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Right Ventricular Function and Prognosis in Patients with Low-Flow, Low-Gradient Severe Aortic Stenosis. - Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography
Patients with low left ventricular ejection fractions and low-flow, low-gradient aortic stenosis (AS) represent a challenging cohort with high morbidity and mortality. The prevalence and clinical impact of right ventricular dysfunction (RVD) on risk stratification and prognosis in these patients is unknown.A retrospective analysis was performed of 65 patients with low-flow, low-gradient AS who underwent low-dose dobutamine stress echocardiography to determine AS severity and to ascertain flow reserve status (â‰¥20% stroke volume increase). Clinical, demographic, and imaging data were prospectively collected. Per guidelines, RVD was defined as tricuspid annular plane systolic excursionÂ <Â 16Â mm in the apical four-chamber view and measured at baseline. Cox proportional hazards modeling was used to risk-adjust comparisons for the end point of all-cause mortality.The mean age was 74Â Â±Â 9Â years, the mean left ventricular ejection fraction was 29Â Â±Â 10%, the mean indexed aortic valve (AV) area was 0.49Â Â±Â 0.1Â cm(2)/m(2), and the mean AV gradient 22Â Â±Â 7Â mmÂ Hg. RVD was present in 37 patients (57% of the study cohort). After a median follow-up period of 13Â months (interquartile range, 5-30Â months), there were 29 AV replacements and 30 deaths. The presence of RVD (hazard ratio, 2.86; 95% CI, 1.21-6.75; PÂ =Â .02) was an independent risk factor associated with all-cause mortality despite many adjustments for potential clinical and echocardiographic confounders such as AV replacement, Society of Thoracic Surgeons Predicted Risk of Mortality score, severity of tricuspid regurgitation, and left ventricular global longitudinal strain.Baseline RVD is prevalent in patients with low-flow, low-gradient AS undergoing dobutamine stress echocardiography. Quantification of right ventricular systolic function in these complex patients provides important prognostic value and risk stratification adjunctive to Society of Thoracic Surgeons Predicted Risk of Mortality score and should be incorporated into the decision-making process.Copyright Â© 2015 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.
Possibility of methane conversion into heavier hydrocarbons using nanosecond lasers. - Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy
Effect of nanosecond lasers on the methane dissociation is experimentally studied by using three different laser wavelengths at 248nm, 355nm and 532nm. C2H2 generation is measured as a major reaction product in experiments and the energy consumptions in production of this component are measured as 5.8MJ/mol, 3.1MJ/mol and 69.0MJ/mol, for 355nm, 532nm and 248nm wavelengths, respectively. The mechanism of conversion and production of new stable hydrocarbons is also theoretically investigated. It is found that in theoretical calculations, the ion-molecule reactions should be included and this leads to a unique approach in proper explanation of the experimental measurements.Copyright Â© 2015 Elsevier B.V. All rights reserved.
Improving the accuracy of HES comorbidity codes by better documentation in surgical admission proforma. - British journal of hospital medicine (London, England : 2005)
Poor documentation in medical notes can affect the quality of the source document for coding which can lead to inaccurate coding. This study aimed to determine the accuracy of Hospital Episode Statistics (HES) data for comorbidities and to establish whether better documentation in admission clerking proforma can improve the accuracy of codes for comorbidities in general surgical patients.A clinical audit was conducted to assess the accuracy, sensitivity, specificity, positive predictive value and negative predictive value of HES codes for comorbidities in general surgical patients before and after implementing better documentation in admission clerking proforma. The following comorbidities were included: hypertension, ischaemic heart disease, diabetes, asthma, chronic obstructive pulmonary disease, cerebrovascular disease, chronic kidney disease and hypercholesterolaemia. Medical notes were used as reference standard and a target standard of 98% was determined for the above measures.Overall, on the initial audit, HES codes had substandard accuracy (90.5%, kappa = 0.599), sensitivity (47.71%, 95% confidence interval 38.05-57.49%) and negative predictive value (89.60%, 95% confidence interval 86.73-92.03%). HES codes for comorbidities were 100% specific with positive predictive value of 100%. Implementing better documentation in the admission clerking proforma improved the accuracy (99.67%, kappa = 0.985), sensitivity (97.4%, 95% confidence interval 90.93-99.68%) and negative predictive value (99.62%, 95% confidence interval 98.63-99.95%) significantly from the baseline (P<0.0001).Although HES codes can confidently predict the actual presence of the comorbidities, they have substandard accuracy and ability to rule out the presence of the comorbidities. Better documentation in clerking proforma can improve the accuracy and 'ruling out' ability of the HES codes. This can be achieved by improving knowledge and accountability of clinicians about documenting comorbidities.
