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Biomedical subjects

S Green

Publications and source records attributed to S Green.

At least 73 records · Page 4Linked to original sources

TestSmart-high production volume chemicals: an approach to implementing alternatives into regulatory toxicology.

This article examines the status and application of alternatives defined as replacements, refinements, and reduction for screening high production volume (HPV) chemicals. It specifically focuses on the Screening Information Data Set (SIDS), a series of toxicological tests recommended by the Organization for Economic Cooperation and Development to screen such chemicals. Alternative tests associated with acute, repeat-dose, genetic, and reproductive and developmental toxicity were examined at 2 meetings of academic, industry, and regulatory scientists and their status determined. Tests were placed in 1 of 3 categories: ready for immediate use, in need of or currently undergoing validation, or needing research/developmental work. With respect to traditional acute toxicity testing, the basal cytotoxicity approach was placed in the category of research with the up-and-down, fixed-dose, limit test, and the acute toxic class categorized as available for immediate use and the neutral red assay under validation. Cell culture methods that could provide information on acute target organ toxicity were all categorized in the research stage. Studies of the Ah receptor were placed under validation. All alternative tests for repeat-dose toxicity were placed in the category of research. With regard to genetic toxicity, the Ames, mouse lymphoma, and Chinese hamster ovary methods were considered ready for immediate use, while the in vitro micronucleus and Syrian hamster ovary assays were placed in the validation category. All alternatives for developmental toxicity, with the exception of gene chip technology, were placed in the category of validation. Gene chip technology is considered to be in the research stage. For reproductive toxicity, sperm motility and morphology were considered as ready for immediate use, with the other assays categorized as needing validation or in the research stage. Follow-up to these results is obvious. Work needs to be conducted to move those tests from the research stage to the validation and use stage. This is one approach to the development of alternatives to SIDS. Progress along these lines would apply not only to SIDS but also to toxicology in general.

Animal Testing Alternatives↗

Effect of propionyl-L-carnitine on exercise performance in peripheral arterial disease.

BACKGROUND: Supplementation with propionyl-L-carnitine (PLC) may be of use in improving the exercise capacity of people with peripheral arterial disease. METHODS: After a 2-wk exercise familiarization phase, seven subjects displaying intermittent claudication were studied over a 12-wk period consisting of three 4-wk phases, baseline (B), supplementation (S), and placebo (P). PLC was supplemented at 2 g x d(-1), and subjects were blinded to the order of supplementation. Unilateral calf strength and endurance were assessed weekly. Walking performance was assessed at the end of each phase using an incremental protocol, during which respiratory gases were collected. RESULTS: Although there was not a significant increase in maximal walking time ( approximately 14%) in the whole group, walking time improved to a greater extent than the individual baseline coefficient of variation in four of the seven subjects. The changes in walking performance were correlated with changes in the respiratory exchange ratio both at steady state (r = 0.59) and maximal exercise (r = 0.79). Muscle strength increased significantly from 695 +/- 198 N to 812 +/- 249 N by the end of S. Changes in calf strength from B to S were modestly related to changes in walking performance (r = 0.56). No improvements in calf endurance were detected throughout the study. CONCLUSIONS: These preliminary data suggest that, in addition to walking performance, muscle strength can be increased in PAD patients after 4 wk of supplementation with propionyl-L-carnitine.

Adult↗

Framework growth after reconstruction for microtia: is it real and what are the implications?

