Search PubMed⌕ Search

Biomedical subjects

S Green

Publications and source records attributed to S Green.

At least 55 records · Page 3Linked to original sources

Haemodynamic limitations and exercise performance in peripheral arterial disease.

It has been frequently argued that haemodynamic limitations are poor predictors of exercise performance in people with peripheral arterial disease (PAD) and intermittent claudication. This review has tried to address this argument through a review of published data that appears to support or counterbalance it, brief consideration of some of the methodological limitations associated with these data, as well as some other considerations. The main argument rests primarily upon data about the resting ankle-brachial index (ABI) and/or blood flow after calf exercise or an ischaemic challenge; whereas the counter argument rests mainly on data about blood flow during walking or cyding exercise. Consideration of the limitations of all methods suggests that the measurement of blood flow during exercise has the greatest value in explaining differences in exercise performance amongst claudicants; whereas the other methods are relatively limited in their explanatory value. This strengthens the counter argument and undermines the main argument proposed by others. Consequently, asserting that haemodynamic limitations are poor predictors of exercise performance in claudicants is not justified in light of available evidence.

Exercise Test↗

Quantitative and functional differences in CD8+ lymphocyte responses in resolved acute and chronic hepatitis C virus infection.

CD8+ T lymphocyte responses are important in the clearance of viral infections. In chronic infections they may contribute to pathogenesis. To investigate the role of CD8+ T lymphocyte responses in viral clearance and chronic hepatitis C we have compared hepatitis C virus (HCV) specific cytotoxicity and interferon-gamma (IFN-gamma) production in patients with resolved-acute, and chronic HCV infection. CD8+ T cell responses to a panel of 13 HCV T cell peptide epitopes were studied using Elispot assays of IFN-gamma production and chromium release cytotoxicity assays. Responses of seven patients with resolved acute HCV infection were compared with those of 14 chronically infected patients. HCV-specific cytotoxicity differentiated the two populations of patients. The majority (71%) of patients with resolved acute infection tested positive to 42% of relevant peptides compared with the minority (28%) of patients with chronic hepatitis C (P=0.03) who responded to only 8% of relevant peptides (P=0.0009). In contrast, HCV-specific IFN-gamma production was detected in 86% of patients with either resolved or chronic infection in response to 42% and 35%, respectively, of relevant peptides tested (not significant). In patients with chronic infection the magnitude of the HCV-specific IFN-gamma production was inversely correlated to viral load (R2=0.52; P=0.042). Failure to clear HCV infection may be attributable to the presence of noncytolytic IFN-gamma producing CD8+ T lymphocytes in chronically infected patients. However these CD8+ T cells may play a beneficial role in contributing to the control of viral load in chronic hepatitis C.

Acute Disease↗

Skeletal muscle mitochondrial ATP production rate and walking performance in peripheral arterial disease.

This study tested the hypotheses that skeletal muscle mitochondrial ATP production rate (MAPR) is impaired in patients with peripheral arterial disease (PAD) and that it relates positively to their walking performances. Seven untrained patients, eight exercise-trained patients and 11 healthy controls completed a maximal walking test and had muscle sampled from the gastrocnemius medialis muscle. Muscle was analysed for its MAPR in the presence of pyruvate, palmitoyl-L-carnitine or both, as well as citrate synthase (CS) activity. MAPRs were not different between untrained PAD and controls. In contrast, MAPRs (pyruvate) were significantly higher in trained PAD vs. controls. MAPR (pyruvate combinations) was also significantly higher in trained than untrained PAD muscle. MAPR and CS activity were highly correlated with walking performance in patients, but not in controls. These data do not support the hypothesis that isolated mitochondria are functionally impaired in PAD and demonstrate that the muscle mitochondrial capacity to oxidize carbohydrate is positively related to walking performance in these patients.

Adenosine Triphosphate↗

Physiological and symptomatic responses to cycling and walking in intermittent claudication.

To shed light on the potential efficacy of cycling as a testing modality in the treatment of intermittent claudication (IC), this study compared physiological and symptomatic responses to graded walking and cycling tests in claudicants. Sixteen subjects with peripheral arterial disease (resting ankle: brachial index (ABI) < 0.9) and IC completed a maximal graded treadmill walking (T) and cycle (C) test after three familiarization tests on each mode. During each test, symptoms, oxygen uptake (VO2), minute ventilation (VE), respiratory exchange ratio (RER) and heart rate (HR) were measured, and for 10 min after each test the brachial and ankle systolic pressures were recorded. All but one subject experienced calf pain as the primary limiting symptom during T; whereas the symptoms were more varied during C and included thigh pain, calf pain and dyspnoea. Although maximal exercise time was significantly longer on C than T (690 +/- 67 vs. 495 +/- 57 s), peak VO2, peak VE and peak heart rate during C and T were not different; whereas peak RER was higher during C. These responses during C and T were also positively correlated (P < 0.05) with each other, with the exception of RER. The postexercise systolic pressures were also not different between C and T. However, the peak decline in ankle pressures from resting values after C and T were not correlated with each other. These data demonstrate that cycling and walking induce a similar level of metabolic and cardiovascular strain, but that the primary limiting symptoms and haemodynamic response in an individual's extremity, measured after exercise, can differ substantially between these two modes.

