Biomedical subjects

T R Magee

Publications and source records attributed to T R Magee.

At least 37 records · Page 2Linked to original sources

PubMed2002

Gene expression in Peyronie's disease.

Currently, surgical intervention is the only efficacious treatment for Peyronie's disease (PD), a fibromatosis of the tunica albuginea of the penis. Therapies based on the molecular pathways for this disease could provide alternatives to surgical treatment but only recently has the pathophysiology of the Peyronie's disease plaque been investigated at the molecular level. In this review, we examine the current knowledge of gene expression in the PD plaque and the relationship of PD with other fibrotic conditions such as Dupytren's disease. TGFbeta1, along with other growth factors, pro-fibrotic genes, and collagen, are expressed in fibroblasts and myofibroblasts. Myofibroblasts are normally involved in wound contracture and largely eliminated via apoptosis during the late stages of wound remodeling. In the PD plaque, however, these cells persist and may play an important role in the PD plaque fibrosis. The expression levels of TGFbeta1 and pro- and anti-fibrotic gene products, along with the nitric oxide/reactive oxygen species (NO/ROS) ratio in the tunica albuginea, appear to be essential for the formation and progression of the PD plaque and effect the expression of multiple genes. This can be assessed with the recently developed DNA-based chip arrays and results with the PD plaque have been encouraging. OSF-1 (osteoblast recruitment), MCP-1 (macrophage recruitment), procollagenase IV (collagenase degradation), and other fibrotic genes have been identified as being possible candidate regulatory genes. Finally, possible therapeutic avenues for gene-based therapy in the treatment of PD are discussed that may eventually reduce the need for surgical intervention.

Animals↗

PubMed2002

Management of popliteal aneurysm.

BACKGROUND: The best management of patients with a popliteal aneurysm has yet to be established. This paper describes an experience of managing both patent and acutely thrombosed popliteal aneurysms. METHODS: A prospective study was carried out of all patients who presented with a popliteal aneurysm from January 1988 to December 2001. Since 1993 asymptomatic popliteal aneurysms less than 3 cm in diameter without distortion have been managed conservatively. Ultrasonography was repeated at 6-month intervals. These results were compared with conservative management of popliteal aneurysms greater than 3 cm in diameter in patients who declined or were unfit for operation, and with the outcome of patients who underwent elective bypass of a popliteal aneurysm. RESULTS: Fifty-eight patients (two women) presented with 92 popliteal aneurysms. Some 39 had a thrombosed aneurysm and these patients were significantly more likely to have bilateral aneurysms (P < 0.001). Of patent popliteal aneurysms managed conservatively, none below 3 cm in diameter thrombosed. The risk of postoperative complications was greater after repair of a thrombosed than a patent aneurysm (P < 0.005). Preoperative lysis for a thrombosed popliteal aneurysm was associated with more complications than operation and on-table lysis (P < 0.05). CONCLUSION: Careful monitoring of asymptomatic popliteal aneurysms less than 3 cm in diameter is safe. Preoperative lysis is associated with increased risks compared with operation alone in patients with a thrombosed popliteal aneurysm.

Aged↗

PubMed2001

Early results of retrograde transpopliteal angioplasty of iliofemoral lesions.

PURPOSE: To assess whether the retrograde transpopliteal approach is a safe, practical and effective alternative to femoral puncture for percutaneous transluminal angioplasty (PTA). METHODS: Forty PTAs in 38 patients were evaluated. Intentional subintimal recanalization was performed in 13 limbs. Ultrasound evaluation of the popliteal fossa was carried out 30 min and 24 hr postprocedurally in the first 10 patients to exclude local complications. All patients had a follow-up of at least 6 weeks. RESULTS: The indication for PTA was critical ischemia in seven limbs and disabling claudication in the remainder. Stenoses (single or multiple) were present in 24 and occlusion in 15. The superficial femoral artery (SFA) was the commonest segment affected (36) followed by common femoral artery (CFA) in four and iliac artery in four. Technical success was achieved in 38 of 39 limbs where angioplasty was carried out. In one limb no lesion was found. Immediate complications were distal embolization in two and thrombosis in one. None of these required immediate surgery. There were no puncture site hematomas or popliteal arteriovenous fistulae. Symptomatic patency at 6 weeks was 85%. Further reconstructive surgery was required in three limbs and amputation in two. CONCLUSION: The transpopliteal approach has a high technical success rate and a low complication rate with a potential to develop into an outpatient procedure. It should be considered for flush SFA occlusions or iliac disease with tandem CFA/SFA disease where the contralateral femoral approach is often technically difficult.

