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The role of C1q in recognition of apoptotic epithelial cells and inflammatory cytokine production by phagocytes during Helicobacter pylori infection. - Journal of inflammation (London, England)
Gastric epithelial cells (GECs) undergo apoptosis during H. pylori infection and phagocytes within the mucosa engulf these cells. The recognition and clearance of apoptotic cells is a multifactorial process, enhanced by the presence of various bridging molecules and opsonins which are abundant in serum. However, it is not clear how recognition or clearance may differ in the context of H. pylori infection induced apoptosis. In addition, efferocytosis of sterile apoptotic cells is known to confer anti-inflammatory properties in the engulfing phagocyte, however it is unknown if this is maintained when phagocytes encounter H. pylori-infected cells. Thus, the ability of macrophages to bind and engulf gastric epithelial cells rendered apoptotic by H. pylori infection and the association of these interactions to the modulation of phagocyte inflammatory responses was investigated in the absence and presence of serum with a particular focus on the role of serum protein C1q.Control (uninfected) or H. pylori-infected AGS cells were co-cultured with THP-1 macrophages in the presence or absence of serum or serum free conditionsâ€‰+â€‰C1q protein (40-80Â Î¼g/mL). Binding of AGS cells to THP-1 macrophages was assessed by microscopy and cytokine (IL-6 and TNF-Î±) release from LPS stimulated THP-1 macrophages was quantified by ELISA.We show that macrophages bound preferentially to cells undergoing apoptosis subsequent to infection with H. pylori. Binding of apoptotic AGS to THP-1 macrophages was significantly inhibited when studied in the absence of serum and reconstitution of serum-free medium with purified human C1q restored binding of macrophages to apoptotic cells. Co-culture of sterile apoptotic and H. pylori-infected AGS cells both attenuated LPS-stimulated cytokine production by THP-1 macrophages. Further, direct treatment of THP-1 macrophages with C1q attenuated LPS stimulated TNF-Î± production.These studies suggest that C1q opsonizes GECs rendered apoptotic by H. pylori. No differences existed in the ability of infected or sterile apoptotic cells to attenuate macrophage cytokine production, however, there may be a direct role for C1q in modulating macrophage inflammatory cytokine production to infectious stimuli.
Increased hippocampal excitability in the 3xTgAD mouse model for Alzheimer's disease in vivo. - PloS one
Mouse Alzheimer's disease (AD) models develop age- and region-specific pathology throughout the hippocampal formation. One recently established pathological correlate is an increase in hippocampal excitability in vivo. Hippocampal pathology also produces episodic memory decline in human AD and we have shown a similar episodic deficit in 3xTg AD model mice aged 3-6 months. Here, we tested whether hippocampal synaptic dysfunction accompanies this cognitive deficit by probing dorsal CA1 and DG synaptic responses in anaesthetized, 4-6 month-old 3xTgAD mice. As our previous reports highlighted a decline in episodic performance in aged control mice, we included aged cohorts for comparison. CA1 and DG responses to low-frequency perforant path stimulation were comparable between 3xTgAD and controls at both age ranges. As expected, DG recordings in controls showed paired-pulse depression; however, paired-pulse facilitation was observed in DG and CA1 of young and old 3xTgAD mice. During stimulus trains both short-latency (presumably monosynaptic: 'direct') and long-latency (presumably polysynaptic: 're-entrant') responses were observed. Facilitation of direct responses was modest in 3xTgAD animals. However, re-entrant responses in DG and CA1 of young 3xTgAD mice developed earlier in the stimulus train and with larger amplitude when compared to controls. Old mice showed less DG paired-pulse depression and no evidence for re-entrance. In summary, DG and CA1 responses to low-frequency stimulation in all groups were comparable, suggesting no loss of synaptic connectivity in 3xTgAD mice. However, higher-frequency activation revealed complex change in synaptic excitability in DG and CA1 of 3xTgAD mice. In particular, short-term plasticity in DG and CA1 was facilitated in 3xTgAD mice, most evidently in younger animals. In addition, re-entrance was facilitated in young 3xTgAD mice. Overall, these data suggest that the episodic-like memory deficit in 3xTgAD mice could be due to the development of an abnormal hyper-excitable state in the hippocampal formation.
Brain angiogenesis inhibitor 1 is expressed by gastric phagocytes during infection with Helicobacter pylori and mediates the recognition and engulfment of human apoptotic gastric epithelial cells. - FASEB journal : official publication of the Federation of American Societies for Experimental Biology
After Helicobacter pylori infection in humans, gastric epithelial cells (GECs) undergo apoptosis due to stimulation by the bacteria or inflammatory cytokines. In this study, we assessed the expression and function of brain angiogenesis inhibitor 1 (BAI1) in the engulfment of apoptotic GECs using human tissue and cells. After induction of apoptosis by H. pylori or camptothecin, there was a 5-fold increase in the binding of apoptotic GECs to THP-1 cells or peripheral blood monocyte-derived macrophages as assayed by confocal microscopy or conventional and imaging flow cytometry. Binding was impaired 95% by pretreating apoptotic cells with annexin V, underscoring the requirement for phosphatidylserine recognition. The phosphatidylserine receptor BAI1 was expressed in human gastric biopsy specimens and gastric phagocytes. To confirm the role of BAI1 in apoptotic cell clearance, the functional domain of BAI1 was used as a competitive inhibitor or BAI1 expression was inhibited by small interfering RNA. Both approaches decreased binding and engulfment >40%. Exposing THP-1 cells to apoptotic cells inhibited IL-6 production from 1340 to <364 pg/ml; however, this decrease was independent of phagocytosis. We conclude that recognition of apoptotic cells by BAI1 contributes to their clearance in the human gastric mucosa and this is associated with anti-inflammatory effects.