Historically, fashioning an auricle for a patient born with microtia has been one of the most challenging endeavors in the repertoire of reconstructive surgeons. Despite many ideas advanced on types of materials for the auricular framework, the hands-down favorite and today's medium of choice is autogenous costal cartilage. A subject that remains up for discussion, however, is the question of growth potential in these cartilaginous frameworks. Popularization of the surgical technique for auricular reconstruction has led to much bandying about of opinions on this very important question of growth. Although previous reports allude to the probability of an increase in auricular size after reconstruction, this report is the first to document changes in auricular size with measurements taken directly from patients at the time of graft implantation and during subsequent long-term follow-up. The goals of this study are to define the behavior of the autogenous framework after reconstruction of the microtic auricle. This information serves to clarify the issue of proper framework sizing and to make evident the early age at which reconstruction can begin. The records of patients who underwent costal cartilage auricular reconstruction for grade III microtia between 1990 and 1996 were reviewed, and a cohort of 10 patients was chosen for inclusion based on availability for follow-up and lack of any interval modifications of their cartilaginous framework. The average age was 6.7 years, and the average time interval from initial reconstruction to follow-up was 3.2 years. Measurements of the auricular framework height and width were taken at implantation and at time of final follow-up, and measurements were recorded of the normal ears of patients with unilateral microtia. The mean auricular size was examined for significance of interval change using the two-sample Student's t tests, assuming unequal variances. The results revealed an average height increase of 5 mm (10.4 percent) in the study population. Auricular width changes averaged 2.75 mm (7.02 percent). Growth trends revealed a distinct tendency toward increasing auricular framework size over time, with slowing as patients neared adolescence. Comparison of the reconstructed auricle to the normal ear of each patient with unilateral microtia showed that the reconstructed ear paralleled the growth of the normal side, with no statistically significant differences in height or width at follow-up. This is the first report of auricular framework behavior based on patients having direct measurement of their framework initially and in long-term follow-up. This patient sample underscores a clear pattern of growth in the reconstructed auricles paralleling that of the normal ears. The implications of this finding are important in that the initial oversizing of the framework becomes unnecessary. Moreover, the decision as to age at initial reconstruction is not affected by anticipated growth rates.

Anthropometry↗

A systematic review of physical interventions for patellofemoral pain syndrome.

OBJECTIVE: Physical interventions (nonpharmacological and nonsurgical) are the mainstay of treatment for patellofemoral pain syndrome (PFPS). Physiotherapy is the most common of all physical interventions and includes specific vastus medialis obliquus or general quadriceps strengthening and/or realignment procedures (tape, brace, stretching). These treatments appear to be based on sound theoretical rationale and have attained widespread acceptance, but evidence for the efficacy of these interventions is not well established. This review will present the available evidence for physical interventions for PFPS. DATA SOURCES: Computerized bibliographic databases (MEDLINE, Current Contents, CINAHL) were searched, including the keywords "patellofemoral," "patella," and "anterior knee pain," combined with "treatment," "rehabilitation," and limited to clinical trials through October 2000. STUDY SELECTION: The critical eligibility criteria used for inclusion were that the study be a controlled trial, that outcome assessments were adequately described, and that the treatment was a nonpharmacological, nonsurgical physical intervention. RESULTS: Of the 89 potentially relevant titles, 16 studies were reviewed and none of these fulfilled all of the requirements for a randomized, controlled trial. Physiotherapy interventions were evaluated in eight trials, and the remaining eight trials examined different physical interventions. Significant reductions in PFPS symptoms were found with a corrective foot orthosis and a progressive resistance brace, but there is no evidence to support the use of patellofemoral orthoses, acupuncture, low-level laser, chiropractic patellar mobilization, or patellar taping. Overall the physiotherapy interventions had significant beneficial effects but these interventions were not compared with a placebo control. There is inconclusive evidence to support the superiority of one physiotherapy intervention compared with others. CONCLUSIONS: The evidence to support the use of physical interventions in the management of PFPS is limited. There appears to be a consistent improvement in short-term pain and function due to physiotherapy treatment, but comparison with a placebo group is required to determine efficacy, and further trials are warranted for the other interventions.

Adolescent↗

When approved is not enough: development of a supervision consultation model.

The dramatic increase in the literature that addresses family therapy training and supervision over the last decade has been predominantly in the area of theory, rather than practice. This article describes the development of a meta-supervisory learning context for approved supervisors and provides examples of interactions between supervisors that subsequently influenced both therapy and supervision. We delineate the assumptions that inform our work and offer specific guidelines for supervisors who wish to implement a similar model in their own contexts. We provide suggestions for a proactive refiguring of supervision that may have profound effects and benefits for supervisors and supervisees alike.

