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Biomedical subjects

John F Thompson

Publications and source records attributed to John F Thompson.

103 records · Page 6Linked to original sources
PubMed2002

Improving doctors' letters.

Information contained in letters of referral and reply often does not meet the information needs of letter recipients. Missing reports of previous investigations and insufficient detail in the referral letter to specialists are the most serious and common problems. General practitioners prefer structured, computer-generated letters to unstructured, dictated letters. Referring surgeons and GPs identify delay in receiving the reply letter and insufficient detail as relatively common problems after a new patient consultation. They want the reply letter to describe the proposed treatment, expected outcomes and any psychosocial concerns, yet these items are often omitted. A letter content and format prompt card has the potential to enhance the quality of correspondence between medical specialists and referring doctors. Specialist medical bodies should consider preparing prompt cards (setting out preferred information content and format for letters) to distribute to their members.

Correspondence as Topic↗
PubMed2002

Adjuvant immunotherapy of patients with high-risk melanoma using vaccinia viral lysates of melanoma: results of a randomized trial.

PURPOSE: Patients with high-risk melanoma treated by immunotherapy with vaccinia viral lysates were found in phase II studies to have improved survival compared with historical controls. We therefore elected to test this therapy in a phase III study. PATIENTS AND METHODS: A prospective, randomized, multicenter trial to determine whether immunotherapy with a vaccine prepared from vaccinia melanoma cell lysates (VMCL) over a 2-year period after definitive surgery would improve relapse-free survival (RFS) and overall survival (OS) in patients with American Joint Committee on Cancer stage IIB and III melanoma compared with a control group treated only with surgery. RESULTS: A total of 700 patients were randomized: 353 to VMCL and 347 to no immunotherapy. Seventy-seven percent had lymph node (LN) metastases and 66% had clinically detected LN metastases. Analysis on the basis of all eligible, randomized patients (n = 675) found, after a median follow-up period of 8 years, a median OS of 88 months in the control versus 151 months in the treated group (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.64 to 1.02; P =.068 by stratified univariate Cox analysis). At 5 and 10 years, survival rates for control and treated patients were 54.8% v 60.6% and 41% v 53.4%, respectively. Median RFS was 43 months in the control group compared with 83 months in the treated group (HR, 0.86; 95% CI, 0.7 to 1.07; P =.17). RFS at 5 years was 50.9% for the treated group and 46.8% for the control group. There were no selective benefits from the vaccine for particular subsets of patients. CONCLUSION: Immunotherapy with VMCL was not associated with a statistically significant improvement in OS or RFS, with CIs not ruling out important gains from such treatment.

Adult↗
PubMed2002

Identification of IEX-1 as a biomechanically controlled nuclear factor-kappaB target gene that inhibits cardiomyocyte hypertrophy.

Biomechanical strain is a stimulus for cardiomyocyte hypertrophy and heart failure, but the underlying molecular mechanisms remain incompletely understood. Using an in vivo murine model of pressure overload and an in vitro model of mechanical stimulation of primary cardiomyocytes, we identified iex-1 as a gene activated during the early response of cardiomyocytes to hypertrophic stimuli and as a gene product that inhibits hypertrophy without affecting cardiomyocyte viability. On stimulation of cardiomyocytes, iex-1 mRNA and protein expression increased and translocation of the gene product to the cardiomyocyte nucleus occurred. iex-1 has previously been proposed as a mediator of NF-kappaB-dependent cell survival and growth in tumor cells. Here, we demonstrate that the biomechanical induction of iex-1 in cardiomyocytes was NF-kappaB-dependent, as overexpression of the NF-kappaB inhibitor IkappaBalpha completely inhibited strain-mediated iex-1 mRNA accumulation. The functional role of iex-1 was investigated by overexpressing wild-type iex-1 with replication-defective adenoviral gene transfer. Overexpression of iex-1 abolished cardiomyocyte hypertrophy by mechanical strain, phenylephrine, or endothelin-1 at levels that did not affect cell viability. These studies identify iex-1 as a biomechanical stress-inducible and NF-kappaB-dependent gene in cardiac muscle cells during the acute phase of hypertrophy with negative growth regulatory effects that may counterbalance early hypertrophic responses in activated cardiomyocytes.

Adenoviridae↗
PubMed2002

Prognostic factors after isolated limb infusion with cytotoxic agents for melanoma.