Oxygen levels determine the ability of glucocorticoids to influence neutrophil survival in inflammatory environments. - Journal of leukocyte biology
GCs are highly effective in treating a wide range of inflammatory diseases but are limited in their ability to control neutrophilic lung inflammation in conditions such as COPD. Neutrophil apoptosis, a central feature of inflammation resolution, is delayed in response to microenvironmental cues, such as hypoxia and inflammatory cytokines, present at inflamed sites. GCs delay neutrophil apoptosis in vitro, and this may therefore limit the ability of GCs to control neutrophilic inflammation. This study assesses the effect GCs have on hypoxia- and inflammatory cytokine-induced neutrophil survival. Human neutrophils were treated with GCs in the presence or absence of GM-CSF or inflammatory macrophage-CM at a range of oxygen concentrations (21-1% oxygen). Neutrophil apoptosis and survival were assessed by flow cytometry and morphological analysis and neutrophil function, by stimulus-induced shape change and respiratory burst. Dexamethasone promoted neutrophil survival at 21%, 10%, and 5% oxygen but not at 1% oxygen. Interestingly, GM-CSF and inflammatory CM increased neutrophil survival significantly, even at 1% oxygen, with cells remaining functionally active at 96 h. Dexamethasone was able to reduce the prosurvival effect of GM-CSF and inflammatory CM in a hypoxic environment. In conclusion, we found that GCs do not augment neutrophil survival in the presence of severe hypoxia or proinflammatory mediators. This suggests that GCs would not promote neutrophil survival at sites of inflammation under these conditions.
Mild aphasia: is this the place for an argument? - American journal of speech-language pathology / American Speech-Language-Hearing Association
Individuals with mild aphasia often report significant disruption to their communication despite seemingly minor impairment. This study explored this phenomenon through examining conversations of a person with mild aphasia engaging in argumentation--a skill she felt had significantly deteriorated after her stroke.A person with mild aphasia and her husband recorded 4 conversations involving topical issues. The discourse dynamics and lexical-grammatical content were analyzed using systemic functional linguistic (Halliday & Matthiessen, 2004) and conversation analysis (Sacks, Schegloff, & Jefferson, 1974) frameworks.The couple demonstrated similarities in the types of conversational moves, but the language of the person with aphasia was more nonspecific and simplified, manifesting in difficulties developing a logical argument and responding to the partner's line of argument. In addition, the nonaphasic speaker recurrently overlapped the aphasic speaker in order to request clarification of particular points, highlighting the types of behaviors that can occur in this form of higher level language activity.The complex argument task and the multilevel and multi-approach analysis are useful tools for examining persons with mild aphasia, revealing aspects that are often overlooked in standard tests. Treatment could incorporate more complex notions such as evaluative language and the role of overlap in complex conversations.
Paying health workers for performance in a fragmented, fragile state: reflections from Katanga Province, Democratic Republic of Congo. - Health policy and planning
The health financing system in the Democratic Republic of Congo (DRC) presents an extreme example of low government investment, high dependency on user fees and poor harmonization across donors. Within this context, performance-based financing mechanisms are being implemented by various donors in the expectation that they will improve health worker motivation and service delivery performance. Drawing on qualitative and quantitative data at different levels of the health system, this study focuses on one such programme in Katanga Province, which combines paying for performance (P4P) with a reduction in fees to users. Despite adding considerably to facility resources (providing the majority of the resources in the case study facilities), there was no evidence of benefits in terms of any of the service inputs, processes or outputs measured. The findings suggest that the positive effects on health worker motivation cannot be taken as a given, particularly, when staff are often expected to increase their workload to achieve the performance objectives and when another source of income, the income from user fees, may be reduced due to a fall in the prices of services. Moreover, in a context where health workers were already almost entirely dependent on users for their remuneration before the donor programme was introduced, the incentive effects of a performance contract may be muted. In addition, other income sources have particular value for staff, it seems-even though salaries and government allowances were low, and frequently delayed, health workers were highly dissatisfied at not receiving them. Salaries were seen as a more assured and long-term source of funding and an important recognition of their role as agents of the state. The authors conclude that while there may be a role for P4P in fragile contexts such as the DRC, to be effective it needs to be rooted in wider financing and human resource policy reforms.
