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Dihydrofolate-Reductase Mutations in Plasmodium knowlesi Appear Unrelated to Selective Drug Pressure from Putative Human-To-Human Transmission in Sabah, Malaysia. - PloS one
Malaria caused by zoonotic Plasmodium knowlesi is an emerging threat in Eastern Malaysia. Despite demonstrated vector competency, it is unknown whether human-to-human (H-H) transmission is occurring naturally. We sought evidence of drug selection pressure from the antimalarial sulfadoxine-pyrimethamine (SP) as a potential marker of H-H transmission.The P. knowlesi dihdyrofolate-reductase (pkdhfr) gene was sequenced from 449 P. knowlesi malaria cases from Sabah (Malaysian Borneo) and genotypes evaluated for association with clinical and epidemiological factors. Homology modelling using the pvdhfr template was used to assess the effect of pkdhfr mutations on the pyrimethamine binding pocket.Fourteen non-synonymous mutations were detected, with the most common being at codon T91P (10.2%) and R34L (10.0%), resulting in 21 different genotypes, including the wild-type, 14 single mutants, and six double mutants. One third of the P. knowlesi infections were with pkdhfr mutants; 145 (32%) patients had single mutants and 14 (3%) had double-mutants. In contrast, among the 47 P. falciparum isolates sequenced, three pfdhfr genotypes were found, with the double mutant 108N+59R being fixed and the triple mutants 108N+59R+51I and 108N+59R+164L occurring with frequencies of 4% and 8%, respectively. Two non-random spatio-temporal clusters were identified with pkdhfr genotypes. There was no association between pkdhfr mutations and hyperparasitaemia or malaria severity, both hypothesized to be indicators of H-H transmission. The orthologous loci associated with resistance in P. falciparum were not mutated in pkdhfr. Subsequent homology modelling of pkdhfr revealed gene loci 13, 53, 120, and 173 as being critical for pyrimethamine binding, however, there were no mutations at these sites among the 449 P. knowlesi isolates.Although moderate diversity was observed in pkdhfr in Sabah, there was no evidence this reflected selective antifolate drug pressure in humans.
Outcomes for hypopharyngeal carcinoma treated with organ-preservation therapy. - Head & neck
This study assessed outcomes of patients with hypopharyngeal carcinoma treated with organ-preservation therapy utilizing intensity-modulated radiation therapy (IMRT).The medical records of 98 patients treated with definitive IMRT +/- chemotherapy from 2001 to 2013 for nonmetastatic hypopharyngeal cancer were retrospectively reviewed.Patients were treated to doses of 66 to 72 Gy. Eighty-three patients (85%) received chemotherapy. With median follow-up of 35 months, 2-year overall survival (OS), locoregional control, progression-free survival (PFS), and laryngectomy-free survival rates were 74%, 77%, 67%, and 65%, respectively. Functional laryngeal preservation rate was 76% at 2 years. N3 disease correlated with worse OS (p < .01). Concurrent chemotherapy correlated with improved locoregional control (p = .03) and complete response to induction chemotherapy correlated with improved OS and PFS (p = .02). Actuarial 2-year and 5-year grade 3 treatment toxicities were 17% and 21%, respectively.Favorable disease outcomes and functional laryngeal preservation rates can be achieved with IMRT for patients with hypopharyngeal cancer. Â© 2016 Wiley Periodicals, Inc. Head Neck, 2016.Â© 2016 Wiley Periodicals, Inc.
