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Diabetic retinopathy and systemic factors. - Middle East African journal of ophthalmology
Diabetic retinopathy, an oculardisease, is governed by systemic as well as local ocular factors. These include primarily chronic levels of blood glucose. Individuals with chronically elevated blood glucose levels have substantially more, and more severe, retinopathy than those with lower blood glucose levels. The relationship of blood glucose to retinopathy is continuous, with no threshold although individuals with hemoglobin A1c levels (a measure of chronic glycemia) <6.5%, generally develop little or no retinopathy. Blood pressure levels have been claimed to influence retinopathy development and progression, but multiple controlled clinical trials of antihypertensive agents in diabetic subjects have produced only weak evidence of benefit from blood pressure lowering on the incidence and progression of diabetic retinopathy. Elevated blood lipids seem to play a role in the progression of retinopathy, and two trials of fenofibrate, a lipid-lowering agent that has not proved effective in preventing cardiovascular disease, have shown benefit in preventing retinopathy progression. The mechanism of this effect may not, however, be directly related to the reduction in blood lipids. Finally, there is strong, but only circumstantial, evidence for a genetic or epigenetic influence on the pathogenesis of diabetic retinopathy. Despite the power of large-scale epidemiologic studies and modern molecular biological and computational techniques, the gene or genes, which predispose or protect against the development and progression of diabetic retinopathy remain elusive.
Blood pressure control for diabetic retinopathy. - The Cochrane database of systematic reviews
Diabetic retinopathy is a common complication of diabetes and a leading cause of visual impairment and blindness. Research has established the importance of blood glucose control to prevent development and progression of the ocular complications of diabetes. Simultaneous blood pressure control has been advocated for the same purpose, but findings reported from individual studies have supported varying conclusions regarding the ocular benefit of interventions on blood pressure.The primary aim of this review was to summarize the existing evidence regarding the effect of interventions to control or reduce blood pressure levels among diabetics on incidence and progression of diabetic retinopathy, preservation of visual acuity, adverse events, quality of life, and costs. A secondary aim was to compare classes of anti-hypertensive medications with respect to the same outcomes.We searched a number of electronic databases including CENTRAL as well as ongoing trial registries. We last searched the electronic databases on 25 April 2014. We also reviewed reference lists of review articles and trial reports selected for inclusion. In addition, we contacted investigators of trials with potentially pertinent data.We included in this review randomized controlled trials (RCTs) in which either type 1 or type 2 diabetic participants, with or without hypertension, were assigned randomly to intense versus less intense blood pressure control, to blood pressure control versus usual care or no intervention on blood pressure, or to different classes of anti-hypertensive agents versus placebo.Pairs of review authors independently reviewed titles and abstracts from electronic and manual searches and the full text of any document that appeared to be relevant. We assessed included trials independently for risk of bias with respect to outcomes reported in this review. We extracted data regarding trial characteristics, incidence and progression of retinopathy, visual acuity, quality of life, and cost-effectiveness at annual intervals after study entry whenever provided in published reports and other documents available from included trials.We included 15 RCTs, conducted primarily in North America and Europe, that had enrolled 4157 type 1 and 9512 type 2 diabetic participants, ranging from 16 to 2130 participants in individual trials. In 10 of the 15 RCTs, one group of participants was assigned to one or more anti-hypertensive agents and the control group received placebo. In three trials, intense blood pressure control was compared to less intense blood pressure control. In the remaining two trials, blood pressure control was compared with usual care. Five of the 15 trials enrolled type 1 diabetics, and 10 trials enrolled type 2 diabetics. Six trials were sponsored entirely by pharmaceutical companies, seven trials received partial support from pharmaceutical companies, and two studies received support from government-sponsored grants and institutional support.Study designs, populations, interventions, and lengths of follow-up (range one to nine years) varied among