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Biomedical subjects

R Morgan

Publications and source records attributed to R Morgan.

At least 37 records · Page 2Linked to original sources
PubMed2001

Use of metallic stents and balloons in the esophagus and gastrointestinal tract.

The majority of malignant and benign strictures in the esophagus and GI tract can be treated with use of minimally invasive alternatives to surgery such as balloon dilation or metallic stents. Virtually any obstructing lesion in the esophagus, stomach, duodenum, colon, and rectum can be treated with these methods with use of interventional radiologic or endoscopic techniques. In general, metallic stents are reserved for malignant strictures and balloon dilation is indicated for benign lesions. Patients with malignant esophageal fistulas and perforations can be palliated effectively and promptly by sealing the fistula or leak by deployment of a covered stent. Patients with malignant disease may benefit from a treatment regime that includes metallic stent placement, chemotherapy, radiation therapy and/or brachytherapy, although the efficacy of such combined therapies has yet to be defined. Further refinements to stent design are required. The ideal stent would be resistant to tumor ingrowth and migration. Placing a coating material on uncovered stents to prevent tumor ingrowth may achieve these aims. Finally, a biodegradable stent that dissolves before the development of intimal hyperplasia might enable stents to be used to treat benign strictures.

Catheterization↗
PubMed2001

ERM-dependent movement of CD43 defines a novel protein complex distal to the immunological synapse.

The large mucin CD43 is actively excluded from T cell/APC interaction sites, concentrating in a membrane domain distal to the site of TCR engagement. The cytoplasmic region of CD43 was necessary and sufficient for this antipodal movement. ERM cytoskeletal adaptor proteins colocalized with CD43 in this domain. An ERM dominant-negative mutant blocked the distal accumulation of CD43 and another known ERM binding protein, Rho-GDI. Inhibition of ERM function decreased the production of IL-2 and IFNgamma, without affecting PKC(theta) focusing or CD69 upregulation. These results indicate that ERM proteins organize a complex distal to the T cell/APC interaction site and provide evidence that full T cell activation may involve removal of inhibitory proteins from the immunological synapse.

Animals↗
PubMed2001

Power output of legs during high intensity cycle ergometry: influence of hand grip.

Traditionally, leg cycle ergometry is used to assess the power output of the lower limbs. However, it is suspected that the upper body makes a significant, albeit as yet unknown, contribution to the measured power output, and as such, the lean mass of the whole body should be considered during ergometric assessment. To test this idea, indices of mechanical power output were obtained from 11 subjects during high intensity leg cycle ergometry tests (20 second duration; 75 grams per kilogram total body mass) using two protocols: one with a standard handle-bar grip (with grip) and one with supinated wrists (without-grip). Peak mechanical power, mean mechanical power, fatigue index and total mechanical work values were calculated for each subject during each test and the sample mean differences associated with the two protocols were compared using paired Student t-tests. The with-grip protocol yielded significantly greater peak mechanical power output than the without-grip protocol (886+/-124 W and 815+/-151 W, respectively), suggesting a significant upper body contribution to the maximum power output measured for the legs. As a first step towards quantifying the upper body involvement during leg cycle ergometry, surface electromyography of the forearm musculature was measured in a twelfth subject whilst performing each of the test protocols. During the with-grip ergometer tests, the intensity of electrical activity in the forearm musculature was similar, if not greater than, the intensity of electrical activity recorded for the forearm musculature during 100% maximum voluntary hand grip-dynamometer contractions, suggesting maximum isometric-type forearm muscle contraction during the with-grip leg ergometry tests. These findings suggest that the performance of traditional-style leg cycle ergometry requires a muscular contribution from the whole body. As such, researchers should be mindful of this, both in terms of the allocation of ergometer loads, and in the analysis of blood-borne metabolites.

Adult↗
PubMed2001

Tandem-cycle high-dose melphalan and cisplatin with peripheral blood progenitor cell support in patients with breast cancer and other malignancies.

