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Biomedical subjects

R J Powell

Publications and source records attributed to R J Powell.

At least 37 records · Page 2Linked to original sources

Quantitative and qualitative analysis of the balance between type 1 and type 2 cytokine-producing CD8(-) and CD8(+) T cells in systemic lupus erythematosus.

The production of type 1 (IFN-gamma, IL-2) and type 2 (IL-4, IL-5, IL-10, IL-13) cytokines by CD8(-) and CD8(+) T cells from systemic lupus erythematosus (SLE) patients and normal subjects was investigated using an intracellular cytokine-staining technique. This flow cytometric method facilitates analysis of both surface markers and cytoplasmic cytokines, after a short term (6 h) culture with or without phorbol myristate acetate and ionomycin (PMA/I) stimulation. In SLE patients, more unstimulated T cells produced IL-10 in comparison with controls; other cytokines were not detected in unstimulated cells. The percentage of IL-10-secreting T cells did not significantly increase after PMA/I stimulation of cells from SLE patients. The mean intensity of fluorescence (MIF) of intracellular IL-4 staining was significantly higher in CD8(-) T cells of SLE patients than controls. Significantly fewer CD8(-) and CD8(+) T cells from SLE patients secreted IFN-gamma after PMA/I stimulation compared with controls. The MIF and percentage of IL-2, IL-5, and IL-13-secreting cell subsets were not significantly different between SLE patients and controls. These findings indicate that T cells of SLE patients are already stimulated to produce IL-10 in vivo, which may result in downregulation of IFN-gamma secreting CD8(-) and CD8(+) T cells observed following PMA/I stimulation. Thus, the population size of Th1 and Tc1 cells are reduced in SLE patients whereas the effector function of Th2 cells, with respect to IL-4 production, is enhanced in SLE patients. Furthermore, although the balance between Th1/Th2 and between Tc1/Tc2 is disrupted in SLE patients, it is significantly biased in favour of the Th2 subset only.

Adult↗

Retroviral activity in Behçet's syndrome and systemic lupus erythematosus detected by a PCR-based reverse transcriptase assay.

The objective of this study was to assess retroviral activity in Behçet's syndrome (BS) and systemic lupus erythematosus (SLE) patients. Serum and peripheral blood mononuclear cells (PBMC) were obtained from patients and normal volunteers and PBMC cultured with and without phytohaemagglutinin stimulation. Reverse transcriptase (RT) activity in serum and culture supernatants was measured using a sensitive polymerase chain reaction-based assay. An RT activity above the levels in normal controls was detected in a minority of patients with BS (2/15) and SLE (1/13) and was typically present in all three types of sample. Elevated levels of RT activity were not detected in follow-up samples from the two BS patients. Our findings indicate that elevated RT activity is present in only a minority of patients with BS and SLE. Simultaneously elevated activity in all three sample types implicates PBMC as the source of this retroviral activity.

Adult↗

Tacrolimus (FK506) in the management of high-risk corneal and limbal grafts.

OBJECTIVE: To assess the efficacy and side effects of tacrolimus in the management of patients with high-risk corneal and limbal grafts. DESIGN: Noncomparative case series. PARTICIPANTS: Seventeen patients (23 grafts) were treated with tacrolimus; 15 patients (20 host corneas) had two or more quadrants of stromal vascularization, 6 patients had stem cell deficiency, and 6 patients had glaucoma. Seven patients had received one previous graft, six patients had two previous grafts, and four patients had three previous grafts. INTERVENTION: Patients with high-risk corneal and limbal grafts were treated with systemic tacrolimus at a mean optimum dosage of 4.4 mg daily (range, 2-12 mg daily). MAIN OUTCOME MEASURES: Graft survival, visual acuity. RESULTS: No patient has had irreversible graft rejection while receiving tacrolimus. The follow-up period ranges from 12 to 46 months, with a mean of 24 months. Three patients have had reversible graft rejection associated with low tacrolimus levels. Nine patients have stopped treatment; two had reversible rejection within 2 months of stopping, and five grafts remain clear. The other four patients stopped treatment because of graft failure, which was not considered to be rejection related. Eight patients remain on treatment, and all have clear grafts. CONCLUSIONS: Tacrolimus (FK506) is effective in prevention of rejection in patients with high-risk corneal and limbal grafts.

Epithelial Cells↗

Seasonal differences in finger skin temperature and microvascular blood flow in healthy men and women are exaggerated in women with primary Raynaud's phenomenon.

