Biomedical subjects
Publications and source records attributed to Michael Cohen.
In-training are one way to evaluate the residents during their training. Currently, the American Board of Podiatric Surgery supplies the examination. Various residency directors were questioned regarding its use and importance.
We discuss the exact solutions of various models of the statistics of dimer coverings of a Bethe lattice. We reproduce the well-known exact result for noninteracting hard-core dimers by both a very simple geometrical argument and a general algebraic formulation for lattice statistical problems. The algebraic formulation enables us to discuss loop corrections for finite dimensional lattices. For the Bethe lattice we also obtain the exact solution when either (a) the dimers interact via a short-range interaction or (b) the underlying lattice is anisotropic. We give the exact solution for a special limit of dimers on a Bethe lattice in a quenched random potential in which we consider the maximal covering of dimers on random clusters at site occupation probability p. Surprisingly the partition function for "maximal coverage" on the Bethe lattice is identical to that for the statistics of branched polymers when the activity for a monomer unit is set equal to -p. Finally we give an exact solution for the number of residual vacancies when hard-core dimers are randomly deposited on a one dimensional lattice.
Histone deacetylase inhibitors (HDACIs) represent a promising new class of antineoplastic agents that affect proliferation, differentiation, and apoptosis in both solid and hematologic malignancies. In addition, HDACIs can alter the expression of at least one cellular adhesion molecule, the coxsackie and adenovirus receptor, in bladder cancer. Because HDACIs can increase expression of a known cellular adhesion molecule, we hypothesized that migration and/or invasion may also be affected. We evaluated this hypothesis using valproic acid (VPA), a commonly prescribed anticonvulsant recently shown to have potent HDACI activity, in the bladder cancer cell lines T24 TCC-SUP, HT1376, and RT4. Analyses of cell migration and invasion were both qualitative (fluorescent microscopy) and quantitative (static and dynamic migration/invasion assays). Our results show that acute VPA treatment (72 h) causes a dose-dependent decrease in invasion for all bladder cancer cell lines, except RT4, a noninvasive papilloma. Migration, in contrast, was not affected by VPA treatment. The inhibitory effect of VPA may be cancer type-specific, because there was no difference in invasion between treated and untreated prostate cancer cell lines LNCaP, PC3, and DU145. Furthermore, when administered chronically (34 days), VPA significantly inhibits growth of T24t tumor xenografts. Our data suggest that VPA exerts some of its antineoplastic effects by inhibiting invasion as well as tumor growth, and thus it may represent a novel adjuvant strategy for patients at high risk of recurrence and/or progression of muscle invasive bladder cancer.
We examined exposure to the World Trade Center attack and changes in cigarette smoking and drinking among 2731 New York City public high-school students evaluated 6 months after the attack. Increased drinking was associated with direct exposure to the World Trade Center attack (P < .05). Increased smoking was not directly associated with exposure to the World Trade Center attack but was marginally significantly associated with posttraumatic stress disorder (P= .06). Our findings suggest that targeted substance-use interventions for youths may be warranted after large-scale disasters.
This study used quantitative PCR in the murine model to compare the ability of a limb allograft vs. a comparable dose of marrow suspension to induce chimerism. Female C57Bl/6 mice received a vascularized hindlimb allograft, a comparable dose of 5 x 10 (6) donor bone marrow cells, or a standard dose (20 x 10 (6)) of marrow suspension from male Balb/c donors. All recipients were treated with a regimen based on CD40 costimulation blockade and T cell depletion. Y chromosome-specific quantitative PCR was used to measure chimerism. Most recipients of limb allografts demonstrated low levels of chimerism after 1 week (3/4) and 1 month (3/4). Most recipients of 5 x 10 (6) marrow cells had low levels of chimerism at 1 week (4/6) and only 1/5 after 1 month. All recipients of 20 x 10 (6) cells except one demonstrated either low or high levels of chimerism after 1 week (5/5) and 1 month (5/6). The marrow component of a limb allograft is thus more effective at inducing microchimerism compared to a comparable dose of bone marrow suspension.
