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Biomedical subjects

S Armstrong

Publications and source records attributed to S Armstrong.

At least 55 records · Page 3Linked to original sources

Peripheral arterial compliance is lower in Afro-Caribbeans compared to white Caucasians with type 2 diabetes after adjustment for blood pressure.

Arterial compliance declines with age. However this decline occurs more rapidly in both the hypertensive and diabetic states. Afro-Caribbeans have a higher prevalence of hypertension and other complications of diabetes than the indigenous white Caucasian population. We hypothesise that accelerated decline in arterial compliance may account for this racial difference. Forty-one volunteers, age 62.5 +/- 6.8 years (mean +/- s.d., range 48-75), were selected from diabetic clinics. Twenty-one were Caucasian and 20 were Afro-Caribbean. Pulse wave velocity (PWV) was measured using non-invasive techniques: the 'Complior' system was used to record PWV in the carotid-to-radial (C-R) and carotid-to-femoral (C-F) regions. Central arterial compliance (CAC) was measured by simultaneous aortic flow velocimetry and carotid artery applanation tonometry. The duration of diabetes was taken as the time from clinical diagnosis. Baseline characteristics in the two racial groups were comparable for age, BMI, cholesterol, HbA1c, blood pressure and duration of diabetes. Comparing the PWV in the C-F region showed that the mean PWV was 13.84 +/- 0.28 m/sec in the Caucasians and 13.97 +/- 0.34 m/sec in the Afro-Caribbeans (P = 0. 86) whereas in the C-R region the mean PWV was 11.13 +/- 0.28 m/sec in Caucasians and 12.10 +/- 0.34 m/sec in the Afro-Caribbeans (P = 0. 03). In agreement with the C-F findings there was no statistical difference in CAC between the two races. Adjustment of PWV in the carotid-radial (C-R) region for systolic and diastolic blood pressure, confirmed that the racial differences were independent of blood pressure (difference 0.91 m/sec, P = 0.046 after adjustment for diastolic pressure and 0.89 m/sec, P = 0.056 after adjustment for both systolic and diastolic blood pressure). Accelerated decline in peripheral arterial compliance may account for the increased stroke rate with diabetes in Afro-Caribbeans.

Adaptation, Physiological↗

Pharmacokinetics of carprofen enantiomers in equine plasma and synovial fluid - a comparison with ketoprofen.

Carprofen is a Non Steroidal Anti-Inflammatory Drug (NSAID) which is widely used for the treatment of musculoskeletal disorders in horses. The commercial preparation is a racemic mixture of two enantiomers (R and S carprofen). We used HPLC to measure plasma and synovial fluid R and S carprofen concentrations following a single intravenous (i.v.) dose, and computer modelling to determine the pharmacokinetic parameters of the enantiomers in these two body fluids. A comparison was made with results from an identical experiment using ketoprofen. The plasma elimination half lives of R and S carprofen were 20 and 16 times longer than those of R and S ketoprofen, and clearance was considerably slower for carprofen than ketoprofen. Plasma R carprofen concentrations were higher than S carprofen concentrations throughout the 48-h period. Ketoprofen was no longer detectable in synovial fluid after 5 h (S enantiomer) or 12 h (R enantiomer), whereas synovial fluid carprofen concentrations did not peak until 12 h and were still detectable at 48 h. Synovial fluid concentrations of both carprofen enantiomers were significantly lower than plasma concentrations, probably due to high plasma protein binding which could limit transfer through the synovial membrane. Our results indicate significant differences between carprofen and ketoprofen and between the two carprofen enantiomers.

Animals↗

Methodological and clinical challenges in evaluating treatment outcome of substance-related disorders and comorbidity.

OBJECTIVE: To review the steps required to develop an outcome evaluation package and to report on the 12-month outcome of an integrated day program. METHOD: Based on the identification of salient outcome predictors, standardized instruments were selected. A cohort of 78 patients was assessed at the time of admission to the program, at discharge, and 3, 6, and 12 months afterward. RESULTS: Improvements were sustained over 1 year in all areas including treatment needs, quality of life, and readiness to change. CONCLUSIONS: The gap between the "cultures" of treatment and research must be narrowed. Following evidence of a program's general effectiveness through outcome monitoring, a randomized control design is optimal for specific interventions. The optimal length of follow-up depends on the perceived confounds.