Aged↗

PubMed2001

Stenting for localised arterial stenoses in the aorto-iliac segment.

OBJECTIVE: to determine complications and patency following angioplasty (PTA) and stenting of aorto-iliac stenoses. SETTING: District General Hospital in U.K. DESIGN: prospective observational study. PATIENTS AND METHODS: between December 1994 and June 2000, 50 patients (38 men), median age 64 (41-89) years underwent aorto-iliac stenting. A total of 61 stents were placed. Indications were intermittent claudication in 38 and rest pain, ulceration or gangrene in 12. Sites stented were aorta 11, common iliac artery 32, external iliac artery 14, common and external iliac arteries two. Bilateral iliac procedures were carried out in nine. Two stents were used to correct residual stenoses after aortic stenting. Some 11 recurrent stenoses were treated. The other reasons for stenting were residual stenoses greater than 30% after PTA, tight calcified stenoses or when a stenosed iliac artery was being used as a donor prior to crossover or femoropopliteal bypass. RESULTS: two immediate technical failures occurred due to malposition. Residual stenoses were corrected by PTA. Two further patients sustained minor complications. None of the aortic stents occluded through two required secondary procedures. Primary-assisted patency was thus 100% at three years. Primary patency following iliac stenting for claudication and critical ischaemia were 97% and 86% at three years respectively. CONCLUSION: PTA and stenting of aorto-iliac stenoses can be safely achieved with durable results.

Adult↗

PubMed2001

Methicillin resistant Staphylococcus aureus in patients undergoing major amputation.

OBJECTIVES: To examine the impact of MRSA infection on patients undergoing major amputation. SETTING: District General Hospital. METHODS: Patients having had major amputation and positive MRSA cultures January 1995-December 1999 were included. Outcome was compared with a randomly chosen group of patients having major amputation but no positive MRSA culture from the same time period. RESULTS: overall 21% of patients undergoing amputation were MRSA positive. Some 28 patients (30 amputations) with MRSA positive cultures were compared with 44 patients (54 amputations) who did not have positive cultures for MRSA. MRSA was isolated from the wound in 17 of 30 amputations. More patients in the control group had a below knee amputation (38 of 54 compared with 12 of 30, p<0.02). Mortality in MRSA positive patients was higher than controls, (12 of 28, 43%, versus 4 of 44, 9%, p<0.01). Primary healing was achieved in only 4 of 17 (24%) amputations where MRSA was isolated from the wound. This compared with 31 of 54 (57%) controls (p<0.05). Delayed healing due to chronic infection was also more likely in MRSA positive patients (p<0.01). CONCLUSION: In view of the high morbidity and mortality in patients with MRSA positive isolates specific antibiotic prophylaxis against MRSA should be considered in patients undergoing major amputation.

Adult↗

PubMed2001

Patency following successful thrombolysis of occluded vascular grafts.

AIM: to determine patency after successful lysis of occluded bypass grafts. METHODS: data were collected from four centres with a wide experience of thrombolysis. Outcome following successful lysis was determined from prospectively collected data or case notes. Data from 75 patients, 53 men, were analysed. RESULTS: median age at time of lysis was 68 years (range 33-88). Median age of graft was 12 months (range 1-120). Patency at 12 months was 33% (95% conf. interval: 21-44%). There were no differences in patency depending on whether the graft was above or below the inguinal ligament or whether an additional procedure eg. percutaneous or vein patch angioplasty was carried out. However in those 48 cases when lysis was deemed complete, i.e. there was restoration of graft patency and at least one vessel run off patency at 12 months was 39% compared with 17% if lysis was incomplete (p=0.04). CONCLUSIONS: at the present time it is difficult to justify routine thrombolysis of occluded grafts when patency, based on intention to treat, is approximately 20% at one year. Following successful graft lysis the role of anticoagulation and careful graft surveillance require further investigation.