Proposed Staging System for Patients With HPV-Related Oropharyngeal Cancer Based on Nasopharyngeal Cancer N Categories. - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Patients with human papillomavirus (HPV)-related oropharyngeal cancer (OPC) generally present with more advanced disease but have better survival than patients with HPV-unrelated OPC. The current American Joint Commission on Cancer (AJCC)/Union for International Cancer Control (UICC) TNM staging system for OPC was developed for HPV-unrelated OPC. A new staging system is needed to adequately predict outcomes of patients with HPV-related OPC.Patients with newly diagnosed HPV-positive OPC (by p16 immunohistochemistry or in situ hybridization) treated at our institution from January 2003 through December 2012 were included. By using recursive partitioning analysis (RPA), we developed new stage groupings with both traditional OPC regional lymph node (N) categories and nasopharyngeal carcinoma (NPC) N categories. Survival was estimated by the Kaplan-Meier method, and the relationship between stage and survival was examined by using Cox proportional hazards regression analysis.A total of 661 patients with HPV-positive OPC met the inclusion criteria. With the traditional TNM staging system, there was no difference in survival between stages (P = .141). RPA with NPC N categories resulted in more balanced stage groups and better separation between groups for 5-year survival than RPA with traditional OPC N categories. With the stage groupings that were based in part on NPC N categories, the risk of death increased with increasing stage (P for trend < .001), and patients with stage III disease had five times the risk of death versus patients with stage IA disease.New stage groupings that are based on primary tumor (T) categories and NPC N categories better separate patients with HPV-positive OPC with respect to survival than does the current AJCC/UICC TNM staging system. Although confirmation of our findings in other patient populations is needed, we propose consideration of NPC N categories as an alternative to the traditional OPC N categories in the new AJCC/UICC TNM staging system that is currently being developed.Â© 2016 by American Society of Clinical Oncology.
Sensitive Detection of Plasmodium vivax Using a High-Throughput, Colourimetric Loop Mediated Isothermal Amplification (HtLAMP) Platform: A Potential Novel Tool for Malaria Elimination. - PLoS neglected tropical diseases
Plasmodium vivax malaria has a wide geographic distribution and poses challenges to malaria elimination that are likely to be greater than those of P. falciparum. Diagnostic tools for P. vivax infection in non-reference laboratory settings are limited to microscopy and rapid diagnostic tests but these are unreliable at low parasitemia. The development and validation of a high-throughput and sensitive assay for P. vivax is a priority.A high-throughput LAMP assay targeting a P. vivax mitochondrial gene and deploying colorimetric detection in a 96-well plate format was developed and evaluated in the laboratory. Diagnostic accuracy was compared against microscopy, antigen detection tests and PCR and validated in samples from malaria patients and community controls in a district hospital setting in Sabah, Malaysia.The high throughput LAMP-P. vivax assay (HtLAMP-Pv) performed with an estimated limit of detection of 1.4 parasites/ Î¼L. Assay primers demonstrated cross-reactivity with P. knowlesi but not with other Plasmodium spp. Field testing of HtLAMP-Pv was conducted using 149 samples from symptomatic malaria patients (64 P. vivax, 17 P. falciparum, 56 P. knowlesi, 7 P. malariae, 1 mixed P. knowlesi/P. vivax, with 4 excluded). When compared against multiplex PCR, HtLAMP-Pv demonstrated a sensitivity for P. vivax of 95% (95% CI 87-99%); 61/64), and specificity of 100% (95% CI 86-100%); 25/25) when P. knowlesi samples were excluded. HtLAMP-Pv testing of 112 samples from asymptomatic community controls, 7 of which had submicroscopic P. vivax infections by PCR, showed a sensitivity of 71% (95% CI 29-96%; 5/7) and specificity of 93% (95% CI87-97%; 98/105).This novel HtLAMP-P. vivax assay has the potential to be a useful field applicable molecular diagnostic test for P. vivax infection in elimination settings.
Outcomes of Primary Transconjunctival 23-Gauge Vitrectomy in the Diagnosis and Treatment of Presumed Endogenous Fungal Endophthalmitis. - Ocular immunology and inflammation
To report the outcomes of primary transconjunctival 23-gauge (23-G) vitrectomy in the diagnosis and treatment of presumed endogenous fungal endophthalmitis (EFE).Retrospective analysis of patients with EFE who underwent diagnostic transconjunctival 23-G vitrectomy at a tertiary referral center.Nineteen eyes of 15 patients with EFE were included in the study. Four patients had bilateral and 11 patients unilateral disease. Sixteen eyes of 15 patients underwent 23-G vitrectomy to confirm the diagnosis using vitreous culture, polymerase chain reaction, and histopathologic examinations. All affected eyes were treated with intravitreal amphotericin B 5 Âµg/0.1 mL. Fourteen patients received additional systemic antifungal therapy. Diagnostic 23-G vitrectomy confirmed the diagnosis of EFE in 75% of the eyes (12/16). Candida was found to be a causative agent in 62.5% and Aspergillus in 12.5% of the eyes. Retinal detachment was the most common complication (42% of eyes).EFE can be easily confirmed using primary 23-G vitrectomy.