Aged↗

A preliminary comparative study of two treatment planning systems developed for boron neutron capture therapy: MacNCTPlan and SERA.

Two treatment planning systems have been specifically developed for BNCT: MacNCTPlan by the Harvard-MIT group and the SERA system developed by the INEEL/Montana State University group. In order to compare the dose components computed by the treatment planning systems, and therefore the clinical results available, it is important to first compare the basic features of the codes. This study investigated the effect of the reconstruction techniques and the form of the cross-section libraries used by the two treatment planning systems on the thermal neutron fluence distributions. Six mono-directional neutron sources of 0.0253 eV, 1 keV, 5 keV, 10 keV, 100 keV, and 1 MeV were directed onto simple geometric phantoms filled with water. The general-purpose Monte Carlo radiation transport code MCNP was used as a reference tool in this study. For the examples studied, it is found that the methods used for geometry representation (in MacNCTPlan) and for cross-section representation (in SERA) were found to impact directly on the accuracy of the calculated results.

Boron Neutron Capture Therapy↗

How reliably do rheumatologists measure shoulder movement?

OBJECTIVE: To assess the intrarater and interrater reliability among rheumatologists of a standardised protocol for measurement of shoulder movements using a gravity inclinometer. METHODS: After instruction, six rheumatologists independently assessed eight movements of the shoulder, including total and glenohumeral flexion, total and glenohumeral abduction, external rotation in neutral and in abduction, internal rotation in abduction and hand behind back, in random order in six patients with shoulder pain and stiffness according to a 6x6 Latin square design using a standardised protocol. These assessments were then repeated. Analysis of variance was used to partition total variability into components of variance in order to calculate intraclass correlation coefficients (ICCs). RESULTS: The intrarater and interrater reliability of different shoulder movements varied widely. The movement of hand behind back and total shoulder flexion yielded the highest ICC scores for both intrarater reliability (0.91 and 0.83, respectively) and interrater reliability (0.80 and 0.72, respectively). Low ICC scores were found for the movements of glenohumeral abduction, external rotation in abduction, and internal rotation in abduction (intrarater ICCs 0.35, 0.43, and 0.32, respectively), and external rotation in neutral, external rotation in abduction, and internal rotation in abduction (interrater ICCs 0.29, 0.11, and 0.06, respectively). CONCLUSIONS: The measurement of shoulder movements using a standardised protocol by rheumatologists produced variable intrarater and interrater reliability. Reasonable reliability was obtained only for the movement of hand behind back and total shoulder flexion.

Aged↗

Screening breast cancer patients for ATM mutations and polymorphisms by using denaturing high-performance liquid chromatography.

All 62 coding exons of the ATM gene, along with 10-20 bases of the intronic region flanking each exon, were screened for DNA base sequence alterations by using denaturing high-performance liquid chromatography (DHPLC) in a series of 52 breast cancer patients. Six (12%) of these patients exhibited a total of eight different novel germ-line mutations that do not represent common polymorphisms. Of these, three patients possessed four nonconservative missense mutations while two conservative missense and two synonymous mutations were detected in the other three patients. In addition, 43 patients were found to have a total of 141 DNA sequence variations representing 21 different common polymorphisms and rare variants. An analysis of the relationship between the presence of a novel ATM mutation and either patient demographics or tumor properties demonstrated a significant difference between African Americans (3/7 = 43%) and other ethnic groups (3/45 = 7%, P = 0.026). None of the other characteristics examined was found to be related to mutation status.

Adult↗

The TestSmart-HPV Program--development of an integrated approach for testing high production volume chemicals.

The TestSmart program was developed in response to the High Production Volume Chemical Challenge, a voluntary initiative under which chemical producers provide basic toxicity data on chemicals produced in greater than one million pounds annually. Specifically, under the Challenge, chemical producers will generate data as needed to complete the Screening Information Data Set (SIDS), as defined by the Organization for Economic Cooperation and Development (OECD). The TestSmart program is a collaborative effort of the Johns Hopkins Center for Alternatives to Animal Testing, the Environmental Defense Fund, Carnegie-Mellon University, and the University of Pittsburgh. The goal of the TestSmart program is to provide a humane and efficient approach to collecting SIDS data. The program has two objectives, one immediate and the other more long term. The immediate objective has been to make recommendations to reduce the number of animals used in collecting SIDS data under the Challenge. This was accomplished, through a group process, by examining the current status of alternative methods for SIDS endpoints and by providing an assessment of the "state of readiness" of current and potential future alternatives. The long-term objective is to provide a model for other programs to follow the TestSmart concept of a more efficient and humane approach to obtain toxicological data of interest to regulators and the public.