Top-down microfabrication techniques were used to create silicon-based membranes consisting of arrays of uniform channels having a width as small as 7 nm. The measurement of diffusion kinetics of solutes across these membranes under sink conditions reveals non-Fickian behavior as the nanopore width approaches the hydrodynamic diameter of the solute. Zero-order diffusion of interferon is observed at channel width of 20 nm, and the same phenomenon occurs with albumin and 13-nm-wide channels, whereas Fickian diffusion kinetics is seen at 26 nm and larger pore sizes. A prototypical drug delivery device is described that is fitted with a 13-nm nanopore membrane and loaded with radio-labeled BSA. Following subcutaneous implantation in rats, diffusion from the device provided prolonged levels of BSA in the blood. Such a nonmechanical device offers important advantages in drug delivery applications, including zero-order release and high loading capacity.
CONTEXT: Children exposed to a traumatic event may be at higher risk for developing mental disorders. The prevalence of child psychopathology, however, has not been assessed in a population-based sample exposed to different levels of mass trauma or across a range of disorders. OBJECTIVE: To determine prevalence and correlates of probable mental disorders among New York City, NY, public school students 6 months following the September 11, 2001, World Trade Center attack. DESIGN: Survey. SETTING: New York City public schools. PARTICIPANTS: A citywide, random, representative sample of 8236 students in grades 4 through 12, including oversampling in closest proximity to the World Trade Center site (ground zero) and other high-risk areas. MAIN OUTCOME MEASURE: Children were screened for probable mental disorders with the Diagnostic Interview Schedule for Children Predictive Scales. RESULTS: One or more of 6 probable anxiety/depressive disorders were identified in 28.6% of all children. The most prevalent were probable agoraphobia (14.8%), probable separation anxiety (12.3%), and probable posttraumatic stress disorder (10.6%). Higher levels of exposure correspond to higher prevalence for all probable anxiety/depressive disorders. Girls and children in grades 4 and 5 were the most affected. In logistic regression analyses, child's exposure (adjusted odds ratio, 1.62), exposure of a child's family member (adjusted odds ratio, 1.80), and the child's prior trauma (adjusted odds ratio, 2.01) were related to increased likelihood of probable anxiety/depressive disorders. Results were adjusted for different types of exposure, sociodemographic characteristics, and child mental health service use. CONCLUSIONS: A high proportion of New York City public school children had a probable mental disorder 6 months after September 11, 2001. The data suggest that there is a relationship between level of exposure to trauma and likelihood of child anxiety/depressive disorders in the community. The results support the need to apply wide-area epidemiological approaches to mental health assessment after any large-scale disaster.
OBJECTIVE: Immunoisolating membranes protect transplanted xenogeneic tissue by physically isolating them from the host. However, most are commercial filter membranes that do not possess all the features needed for immunoisolation. Silicon nanopore membranes are thin layers of silicon containing tens of thousands of nanometer-sized channels, which allow passive diffusion of small molecules. They are excellent size-selective barriers, and the objective of this study was to further characterize their immunoprotective properties and make comparisons with commercial filter membranes. METHODS: Diffusion across membranes was studied using molecules of different sizes, including fluorescein isothiocyanate-dextrans (relative molecular sizes of 4.4 kDa, 20 kDa, and 70 kDa), glucose (0.18 kDa), insulin (6.1 kDa), and immunoglobulin G (IgG) (150 kDa). Protection from complement-mediated lysis was analyzed by a hemolysis assay. Comparative studies were done with filter membranes that have been reported as immunoisolation barriers. To evaluate if silicon nanopore membranes changed insulin response patterns for glucose-stimulated islets, macrocapsules were constructed with nanopore membranes and filled with pancreatic islets, and dynamic perifusion studies were performed. RESULTS: Relative to commercial membranes, silicon nanopore membranes showed high rates of diffusion for glucose and insulin, and acted as efficient barriers to complement proteins and IgG. No other commercial membrane showed comparable diffusion and immunoisolating properties. Islets placed within the macrocapsule exhibited glucose-responsive insulin secretion in perifusion studies. CONCLUSIONS: Silicon nanopore membranes possess unique and desirable diffusion properties as immunoisolation membranes and allow rapid response times for the stimulation of islets by glucose. These features are attributed to the physical properties of the membranes, namely, the straight channels, adequate porosity, and the 5 microm thickness.