Adult↗

Implications of depression on outcome from alcohol dependence: a 3-year prospective follow-up.

The prognostic implications of comorbid depression for outcome from alcohol dependence are unclear. It has been suggested that drinking may represent self-medication of depressive disorders and, alternatively, that the pharmacological properties of alcohol induce episodes of depression. In the present study, these questions were investigated by following 84 alcohol-dependent individuals seeking treatment (34% women) for 3 years in a naturalistic, prospective design. During the follow-up period, depressive and drinking outcomes were significantly related. However, there was no evidence that drinking reliably preceded depressive episodes or that depressive episodes precipitated heavy drinking. Despite their high co-occurrence, this study did not find evidence of a strong, direct causal relationship between these phenomena.

Adolescent↗

Effects of R and S enantiomers and a racemic mixture of carprofen on the production and release of proteoglycan and prostaglandin E2 from equine chondrocytes and cartilage explants.

OBJECTIVE: To examine effects of carprofen (enantiomers and a racemic mixture) on the metabolism of equine chondrocytes. SAMPLE POPULATION: Cartilage from clinically normal horses. PROCEDURE: Effects of carprofen on proteoglycan neosynthesis, glycosaminoglycan (GAG) release and prostaglandin (PG) E2 production by unstimulated chondrocyte monolayers and cartilage explants were examined, as were similar variables in monolayers and explants exposed to carprofen and recombinant human interleukin 1beta (IL-1). Carprofen (enantiomers and racemic mixture) was used alone or along with IL-1 on monolayers and explant cultures. Medium was collected 48 to 96 hours later, and cartilage was digested. Proteoglycan synthesis was assessed as the amount of 35S-labeled proteoglycan in medium and digested cartilage. Total GAG content of the medium and digested cartilage was measured, and proteoglycan degradation was calculated. Radioimmunoassay was used to measure PGE2 production. RESULTS: Carprofen significantly decreased PGE2 production by unstimulated chondrocytes and antagonized an IL-1-induced increase in PGE2 production. Carprofen significantly increased proteoglycan synthesis in unstimulated monolayers and explants. Concurrently, there was a decrease in GAG release by explants. Use of IL-1 significantly decreased proteoglycan synthesis, but the highest concentrations of carprofen partially reversed this effect in chondrocyte monolayers. CONCLUSIONS: Carprofen had a potentially beneficial effect on proteoglycan metabolism of equine chondrocytes. This effect was sufficiently strong at the highest concentrations to overcome inhibitory effects of IL-1 on proteoglycan synthesis. Carprofen also inhibited PGE2 production by unstimulated and IL-1-stimulated chondrocytes. Carprofen induced these enantiomer-specific effects. CLINICAL RELEVANCE: Use of carprofen in osteoarthritic horses may induce beneficial changes in articular cartilage matrix.

Animals↗

Alloantigen gene therapy for squamous cell carcinoma of the head and neck: results of a phase-1 trial.

OBJECTIVE: To determine the safety and efficacy of an immunogenic gene therapy using a drug designed to produce expression of a foreign class I major histocompatibility complex protein in patients with head and neck cancer. DESIGN: Phase 1 prospective clinical trial. SETTING: Academic medical setting. PATIENTS: Nine patients with advanced head and neck squamous cell carcinoma who had failed conventional therapy and did not express HLA-B7, a class I major histocompatibility complex protein. INTERVENTION: Patients were treated with Allovectin-7 (Vical Inc, San Diego, Calif) by direct intratumoral injection. Allovectin-7 contains a plasmid complementary DNA complexed with a cationic lipid, which results in expression of HLA-B7. MAIN OUTCOME MEASURES: Patients were assessed for any toxic effects and for any change in tumor volume. Biopsy specimens obtained before and after therapy were evaluated by immunohistochemistry to detect HLA-B7 expression and with the terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assay to detect any induction of apoptosis. RESULTS: There were no toxic effects of the gene therapy. In 4 of these 9 patients there was a partial response to treatment, evidenced by a gradual reduction in tumor size. One patient has remained alive for more than 17 months since commencing treatment, with no clinical evidence of disease but with persistent histological evidence of cancer. Analysis of the biopsy specimens from 2 of the patients who responded to therapy demonstrated HLA-B7 expression. The TUNEL assay demonstrated extensive apoptosis in both of these patients, suggesting that this may be the mechanism of tumor reduction. CONCLUSIONS: These data demonstrate the potential efficacy and lack of toxicity of this form of alloantigen gene therapy. A multi-institutional study has been initiated to expand on these findings.

