Acute, Low-dose CO Inhalation does not Alter Energy Expenditure during Submaximal Exercise.

Carbon monoxide, a gas known most widely for its toxic effects at high doses, is receiving increased attention for its role as a physiological signaling molecule and potential therapeutic agent when administered in low doses. We sought to quantify any changes to oxygen consumption and energy expenditure during submaximal exercise after low-dose CO inhalation. 9 active individuals completed 4 graded submaximal exercise tests, with each test occurring during a separate visit. For their first exercise test, subjects inhaled CO or room air (1.2 mL·kg(-1) body mass) in a randomized, subject-blind fashion. A second test was repeated 24 h later when the inhaled gas should have cleared the system. Subjects repeated study procedures with the alternate dose after a washout period of at least 2 days. Low-dose CO administration did not affect oxygen consumption or energy expenditure during submaximal exercise immediately or 24 h following its administration. Increases in heart rate, blood [lactate], and perceived exertion were observed following acute CO inhalation but these effects were absent after 24 h. The results of this study suggest that low-dose CO administration does not influence the energetics of submaximal exercise, but it acutely increases the relative intensity associated with absolute workloads below the lactate threshold.

Atlas-based knee osteophyte assessment with ultrasonography and radiography: relationship to arthroscopic degeneration of articular cartilage.

OBJECTIVES: To investigate intra- and inter-reader agreement of ultrasonography (US) and conventional radiography (CR) for the evaluation of osteophyte presence and size within the tibiofemoral joint. In addition, to correlate these findings with arthroscopic degeneration of the articular cartilage. METHOD: Forty adult patients with knee pain were enrolled in this study. Knee CR and US scanning of the medial and lateral bone margins were performed on all patients. A novel atlas for the US grading of knee osteophytes was used in the evaluation. The number and size of the osteophytes were evaluated semi-quantitatively in two rounds from both the CR images (four readers) and the US images (14 readers). The Noyes grading system was used for the evaluation of arthroscopic degeneration of the articular cartilage in 26 patients. RESULTS: On average, intra- and inter-reader US and CR agreement was substantial and comparable to each other (κ = 0.60-0.72). US detected more osteophytes than CR at both the medial (65% vs. 48%) and lateral (70% vs. 60%) compartments. A statistically significant correlation between CR- or US-based osteophyte and arthroscopy grades was observed only for US at the medial compartment (rs = 0.747, p < 0.001). CONCLUSIONS: The detection of knee osteophytes using the novel US atlas is as reproducible as reading conventional radiographs. US is more sensitive to detect knee osteophytes than CR. Furthermore, osteophytes detected with US correlate significantly with arthroscopic cartilage changes at the medial knee compartment whereas those detected by CR do not.

[Cost of Illness of HIV Patients under Anteretroviral Therapy in Germany - Results of the 48-Week Interim Analysis of the Prospective Multicentre Observational Study 'CORSAR']. / Krankheitskosten von HIV-Patienten unter antiretroviraler Therapie in Deutschland - Ergebnisse einer 48-Wochen-Interimsanalyse im Rahmen der prospektiven multizentrischen Kohortenstudie "CORSAR".

