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Biomedical subjects

T Porter

Publications and source records attributed to T Porter.

At least 19 recordsLinked to original sources
PubMed2004

The ED-EQoL: the development of a new quality of life measure for patients with erectile dysfunction.

PURPOSE: To identify the important issues which have an impact on the quality of life (QoL) of men suffering from erectile dysfunction (ED) and to generate a new ED-specific QoL questionnaire ready to undergo further psychometric testing. METHODS: QoL issues relating to ED were generated through in-depth qualitative interviews of 29 patients, literature review and consultation with other healthcare professionals. The issues were formulated into a questionnaire, which was piloted using 40 patients with ED and subsequently refined using well-established principles of questionnaire development. RESULTS: The qualitative interviews revealed numerous psychosocial problems associated with ED, which were operationalised into a 40-item questionnaire. Pilot testing allowed the questionnaire to be reduced to a manageable 15-item final questionnaire while maintaining face and content validity and the potential to discriminate between men with varying degrees of affected QoL. This questionnaire had a Cronbach's alpha of 0.94. CONCLUSIONS: A new ED-specific QoL measure has been developed using appropriate methodology. Qualitative techniques identified a range of psychosocial morbidity in men with ED, leading to a simple but robust instrument with face and content validity. This questionnaire, Erectile Dysfunction-Effect on quality of life (ED-EQoL), has now undergone psychometric testing for validity and reliability.

Adult↗
PubMed2001

Psychosocial implications of clinical trials on patients with age-related macular degeneration and pathologic myopia as seen in the photodynamic therapy trials.

Photodynamic therapy is a combination of the systemically injected photosensitizing drug, verteporfin, and the subsequent exposure of the affected retina to a low-beam diode laser. Eligible participants in the photodynamic therapy clinical trial were those with "wet" cases of age-related macular degeneration with subfoveal, predominantly classic lesions. The expected outcome of the treatment is to preserve vision, not to restore lost vision. Study participants are frustrated in their performance of daily activities and often have unrealistic expectations of photodynamic therapy treatment outcomes (eg, improved vision). Frustration and fear are evident at visits during which their actual vision loss is measured. One of our goals is to help the patients have realistic expectations of treatment outcomes.

Activities of Daily Living↗
PubMed2000

Ten-fold augmentation of endothelial uptake of vascular endothelial growth factor with ultrasound after systemic administration.

OBJECTIVES: In this study, the feasibility of delivering and enhancing the uptake of vascular endothelial growth factor (VEGF) into the intact endothelium by using ultrasound (US) facilitation was determined. BACKGROUND: A limitation of tissue-targeted drug delivery is the need for direct arterial cannulation. We postulate a mechanism by which agents injected intravenously may be targeted to a tissue using US and ultrasonic contrast agents. METHODS: We used a rat model to test the ability of US and an ultrasonic contrast agent perflurocarbon exposed sonicated dextrose albumin (PESDA) to increase uptake of VEGF in the myocardium. Continuous wave Doppler US (0.6 W/cm2 at 1 MHz for 15 min) was applied to the chest wall overlying the myocardium during intravenous injection with either VEGF (100 microg/kg) alone or a combination of VEGF and PESDA (0.1%). Control rats had VEGF infused without US or PESDA. The VEGF uptake was measured quantitatively in the heart, lung, liver and kidneys by enzyme-linked immunosorbent assay (ng/g of tissue) and morphologically by fluorescence microscopy. RESULTS: There was an eight-fold increase in VEGF uptake in the heart by US alone (16.86 +/- 1.56 vs. 2.11 +/- 0.953 ng/g of tissue, p < 0.0001) and a 13-fold increase with US + PESDA (26.78 +/- 2.88 vs. 2.11 +/- 0.953 ng/g of tissue, p < 0.0001) compared with control rats. Fluorescence microscopy revealed deposition of VEGF in the endothelium of small intramyocardial arterioles. CONCLUSIONS: These results show a marked increase in endothelial VEGF uptake with US and US + PESDA. Thus, US may be used to augment endothelial VEGF uptake 10-fold to 13-fold.

Animals↗
PubMed1999

rhBMP-collagen sponges as osteoinductive devices: effects of in vitro sponge characteristics and protein pI on in vivo rhBMP pharmacokinetics.

