperfusion strategy, and decreases at less than 20% in case of such treatment. The thrombolytic use is limited in those patients, coronary angioplasty is taking an important place in this reperfusion therapy, but is not well evaluated in patients older than 80 years. Prospective registry of patients older than 80 years admitted in Hôpital Bichat for acute myocardial infarction within the first 6 hours (n = 92), between 1990 january to 1999 december. Eight patients (10%) received a thrombolytic therapy. Coronary angiogram was achieved in eighty patients (87%). In 58 (63%) patients a coronary angioplasty was performed. The success rate of the coronary angioplasty was 86%. In-hospital mortality rate was 26% (death in 24 patients), 20% in the absence of cardiogenic shock and 62% when this complication was noted. Two patients (2%) were treated by emergent coronary artery bypass surgery. The results comparison between the periods of 1990 to 95 and 1955 to 99 showed, a real trend of decrease mortality rate (28 to 13% in the absence of cardiogenic shock, p = 0.10), an increase of the proportion of patients treated by angioplasty. These results are more and more encouraging. Coronary reperfusion by primary angioplasty in possible in patients older than 80 years with a low rate of complications. Technical progress such as stents and GpIIb/IIIa inhibitors must be evaluated in this population.

Aged↗
PubMed2002

[Aortic dissection and aberrant right subclavian artery: CT and MR findings].

A case of aortic dissection extending to an aberrant right subclavian artery seen at CT and MRI is reported. The clinical and imaging patterns of this rare disease are described and compared with those of the literature. Multiplanar views are, in this particular case, very useful for a precise assessment of the involved aberrant artery.

Aortic Dissection↗
PubMed2002

[Quality of medical database to valorize the DRG model by ISA cost indicators].

BACKGROUND: The use of the French version of the DRG model is focused on cost allocation, based on the case-mix system and the use a weight called ISA (Synthetic Index of Activity) for each DRG. However, this administrative database is becoming more and more used by both researchers and health policy makers for health planning and benchmarking. In France, data abstraction and coding of medical records is done by physicians. The objective of this study was to determine the accuracy of a database of the discharge summaries used for DRGs and to compare consequences of inappropriate coding on budget estimation and risk adjustment. METHODS: Samples of discharge summaries from six cardiology units were recoded by trained physicians in data abstracting and coding. Comparison between initial and recoded diagnoses (errors on main diagnosis or on comorbidities) used by the DRG system algorithm, and the original and final case-mix were performed. The before and after abstracted data were stratified and compared by principal diagnosis (myocardial infarction or congestive heart failure) and discharge status (dead or alive). MAIN RESULTS: Comorbidities were underreported by physicians of cardiology units compared to reabstracted data (mean number of secondary diagnoses per summary: 2.1 vs. 3.6, p<0.001), especially those which had a minimal impact on the DRG classification. In spite of a 15% rate of wrong DRGs, there was no significant difference in the total amount of ISA after data reviewing. Underreporting of comorbidities is more important for medical records of dead patients at discharge but, without significant effect on rate of change in DRG and amount of ISA. CONCLUSION: Discharge summaries used in the French DRGs system consistently underestimate the presence of comorbid conditions, which has direct implications for policy-makers comparing performance between hospital units. Both clinical practitioners and policy makers should be aware of this bias when assessing patient's quality of care or performing health planning through discharge summaries.

Age Factors↗
PubMed2001

Extracellular matrix remodeling in the vascular wall.

The extracellular matrix provides a structural framework essential for the functional properties of vessel walls. The three dimensional organization of the extracellular matrix molecules--elastin, collagens, proteoglycans and structural glycoproteins--synthesized during fetal development--is optimal for these functions. Early in life, the vessel wall is subjected to injury: lipid deposition, hypoxia, enzyme secretion and reactive oxygen species production during inflammatory processes, and the extracellular matrix molecules are hydrolyzed by proteases--matrix metalloproteinases, leukocyte elastase, etc. In uninjured arteries and veins, some proteases are constitutively expressed, but through the control of their activation and/or their inhibition by inhibitors, these proteases have a very low activity. During the occurrence of vascular pathologies--atherosclerosis, hypertension, varicosis, restenosis, etc.--the balance between proteases and their inhibitors is temporally destroyed through the induction of matrix metalloproteinase gene expression or the secretion of enzymes by inflammatory cells. Smooth muscle cells, the most numerous cells in vascular walls, have a high ability to respond to injury through their ability to synthesize extracellular matrix molecules and protease inhibitors. However, the three dimensional organization of the newly synthesized extracellular matrix is never functionally optimal. In some other pathologies--aneurysm--the injury overcomes the responsive capacity of smooth muscle cells and the quantity of extracellular matrix decreases. In conclusion, care should be taken to maintain the vascular extracellular matrix reserve and any therapeutic manipulation of the protease/inhibitor balance must be perfectly controlled, because an accumulation of abnormal extracellular matrix may have unforeseen adverse effects.

