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Biomedical subjects

M D Cohen

Publications and source records attributed to M D Cohen.

At least 19 recordsLinked to original sources
PubMed2003

Persistent organic pollutants in the dusts that settled across lower Manhattan after September 11, 2001.

The explosion and collapse of the World Trade Center (WTC) was a catastrophic event that produced an aerosol impacting many workers, residents, and commuters during the first few days after September 11, 2001. During the initial days that followed, 14 bulk samples of the settled dust were collected at locations surrounding the epicenter of the disaster, including one indoor location. Some samples were analyzed for many potential hazards, including inorganic and organic constituents as well as morphology. The results of the analyses for persistent organic pollutants are described herein, including polycyclic aromatic hydrocarbons, polychlorinated biphenyls, and select organochlorine pesticides on settled dust samples. The sigma86-PCBs comprising less than 0.001% by mass of the bulk in the three bulk samples analyzed indicated that PCBs were of limited significance in the total settled dust across lower Manhattan. Likewise, organochlorine pesticides, including chlordanes, hexachlorobenzene, heptachlor, 4,4'-DDE, 2,4'-DDT, 4,4'-DDT, and Mirex, were found at low concentrations in the bulk samples. Conversely, the sigma37-PAHs comprised up to nearly 0.04% (<0.005-0.039%) by mass of the bulk settled dust in the six bulk samples. Further size segregation of these three initial bulk samples and seven additional samples indicates that sigma37-PAHs were found in higher concentrations on relatively large particles (10-53 microm), representing up to 0.04% of the total dust mass. Significant concentrations were also found on fine particles (<2.5 microm), often accounting for approximately 0.005% by mass. We estimate that approximately 100-1000 tons of sigma37-PAHs were spread over a localized area immediately after the WTC disaster on September 11.

Aircraft↗
PubMed2001

Evolution of cooperation without reciprocity.

A long-standing problem in biological and social sciences is to understand the conditions required for the emergence and maintenance of cooperation in evolving populations. For many situations, kin selection is an adequate explanation, although kin-recognition may still be a problem. Explanations of cooperation between non-kin include continuing interactions that provide a shadow of the future (that is, the expectation of an ongoing relationship) that can sustain reciprocity, possibly supported by mechanisms to bias interactions such as embedding the agents in a two-dimensional space or other context-preserving networks. Another explanation, indirect reciprocity, applies when benevolence to one agent increases the chance of receiving help from others. Here we use computer simulations to show that cooperation can arise when agents donate to others who are sufficiently similar to themselves in some arbitrary characteristic. Such a characteristic, or 'tag', can be a marking, display, or other observable trait. Tag-based donation can lead to the emergence of cooperation among agents who have only rudimentary ability to detect environmental signals and, unlike models of direct or indirect reciprocity, no memory of past encounters is required.

Altruism↗
PubMed2001

Outcomes of treatment of children and adolescents with recurrent non-Hodgkin's lymphoma and Hodgkin's disease with dexamethasone, etoposide, cisplatin, cytarabine, and l-asparaginase, maintenance chemotherapy, and transplantation: Children's Cancer Group Study CCG-5912.

PURPOSE: To determine the toxicity and response rate in children treated with dexamethasone, etoposide, cisplatin, high-dose cytarabine, and L-asparaginase (DECAL) for recurrent non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD). PATIENTS AND METHODS: Ninety-seven children with recurrent NHL (n = 68) or HD (n = 29) were enrolled. Treatment consisted of two cycles of DECAL, then bone marrow transplantation or up to four cycles of ifosfamide, mesna, and etoposide alternating with DECAL maintenance therapy. RESULTS: After two cycles of DECAL induction therapy, complete response (CR) or partial response (PR) was reported in 19 (65.5%; 10 CRs and nine PRs) of 29 patients with HD and 29 (41.6%; 23 CRs and six PRs) of 68 patients with NHL. When only 24 patients with HD and 58 patients with NHL who were assessable for response were considered, the response rates were 79.2% (19 of 24 patients) and 50.0% (29 of 58 patients), respectively. Five-year event-free survival was 26% +/- 9% and 23% +/- 5% in patients with HD and NHL, respectively. Five-year survival was 31% +/- 14% and 30% +/- 6%, respectively. Although median time to treatment failure was significantly longer in patients with HD (EFS, P =.002; survival, P =.011), this difference did not translate into a higher long-term survival. Grade 3 or 4 toxic effects were observed during induction in 70 (72%) of 97 patients and during maintenance in 45 (70%) of 64 courses of DECAL therapy. Pancytopenia and systemic infections in particular were frequently observed. Other toxic effects were uncommon. Although not a formal part of the therapy or the study design, 42 patients who responded to therapy who underwent bone marrow transplant did not show any benefit from this approach. CONCLUSION: DECAL is an effective and tolerable salvage regimen for treating patients with recurrent NHL and HD.