BACKGROUND: Isolated limb perfusion (ILP) with cytotoxic agents is a remarkably effective but complex technique used to treat locally recurrent and metastatic melanoma confined to a limb. Isolated limb infusion (ILI), essentially a low-flow ILP performed without oxygenation via percutaneous catheters, has been developed as a simpler alternative. METHODS: The outcome in 135 patients treated by ILI was reviewed. RESULTS: The overall response rate in the treated limb was 85% (complete response [CR] rate 41%, partial response rate 44%). Median response duration response was 16 months (24 months for patients with CR). Median patient survival was 34 months. In those with a CR, the median survival was 42 months. CR rate and survival time decreased with increasing disease stage. Patients aged >70 years had a better overall response than younger patients. On multivariate analysis, factors associated with an improved outcome were a lower stage of disease, a final limb temperature >37.8 degrees C, and a tourniquet time >40 minutes. CONCLUSIONS: The frequency and duration of responses after ILI were comparable to those achieved by conventional ILP. The ILI technique is particularly useful for older patients who might not be considered suitable for conventional ILP.

Aged↗
PubMed2002

Epidermal growth factor reduces ischemia-reperfusion injury in rat small intestine.

OBJECTIVE: To measure the effect of pre-ischemic administration of intraluminal epidermal growth factor on the changes in intestinal permeability induced by 30 mins of superior mesenteric artery occlusion, followed by 2 hrs of reperfusion. DESIGN: Prospective, randomized, placebo-controlled experimental study. SETTING: University basic science research laboratory. SUBJECTS: Healthy, young, adult, male Sprague-Dawley rats. INTERVENTIONS: A 10-cm segment of small intestine was isolated and studied in situ in rats that were anesthetized with fentanyl and mechanically ventilated. Intestinal ischemia-reperfusion injury was induced by temporary occlusion of the superior mesenteric artery for 30 mins, followed by 2 hrs of reperfusion. Three groups were studied: time controls with a sham operation, saline-treated ischemia-reperfusion, and epidermal growth factor-treated ischemia-reperfusion. Epidermal growth factor, 100 ng/min, was infused intraluminally, beginning 30 mins before and continued until 40 mins after ischemia. MEASUREMENTS AND MAIN RESULTS: Intestinal permeability was measured for each 10-min time period by using chromium-labeled EDTA. Histopathologic injury was assessed by light microscopy. After superior mesenteric artery occlusion, intestinal permeability increased approximately ten-fold and was sustained for 2 hrs of reperfusion in saline-treated rats. Pretreatment with epidermal growth factor significantly reduced the permeability changes during reperfusion by >60% compared with saline-treated animals (p <.05). Histopathologic sections revealed apparently more extensive loss of epithelial cells and mucosal disruption in saline-treated intestine compared with epidermal growth factor-treated intestine. CONCLUSION: Pre-ischemic administration of intraluminal epidermal growth factor significantly protects against intestinal ischemia-reperfusion injury.

Animals↗
PubMed2002

Direct biomechanical induction of endogenous calcineurin inhibitor Down Syndrome Critical Region-1 in cardiac myocytes.

Signaling through the protein phosphatase calcineurin may play a critical role in cardiac hypertrophy. The gene for Down Syndrome Critical Region-1 (DSCR1) encodes a protein that is an endogenous calcineurin inhibitor. This study was designed to test the hypothesis that DSCR1 is directly induced by biomechanical stimuli. Neonatal rat cardiac myocytes were exposed to biaxial cyclic mechanical strain; mechanical strain upregulated DSCR1 mRNA expression in a time- and amplitude-dependent manner (3.4 +/- 0.2-fold at 8% strain for 6 h, n = 11, P < 0.01), and this induction was angiotensin II and endothelin I independent. Biomechanical induction of DSCR1 mRNA was partially blocked by calcineurin inhibition with cyclosporine A (30 +/- 5%, n = 3, P < 0.01). DSCR1 promoter-reporter experiments showed that mechanical strain induced DSCR1 promoter activity by 2.3-fold and that this induction was completely inhibited by cyclosporin A. Furthermore, DSCR1 gene expression was increased in the left ventricles of mice with pressure-overload hypertrophy induced by transverse aortic banding. These data demonstrate that biomechanical strain directly induces gene expression for the calcineurin inhibitor DSCR1 in cardiac myocytes, indicating that mechanically induced DSCR1 may regulate the hypertrophic response to mechanical overload.

Animals↗
PubMed2002

Surgical management of cerebral metastases from melanoma: outcome in 147 patients treated at a single institution over two decades.