BACKGROUND: With the introduction of highly active combined antiretroviral therapy (c-ART) mortality and morbidity of HIV patients declined substantially. Earlier studies reported that c-ART was able to save health-care costs due to a reduction of other direct medical costs, particularly for inpatient treatments and concomitant medication. To date, analyses of costs and health-related quality of life (HRQOL) of patients under c-ART are lacking in Germany. Hence, this study aims to estimate the current cost of illness and HRQOL of HIV-patients under c-ART in different treatment lines. METHODS: A multicenter, prospective observational study was carried out in 12 specialised German centres for infectious diseases: 8 private practices/outpatient centres and 4 specialised hospitals offering both inpatient and outpatient services. Demographic, clinical and medication data were derived from patient records. Resource utilisation, information on productivity, out of pocket costs and HRQOL (EQ-5D) were collected every 12 weeks via a patient questionnaire. All costs were calculated based on price information from publicly accessible databases. RESULTS: N=1,154 patients were included in the analysis. Mean direct disease-related costs of -patients under c-ART amounted to 22,563 Euro/year. Patients beyond the 3(rd) line of treatment -incurred considerably higher costs 24,654 Euro/year. In the 1(st) treatment line, c-ART accounted for 83.2% of the total direct costs, in the 2(nd)/3(rd) line for 80.8% and in >3(rd) line for 83.4%, respectively. Indirect costs due to impaired productivity were higher in the 2(nd)/3(rd) treatment line (2,843 Euro) compared to the 1(st) (1,604 Euro) and >3(rd) (1,752 Euro) treatment lines, respectively. The average HRQOL (EQ-5D) varied between 0.77 (self-assessment via visual analogue scale) and 0.91 (utility score based on the German time trade-off tariff). CONCLUSIONS: Over the last decade, cost of illness of HIV patients under c-ART decreased slightly with average costs per year still being substantial. Main cost driver of overall costs is c-ART. There have been, however, noticeable shifts between different cost domains.

Multicenter study of ultrasound real-time tissue elastography in 779 cases for the assessment of breast lesions: improved diagnostic performance by combining the BI-RADS®-US classification system with sonoelastography.

PURPOSE: Hitachi real-time tissue elastography (HI-RTE) is an ultrasound technique that facilitates the estimation of tissue elasticity. Our study evaluates whether sonoelastography improves the differentiation of benign and malignant breast lesions. MATERIALS AND METHODS: In a multicenter approach sonoelastography of focal breast lesions was carried out in 779 patients with subsequent histological confirmation. We present data from 3 study centers (Berlin, Bielefeld, Homburg/Saar) focusing on the sensitivity (SE), specificity (SP) and the positive (PPV) and negative predictive value (NPV) of sonoelastography. In addition we performed an analysis of the diagnostic performance, expressed by the pretest and posttest probability of disease (POD), in BI-RADS®-US 3 or 4 lesions as these categories can imply both malignant and benign lesions and a more precise prediction would be a preferable aim. RESULTS: Sonoelastography demonstrated an improved SP (89.5 %) and an excellent PPV (86.8 %) compared to B-mode ultrasound (76.1 % and 77.2 %). Especially in dense breasts ACR III-IV, the SP was even higher (92.8 %). In BI-RADS-US 3 lesions, a suspicious elastogram significantly modified the POD from 8.3 % to a posttest POD of 45.5 %. In BI-RADS-US 4 lesions, we found a pretest POD of 56.6 %. The posttest POD changed significantly to 24.2 % with a normal elastogram and to 81.5 % with a suspicious elastogram. CONCLUSION: Our data demonstrates that the complementary use of sonoelastography definitely improves the performance in breast diagnostics. Finally we present a protocol of how sonoelastography can be integrated into our daily practice.

[Chance or causality: problems recognizing laryngeal carcinoma as a result of occupational exposition to noxious substances of blue collar worker employed in the rubber industry]. / Zufall oder Kausalität--zur Problematik der Anerkennung von Larynxkarzinomen bei Arbeitern der Gummi-Industrie.

BACKGROUND: Laryngeal cancer as an occupational disease in the rubber industry is under subject of continuous epidemiological research because of the lack of stable statistical data. METHOD: Epidemiological studies published in the period between 1982 and 2006 were analysed in regard of the risks employment and laryngeal carcinoma. 23 own cases of medical expert opinion and the documentation of the German Occupational Cooperatives were analysed. RESULTS: A significant statistical correlation between a specific exposition to cancerogenics in the rubber industry and a development of laryngeal carcinoma could not be found in the literature, still there is evidence for an increased mortality. It points to asbestos, talcum, dust as one risk factor. CONCLUSION: Recognition and compensation for laryngeal carcinoma according to [section sign] 9 Abs. 2 SGB VII is possible after intense individual investigation, although up to now no clear statistical evidence for the coincidence between employment in the rubber industry and general could be proven.