Adolescent↗
PubMed2001

Ozone-induced modulation of cell-mediated immune responses in the lungs.

Most pulmonary immunotoxicology studies of ambient pollutants have been broadly designed to discern if overall humoral or cell-mediated immunity (CMI) was altered; few have assessed effects on particular aspects of immune function. We hypothesized that effects from ozone (O3) exposure on pulmonary CMI are linked in part to changes in local immune cell capacities to form and/or to interact with immunoregulatory cytokines. Rats exposed to 0.1 or 0.3 ppm O3 4 h/day 5 days/week, for 1 or 3 weeks were assessed for resistance to, and pulmonary clearance of, a subsequent Listeria monocytogenes challenge. In situ cytokine release and immune cell profiles were also analyzed at different stages of the antilisterial response. Although O3 exposure modulated CMI, effects were not consistently concentration- or duration-dependent. Exposure did not effect cumulative mortality from infection, but induced concentration-related effects upon morbidity onset and persistence. All 1-week exposed rats had listeric burdens trending higher than controls; 0.3 ppm rats displayed continual burden increases rather than any onset of resolution. Rats exposed for 3 weeks had no O3-related changes in clearance. No exposure-related effect on neutrophil or pulmonary macrophage (PAM) numbers or percentages was noted. Bacterial burden analyses with respect to cell type showed that Listeria:PAM ratios in 0.3 ppm rats ultimately became greatest compared to all other rats. In situ IL-1alpha and TNFalpha levels were consistently higher in O3-exposed rats. All rats displayed increasing in situ IFNgamma levels as infection progressed, but no constant relationship was evident between IFNgamma and initial IL-1alpha/TNFalpha levels in O3-exposed hosts. It seems that short-term (i.e., 1 week) repeated O3 exposures imparted more effects upon CMI than a more prolonged (i.e., 3 week) regimen, with effects manifesting at the level of the PAM and in the cytokine network responsible for immunoactivation.

Animals↗
PubMed2001

Improving clinical histories on radiology requisitions.

PURPOSE: The Health Care Financing Administration (HCFA) regards billing for radiologic examinations without an appropriate indication as unlawful, and both the referring physician and the radiologist are liable. HCFA regulations are interpreted as requiring that all requisitions for radiologic examinations include a current diagnosis and appropriate indication for the study. The purpose of this investigation was to determine the rates at which requisitions currently meet these criteria and to assess the effectiveness of a simple intervention designed to improve them. MATERIALS AND METHODS: One hundred fifty consecutive chest radiography requisitions were examined to determine the rate at which current diagnoses and appropriate indications were present. An intervention was then implemented that included a month-long effort to inform referring physicians and radiologists of HCFA regulations, followed by a 1-week period during which requested examinations were not performed unless accompanied by a clinical diagnosis and appropriate indication. Another 150 consecutive chest radiography requisitions were then assessed to determine the effect of the intervention. A 3-month follow-up sample of a third set of 150 consecutive requisitions was then obtained. RESULTS: The intervention produced a 69% decrease in the rate at which current diagnoses were missing from requisitions, and a 61% decrease in the corresponding rate for appropriate indications. Both results are significant with chi2 analysis at the P = .001 level. After 3 months with no additional intervention, rates decayed back toward baseline, with only a 35% remaining decrease for current diagnosis and an 18% decrease for appropriate indication. CONCLUSION: The intervention performed in this study significantly reduces the rate of noncompliance with HCFA regulations. However, this improvement decays over time if it is not reinforced.

Centers for Medicare and Medicaid Services, U.S.↗
PubMed2001

Practical strategies for detecting and confirming vancomycin-intermediate Staphylococcus aureus: a tertiary-care hospital laboratory's experience.

The clinical microbiology laboratory plays a critical role in the detection of Staphylococcus aureus with decreased susceptibility to vancomycin. Staff education and rapid laboratory response are of utmost importance. We report on our laboratory's experience and provide recommendations for the identification and confirmation of vancomycin-intermediate S. aureus.

Algorithms↗
PubMed2000

Activity-based cost analysis: a method of analyzing the financial and operating performance of academic radiology departments.