We evaluated the feasibility of tandem-cycle high-dose chemotherapy (HDCT) with cisplatin, melphalan, and peripheral blood progenitor cells (PBPCs). Fifty patients with high-risk primary (n = 17) or stage IV breast cancer (n = 29) or other malignancies (n = 4) received 2 cycles of intravenous melphalan, 20 to 151.8 mg/m2, and cisplatin, 200 mg/m2, followed by granulocyte-macrophage colony-stimulating factor (GM-CSF) or G-CSF. Starting at 40 mg/m2 of melphalan, patients also received PBPCs. Delayed platelet recovery defined the maximum tolerated dose (MTD) for melphalan at 101.2 mg/m2 per cycle. There were no treatment-related deaths. Cycle 2 was delivered at a median of 1.7 months after cycle 1; 72% of patients treated at the MTD received both cycles. Cycle 2 was omitted when patients refused it or had disease progression or toxicities, primarily prolonged thrombocytopenia. Complete response rates in stage IV breast cancer patients increased from 28% pre-HDCT to 55% after cycle 2. At a median follow-up of 4.6 years (range, 1.5-8.1 years), 11 of 29 patients with stage IV breast carcinoma were alive with 5-year projected progression-free and overall survival rates of 19% (95% confidence interval [CI], 7%-41%) and 39% (95% CI, 20%-62%), respectively. Five-year projected progression-free and overall survival rates for patients with stage IV breast cancer in complete response following HDCT versus all others were 35% (95% CI, 15%-70%) versus 0% (P = .01) and 61% (95% CI, 35%-91%) versus 10% (95% CI, 2%-60%) (P = .003; log-rank test), respectively. Estrogen-receptor positivity was predictive of reduced risk of progression (relative risk [RR], 0.25; 95% CI, 0.10-0.65; P = .003) and death (RR, 0.27; 95% CI, 0.10-0.72; P = .009) after adjusting for response status. Five-year projected relapse-free and overall survival rates were 71% (95% CI, 43%-96%) and 82% (95% CI, 56%-100%), respectively, for the 17 patients with high-risk primary breast cancer. Tandem-cycle high-dose melphalan and cisplatin with PBPCs is feasible. Preliminary data suggest significant activity in selected patients with stage IV responding breast carcinoma.

Adult↗
PubMed2001

Survey of hospital doctors' attitudes and knowledge of oral conditions in older patients.

The study was designed to assess the views and knowledge of hospital doctors in general and geriatric medicine on oral health in older people. Eighty two doctors in general and geriatric medicine at two hospitals were shown 12 colour slides of oral mucosal conditions and asked to give a diagnosis for each slide and complete a questionnaire. Completed questionnaires with the answers to the coloured slides were returned completed by 70 doctors. The majority of doctors (84%) felt it was important to examine older patients' mouths, however only 19% (chi(2) p=0.0001) routinely do so. If asked to prescribe nystatin by the nursing staff, 30% said they would do so without examining the mouth itself. Only 9% of doctors knew that wearing dentures was a specific risk factor for oral candidiasis (chi(2) p=0.001). Altogether 56% of doctors did not feel confident in examining the oral cavity and most (77%) did not think they had had sufficient training in this examination. Only two doctors correctly diagnosed all of the slides. An early squamous carcinoma was misdiagnosed by 80% of the doctors (chi(2) p=0.0001). Hospital doctors do not routinely inspect older patients' mouths. Even if shown slides of typical oral mucosal lesions many hospital doctors are unable to diagnose them. Issues on training need to be addressed. From the patients' point of view a public health campaign is required to educate older people on the need for a regular dental review and be aware that doctors may not be able to diagnose serious oral conditions.

Aged↗
PubMed2001

Autoradiographic localisation and contractile properties of prostatic endothelin receptors in patients with bladder outlet obstruction.

OBJECTIVES: Previous studies have used endothelin (ET) receptor agonists and antagonists to localise ET receptor subtypes in prostatic tissue. We have utilised high affinity ET(A) ([(125)I]PD151242) and ET(B) ([(125)I]BQ3020) receptor-specific radioligands to determine the density and distribution of ET receptor subtypes in prostatic tissues obtained from patients with symptomatic benign prostatic hyperplasia (BPH). The contractile properties of the ET receptor subtypes as well as the effect of ET-1 on alpha(1)-adrenergic receptor-mediated prostatic smooth muscle contraction were assessed. PATIENTS AND METHODS: Saturation binding and quantitative autoradiographic studies were performed using specific radioligands for ET(A) and ET(B) receptors on prostate sections obtained from patients with bladder outflow obstruction secondary to BPH. In vitro isometric tension studies were carried out to characterise the ET receptor subtypes in prostatic smooth muscle strips from the same group of patients. In addition, the effect of ET-1 on alpha(1)-adrenergic receptor-induced prostatic smooth muscle contraction was also investigated. RESULTS: There were dense ET(A) and ET(B) receptor-binding sites in the prostatic stroma. ET(A) receptor-binding sites were also prominent on the prostatic epithelium. ET-1 and sarafotoxin 6 c (ET(B) receptor agonist) elicited prostatic smooth muscle contraction (-log EC(50) 8.31+/-0.15 and 8.22+/-0.22 M, respectively). Both BQ123 (ET(A) antagonist) and BQ788 (ET(B) antagonist) significantly inhibited ET-1- and S6c-mediated prostatic smooth muscle contractile responses, respectively. ET-1 at sub-threshold concentrations significantly enhanced alpha(1)-adrenergic receptor-mediated prostatic smooth muscle contractile responses. CONCLUSIONS: ET(A) receptor-binding sites are prominent in both prostatic stroma and epithelium, whereas ET(B) receptor-binding sites were predominantly seen in the prostatic stroma in symptomatic BPH. Both ET(A) and ET(B) receptors mediate prostatic smooth muscle contraction. ET-1 enhances alpha(1)-adrenergic receptor-mediated contractile responses, suggesting that ET may play a pathophysiological role in bladder outlet obstruction associated with BPH.