OBJECT: The aim of this study was to review the outcome of patients who underwent surgery for treatment of cerebral metastatic melanoma. METHODS: A retrospective analysis was performed in 147 patients with cerebral metastases from melanoma who were treated surgically at a single institution between 1979 and 1999. Almost all patients underwent postoperative wholebrain radiation therapy. The mean patient age was 53 years (range 17-76 years); 69% of patients were male. A single cerebral metastasis was identified in 84% of patients, although 56% had synchronous extracranial metastases. The 30-day postoperative mortality rate was 2% and neurological symptoms resolved or improved in 78% of patients. Recurrence of intracerebral disease was seen in 55% of patients and 26% died of intracerebral metastases. Twenty-four patients underwent reoperation for recurrent cerebral disease. The median survival duration from the time of surgery for all patients was 8.5 months; the 3- and 5-year survival rates were 9% and 5%, respectively. Factors that significantly influenced survival on univariate analysis were the number of cerebral metastases (p = 0.015), a macroscopically complete excision (p < 0.05), and reoperation for recurrence (p = 0.02). The presence of extracranial metastases did not significantly influence survival. On multivariate analysis only the number of cerebral metastases significantly affected survival (p = 0.04). CONCLUSIONS: For the majority of patients with cerebral metastases from melanoma, surgery with adjuvant radiation therapy is a treatment option that improves neurological symptoms and produces minimal morbidity. Long-term survival (> 3 years) most likely occurs in patients with a single cerebral metastasis and no demonstrable extracranial disease. Reoperation for recurrent cerebral disease may be appropriate in selected cases.

Adolescent↗
PubMed2001

Intestinal and multivisceral transplantation.

Intestinal transplantation has been gradually instituted in the management of intestinal failure. More than 200 cases including isolated intestinal transplant, liver/intestinal transplant, and multivisceral transplant have been performed worldwide,with 1-year graft and patient survival rates of 66% and 54%,respectively. Indications for the procedure include short bowel syndrome and functional abnormalities secondary to a variety of diseases or conditions. Tacrolimus-based immunosuppression regimens have been used universally with improved outcomes. The major contributors to the morbidity and mortality include rejection,infection, and technical complications. Of those, control of rejection remains the most difficult dilemma and it will be the key to improved patient and graft survival.

Digestive System Surgical Procedures↗
PubMedDate not supplied

Cutaneous melanoma.

Episodic exposure of fair-skinned individuals to intense sunlight is thought to be responsible for the steadily increasing melanoma incidence worldwide over recent decades. Rarely, melanoma susceptibility is increased more than tenfold by heritable mutations in the cell cycle regulatory genes CDKN2A and CDK4. Effective treatment requires early diagnosis followed by surgical excision with adequately wide margins. Sentinel lymph node biopsy provides accurate staging, but no published results are yet available from clinical trials designed to assess the therapeutic efficacy of early complete regional node dissection in those with metastatic disease in a sentinel node. Magnetic resonance spectroscopy is one technique under investigation for non-invasive, in-situ assessment of sentinel nodes. Localised metastatic disease is best treated surgically. No postoperative adjuvant therapy is of proven value for improving overall survival, although numerous clinical trials of vaccines and cytokines are in progress. Medical therapies have contributed little to the control of established metastatic disease, but molecular pathways recently identified as being central to melanoma growth and apoptosis are under intense investigation for their potential as therapeutic targets.

Combined Modality Therapy↗
PubMedDate not supplied

An evidence-based staging system for cutaneous melanoma.

A completely revised staging system for cutaneous melanoma was implemented in 2003. The changes were validated with a prognostic factors analysis involving 17,600 melanoma patients from prospective databases. This major collaborative study of predicting melanoma outcome was conducted specifically for this project, and the results were used to finalize the criteria for this evidence-based staging system. In fact, this was the largest prognostic factors analysis of prospectively followed melanoma patients ever conducted. Important results that shaped the staging criteria involved both the tumor-node-metastasis (TNM) criteria and stage grouping for all four stages of melanoma. Major changes in the staging include: (1) melanoma thickness and ulceration are the dominant predictors of survival in patients with localized melanoma (Stages I and II); deeper level of invasion (ie, IV and V) was independently associated with reduced survival only in patients with thin or T1 melanomas. (2) The number of metastatic lymph nodes and the tumor burden were the most dominant predictors of survival in patients with Stage III melanoma; patients with metastatic nodes detected by palpation had a shorter survival compared with patients whose nodal metastases were first detected by sentinel node excision of clinically occult or "microscopic" metastases. (3) The site of distant metastases (nonvisceral versus lung versus all other visceral metastatic sites) and the presence of elevated serum lactate dehydrogenase (LDH) were the dominant predictors of outcome in patients with Stage IV or distant metastases. (4) An upstaging was implemented for all patients with Stage I, II, and III disease when a primary melanoma is ulcerated by histopathological criteria. (5) Satellite metastases around a primary melanoma and in-transit metastases were merged into a single staging entity that is grouped into Stage III disease. (6) A new convention was implemented for defining clinical and pathological staging so as to take into account the new staging information gained from lymphatic mapping and sentinel node biopsy.

Databases, Factual↗