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Cytokines in Chronic Rhinosinusitis. Role in Eosinophilia and Aspirin-exacerbated Respiratory Disease. - American journal of respiratory and critical care medicine
The mechanisms that underlie the pathogenesis of chronic rhinosinusitis without nasal polyps (CRSsNP), chronic rhinosinusitis with nasal polyps (CRSwNP), and aspirin-exacerbated respiratory disease (AERD) are not clear.To first evaluate the inflammatory profiles of CRSsNP and CRSwNP tissues and then to investigate whether clinical differences observed between CRSwNP and AERD are in part secondary to differences in inflammatory mediator expression within nasal polyp (NP) tissues.Expression levels of numerous inflammatory mediators were determined by quantitative real-time polymerase chain reaction, ELISA, and multiplex immunoassay.CRSwNP NP had increased levels of type 2 mediators, including IL-5 (Pâ€‰<â€‰0.001), IL-13 (Pâ€‰<â€‰0.001), eotaxin-2 (P â€‰<â€‰0.001), and monocyte chemoattractant protein (MCP)-4 (Pâ€‰<â€‰0.01), compared with sinonasal tissue from subjects with CRSsNP and control subjects. Expression of IFN-Î³ messenger RNA or protein was low and not different among the chronic rhinosinusitis subtypes examined. Compared with CRSwNP, AERD NP had elevated protein levels of eosinophil cationic protein (ECP) (Pâ€‰<â€‰0.001), granulocyte-macrophage colony-stimulating factor (GM-CSF) (Pâ€‰<â€‰0.01), and MCP-1 (Pâ€‰=â€‰0.01), as well as decreased gene expression of tissue plasminogen activator (tPA) (Pâ€‰=â€‰0.02). Despite the higher eosinophilia in AERD, there was no associated increase in type 2 mediator protein levels observed.CRSwNP was characterized by a predominant type 2 inflammatory environment, whereas CRSsNP did not reflect a classic type 1 milieu, as has been suggested previously. AERD can be distinguished from CRSwNP by elevated ECP levels, but this enhanced eosinophilia is not associated with elevations in traditional type 2 inflammatory mediators associated with eosinophil proliferation and recruitment. However, other factors, including GM-CSF, MCP-1, and tPA, may be important contributors to AERD pathogenesis.
Epidemiological transition of colorectal cancer in developing countries: environmental factors, molecular pathways, and opportunities for prevention. - World journal of gastroenterology : WJG
Colorectal cancer (CRC) is one of the leading causes of cancer and cancer-related mortality worldwide. The disease has been traditionally a major health problem in industrial countries, however the CRC rates are increasing in the developing countries that are undergoing economic growth. Several environmental risk factors, mainly changes in diet and life style, have been suggested to underlie the rise of CRC in these populations. Diet and lifestyle impinge on nuclear receptors, on the intestinal microbiota and on crucial molecular pathways that are implicated in intestinal carcinogenesis. In this respect, the epidemiological transition in several regions of the world offers a unique opportunity to better understand CRC carcinogenesis by studying the disease phenotypes and their environmental and molecular associations in different populations. The data from these studies may have important implications for the global prevention and treatment of CRC.
Chronic rhinosinusitis and age: is the pathogenesis different? - Expert review of anti-infective therapy
Chronic rhinosinusitis (CRS) is a common disease with a significant impact on quality of life, which is seen across all age groups. There are differences in symptomatology, histopathology and associated diseases when comparing pediatric versus adult patients with CRS. Nasal polyposis tends to be less commonly seen in pediatric CRS compared with adults except in children with cystic fibrosis or allergic fungal rhinosinusitis. The differences in histopathology of CRS in different age groups include higher cellularity and more prominent lymphocytic infiltration in children compared with adults who tend to have a stronger eosinophilic infiltration and more prominent glandular hyperplasia. There are data supporting a stronger association of gastroesophageal reflux disease and otitis media with CRS in children compared with adults. Adenoids may play a role in pediatric, but not adult CRS. Immunodeficiencies and asthma are strongly associated with CRS in all age groups. There is a paucity of data on pathophysiology of disease on elderly CRS.