Life cycle assessment part 1: framework, goal and scope definition, inventory analysis, and applications.

Sustainable development requires methods and tools to measure and compare the environmental impacts of human activities for the provision of goods and services (both of which are summarized under the term "products"). Environmental impacts include those from emissions into the environment and through the consumption of resources, as well as other interventions (e.g., land use) associated with providing products that occur when extracting resources, producing materials, manufacturing the products, during consumption/use, and at the products' end-of-life (collection/sorting, reuse, recycling, waste disposal). These emissions and consumptions contribute to a wide range of impacts, such as climate change, stratospheric ozone depletion, tropospheric ozone (smog) creation, eutrophication, acidification, toxicological stress on human health and ecosystems, the depletion of resources, water use, land use, and noise-among others. A clear need, therefore, exists to be proactive and to provide complimentary insights, apart from current regulatory practices, to help reduce such impacts. Practitioners and researchers from many domains come together in life cycle assessment (LCA) to calculate indicators of the aforementioned potential environmental impacts that are linked to products-supporting the identification of opportunities for pollution prevention and reductions in resource consumption while taking the entire product life cycle into consideration. This paper, part 1 in a series of two, introduces the LCA framework and procedure, outlines how to define and model a product's life cycle, and provides an overview of available methods and tools for tabulating and compiling associated emissions and resource consumption data in a life cycle inventory (LCI). It also discusses the application of LCA in industry and policy making. The second paper, by Pennington et al. (Environ. Int. 2003, in press), highlights the key features, summarises available approaches, and outlines the key challenges of assessing the aforementioned inventory data in terms of contributions to environmental impacts (life cycle impact assessment, LCIA).

[Solutions for off-label therapy]. / Off-Label-Therapie: Lösungsmöglichkeiten.

About 25% of administrations are for off-label indications. The treatment of many rheumatic diseases includes off-label use. Reimbursement from the health insurance is possible if no other approved therapy is available, and if scientific studies prove the effectiveness of the drug.

Predictive value of sperm chromatin condensation (aniline blue staining) in the assessment of male fertility.

A case control study was carried out to determine the value of sperm chromatin condensation in the assessment of male fertility. A total of 165 semen samples from 90 patients (cases) and 75 healthy donors (control) were examined for chromatin condensation (aniline blue staining), as well as conventional sperm parameters, notably sperm morphology, sperm count, and progressive motility. Whereas only 55 +/- 12.0% of the samples from the infertile patients were unstained by aniline blue (chromatin condensed), 78 +/- 19.0% of the samples in the control group did not take up the stain (chromatin condensed). A significant difference (p < .001) was observed between the two groups. Similarly, the difference between the mean percentage of morphologically normal spermatozoa for the infertile patients (12.1 +/- 1.2%) and the control (23.9 +/- 1.9%) was very significant (p < .001). In addition, only 50 out of the 90 patients (55.5%) had a normal sperm count, whereas all the 75 (100%) were normal in the control group. By comparing between the two groups a significant difference (p < .001) was also observed. Furthermore, a significant difference (p < .001) was also found between the cases and the control with regard to the percentage of spermatozoa illustrating linear progressive motility (40 +/- 9.7% vs. 70 +/- 12.3%). However, no correlation was found between sperm chromatin condensation and morphology, count, and motility. This study suggests that chromatin condensation constitutes a valuable parameter in the assessment of male fertility, completely independent of conventional sperm parameters. Consequently, the inclusion of chromatin condensation to routine laboratory investigations of semen prior to assisted reproduction is strongly recommended.

Distance learning in graduate health administration education: a case study from Washington State University.

Some scholars have viewed distance learning as cause for concern, a potential degradation to the educational process. Others have said it provides the access that is not possible with traditional education and therefore expands the options for reaching diverse populations of students. Many are not certain where this educational toolis headed but know that it will have a big effect on the population of both students and faculty in educational institutions. Indeed, the direction of distance learning has the attention of many that previously attempted to ignore it as a passing trend in the educational process. Washington State University (WSU) at Spokane and its Health Policy and Administration (HPA) Program have been involved with distance education for more than a decade. The purpose here is to share this decade of experience. The academic and administrative experience of faculty, staff, and students are documented and discussed with the intent of showing both the advantages and disadvantages of distance learning. Some of the lessons learned are shared along with challenges in maintaining quality in the delivery of graduate education in health administration and other fields as we move forward in adopting distance learning tools and techniques.

