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Biomedical subjects

J F Thompson

Publications and source records attributed to J F Thompson.

At least 19 recordsLinked to original sources

Detection of metastatic disease in patients with uveal melanoma using positron emission tomography.

OBJECTIVE: Positron emission tomography with [(18)F]fluorodeoxyglucose (FDG-PET) is of proven value in the detection of metastases in patients with cutaneous melanoma. However, little is known about its value in uveal melanoma (UM). In this study the results of FDG-PET in patients with UM were evaluated. METHODS: Patients with UM recorded in the Sydney Melanoma Unit database who had been assessed with FDG-PET were selected. Comparative data (imaging or histopathology) providing information about metastatic disease were obtained within 14 weeks of the FDG-PET study and compared with the FDG-PET result. Sensitivity, specificity, accuracy, and positive and negative predictive values for the detection of liver metastases (LMs) by FDG-PET were calculated. RESULTS: FDG-PET was performed in 22 patients with UM between April 1993 and March 2003. The presence of at least one focus of metastatic melanoma was confirmed in 14 of 18 patients with positive FDG-PET, and three of four negative FDG-PET studies were confirmed. LMs were demonstrated by FDG-PET in 17 patients. In 15 of these patients this finding was confirmed with anatomical imaging. In two patients LMs indicated by FDG-PET initially appeared to be false positive, but in one of them the diagnosis was confirmed after longer follow-up. Seven of the confirmed lesions were isolated LMs. For LMs FDG-PET showed sensitivity, specificity and accuracy of 100%, 67% and 90% respectively, a positive predictive value of 88% and a negative predictive value of 100%. CONCLUSION: FDG-PET is a valuable investigation for the detection of LMs in UM patients. It appears to be particularly useful in the detection of isolated LMs that are potentially resectable.

Adult↗

Use of a pneumatic tourniquet improves outcome following trans-tibial amputation.

BACKGROUND: It is traditionally taught that a pneumatic tourniquet is contraindicated for trans-tibial amputations in patients with peripheral arterial disease. However, tourniquets are used successfully during total knee arthroplasty in elderly patients. Vascular patients undergoing a trans-tibial amputation have a high perioperative mortality and morbidity-notably the need for wound revision or a higher amputation level. We hypothesised that a tourniquet, used during amputation, would reduce blood loss and subsequent complications without compromising healing. METHODS: This was a prospective non-randomized study of 89 adult patients who underwent a trans-tibial amputation between January 2001 and December 2003. The endpoints were: haemoglobin levels, the need for blood transfusion, perioperative morbidity, revision rate and mortality. Patients were divided into two groups: a group with a pneumatic tourniquet (n=42) and a group without (n=47). RESULTS: The haemoglobin fall was 14.8% in the non-tourniquet group and 5.6% in the tourniquet group, with a higher need for transfusion in the non-tourniquet group. The revision rate was 14.3% in the tourniquet group and significantly higher in the non-tourniquet group (38.3%). Mortality was similar in both groups: 7.1% for the tourniquet and 6.4% for the non-tourniquet group. CONCLUSION: The use of a pneumatic tourniquet is safe and significantly reduces both blood loss and transfusion requirements during trans-tibial amputation. A pneumatic tourniquet reduces revision rates by over 50%, with subsequent cost savings.

Adult↗

Complex iliac and bilateral common femoral artery aneurysms: a novel hybrid procedure.

A 74-year-old man presented with a right common iliac artery aneurysm and bilateral common femoral artery aneurysms. These aneurysms were repaired by a hybrid procedure. A one-stage approach was chosen including an endovascular stent-graft and femoro-iliaco-femoral Y-bypass grafting. The authors describe a novel combined open and endovascular approach to repair these complex aneurysms.

Aged↗

Most patients with varicose veins have fears or concerns about the future, in addition to their presenting symptoms.

INTRODUCTION: This study aimed to document fears and concerns of patients about their varicose veins. REPORT: Completed questionnaires about symptoms and concerns were brought to clinic by 62% (203/329) patients referred with uncomplicated primary varicose veins. 'Concerns, worries or fears' about their veins were reported by 79%. These were seldom mentioned in referral letters, and included fears about thrombosis (31%), trauma (16%), ulcers (15%) and general concerns about the future (57%). DISCUSSION: Many patients have unrecognised fears and concerns about their varicose veins. Specific enquiry and reassurance about these is part of good management and may avoid unnecessary treatment.