the included trials. Overall, the quality of the evidence for individual outcomes was low to moderate. For the primary outcomes, incidence and progression of retinopathy, the quality of evidence was downgraded due to inconsistency and imprecision of estimates from individual studies and differing characteristics of participants.For primary outcomes among type 1 diabetics, one of the five trials reported incidence of retinopathy and one trial reported progression of retinopathy after 4 to 5 years of treatment and follow-up; four of the five trials reported a combined outcome of incidence and progression over the same time interval. Among type 2 diabetics, 5 of the 10 trials reported incidence of diabetic retinopathy and 3 trials reported progression of retinopathy; one of the 10 trials reported a combined outcome of incidence and progression during a 4- to 5-year follow-up period. One trial in which type 2 diabetics participated had reported no primary (or secondary) outcome targeted for this review.The evidence from these trials supported a benefit of more intensive blood pressure control intervention with respect to 4- to 5-year incidence of diabetic retinopathy (estimated risk ratio (RR) 0.80; 95% confidence interval (CI) 0.71 to 0.92) and the combined outcome of incidence and progression (estimated RR 0.78; 95% CI 0.63 to 0.97). The available evidence provided less support for a benefit with respect to 4- to 5-year progression of diabetic retinopathy (point estimate was closer to 1 than point estimates for incidence and combined incidence and progression, and the CI overlapped 1; estimated RR 0.88; 95% CI 0.73 to 1.05). The available evidence regarding progression to proliferative diabetic retinopathy or clinically significant macular edema or moderate to severe loss of best-corrected visual acuity did not support a benefit of intervention on blood pressure: estimated RRs and 95% CIs 0.95 (0.83 to 1.09) and 1.06 (0.85 to 1.33), respectively, after 4 to 5 years of follow-up. Findings within subgroups of trial participants (type 1 and type 2 diabetics; participants with normal blood pressure levels at baseline and those with elevated levels) were similar to overall findings.The adverse event reported most often (7 of 15 trials) was death, yielding an estimated RR 0.86 (95% CI 0.64 to 1.14). Hypotension was reported from three trials; the estimated RR was 2.08 (95% CI 1.68 to 2.57). Other adverse ocular events were reported from single trials.Hypertension is a well-known risk factor for several chronic conditions in which lowering blood pressure has proven to be beneficial. The available evidence supports a beneficial effect of intervention to reduce blood pressure with respect to preventing diabetic retinopathy for up to 4 to 5 years. However, the lack of evidence to support such intervention to slow progression of diabetic retinopathy or to prevent other outcomes considered in this review, along with the relatively modest support for the beneficial effect on incidence, weakens the conclusion regarding an overall benefit of intervening on blood pressure solely to prevent diabetic retinopathy.
Role of electrophysiological studies in predicting risk of ventricular arrhythmia in early repolarization syndrome. - Journal of the American College of Cardiology
The early repolarization (ER) pattern is associated with an increased risk of arrhythmogenic sudden death. However, strategies for risk stratification of patients with the ER pattern are not fully defined.This study sought to determine the role of electrophysiology studies (EPS) in risk stratification of patients with ER syndrome.In a multicenter study, 81 patients with ER syndrome (age 36 Â± 13 years, 60 males) and aborted sudden death due to ventricular fibrillation (VF) were included. EPS were performed following the index VF episode using a standard protocol. Inducibility was defined by the provocation of sustained VF. Patients were followed up by serial implantable cardioverter-defibrillator interrogations.Despite a recent history of aborted sudden death, VF was inducible in only 18 of 81 (22%) patients. During follow-up of 7.0 Â± 4.9 years, 6 of 18 (33%) patients with inducible VF during EPS experienced VF recurrences, whereas 21 of 63 (33%) patients who were noninducible experienced recurrent VF (p = 0.93). VF storm occurred in 3 patients from the inducible VF group and in 4 patients in the noninducible group. VF inducibility was not associated with maximum J-wave amplitude (VF inducible vs. VF noninducible; 0.23 Â± 0.11 mV vs. 0.21 Â± 0.11 mV; p = 0.42) or J-wave distribution (inferior, odds ratio [OR]: 0.96 [95% confidence interval (CI): 0.33 to 2.81]; p = 0.95; lateral, OR: 1.57 [95% CI: 0.35 to 7.04]; p = 0.56; inferior and lateral, OR: 0.83 [95% CI: 0.27 to 2.55]; p = 0.74), which have previously been demonstrated to predict outcome in patients with an ER pattern.Our findings indicate that current programmed stimulation protocols do not enhance risk stratification in ER syndrome.Copyright Â© 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Prevalence and significance of rare RYR2 variants in arrhythmogenic right ventricular cardiomyopathy/dysplasia: results of a systematic screening. - Heart rhythm : the official journal of the Heart Rhythm Society
Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a genetic disease predominantly caused by desmosomal gene mutations that account for only ~50% of cases. Ryanodine receptor 2 (RYR2) gene mutations usually cause catecholaminergic polymorphic ventricular tachycardia but have been associated with a peculiar phenotype named ARVC2.We aimed to determine the prevalence and phenotype associated with RYR2 mutations in a large ARVC/D population.We analyzed the whole RYR2 coding sequence by Sanger sequencing in 64 ARVC/D probands without desmosomal gene mutations.We have identified 6 rare missense variants: p.P1583S, p.A2213S, p.G2367R, p.Y2932H, p.V3219M, and p.L4670V. It corresponds to a 9% prevalence of rare RYR2 variants in the ARVC/D population (6 of 64 probands), which is significantly higher than the estimated frequency of rare RYR2 variants in controls (Fisher exact test, P = .03). Phenotypes associated with RYR2 variants were similar to desmosome-related ARVC/D, associating typical electrocardiographic abnormalities at rest, frequent monomorphic ventricular tachycardia, right ventricular dilatation, wall motion abnormalities, and fibrofatty replacement when histopathological examination was available.In this first systematic screening of the whole coding region of the RYR2 gene in a large ARVC/D cohort without mutation in desmosomal genes, we show that putative RYR2 mutations are frequent (9% of ARVC/D probands) and are associated with a conventional phenotype of ARVC/D, which is in contrast with previous findings. The results support the role of the RYR2 gene in conventional ARVC/D.Copyright Â© 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
Gender-related safety and efficacy of cardiac resynchronization therapy. - Clinical cardiology
Cardiac resynchronization therapy (CRT) is an established therapy for patients with chronic heart failure (CHF) and a broad QRS complex. Gender-related safety and efficacy data are necessary for informed patient decision-making for female patients with CHF. The aim of the study was to assess the effects of gender on the outcome of CRT in highly symptomatic heart failure patients.Gender may have an effect on the outcome of heart failure patients undergoing cardiac resynchronisation therapy.The study analyzed the 2-year follow-up of 393 New York Heart Association (NYHA) class III/IV patients with a class I CRT indication enrolled in the Management of Atrial Fibrillation Suppression in AF-HF Comorbidity Therapy (MASCOT) study.In female patients (n = 82), compared with male patients (n = 311), CHF was more often due to dilated cardiomyopathy (74% vs 44%, respectively; P < 0.0001). Females also had a more impaired quality-of-life score and a smaller left ventricular end-diastolic diameter (LVEDD). Women were less likely than men to have received a CRT defibrillator (35% vs 61%, respectively; P < 0.0001). After 2 years, the devices had delivered more biventricular pacing in women than in men (96% Â± 13% vs 94% Â± 13%, respectively; P < 0.0004). Women had a greater reduction in LVEDD than did men (-8.2 mm Â± 11.1 mm vs -1.1 mm Â± 22.1 mm, respectively; P < 0.02). Both genders improved similarly in NYHA functional class. Women reported greater improvement than men in quality-of-life score (-21.1 Â± 26.5 vs -16.2 Â± 22.1, respectively; P < 0.0001). After adjustment for cardiovascular history, women had lower all-cause mortality (P = 0.0007), less cardiac death (P = 0.04), and fewer hospitalizations for worsening heart failure (P = 0.01).Females exhibited a better response to CRT than did males. Because females have such impressive benefits from CRT, improved screening and advocacy for CRT implantation in women should be considered.Â© 2013 Wiley Periodicals, Inc.
TRPV1 antagonist with high analgesic efficacy: 2-Thio pyridine C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides. - Bioorganic & medicinal chemistry
A series of 2-thio pyridine C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides were investigated as hTRPV1 antagonists. Among them, compound 24S showed stereospecific and excellent TRPV1 antagonism of capsaicin-induced activation. Further, it demonstrated strong anti-allodynic in a rat neuropathic pain model. Consistent with its action in vitro being through TRPV1, compound 24S blocked capsaicin-induced hypothermia in mice. Docking analysis of 24S with our hTRPV1 homology model was performed to identify its binding mode.Copyright Â© 2013 Elsevier Ltd. All rights reserved.