Complications of triple pregnancy following intracytoplasmic sperm injection: a case report.

A case is presented of pregnancy and delivery of triplets following intracytoplasmic sperm injection (ICSI) therapy. Although the outcome was satisfactory, with the birth of normal children free from any malformation, most of the obstetric and particularly the neonatal complications that can be associated with this therapy are illustrated in this case. In addition, from point of view of medical costs, concerns are raised about the current policy of multiple embryo transfer which is directly responsible for the high rate of multiple gestations observed in the IVF/ICSI programme. The authors consequently recommend a policy of transferring not more than two embryos per treatment cycle.

[Imaging diagnosis in suspected inflammatory rheumatoid axial skeleton diseases (sacroilitis)]. / Bildgebende Diagnostik bei Verdacht auf entzündlich rheumatische Achsenskeletterkrankungen (Sakroiliitis).

Involvement of the sacroiliac joints is a hallmark of the spondyloarthropathies, especially in ankylosing spondylitis. The conventional diagnostic imaging of sacroiliitis in early stages might cause problems, because sensitivity of conventional radiographic methods is known to be too low in early stages of the disease. Magnetic resonance imaging of the sacroiliac joints certainly enables one to detect acute as well as chronic inflammatory changes in all stages of the disease. The potential disadvantages of this method are the dependency on the examiner, the lack of standardization, and the relatively high costs. Therefore, the "Workgroup of Diagnostic Imaging in Rheumatology of the Regional Center of Rheumatology of Berlin" including experienced rheumatologists, skeletal radiologists, and orthopedists acquired an imaging graduation for detection of sacroiliitis in consideration of the clinical background, the technical details of the methods, questions of ionizing radiation exposure, and cost effectiveness.

Accurate and cost-effective evaluation of breast masses in males.

BACKGROUND: Because the majority of breast masses in males are benign and need not be excised if asymptomatic, we studied the combination of physical examination (PE) and fine needle aspiration (FNA), with or without mammography, as a diagnostic alternative to routine surgical biopsy of these lesions. METHODS: A diagnostic test study and cost-effectiveness analysis was performed in three participating multidisciplinary breast clinics, involving a consecutive sample of 51 males with unilateral breast masses. Each lesion was tested with both PE and FNA; 13 were also studied with mammography, and each test was scored as benign or suspicious. Lesions for which all tests were benign were followed up clinically (mean 19 months). Lesions for which any test was suspicious were excised. RESULTS: All tests were benign in 38 cases. No cancers developed at the index sites during follow-up of these lesions, including 8 excisional biopsies done for symptoms (negative predictive value and specificity 100%). Open biopsy confirmed malignancy in all 6 cases for which all tests were suspicious (positive predictive value and sensitivity 100%). In all 7 cases where the tests were not in agreement, open biopsy was benign. In these cases FNA (2 false positives) proved more accurate than PE (5 false positives). Mammography added no additional diagnostic information to the combination of PE and FNA. Compared with routine open biopsy, the combination of PE and FNA avoided surgical biopsy in 30 of the 51 lesions, and was associated with an average decrease in charges of up to $510 per case. CONCLUSIONS: The combination of PE and FNA for the evaluation of breast masses in males is diagnostically accurate and results in a reduction in patient charges compared with routine open biopsy.

Evaluation of low cost in-line milk samplers for estimating individual cow somatic cell counts.

