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Biomedical subjects

D Cohen

Publications and source records attributed to D Cohen.

At least 91 records · Page 5Linked to original sources
PubMed2001

Cost effectiveness of cardiovascular disease prevention strategies: a perspective on EU food based dietary guidelines.

For policymakers considering strategy options for the prevention of cardiovascular disease (CVD) the distinction between effectiveness and cost effectiveness is critical. When cost limitations apply, an evaluation of cost effectiveness is essential if a rational decision is to be made. Policy changes and resource reallocation have opportunity costs, and therefore it is necessary to compare the cost of health gains achievable by means of different policies. Here the broad question is: How cost effective are diet change strategies compared to other measures aimed at reducing cardiovascular disease in EU member states? An overview of published studies of cost-effectiveness in the primary and secondary prevention of cardiovascular disease was conducted. Few comprehensive studies were available. Estimated costs per life year gained were as follows: population-based healthy eating Pound Sterling 14-560; smoking cessation Pound Sterling 300-790; nurse screening and life style advice Pound Sterling 900 (minimum); simvastatin (HMGCoA reductase inhibitor) Pound Sterling 6200-11,300. Cost effectiveness is dependent on the underlying level of CVD risk in the target population, and the duration of the achieved alterations in behaviours and risk factors. The limited evidence from these studies tends to support the view that health protection strategies which promote healthy eating are likely to be more cost-effective than strategies involving modern cholesterol-lowering drugs, screening and advice in primary care, and are comparable to or less expensive per year of life saved than anti-smoking strategies. Given the considerable diversity in food habits, health care and public health systems among current and prospective EU member states, careful appraisal of the policy options within each member state is desirable to ensure that health gain is maximised. EU wide food based dietary guidelines are potentially the basis of large health gains in Europe, and cost-effectiveness studies tend to support their adoption.

Cardiovascular Diseases↗
PubMed2001

Autologous blood transfusion in total knee replacement surgery.

We compared allogeneic blood usage for two groups of patients undergoing total knee replacement surgery (TKR). Patients were randomized to receive either their post-operative wound drainage as an autotransfusion (n=115) after processing or to have this wound drainage discarded (n=116). Allogeneic blood was transfused in patients of either group whose haemoglobin fell below 9 g dl(-1). Only 7% of patients in the autotransfusion group required an allogeneic transfusion compared with 28% in the control group (P<0.001). There was no hospital mortality and only 3% mortality from all causes at the study completion, which spanned 6 months to 3 yr. There was a higher incidence of infection requiring intervention in the allogeneic group (P<0.036). Total patient costs were Pound Sterling 113 greater in the autotransfusion group. We conclude that in this type of surgery post-operative cell salvage is a safe and effective method for reducing allogeneic blood use.

Adult↗
PubMed2001

A comparison of characteristics of Kevorkian euthanasia cases and physician-assisted suicides in Oregon.

PURPOSE: The sociodemographic and clinical characteristics of Kevorkian euthanasia cases were compared with Oregon physician-assisted suicide (PAS) cases and U.S. mortality data. DESIGN AND METHODS: Two hundred variables were coded from medical examiner reports on all 69 Kevorkian euthanasia cases who died and were autopsied by the Oakland County Medical Examiner. Data on the 43 Oregon PAS cases in the first two years and U.S. mortality data were obtained from published sources. RESULTS: Only 25% of patients euthanized by Kevorkian were terminally ill as compared to 100% of Oregon PAS cases. PAS cases were significantly more likely to have cancer (72%) than euthanasia cases (29%). Women and those who were divorced or had never married were significantly more likely to seek euthanasia than would have been predicted by national mortality statistics. IMPLICATIONS: Gender and marital status appeared to influence decisions to seek an assisted death, and research on the role of these factors in end-of-life decision making is merited.

Adult↗
PubMed2001

Phenomenology, psychosocial correlates, and treatment seeking in major depression and dysthymia of adolescence.