Aged↗
PubMed2001

Efficacy and safety of sildenafil citrate in the treatment of men with mild to moderate erectile dysfunction.

BACKGROUND: Erectile dysfunction is a common, multi-factorial disorder. AIMS: To evaluate the efficacy, tolerability and frequency of use of sildenafil citrate in men with mild to moderate erectile dysfunction of no established organic cause. METHOD: This double-blind, randomised, placebo-controlled, flexible-dose, two-way crossover study was conducted at four centres in the UK in 44 men with mild to moderate erectile dysfunction of no clinically obvious organic cause. The study included two 28-day treatment periods, during which time sildenafil or placebo (25-75 mg, based on efficacy) was taken as required. RESULTS: Compared with placebo, sildenafil was associated with increases in frequency of use, erections adequate for sexual intercourse and level of sexual satisfaction (P:<0.0001). More patients receiving sildenafil stated they would use the treatment again compared with those receiving placebo (P:<0.0001). There were no discontinuations due to sildenafil treatment. CONCLUSIONS: Sildenafil is effective and well tolerated in men with mild to moderate erectile dysfunction of no clinically identifiable organic cause.

Adolescent↗
PubMed2001

Rotational digital subtraction angiography of the renal arteries: technique and evaluation in the study of native and transplant renal arteries.

Rotational digital subtraction angiography (RDSA) allows multidirectional angiographic acquisitions with a single injection of contrast medium. The role of RDSA was evaluated in 60 patients referred over a 7-month period for diagnostic renal angiography and 12 patients referred for renal transplant studies. All angiograms were assessed for their diagnostic value, the presence of anomalies and the quantity of contrast medium used. The effective dose for native renal RDSA was determined. 41 (68.3%) native renal RDSA images and 8 (66.7%) transplant renal RDSA images were of diagnostic quality. Multiple renal arteries were identified in 9/41 (22%) native renal RDSA diagnostic images. The mean volume of contrast medium in the RDSA runs was 51.2 ml and 50 ml for native and transplant renal studies, respectively. The mean effective dose for 120 degrees native renal RDSA was 2.36 mSv, equivalent to 1 year's mean background radiation. Those RDSA images that were non-diagnostic allowed accurate prediction of the optimal angle for further static angiographic series, which is of great value in transplant renal vessels.

Anastomosis, Surgical↗
PubMed2001

Diagnostic angiography performed by nurses.

The aim of this study was to assess the feasibility of a nurse performing diagnostic angiography. After a theoretical and practical training course on the techniques of arterial catheterization, the nurse performed diagnostic angiography under supervision on 68 patients. Patients with impalpable femoral pulses or scarred groins as well as obese patients were excluded. Successful arterial catheterization was achieved in 58 (85%) patients. Complications were limited to a severe haematoma requiring surgery in one patient and seven minor self-limiting haematomas. On this evidence, it is feasible and safe for appropriately trained nurses to perform angiography in radiology departments that have limited radiology staffing levels and no non-invasive alternations to catheter-based angiography.

Angiography↗
PubMed2001

Phase I trial of 96-hour continuous infusion of dexrazoxane in patients with advanced malignancies.

