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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

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Effect of breathing on the detection of in vivo simulated pulmonary nodules by spiral CT.

OBJECTIVE: To determine the effect of breathing on the detection of small dense pulmonary nodules of threshold conspicuity by spiral computed tomography (SCT). MATERIALS AND METHODS: Forty pulmonary nodules of high density were created by endobronchial deployment of 2 and 4mm diameter beads in the peripheral airways of five anaesthetized dogs. SCT was performed during induced breath-hold and quiet breathing, using 5 mm collimation, pitch 2 and reconstruction of contiguous 5 mm slices. Scans were reviewed by six radiologists. Detection rates were measured as the number of nodules seen by at least one reader. The data was modelled using ordinal logistic regression for repeated measures, and the Wald Chi-square statistic used to test if there was a breath-hold vs. breathing effect on reader confidence level. RESULTS: There was no difference in detection rates for breath-hold vs. breathing SCT (28 vs. 25, respectively; P=0.48). This was also true when only the 2 mm nodules (n=24) were considered (12 vs. 11, respectively; P=0.77). Reader confidence level was significantly higher for breath-hold vs. breathing SCT (Wald Chi-square statistic with 6 degrees of freedom=19.0; P=0.0041). CONCLUSION: SCT can be performed during quiet breathing without a significant reduction the overall detection rate for small dense pulmonary nodules, though reader diagnostic confidence level is reduced.

Animals↗

Structural and functional reconstruction after resection of aneurysmal bone cyst of the fifth metatarsal: a case study.

We report a case of a primary benign bone tumor (aneurysmal bone cyst [ABC]) involving the distal portion of the fifth metatarsal, identified in an adolescent. The tumor, histologically identified as an ABC with reparative giant cell reaction, became symptomatic. Treatment included resection, followed by reconstruction of the fifth metatarsal using grafts of autologous bone with preservation of function in the metatarsophalangeal joint. The basis for selecting this form of treatment is discussed, as well as the natural history of ABC and giant cell reparative granuloma. Restoration of form and function is illustrated by this case study with a 23-month follow-up.

Adult↗

Maximum intensity projection images in the detection of simulated pulmonary nodules by spiral CT.

This study was undertaken to investigate the use of maximum intensity projection (MIP) images in the detection of pulmonary nodules by spiral CT (SCT). 40 pulmonary nodules of high density were created by endobronchial deployment of 2 and 4 mm beads in the peripheral airways of five anesthetized dogs. Standard SCT was performed with 5 mm collimation, pitch 2 and reconstruction of contiguous slices. MIP images were generated from overlapped slabs of seven consecutive 3 mm slices, reconstructed at 2 mm intervals and acquired at pitch 2. Scans were reviewed by six radiologists. The data were modelled using ordinal logistic regression for repeated measures, and the Wald chi 2 statistic used to test if there was a difference in nodule detection and reader confidence level between the two techniques. MIP imaging increased the odds of nodule detection by 2.18 (p = 0.0002). Reader confidence level for nodule detection was significantly higher with MIP images (p < 0.00001). MIP images improve the detection rate for small high density pulmonary nodules and increase reader confidence level, when compared with standard SCT.

Animals↗

Making sense of musculoskeletal disorders.

Evaluating musculoskeletal disorders can be challenging and time-consuming. Grouping the information from the history and physical examination into broad categories, inflammatory vs. non-inflammatory and local vs. systemic, serves as a general approach.

Diagnosis, Differential↗

Hyaluronic acid treatment (viscosupplementation) for OA of the knee.

Viscosupplementation may be useful in the treatment of OA of the knee when other medical forms of therapy are contraindicated, toxic, or have failed. It may have a role in managing the patient with moderate to severe OA of the knee before considering total knee arthroplasty (Table 2). Viscosupplementation or medical treatment does not replace the need for thigh muscle strengthening or for overweight patients to lose weight. Whether or not efficacy will demand or warrant earlier or repeated use of hyaluronic acid-like products remains to be seen.

Humans↗

Effects of vanadium upon polyl:C-induced responses in rat lung and alveolar macrophages.

