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Biomedical subjects

K A Myers

Publications and source records attributed to K A Myers.

At least 19 recordsLinked to original sources
PubMed2006

Outcome of ultrasound-guided sclerotherapy for varicose veins: medium-term results assessed by ultrasound surveillance.

OBJECTIVE: To estimate medium-term success after a technique for ultrasound-guided sclerotherapy for superficial chronic venous disease. DESIGN: A prospective study in a single unit with ultrasound surveillance after treatment. MATERIALS: Results after 1189 treatment sessions for 807 venous saphenous veins and related tributaries or non-saphenous tributaries in 489 patients. METHODS: Univariate life table analysis determined primary and secondary success rates. Multivariate Cox regression analysis detected covariates that affected outcome. RESULTS: Primary and secondary success rates at 36 months for all veins were 52.4% (95%CI 46-58%) and 76.8% (95%CI 71-82%). Cox regression analysis for primary success for all veins showed significantly worse results for saphenous veins compared to tributaries (HR 3.72 - 95%CI 1.9 to 7.3). Cox regression for all saphenous veins showed independently worse results for patients less than 40 years age (HR 2.16 - 95%CI 1.27-3.66), small compared to great saphenous veins (HR 1.58 - 95%CI 1.11-2.24), veins greater than 6mm diameter compared to smaller veins (HR 2.22 - 95%CI 1.40-3.50), liquid compared to foam sclerotherapy (HR 2.20 - 95%CI 1.28-3.78), lower volumes of sclerosant compared to volumes greater than 12 ml (HR 0.51 - 95%CI 0.33-0.81) and highly diluted compared to concentrated sclerosant (HR 2.05 - 95%CI 1.21-3.46) with worse results using highly diluted or undiluted 3% sclerosant compared to a 1.5% concentration. There were no significant differences for primary success for saphenous veins for date of procedure, sex, side, primary or recurrent varicose veins, or commercial type of sclerosant. CONCLUSIONS: Ultrasound-guided sclerotherapy gives satisfactory results if it is accepted that treatment may need to be repeated to achieve secondary success. Results provide a basis for further research to explore factors that might affect outcome. Younger patients with larger diameter saphenous veins may warrant alternative forms of treatment, particularly for small saphenous reflux.

Adult↗
PubMed2005

Biomechanical implications of the negative heel rocker sole shoe: gait kinematics and kinetics.

Rocker sole shoes are commonly prescribed to diabetic patients with insensate feet. Recent passage of the therapeutic shoe bill has drawn an increased focus to prescription rehabilitative footwear. The purpose of this work is to investigate the dynamics of lower extremity joints (hip, knee and ankle) with the application of a negative heel rocker sole shoe under controlled lab conditions. Forty normal adults volunteered for gait evaluations using controlled baseline and prescription negative heel rocker sole shoes. Three-dimensional motion analysis techniques were used to acquire kinematic and kinetic data using a six-camera Vicon 370 motion system and two AMTI force plates. No significant change in walking speed or stride length was seen with the negative heel rocker shoe, although cadence was increased. The most significant kinematic changes with the application of the negative heel shoe occurred at the ankle in the sagittal plane with increased plantarflexion at terminal stance. Significant hip and knee changes were also noted with increased mid-stance hip extension and knee flexion. The most significant kinetic effects were seen in the transverse plane followed by changes in the sagittal and coronal planes. Changes in power were mostly noted in the sagittal plane. Other statistically significant changes in gait kinematics and kinetics were observed, although the magnitudes and durations were limited and as a result were not considered clinically significant. The study results indicated the negative heel rocker shoe significantly altered proximal joint metrics (hip and knee). The most significant distal joint alterations were seen in sagittal plane ankle kinetics. These kinematic and kinetic changes, along with previously studied effects of pressure relief at the metatarsal heads, should aid medical professionals in prescribing prophylactic footwear.

Adult↗
PubMed2005

In vivo evaluation of an EIAV vector for the systemic genetic delivery of therapeutic antibodies.