Anecdotes as Topic↗

Pelvic floor reeducation for stress incontinence: comparing three methods.

Stress urinary incontinence is a common problem among women of all ages but may resolve with pelvic floor reeducation in many cases. Compliance to a regimen of pelvic floor muscle exercises is poor and many devices have been produced to make exercising these muscles more effective and interesting. This article describes a study in which two such devices -- vaginal cones and pressure biofeedback -- were compared with pelvic floor exercises alone. The results show that there is no statistically significant difference between the three modalities; all treatments produced significant improvement in symptoms and quality of life scores.

Adult↗

Mechanisms of hemorrhage in dengue without circulatory collapse.

To characterize the molecular basis for the hemostatic defects of dengue infections, a study was conducted in Bangkok, Thailand. Febrile children (n = 68) hospitalized with suspected dengue were enrolled before their clinical syndromes were classified as either dengue fever (DF) or dengue hemorrhagic fever (DHF). Hospital course and outcome were recorded; blood was obtained during the febrile illness (S1), after defervescence (S2), and 1 month after onset of disease (S4). Patients were classified as DF (n = 21) and DHF grades 1, 2, and 3; (DHF1, n = 8; DHF2, n = 30; and DHF3, n = 9). All had marked thrombocytopenia. Bleeding scores were assigned on the basis of bleeding site. Although there was no correlation between bleeding scores and pleural effusion index (a measure of vascular leakage) or bleeding scores and platelet counts, there was a correlation between pleural effusion index and platelet counts. Bleeding scores did not correlate with hemostatic data. Activated partial thromboplastin time was prolonged, with trends toward decreased fibrinogen and increased levels of prothrombin fragment F1.2 in the acute-phase samples. However, no factor level was dramatically decreased. We conclude that most patients with DF or DHF, even without overt hemorrhage, have consumptive coagulopathy. Nevertheless, hemorrhage in dengue without circulatory collapse is most likely due to activation of platelets rather than coagulopathy, which is well compensated. Our data suggest that vascular alteration may be the principal factor involved in the association of thrombocytopenia and hemorrhage with disease severity.

Adolescent↗

Pathogen testing of ready-to-eat meat and poultry products collected at federally inspected establishments in the United States, 1990 to 1999.

The Food Safety and Inspection Service (FSIS) conducted microbiological testing programs for ready-to-eat (RTE) meat and poultry products produced at approximately 1,800 federally inspected establishments. All samples were collected at production facilities and not at retail. We report results here for the years 1990 through 1999. Prevalence data for Salmonella, Listeria monocytogenes, Escherichia coli O157:H7, or staphylococcal enterotoxins in nine different categories of RTE meat and poultry products are presented and discussed. The prevalence data have certain limitations that restrict statistical inferences, because these RTE product-testing programs are strictly regulatory in nature and not statistically designed. The cumulative 10-year Salmonella prevalences were as follows: jerky, 0.31%; cooked, uncured poultry products, 0.10%; large-diameter cooked sausages, 0.07%; small-diameter cooked sausages, 0.20%; cooked beef, roast beef, and cooked corned beef, 0.22%; salads, spreads, and pâtés, 0.05%; and sliced ham and luncheon meat, 0.22%. The cumulative 3-year Salmonella prevalence for dry and semidry fermented sausages was 1.43%. The cumulative 10-year L. monocytogenes prevalences were as follows: jerky, 0.52%; cooked, uncured poultry products, 2.12%; large-diameter cooked sausages, 1.31%; small-diameter cooked sausages, 3.56%; cooked beef, roast beef, and cooked corned beef, 3.09%; salads, spreads, and pâtés, 3.03%; and sliced ham and luncheon meat, 5.16%. The cumulative 3-year L. monocytogenes prevalence for dry and semidry fermented sausages was 3.25%. None of the RTE products tested for E. coli O157:H7 or staphylococcal enterotoxins was positive. Although FSIS and the industry have made progress in reducing pathogens in these products, additional efforts are ongoing to continually improve the safety of all RTE meat and poultry products manufactured in federally inspected establishments in the United States.

