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Biomedical subjects

A Coutts

Publications and source records attributed to A Coutts.

At least 19 recordsLinked to original sources

Changes in selected biochemical, muscular strength, power, and endurance measures during deliberate overreaching and tapering in rugby league players.

The purpose of this study was to examine the influence of overreaching on muscle strength, power, endurance and selected biochemical responses in rugby league players. Seven semi-professional rugby league players (.VO(2max) = 56.1 +/- 1.7 mL . kg (-1) . min (-1); age = 25.7 +/- 2.6 yr; BMI = 27.6 +/- 2.0) completed 6 weeks of progressive overload training with limited recovery periods. A short 7-day stepwise reduction taper immediately followed the overload period. Measures of muscular strength, power and endurance and selected biochemical parameters were taken before and after overload training and taper. Multistage fitness test running performance was significantly reduced (12.3 %) following the overload period. Although most other performance measures tended to decrease following the overload period, only peak hamstring torque at 1.05 rad . s (-1) was significantly reduced (p < 0.05). Following the taper, a significant increase in peak hamstring torque and isokinetic work at both slow (1.05 rad . s (-1)) and fast (5.25 rad . s (-1)) movement velocities were observed. Minimum clinically important performance decreases were measured in a multistage fitness test, vertical jump, 3-RM squat and 3-RM bench press and chin-up (max) following the overload period. Following the taper, minimum clinically important increases in the multistage fitness test, vertical jump, 3-RM squat and 3-RM bench press and chin-up (max) and 10-m sprint performance were observed. Compared to resting measures, the plasma testosterone to cortisol ratio, plasma glutamate, plasma glutamine to glutamate ratio and plasma creatine kinase activity demonstrated significant changes at the end of the overload training period (p < 0.05). These results suggest that muscular strength, power and endurance were reduced following the overload training, indicating a state of overreaching. The most likely explanation for the decreased performance is increased muscle damage via a decrease in the anabolic-catabolic balance.

Adult↗

Clinical and functional results of open operative repair for Achilles tendon rupture in a non-specialist surgical unit.

We followed up 25 patients (average age 47.9 years, range 22 to 77) after open repair of their Achilles tendon rupture. All had been operated on by a single general surgeon using an end-to-end reabsorbable suture, and immobilised in a plaster of Paris cast for six weeks. All patients had been discharged from follow up by 18 weeks from the operation. At an average of 3.4 years (range six months to 9.25 years), 18 had "excellent", six (24%) "good" and one (4%) "satisfactory" results. All but one patient were able to walk on tiptoes, and 20 of the 22 patients examined directly walked without a limp. Ultrasonography showed the injured tendons to be on average 2.3 times thicker in the antero-posterior diameter and 1.7 times thicker in the transverse diameter. In the hands of a single non-specialist but fully trained general surgeon, this management regimen produced full return to pre-operative activities in the majority of patients, and a low rate of local complications. The macroscopic and ultrasonographic appearance of the operated tendon remained abnormal, but this was not associated with any overt clinical disturbance

Achilles Tendon↗

Release of biologically active TGF-beta from airway smooth muscle cells induces autocrine synthesis of collagen.

In severe or chronic asthma, there is an increase in airway smooth muscle cell (ASMC) mass as well as an increase in connective tissue proteins in the smooth muscle layer of airways. Transforming growth factor-beta (TGF-beta) exists in three isoforms in mammals and is a potent regulator of connective tissue protein synthesis. Using immunohistochemistry, we had previously demonstrated that ASMCs contain large quantities of TGF-beta1-3. In this study, we demonstrate that bovine ASMC-derived TGF-beta associates with the TGF-beta latency binding protein-1 (LTBP-1) expressed by the same cells. The TGF-beta associated with LTBP-1 localizes TGF-beta extracellularly. Furthermore, plasmin, a serine protease, regulates the secretion of a biologically active form of TGF-beta by ASMCs as well as the release of extracellular TGF-beta. The biologically active TGF-beta released by plasmin induces ASMCs to synthesize collagen I in an autocrine manner. The autocrine induction of collagen expression by ASMCs may contribute to the irreversible fibrosis and remodeling seen in the airways of some asthmatics.