BACKGROUND: Subjective evaluations of the appearance outcome of autologous breast reconstruction are usually performed by surgeons and not by patients. Such surgeon-based evaluations are rarely reproducible and show little interobserver agreement. Among existing patient-based subjective scales, none has been tested for reliability, and no study to date has evaluated the reliability when both surgeons and patients use the same scale. METHODS: The authors developed a new instrument for assessing the appearance of autologous breast reconstruction. The instrument's use by four plastic surgeons and 36 transverse rectus musculocutaneous flap patients was assessed for test-retest reliability, internal consistency, surgeon-patient and surgeon-surgeon interobserver agreement, and interitem correlation. RESULTS: The instrument demonstrated high overall internal consistency when used by patients (Cronbach alpha = 0.92). Test-retest reliability on each aesthetic subitem in the scale was higher among patients than among surgeons (weighted kappa range, 0.57 to 0.88 versus 0.25 to 0.66). Interrater agreement was poor among both patients and surgeons (weighted kappa, 0.0 to 0.39). Poor correlation was found between surgeons' evaluations of aesthetic subitems and patients' overall appearance and overall satisfaction scores. CONCLUSIONS: The instrument both demonstrates better internal consistency and is more reliable when used by patients to evaluate their own reconstructions. By contrast, the instrument's use by surgeons is not as internally consistent and reproducible. The poor interobserver agreement among surgeons and the weak correlation between surgeon and patient evaluations suggest that patient input regarding item-specific criteria should be included in evaluations of breast reconstructions.
BACKGROUND: Scleral show or ectropion is a known complication of lower eyelid surgery. It is particularly problematic after lower eyelid blepharoplasty when the orbicularis oculi muscle is transected or after other procedures are performed that denervate the lower eyelid. The purpose of this study was to determine whether a dominant motor branch exists to the lower lid orbicularis oculi muscle, using anatomic dissection and histologic analysis. METHODS: Sixteen fresh facial cadaver halves were dissected using the operative microscope to identify and measure nerve branches. The nerves were then harvested, sectioned, and stained with toluidine blue dye for histomorphometric analysis. Nerves were categorized as either lateral or medial to a vertical line marked at the lateral edge of the limbus of the eye. RESULTS: Eighty-seven percent and 47 percent of cadaver halves had one and two nerve branches lateral to the limbus, respectively. Eighty percent and 47 percent of cadaver halves had one and two nerve branches medial to the lateral limbus, respectively. The nerve branches entered the inferior edge of the orbicularis oculi muscle between 0.88 cm (+/-0.36 cm) and 2.73 cm (+/-0.46 cm) from the lateral canthus. There was no correlation noted between fascicular counts and distance from the lateral canthus. CONCLUSIONS: Multiple motor nerves exist to the lower eyelid. Branches are found medial and lateral to the lateral limbus, and no nerve branch is dominant.
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The inadequacy of conventional insulin therapy for the treatment of Type I diabetes has stimulated research on several therapeutic alternatives, including insulin pumps and controlled release systems for insulin. One of the most physiological alternatives to insulin injections is the transplantation of insulin-secreting cells. It is the beta cells of the islets that secrete insulin in response to increasing blood glucose concentrations. Ideally, transplantation of such cells (allografts or xenografts) could restore normoglycemia. However, as with most tissue or cellular transplants, the cellular grafts, particularly xenografts, are subjected to immunorejection in the absence of chronic immunosuppression. Thus, it is of great interest to develop new technologies that may be used for islet cell replacement. This research proposal describes a new approach to cellular delivery based on micro- and nanotechnology. Utilizing this approach, nanoporous biocapsules are bulk and surface micromachined to present uniform and well-controlled pore sizes as small as 7 nm, tailored surface chemistries, and precise microarchitectures, in order to provide immunoisolating microenvironments for cells. Such a design may overcome some of the limitations associated with conventional encapsulation and delivery technologies, including chemical instabilities, material degradation or fracture, and broad membrane pore sizes.