Chronic rhinosinusitis with nasal polyps is characterized by B-cell inflammation and EBV-induced protein 2 expression. - The Journal of allergy and clinical immunology
Despite the high prevalence and morbidity of chronic rhinosinusitis (CRS), little is known about the mechanisms that underlie its pathogenesis. Recent studies have suggested that B cells might play an important role in CRS.We sought to thoroughly characterize B lineage cells within sinus tissues of patients with CRS and healthy control subjects and to determine whether levels of EBV-induced protein 2, which is known to play an important role in the development of B-cell responses, were increased in patients with CRS.Cells isolated from sinus tissues of patients with CRS and healthy control subjects were characterized by means of flow cytometry and immunohistochemistry. Local production of antibodies was measured in tissue extracts, nasal lavage fluid, and sera by using multiplex bead arrays and ELISA. Quantitative RT-PCR, ELISA, and Western blotting were used to assess gene and protein expression from tissue extracts.Nasal polyps (NPs) from patients with CRS had increased levels of both B cells and plasma cells compared with uncinate tissue from healthy control subjects (P<.05). NPs also contained significantly increased levels of several antibody isotypes compared with normal uncinate tissue (P<.05), but no differences in circulating antibody levels were found. Interestingly, levels of EBV-induced protein 2 were also increased in NPs (P<.05) and were positively correlated with expression of plasma cell markers (CD138 and B lymphocyte-induced maturation protein) in sinus tissue.B cells and plasma cells are enriched in NPs, actively produce antibodies locally, and might contribute to chronic inflammation in patients with CRS. Elucidating the mechanisms that underlie this excessive local B-cell response might provide novel insights for the development of improved therapeutic strategies.Copyright Â© 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Management of allergic bronchopulmonary aspergillosis: a review and update. - Therapeutic advances in respiratory disease
Since the first description of allergic bronchopulmonary aspergillosis (ABPA) in the 1950s there have been numerous studies that have shed light on the characteristics and immunopathogenesis of this disease. The increased knowledge and awareness have resulted in earlier diagnosis and treatment of patients with this condition. This article aims to provide a summary and updates on ABPA by reviewing the results of recent studies on this disease with a focus on articles published within the last 5 years. A systematic search of PubMed/Medline with keywords of ABPA or allergic bronchopulmonary aspergillosis was performed. All selected articles were reviewed with a focus on findings of articles published from December 2006 to December 2011. The relevant findings are summarized in this paper.
Transitions at CpG dinucleotides, geographic clustering of TP53 mutations and food availability patterns in colorectal cancer. - PloS one
Colorectal cancer is mainly attributed to diet, but the role exerted by foods remains unclear because involved factors are extremely complex. Geography substantially impacts on foods. Correlations between international variation in colorectal cancer-associated mutation patterns and food availabilities could highlight the influence of foods on colorectal mutagenesis.To test such hypothesis, we applied techniques based on hierarchical clustering, feature extraction and selection, and statistical pattern recognition to the analysis of 2,572 colorectal cancer-associated TP53 mutations from 12 countries/geographic areas. For food availabilities, we relied on data extracted from the Food Balance Sheets of the Food and Agriculture Organization of the United Nations. Dendrograms for mutation sites, mutation types and food patterns were constructed through Ward's hierarchical clustering algorithm and their stability was assessed evaluating silhouette values. Feature selection used entropy-based measures for similarity between clusterings, combined with principal component analysis by exhaustive and heuristic approaches.Mutations clustered in two major geographic groups, one including only Western countries, the other Asia and parts of Europe. This was determined by variation in the frequency of transitions at CpGs, the most common mutation type. Higher frequencies of transitions at CpGs in the cluster that included only Western countries mainly reflected higher frequencies of mutations at CpG codons 175, 248 and 273, the three major TP53 hotspots. Pearson's correlation scores, computed between the principal components of the datamatrices for mutation types, food availability and mutation sites, demonstrated statistically significant correlations between transitions at CpGs and both mutation sites and availabilities of meat, milk, sweeteners and animal fats, the energy-dense foods at the basis of "Western" diets. This is best explainable by differential exposure to nitrosative DNA damage due to foods that promote metabolic stress and chronic inflammation.
Epidemiology and molecular genetics of colorectal cancer in iran: a review. - Archives of Iranian medicine
Although the incidence of colorectal cancer in Iranian older age subjects is currently very low compared to Western population, the younger generation is experiencing an accelerated rate approaching the Western rates and the burden of disease will increase dramatically in near future. The high frequency of positive family history of colorectal cancer in Iranian patients indicates that a significant number of colorectal cancers in Iran arise in family members and relatives of colorectal cancer patients. It is clear that the familial clustering of colorectal cancer is more often seen in younger probands and cancer located in the right side of the colon. These epidemiologic findings call for a broader attempt to promote public awareness and screening strategies in those families with a member affected by colorectal cancer, especially at younger age or with proximal tumors. Based on our present understanding, the possibility of preventing or curing most colon and rectal cancers is now plausible. The molecular biology of colon cancer has been the subject of many researches and is better understood than those for any other solid cancer and have established an important example for cancer research. It is now clear that colorectal cancer develops as the result of genetic and epigenetic alterations that lead to malignant transformation of normal mucosa. In spite of these scientific progresses and the fact that screening can reduce the rate of death by detecting early cancer or premalignant polyps, the rate of screening is very low globally and negligible in Iran and many other developing countries which is due to cost, resistance by physicians, patients, and the healthcare system. In Iran screening should at least be started in family members at earlier age with colonoscopy as the preferred modality of screening method.