Animals↗

The effects of chloroquine on bleeding time and disappearance of platelet 5-hydroxytryptamine in rabbits.

BACKGROUND: Chloroquine inhibits platelet aggregation in vitro and in vivo. Because inhibition of platelet aggregation may prolong bleeding time, the effect of chloroquine administration on bleeding time and disappearance of platelet serotonin, which may affect bleeding time, were studied. METHODS AND RESULTS: Platelets were harvested from 12 rabbits. They were labelled with (111)In to tag individual platelets and (14)C-labelled 5-hydroxytryptamine (5HT) or serotonin. Doubly labelled platelets from the rabbits were returned to their donors. At timed intervals, from 2 to 66 hours, blood samples were drawn and platelets collected. (111)In and (14)C were separately counted. In 6 experiments, the animals served as control and received normal saline intraperitoneally (IP) daily for 4 days; the other 6 rabbits served as test and were given a therapeutic dose of chloroquine phosphate (10 mg/kg, IP) daily for 4 days. Indium disappeared in an exponential fashion in both control and test groups. The fraction of indium disappearing per hour was significantly less in chloroquine-treated rabbits than in control rabbits (P <.001). Ninety-nine percent of the indium-labelled platelets disappeared in 7.0 days in chloroquine-treated rabbits and 5.8 days in control rabbits (P <.001). Bleeding times in chloroquine-treated and control rabbits were not significantly different (64.8 +/- 2.2 vs. 62.3 +/- 4.0 sec, respectively). However, the labelled platelet serotonin disappeared more slowly in chloroquine-treated rabbits than in control rabbits. (K for chloroquine-treated and control rabbits was 0.0096 +/- 0.0064 and 0. 0254 +/- 0.0016; respectively, P <.001). CONCLUSION: Chloroquine prolongs platelet survival but does not affect bleeding time in rabbits. Chloroquine also slows down the disappearance of labelled platelet serotonin. We propose that chloroquine increases the recycling of platelet 5HT, passing it on from platelet to platelet in rabbits and this may have a role in the maintenance of hemostasis.

Animals↗

Characterization of cerebral white matter damage in preterm infants using 1H and 31P magnetic resonance spectroscopy.

The biochemical characteristics of white matter damage (WMD) in preterm infants were assessed using magnetic resonance spectroscopy (MRS). The authors hypothesized that preterm infants with WMD at term had a persisting cerebral lactic alkalosis and reduced N-acetyl aspartate (NAA)/ creatine plus phosphocreatine (Cr), similar to that previously documented in term infants weeks after perinatal hypoxiaischemia (HI). Thirty infants (gestational age 27.9 +/- 3.1 weeks, birth weight 1,122 +/- 445 g) were studied at postnatal age of 9.8 +/- 4.1 weeks (corrected age 40.3 +/- 3.9 weeks). Infants were grouped according to the presence or absence of WMD on magnetic resonance (MR) images. The peak area ratios of lactate/Cr, NAA/Cr, myo-inositol/Cr, and choline (Cho)/Cr were measured from an 8-cm3 voxel in the posterior periventricular white matter (WM) using proton MRS. Intracellular pH (pHi) was calculated using phosphorus MRS. Eighteen infants had normal WM on MR imaging; 12 had WMD. For infants with WMD, lactate/Cr and myo-inositol/Cr were related (P < 0.01); lactate/Cr and pHi were not (P = 0.8). In the WMD group, mean lactate/Cr and myo-inositol/Cr were higher (P < 0.001, P < 0.05, respectively) than the normal WM group. There was no difference in the NAA/Cr, Cho/Cr, or pHi between the two groups, although pHi was not measured in all infants. These findings suggest that WMD in the preterm infant at term has a different biochemical profile compared with the term infant after perinatal HI.

Brain↗

Changes in HIV-related risk behaviors following drug abuse treatment.