Osteoinductive devices, comprised of biodegradable collagen scaffolds and recombinant human Bone Morphogenetic Proteins (rhBMPs), are being currently pursued for local bone induction. To better understand the biological performance of such devices, we have carried out a series of studies to investigate the effects of sponge properties and protein structural features on the pharmacokinetics of implanted rhBMPs. The results indicated little dependence of the rhBMP-2 pharmacokinetics on the in vitro determined sponge properties. The protein isoelectric point (pI), on the other hand, was found to significantly affect the initial implant retention of rhBMPs, but not the subsequent pharmacokinetics. A 100-fold difference in the implant-retained dose could be observed depending on the type of rhBMP implanted. We conclude that protein structural features are important variables controlling in vivo pharmacokinetics of rhBMPs, and possibly the osteoinductive potency of the devices.

Biocompatible Materials↗
PubMed1999

Effect of high-intensity focused ultrasound on whole blood with and without microbubble contrast agent.

Using human whole blood samples with and without contrast agent (CA), we evaluated the effect of exposures to focused, continuous wave (CW) 1.1-MHz ultrasound for durations of 10 ms to 1 s at spatial average intensities of 560 to 2360 W/cm2. Cavitation was monitored with a passive cavitation detector and hemolysis was determined with spectroscopy. In whole blood alone, no significant cavitation, heating or hemolysis was detected at any exposure condition. Conversely, cavitation and hemolysis, but not heating, were detected in whole blood with CA. A CA concentration as low as 0.28 microL CA per mL whole blood at an intensity of 2360 W/cm2 for 1 s resulted in measurable cavitation and a 6-fold increase in hemolysis compared to shams. Cavitation and hemolysis increased proportional to the concentration of CA and duration of exposure. In samples containing 4.2 microL CA per mL whole blood exposed for 1 s, a threshold was seen at 1750 W/cm2 where cavitation and hemolysis increased 10-fold compared to exposures at lower intensities. HIFU exposure of whole blood containing CA leads to significant hemolysis in vitro and may lead to clinically significant hemolysis in vivo.

Albumins↗
PubMed1998

Antibodies to TR2 (herpesvirus entry mediator), a new member of the TNF receptor superfamily, block T cell proliferation, expression of activation markers, and production of cytokines.

TR2 (TNFR-related 2) is a recently identified member of the TNFR family with homology to TNFRII. We have demonstrated previously that TR2 mRNA is expressed in resting and activated human T cells and that TR2-Ig partially inhibits an allogeneic mixed leukocyte proliferation response. We now characterize TR2 further by the use of specific mAbs. Flow-cytometry analysis using TR2 mAbs confirmed that resting PBL express high levels of cell surface TR2, and that TR2 is widely expressed on all freshly isolated lymphocyte subpopulations. However, stimulation of purified T cells with either PHA or PHA plus PMA resulted in decreased surface expression within 48 h of activation before returning to resting levels at 72 h. TR2 mAbs inhibited CD4+ T cell proliferation in response to stimulation by immobilized CD3 or CD3 plus CD28 mAbs. Assay of culture supernatants by ELISA showed inhibition of TNF-alpha, IFN-gamma, IL-2, and IL-4 production, which, for IL-2 and TNF-alpha was also confirmed by intracellular cytokine staining. Furthermore, expression of activation markers on CD4+ T cells, including CD25, CD30, CD69, CD71, and OX40 (CD134), was inhibited. TR2 mAbs inhibited proliferation in a three-way MLR, and a response to soluble recall Ag, tetanus toxoid. In conclusion, these results suggest that TR2 is involved in the activation cascade of T cell responses and TR2 mAbs prevent optimal T cell proliferation, cytokine production, and expression of activation markers.

Animals↗
PubMed1998

Effect of blood and microbubble oxygen and nitrogen content on perfluorocarbon-filled dextrose albumin microbubble size and efficacy: in vitro and in vivo studies.

We hypothesized, on the basis of in vitro observations, that a higher oxygen partial pressure within perfluorocarbon-containing microbubbles (PCMB) would enhance inward nitrogen diffusion after venous injection, leading to improved myocardial contrast. The in vitro studies measured PCMB size and concentration after injection into arterial blood that was obtained during inhalation of either room air or 100% oxygen. We then compared the myocardial contrast produced from PCMB sonicated in the presence of either a nitrogen-free environment (100% oxygen) or room air in three closed chest dogs. PCMB exposed to oxygenated blood in vitro were significantly smaller after insonation than PCMB exposed to arterial blood obtained during room air inhalation, confirming the important role of dissolved nitrogen in stabilizing PCMB size. In vivo studies demonstrated that intravenous PCMB sonicated with 100% oxygen produced significantly greater anterior and posterior myocardial contrast than PCMB sonicated in the presence of room air.