Adult↗

The Hancock II bioprosthesis at 12 years.

BACKGROUND: The Hancock II bioprosthesis has been used for heart valve replacement since 1982 in our institution. We previously reported its clinical performance at 8 years and at 10 years. This is a progress report on its performance at 12 years. METHODS: From 1982 to 1994 the Hancock II bioprosthesis was used for aortic valve replacement (AVR) in 723 patients and for mitral valve replacement (MVR) in 328 patients. The mean age of the patients was 65 years for both groups. Coronary artery disease was present in 42% of patients who had AVR and 45% of patients who had MVR. Patients have been followed up prospectively at annual intervals; the mean follow-up was 68+/-40 months for AVR and 66+/-43 months for MVR; it was 99% complete. RESULTS: There were 36 (5%) operative and 159 late deaths in the AVR group, and 26 (8%) operative and 92 late deaths in the MVR. The actuarial survival at 12 years was 54%+/-4% for AVR and 42%+/-5% for MVR. Age greater than 65 years and coronary artery disease had a profound effect on late survival. At 12 years the freedom from thromboembolism was 86%+/-2% for AVR and 90% +/-2% for MVR; from endocarditis, 95%+/-1% for both groups; from primary tissue failure, 94%+/-2% for AVR and 82%+/-5% for MVR; and from valve reoperation, 89% +/-3% for AVR and 78%+/-5% for MVR. There was no primary tissue failure at 12 years in patients older than 65 years who had AVR. CONCLUSIONS: The clinical performance of the Hancock II has been very satisfactory and this bioprosthesis appears to be more durable than its predecessors.

Adolescent↗

Aortic valve replacement with stentless and stented porcine valves: a case-match study.

OBJECTIVES: To assess the potential benefits of the hemodynamic superiority of stentless valves, we conducted a case-match study among patients who underwent aortic valve replacement with two types of porcine bioprostheses: the Toronto SPV and the stented Hancock II bioprosthesis. METHODS: Preoperative clinical variables predictive of death after aortic valve replacement were determined by a stepwise logistic regression analysis in a series of 908 consecutive patients who received porcine aortic bioprostheses during a 14-year interval. Advanced age, New York Heart Association functional class IV, left ventricular ejection fraction of less than 30%, and coronary artery disease were independent predictors of death. On the basis of these four variables, 198 pairs of patients who survived aortic valve replacement with stentless and stented porcine valves were matched. The follow-up, truncated to the shortest interval for each matched pair, was 43 +/- 24 months for both groups. RESULTS: At 8 years the actuarial survival was 91% +/- 4% for the Toronto SPV group and 69% +/- 8% for the Hancock II group (p = 0.006); the freedom from cardiac-related death was 95% +/- 4% for the Toronto SPV and 81% +/- 8% for the Hancock II (p = 0.01); the freedom from any valve-related complication was 81% +/- 5% for the Toronto SPV and 50% +/- 10% for the Hancock II (p = 0.008). A Cox proportional hazard model demonstrated a significant reduction in cardiac mortality rates and valve-related morbidity in patients who received the Toronto SPV bioprosthesis. CONCLUSIONS: Although it is possible that confounding factors may have played a role in the clinical outcomes of this case-control study, the study suggests that aortic valve replacement with a stentless porcine valve enhances survival. This is believed to be due to the hemodynamic superiority of these valves.

Adult↗

Long-term results of mitral valve repair for myxomatous disease with and without chordal replacement with expanded polytetrafluoroethylene sutures.