PURPOSE: To develop a methodology for an activity-based cost (ABC) analysis in an academic radiology department, to test the hypothesis that the business of academic radiology can be separated into three distinct businesses-clinical activity, teaching, and research-and to determine the effect of the current teaching paradigm on clinical productivity. MATERIALS AND METHODS: Forty-seven key departmental activities were defined and distributed among the teaching, research, and clinical businesses. Individual radiologists determined the time spent in each of these activities by completing a detailed log of every activity performed during 2 weeks. All departmental revenue and costs were assigned to each activity in each of the three businesses. RESULTS: The methodology provided a successful understanding of the relative costs of each of the businesses of teaching, research, and clinical activity. It also provided the departmental costs of performing the separate activities typical of each business. Key findings included the following: Faculty spends 72% of time in clinical activities, research is the most expensive service per direct activity hour, and clinical reads (23%) are the single largest departmental cost element. CONCLUSION: ABC analysis can separate academic radiology into three businesses-teaching, research, and clinical-and provide a detailed understanding of the cost structure of each. This analysis identifies opportunities for improved quality of service, productivity, and cost within each business.

Cost Allocation↗
PubMed2000

Lymphomas in patients with connective tissue disease. Comparison of p53 protein expression and latent EBV infection in patients immunosuppressed and not immunosuppressed with methotrexate.

Cell cycle dysregulation as measured by p53 protein expression and latent Epstein-Barr (EBV) infection are important in the pathogenesis of lymphoma, particularly in immunosuppressed patients. Although latent EBV commonly is detected in lymphomas arising in patients with connective tissue disease who are immunosuppressed with methotrexate, p53 protein expression has not been reported. We compared the immunohistologic expression of p53 protein and the incidence of latent EBV infection in lymphomas arising in patients with connective tissue disease treated and not treated with methotrexate. Increased p53 staining was detected in 10 of 11 lymphomas arising in patients after methotrexate therapy vs 5 of 11 in patients not treated with methotrexate. Latent EBV was detected in 7 of 13 lymphomas arising in patients after methotrexate therapy vs 2 of 11 in patients not treated with methotrexate. Concordant p53 expression and latent EBV were detected in 5 of 7 lymphomas arising after treatment with methotrexate, including 1 that regressed after methotrexate therapy was withdrawn. These findings suggest that cell cycle dysregulation and EBV-related transformation are important in the pathogenesis of lymphomas arising in patients with connective tissue disease who are immunosuppressed with methotrexate.

Adolescent↗
PubMed1999

Distinguishing primary angiitis of the central nervous system from cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: the importance of family history.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetically linked neurologic disease characterized by recurrent strokes and progressive or stepwise dementia, with or without migraine-like headaches, seizures, and pseudobulbar palsy. We describe a patient referred with a diagnosis of treatment-refractory primary angiitis of the central nervous system. Meningocortical and skin biopsies confirmed that the patient had CADASIL. Clinical and radiographic differences in these disorders may be subtle, but awareness of them is crucial if the patient is to avoid unnecessary exposure to potentially deleterious immunosuppressive therapy.

Dementia, Multi-Infarct↗
PubMed1999

Studies of iodixanol in the rabbit lung and peritoneum.

OBJECTIVE: To evaluate a new water-soluble contrast agent, iodixanol. The study evaluates absorption from the peritoneal cavity and toxicity in the lung. MATERIALS AND METHODS: Thirty New Zealand white rabbits were given the study agent and comparative agents into an endotracheal tube. Serial chest radiographs were evaluated for development of pulmonary edema. All lungs were evaluated histopathologically for toxic inflammatory response. Fifteen different rabbits were given intraperitoneal injection of the study and comparative contrast agents. Serial abdomen radiographs, taken up to 24 h after injection, were evaluated for contrast absorption from the peritoneal cavity. RESULTS: Evaluation of indicators of pulmonary edema demonstrated that iodixanol caused the same or less pulmonary edema than comparative agents. Histopathologic analysis showed that iodixanol caused less macrophage response than saline (P = 0.010), the same lymphocyte infiltration as saline (P = 0.472), the same neutrophil response as saline (P = 0.297), and the same vasculitic reaction as saline (P = 0.128). Compared to iohexol 270, iodixanol caused the same macrophage infiltrate (P = 0.924), the same lymphocyte infiltration (P = 0.523), more neutrophil reaction (P = 0.007), and less vasculitic reaction (P = 0.042). Iodixanol was rapidly absorbed from the peritoneal cavity. CONCLUSION: Iodixanol is a new contrast agent that is isotonic at all clinically useful iodine concentrations. It appears safe in the lung and is absorbed from the peritoneal cavity.