Animals↗

Analysis of plasma viral RNA levels during acute dengue virus infection using quantitative competitor reverse transcription-polymerase chain reaction.

There is increasing recognition of the potential importance of viral burden in the pathogenesis of dengue hemorrhagic fever (DHF). There is little data available, however, describing the kinetics of viral replication in humans with natural dengue virus (DV) infection. Standard procedures for measuring titers of infectious virus in clinical specimens are either laborious or insensitive. We developed a method for measurement of DV RNA in plasma samples based on reverse transcription-polymerase chain reaction (RT-PCR) using a mutant RNA target as a competitor. This technique was reproducible and accurate for samples containing any of the four DV serotypes, and could be applied to samples containing as few as 250 copies of RNA per reaction. We examined plasma viral RNA levels in 80 children with acute DV infection; sequential plasma samples were tested in 34 of these children. Plasma viral RNA levels ranged as high as 10(9) RNA copies/ml, and correlated with titers of infectious virus measured in mosquitoes (r= 0.69). Plasma viral RNA levels fell rapidly during the last several days of the febrile period. We did not find a significant difference in maximal plasma viral RNA levels between children with DHF and children with dengue fever, but peak viral RNA levels were identified in only 16 subjects. We conclude that this quantitative RT-PCR method will be valuable for further studies of natural DV infections.

Adolescent↗

Kaiser Permanente's "metadata-driven" national clinical intranet.

This paper describes the approach taken to build Kaiser Permanente's national clinical intranet. A primary objective for the site is to facilitate resource discovery, which is enabled by the use of "metadata", or data (fields and field values) that describe the various resources available. Users can perform full text queries and/or fielded searching against the metadata. Metadata serves as the organizing principle of the site--it is used to index documents, sort search results, and structure the site's table of contents. The site's use of metadata--what it is, how it is created, how it is applied to documents, how it is indexed, how it is presented to the user in the search and the search results interface, and how it is used to construct the table of contents for the web site--will be discussed in detail. The result is that KP's national clinical intranet has coupled the power of Internet-like full text search engines with the power of MedLine-like fielded searching in order to maximize search precision and recall. Organizing content on the site in accordance with the metadata promotes overall consistency. Issues currently under investigation include how to better exploit the power of the controlled terminology within the metadata; whether the value gained is worth the cost of collecting metadata; and how automatic classification algorithms might obviate the need for manual document indexing.

Computer Communication Networks↗

Interstitial and arterial-venous [K+] in human calf muscle during dynamic exercise: effect of ischaemia and relation to muscle pain.

Changes in the concentration of interstitial K+ surrounding skeletal muscle fibres ([K+]I) probably play some role in the regulation of cardiovascular adjustments to muscular activity, as well as in the aetiology of muscle pain and fatigue during high-intensity exercise. However, there is very little information on the response of [K+]I to exercise in human skeletal muscle. Five young healthy subjects performed plantar flexion exercise for four 5 min periods at increasing power outputs ( approximately 1-6 W) with 10 min intervening recovery periods, as well as for two 5 min periods with ischaemia at approximately 1 and approximately 3 W. Microdialysis probes were inserted into the gastrocnemius medialis muscle of the right leg to measure [K+]I, and K+ release from the plantar flexors during and after incremental exercise was calculated from plasma flow and arterial-venous differences for K+. Calf muscle pain was assessed using a visual analogue scale. On average, [K+]I was 4.4 mmol l(-1) at rest and increased during minutes 3-5 of incremental exercise by approximately 1-7 mmol l(-1) as a positive function of power output. K+ release also increased as a function of exercise intensity, although there was a progressive increase by approximately 1-6 mmol l-1 in the [K+] gradient between the interstitium and arterial-venous plasma. [K+]I was lower during ischaemic exercise than control exercise. In contrast to this effect of ischaemia on [K+]I, muscle pain was relatively higher during ischaemic exercise, which demonstrates that factors other than changes in [K+]I are responsible for ischaemic muscle pain. In conclusion, this study has demonstrated that during 5 min of dynamic exercise, [K+]I increases during the later period of exercise as a positive function of exercise intensity, ischaemia reduces [K+]I during rest and exercise, and the increase in [K+]I is not responsible for muscle pain during ischaemic exercise.