Near-vision impairment and unresolved vision problems in Indigenous Australian adults. - Clinical & experimental ophthalmology
â€‚ To describe near-vision impairment, self-reported unresolved vision problems and barriers to having near-vision correction in Indigenous Australians.â€‚ A nationwide population-based study designed to determine the causes and prevalence of vision loss and utilization of eye care services.â€‚ Indigenous Australians aged â‰¥40â€ƒyears.â€‚ Using a multistage random cluster sampling methodology, 30 geographical areas stratified by remoteness were selected to obtain a representation of Indigenous Australians. Visual acuity was conducted using a standard E chart. A questionnaire collected data on eye health, eye care service utilization and vision-related quality of life.â€‚ Near-vision impairment defined as presenting binocular near visual acuity
Prevalence of self-reported diabetes and diabetic retinopathy in indigenous Australians: the National Indigenous Eye Health Survey. - Clinical & experimental ophthalmology
To assess the prevalence of diabetes and diabetic retinopathy in indigenous Australians aged â‰¥40 years.The National Indigenous Eye Health Survey used a stratified, multistage cluster probability sampling frame to provide a representative sample of the indigenous Australian population.One thousand one hundred and eighty-nine eligible indigenous adults were examined using standardized procedures.Each participant underwent a comprehensive eye examination included presenting and best corrected visual acuity, visual field, fundus and lens photography.Diabetic retinopathy.The prevalence of diabetes in the 1189 eligible indigenous adults was 37.3% (95% confidence interval: 34.6-40.2%). The prevalence of diabetic retinopathy among 394 people with diabetes was 29.7% (95% confidence interval: 25.2-34.2%), and 17.8% (95% confidence interval: 14.0-21.6%), 8.9% (95% confidence interval: 6.1-11.7%) and 3.1% (95% confidence interval: 1.3-4.7%) for mild or moderate diabetic retinopathy, clinically significant macular oedema and severe or proliferative diabetic retinopathy, respectively. Diabetic retinopathy was presented in 6.3% in those who did not report diabetes. The risk of diabetic retinopathy increased with duration of diabetes (the adjusted odds ratios were 3.4 for 10-19 years, 6.1 for 20-29 years and 25.8 for â‰¥30 years).The prevalence of self-reported diabetes in indigenous Australians is more than eight times higher than that in non-indigenous Australians. The prevalence of diabetic retinopathy in people with diabetes is similar to that of non-indigenous Australians.Â© 2011 The Authors. Clinical and Experimental Ophthalmology Â© 2011 Royal Australian and New Zealand College of Ophthalmologists.
Mindfulness meditation for women with chronic pelvic pain: a pilot study. - The Journal of reproductive medicine
Chronic pelvic pain (CPP) is a common condition that can be difficult to treat. Mindfulness meditation improves outcomes in patients with cancer pain, low back pain and migraine headaches. This study evaluates feasibility and efficacy of mindfulness for patients with CPP.Women with CPP were enrolled in an 8-week mindfulness program. Pre-assessments and post-assessments included daily pain scores, the Short Form-36 Health Status Inventory, Kentucky Inventory of Mindfulness Score and the Inventory of Depressive Symptomatology.Twelve out of 22 enrolled subjects completed the program and had significant improvement in daily maximum pain scores (p = 0.02), physical function (p = 0.01), mental health (p = 0.01) and social function (p = 0.02). The mindfulness scores improved significantly in all measures (p < 0.01).Data from this pilot study show the feasibility of mindfulness meditation in women with CPP. Initial pilot data suggest that quality of life and mindfulness outcomes may improve with mindfulness meditation and justify further investigation with a randomized, controlled trial.
Sampling and recruitment methodology for a national eye health survey of Indigenous Australians. - Australian and New Zealand journal of public health
To review the process of sample selection and highlight the methodological difficulties encountered during a nationwide survey of Indigenous Australians, to determine the prevalence and causes of vision impairment and evaluate access to and utilisation of eye care services.Using a multi-stage, random cluster sampling methodology, 30 geographic areas stratified by remoteness, were selected to provide a representative population of approximately 3,000 Indigenous Australians aged 5-15 and 40 years and older, and a small non-Indigenous sample in selected remote areas. Recruitment was adapted to local conditions. The rapid assessment methodology included a questionnaire, tests of visual acuity, trachoma grading, frequency doubling perimetry and non-mydriatic fundus photography.The number of people examined was 2883/3662 (78.7%) Indigenous and 136 (83.4%) non-Indigenous. The percentage of the expected population who were enumerated during the survey varied; discrepancies were largest in urban areas (34.5%) compared to very remote areas (97.1%).The unexpected variation in predicted population numbers and participation rates could be explained in part by local circumstances, degree of urbanisation, interpretation of the definition of 'Indigenous' and time constraints.For successful recruitment, a community-specific approach is essential, including collaboration with local organisations and liaison with health workers of each gender.Â© 2010 The Authors. ANZJPH Â© 2010 Public Health Association of Australia.
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