Lentiviral-based vectors hold great promise as gene delivery vehicles for the treatment of a wide variety of diseases. We have previously reported the development of a nonprimate lentiviral vector system based on the equine infectious anaemia virus (EIAV), which is able to efficiently transduce dividing and nondividing cells both in vitro and in vivo. Here, we report on the application of EIAV vectors for the systemic delivery of an antibody fusion protein designed for the treatment of cancer. The therapeutic potential of a single chain antibody against the tumour-associated antigen, 5T4, fused to immune enhancer moieties has been demonstrated in vitro and here we evaluate the genetic delivery of a 5T4 scFv fused to B7.1 (scFvB7) using an EIAV vector. The kinetics and concentration of protein produced following both intravenous (i.v.) and intramuscular (i.m.) administration was determined in immune competent adult mice. In addition, the immune response to the EIAV vector and the transgene were determined. Here, we show that a single injection of EIAV expressing scFv-B7 can give rise to concentrations of protein in the range of 1-5 microg/ml that persist in the sera for more than 50 days. After a second injection, concentrations of scFv-B7.1 rose as high as 20 microg/ml and levels greater than 2 microg/ml were present in the sera of all mice injected i.v. after 210 days despite the detection of antibodies against both the transgene and viral envelope for the duration of this study. These results demonstrate the potential of EIAV as a gene therapy vector for long-term production of therapeutic recombinant proteins.

Animals↗
PubMed2003

Prevention of venous thrombosis with elastic stockings during long-haul flights: the LONFLIT 5 JAP study.

The aim of this study was to evaluate deep venous thrombosis (DVT) prophylaxis with specific elastic stockings in long-haul flights (11-13 hours), in high-risk subjects. A group of 300 subjects was included; 76 were excluded for several problems including concomitant treatments; 224 were randomized into two groups (stockings vs. controls) to evaluate prophylaxis with below-knee stockings. An exercise program was used in both groups. Scholl (UK) Flight Socks (14-17 mmHg of pressure at the ankle) were used. DVT was diagnosed with ultrasound scanning. The femoral, popliteal, and tibia] veins were scanned before and within 90 minutes after the flights. Of the 205 included subjects, 102 controls and 103 treated subjects completed the study. Drop-outs were due to flight connection problems. Age, gender, and risk distributions were comparable in the two groups. In the treatment group (103 subjects; mean age, 42; SD 9; M:F, 55:48), one limited, distal DVT was observed (0.97%). In the control group (102 subjects; mean age, 42.1; SD 10.3; M:F, 56:46), six subjects (5.8%) had a DVT. There were no superficial thromboses. The difference in DVT incidence is significant (p<0.0025; six times greater in the control group). Intention-to-treat analysis counts 18 failures in the control group (12 lost to follow-up + six thromboses) of 112 subjects (15.8%) versus eight failures (7.3%) in the treatment group (p<0.05). The tolerability of the stockings was very good and there were no complaints or side effects. All events were asymptomatic. Considering these observations, Scholl Flight Socks are effective in reducing the incidence of DVT in high-risk subjects.

Adult↗
PubMed2001

The rational clinical examination. Does this patient have clubbing?

CONTEXT: The association between digital clubbing and a host of diseases has been recognized since the time of Hippocrates. Although the features of advanced clubbing are familiar to most clinicians, the presence of early clubbing is often a source of debate. OBJECTIVE: To perform a systematic review of the literature for information on the precision and accuracy of clinical examination for clubbing. DATA SOURCES: The MEDLINE database from January 1966 to April 1999 was searched for English-language articles related to clubbing. Bibliographies of all retrieved articles and of standard textbooks of physical diagnosis were also searched. STUDY SELECTION: Studies selected for data extraction were those in which quantitative or qualitative assessment for clubbing was described in a series of patients. Sixteen studies met these criteria and were included in the final analysis. DATA EXTRACTION: Data were extracted by both authors, who independently reviewed and appraised the quality of each article. Data extracted included quantitative indices for distinguishing clubbed from normal digits, precision of clinical examination for clubbing, and accuracy of clubbing as a marker of selected diseases. DATA SYNTHESIS: The profile angle, hyponychial angle, and phalangeal depth ratio can be used as quantitative indices to assist in identifying clubbing. In individuals without clubbing, values for these indices do not exceed 176 degrees, 192 degrees, and 1.0, respectively. When clinicians make a global assessment of clubbing at the bedside, interobserver agreement is variable, with kappa values ranging between 0.39 and 0.90. Because of the lack of an objective diagnostic criterion standard, accuracy of physical examination for clubbing is difficult to determine. The accuracy of clubbing as a marker of specific underlying disease has been determined for lung cancer (likelihood ratio, 3.9 with phalangeal depth ratio in excess of 1.0) and for inflammatory bowel disease (likelihood ratio, 2.8 and 3.7 for active Crohn disease and ulcerative colitis, respectively, if clubbing is present). CONCLUSIONS: We recommend use of the profile angle and phalangeal depth ratio as quantitative indices in identifying clubbing. Clinical judgment must be exercised in determining the extent of further evaluation for underlying disease when these values exceed 180 degrees and 1.0, respectively.