OBJECTIVE: To compare phenomenology, psychosocial correlates, and treatment seeking in DSM-Itt-R major depression and dysthymia among adolescents diagnosed as cases in a community-based study. METHOD: A self-report questionnaire, including psychosocial data, life events, eating behaviors, depressive symptoms, substance use, pathological behaviors, and family and school functioning was administered to a nonselected sample (N = 3,287, 93.2% of targeted population) of adolescents aged 11 to 20 years from several Haute-Marne communities in France in 1988-1989. Subgroups of subjects (n = 205, 84.7% of eligible subjects) were interviewed with a structured diagnostic schedule, and adolescents with major depression (n = 49), dysthymia (n = 21) and controls (n = 135) were compared. RESULTS: Nearly 30% of controls had at least one current symptom of depression. Patterns of affective symptoms were similar in major depression and dysthymia, but significant differences emerged in comorbid conditions (more anxiety disorders, suicidal behaviors, and alcohol intoxications associated with major depression) and stressor at onset (more severe in major depression). Experiences of loss during the prior 12 months were associated with both forms of affective disorder, while poor family relationships were specific correlates of dysthymia. In contrast, peer relationships and pathological behaviors did not differ between depressed subjects and controls. Although psychosocial functioning was significantly impaired in both groups of depressed adolescents, treatment seeking was limited to 34.7% for major depressive subjects and 23.8% for dysthymic subjects. CONCLUSION: The results provide evidence that major depression and dysthymia in adolescence are equally severe but may have distinct patterns in associated factors. Despite free access to health care, the rate of treatment seeking for mood disorders in France is similar to that reported in U.S. studies.

Adolescent↗
PubMed2001

Genetic analysis of case/control data using estimated haplotype frequencies: application to APOE locus variation and Alzheimer's disease.

There is growing debate over the utility of multiple locus association analyses in the identification of genomic regions harboring sequence variants that influence common complex traits such as hypertension and diabetes. Much of this debate concerns the manner in which one can use the genotypic information from individuals gathered in simple sampling frameworks, such as the case/control designs, to actually assess the association between alleles in a particular genomic region and a trait. In this paper we describe methods for testing associations between estimated haplotype frequencies derived from multilocus genotype data and disease endpoints assuming a simple case/control sampling design. These proposed methods overcome the lack of phase information usually associated with samples of unrelated individuals and provide a comprehensive way of assessing the relationship between sequence or multiple-site variation and traits and diseases within populations. We applied the proposed methods in a study of the relationship between polymorphisms within the APOE gene region and Alzheimer's disease. Cases and controls for this study were collected from the United States and France. Our results confirm the known association between the APOE locus and Alzheimer's disease, even when the epsilon 4 polymorphism is not contained in the tested haplotypes. This suggests that, in certain situations, haplotype information and linkage disequilibrium-induced associations between polymorphic loci that neighbor loci harboring functional sequence variants can be exploited to identify disease-predisposing alleles in large, freely mixing populations via estimated haplotype frequency methods.

Aged↗
PubMed2001

Intracellular levels of two cyclosporin derivatives valspodar (PSC 833) and cyclosporin a closely associated with multidrug resistance-modulating activity in sublines of human colorectal adenocarcinoma HCT-15.

P-Glycoprotein, which mediates multidrug resistance (MDR) in cancer chemotherapy, is a principal target of cyclosporin A and [3'-keto-Bmt(1)]-[Val(2)]-cyclosporin (valspodar; PSC 833). To clarify mechanisms contributing to the different MDR-modulating activities of valspodar and cyclosporin A, we investigated the relation of the intracellular levels of the two cyclosporin derivatives to their modulating effect on MDR in different P-glycoprotein-expressing human colorectal carcinoma HCT-15 cells (parental HCT-15 and adriamycin-resistant sublines). In this study, valspodar was found to be much more potent than cyclosporin A in both sensitizing resistant cells to MDR-related anticancer drugs (e.g., adriamycin, vincristine and paclitaxel (taxol)) and increasing 2-[6-amino-3-imino-3H-xanthen-9-yl]benzoic acid methyl ester (rhodamine 123) retention and [G-(3)H]vincristine sulfate ([(3)H]vincristine) accumulation in these cells. Furthermore, a good correlation was detected between P-glycoprotein levels and the MDR-reversing effect of valspodar. In contrast, the effects of cyclosporin A could not be linked to P-glycoprotein levels in the MDR cells. In addition, the intracellular accumulation of valspodar was found to be 3 - 6 fold higher than that of cyclosporin A in four sublines and verapamil, an inhibitor of P-glycoprotein-mediated transport, enhanced the accumulation of cyclosporin A, but not valspodar. These results suggested that valspodar accumulation is not actively regulated by the P-glycoprotein-mediated efflux system.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Ablation spectra of the human cornea.