P53 mutations in colorectal cancer from northern Iran: Relationships with site of tumor origin, microsatellite instability and K-ras mutations. - Journal of cellular physiology
CRC-associated P53 mutations have not been studied extensively in non-Western countries at relatively low CRC risk. We examined, for the first time, 196 paraffin-embedded CRC cases from Northern Iran for mutations in P53 exons 5-8 using PCR-direct sequencing. P53 status and mutation site/type were correlated with nuclear protein accumulation, clinicopathologic variables and data on K-ras mutations and high-level microsatellite instability (MSI-H). We detected 96 P53 mutations in 87 (44.4%) cases and protein accumulation in 84 cases (42.8%). P53 mutations correlated directly with stage and inversely with MSI-H. Distal CRCs were more frequently mutated at major CpG hotspot codons [248 (8/66, 12.1%), 175 (7/66, 10.6%), and 245 (7/66, 10.6%)], while in proximal tumors codon 213, emerged as most frequently mutated (5/28, 17.9% vs. 3/66, 4.5%, P = 0.048). Transitions at CpGs, the most common mutation type, were more frequent in non-mucinous (25% vs. 10.4% in mucinous, P = 0.032), and distal CRC (27% vs. 12.5% in proximal, P = 0.02), and correlated with K-ras transversions. Transitions at non-CpGs, second most common P53 mutation, were more frequent in proximal tumors (15.6% vs. 4.7% in distal, P = 0.01), and correlated with K-ras transitions and MSI-H. Overall frequency and types of mutations and correlations with P53 accumulation, stage and MSI-H were as reported for non-Iranian patients. However P53 mutation site/type and correlations between P53 and K-ras mutation types differed between proximal and distal CRC. The codon 213 P53 mutation that recurred in proximal CRC was previously reported as frequent in esophageal cancer from Northern Iran.(c) 2008 Wiley-Liss, Inc.
Gender effect on clinical features of achalasia: a prospective study. - BMC gastroenterology
Achalasia is a well-characterized esophageal motor disorder but the rarity of the disease limits performing large studies on its demographic and clinical features.Prospectively, 213 achalasia patients (110 men and 103 women) were enrolled in the study. The diagnosis established by clinical, radiographic, and endoscopic as well as manometry criteria. All patients underwent a pre-designed clinical evaluation before and within 6 months after the treatment.Solid dysphagia was the most common clinical symptom in men and women. Chest pain was the only symptom which was significantly different between two groups and was more complained by women than men (70.9% vs. 54.5% P value = 0.03). Although the occurrence of chest pain significantly reduced after treatment in both groups (P < 0.001), it was still higher among women (32% vs. 20.9% P value = 0.04). In both sexes, chest pain did not relate to the symptom duration, LES pressure and type of treatment patients received. Also no significant relation was found between chest pain and other symptoms expressed by men and women before and after treatment. Chest pain was less frequently reported by patients over 56 yrs of age in comparison to those less than 56 yrs (p < 0.05).It seems that chest pain is the distinct symptom of achalasia which is affected by sex as well as age and does not relate to the duration of illness, LESP and the type of treatment achalasia patients receive.
Incidence and age distribution of colorectal cancer in Iran: results of a population-based cancer registry. - Cancer letters
Epidemiologic patterns of colorectal cancer (CRC) in Iran have not been studied adequately. In a recent cancer registry and active cancer surveillance, we collected data on the incidence of colorectal tumors in five provinces of Iran from 1996 to 2000. In total, 2055 were registered in this study. Age-adjusted rates of CRC in Iranian males and females were 8.2 and 7.0/100,000, respectively. Seventeen percent of the cases were younger than 40 years of age at the time of diagnosis. This proportion was similar to proportions seen in many other Middle-Eastern countries, but much higher than those seen in Western countries. A comparison of age-specific rates between Iran and the US showed similar rates in young (<40 years) Iranians and Americans, but much lower rates in older (>/=40) Iranians. We conclude that Iran is still a country with low-risk of CRC, particularly for older individuals. The high proportions of young CRC cases seen in Iran, and probably many neighboring countries, are due to the young age-structure of these countries and relatively low rates of CRC in older individuals.
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