Adult↗

PubMed2001

Aging-related expression of inducible nitric oxide synthase and markers of tissue damage in the rat penis.

Erectile dysfunction in the aging male results in part from the loss of compliance of the corpora cavernosal smooth muscle due to the progressive replacement of smooth muscle cells by collagen fibers. We have examined the hypothesis that a spontaneous local induction of inducible nitric oxide synthase (iNOS) expression and the subsequent peroxynitrite formation occurs in the penis during aging and that this process is accompanied by a stimulation of smooth muscle apoptosis and collagen deposition. The penile shaft and crura were excised from young (3-5 mo old) and old (24-30 mo old) rats, with or without perfusion with 4% formalin. Fresh tissue was used for iNOS and proteasome 2C mRNA determinations by reverse transcription polymerase chain reaction assay, ubiquitin mRNA by Northern blot, and iNOS protein by Western blot. Penile sections from perfused animals were embedded in paraffin and immunostained with antibodies against iNOS and nitrotyrosine, submitted to the TUNEL assay for apoptosis, or stained for collagen, followed by image analysis quantitation. A 4.1-fold increase in iNOS mRNA was observed in the old versus young tissues, paralleled by a 4.9-fold increase in iNOS protein. The proteolysis marker, ubiquitin, was increased 1.9-fold, whereas a related gene, proteasome 2c, was not significantly affected. iNOS immunostaining was increased 3.6-fold in the penile smooth muscle of the old rats as compared with the young rats. The peroxynitrite indicator nitrotyrosine was increased by 1.6-fold, accompanied by a 3.6-fold increase in apoptotic cells and a 2.0-fold increase in collagen fibers in the old penis. In conclusion, aging in the penis is accompanied by an induction of iNOS and peroxynitrite formation that may lead to the observed increase in apoptosis and proteolysis and may counteract a higher rate of collagen deposition in the old penis.

Aging↗

PubMed2001

Is a palpable short saphenous vein a useful clinical sign in varicose vein assessment?

The short saphenous vein (SSV) may be palpable in the popliteal fossa in patients with varicose veins. A prospective study has been carried out to determine the significance of this sign in the presence of primary varicose veins. The SSV was assessed by palpation of the popliteal fossa with the knee slightly flexed. Hand-held Doppler insonation (HHD) was also used in the out-patient clinic. All patients had SSV assessment by duplex scanning. One hundred and sixty legs were examined. In 68 the SSV was palpable; 39 (57%) of these had SSV reflux on duplex examination. When the SSV was not palpable (92 legs), only 1% (1 leg) refluxed on duplex scanning. SSV palpability had a 98% sensitivity, 75% specificity, 57% positive predictive value (PPV), and 99% negative predictive value (NPV). In comparison, HHD had 80% sensitivity, 87% specificity, 67% PPV and 93% NPV. The combined tests had 78% sensitivity, 73% specificity, 76% PPV and 100% NPV. Palpation of the SSV is a valuable part of clinical examination. If the SSV is not palpable, it is unlikely to reflux.

Adult↗

PubMed2001

Transmetatarsal amputation: an 8-year experience.

This study retrospectively reviews an 8-year consecutive series of transmetatarsal amputation (TMA) for forefoot ischaemia in diabetic and non-diabetic patients. Forty-one patients had TMA. Peri-operative mortality was 17% (7/41). A healed stump was achieved in 19 patients (46%) and 18 of these patients were independently mobile, or mobile with sticks. Non-diabetic patients (8/12) healed significantly better than diabetics (11/29). Median time to healing was 7 months (range 3-20 months). All non-healed survivors had a higher amputation (14 below-knee, 1 Syme's). A healed TMA gives good mobility, but prediction of who will heal after operation is unreliable. Time to healing is often lengthy, and failed healing results in higher amputation. These issues need to be fully discussed with the patient who is considered for TMA.

Adult↗

PubMed2000

Identification of retinoic acid-responsive elements on the HNF1alpha and HNF4alpha genes.