Ablation of human corneal tissue with 193 nm excimer laser energy generates fluorescence in the near ultraviolet and visible regions of the spectrum. The fluorescence spectra from five human corneas were collected during ablation in vitro. We find that the fluorescence spectrum changes continuously as the cornea is ablated from the epithelial surface towards the endothelium. We reduced the dimensionality of the large data set resulting from each cornea by a principal components analysis. The three most significant principal component eigenvectors suffice to describe the observed spectral evolution, and independent analysis of each tissue sample produces a similar set of eigenvectors. The evolution of the calculated eigenvector weighting factors during ablation then corresponds to the observed spectral evolution. In fact, this evolution is qualitatively consistent between corneas. We suggest that this spectral evolution offers promise as a real-time surgical feedback tool.

Algorithms↗
PubMed2001

Activation of Elk-1, an Ets transcription factor, by glucose and EGF treatment of insulinoma cells.

Elk-1, a member of the ternary complex factor family of Ets domain proteins that bind serum response elements, is activated by phosphorylation in a cell-specific manner in response to growth factors and other agents. The purpose of the current study was to determine whether Elk-1 activation contributes to glucose-/depolarization-induced Ca(2+)-dependent induction of immediate early response genes in pancreatic islet beta-cells. The results of experiments in insulinoma (MIN6) cells demonstrated that Elk-1-binding sites (Ets elements) in the Egr-1 gene promoter contribute to transcriptional activation of the gene. Treatment with either epidermal growth factor (EGF), a known inducer of beta-cell hyperplasia, glucose, or KCl-induced depolarization resulted in Ser(383) phosphorylation and transcriptional activation of Elk-1 (4 +/- 0.3-, P = 0.003, 2.3 +/- 0.19-, P = 0.002, and 2.2 +/- 0.1- fold, P = 0.001 respectively). The depolarization response was inhibited by the Ca(2+) channel blocker verapamil and by the MEK inhibitor PD98059 (53 +/- 6 and 55 +/- 0.5%, respectively). EGF-induced activation of Elk-1 was also inhibited by PD98059 (60 +/- 5%). A dominant negative Ras produced partial inhibition (42%) of the depolarization-induced Elk-1 transcriptional activation. Transfection with a constitutively active Ca(2+)/calmodulin kinase IV plasmid also resulted in Elk-1 transcriptional activation. Experiments with p38, phosphatidylinositol 3-kinase, and protein kinase A inhibitors indicated that these pathways are not involved. We conclude that Elk-1 activation contributes to glucose-/depolarization-induced Ca(2+)-dependent induction of immediate early growth response genes in pancreatic islet beta-cells. Furthermore, the results demonstrated a convergence of nutrient- and growth factor-mediated signaling pathways on Elk-1 activation through induction of Ras/mitogen-activated protein kinase ERK-1 and -2. The role of these pathways in the glucose-induced proliferation of islet beta-cells can now be assessed.

Blotting, Western↗
PubMed2001

The genetic basis of plasma variation in adiponectin, a global endophenotype for obesity and the metabolic syndrome.

Here we present the first genetic analysis of adiponectin levels, a newly identified adipocyte-derived protein. Recent work has suggested that adiponectin may play a role in mediating the effects of body weight as a risk factor for coronary artery disease. For this analysis we assayed serum levels of adiponectin in 1100 adults of predominantly northern European ancestry distributed across 170 families. Quantitative genetic analysis of adiponectin levels detected an additive genetic heritability of 46%. The maximum LOD score detected in a genome wide scan for adiponectin levels was 4.06 (P = 7.7 x 10(-6)), 35 cM from pter on chromosome 5. The second largest LOD score (LOD = 3.2; P = 6.2 x 10(-5)) was detected on chromosome 14, 29 cM from pter. The detection of a significant linkage with a quantitative trait locus on chromosome 5 provides strong evidence for a replication of a previously reported quantitative trait locus for obesity-related phenotypes. In addition, several secondary signals offer potential evidence of replications for additional previously reported obesity-related quantitative trait loci on chromosomes 2 and 10. Not only do these results identify quantitative trait loci with significant effects on a newly described, and potentially very important, adipocyte-derived protein, they also reveal the emergence of a consistent pattern of linkage results for obesity-related traits across a number of human populations.