Adult↗

Detection of unsuspected spinal cord compression in melanoma patients by 18F-fluorodeoxyglucose-positron emission tomography.

AIM: Positron emission tomography (PET) using (18)F-fluorodeoxyglucose can detect early or small metastatic deposits of melanoma and guide subsequent correlative anatomical imaging and treatment. The aim of this study was to assess the value of PET in demonstrating spinal cord compression by otherwise unsuspected metastatic disease. METHODS: Reports of 1365 PET studies performed on patients with melanoma were reviewed. Fifty patients considered to be at risk of spinal cord compression on the basis of PET were identified and 35 patients were analysed. Magnetic resonance imaging and computed tomography were used to confirm or refute the diagnosis. The symptoms and signs at the time of PET and follow-up status were compared between patients with and without confirmed spinal cord compression. RESULTS: In nine patients (26%) compression of the spinal cord or adjacent neurological structures was confirmed and eight of these patients had immediate treatment. Survival was poor in both patient groups, but three patients with confirmed compression maintained good neurological functional status following treatment. CONCLUSION: PET can detect imminent, unsuspected spinal cord compression in patients with metastatic melanoma. Immediate anatomical imaging of the spine is recommended in patients who have evidence of spinal cord compression on PET.

Adult↗

An association study of 43 SNPs in 16 candidate genes with atorvastatin response.

Variation in individual response to statin therapy has been widely studied for a potential genetic component. Multiple genes have been identified as potential modulators of statin response, but few study findings have replicated. To further examine these associations, 2735 individuals on statin therapy, half on atorvastatin and the other half divided among fluvastatin, lovastatin, pravastatin and simvastatin were genotyped for 43 SNPs in 16 genes that have been implicated in statin response. Associations with low-density lipoprotein cholesterol (LDL-C) lowering, total cholesterol lowering, HDL-C elevation and triglyceride lowering were examined. The only significant associations with LDL-C lowering were found with apoE2 in which carriers of the rare allele who took atorvastatin lowered their LDL-C by 3.5% more than those homozygous for the common allele and with rs2032582 (S893A in ABCB1) in which the two groups of homozygotes differed by 3% in LDL-C lowering. These genetic effects were smaller than those observed with the demographic variables of age and gender. The magnitude of all the differences found is sufficiently small that genetic data from these genes should not influence clinical decisions on statin administration.

Aged↗

Activation of the extracellular signal regulated kinase (ERK) pathway in human melanoma.

BACKGROUND: Several studies suggest that melanoma may be resistant to treatment because of resistance to apoptosis and that this may be the result of activation of the extracellular signal regulated kinase (ERK1/2) pathway. AIMS: To test this hypothesis by examining the expression of ERK1/2 and its activated form in histological sections of melanoma and its relation to known prognostic features of the disease. MATERIALS/METHODS: Immunohistochemistry with antibodies to ERK1/2 and phosphorylated ERK (p-ERK) was performed on formalin fixed sections from 42 primary melanomas, 38 metastases, and 20 naevi. Fourteen of the primary melanomas were in the radial and 28 in the vertical growth phase. RESULTS: ERK1/2 was widely expressed (100%) in all the (pigmented) lesions studied. p-ERK1/2 expression was much lower in compound (32.4%) and dysplastic (54.5%) naevi than in primary melanoma (nodular 78.8%, superficial spreading 67%) and subcutaneous metastases (76.3%). p-ERK expression was much lower in lymph node metastases (48.5%), suggesting that the microenvironment may influence the activation of ERK. There was a (non-significant) trend for p-ERK expression to be higher in thick (>1.0 mm) versus thin (< or =1.0 mm) melanoma (p = 0.23). There was a trend for overall survival to be related to p-ERK expression in patients with melanoma over 1 mm in thickness. CONCLUSIONS: Expression of activated ERK1/2 in melanocytic lesions appears to be related to malignant potential so that activation of ERK1/2 may be important in melanoma progression. These results provide important histological support for the proposal that inhibition of this signalling pathway may be useful in treatment of melanoma.

Adolescent↗

Sentinel node biopsy provides more accurate staging than elective lymph node dissection in patients with cutaneous melanoma.