Hepatocyte nuclear factor 1alpha (HNF1alpha) and HNF4alpha are liver-selective transcription factors and are essential for hepatocyte differentiation. This study demonstrates that HNF1alpha as well as HNF4alpha genes contain a direct repeat with a space of one nucleotide (DR1)-retinoic acid (RA) response element that can be bound and regulated by RA and retinoid x receptor alpha (RXRalpha) complex. Transient transfection experiments showed that RA increased the promoter activity of the HNF1alpha and HNF4alpha genes in Hep3B cells. Overexpression of RXRalpha further enhanced the activities of both genes. Two putative RXRalpha binding sites on the HNF1alpha (-295 to -276) and HNF4alpha (-418 to -399) genes have been characterized. By transient transfection, both sites positively responded to RA, and overexpression of RXRalpha in Hep3B cells increased the regulatory effect. Gel mobility shift assay demonstrated that these two DR-1 sites could be bound by RXRalpha specifically. These data suggest that the differentiation effect of RA on hepatocyte may be due to direct interaction of RXRalpha with the RA-responsive elements on the HNF1alpha and HNF4alpha genes.

Alitretinoin↗

PubMed2000

Fatty acyl-CoAs inhibit retinoic acid-induced apoptosis in Hep3B cells.

Retinoic acid (RA) induces apoptosis in Hep3B human hepatoma cells. 9-Cis-RA (c-RA) had a similar effect as all-trans-RA (t-RA) in inducing cell death in Hep3B cells. RA-induced Hep3B-cell death was associated with inhibited expression of the hepatocyte nuclear factor 4 (HNF-4) gene. Palmitoyl-CoA ((C16:0)-CoA), the reported HNF-4 ligand, prevented RA-induced apoptosis. The effect of (C16:0)-CoA was specific, since palmitic acid and co-enzyme A had no effect in preventing RA-induced apoptosis. Bovine serum albumin (BSA) also prevented RA-induced apoptosis. However, in contrast to BSA, which induced cell growth, (C16:0)-CoA alone had no effect on cell growth. Investigating the possible role of HNF-4 in apoptosis, the reported HNF-4 antagonist (C18:0)-CoA was employed, and it also prevented RA-induced apoptosis. By transient transfection, overexpression of HNF-4 did not prevent RA-induced apoptosis. The induction and prevention of apoptosis caused by RA and (C16:0)-CoA were associated, respectively with the induction and inhibition of the expression of transforming growth factor beta (TGFbeta), which is known to play a role in apoptosis. Furthermore, RA and (C16:0)-CoA can regulate AP-1, which is a key regulator of the TGFbeta gene. Our data indicate that fatty acyl-CoAs can prevent RA-induced apoptosis and that TGFbeta, rather than HNF-4, may play a role in these regulatory processes. Our data also suggest that (C16:0)-CoA and (C18:0)-CoA are not the agonist and antagonist for HNF4, respectively in the Hep3B cell system.

Alitretinoin↗

PubMed2000

Is a reduction in residual volume a sub-clinical manifestation of hydrogen sulfide intoxication?

BACKGROUND: A number of employees at an aircraft factory were accidentally exposed to hydrogen sulfide. Because of concern that this may have resulted in lung injury, forty-seven workers were referred for clinical and physiological evaluation. METHODS: Comprehensive pulmonary function tests were performed including spirometry, flow volume curves, static lung volumes, and diffusion capacity for carbon monoxide. RESULTS: The results obtained indicated that ten people (23%) had an isolated reduction in residual volume. This was an unexpected finding as other physiological indices of lung function were within normal limits. Clinical examination was also normal, therefore, radiological investigations were considered inappropriate. CONCLUSIONS: It is suggested that the decrement in residual volume, in the presence of other normal indices of lung function, could represent a sub-acute manifestation of hydrogen sulfide intoxication.

Aircraft↗

PubMed2000

Maintenance of patency following remote superficial femoral artery endarterectomy.