Association between Landscape Factors and Spatial Patterns of Plasmodium knowlesi Infections in Sabah, Malaysia. - Emerging infectious diseases
The zoonotic malaria species Plasmodium knowlesi has become the main cause of human malaria in Malaysian Borneo. Deforestation and associated environmental and population changes have been hypothesized as main drivers of this apparent emergence. We gathered village-level data for P. knowlesi incidence for the districts of Kudat and Kota Marudu in Sabah state, Malaysia, for 2008-2012. We adjusted malaria records from routine reporting systems to reflect the diagnostic uncertainty of microscopy for P. knowlesi. We also developed negative binomial spatial autoregressive models to assess potential associations between P. knowlesi incidence and environmental variables derived from satellite-based remote-sensing data. Marked spatial heterogeneity in P. knowlesi incidence was observed, and village-level numbers of P. knowlesi cases were positively associated with forest cover and historical forest loss in surrounding areas. These results suggest the likelihood that deforestation and associated environmental changes are key drivers in P. knowlesi transmission in these areas.
Emotional Freedom Techniques in the Treatment of Unhealthy Eating Behaviors and Related Psychological Constructs in Adolescents: A Randomized Controlled Pilot Trial. - Explore (New York, N.Y.)
In Australia and throughout much of the world, rates of obesity continue to climb as do the prevalence of eating disorders, particularly in adolescents. Psychological consequences of childhood obesity include low self-esteem, depression, body dissatisfaction, and social maladjustment (Young-Hyman et al., 2012).This feasibility study sought to examine the impact of a six-week Emotional Freedom Techniques (EFT) group treatment program upon eating behaviours, self-esteem, compassion, and psychological symptoms.Forty-four students were randomly allocated to either the EFT group or the waitlist control group.Results revealed a delayed effect for both groups at post-intervention, with improved eating habits, self-esteem, and compassion at follow-up. Findings provide preliminary support for EFT as an effective treatment strategy for increasing healthy eating behaviours and improving associated weight-related psychopathology.Copyright Â© 2016 Elsevier Inc. All rights reserved.
The adult prevalence of HIV in Zambia: results from a population based mobile testing survey conducted in 2013-2014. - AIDS research and therapy
To estimate the adult prevalence of HIV among the adult population in Zambia and determine whether demographic characteristics were associated with being HIV positive.A cross sectional population based survey to asses HIV status among participants aged 15Â years and above in a national tuberculosis prevalence survey. Counselling was offered to participants who tested for HIV. The prevalence was estimated using a logistic regression model. Univariate and multivariate associations of social demographic characteristics with HIV were determined.Of the 46,099 individuals who were eligible to participate in the survey, 44,761 (97.1Â %) underwent pre-test counselling for HIV; out of which 30,605 (68.4Â %) consented to be tested and 30, 584 (99.9Â %) were tested. HIV prevalence was estimated to be 6.6Â % (95Â % CI 5.8-7.4); with females having a higher prevalence than males 7.7Â % (95Â % CI 6.8-8.7) versus 5.2Â % (95Â % CI 4.4-5.9). HIV prevalence was higher among urban (9.8Â %; 95Â % CI 8.8-10.7) than rural residents (5.0Â %; 95Â % CI 4.3-5.8). The risk of HIV was double among urban dwellers than among their rural counterparts. Being divorced or widowed was associated with a threefold higher risk of being HIV positive than being never married. The risk of being HIV positive was four times higher among those with tuberculosis than those without tuberculosis.HIV prevalence was lower than previously estimated in the country. The burden of HIV showed sociodemographic disparities signifying a need to target key populations or epidemic drivers. Mobile testing for HIV on a national scale in the context of TB prevalence surveys could be explored further in other settings.