Data Interpretation, Statistical↗
PubMed2001

Vascular ultrasound surveillance after endovascular intervention for occlusive iliac artery disease.

This paper describes vascular ultrasound surveillance after endovascular intervention for occlusive iliac artery disease. There were 105 patients who had 198 procedures in 155 limbs, consisting of 110 balloon dilatations and 88 stentings. The patients were referred to the vascular diagnostic service by several surgeons. All procedures had been considered to be initially technically successful. Colour-Doppler duplex ultrasound studies were performed shortly before and at serial intervals after operation to determine patency rates. Univariate life table analysis showed 69% primary and 96% assisted primary patency at four years. Primary patency rates at four years were significantly worse for stentings (60%) compared to balloon dilatations (71%) (P<0.05). Maximum peak systolic velocities (PSV) were recorded from the treated arteries. Receiver operating characteristics curves showed that PSV >300 cm/s was most accurate for predicting technical failure. Haemodynamic success rates at four years were 72% for PSV >300 cm/s. Results for procedures that were initially successful indicate that long-term primary patency rates for iliac endovascular intervention are acceptable and that assisted primary patency rates are excellent.

Aged↗
PubMed2001

Venous thromboembolism from air travel: the LONFLIT study.

The LONFLIT study was planned to evaluate the incidence of deep venous thrombosis (DVT) occurring as a consequence of long flights. In the Lonflit study 355 subjects at low-risk for DVT and 389 at high-risk were studied. Low-risk subjects had no cardiovascular disease and used no drugs. All flights were in economy class. The average flight duration was 12.4 hours (range, 10-15 hr). The mean age of the studied subjects was 46 years (range 20-80 yr, SD 11; 56% males). DVT diagnosis was made by ultrasound scans after the flights (within 24 hours). In low-risk subjects no events were recorded while in high-risk subjects 11 had DVT (2.8%) with 13 thromboses in 11 subjects and 6 superficial thromboses (total of 19 thrombotic events in 389 patients [4.9%]). In the Lonflit2 study the authors studied 833 subjects (randomized into 422 control subjects and 411 using below-knee stockings). Mean age was 44.8 years (range, 20-80 yr, SD 12; 57% males). The average flight duration was 12.4 hours. Scans were made before and after the flights. In the control group there were 4.5% of subjects with DVT while only 0.24% of subjects had DVT in the stockings group. The difference was significant. The incidence of DVT observed when subjects were wearing stockings was 18.75 times lower than in controls. Long-haul flights are associated to DVT in some 4-5% of high-risk subjects. Below-knee stockings are beneficial in reducing the incidence of DVT.

Adult↗
PubMed2001

Giacomini's observations on the superficial veins of the abdominal limb and principally the external saphenous.

Carlo Giacomini, later Professor of Anatomy at the University of Turin, Italy, presented a thesis on superficial and deep lower limb venous anatomy in July 1873. This resulted in his name being associated with a vein that he described in detail that passes up deep to the fascia on the back of the thigh. However, the precise nature of his detailed and insightful observations have not previously been presented, at least for the past century. The Authors were able to find and translate the original manuscript, and the first section on the superficial veins is presented here. Giacomini documented the several variations in the origin and terminations, and anterograde and retrograde flow in this vein that have only recently been rediscovered by duplex ultrasound scanning. Much can be learned from his descriptions by all who are involved in treating chronic venous disease.