Animals↗
PubMed1998

The role of the plain X-ray in the assessment of prostatic symptoms.

OBJECTIVE: To assess the contribution of a plain X-ray of the kidney, ureters and bladder (KUB) to the assessment of patients presenting with symptoms of bladder outlet obstruction. PATIENTS AND METHODS: All patients presenting to the 'Prostate' clinic at Weston General Hospital during the 12 months from 1 May 1993 to 30 April 1994 were assessed clinically by a history, examination and routine investigations that included a KUB examined and reported by a radiologist. Patients were followed and treatment instituted as deemed appropriate. The contribution made to the management of the patient by the KUB was assessed. RESULTS: Of the 292 patients, 234 had no relevant abnormality detected: four patients had evidence of a bladder calculus, whilst in four osteosclerotic areas were noted on the pelvis and lumbar spine. Of the remainder, 14 (5%) had upper urinary tract calcification. In no patients did the KUB influence their immediate management. Those with asymptomatic upper tract stones were offered a yearly follow-up. CONCLUSIONS: The routine use of the KUB as a means of investigating lower urinary tract symptoms in the male may no longer be necessary.

Calcinosis↗
PubMed1998

Prophylaxis for transrectal prostatic biopsies: a randomized controlled study of intravenous co-amoxiclav given as a single dose compared with an intravenous dose followed by oral co-amoxiclav for 24 h.

OBJECTIVE: To compare in a randomized prospective study the infective complication rates of a single intravenous dose of co-amoxiclav given alone before transrectal prostatic biopsy with an intravenous dose followed by oral co-amoxiclav for 24 h. PATIENTS AND METHODS: Eighty-three patients undergoing prostatic biopsy were randomized to receive 1.2 g co-amoxiclav intravenously and then either three further doses of oral co-amoxiclav (Group 1) or no further antibiotics (Group 2). The evaluation included analysis of a mid-stream urine (MSU) sample before and 72 h after biopsy, and the recording of oral temperatures and symptoms in the first 44 patients. Patients with symptomatic urinary tract infections (UTIs), prostatitis, indwelling catheters, diabetes and those receiving steroid therapy were excluded. RESULTS: Eight patients, four from each treatment arm, were found to have asymptomatic UTIs from their MSU before biopsy. Excluding these patients, four patients (11%) from Group 1 and six from Group 2 (16%) had positive MSUs at 72 h; two patients from Group 2 and one from Group 1 required admission to hospital. Of the patients returning symptom and temperature charts, a further six (14%; three from each group) reported signs and symptoms suggestive of infection despite negative urine cultures. CONCLUSIONS: There was no statistically significant difference in the rate of positive MSUs between the groups. The incidence of infections was considerably higher than in previously published series where other antibiotics were used, suggesting that co-amoxiclav is not the drug of choice for transrectal prostatic biopsy.

Administration, Oral↗
PubMed1998

Correlation between quantitative angiographic lesion severity and myocardial contrast intensity during a continuous infusion of perfluorocarbon-containing microbubbles.

The purpose of this study was to determine whether quantitative measurements of myocardial videointensity (MVI) during continuous intravenous infusions of microbubbles could detect differences in coronary artery stenosis severity during dobutamine stress echocardiography. Coronary artery stenoses were created in seven dogs by progressively tightening a snare around the coronary artery. Intravenous infusions of perfluorocarbon microbubbles were given during dobutamine stress. The initial rate of myocardial contrast enhancement (slope), peak myocardial contrast (peak MVI) at the longest pulsing interval, and the product (slope * peak MVI) were compared as ratios in the stenosed versus adjacent normal perfusion beds. Twenty-two coronary stenoses were compared (range 16% to 80% in diameter). There was a strong correlation between both slope ratios and slope * peak MVI ratios and percent stenosis (r = -0.89 for both, p<0.001). The rate of contrast replenishment during a continuous infusion of microbubbles can be used to determine both the presence and severity of coronary stenoses during stress echocardiography.