AIMS: Patients with primary Raynaud's phenomenon (PRP) have more severe symptoms in the winter. The aetiology of this is more complex than simply increased vasoconstriction in response to the immediate ambient temperature. The aim of this study was to investigate differences in skin temperature (Tsk), microvascular blood flow and responses to endothelium-dependent and independent vasodilators in healthy controls, and women with PRP under identical environmental temperatures but in different seasons. METHODS: Ten women with PRP were compared with age matched women (10) and men (10). Finger skin responses were recorded immediately on arrival, after stabilizing in a temperature regulated laboratory at 22-24 degrees C, and at matched warm (35 degrees C) and cold (15 degrees C) Tsk in the winter and summer. Baseline red blood cell flux (r.b.c. flux), and the change in flux in response to iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) were recorded by laser Doppler fluxmetry at the warm and cold Tsk. RESULTS: Arrival Tsk were significantly cooler for all subjects during the winter (mean seasonal difference -2.6 degrees C, P < 0.0001), and markedly colder in subjects with PRP (mean seasonal difference -3.5 degrees C, P < 0.0005). Statistically significant seasonal differences persisted in all subjects at stable Tsk despite an identical laboratory temperature (mean difference 1.3 degrees C, P < 0.0001). To achieve comparable controlled finger Tsk a significantly colder local environment was required for male controls (mean of -2.1 degrees C, P < 0.0001), and a significantly warmer environment for subjects with PRP (mean of + 2.4 degrees C, P < 0.0001) compared with female controls. This needed to be warmer in the winter, by a mean of 2.4 degrees C, than the summer for all subjects. Vasodilatation in response to ACh, but not SNP, was significantly smaller (P < 0.0001) in the PRP group compared with the female controls for all visits, with most of this difference arising in the winter visits (P < 0.01). CONCLUSIONS: There is a seasonal and persistent influence on finger Tsk, and microvascular blood flow in healthy men and women, which modifies the observed responses to immediate changes in finger Tsk. The seasonal differences are greater in women than men, and are further exaggerated in women with PRP, in whom this is associated with reduced endothelium-dependent vasodilatation.

Acetylcholine↗

Investigation for immunodeficiency in patients with recurrent ENT infections.

Patients suffering with primary immunodeficiency frequently present to ear, nose, and throat (ENT) clinics, but the diagnosis is rarely made at this time. Early diagnosis of these patients would help to prevent morbidity and even mortality. Normal results from a simple panel of blood tests will exclude the commonest immune deficiencies. An abnormal result from these tests, or a strong suspicion despite normal initial testing, should prompt discussion with an immunologist.

Humans↗

Early results of infragenicular revascularization based solely on duplex arteriography.

PURPOSE: Recent reports have both advocated and questioned the utility of duplex arteriography (DA) as the sole preoperative imaging modality for planning infragenicular revascularization. This study compares the outcome of patients with critical limb ischemia who underwent infragenicular vein grafts on the basis of DA alone versus conventional preoperative contrast arteriography (CA). METHODS: The study group is composed of 23 consecutive patients who underwent infragenicular vein bypass grafting solely on the basis of preoperative DA from 1998 to 1999. They were compared with 50 consecutive patients who underwent infragenicular vein bypass grafting after CA from 1996 to 1998. Peak systolic velocity and end-diastolic velocity of potential target arteries were recorded during DA studies. In situ saphenous vein grafts were used preferentially, and technical adequacy of all grafts was assessed with completion duplex or arteriography. RESULTS: DA and CA groups were comparable on the basis of age and risk factors. In one limb (4%), the target artery selected by DA was abandoned because of dense calcification. No other revision in target or inflow artery was required on the basis of intraoperative completion studies. At 1 year, primary graft patency (78% vs 70%, P =.72) and limb salvage (70% vs 81%, P =.21) were comparable between the two groups. In the DA group, mean preoperative target artery peak systolic velocity in patent versus failed grafts was 49 +/- 18 cm/s versus 31 +/- 9 cm/s (P =.04), whereas mean end-diastolic velocity was 22 +/- 7 cm/s versus 14 +/- 8 cm/s (P =.08). CONCLUSION: Infragenicular revascularization directed by DA alone provides early graft patency and limb salvage rates comparable to similar procedures that are based on CA. Preoperative DA target artery velocities may predict outcome and improve target selection. These initial results justify further clinical testing of DA as the primary imaging modality for planning infragenicular vein grafts.

Angiography↗

Results of endovascular superficial femoral endarterectomy.