OBJECTIVE: This study was carried out to evaluate the long-term results of mitral valve repair for mitral regurgitation caused by myxomatous disease of the mitral valve and the late effects of chordal replacement with expanded polytetrafluoroethylene sutures in this operation. METHODS: A total of 324 patients with mitral regurgitation caused by myxomatous disease underwent mitral valve repair from 1981 to 1995; the group comprised 241 men and 83 women whose mean age was 58 +/- 14 years. Chordal replacement with expanded polytetrafluoroethylene sutures has been performed in 165 patients since 1985. Most of the patients who had chordal replacement with expanded polytetrafluoroethylene sutures had prolapse of the anterior leaflet or prolapse of both leaflets, whereas most patients who had mitral valve repair without chordal replacement had prolapse of the posterior leaflet. Patients were followed up at annual intervals and had a Doppler echocardiographic study. The follow-up was complete and extended from 6 to 156 months (mean 36 +/- 30 months). RESULTS: Two operative and 21 late deaths occurred (14 cardiac and 7 noncardiac). At 10 years the actuarial survival was 75% +/- 5%, the freedom from stroke was 94% +/- 2%, the freedom from transient ischemic attacks was 92% +/- 4%, the freedom from endocarditis was 99% +/- 1%, the freedom from mitral valve reoperation was 96% +/- 1%, and the freedom from severe mitral regurgitation was 93% +/- 3%. Chordal replacement with expanded polytetrafluoroethylene sutures had no effect on any of these end points. CONCLUSIONS: Mitral valve repair was feasible in most patients with mitral regurgitation caused by myxomatous disease and it was associated with low rates of valve-related complications. Chordal replacement with expanded polytetrafluoroethylene had no adverse effect on the late outcome and was believed to have increased the probability of mitral valve repair.

Adolescent↗

Surgical repair of postinfarction ventricular septal defect by infarct exclusion.

Repair of postinfarction ventricular septal defect (VSD) by infarct exclusion has been used for a decade in our unit. It involves securing a glutaraldehyde-preserved bovine pericardial patch to the endocardium of the left ventricle all around the necrotic myocardium to exclude the VSD and the infarct from the left ventricular cavity. Fifty-two patients with postinfarction VSD underwent this type of repair from 1987 to 1996. Thirty-four patients were in shock when undergoing operation; 26 had anterior VSD and 26 had posterior. Ten patients died perioperatively, for surgical mortality of 19%. Three patients developed recurrent VSD; one died and two survived. Preoperative cardiogenic shock and age older than 70 years were associated with an increased operative mortality. Operative survivors were followed up from 6 to 135 months, mean of 65 months. The actuarial survival at 8 years was 59% +/- 6%. Repair of postinfarction VSD by infarct exclusion is a relatively simple operative procedure and seems to have improved the results of surgery in patients with posterior VSD.

Actuarial Analysis↗

Cytogenetics for the model system Arabidopsis thaliana.

A detailed karyotype of Arabidopsis thaliana is presented using meiotic pachytene cells in combination with fluorescence in situ hybridization. The lengths of the five pachytene bivalents varied between 50 and 80 microns, which is 20-25 times longer than mitotic metaphase chromosomes. The analysis confirms that the two longest chromosomes (1 and 5) are metacentric and the two shortest chromosomes (2 and 4) are acrocentric and carry NORs subterminally in their short arms, while chromosome 3 is submetacentric and medium sized. Detailed mapping of the centromere position further revealed that the length variation between the pachytene bivalents comes from the short arms. Individual chromosomes were unambiguously identified by their combinations of relative lengths, arm-ratios, presence of NOR knobs and FISH signals with a 5S rDNA probe and chromosome specific DNA probes. Polymorphisms were found among six ecotypes with respect to the number and map positions of 5S rDNA loci. All ecotypes contain 5S rDNA in the short arms of chromosomes 4 and 5. Three different patterns were observed regarding the presence and position of a 5S rDNA locus on chromosome 3. Repetitive DNA clones enabled us to subdivide the pericentromeric heterochromatin into a central domain, characterized by pAL1 and 106B repeats, which accommodate the functional centromere and two flanking domains, characterized by the 17 A20 repeat sequences. The upper flanking domains of chromosomes 4 and 5, and in some ecotypes also chromosome 3, contain a 5S rDNA locus. The detection of unique cosmids and YAC sequences demonstrates that detailed physical mapping of Arabidopsis chromosomes by cytogenetic techniques is feasible. Together with the presented karyotype this makes Arabidopsis a model system for detailed cytogenetic mapping.

Arabidopsis↗

Corneal melting and scleromalacia perforans in a patient with pyoderma gangrenosum and acute myeloid leukemia.