BACKGROUND: Remote superficial femoral artery endarterectomy (RSFE) is a minimally invasive means of superficial femoral artery revascularisation. It comprises a single groin incision and securing of the distal cut end of atheroma with an intraluminal stent. AIM: To determine medium-term results of RSFE, with particular reference to costs of maintaining patency. METHODS: Stenosis development, and patency of 25 RSFE were compared with 25 randomly selected in situ vein bypasses with similar follow-up (18-33 months). RESULTS: Following RSFE 17 stenoses were identified by duplex surveillance. Half of those arteries patent at 1 yr had stenoses. Angioplasty (PTA) was carried out for 11 stenoses. Four stenoses developed more than 12 months following RSFE. One patient died and nine arteries occluded during follow-up. Primary and primary- assisted patency at 18 months were 31 and 63% respectively. By contrast six stenoses were identified in 25 in situ grafts, all within one year. Four PTAs were carried out. Three grafts occluded. Excluding cost of three monthly duplex surveillance the cost of maintaining RSFE patency was approximately five times that of maintaining in situ bypass patency. CONCLUSION: The initial cost advantage of RSFE is offset by the increased costs of maintaining patency. Duplex surveillance probably needs to be continued indefinitely.

Aged↗

PubMed2000

The effect of intraoperative autotransfusion on antibiotic pharmacokinetics during elective abdominal aortic aneurysm repair.

AIM: Blood loss during aortic surgery has been reduced by the use of cell-salvage techniques (CS). Antibiotics are used routinely to prevent prosthetic graft infection. The influence of CS on antibiotic levels is unknown. This study measured antibiotic levels in serum and cell-salvage fluid during aortic reconstruction. METHODS: Teicoplanin, a glycopeptide with activity against gram positive bacteria was the antibiotic studied. Serial blood levels were measured after a single intravenous dose (400 mg) in five patients undergoing elective aortic aneurysm repair. Patient ages ranged from 67 to 82 yr. Cell-salvage (Dideco compact A75171) fluid was also assayed. SETTING: District General Hospital RESULTS: Serum teicoplanin levels peaked at mean 67.8 mg/l (SD 8.9 mg/l) 5 min after administration, and fell to mean 2.88 mg/l (SD 0.4 mg/l) at 720 min. This is less than levels in healthy volunteers but above the MIC90 for most Gram positive bacterial pathogens encountered in aortic surgery. Teicoplanin levels in discarded CS fluid at the end of the procedure were 0.56 mg/l (SD 0.71 mg/l). CONCLUSIONS: Teicoplanin blood levels are reduced during aortic surgery. Levels remain adequate for antibacterial prophylaxis for 12 h postoperatively other than for methicillin-resistant staphylococcus epidermidis (MRSE). Compared with patients undergoing arterial reconstruction without the use of a cell-salvage device there is no significant loss due to CS use.

Aged↗

PubMed2000

Carotid duplex imaging: variation and validation.

BACKGROUND: Duplex imaging is increasingly used as the only investigation before carotid endarterectomy, but many different criteria exist in the literature for the detection of a severe (70-99 per cent) carotid stenosis. This study aimed to investigate current practice in carotid duplex imaging in Great Britain and Ireland. METHODS: A postal questionnaire was sent to 86 vascular surgical units. RESULTS: The median number of scans performed per year was 450 (range 60-4500). Thirty-six per cent of units who responded used peak systolic : end diastolic velocity ratio to calculate carotid stenosis. Overall, nine different major duplex criteria were used to grade carotid stenosis in 14 different systems of percentage bands. Only 51 per cent of units verified their duplex criteria against angiography. Eighteen per cent of units used two or more different types of duplex scanner and applied the same diagnostic criteria to each machine. CONCLUSION: A wide variation in diagnostic duplex criteria and methods of grading stenosis exists among vascular units. Internal validation is not performed routinely. Standardization of duplex criteria would ensure greater consistency, but would not replace the need for validation of results within each unit.

Carotid Artery, Internal↗

PubMed2000

The long-term outcome after axillo-axillary bypass grafting for proximal subclavian artery disease.