BACKGROUND: In most major melanoma treatment centers, sentinel node biopsy (SNB), with complete regional lymph node dissection when a positive sentinel node is found, has now replaced elective lymph node dissection (ELND) for patients with primary cutaneous melanomas who are considered to be at moderate to high risk of nodal recurrence. As for ELND, however, no overall survival benefit for the SNB procedure has yet been demonstrated. The objective of this study was to compare the nodal staging accuracy and duration of survival for SNB and ELND. METHODS: A retrospective cohort study was conducted among patients with American Joint Committee on Cancer (AJCC) stage II disease treated at a single center between 1983 and 2000 with either SNB (n = 672) or ELND (n = 793). Multivariate analyses were performed using the logistic regression model for nodal staging accuracy and Cox's proportional hazards regression model for survival. RESULTS: Patient factors that influenced nodal positivity included age, Breslow thickness, ulceration, head or neck primary, and operation type (SNB or ELND). SNB was superior to ELND in the detection of micrometastases (odds ratio 1.23, 95% CI, 1.06 - 1.43) but operation type did not influence survival (P =.24). CONCLUSIONS: Sentinel node biopsy identified more nodal micrometastases than ELND but did not influence survival, although complete regional node dissection was performed in all patients who were SNB positive. This increase in staging accuracy likely results from the reliable identification of the appropriate lymph node field by preoperative lymphoscintigraphy, along with more detailed pathologic examination of the nodes removed by SNB.

Cohort Studies↗

Determinants of outcome in melanoma patients with cerebral metastases.

PURPOSE: To analyze prognostic factors, effects of treatment, and survival for patients with cerebral metastases from melanoma. PATIENTS AND METHODS: All melanoma patients with cerebral metastases treated at the Sydney Melanoma Unit between 1952 and 2000 were identified. From 1985 to 2000, patients were diagnosed and treated using consistent modern techniques and this cohort was analyzed in detail. Multivariate analysis of prognostic factors for survival was performed. RESULTS: A total of 1137 patients with cerebral metastases were identified; 686 were treated between 1985 and 2000. For these 686 patients, the median time from primary diagnosis to cerebral metastasis was 3.1 years (range, 0 to 41 years). A total of 646 patients (94%) have died as a result of melanoma. The median survival from the time of diagnosis of cerebral metastasis was 4.1 months (range, 0 to 17.2 years). Treatment was as follows: surgery and postoperative radiotherapy, 158 patients; surgery alone, 47 patients; radiotherapy alone, 236 patients; and supportive care alone, 210 patients. Median survival according to treatment received for these four groups was 8.9, 8.7, 3.4, and 2.1 months, respectively; the differences between surgery and nonsurgery groups were statistically significant. On multivariate analysis, significant factors associated with improved survival were surgical treatment (P <.0001), no concurrent extracerebral metastases (P <.0001), younger age (P =.0007), and longer disease-free interval (P =.036). Prognostic factors analysis confirmed the important influence of patient selection on treatment received. CONCLUSION: This large series documents the characteristics of patients who developed cerebral metastases from melanoma. Median survival was dependent on treatment, which in turn was dependent on patient selection.

Adolescent↗

Double isolated limb infusion with cytotoxic agents for recurrent and metastatic limb melanoma.

Metastatic melanoma confined to a limb can be treated effectively by isolated limb infusion (ILI) with cytotoxic drugs. The present study was undertaken to determine whether electively performing a second ILI procedure after 4 weeks increases the frequency and/or duration of response, and also to assess the value of a second ILI when disease recurrence or progression in a limb occurs after a first ILI. In 47 patients, a planned double ILI protocol achieved an overall response (OR) rate of 88% (complete response (CR) 41%, partial response (PR) 47%, median duration of response 18 months). Response rates after double ILI were similar to those in 81 patients treated with a single ILI over the same time period (CR 41%, PR 41%), without significant differences in response duration. After double ILI more patients experienced Wieberdink Grade III or IV limb toxicity. Following a second ILI for progression after an initial ILI (n=14), the OR rate was 71%, with a 5 month median duration of response. Since elective double ILI increases toxicity without increasing efficacy, performance of a single ILI is the preferred treatment option for melanoma confined to a limb. However, a second ILI can be of value if limb disease recurs or progresses following a previous ILI.