The Dairy Herd Improvement Fund of Victoria recently identified a requirement for a simple and inexpensive in-line sampler to enable dairy farmers to collect representative milk samples for counting somatic cells. We found that the currently available simple in-line milk samplers, when connected to standard 35 ml collection vessels, terminate sampling early in a milking, and thus provide samples that are unrepresentative of the whole milking. We showed that cell count during a milking varies greatly, tending to be high for the first 1-21. Analyses of resulting samples will thus tend to overestimate cell counts if samplers are used in their traditional way. We found greater sampling rates in high-line compared with low-line milking systems, and consequently developed modified samplers suitable for both situations. Our samplers utilize low sampling rates (approximately 1-3%) and large collection vessels (450 ml). Compared with currently available simple in-line samplers, our type of sampler provided milk samples considerably more representative of the entire milking for the majority of cows. In conjunction with subsampling, they provided samples of appropriate size (12.5 ml minimum to 25 ml maximum) for testing fat, protein, lactose and cell count. Cell count results indicated that errors associated with the use of currently available simple in-line samplers could frequently be > 200%. In contrast, we found that use of our samplers gave an estimate for cell count that was only slightly higher (mean 20%) than that from samples collected by an approved Tru-Test sampler.

A third kidney transplant: cost-effective treatment for end-stage renal disease?

Given the organ donor shortage, some question whether a third kidney transplant can be justified. We studied the outcome of 51 third transplants (mean age 28 +/- 2 yr) done between 1 January 1985 and 31 December 1994. We compared hospital stay (mean +/- S.E.), cost, readmissions, readmission days, and outcome of third (vs. first and second) transplants. We found that patient survival for third transplants was equivalent to first and second transplants; graft survival was not as good. However, when third transplant recipients with recurrent disease (specifically, hemolytic uremic syndrome and focal sclerosis) were excluded from our analysis, we found no difference in 5-yr graft survival (vs. first or second transplant recipients). Of the 51 third transplant recipients, 41 had a cadaver donor transplant. Third cadaver transplant recipients tended to have a longer hospital stay (p = NS) than first cadaver transplant recipients but had no more readmissions or readmission days than first and second cadaver transplant recipients. Employment data are available for 28 third transplant recipients; 16 (57%) are currently working or going to school. Of the 21 recipients who responded to quality of life questionnaires, 17 (81%) reported being healthy and all 21 (100%) said transplantation was not a drawback to their health. We conclude that third transplants should be considered for selected patients with renal failure whose first and second transplants have failed. Such patients can often be successfully transplanted.

Diagnosis of palpable breast lesions in younger women by the modified triple test is accurate and cost-effective.

OBJECTIVE: To study the accuracy and cost of diagnosing palpable breast lesions in younger patients using a modified triple test (MTT: physical examination, ultrasonography instead of mammography, and fine-needle aspiration). DESIGN: Diagnostic test study and cost-effectiveness estimate. SETTING: Multidisciplinary university breast clinic. PATIENTS: Fifty-five women below the recommended age of screening mammography (mean age, 33 years) with unilateral, palpable breast lesions. INTERVENTION: Each lesion was tested by all 3 elements of MTT, and each element was interpreted as benign, suspicious, or malignant. MAIN OUTCOME MEASURES: Patients with MTTs in which all elements were concordant (in agreement) and benign were evaluated clinically (mean follow-up, 11 months). Patients in whom the results of fine-needle aspiration were scored as suspicious or malignant underwent open confirmatory biopsy. RESULTS: Forty-eight patients had concordant benign MTTs, including 14 patients with breast cysts. No cancers developed at the index sites during follow-up, including 5 biopsies done at the patients' request (negative predictive value and specificity, 100%). Fine-needle aspiration and physical examination were more accurate than ultrasonography in the 7 cases in which MTT was nonconcordant. Compared with the criterion standard (physical examination and open biopsy), use of MTT under the conditions of this study could avoid open biopsies in almost all cases, with average savings in charges of up to $623 per case. CONCLUSION: Use of MTT for the diagnosis of unilateral, palpable breast lesions in younger women yields high diagnostic accuracy without the need for routine open biopsy, resulting in an overall reduction in patient charges.

[The German Alzheimer Family Groups. An assessment of current status]. / Die deutschen Alzheimer-Angehörigengruppen. Eine Bestandsaufnahme.