OBJECTIVES: to investigate the outcome of patients undergoing axillo-axillary bypass grafting for symptomatic subclavian artery stenoses or occlusions. DESIGN: retrospective case-note review and prospective review of patients available for follow-up. PATIENTS AND METHODS: sixteen patients had axillo-axillary grafts in a 17-year period. Ten patients were available for review and assessed clinically, by measurement of arm blood pressures, and by duplex scanning of their grafts. RESULTS: one patient died and three grafts occluded within 30 days of operation. Nine out of 10 grafts scanned were patent, with three further grafts clinically patent at death. Overall secondary patency was 75% at a combined median follow-up of 56 months (range 12-204 months). Recurrent symptoms occurred in two patients, one with an occluded graft and one with a patent graft. CONCLUSION: axillo-axillary bypass grafts give good long-term symptom-free results.

Axillary Artery↗

PubMed2000

Remote superficial femoral artery endarterectomy: medium-term results.

BACKGROUND: the aim of this study is to determine the medium-term results following successful remote superficial-femoral endarterectomy (RSFE). SETTING: district general hospital in United Kingdom. METHODS: RSFE comprises a single incision over the origin of the superficial femoral artery. The endarterectomy is carried out in a closed fashion from above. The cut end of distal atheroma is secured with a stent. Twenty-five limbs were followed up with three monthly duplex scans and angiography if any abnormality was suggested. All patients presented with intermittent claudication; in addition three had rest pain and three ulceration or gangrene. The length of atheromatous core removed was 10-30 cm. RESULTS: all patients had a follow-up of at least one year (range 12-27 months). Eleven arteries developed 14 stenoses. Nine became apparent within nine months of RSFE. The cumulative risk of stenoses developing in patent arteries was 24% at 6 and 63% at 12 months. Eleven angioplasties (PTA) of these stenoses were undertaken. Nine of these remain patent at a median of 12 months after PTA. At one year primary patency was 10 of 25 (40%), primary-assisted patency 18 of 25 (72%) and secondary patency 19 of 25 (76%) and at two years 29%, 57% and 57% respectively. CONCLUSIONS: RSFE is worth considering for superficial femoral artery occlusive disease, particularly in high-risk patients without suitable vein and with limited life expectancy. Careful duplex surveillance is important. Until stenoses can be prevented, the widespread use of RSFE cannot be recommended.

Aged↗

PubMed2000

Iliac occlusions: stenting or crossover grafting? An examination of patency and cost.

OBJECTIVES: Percutaneous transluminal angioplasty with stenting is perceived to be a less invasive and cheaper option for the treatment of iliac artery occlusion than surgical reconstruction. We have carried out a prospective observational study of all patients undergoing an iliac stent or femorofemoral crossover graft for iliac artery occlusion to assess the cost effectiveness of the two approaches in a district general hospital. METHODS: Fifty-one patients underwent primary angioplasty with stenting and 87 patients crossover grafting. Patients were all assessed 2 months after their procedure and then at intervals over the following years. RESULTS: In 13 cases, it was impossible to place the stent successfully. In a further 10 patients, major complications occurred which were mainly thromboembolic. Fifteen patients underwent crossover grafting after failure to insert a stent, or after stent occlusion. No major complications occurred following crossover grafting. The median length of stay following successful stenting was 1 day; the following crossover grafting was 4 days. The mean stay was higher in each group (2.5 and 5.8 days) and is a more accurate parameter for estimation of cost, which for iliac stenting is estimated at pound1912 versus pound3072 for crossover grafting. The mean additional cost of those patients sustaining complications after stenting was pound2481. On an <<< >>> basis, patency following stent insertion at 6 months was 52%; patency after bypass was 100% (p <0.0001). If any complication occurs after stenting, the cost advantage of the procedure is lost. In those patients without complication, the initial cost benefit of iliac stenting is lost within 6 months, as patients require further intervention, usually as a crossover graft, when the stent occludes. Crossover grafting is a durable low-risk procedure. CONCLUSIONS: We suggest that stenting of occluded iliac arteries should be reserved for those patients with limited life expectancy. Patients who are younger and fitter should be offered femorofemoral crossover grafting as a primary procedure until research enables identification of those patients who are most likely to maintain long-term patency after stenting.

Aged↗