Use of pagers with an alarm escalation system to reduce cardiac monitor alarm signals. - Journal of nursing care quality
Alarm fatigue desensitizes nurses to alarm signals and presents potential for patient harm. This project describes an innovative method of communicating cardiac monitor alarms to pagers using an alarm escalation algorithm. This innovation was tested on 2 surgical progressive care units over a 6-month period. There was a significant decrease in mean frequency and duration of high-priority monitor alarms and improvement in nurses' perception of alarm response time, using this method of alarm communication.
Conservative management of thyroglobulin-positive, nonlocalizable thyroid carcinoma. - Head & neck
The purpose of this study was to demonstrate a role for observation of patients with differentiated thyroid cancer (DTC) with persistent, nonlocalizable disease.Our study was conducted on outpatients seen at our institution from 1999 to 2009 having total thyroidectomy, radioactive iodine (RAI) ablation, measurable serum thyroglobulin (Tg), and no evidence of disease on whole body or positron emission tomography (PET) scans.Nineteen patients in our study group aged 20 to 73 with an average follow-up of 5.5 years (range, 2-12 years); all were treated with postoperative RAI (99-210 mCi, average 119). Mean Tg ranged from 0.41 to 4.34. Tg levels remained stable or gradually decreased in all patients.After total thyroidectomy and RAI therapy, patients may present with mildly elevated Tg values without localizable disease. These patients may have additional RAI treatments based on the Tg elevation. However, our clinical experience has shown that many of these patients will have Tg levels that either achieve stability or decrease over time without further treatment.Copyright Â© 2013 Wiley Periodicals, Inc.
Risk analysis of unilateral severe-to-profound sensorineural hearing loss in children. - International journal of pediatric otorhinolaryngology
To explore the etiology of pediatric unilateral severe-to-profound sensorineural hearing loss (USPSNHL) and the risk of hearing loss in the contralateral ear.Pediatric patients with USPSNHL referred to a tertiary children's hospital for unilateral bone-anchored hearing aid implantation were identified for study. Clinical charts, audiograms, and radiographic imaging of the temporal bones were reviewed.Eighty-four children with USPSNHL were reviewed (40 male, 44 female). The etiology of USPSNHL could be identified in 35 patients (41.7%), with perinatal events (16.2%) and family history of hearing loss (10.0%) being the most common identifiable risk factors. Forty percent of children with available newborn hearing screens passed in both ears but later developed USPSNHL. Progressive unilateral hearing loss leading to USPSNHL was found in 21% percent of patients. No patient experienced worsening hearing in the contralateral ear (mean follow-up=31.9 months). Of the 49 temporal bone scans available for review, 40.8% demonstrated aberrant inner ear anatomy, including semicircular canal dysplasia (10.2%), cochlear aperture stenosis (10.2%), hypoplastic cochlea (8.1%), enlarged vestibular aqueduct (14.3%), incomplete partition I/II (6.1%), and anomalous internal auditory canal (2.0%).Pediatric USPSNHL can be attributed to a variety of sources with a cause identifiable in approximately 40% of patients. Temporal bone CT scan acquisition appears to be relatively high yield in this patient population, but only rarely do results have clinical implications. Early follow-up suggests that this population of children with USPSNHL does not appear to have a significantly increased risk for hearing loss in the contralateral ear.Copyright Â© 2013 Elsevier Ireland Ltd. All rights reserved.
2-(3-Fluoro-4-methylsulfonylaminophenyl)propanamides as potent TRPV1 antagonists: structure activity relationships of the 2-oxy pyridine C-region. - European journal of medicinal chemistry
The structure activity relationships of 2-oxy pyridine derivatives in the C-region of N-(6-trifluoromethyl-pyridin-3-ylmethyl) 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as hTRPV1 antagonists were investigated. The analysis indicated that the lipophilicity of the 2-oxy substituents was critical for potent antagonism and 4 or 5 carbons appeared to be optimal for activity. Multiple compounds proved to have comparable activity to 1, which had been reported as the most potent antagonist for capsaicin activity among the previous series of compounds. Further analysis of compounds 22 (2-isobutyloxy) and 53 (2-benzyloxy) in the formalin test in mice demonstrated strong analgesic activity with full efficacy. Docking analysis of 53S using our hTRPV1 homology model indicated that the A- and B-region 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamide made important hydrophobic and hydrogen bonding interactions with Tyr511 and that the C-region 6-trifluoromethyl and 2-benzyloxy groups of pyridine occupied the two hydrophobic binding pockets, respectively.Copyright Â© 2013 Elsevier Masson SAS. All rights reserved.
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