Aneurysm↗
PubMed2000

The natural history of incidental renal artery stenosis in patients with aortoiliac vascular disease.

PURPOSE: To examine the association between incidentally discovered renal artery stenosis and deterioration of renal function as determined by the change in serum creatinine concentration over time. SUBJECTS AND METHODS: We performed a retrospective review of consecutive patients who underwent aortography for aortoiliac vascular disease. Angiograms were reviewed for renal artery stenosis, defined as a narrowing of at least 20% compared with adjacent normal renal artery. For patients with at least 180 days of subsequent follow-up, the change in serum creatinine concentration per year was compared in patients who had or did not have renal artery stenosis. RESULTS: Of the 201 patients, 96 (48%) had some degree of renal artery stenosis in one or both renal arteries, including 53 (26%) who had at least one stenosis > or= 50% and 40 (20%) who had bilateral stenoses. The only clinical predictor of renal artery stenosis was a history of coronary artery disease (odds ratio = 2.0, 95% confidence interval: 1.2 to 3.8, P = 0.001). Among the 174 patients with > or =180 days of follow-up, there was no statistically significant difference (P = 0.88) in the mean change in serum creatinine concentration per year in the 78 patients with renal artery stenosis (0.06+/-0.33 mg/dL per year) as compared with the 96 patients without renal artery stenosis (0.06+/-0.22 mg/dL per year). Grouping the patients by the maximal percentage of stenosis did not reveal any difference in the mean changes in serum creatinine concentration per year. CONCLUSIONS: Although renal artery stenosis is a common incidental finding in patients with atherosclerotic vascular disease, it is an uncommon cause of progressive renal disease.

Aged↗
PubMed2000

Cigarette smoking in multicultural, urban high school students.

PURPOSE: To profile patterns of cigarette use among a multiethnic population of high school students, and identify important factors associated with cigarette use by ethnicity, in order to plan effective health promotion strategies. METHODS: This cross-sectional study involved the completion of a lifestyle questionnaire by 1236 Grade 9-13 students (86% response rate) from 62 randomly selected classrooms in three urban high schools in Toronto. Chi-square analysis of the association between tobacco use and other variables took account of the clustered sample using CSAMPLE in Epi Info. RESULTS: The students self-identified their ethnicity as follows: 388 Canadian, 269 European, 171 East Indian, 137 Asian, 76 West Indian, and 194 "other." Students who identified themselves as Canadians were significantly more likely to be current smokers (29%) than students reporting other ethnicities (13%). There was no apparent increase in smoking rates for immigrants after 2 or more years in Canada. Current drinking, sexual activity, and especially friends smoking was most strongly associated with current smoking for most ethnic groups, although the relative importance of these variables was not identical for all groups. CONCLUSIONS: Prevention programs may benefit from a focus on the influence of peer smoking and on the grouping together of lifestyle factors associated with smoking for students in all ethnic groups in this multicultural city.

Adolescent↗
PubMed2000

Cold agglutinin disease in a patient with uterine sarcoma.

Cold agglutinin disease is a rare clinical scenario. It is usually associated with infection, drug reaction, and hematologic malignancy, such as non-Hodgkin lymphoma or lymphocytic leukemia. We report a case of cold agglutinin disease in a patient with solid-tumor uterine sarcoma. Immunological dysregulation has been proposed as the pathogenesis for this disease. We also summarize recently reported cases of cold agglutinin disease, the underlying conditions, and advances in the management of cold agglutinin disease.

Adrenal Cortex Hormones↗
PubMed1999

Isolation of differentially expressed genes by cloning transcriptionally active DNA fragments.

During studies of erythroid cell growth and differentiation induced by erythropoietin (Epo), we developed a method that allows the identification and isolation of genes based upon their transcriptional activity. Transcriptionally active genomic DNA fragments from Epo-treated cells and control cells are purified from inactive chromatin using mercury affinity chromatography, based on the mechanism that the thiol groups of histone H3 on transcriptionally active chromatin are exposed to the solvent and therefore are easily accessible. Using the purified genomic DNA fragments from the two populations of cells, a subtractive hybridization strategy is used to isolate and clone genes that are differentially expressed in the absence or in the presence of Epo.

Animals↗