OBJECTIVES: To measure changes in HIV-related injection drug and sexual risk behaviors following drug treatment in a therapeutic community program. METHODS: We conducted a prospective cohort study of 261 drug users, randomly assigned to day or residential treatment. Participants were interviewed 2 weeks after entering treatment and 6, 12 and 18 months later (follow-up rate: 83%). RESULTS: Greater reductions in injection risk behaviors were associated with more time in treatment and the later waves of measurement. Wave was also associated with a reduction of sexual risk behavior. CONCLUSIONS: Drug abuse treatment was associated with a decrease in HIV-related risk behavior.

Adult↗

The pathophysiological role of estrogen receptor variants in human breast cancer.

The accumulated evidence supports the expression of estrogen receptor variants at both the mRNA and protein levels. The relative level of expression of some estrogen receptor variant mRNAs and possibly progesterone receptor variant mRNAs is altered during breast tumorigenesis and breast cancer progression. The altered expression of estrogen receptor variants may effect estrogen signal transduction as well as the interpretation of assays where the estimation of estrogen receptor levels is used as a guide to treatment strategies and prognosis.

Breast Neoplasms↗

The "minor" problems of pregnancy: a review.

The so-called minor problems of pregnancy are often a significant cause of discomfort and anxiety to women, who look to the health professional for up-to-date advice and explanation.

Female↗

Estrogen receptor variants and mutations.

There is a large and increasing body of experimental and clinical data supporting the existence or variant estrogen receptor (ER) proteins in both normal and neoplastic estrogen target tissues including human breast. Therefore, future examination of ER signal transduction and/or measurement of ER protein must take into account variant ER expression. The functions of variant ER proteins, either physiological or pathological, remain unclear, although a role(s) for some ER variants in breast tumorigenesis and breast cancer progression would be consistent with the accumulated data. Possible tissue specific expression leads to the speculation that ER variants may have a role in tissue specific estrogen action. The following review focuses on the current knowledge available in the scientific literature with respect to the type and characteristics of estrogen receptor variants and mutations that have been identified to occur naturally in tissues and cell lines.

Animals↗

Oestrogen receptor variants and mutations in human breast cancer.

Several oestrogen receptor variant and mutated mRNA species have been identified in human breast samples and cell lines. Over-expression and altered expression of some of these mRNAs have been correlated with breast tumourigenesis and progression. The following review focuses on the current knowledge available in the scientific literature with respect to the type and characteristics of oestrogen receptor variants and mutations that have been identified as occurring naturally in human breast tissues and cell lines.

Animals↗

Feasibility of monitoring patient based health outcomes in a routine hospital setting.

OBJECTIVE: To assess the feasibility of monitoring health outcomes in a routine hospital setting and the value of feedback of outcomes data to clinicians by using the SF 36 health survey questionnaire. DESIGN: Administration of the questionnaire at baseline and three months, with analysis and interpretation of health status data after adjustments for sociodemographic variables and in conjunction with clinical data. Exploration of usefulness of outcomes data to clinicians through feedback discussion sessions and by an evaluation questionnaire. SETTING: One gastroenterology outpatient department in Aberdeen Royal Hospitals Trust, Scotland. PATIENTS: All (573) patients attending the department during one month (April 1993). MAIN MEASURES: Ability to obtain patient based outcomes data and requisite clinical information and feed it back to the clinicians in a useful and accessible form. RESULTS: Questionnaires were completed by 542 (95%) patients at baseline and 450 (87%) patients at follow up. Baseline health status data and health outcomes data for the eight different aspects of health were analysed for individual patients, key groups of patients, and the total recruited patient population. Significant differences were shown between patients and the general population and between different groups of patients, and in health status over time. After adjustment for differences in sociodemography and main diagnosis patients with particularly poor scores were identified and discussed. Clinicians judged that this type of assessment could be useful for individual patients if the results were available at the time of consultation or for a well defined group of patients if used as part of a clinical trial. CONCLUSIONS: Monitoring routine outcomes is feasible and instruments to achieve this, such as the SF 36 questionnaire, have potential value in an outpatient setting. IMPLICATIONS: If data on outcomes are to provide a basis for clinical and managerial decision making, information systems will be required to collect, analyse, interpret, and feed it back regularly and in good time.