Adiponectin↗
PubMed2001

Selective susceptibility of transformed T lymphocytes to induction of apoptosis by PSC 833, an inhibitor of P-glycoprotein.

P-glycoprotein is a cellular efflux pump. The P-glycoprotein inhibitor PSC 833 causes apoptosis of cancer cells and induces a rise in the intracellular levels of ceramide. Our aims were to determine whether a cause and effect relationship exists between these two actions of PSC 833, and to assess whether the PSC 833-induced apoptosis is restricted to transformed cells. Apoptosis was determined by flow cytometry and radioactive quantitation of DNA fragmentation. PSC 833 induced apoptosis in the human T leukemia cell lines: Molt-4 and Jurkat. Analysis of the apoptosis in Molt-4 and Jurkat cells revealed that PSC 833 induced a rise in the cellular ceramide levels (as measured by the DG kinase assay). PSC 833-induced apoptosis was significantly reduced by specific inhibitors of ceramide de novo synthesis (i.e., fumonisin B1 and L-cycloserine). On the other hand, PSC 833 did not induce apoptosis in normal peripheral blood T cells regardless of whether these cells were quiescent, activated, or proliferating. Our results suggest that PSC 833 induces apoptotic death in human transformed T lymphocytes through an increase in ceramide de novo synthesis. In addition, normal lymphocytes are not susceptible to induction of apoptosis by PSC 833. This difference between normal lymphocytes and leukemia cells presents a potential target for chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

A comparison of antecedents of homicide-suicide and suicide in older married men.

The authors compared characteristics of 27 older men who perpetrated a spousal homicide-suicide and 36 age-matched married men who committed suicide in west central Florida between 1988 and 1994. Data were collected as part of an ongoing retrospective study of homicide and suicide among older adults in Florida. Men who committed suicide had significantly more disease conditions than homicide-suicide perpetrators (P<0.0001). Half of the latter were in caregiving roles, vs. 17% of the suicides (chi(2)=5.40; P=0.027). Depression was a prominent premorbid feature of both groups, but none of the perpetrators tested positive for antidepressants postmortem.

Caregivers↗
PubMed2001

Effect of "inside-out" and "outside-in" attitude displays on off-axis tracking in pilots and nonpilots.

BACKGROUND: Pilots employing helmet-mounted displays spend sustained periods of time looking off-axis, necessitating the inclusion of attitude symbology on the helmet to maintain spatial awareness. We examined how fundamentally different attitude references, a moving-horizon ("inside-out") or a moving-aircraft ("outside-in"), affected pilot and nonpilot attitude control when looking on- or off-axis. Both a rear-view and a side-view outside-in perspective were depicted to investigate the effect of control-display compatibility. METHODS: Subjects performed a compensatory pitch-roll tracking task either looking on-axis or 90 degrees off-axis using three symbologies: 1) a compressed pitch ladder with horizon line; 2) a 3-D aircraft representation viewed from the rear; and 3) a 3-D aircraft representation viewed from the side. Tracking error in roll and pitch, control bias, and subjective ratings were collected and analyzed. RESULTS: There was no significant difference in the tracking performance of U.S. Air Force pilots in pitch and roll using the inside-out or outside-in rear-view formats on- and off-axis, although they preferred the inside-out format. Nonpilots tracked significantly better using the outside-in rear-view format, which they also preferred. Both groups tracked poorly using the outside-in side-view format and control-display compatibility had no important effect. CONCLUSIONS: Pilots are equally adept using outside-in and inside-out displays. Given that an outside-in display may better reflect a person's inherent frame of reference for orientation (as evidenced by the nonpilots' superior performance with it), the results seem to indicate that pilots, through experience, have adapted to an inside-out frame of reference.

Accommodation, Ocular↗
PubMed2001

How to invest in social capital.