Animals↗
PubMed1999

Symposium overview: alterations in cytokine receptors by xenobiotics.

A symposium entitled Alterations in Cytokine Receptors by Xenobiotics was held at the 37th Annual Meeting of the Society of Toxicology (SOT) in Seattle, Washington. The symposium was sponsored by the Immunotoxicology Specialty Section of SOT and was designed to present information on the effect of several different classes of xenobiotics on various aspects of receptor function (i.e., post-receptor signal transduction of receptor expression), or the involvement of cytokine receptors in the action of the toxicant under consideration. This symposium brought together scientists in the area of receptor immunobiology whose expertise in receptor modulation encompassed those major signaling agents involved in the normal immune response, i.e., proinflammatory cytokines, chemokines, interleukins, and interferons. The following is a summary of each of the individual presentations.

Animals↗
PubMed1999

Technique for construction of an in vivo model of simulated pulmonary metastases.

RATIONALE AND OBJECTIVES: Existing methods used to simulate pulmonary metastases are unsatisfactory. The aim of this study was to create a simple in vivo model of pulmonary metastases by endobronchial deployment of small high-density beads in anesthetized dogs. METHODS: Commercially available decorative beads measuring 2 and 4 mm in diameter and of high density (600 to 1200 Hounsfield units) were deployed in the peripheral airways of anesthetized dogs using catheter and guide wire manipulations through an endotracheal tube. RESULTS: A total of 65 beads were placed in five dogs. Computed tomography demonstrated that 41 (63%) were satisfactorily located in the lung periphery, 9 (14%) were unsatisfactorily located in large airways, and 15 (23%) were not visible. CONCLUSIONS: The endobronchial deployment of small high-density beads in the peripheral airways of anesthetized dogs is a novel and effective technique for creation of an in vivo model of pulmonary metastases.

Animals↗
PubMed1999

Approach to the patient with suspected vasculitis.

By taking a careful patient history, conducting a thorough physical examination, knowing the clinical features of vasculitis, and using selected laboratory tests, the physician can diagnosis vasculitis tentatively. Recognizing the pattern of organ involvement provides a clue to the type of vasculitis present. Serologic laboratory tests for ANCAs or hepatitis B or C may help confirm the presence of the underlying vasculitis, and a definitive diagnosis can be confirmed by a biopsy of involved tissue or by angiography.

Diagnostic Imaging↗
PubMed1998

Immunotoxicologic effects of inhaled chromium: role of particle solubility and co-exposure to ozone.

Soluble and insoluble hexavalent chromium (Cr6+) agents are concomitantly released with ozone (O3) during welding. Although pulmonary/immunologic implications from exposure to each agent individually have been investigated, the effects from simultaneous exposure, as occurs under actual working conditions, are unclear. To investigate immunomodulatory effects of inhaled Cr6+, F-344 rats were exposed for 5 h/day, 5 days/week for 2 or 4 weeks to atmospheres containing soluble potassium chromate (K2CrO4) or insoluble barium chromate (BaCrO4), each alone at 360 micrograms Cr/m3 or in combination with 0.3 ppm O3. One day after the final exposure, rats were euthanized, their lungs were lavaged, and pulmonary macrophages (PAM) were recovered for assessment of basal and inducible functions. Rats inhaling K2CrO4-containing atmospheres had greater levels of total recoverable cells, neutrophils, and monocytes in bronchopulmonary lavage compared to rats exposed to insoluble Cr6+ atmospheres, O3 alone, or air; these rats also had a reduced percentage of PAM, although total PAM levels remained unaffected. Although Cr exposure-related changes in PAM functionality were evident, any dependence upon Cr solubility was variable. K2CrO4-containing atmospheres modulated PAM-inducible interleukins-1 and -6, and tumor necrosis factor-alpha production to a greater degree than those containing BaCrO4. Conversely, BaCrO4-containing atmospheres affected PAM basal nitric oxide production and interferon-gamma-primed/zymosan-stimulated reactive oxygen intermediate production to a greater extent than did those containing K2CrO4. In none of the PAM assays did co-inhalation of O3 result in a modulation of the effects obtained with either Cr6+ compound itself. The results indicate that, while immunomodulatory effects of inhaled Cr6+ upon PAM are related to particle solubility, the co-inhalation of O3 apparently does not cause further modifications of the metal-induced effects.

Administration, Inhalation↗