Adolescent↗

Expression of insulin-like growth factor binding proteins by T-47D human breast cancer cells: regulation by progestins and antiestrogens.

We have used ligand blotting and Northern blotting techniques to examine the effects of progestins and antiestrogens on expression of insulin-like growth factor binding proteins (IGFBPs) by T-47D human breast cancer cells under conditions where these agents are growth inhibitory. Under basal conditions, conditioned medium from T-47D cells was found to contain IGFBPs of 39, 33, and 27 kDa. Northern blot and/or Western blot analysis have identified these as IGFBP 2, 5, and 4, respectively. Medroxyprogesterone acetate (MPA) treatment resulted in a time- and dose-dependent decrease in IGFBP 4 and 5 mRNA abundance and secretion of these proteins, while little if any effect was observed on IGFBP 2 expression. A decrease in the steady state mRNA levels for IGFBP 4 and 5 was observed with as little as 0.1 nM MPA. Using 10 nM MPA a maximum decrease in IGFBP 4 and 5 mRNA levels was observed between 12 and 24 hours. While RU 486 alone had little or no effect on IGFBP 4 expression, it inhibited the effect of MPA. However, in the same samples, IGFBP 5 expression was inhibited by RU 486, and RU 486 was unable to reverse the effects of progestins on the expression of IGFBP 5. Furthermore, another synthetic progestin, Org 2058, but not dexamethasone, inhibited IGFBP 4 and IGFBP 5 expression. The antiestrogen ICI 164384 also transiently decreased the steady state mRNA levels of both IGFBP 4 and IGFBP 5. Regulation of expression of the IGFBPs by these agents suggests a potential role for the IGFBPs in the growth response of T-47D cells to these agents.

Breast Neoplasms↗

Non-Hodgkin's lymphoma in elderly patients: a phase II study of MCOP chemotherapy in patients aged 70 years or over with intermediate- or high-grade histology.

During the period 1 January 1988 to 31 July 1991, 74 patients were seen with intermediate- or high-grade non-Hodgkin's lymphoma who were aged 70 years or over. Of these 74 patients, 20 were treated with radiotherapy alone, and 46 were judged as suitable for treatment with the chemotherapy regime MCOP (mitoxantrone, cyclophosphamide, vincristine and prednisolone). Involved field radiotherapy (35-40 Gy in 20 fractions over 4 weeks) was given to 14 of the 21 patients with stage IA and IIA disease, and 6 of the 25 patients with stage III and IV disease after completion of chemotherapy. The complete response rate was 63% at the completion of all treatment (6 months), and 39% at 12 months. There were no treatment-related deaths, and the 3-year cause-specific survival was 26% (overall survival 21%). For patients aged 70-75 years, the 3-year cause-specific survival was 34% in comparison to 17% for those patients aged 76-93 years. The chemotherapy was well tolerated by those patients aged 70 years and over, 70% of the patients did not vomit and no patients had significant vincristine neuropathy. There were only four infections associated with neutropenia. All patients completing six cycles had moderate, patchy alopecia. This MCOP regime is suitable for patients aged 70 years and over with intermediate- and high-grade non-Hodgkin's lymphoma. The survival of patients is comparable to that obtained with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) with less apparent toxicity.

Aged↗

Regulation of gene expression in T-47D human breast cancer cells by progestins and antiprogestins.

The molecular mechanisms by which progestins and antiprogestins inhibit human breast cancer cell growth are essentially unknown. The mechanisms by which they mediate growth inhibition in human breast cancer cells and the expression of the putative autocrine/paracrine growth factors, epidermal growth factor and transforming growth factors alpha and beta-1 were studied under conditions in which progestin and antiprogestin inhibit the growth of T-47D human breast cancer cells in culture. Under the same conditions, the expression of genes such as c-myc, c-jun and c-fos, which are known to have important roles in growth and differentiation, has been measured. The results indicate that progestins and antiprogestins differentially regulate expression of these genes. The data are consistent with the conclusion that the mechanism of growth inhibition of these two agents differs, although an initial interaction with the progesterone receptor is a necessary first step in initiating the as yet ill-defined cascade of events leading to growth inhibition.