Adult↗

A randomized, double-blind trial comparing azithromycin and clarithromycin in the treatment of disseminated Mycobacterium avium infection in patients with human immunodeficiency virus.

Two hundred and forty-six patients infected with human immunodeficiency virus (HIV) who also had disseminated Mycobacterium avium complex received either azithromycin 250 mg every day, azithromycin 600 mg every day, or clarithromycin 500 mg twice a day, each combined with ethambutol, for 24 weeks. Samples drawn from patients were cultured and clinically assessed every 3 weeks up to week 12, then monthly thereafter through week 24 of double-blind therapy and every 3 months while on open-label therapy through the conclusion of the trial. The azithromycin 250 mg arm of the study was dropped after an interim analysis showed a lower rate of clearance of bacteremia. At 24 weeks of therapy, the likelihood of patients' developing 2 consecutive negative cultures (46% vs. 56%, P=.24) or 1 negative culture (59% vs. 61%, P=.80) was similar for azithromycin 600 mg (n=68) and clarithromycin (n=57), respectively. The likelihood of relapse was 39% versus 27% (P=.21) on azithromycin compared with clarithromycin, respectively. Of the 6 patients who experienced relapse, none of those randomized to receive azithromycin developed isolates resistant to macrolides, compared with 2 of 3 patients randomized to receive clarithromycin [corrected]. Mortality was similar in patients comprising each arm of the study (69% vs. 63%; hazard, 95.1% confidence interval, 1.1 [0.7, 1.7]). Azithromycin 600 mg, when given in combination with ethambutol, is an effective agent for the treatment of disseminated M. avium disease in patients infected with HIV.

AIDS-Related Opportunistic Infections↗

Blood flow and oxygenation in peritendinous tissue and calf muscle during dynamic exercise in humans.

1. Circulation around tendons may act as a shunt for muscle during exercise. The perfusion and oxygenation of Achilles' peritendinous tissue was measured in parallel with that of calf muscle during exercise to determine (1) whether blood flow is restricted in peritendinous tissue during exercise, and (2) whether blood flow is coupled to oxidative metabolism. 2. Seven individuals performed dynamic plantar flexion from 1 to 9 W. Radial artery and popliteal venous blood were sampled for O2, peritendinous blood flow was determined by 133Xe-washout, calf blood flow by plethysmography, cardiac output by dye dilution, arterial pressure by an arterial catheter-transducer, and muscle and peritendinous O2 saturation by spatially resolved spectroscopy (SRS). 3. Calf blood flow rose 20-fold with exercise, reaching 44 +/- 7 ml (100 g)-1 min-1 (mean +/- s.e.m. ) at 9 W, while Achilles' peritendinous flow increased (7-fold) to 14 +/- 4 ml (100 g)-1 min-1, which was 18 % of the maximal flow established during reactive hyperaemia. SRS-O2 saturation fell both in muscle (from 66 +/- 2 % at rest to 57 +/- 3 %, P < 0.05) and in peritendinous regions (58 +/- 4 to 52 +/- 4 %, P < 0.05) during exercise along with a rise in leg vascular conductance and microvascular haemoglobin volume, despite elevated systemic vascular resistance. 4. The parallel rise in calf muscle and peritendinous blood flow and fall in O2 saturation during exercise indicate that blood flow is coupled to oxidative metabolism in both tissue regions. Increased leg vascular conductance accompanied by elevated microvascular haemoglobin volume reflect vasodilatation in both muscle and peritendinous regions. However, peak exercise peritendinous blood flow reaches only approximately 20 % of its maximal blood flow capacity.

Achilles Tendon↗

Estrogen receptor (ER) and progesterone receptor (PgR), by ligand-binding assay compared with ER, PgR and pS2, by immuno-histochemistry in predicting response to tamoxifen in metastatic breast cancer: a Southwest Oncology Group Study.