The Yin and Yang of Antiviral Innate Immunity in Central Nervous System. - Current pharmaceutical design
The innate immune system provides protection against invading neurotropic viruses. It acts as the first line of defense against invading viruses and plays an elementary role in their pathogenesis. The list of viruses capable of infecting human central nervous system (CNS) is quite long, most important of them are Japanese Encephalitis virus (JEV), rabies virus, West Nile virus (WNV), herpes simplex virus (HSV), St. Louis encephalitis virus (SLEV), La Crosse virus, tick borne encephalitis virus (TEBE) and polio virus. Germ line pattern recognition receptors (PRRs) such as Toll like receptors (TLRs), nucleotide binding oligomerization domain (NOD) - like receptors (NLRs), retinoic acid-inducible gene I (RIG-I) -like helicases or RIG-I-like receptors (RLRs) and cytosolic DNA sensors recognize the pathogen associated molecular patterns (PAMPs) and initiate an immune response against invading pathogen. Although PRRs were originally characterized in peripheral immune cells but accumulating evidence also suggest their crucial roles in CNS to combat against neurotropic viruses. In this review, we will highlight the recent developments in our understating of the mechanisms by which PRRs in resident brain cells provide protection against invading neurotropic viruses.
Pediatric Melanoma and Atypical Melanocytic Neoplasms. - Cancer treatment and research
Melanoma is uncommon in the pediatric age range, but is increasing in frequency and often presents with atypical features compared to the classic ABCDE criteria common to adult melanoma cases. Moreover, many melanocytic neoplasms in childhood pose diagnostic challenges to the pathologist, and sometimes cannot be unequivocally classified as benign nevi or melanoma. This chapter addresses the evaluation and management of pediatric patients with melanoma and atypical melanocytic neoplasms, including the roles of and unresolved questions surrounding sentinel lymph node biopsy, completion lymphadenectomy, adjuvant therapy, and treatment of advanced disease.
Aggressive Aortic Arch and Carotid Replacement Strategy for Type A Aortic Dissection Improves Neurologic Outcomes. - The Annals of thoracic surgery
International registries for acute type A aortic dissection (TAAD) demonstrate stagnant operative mortality rates in excess of 20% and stroke rates of 9% to 25%, with little global emphasis on stroke reduction or carotid involvement. Cerebral malperfusion with TAAD has been linked to poorer outcome. We hypothesize that concomitant carotid dissection or complex dissection flaps in the arch play a major role in stroke development and that aggressive reconstruction of the arch and carotid arteries can improve neurologic outcomes in TAAD.A standardized protocol focused on expedient care, neurocerebral protection, and common carotid and total arch reconstruction was developed for 264Â consecutive TAADs. Arch and complete carotid replacement was based on arch dissection anatomy, carotid involvement, or an intraarch tear. Neurocerebral monitoring with continuous electroencephalogram/somatosensory evoked potentials was used in all cases.The postoperative stroke and hospital mortality rates were 3.4% and 9.1%, and stroke rates by extent of arch replacement were 4%, 3%, and 0% for hemiarch, total arch, and total arch with complete carotid replacement, respectively. An intraoperative change in the electroencephalogram/somatosensory evoked potentials was strongly predictive of stroke and had a negative predictive value of 98.2%.An algorithmic approach to TAAD including (1) rapid transport-to-incision-to-cardiopulmonary bypass established centrally, (2) neurocerebral monitoring, (3) liberal use of total arch replacement for clearly defined indications (and hemiarch for all others), and (4) common carotid arterial replacement for concomitant carotid dissections significantly improves outcomes.Copyright Â© 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Assessing vascular effects of adding bevacizumab to neoadjuvant chemotherapy in osteosarcoma using DCE-MRI. - British journal of cancer
The purpose of this study was to assess the impact of bevacizumab alone and in combination with cytotoxic therapy on tumour vasculature in osteosarcoma (OS) using DCE-MRI.Six DCE-MRI and three (18)F-FDG PET examinations were scheduled in 42 subjects with newly diagnosed OS to monitor the response to antiangiogenic therapy alone and in combination with cytotoxic therapy before definitive surgery (week 10). Serial DCE-MRI parameters (K(trans), v(p), and v(e)) were examined for correlation with FDG-PET (SUV(max)) and association with drug exposure, and evaluated with clinical outcome.K(trans) (P=0.041) and v(p) (P=0.001) significantly dropped from baseline at 24 h after the first dose of bevacizumab alone, but returned to baseline by 72â€‰h. Greater exposure to bevacizumab was correlated with larger decreases in v(p) at day 5 (P=0.04) and week 10 (P=0.02). A lower K(trans) at week 10 was associated with greater percent necrosis (P=0.024) and longer event-free survival (P=0.034).This is the first study to demonstrate significant changes of the plasma volume fraction and vascular leakage in OS with bevacizumab alone. The combination of demonstrated associations between drug exposure and imaging metrics, and imaging metrics and patient survival during neoadjuvant therapy, provides a compelling rationale for larger studies using DCE-MRI to assess vascular effects of therapy in OS.