Counselling the relatives of psychiatric patients is becoming increasingly important. This includes the relatives of patients with Alzheimer's disease. Since little is known about the organization and function of support groups for family caregivers of Alzheimer patients, in 1994 we wrote to all such groups known to us and asked them to fill in a questionnaire. The response rate was 85% (84/99), and 66 of the forms could be used for further analysis. The results were as follow: Most groups for relatives of Alzheimer patients admitted new members at any time. 69% had existed for more than 1 year and 19% for more than 5 years. 81% consisted of 6-15 participants. 73% of the groups met once in a month. Health professionals organized the groups in 65% of cases. The main topics were trading information about the disease and support as well as daily care requirements. 73% of the groups were associated with health institutions or nationwide support organizations. Public relations were managed by personal contacts and press reports; did the groups rarely advertise. Based on a review of the literature, the impact of structure upon the function of groups is discussed.

Antitrust implications of health care reform.

Antitrust issues affect the insurance industry, hospital industry, and physicians. The authors explore the history of antitrust issues in the health care field and implications for future developments. Interest in antitrust has increased due to current merger and acquisition activities in the industry. With the failure of the Health Security Act, health care reform will be left to private industry. Will there be increasing or decreasing antitrust activity by the Department of Justice and Federal Trade Commission?

Use of the "triple test" for palpable breast lesions yields high diagnostic accuracy and cost savings.

BACKGROUND: The "triple test" for palpable breast lesions consists of physical examination, mammography, and fine-needle aspiration. METHODS: Forty-six lesions in 43 patients were subjected to all three components of the triple test, followed by confirmatory open biopsy. RESULTS: In all 21 cases where the triple test was concordant (elements had either all malignant or all benign results), pathologic analysis of open biopsy samples was confirmatory (predictive value and sensitivity 100%). Fine-needle aspiration was the most reliable element of the triple test in cases where the elements of the test were nonconcordant (negative predictive value and sensitivity of 95% and 96%, respectively). CONCLUSIONS: The triple test was 100% accurate in the diagnosis of palpable breast lesions when all three elements were concordant. Cost analysis revealed that elimination of confirmatory open biopsy in such cases and also in cases in which the fine-needle aspiration and one other element of the test had a suspicious or malignant result, could yield an average per-case cost savings of up to $1,412 compared to triple test followed by routine confirmatory open biopsy.

Elicitation of a systemic and protective anti-melanoma immune response by an IL-2-based vaccine. Assessment of critical cellular and molecular parameters.

We have established a model for the immunologic rejection of melanoma cells. Using a receptor-mediated, adenovirus-augmented gene delivery system (transferrinfection) we have shown that, upon transfection with an IL-2 gene construct, MHC class I+/class II- murine M-3 cells lose their tumorigenicity in both athymic and euthymic mice. More importantly, we found that these melanoma cells, which produce high levels of IL-2, can be used to induce a long-lasting anti-tumor immune response in syngeneic euthymic DBA/2 mice but not in athymic animals. This immune response, which can also be elicited by coadministration of nonmodified, irradiated M-3 cells and IL-2-transduced fibroblasts, results in the rejection of a subsequent challenge with M-3 cells or, in the elimination of preexisting M-3 cancer cell deposits. We found that transfer of T cell-enriched, but not of T cell-depleted, splenocytes from immunized mice conferred protection against M-3 cells, but not against unrelated KLN 205 cancer cells. Transfer of either CD4+ or CD8+ T cells led to only partial protection against challenge with wild-type M-3 cells. Our further observations that T cell-enriched, but not T cell-depleted splenocytes of immunized animals are capable of tumor-specific lytic activity and that this activity resides in the CD8+ cell population are compatible with the assumption that MHC class I-restricted T cell cytotoxicity is a biologically relevant effector mechanism in this model. That other mechanisms also contribute to melanoma cell destruction is evidenced by the presence of large numbers of macrophages and granulocytes in addition to T cells at the challenge sites of immunized mice.