Breast Neoplasms↗

SF 36 health survey questionnaire: I. Reliability in two patient based studies.

OBJECTIVE: To assess the reliability of the SF 36 health survey questionnaire in two patient populations. DESIGN: Postal questionnaire followed up, if necessary, by two reminders at two week intervals. Retest questionnaires were administered postally at two weeks in the first study and at one week in the second study. SETTING: Outpatient clinics and four training general practices in Grampian region in the north east of Scotland (study 1); a gastroenterology outpatient clinic in Aberdeen Royal Hospitals Trust (study 2). PATIENTS: 1787 patients presenting with one of four conditions: low back pain, menorrhagia, suspected peptic ulcer, and varicose veins and identified between March and June 1991 (study 1) and 573 patients attending a gastroenterology clinic in April 1993. MAIN MEASURES: Assessment of internal consistency reliability with Cronbach's alpha coefficient and of test-retest reliability with the Pearson correlation coefficient and confidence interval analysis. RESULTS: In study 1, 1317 of 1746 (75.4%) correctly identified patients entered the study and in study 2, 549 of 573 (95.8%). Both methods of assessing reliability produced similar results for most of the SF 36 scales. The most conservative estimates of reliability gave 95% confidence intervals for an individual patient's score difference ranging from -19 to 19 for the scales measuring physical functioning and general health perceptions, to -65.7 to 65.7 for the scale measuring role limitations attributable to emotional problems. In a controlled clinical trial with sample sizes of 65 patients in each group, statistically significant differences of 20 points can be detected on all eight SF 36 scales. CONCLUSIONS: All eight scales of the SF 36 questionnaire show high reliability when used to monitor health in groups of patients, and at least four scales possess adequate reliability for use in managing individual patients. Further studies are required to test the feasibility of implementing the SF 36 and other outcome measures in routine clinical practice within the health service.

Adolescent↗

Bone marrow involvement in non-Hodgkin's lymphoma in Zimbabwe.

Lymph node and bone marrow trephine biopsies of seventy two consecutive cases of non-Hodgkin's lymphoma occurring among black Zimbabweans were reviewed to determine bone marrow involvement. The bone marrow was involved in 23.6% of patients but the proportion of bone marrow positive cases was highest in low grade lymphomas, though these were the least common type of lymphoma encountered. Cells infiltrating the marrow showed high degree of concordance with corresponding lymph node histology. Low grade lymphomas (CLL excluded) had a predominantly diffuse pattern of marrow involvement while intermediate and high grade lymphomas had nearly equal proportions with diffuse and focal patterns. Bone-marrow involvement did not make a significant difference to the staging of non-Hodgkin's lymphoma as most cases not involving the marrow also presented with advanced disease. Mean age of patients was negatively correlated with histological grade but was not related to bone marrow involvement. Central nervous system involvement occurred mostly in the high grade lymphomas and was proportionately distributed between bone marrow positive and negative cases. 40% of non-Hodgkin's lymphoma were associated with HIV infection but HIV-associated lymphoma surprisingly very rarely infiltrated the bone marrow.

Adult↗

Mechanisms of growth inhibition by antiestrogens and progestins in human breast and endometrial cancer cells.

Marked changes in both growth factor and proto-oncogene expression occur due to treatment of hormonally-responsive human cancers with progestins and antiestrogens. In human endometrial cancer cell lines the antiproliferative effects of progestins and antiestrogens in a particular cell line appear to be associated with similar effects on growth factor and/or proto-oncogene expression. This suggests that although these compounds initially interact with different steroid hormone receptors, the molecular mechanisms of their growth inhibition may be essentially similar. In the case of human breast cancer cell lines, however, the effects of progestins and antiestrogens on gene regulation are often different, suggesting that the molecular mechanisms of progestin and antiestrogen growth inhibition may be essentially dissimilar.

Breast Neoplasms↗