Anatomy↗
PubMed2000

Isolation of a high affinity scFv from a monoclonal antibody recognising the oncofoetal antigen 5T4.

The oncofoetal antigen 5T4 is a 72 kDa glycoprotein expressed at the cell surface. It is defined by a monoclonal antibody, mAb5T4, that recognises a conformational extracellular epitope in the molecule. Overexpression of 5T4 antigen by tumours of several types has been linked with disease progression and poor clinical outcome. Its restricted expression in non-malignant tissue makes 5T4 antigen a suitable target for the development of antibody directed therapies. The use of murine monoclonal antibodies for targeted therapy allows the tumour specific delivery of therapeutic agents. However, their use has several drawbacks, including a strong human anti-mouse immune (HAMA) response and limited tumour penetration due to the size of the molecules. The use of antibody fragments leads to improved targeting, pharmacokinetics and a reduced HAMA. A single chain antibody (scFv) comprising the variable regions of the mAb5T4 heavy and light chains has been expressed in Escherichia coli. The addition of a eukaryotic leader sequence allowed production in mammalian cells. The two 5T4 single chain antibodies, scFv5T4WT19 and LscFv5T4, described the same pattern of 5T4 antigen expression as mAb5T4 in normal human placenta and by FACS. Construction of a 5T4 extracellular domain-IgGFc fusion protein and its expression in COS-7 cells allowed the relative affinities of the antibodies to be compared by ELISA and measured in real time using a biosensor based assay. MAb5T4 has a high affinity, K(D)=1.8x10(-11) M, as did both single chain antibodies, scFv5T4WT19 K(D)=2.3x10(-9) M and LscFv5T4 K(D)=7.9x10(-10) M. The small size of this 5T4 specific scFv should allow construction of fusion proteins with a range of biological response modifiers to be prepared whilst retaining the improved pharmacokinetic properties of scFvs.

Amino Acid Sequence↗
PubMed2000

Nitinol - its use in vascular surgery and other applications.

OBJECTIVES: to describe the physical properties of shape-memory alloys and the surgical, scientific and commercial applications of nitinol, in particular. DESIGN AND METHODS: a Medline, Internet and library search with contributions from commerce to describe the alloy's structure, behaviour and biocompatibility, and design for devices constructed from nitinol. RESULTS: nitinol has the properties of thermal shape memory and superelasticity that make it ideal for many vascular and general surgical prostheses and disposables, and for various commercial applications. CONCLUSIONS: further research into shape-memory alloys from scientific and commercial groups should widen their use in vascular and endovascular surgery.

Alloys↗
PubMed1999

Organisation of the mouse and human 5T4 oncofoetal leucine-rich glycoprotein genes and expression in foetal and adult murine tissues.

The human 5T4 oncotrophoblast leucine-rich glycoprotein may contribute to the process of placentation or metastasis by modulating cell adhesion, shape and motility. To understand better the role of 5T4 in development and cancer, the gene structure has been elucidated from both human and mouse genomic clones and mRNA expression has been studied in foetal and adult mouse tissues. The protein coding region is located within the second of two exons, the first exon comprising solely of 5'-untranslated region. Upstream there are no TATA or CAAT boxes, but there are a number of potential Sp1 binding sites. The murine and human proteins show a homologous domain organisation of the leucine rich repeats (LRR) and associated N- and C-terminal flanking regions, although the hydrophilic sequence which intervenes between the two LRR domains contains six additional amino acids in the mouse. The signal peptide, transmembrane region and cytoplasmic tail sequences are identical as are 6 out of the 7 potential N-linked glycosylation sites. Mouse 5T4 transcripts are abundant in placenta and also highly expressed in embryos while in adult tissues transcripts are restricted to brain and ovary. These patterns of expression and the genomic organisation are discussed in relation to possible function and other recently described LRR containing proteins.

Amino Acid Sequence↗