Aged↗

Isolated limb infusion with fotemustine after dacarbazine chemosensitisation for inoperable loco-regional melanoma recurrence.

BACKGROUND: Isolated limb infusion (ILI) is a simple yet effective alternative to conventional isolated limb perfusion for the treatment of advanced melanoma of the extremities. PATIENTS AND METHODS: The study group comprised 13 patients with very advanced limb disease who had failed to achieve a satisfactory response to one or more ILIs with melphalan, and in whom amputation was the only other realistic treatment option. The aim of this study was to evaluate the efficacy and toxicity of ILI with fotemustine after systemic chemosensitisation with dacarbazine (DTIC). RESULTS: Complete remission was achieved in four patients and partial remission in eight patients, with a median response duration of 3 months. Limb salvage was achieved in five of 12 assessable patients (42%). Limb toxicity peaked 9 days after ILI; two patients experienced Wieberdink grade IV (severe) toxicity and four patients had grade V toxicity (requiring early amputation). CONCLUSIONS: ILI with fotemustine after DTIC chemosensitisation can be successful when gross limb disease has not been controlled by one or more ILIs with melphalan. However, it cannot be recommended as a routine method of treatment for advanced melanoma of the extremities because of the high incidence of severe limb toxicity.

Aged↗

Trends in serum citrulline and acute rejection among recipients of small bowel transplants.

A test for detecting acute cellular rejection (ACR) of small intestinal transplants (ITx) would be a major advance. Small preliminary studies suggest that serum citrulline levels correlate with ACR. The results for a group of 26 isolated intestinal and multivisceral transplant recipients are summarized here. Serum citrulline concentrations were determined by ion exchange chromatography and compared to biopsy-based grade of ACR. Other factors considered included patient and donor age and sex, ischemia time, and serum creatinine. Straight-line fits were employed to describe how each patient's citrulline levels changed over time. Estimated times to achieve normal citrulline (>or=30 micromol/L) ranged from 1 to 730 days posttransplant for 21 patients demonstrating increasing citrulline levels over time. Using stepwise linear regression, patients' ranks for time required to achieve normal citrulline levels were the only independent predictors of both maximum ACR (P <.0001) and average ACR (P =.0059) after 14 days posttransplant. The rate and direction of change in citrulline over time may be an indicator of the risk of acute rejection. We plan to further examine the use of citrulline as a marker for rejection in larger prospective studies.

Adult↗

Cholesteryl ester transfer protein promoter single-nucleotide polymorphisms in Sp1-binding sites affect transcription and are associated with high-density lipoprotein cholesterol.

Genetic variation in the human cholesteryl ester transfer protein (CETP) promoter has been shown to be associated with high-density lipoprotein cholesterol (HDL-C) levels and cardiovascular disease. Some of this variation occurs in Sp1/Sp3 binding sites in the proximal promoter. We find that both the known promoter polymorphism at -629 and the previously uncharacterized polymorphism at -38 are associated with HDL-C levels in vivo and affect transcription in vitro. While the -629 polymorphism is common in all ethnic groups, the -38 polymorphism is found at significant levels (6.4%) only among African Americans. Those homozygous for the less common -38A allele have higher HDL-C levels than those with the more frequent -38G allele. This association was found in a population of African Americans at risk of cardiovascular disease and then replicated in a different population chosen from among patients with extremes of HDL-C. When studied in vitro, the most transcriptionally active allele (-629C/-38G) yields 51% more reporter protein than the least active allele (-629A/-38A) in HepG2 cells. These transcriptional effects reflect the projected impact of increased CETP expression on HDL-C phenotypes seen in vivo.

Black or African American↗

Intestinal transplantation: advances in immunosuppression and surgical techniques.

Campath-1H is being used as induction immunosuppression for intestinal/multivisceral transplantation. Patient and graft survival in this preliminary experience is similar to previous studies but there has been a significant decrease in the incidence and severity of acute rejections without increase of opportunistic infections. Collage of the abdominal wall (transplantation of a composite graft of the abdominal wall) can provide biologic coverage of the newly transplanted abdominal organs if necessary. Partial abdominal exenteration, ex vivo resection, and intestinal autotransplantation may be useful in removing otherwise unresectable lesions of the root of the mesentery.

Graft Rejection↗