BACKGROUND: Endovascular superficial femoral artery (SFA) endarterectomy with a ring stripper/cutter and distal stenting has been suggested to have a patency comparable with above-knee bypass surgery. We report our initial experience with this technique. METHODS: Seventeen patients (13 men and 4 women; mean age, 64 years) with SFA occlusion and above-knee popliteal reconstitution underwent attempted remote endarterectomy with a ring cutter system combined with primary stenting of the distal end point. Analysis was performed in a prospective manner with patency rates determined by Kaplan-Meier life-table analysis. RESULTS: The indication for operation was claudication in 8 patients, rest pain in 6, and tissue loss in 3. Initial technical success was achieved in 11 patients (65%). Reasons for technical failure included SFA perforation (4), inability to traverse a calcified/diseased segment (1), and inability to retract/remove the ring cutter (1). Life-table analysis of all patients revealed a primary patency at 1 year of 26% +/- 11%. Primary-assisted patency was 38% +/- 12% at 1 year, with 59% of patients ultimately requiring surgical bypass grafting. In patients in whom initial technical success was achieved, the 1-year primary and primary-assisted patency rates were 40% and 59%, respectively. There were four reocclusions requiring surgical revascularization with below-knee popliteal (2) or tibial (2) bypass grafting, 1 symptomatic restenosis requiring repeat angioplasty, and 1 symptomatic restenosis treated conservatively. CONCLUSION: The results of endovascular SFA endarterectomy were disappointing, with technical success in less than two thirds of patients and a 1-year primary patency of only 26%. Remote SFA endarterectomy appears less effective than above-knee femoropopliteal bypass grafting, and after early failure, patients may require more distal revascularization for limb salvage.

Angioplasty↗

Vascular smooth muscle cell effect on endothelial cell endothelin-1 production.

Endothelin-1 (ET-1) is a potent mitogen secreted by endothelial cells (ECs) in culture and is a putative factor in vascular lesion development. The purpose of this study was to examine whether smooth muscle cells (SMCs) inhibit EC secretion of ET-1. The effect of SMCs on EC ET-1 and constitutively expressed nitric oxide (NO) synthase activity was examined by using a bilayer co-culture model. SMCs inhibited both EC ET-1 protein and RNA levels, compared with ECs cultured alone. SMCs increased EC NO production when compared with ECs cultured alone. In addition, SMC inhibition of EC ET-1 production could be blocked by the NO synthase inhibitor N(G)-nitro-L-arginine-methyl ester. ECs stimulated SMC proliferation, and the ET-1 AB and B receptor blockers inhibited EC stimulation of SMC proliferation. The ET-1 A blocker had no effect on SMC proliferation. We conclude that SMCs regulate EC ET-1 and ecNOS synthase transcript levels and protein levels. SMC inhibition of ET-1 production by ECs may be mediated through SMC-modulated changes in EC NO activity. Finally, EC stimulation of SMC proliferation in bilayer co-culture is mediated by ET-1 through the ET-1 B receptor.

Analysis of Variance↗

The durability of endovascular treatment of multisegment iliac occlusive disease.

PURPOSE: The effectiveness of endovascular treatment of multisegment iliac occlusive disease (involving two or more common and/or external iliac arteries) was determined. METHODS: All patients who underwent angioplasty or stenting of at least two separate iliac artery segments were identified. Demographic data were recorded. Technical success, hemodynamic success, and aortoiliac primary and primary-assisted patency were analyzed by using the Society for Vascular Surgery and International Society for Cardiovascular Surgery (SVS/ISCVS) criteria. Multivariate, life table analysis was used as a means of determining outcome predictors. RESULTS: Eighty-seven patients underwent 207 iliac artery angioplasties and 115 iliac artery stents, which were performed in 210 iliac segments for disabling claudication in 60% of cases, for rest pain in 17% of cases, and for tissue loss in 23% of cases. Two iliac segments were treated in 64% of patients, three segments were treated in 28% of patients, and four segments were treated in 8% of patients. The complication rate was 11%. Initial hemodynamic success was achieved in 72% of cases. Clinical improvement occurred in 88% of patients. Subsequent endovascular reintervention was required in 29% of patients, whereas surgical inflow procedures were required in 14% of patients to maintain aortoiliac patency. The mean time from the primary intervention to the first reintervention was 10 +/- 3 months. At 6, 12, and 36 months after intervention, the primary patency rates of the aortoiliac segment were 76%, 61%, and 43%, respectively, and the primary assisted patency rates were 95%, 87%, and 72%, respectively. Only the presence of an external iliac artery stenosis adversely affected both primary and assisted-primary patency. At 6, 12, and 36 months, the aortoiliac primary patency rates in patients without the presence of an external iliac artery stenosis were 88%, 78%, and 69%, respectively, compared with 68%, 47%, and 18%, respectively, in patients with external iliac artery lesions (P <. 0001). CONCLUSION: Endovascular therapy for multisegment aortoiliac occlusive disease has acceptable patency rates; however, reintervention is often needed. The presence of external iliac artery disease is a significant predictor of poor outcome.