Animal Testing Alternatives↗

Antihypertensive efficacy and safety of losartan alone and in combination with hydrochlorothiazide in adult African Americans with mild to moderate hypertension.

BACKGROUND: African Americans with hypertension, particularly those with more severe blood pressure elevations, are generally less responsive to monotherapy from any antihypertensive class. These patients usually require treatment with drugs from > or = 2 antihypertensive classes to achieve adequate blood pressure control. OBJECTIVE: The purpose of this study was to assess the antihypertensive efficacy and safety of losartan alone and in combination with hydrochlorothiazide (HCTZ) in African American adults with mild to moderate hypertension. METHODS: In this 12-week, multicenter, double-blind, randomized, parallel-group, placebo-controlled study, African American patients were randomized in a 3:3:1 ratio to I of 3 treatment groups: placebo, losartan monotherapy (50 to 150 mg), or losartan plus HCTZ (50/0 to 50/12.5 to 100/25 mg). Doses were titrated at weeks 4 and 8 if sitting diastolic blood pressure (SiDBP) was > or = 90 mm Hg. Safety was assessed by determining the incidence of clinical and laboratory Adverse events and evaluating mean changes in pulse, body weight, electrocardiographic parameters, and laboratory test results. RESULTS: A total of 440 patients were randomized-188 to placebo, 193 to losartan monotherapy, and 59 to losartan/HCTZ; 391 completed the study. At week 12, the response rate with losartan monotherapy was 45.8%, with a significant (P < or = 0.01) lowering in mean SiDBP by 6.6 mm Hg compared with placebo; the response rate with placebo was 27.2%, with a mean SiDBP reduction of 3.9 mm Hg. Sitting systolic blood pressure (SiSBP) was significantly lowered with losartan monotherapy, by 6.4 mm Hg, compared with placebo (reduction of 2.3 mm Hg). The response rate with losartan/ HCTZ was 62.7%, with reductions in SiSBP and SiDBP of 16.8 mm Hg and 10.8 mm Hg, respectively (P < or = 0.01 vs placebo and losartan monotherapy). The incidence of clinical adverse events was comparable in the 3 treatment groups. CONCLUSIONS: The results of this study suggest that in African American patients, losartan monotherapy was significantly more effective than placebo in lowering SiSBP and SiDBP. Moreover, the losartan/ HCTZ combination regimen resulted in significant and clinically meaningful additional reductions in SiSBP and SiDBP compared with losartan monotherapy or placebo. Losartan monotherapy and the losartan/HCTZ regimens were generally as well tolerated as placebo.

Black or African American↗

Monosomy for the most telomeric, gene-rich region of the short arm of human chromosome 16 causes minimal phenotypic effects.

We have examined the phenotypic effects of 21 independent deletions from the fully sequenced and annotated 356 kb telomeric region of the short arm of chromosome 16 (16p13.3). Fifteen genes contained within this region have been highly conserved throughout evolution and encode proteins involved in important housekeeping functions, synthesis of haemoglobin, signalling pathways and critical developmental pathways. Although a priori many of these genes would be considered candidates for critical haploinsufficient genes, none of the deletions within the 356 kb interval cause any discernible phenotype other than alpha thalassaemia whether inherited via the maternal or paternal line. These findings contrast with previous observations on patients with larger (> 1 Mb) deletions from the 16p telomere and therefore address the mechanisms by which monosomy gives rise to human genetic disease.

Adolescent↗

Haptic perception of the horizontal by blind and low-vision individuals.

We examined haptic perception of the horizontal in visually impaired people. Blind people (late blind and congenitally blind), persons with very low vision, and blindfolded sighted individuals felt raised-line drawings of jars at four angles. They had to demonstrate their understanding that water remains horizontal, despite jar tilt, by selecting the correct raised-line drawing given four choices. Low-vision subjects, with near perfect scores, performed significantly better than the other groups of subjects. While the late-blind and blindfolded sighted subjects performed slightly better than the congenitally blind participants, the difference between the late-blind and congenitally blind groups was nonsignificant. The performance of the congenitally blind subjects indicates that visual experience is not necessary for the development of an understanding that water level stays horizontal, given container tilt.

Adult↗

Cancer prevention in rural youth: teaching goals for health: the pilot.