Dexrazoxane is a bidentate chelator of divalent cations. Pretreatment with short infusions of dexrazoxane prior to bolus doxorubicin has been shown to lessen the incidence and severity of anthracycline-associated cardiac toxicity. However, because of rapid, diffusion-mediated cellular uptake and the short plasma half-life of dexrazoxane, combined with prolonged cellular retention of doxorubicin, dexrazoxane may be more effective when administered as a continuous infusion. Thus, a Phase I pharmacokinetic trial of a 96-h infusion of dexrazoxane was performed. Dexrazoxane doses were escalated in cohorts of 3 to 6 patients per dose level. All patients received granulocyte-colony stimulating factor at a dose of 5 microg/kg/day starting 24 h after completion of the dexrazoxane infusion. Plasma samples were collected and analyzed for dexrazoxane by high-performance liquid chromatography. Urine collections were performed at baseline and during the infusion to determine the renal clearance of dexrazoxane and the excretion rate of divalent cations. Twenty-two patients were enrolled at doses ranging from 125 to 250 mg/m(2)/day. Grade 3 and 4 toxicities included grade 4 thrombocytopenia in 2 patients treated at 250 mg/m(2)/day, grade 3 thrombocytopenia and grade 4 nausea and vomiting in 1 patient treated at 221 mg/m(2)/day, grade 4 diarrhea and grade 3 nausea and vomiting in 1 patient treated at 221 mg/m(2)/day, and grade 3 hypertension in 1 patient treated at 166.25 mg/m(2)/day. Steady-state dexrazoxane levels ranged from 496 microg/l (2.2 microM) to 1639 microg/l (7.4 microM). Dexrazoxane plasma CL(ss) and elimination t(1/2) were 7.2 +/- 1.6 l/h/m(2) and 2.0 +/- 0.8 h, respectively. The mean percentage of administered dexrazoxane recovered in the urine at steady state was 30% (range, 10-66%). Urinary iron and zinc excretion during the dexrazoxane infusion increased in 12 of 18 and 19 of 19 patients by a median of 3.7- and 2.4-fold, respectively. These results suggest that dexrazoxane as a 96-h infusion can be safely administered with granulocyte-colony stimulating factor at doses that achieve plasma levels that have been demonstrated previously to inhibit topoisomerase II activity and to induce apoptosis in vitro. Additional studies will be required to determine whether the combination of continuous infusions of dexrazoxane and doxorubicin would provide enhanced cardioprotection compared with the currently recommended bolus or short infusion schedules.

Aged↗
PubMed2001

Influenza vaccine. Past and present.

The difficulty experienced last year in delivering influenza vaccine, while disappointing, nevertheless provided a unique opportunity for public and private partners to focus attention on the weaknesses in the national influenza vaccine-manufacturing and delivery system. Every effort is being made to ensure the timely distribution of sufficient vaccine to the public during the 2001-2002 influenza season. It is important for providers to target their highest risk patients with the first available influenza vaccine distribution (expected no later than October 2001). Additionally, DHSS regulations require that eligible hospitalized patients and residents of long-term care facilities receive vaccine as a key strategy to improving vaccination rates. Finally, the DHSS will continue intensive influenza surveillance and outreach efforts throughout the 2001-2002 influenza season.

Antiviral Agents↗
PubMed2000

Contribution of LHC II complex to the electric properties of thylakoid membranes: an electric light scattering study of Chl b-less barley mutant.

Electric light scattering measurements demonstrate a strong decline in the permanent electric dipole moment and electric polarizability of both thylakoid membranes and photosystem II-enriched particles of the Chlorina f2 mutant which has severely reduced levels of light-harvesting chlorophyll a/b-binding proteins compared to the wild type barley chloroplasts. The shift in the electric polarizability relaxation to higher frequencies in thylakoids and photosystem II particles from Chlorina f2 reflects higher mobility of the interfacial charges of the mutant than that of the wild type membranes. The experimental data strongly suggest that the major light-harvesting complex of photosystem II directly contribute to the electric properties of thylakoid membranes.

Chlorophyll↗
PubMed2000

Absorption of antisense oligonucleotides in rat intestine: effect of chemistry and length.

An in situ single-pass perfusion model was used to assess the effect of chemical modification and length on permeability and absorption of various oligonucleotides in rat intestine. Phosphorothioate oligodeoxynucleotides (PS-ODN) were compared with oligoribonucleotides with 2'-methoxyethyl (MOE) or 2'-O-methyl (OMe) modifications. A 25-mer PS-OMe-modified oligonucleotide showed relatively poor permeability in this model, as did unmodified 20-mer PS-ODN (permeability coefficient [P(eff)] = 2-8 X 10(-6)cm/sec). Modifying some or all of the oligonucleotides with 2'-MOE groups on deoxyribose and 5'-methylation of the cytosines substantially increased intestinal permeability of oligonucleotides. Both partially and fully modified PS-MOE oligonucleotides showed a (2-4)-fold increase in permeability as compared with unmodified PS-ODN. The presence of a phosphodiester backbone in MOE-modified compounds led to further increases in intestinal permeability. PS-MOE composed of 6, 8, 10, 12, 14, 16, 18, 20, and 22 nucleotides were also examined. It was found that the permeability of these oligonucleotides increased linearly with decreasing length.

Animals↗
PubMed2000

Abdominal trauma in infants and children: prompt identification and early management of serious and life-threatening injuries. Part I: injury patterns and initial assessment.

Evaluation of children with abdominal trauma can be a difficult process. Unique anatomic features predispose children to specific injuries and potentially make identification of life-threatening injuries difficult. While Part I of this review discusses the initial assessment and diagnostic testing in children with abdominal trauma, Part II will review specific injuries and ED management of children with possible abdominal trauma. Knowledge of each of these factors will improve the ability of general and pediatric emergency physicians to expeditiously identify children with potential serious injury and initiate appropriate treatment.

Abdominal Injuries↗