Animals↗
PubMed1996

Isolation of a neutralizing human RSV antibody from a dominant, non-neutralizing immune repertoire by epitope-blocked panning.

We isolated a large panel of human Abs directed against the respiratory syncytial virus (RSV) Ag from combinatorial phage display libraries. Following initial differentiation of the Fabs by BstNI restriction patterns, DNA sequence analysis revealed 10 different classes of VH paired with more than 35 different VL genes. All the Fabs bound with high affinity to the F Ag. However, most Fabs competed with the binding of a representative member of this group, suggesting that the Fabs recognized a common epitope on the F Ag, and none of them neutralized virus in vitro. To suppress repetitive isolation of these non-neutralizing Abs, a representative Fab was included during panning to block this common epitope on the F Ag. By this "epitope-blocked panning" approach, two novel Fabs, encoded by unique VH and VL genes, were isolated from a previously screened library. Competition binding analysis confirmed that the Fabs recognized epitopes distinct from that of the previously isolated Fabs. One of these Fabs, 516, neutralized RSV in cell culture. These activities of Fab-516 were retained upon its genetic conversion to a mAb (IgG1) and expression in mammalian cells. Our results suggest that the RSV F glycoprotein presents a dominant, non-neutralizing epitope to the human immune system, which may serve in evasion of host defenses. However, less prevalent, fusion-inhibiting Abs were revealed by blockade of this epitope during the panning process.

Amino Acid Sequence↗
PubMed1996

Type I IL-1 receptor: ligand specific confirmation differences and the role of glycosylation in ligand binding.

The extracellular domain of the type I Interleukin-1 receptor (sIL-1R) was expressed in Drosophila S2 cells as a secreted 43 kDa glycoprotein, as evidenced by its binding to Concanavalin A and enzymatic deglycosylation. sIL-1R bound IL-1 beta with a K(D) of 2 nM as determined by competition ELISA. N-Glycanase treated sIL-1R had a C. 100 fold lower affinity than glycosylated sIL-1R for IL-1 beta, suggesting that glycosylation is a key component of the IL-1 beta/IL-1 receptor interaction. Crosslinking of sIL-1R to (125)I-IL-1 beta could be competed with unlabelled IL-1 alpha, IL-1 beta, IL-1 receptor antagonist (IL-1ra), and a mutant of IL-1 (Th9Gly) which has reduced bioactivity but wild type receptor binding affinity. Limited proteolysis of sIL-1R in the presence of IL-1 alpha, IL-1 beta, IL-1ra, and Thr9Gly IL-1 beta with several different proteases followed by analysis of sIL-1R by Western blot was used to assess the effect of binding on sIL-1R conformation. While some proteases showed no differences in cleavage patterns or sensitivity between free and bound sIL-1R, others showed differences in either cleavage sites or sensitivity with different ligands. This implies that upon ligand binding there is a conformational change in the receptor which is sensitive to the particular ligand bound, and hence has implications for the ability of different ligands to trigger responses after binding to receptor.

Animals↗
PubMed1995

Current trends in molecular recognition and bioseparation.

Molecular recognition guides the selective interaction of macromolecules with each other in essentially all biological processes. Perhaps the most impactful use of biomolecular recognition in separation science has been in affinity chromatography. The results of the last 26 years, since Cuatrecases, Wilchek and Anfinsen first reported the purification of staphylococcal nuclease, have validated the power of biomolecular specificity for purification. This power has stimulated an explosion of solid-phase ligand designs and affinity chromatographic applications. An ongoing case in point is the purification of recombinant proteins, which has been aided by engineering the proteins to contain Affinity-Tag sequences, such as hexa-histidine for metal-chelate separation and epitope sequence for separation by an immobilized monoclonal antibody. Tag technology can be adapted for plate assays and other solid-phase techniques. The advance of affinity chromatography also has stimulated immobilized ligand-based methods to characterize macromolecular recognition, including both chromatographic and optical biosensor methods. And, new methods such as phage display and other diversity library approaches continue to emerge to identify new recognition molecules of potential use as affinity ligands. Overall, it is tantalizing to envision a continued evolution of new affinity technologies which use the selectivity built into biomolecular recognition as a vehicle for purification, analysis, screening and other applications in separation sciences.

Chromatography, Affinity↗