Hosts exposed to vanadium (V) display a subsequent decrease in their resistance to infectious microorganisms. Our earlier studies with rats inhaling occupationally relevant levels of V (as, ammonium metavanadate, NH4VO3) indicated that several nascent/inducible functions of pulmonary macrophages (PAM) were reduced. In the present study, V-exposed rats were examined to determine whether some of the same effects might also occur in situ. Rats were exposed nose-only to air or 2 mg V/m3 (as NH4VO3) for 8 h/d for 4 d, followed, 24 h later, by intratracheal (it) instillation of polyinosinic:polycytidilic acid (polyl:C) or saline. Analysis of lavaged lung cells/fluids after polyl:C instillation indicated that total lavageable cell/neutrophil numbers and protein levels, while significantly elevated in both exposure groups (as well as in saline-treated V-exposed rats), were always greater in V-exposed hosts. Exposure to V also affected the inducible production of interleukin 6 (IL-6) and interferon gamma (IFN gamma), but apparently not that of tumor necrosis factor-alpha (TNF alpha) or IL-1. Although polyl:C induced significant increases in lavage fluid IL-6 and IFN gamma levels in both exposure groups, levels were greater in V-exposed rats. If calculated with respect to total lavaged protein, however, V-exposed rats produced significantly less cytokine. Following polyl:C instillation, there were no marked exposure-related differences in basal or stimulated superoxide anion production by pooled lavaged cells or PAM specifically. With V-exposed rats, pooled cells recovered 24 h after saline instillation displayed reduced production (in both cases) compared to the air control cells; PAM-specific production was affected only after stimulation. In both exposure groups, polyl:C caused decreased superoxide production in recovered cells. Though less apparent with pooled cells, there was a time post polyl:C instillation-dependent decrease in stimulated PAM-specific superoxide production; this effect was greater in PAM from V-exposed rats than in PAM from air controls. Phagocytic activity of PAM from rats in both exposure groups was significantly increased by polyl:C instillation, although total activity in cells obtained from V-exposed rats was always significantly lower compared to air control cells. Our results indicate that short-term, repeated inhalation of occupationally relevant levels of V by rats modulates pulmonary immunocompetence. Modified cytokine production and PAM functionality in response to biological response modifiers (such as lipopolysaccharide, IFN gamma, or polyl:C) may be, at least in part, responsible for the increases in bronchopulmonary disease in humans occupationally exposed to V.

Administration, Inhalation↗

Combined accelerated tissue-plasminogen activator and platelet glycoprotein IIb/IIIa integrin receptor blockade with Integrilin in acute myocardial infarction. Results of a randomized, placebo-controlled, dose-ranging trial. IMPACT-AMI Investigators.

BACKGROUND: Platelet activation and aggregation may be key components of thrombolytic failure to restore and maintain perfusion in acute myocardial infarction. We performed a placebo-controlled, dose-ranging trial of Integrilin, a potent inhibitor of platelet aggregation, with heparin, aspirin, and accelerated alteplase. METHODS AND RESULTS: We assigned 132 patients in a 2:1 ratio to receive a bolus and continuous infusion of one of six Integrilin doses or placebo. Another 48 patients were randomized in a 3:1, double-blind fashion to receive the highest Integrilin dose from the first phase or placebo. All patients received accelerated alteplase, aspirin, and intravenous heparin infusion; all but two groups also received an intravenous heparin bolus. The highest Integrilin dose group from the nonrandomized phase and the randomized patients were pooled for analysis and compared with placebo-treated patients. The primary end point was Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow at 90-minute angiography. Secondary end points were time to ST-segment recovery, an in-hospital composite (death, reinfarction, stroke, revascularization procedures, new heart failure, or pulmonary edema), and bleeding variables. The highest Integrilin dose groups had more complete reperfusion (TIMI grade 3 flow, 66% versus 39% for placebo-treated patients; P = .006) and a shorter median time to ST-segment recovery (65 versus 116 minutes for placebo; P = .05). The groups had similar rates of the composite end point (43% versus 42% for placebo-treated patients) and severe bleeding (4% versus 5%, respectively). CONCLUSIONS: The incidence and speed of reperfusion can be enhanced when a potent inhibitor of the glycoprotein IIb/IIIa integrin receptor, such as Integrilin, is combined with accelerated alteplase, aspirin, and intravenous heparin.

Adult↗

An unusual case of carcinoma polyarthritis with associated vasculitis.

This report describes a patient who presented with an unusual polyarthritis syndrome. After extensive evaluation, squamous cell carcinoma of the lung was diagnosed. During the course of the illness, the patient developed vasculitic features and "rheumatoid-like" nodules. Two months after the administration of combined-modality therapy for stage IIIA non-small cell lung carcinoma, the signs and symptoms of polyarthritis and vasculitis had disappeared completely. Ten months later, the patient remains in clinical remission. This is the first published report of simultaneous vasculitic and polyarticular manifestations in a patient with carcinoma polyarthritis.

Anti-Inflammatory Agents↗