Results of estrogen receptor (ER) and progesterone receptor (PgR) ligand-binding assays (LBAs) are strongly correlated with ER and PgR by immuno-histochemistry (IHC). To investigate whether ER and PgR by IHC are also strongly correlated with tamoxifen response, time to treatment failure (TTF) and overall survival (OS), the results of the 2 methods were directly compared in 205 patients with ER(+) metastatic breast cancer treated with daily tamoxifen (Southwest Oncology Group protocol 8228) with 9 years median follow-up. pS2, another estrogen-regulated molecule, was also analyzed. Tumors were scored for IHC from 0 to 5, according to the proportion of positively stained cells. These IHC scores for both ER and PgR were significantly associated with LBA levels (p < 0.001). There was a significant direct relationship between higher IHC ER, PgR and pS2 and increasing response to tamoxifen. TTF and OS were also significantly longer for patients with higher ER or PgR, but not pS2, IHC scores. Low, intermediate and high ER or PgR categories showed similar differences in response rates whether defined by LBA or IHC. In logistic regression models which included ER, PgR and pS2 by IHC; ER and PgR by LBA; and menopausal status, only ER (IHC) and pS2 (IHC) retained significance for predicting tamoxifen response (p = 0. 02 and p = 0.005, respectively), along with menopausal status (for PgR by IHC, p = 0.09). Increasing ER and PgR by IHC, as by LBA, are thus significantly associated with a progressively better response and longer survival in ER(+) metastatic breast cancer. pS2 is also predictive in this setting.

Antineoplastic Agents, Hormonal↗

Interventions for shoulder pain.

OBJECTIVES: To review the efficacy of common interventions for shoulder pain. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group trials register, Cochrane Controlled Trials Register, Medline, Embase, Cinahl, and Science Citation Index) up to May 1998, and hand searched major textbooks, bibliographies of relevant literature, the fugitive literature, and the subject indices of relevant journals including: American College of Rheumatology;British College of Rheumatologists; the Biennial Conference of the Manipulative Physiotherapy Association of Australia;International Federation of Manual Therapists conference proceedings; British Orthopaedic Association;and American Orthopaedic Association. SELECTION CRITERIA: Each identified study was assessed for possible inclusion by two independent reviewers based on the blinded methods sections. The determinants for inclusion were that the trial include an intervention of interest (non-steroidal anti-inflammatory drugs, intra-articular or subacromial glucocorticosteroid injection, oral glucocorticosteroid treatment, physiotherapy, manipulation under anaesthesia, hydrodilatation, or surgery); that treatment allocation was randomized; and that the outcome assessment was blinded. DATA COLLECTION AND ANALYSIS: Methodological quality was assessed by two independent, blinded reviewers. Data relating to selection criteria, outcome measurement and treatment effect was extracted from the blinded trials. Range of motion scores were entered as degrees of restriction to movement, and all pain and overall effect scores were transformed to 100 point scales. For continuous outcome measures, where standard deviation was not reported it was either calculated from the raw data or converted from standard error of the mean. If neither of these were reported, authors were contacted in an effort to obtain the missing values. Effect sizes were calculated and combined in a pooled analysis if study population, endpoint and intervention were comparable. MAIN RESULTS: Thirty one trials met inclusion criteria. Mean methodological quality score was 16.8 (9.5 - 22) out of possible score of 40. Selection criteria varied widely even for the same diagnostic label. There was no uniformity in outcome measures used and their measurement properties were rarely reported. Effect sizes for individual trials were small (-1.4 to 3. 0). The results of only three studies investigating rotator cuff tendonitis could be pooled. Benefit of subacromial steroid injection over placebo for improving range of abduction (weighted difference between means (WMD) 35 degrees, 95% CI 14 to 55) was the only positive finding. REVIEWER'S CONCLUSIONS: There is little evidence to support or refute the efficacy of common interventions for shoulder pain. As well as, the need for further well designed clinical trials, more research is needed to establish a uniform method of defining shoulder disorders and developing outcome measures which are valid, reliable and responsive in these study populations.

Humans↗