Explaining retention of healthcare workers in Tanzania: moving on, coming to 'look, see and go', or stay? - Human resources for health
In the United Republic of Tanzania, as in many regions of Sub-Saharan Africa, staff shortages in the healthcare system are a persistent problem, particularly in rural areas. To explore staff shortages and ways of keeping workers in post, we ask, (a) Which cadres are most problematic to recruit and keep in post? (b) How and for what related reasons do health workers leave? (c) What critical incidents do those who stay face? (d) And why do they stay and cope?This is a multi-method paper based on analysis of data collected as part of a cross-sectional health facility study supporting maternal and reproductive health services in the United Republic of Tanzania. Qualitative data were generated through semi-structured interviews with Council Health Management Teams, and Critical Incident Technique interviews with mid-level cadres. Complementary quantitative survey data were collected from district health officials, which are used to support the qualitative themes.Mid-level cadres were problematic to retain and caused significant disruptions to continuity of care when they left. Shortage of highly skilled workers is not only a rural issue but also a national one. Staff were categorised into a clear typology. Staff who left soon after arrival and are described by 'Look, See and Go'; 'Movers On' were those who left due to family commitments or because they were pushed to go. The remaining staff were 'Stayers'. Reasons for wanting to leave included perceptions of personal safety, feeling patient outcomes were compromised by poor care or as a result of perceived failed promises. Staying and coping with unsatisfactory conditions was often about being settled into a community, rather than into the post.The Human Resources for Health system in the United Republic of Tanzania appears to lack transparency. A centralised monitoring system could help to avoid early departures, misallocation of training, and other incentives. The system should match workers' profiles to the most suitable post for them and track their progress and rewards; training managers and holding them accountable. In addition, priority should be given to workplace safety, late night staff transport, modernised and secure compound housing, and involving the community in reforming health services culture and practices.
Trigeminal and sphenopalatine ganglion stimulation for intractable craniofacial pain-case series and literature review. - Acta neurochirurgica
Facial pain is often debilitating and can be characterized by a sharp, stabbing, burning, aching, and dysesthetic sensation. Specifically, trigeminal neuropathic pain (TNP), anesthesia dolorosa, and persistent idiopathic facial pain (PIFP) are difficult diseases to treat, can be quite debilitating and an effective, enduring treatment remains elusive.We retrospectively reviewed our early experience with stimulation involving the trigeminal and sphenopalatine ganglion stimulation for TNP, anesthesia dolorosa, and PIFP between 2010-2014 to assess the feasibility of implanting at these ganglionic sites. Seven patients received either trigeminal and/or sphenopalatine ganglion stimulation with or without peripheral nerve stimulation, having failed multiple alternative modalities of treatment. The treatments were tailored on the physical location of pain to ensure regional coverage with the stimulation.Fluoroscopy or frameless stereotaxy was utilized to place the sphenopalatine and/or trigeminal ganglion stimulator. All patients were initially trialed before implantation. Trial leads implanted in the pterygopalatine fossa near the sphenopalatine ganglion were implanted via transpterygoid (lateral-medial, infrazygomatic) approach. Trial leads were implanted in the trigeminal ganglion via percutaneous Hartel approach, all of which resulted in masseter contraction. Patients who developed clinicallyÂ significant pain improvement underwent implantation. The trigeminal ganglion stimulation permanent implants involved placing a grid electrode over Meckel's cave via subtemporal craniotomy, which offered a greater ability to stimulate subdivisions of the trigeminal nerve, without muscular (V3) side effects. Two of the seven overall patients did not respond well to the trial and were not implanted. Five patients reported pain relief with up to 24-month follow-up. Several of the sphenopalatine ganglion stimulation patients had pain relief without any paresthesias. There were no electrode migrations or post-surgical complications.Refractory facial pain may respond positively to ganglionic forms of stimulation. It appears safe and durable to implant electrodes in the pterygopalatine fossa via a lateral transpterygoid approach. Also, implantation of an electrode grid overlying Meckel's cave appears to be a feasible alternative to the Hartel approach. Further investigation is needed to evaluate the usefulness of these approaches for various facial pain conditions.
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