Bevacizumab dosing strategy in paediatric cancer patients based on population pharmacokinetic analysis with external validation. - British journal of clinical pharmacology
The aim of the present study was to evaluate the pharmacokinetics of bevacizumab and various dosing strategies for this agent in paediatric patients.Data were collected from 232 paediatric patients (1971 concentrations) in five studies, with a wide range of age (0.5â€‰-â€‰21Â years), body weight (BWT; 5.9â€‰-â€‰125Â kg), and regimens (5â€‰-â€‰15Â mg kg(-1) biweekly or triweekly). Data from 152 patients (1427 concentrations) and 80 patients (544 concentrations) were used for model building and external validation, respectively. Steady-state exposure was simulated under BWT-based, body surface area (BSA)-based, ideal body weight (IBW)-based, and tier-based doses. NONMEM and R were used for analyses.Typical estimates of clearance, central volume of distribution (V1), and median half-life were 9.04Â ml h(-1) , 2851Â ml, and 19.6Â days, respectively. Clearance decreased with increasing albumin. Clearance and V1 increased with BWT and were higher in male patients. Clearance and V1 were lower in children with primary central nervous system (CNS) tumours than in children with sarcomas, resulting in 49% higher trough (Cmin) and 29% higher peak (Cmax) concentrations. BWT-adjusted clearance and V1 remained unchanged across ages. Paediatric Cmin was similar to adult Cmin under all dosing strategies. Paediatric Cmax exceeded adult Cmax under tier-based doses.BWT-adjusted pharmacokinetic parameter estimates in paediatric patients were similar to those in adults, and similar across ages. Bevacizumab exposure was higher in children with primary CNS tumours than in children with sarcomas. BSA-based, IBW-based, and tier-based doses offered no substantial advantage over the BWT-based dose currently used in adults for bevacizumab. Given the similarity in pharmacokinetics among many monoclonal antibodies, this may help to develop practical paediatric dosing guidelines for other therapeutic antibodies.Â© 2015 Genentech Inc. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
Colonization and antifungals susceptibility patterns of Candida species isolated from hospitalized patients in ICUs and NICUs. - Journal of nephropathology
Several studies have shown that there are an increasing in invasive candidiasis during 2-3 last decades. Although, Candida albicans is considered as the most common candidiasis agents, other non-albicans such as C. glabrata, C. krusei, C. parapsilosis, and C. tropicalis were raised as infectious agents. Resistance to fluconazole among non-albicans species is an important problem for clinicians during therapy and prophylaxis.The aim of current study was to detect the Candida species from hospitalized neonatal and children in intensive care units (ICUs) and neonatal intensive care units (NICUs). In addition, the susceptibility of isolated agents were also evaluated against three antifungals.In the present study 298 samples including 98 blood samples, 100 urines and 100 swabs from oral cavity were inoculated on CHROMagar Candida. Initial detection was done according to the coloration colonies on CHROMagar Candida . Morphology on cornmeal agar, germ tube formation and growth at 45Â°C were confirmed isolates. Amphotericin B, fluconazole and terbinafine (Lamisil) were used for the susceptibility tests using microdilution method.In the present study 21% and 34% of urines and swabs from oral cavity were positive for Candida species, respectively. The most common species was C. albicans (62.5%) followed by C. tropicalis (15.6%), C. glabrata (6.3%) and Candida species (15.6%). Our study indicated that the most tested species of Candida, 70.3% were sensitive to fluconazole at the concentration of â‰¤8 Î¼g/mL. Whereas 9 (14.1%) of isolates were resistant to amphotericine B at â‰¥8 Î¼g/mL.This study demonstrates the importance of species identification and antifungals susceptibility testing for hospitalized patients in ICUs and NICUs wards.
Association of low serum TGF-Î² level in hantavirus infected patients with severe disease. - BMC immunology
Hantaviruses are emerging zoonotic pathogens which cause hemorrhagic fever with renal syndrome, an immune-mediated pathogenesis is discussed. The aim of the present study was to investigate the role of TGF-Î² expression in acute hantavirus infection.We retrospectively studied 77 patients hospitalised with acute Puumala infection during a hantavirus epidemic in Germany in 2012. Hantavirus infection was confirmed by positive anti-Puumala hantavirus IgG and IgM. Plasma levels of transforming growth factor (TGF)-Î²1 and TGF-Î²2 were analysed. Based on glomerular filtration rate on admission, patients were divided in mild and severe course of disease. Puumala virus RNA was detected by PCR amplification of the viral L segment gene. Out of 77 Puumala virus infected patients, 52 (68%) were male. A seasonal distribution was detected in our cohort with a peak in summer 2012, the highest incidence was observed in the age group of 30-39 years. Puumala virus RNA was detectable in 4/77 cases. Patients with severe disease had a significant longer hospital stay than patients with mild disease (6.2 vs 3.6Â days). Thrombocyte count (186 vs 225 per nl), serum TGF-Î²1 (74 vs 118Â ng/l) and TGF-Î²2 (479 vs 586Â pg/l) were significantly lower in severe compared to mild disease. However, C-reactive protein (CRP) was significantly higher in patients with severe disease (62 vs 40Â mg/l). TGF-Î²1/Cr was the most sensitive and specific marker associated with renal dysfunction.High serum CRP and low serum TGF-Î² in the early phase of hantavirus infection is associated with a severe course of disease. Our results support the hypothesis of an immune-mediated pathogenesis in hantavirus infection.
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