OBJECTIVE: To determine whether transducible peptides that inhibit the oncoproteins HDM2 and Bcl-2 may selectively kill uveal melanoma and retinoblastoma cells. METHODS: Peptides were tested by viability assay, flow cytometry, TUNEL (terminal deoxynucleotidyl transferase-mediated fluorescein-dUTP nick-end labeling) assay, Western blot analysis, and reverse transcription-polymerase chain reaction in cultured eye tumor cells and normal cells. Preclinical studies were performed in a rabbit xenograft model of retinoblastoma. MAIN OUTCOME MEASURES: Cell survival, apoptosis, gene expression, and tumor regression. RESULTS: The anti-Bcl-2 peptide induced apoptosis in tumor cells, but it also caused apoptosis in normal cells in culture and induced retinal damage after intravitreal injection. In contrast, the anti-HDM2 peptide induced rapid accumulation of p53, activation of apoptotic genes, preferential killing of tumor cells, and minimal retinal damage after intravitreal injection. The anti-HDM2 peptide also induced regression of human retinoblastoma cells in rabbit eyes. CONCLUSIONS: Peptide transduction is a promising new approach to molecular eye cancer therapy. Inhibition of HDM2 can selectively activate p53 in transformed cells and may be an effective strategy for inducing apoptosis in eye cancer cells with minimal damage to normal ocular tissues. CLINICAL RELEVANCE: Molecular characteristics of uveal melanoma and retinoblastoma may be used to design novel therapeutic agents that have greater specificity and fewer adverse effects than current therapies.
Integrated dual disorders treatment programs for people with severe mental illness and co-occurring substance use disorder have been implemented in a variety of community mental health center sites across the U.S. and in several other countries over the past 15 years. Consumers who receive services from programs that offer integrated dual diagnosis treatments that are faithful to evidence-based principles achieve significant improvements in their outcomes. Unfortunately, not all programs that attempt implementation are successful, and the quality of high-fidelity programs sometimes erodes over time. This article outlines implementation strategies that have been used by successful programs. As a general rule, success is achieved by involving all major participants (consumers, family members, clinicians, program leaders, and state or county mental health authorities) in the process and attending to the three phases of change: motivating, enacting, and sustaining implementation.
The purpose of this study was to develop an animal model that would grade in-vivo therapeutic modality testing for caustic ingestion. Caustic substances are found in many household items (eg detergents, bleaches, pipe cleaners) and pose a serious threat to health if ingested accidentally or intentionally with resulting injuries including immediate death or chronic debilitating morbidity. This study used 5, 3.8 or 1.8% sodium hydroxide (NaOH) to determine macro/microscopic injury at 10, 30, or 60 minutes. Macroscopic grading was based on gross evaluation of denudation of mucosa, edema, hyperemia, hemorrhage, ulcerations and necrosis. Microscopic grading was based on epithelial viability, cornified epithelial cell differentiation, granular cell differentiation, epithelial cell nuclei, muscle cell viability and muscle cell nuclei. Product concentration was shown a more significant predictor of injury than time of exposure. The grading system presented should provide a reliable method of producing and grading alkaline ingestions for future treatment hypothesis testing.
BACKGROUND: In 1996, an integrated plan of care was implemented to improve quality of care for patients undergoing elective carotid endarterectomy. Goals were to reduce length of stay, costs, number of preoperative and intensive care unit admissions, and use of diagnostic procedures yet maintain good outcomes. OBJECTIVES: To determine whether use of the integrated plan of care met the goals. METHODS: Data on financial and process outcomes, use of angiographic diagnostic procedures, and demographics were retrieved from the hospital's database for all patients who had elective carotid endarterectomy without cerebral infarction. RESULTS: A total of 783 patients met inclusion criteria: 129 before implementation of the plan of care, 66 during the 6-month transition, and 588 after implementation. Preoperative angiography was done in 32% of patients before implementation, 11% during the transition, and 4% after implementation. Percentages of patients admitted to the intensive care unit were 77% before implementation, 24% during transition, and 9% after implementation. Mean lengths of stay were 2.93 days before implementation, 2.12 days during transition, and 1.68 days after implementation. Costs per case were $7798 before implementation, $5750 during transition, and $5387 after implementation. Analysis of variance revealed significant differences between groups in total length of stay (P = .001), preoperative length of stay (P<.001), and costs (P<.001). CONCLUSION: Use of the integrated plan of care reduced length of stay, costs, admissions to intensive care units, and use of cerebral angiography. Use of the plan improved resource utilization while maintaining quality of care.
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