Postoperative endophthalmitis may present in an atypical fashion (absent or minimal anterior chamber reaction) in the presence of underlying immunosuppressive disorder. The authors describe an apparently healthy 58-year-old man who displayed endophthalmitis with minimal anterior chamber reaction following penetrating keratoplasty for granular corneal dystrophy with underlying acute myeloid leukemia. Scleromalacia perforans in association with pyoderma gangrenosum subsequently developed, leading to ciliary staphyloma and corneal melting. Pyoderma gangrenosum is an uncommon, idiopathic skin disease that may also have ocular manifestations.

Anti-Bacterial Agents↗

Venous leg ulcers. Part 4: Wound care.

When assessing a leg ulcer the nurse should note the size and site of the wound, any exudate present and the presence of pain and allergies. A suitable wound dressing can then be selected.

Bandages↗

Compression hosiery.

Compression hosiery is used in the management of venous incompetence, which may result in varicose veins, venous ulceration, deep vein thrombosis and lymphoedema. Accurate patient assessment and measurement is essential to ensure that hosiery is appropriate, fits properly and is worn by the patient.

Bandages↗

Drosophila CBP is a co-activator of cubitus interruptus in hedgehog signalling.

The transcription factor CBP, originally identified as a coactivator for CREB, enhances transcription mediated by many other transcription factors. Mutations in the human CBP gene are associated with Rubinstein-Taybi syndrome, a haploinsufficiency disorder characterized by abnormal pattern formation, but the mechanism by which decreased CBP levels affect pattern formation is unclear. The hedgehog (hh) signalling pathway is an important determinant of pattern formation. cubitus interruptus (ci), a component in hh signalling, encodes a transcription factor homologous to the Gli family of proteins and is required for induction of the hh-dependent expression of patched (ptc), decapentaplegic (dpp) and wingless (wg). Haploinsufficiency for the ci-related transcription factor Gli3 causes phenotypic changes in mice (known as 'extra-toes) and humans (Greig's cephalopolysyndactyly syndrome) that have similarities to Rubinstein-Taybi syndrome. Here we show that Drosophila CBP (dCBP) functions as a coactivator of Ci, suggesting that the dCBP-Ci interaction may shed light on the contribution of CBP to pattern formation in mammals.

Animals↗

Aortic and mitral valve replacement with reconstruction of the intervalvular fibrous body.

OBJECTIVE: The intervalvular fibrous body between the aortic and mitral valves can be damaged by infective endocarditis, degenerative calcification, or multiple previous heart valve operations, making double valve replacement difficult. We have managed this problem by approaching the aortic and mitral valves through the aortic root and the dome of the left atrium. After excising the aortic valve, the diseased fibrous body, and the mitral valve, we suture a properly tailored patch of Dacron fabric or bovine pericardium to the lateral and medial fibrous trigones and to the aortic root, reestablishing the aortic and mitral anuli. A prosthetic mitral valve is implanted and a separate patch is used to close the left atriotomy before implantation of a prosthetic aortic valve. This study was undertaken to determine the efficacy of this operation. METHODS: Forty-three patients underwent reconstruction of the intervalvular fibrous body during aortic and mitral valve replacement because of infective endocarditis with abscess in 14 patients, extensive calcification in 9, lack of fibrous tissue because of multiple previous operations in 10, and to enlarge the aortic and mitral anuli in 10. The group comprised 18 men and 25 women with a mean age of 58 +/- 12 years. Thirty-two patients had had one or more previous heart valve replacements. All patients were in New York Heart Association functional classes III and IV, and 9 patients were in shock before the operation. RESULTS: Seven operative deaths occurred (16%). Early prosthetic valve endocarditis developed in two patients and necessitated reoperation. Follow-up extended from 4 to 108 months, with a mean of 38 months. No patient was lost to follow-up. Six late deaths occurred. The actuarial survival at 6 years was 56% +/- 6%. A Doppler echocardiographic study revealed normal prosthetic valve function and anatomically intact anuli in all 30 long-term survivors. CONCLUSIONS: Reconstruction of the intervalvular fibrous body during aortic and mitral valve replacement is a satisfactory operative approach in patients with complex valve annular pathology.

Animals↗