Angioplasty, Balloon↗

Predicting outcome of angioplasty and selective stenting of multisegment iliac artery occlusive disease.

BACKGROUND: Patients who require angioplasty and stenting of multiple iliac arterial segments often require reintervention to maintain long-term patency. Morphologic predictors and causes of failure are unknown. The purpose of the current study was to define arteriographic predictors of angioplasty and selective stent failure in the treatment of multisegment iliac occlusive disease. METHODS: All iliac segments (two common and two external) of 75 patients who underwent angioplasty and selective stent placement for multisegment iliac occlusive disease (>/= two segments) were scored through use of a modification of the Society of Cardiovascular and Interventional Radiology classification for iliac angioplasty (0 = no lesion; 4 = most severe). Total iliac score was calculated by summing scores from each segment. A separate external iliac score was calculated by adding only the external iliac scores. Arteriograms were reviewed initially and at the time of lesion recurrence and stratified by lesion location and previous intervention. RESULTS: The area of previous endovascular intervention was the site of recurrence in 75% of patients. New lesions, presumably a result of progressive atherosclerosis, occurred in 15% of patients, and lesions occurred in both new and previously treated iliac segments in 10% of patients. Only the external iliac score was an independent predictor of failed endovascular therapy despite reintervention. For patients with an external iliac score of 2 or less, the endovascular primary-assisted patency rates at 6, 12, and 24 months were 96%, 92%, and 89%, respectively. This was improved in comparison with the 90%, 63%, and 45% patency rates observed in patients with an external iliac score of 3 or more (P =.001). Patients with an external iliac score of 3 or more had a significantly lower incidence of hemodynamic and clinical improvement after intervention and a threefold higher need for surgical inflow procedures than patients with an external iliac score of 2 or less. CONCLUSIONS: Lesion formation after treatment of multisegment iliac occlusive disease typically occurs in areas of prior intervention. The extent of external iliac disease can be used to stratify patients with multisegment iliac occlusive disease who will likely respond to endovascular treatment with a durable result. Patients with extensive external iliac disease (score >/= 3) have poor results after angioplasty and selective stenting as applied in this study, even with endovascular reintervention. They are ideal subjects for prospective comparative studies of competing initial therapies, including stenting, endografting, and aortobifemoral bypass grafting.

Aged↗

Pedal branch artery bypass: a viable limb salvage option.

PURPOSE: We reviewed our experience with pedal branch artery (PBA) bypass to confirm the role of these target arteries for limb salvage and to identify patient and technical factors that may be associated with graft patency and limb salvage. METHODS: In this retrospective study we analyzed 24 vein grafts to PBAs performed from 1988 to 1998 for limb salvage in 23 patients who had no suitable tibial, peroneal, or dorsal pedal target arteries. These PBA grafts were compared with 133 perimalleolar posterior tibial, defined at or below the ankle, or dorsalis pedis bypass grafts performed contemporaneously; the Kaplan-Meier life table was used in the analysis of graft patency and limb salvage. Life table analyses and logistic regression analysis of prognostic patient variables were also performed. RESULTS: The PBA bypass represented 3% of infrainguinal revascularizations for chronic critical limb ischemia at our institution over the study period. Patients who received PBA bypasses were more likely to be male (92% vs. 69%, P =.02) with lower incidences of overt coronary artery disease (33% vs. 50%, P =.12) and stroke (0% vs 15%, P =.04), and a higher incidence of end-stage renal disease (21% vs 8%, P =.06) than those undergoing perimalleolar bypass. Seventeen percent of PBA bypasses were performed with the anterior lateral malleolar artery, a vessel not previously described as a common bypass target. Two-year primary patency and limb salvage for PBA versus perimalleolar bypass was 70% versus 80% (P =.16) and 78% versus 91% (P = .28), respectively. Patency and limb salvage rates were no different in bypasses with above-knee or below-knee inflow arteries. CONCLUSION: An autogenous vein bypass to the PBA, though rarely required, provides acceptable primary patency and limb salvage when compared with perimalleolar tibial artery bypass when no suitable, more proximal target arteries are available. The PBA bypass should be considered before major amputation is undertaken.

Aged↗

Papulonecrotic tuberculide and stenosis of the abdominal aorta.

Papulonecrotic tuberculide (PNT) is a rare form of skin tuberculosis affecting predominantly young adults, with a history of immunity to Mycobacterium tuberculosis. We report a case of a young Caucasian female with PNT who was also documented to have a stenotic segment in the abdominal aorta. The difficulty in clarifying and treating the primary disease and the association between a tuberculous infection and Takayasu's arteritis are discussed.

Adolescent↗