Business runs better when people within a company have close ties and trust one another. But the relationships that make organizations work effectively are under assault for several reasons. Building such "social capital" is difficult in volatile times. Disruptive technologies spawn new markets daily, and organizations respond with constantly changing structures. The problem is worsened by the virtuality of many of today's workplaces, with employees working off-site or on their own. What's more, few managers know how to invest in such social capital. The authors describe how managers can help their organizations thrive by making effective investments in social capital. For instance, companies that value social capital demonstrate a commitment to retention as a way of limiting workplace volatility. The authors cite SAS's extensive efforts to signal to employees that it sees them as human beings, not just workers. Managers can build trust by showing trust themselves, as well as by rewarding trust and sending clear signals to employees. They can foster cooperation by giving employees a common sense of purpose through good strategic communication and inspirational leadership. Johnson & Johnson's well-known credo, which says the company's first responsibility is to the people who use its products, has helped the company in time of adversity, as in 1982 when cyanide in Tylenol capsules killed seven people. Other methods of fostering cooperation include rewarding the behavior with cash and establishing rules that get people into the habit of cooperating. Social capital, once a given in organizations, is now rare and endangered. By investing in it, companies will be better positioned to seize the opportunities in today's volatile, virtual business environment.

Commerce↗
PubMed2001

IL-10 receptor dysfunction in macrophages during chronic inflammation.

The immunosuppressive activity of interleukin-10 (IL-10) makes this cytokine a potentially important clinical tool to reduce inflammatory responses in various diseases. Its efficacy as a therapeutic modality is dependent on the responsiveness of immune cells. We report that macrophages from mice chronically infected with the LP-BM5 retrovirus had a reduced capacity to respond to IL-10 in vitro. The ability of IL-10 to inhibit lipopolysaccharide-induced production of tumor necrosis factor (TNF) alpha and IL-6 was significantly reduced in both alveolar and peritoneal macrophages from infected versus uninfected mice. IL-10 hyporesponsiveness was not related to direct infection by the retrovirus, because bone marrow-derived macrophages infected in vitro with LP-BM5 were as responsive to IL-10 as were uninfected bone marrow-derived macrophages. TNF-alpha appeared to contribute to development of IL-10 hyporesponsiveness, because exposure of normal macrophages to TNF-alpha but not interferon-gamma reduced macrophage responsiveness to IL-10. Reverse transcriptase-PCR and flow cytometry demonstrated normal expression of the alpha and beta chains of the IL-10 receptor in macrophages from infected mice, suggesting that IL-10 hyporesponsiveness is not related to a change in receptor expression. The potential role of reduced IL-10 responsiveness in the chronicity of inflammation in this and other diseases is discussed.

Animals↗
PubMed2001

Antibiotic use in acute respiratory infections and the ways patients pressure physicians for a prescription.

OBJECTIVE: We identified those aspects of physician-patient communication that influence physicians to prescribe antibiotics for respiratory infections. STUDY DESIGN: A multimethod comparative case study was performed including descriptive field notes of outpatient visits. POPULATION: We included patients (children and adults) and clinicians in 18 purposefully selected family practices in a midwestern state. A total of 298 outpatient visits for acute respiratory tract (ART) infections were selected for analysis from more than 1600 encounters observed. OUTCOMES MEASURED: Unnecessary antibiotic use and patterns of physician-patient communication were measured. RESULTS: Antibiotics were prescribed in 68% of the ART infection visits, and of those, 79% were determined to be unnecessary according to Centers for Disease Control and Prevention guidelines. Patients were observed to pressure physicians for medication. The types of patterns identified were direct request, candidate diagnosis (a diagnosis suggested by the patient), implied candidate diagnosis (a set of symptoms specifically indexing a particular diagnosis), portraying severity of illness, appealing to life-world circumstances, and previous use of antibiotics. Also, clinicians were observed to rationalize their antibiotic prescriptions by reporting medically acceptable reasons and diagnoses to patients. CONCLUSIONS: Patients strongly influence the antibiotic prescribing of physicians by using a number of different behaviors. To decrease antibiotic use for ART infections, patients should be educated about the dangers and limited benefits of such use, and clinicians should consider appropriate responses to these different patient pressures to prescribe antibiotics.

Acute Disease↗