BACKGROUND: The Goals for Health project is designed to change the cancer-related behaviors of tobacco use and dietary fat and fiber consumption. The intervention teaches health and life skills to rural, minority sixth and seventh graders in rural Virginia and New York. This article presents the results of the pilot. METHODS: Participants were 129 sixth graders at one rural middle school who were surveyed prior to and following delivery of the pilot sixth-grade intervention. RESULTS: Results include significant changes from pre- to post-intervention in several diet and smoking attitude and self-efficacy variables, dietary fat and fiber knowledge, high-fat snack consumption, and dietary fat scores. Multivariate analyses reveal important contributions of personal control over food choices and family and friend influence on change in dietary fat score from pre- to post-intervention. CONCLUSIONS: These pilot program results suggest avenues for dietary and cancer prevention interventions in high-risk, rural adolescents.

Child↗

The measurement of thermal neutron flux depression for determining the concentration of boron in blood.

Boron neutron capture therapy (BNCT) is a form of targeted radiotherapy that relies on the uptake of the capture element boron by the volume to be treated. The treatment procedure requires the measurement of boron in the patient's blood. The investigation of a simple and inexpensive method for determining the concentration of the capture element 10B in blood is described here. This method, neutron flux depression measurement, involves the determination of the flux depression of thermal neutrons as they pass through a boron-containing sample. It is shown via Monte Carlo calculations and experimental verification that, for a maximum count rate of 1 x 10(4) counts/s measured by the detector, a 10 ppm 10B sample of volume 20 ml can be measured with a statistical precision of 10% in 32 +/- 2 min. For a source activity of less than 1.11 x 10(11) Bq and a maximum count rate of less than 1 x 10(4) counts/s, a 10 ppm 10B sample of volume 20 ml can be measured with a statistical precision of 10% in 58 +/- 3 min. It has also been shown that this technique can be applied to the measurement of the concentration of any element with a high thermal neutron cross section such as 157Gd.

Boron↗

A computational study into the use of polyacrylamide gel and A-150 plastic as brain tissue substitutes for boron neutron capture therapy.

A precise evaluation of the dosimetric performance of epithermal neutron beams designed for boron neutron capture theory of brain tumours requires the use of a phantom material that closely matches brain tissue. The aim of this study was to investigate how well polyacrylamide gel (or PAG) and A- 150 plastic performed as substitutes for brain tissue compared with standard phantom materials such as water and polymethyl-methacrylate (or PMMA). Thermal neutron fluence, photon dose and epithermal neutron dose distributions were calculated for the epithermal neutron beam available at the University of Birmingham. The results presented in this paper show that the PAG provides a good simulation of radiation transport in the brain with differences from the real brain of +9.4%, - 10.8% and +5.1% at a depth of 50 mm for thermal neutron fluence, gamma dose and epithermal neutron dose distributions respectively. The polyacrylamide gel presented is therefore a promising substitute for brain tissue that can, as a dosimeter, provide a three-dimensional map of the absorbed dose delivered by the epithermal neutron beam. However, this study does not investigate the agreement between doses derived from magnetic resonance and physical doses for such gels. A- 150 plastic was shown to be a better substitute for brain tissue than PMMA, with differences from brain of -1.9%, -12.4% and - 13.2% at a depth of 50 mm for thermal neutron fluence, gamma dose and epithermal neutron dose distributions respectively, against +21.1%, -16.2% and +19.2% for PMMA. A-150 plastic should therefore be the material of choice for solid phantoms.

Acrylic Resins↗

Adjuvant therapy for very young women with breast cancer: need for tailored treatments.

Breast cancer rarely occurs in women below the age of 35 years. Data from various sources indicate that diagnosis at such an age is associated with a dire prognosis mainly because of a more aggressive presentation. Although the effect of chemotherapy for premenopausal patients is substantial, recent evidence on 2233 patients suggested that very young women with endocrine-responsive tumors had a statistically significantly higher risk of relapse than older premenopausal patients with such tumors. In contrast, results for younger and older premenopausal patients were similar if their tumors were classified as endocrine nonresponsive. Information from studies on 7631 patients who were treated with chemotherapy alone in trials of three major U.S. cooperative groups showed a similar interaction between the effect of age and steroid hormone receptor status of the primary tumor. Better treatments for very young patients are required and may involve ovarian function suppression in addition to other endocrine agents in patients with endocrine responsive tumors and a more precise investigation of chemotherapy and its timing, duration, and intensity in those with endocrine nonresponsive tumors. Very young women with this disease are faced with personal, family, professional, and quality-of-life issues, which further complicate the phase of treatment decision making. The development of more effective therapies for younger patients requires tailored treatment investigations and cannot rely on information predominantly contributed from older premenopausal women.

Adult↗