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Biomedical subjects

J F Thompson

Publications and source records attributed to J F Thompson.

At least 55 records · Page 3Linked to original sources
PubMed2001

Lymph-node metastases in patients with melanoma: what is the optimum management?

Lymph-node metastasis is an indicator of poor prognosis for patients with melanoma. The management of regional nodes is controversial, with continuing debate about whether surgery or radiotherapy of positive lymph nodes improves long-term survival or whether nodal involvement is merely a marker of aggressive disease. However, there is general agreement that systemic chemotherapy is rarely an effective form of management. This review therefore considers surgical and radiotherapeutic aspects of lymph-node management in patients with melanoma. We discuss regional control and survival after lymph-node surgery in retrospective series, randomised trials of elective lymph-node dissection, the role of 'sentinel' lymph-node biopsy, radiobiology and radiotherapy fractionation issues in melanoma treatment, retrospective studies of adjuvant nodal radiotherapy, and finally, randomised trials of adjuvant radiotherapy after lymph-node dissection.

Combined Modality Therapy↗
PubMed2001

Hearing the bad news of a cancer diagnosis: the Australian melanoma patient's perspective.

BACKGROUND: In the past, recommendations on how to break the bad news of a cancer diagnosis have been based on expert opinion. Recently, consensus-based guidelines for medical practitioners have been developed. The objective of this work is to investigate patient preferences for communication practices and to identify any disparities between these guidelines, patient preferences and patient recollections of hearing their diagnosis. PATIENTS AND METHODS: A consecutive sample of 131 newly diagnosed melanoma patients were surveyed approximately 4 months after initial diagnosis to document their preferences and recollections of their communication experiences. RESULTS: Of the 'breaking bad news' recommendations investigated, patients did not strongly endorse the doctor helping tell others of the diagnosis or telling the patient about cancer support services. Very few patients expressed a preference for having another health professional present. One communication feature, the patient feeling confident about getting the best treatment, was endorsed as 'very important' but does not feature in published guidelines. The most notable disparities between guidelines and the reported experiences of patients related to perceived delays in receiving the diagnosis, and having adequate opportunity to ask their clinician questions. CONCLUSION: Current Australian recommendations on how to communicate a diagnosis of cancer were generally supported by the patients' expressed preferences, but several modifications are proposed. IMPLICATIONS: Suggestions are offered to help overcome the disparities identified between recommendations and patients' preferences when a diagnosis of cancer is being communicated.

Adaptation, Psychological↗
PubMed2001

Treatment of refractory hand warts by isolated limb infusion with melphalan and actinomycin D.

We present an immunocompetent man with extensive warts on the hands, refractory to a number of conventional treatment modalities and causing substantial morbidity and impairment of normal function. Isolated limb infusion (regional intra-arterial chemotherapy) with melphalan and actinomycin D was performed, with substantial clearing of the warts within 2 months. Treatment-induced morbidity was limited to mild local erythema and oedema which resolved within 3 weeks. After 9 months' follow up, the patient had only a few residual warts and was able to resume normal activities.

Adult↗
PubMed2001

Sentinel lymph node biopsy in patients with melanoma and breast cancer.

Sentinel lymph node biopsy (SNLB) is a new method for staging regional node fields in patients with cancers that have a propensity to metastasise to lymph nodes. The majority of early experience has been obtained in patients with melanoma and breast cancer. The technique requires the close cooperation of nuclear medicine physicians, surgical oncologists and histopathologists to achieve the desired accuracy. It involves: (i) identification of all lymph nodes that directly drain a primary tumour site (the sentinel nodes) by the use of pre-operative lymphoscintigraphy, (ii) selective excision of these nodes by the surgeon, guided by pre-operative blue dye injection and a gamma detecting probe intra-operatively and (iii) careful histological examination of the sentinel nodes by the histopathologist using serial sections and immunohistochemical stains. If the nodes are normal it can be inferred with a high degree of accuracy that all nodes in the node field are normal. This means that radical dissections of draining node fields can be avoided in patients with normal lymph nodes. A further advantage of lyamphatic mapping is that drainage to sentinel nodes in unusual locations is identified, leading to more accurate nodal staging than could be achieved with routine dissection of the closest node field.

Breast Neoplasms↗
PubMed2001

Graft survival in pediatric liver transplantation.

BACKGROUND/PURPOSE: Liver transplantation is standard therapy for children with a variety of liver diseases. The current shortage of organ donors has led to aggressive use of reduced or split grafts and living-related donors to provide timely liver transplants to these children. The purpose of this study is to examine the impact of these techniques on graft survival in children currently treated with liver transplantation. METHODS: Data were obtained on all patients less than 21 years of age treated with isolated liver transplants performed after January 1, 1996 in an integrated statewide pediatric liver transplant program, which encompasses 2 high-volume centers. Nonparametric tests of association and life table analysis were used to analyze these data (SAS v 6.12). RESULTS: One hundred twenty-three children received 147 grafts (62 at the University of Florida, 85 at the University of Miami). Fifty-two (36%) children were less than 1 year of age at time of transplant, and 80 (55%) were less than 2 years of age. Patient survival rate was identical in the 2 centers (1-year actuarial survival rate, 88.4% and 87.1%). Twenty-five (17%) grafts were reduced, 28 (19%) were split, 6 were from living donors (4%), and 88 (60%) were whole organs. One-year graft survival rate was 80% for whole grafts, 71.6% for reduced grafts, and 64.3% for split grafts (P =.06). Children who received whole organs (mean age, 6.1 years) were older than those who received segmental grafts (mean age, 2.5 years; P <.01). Multifactorial analysis suggested that patient age, gender, and use of the graft for retransplant did not influence graft survival, nor did the type of graft used influence patient survival. CONCLUSIONS: The survival rate of children after liver transplantation is excellent independent of graft type. Use of current techniques to split grafts between 2 recipients is associated with an increased graft loss and need for retransplantation. Improvement in graft survival of these organs could reduce the morbidity and cost of liver transplantation significantly in children.

Age Distribution↗
PubMed2001

Inflammatory bowel disease associated with immune thrombocytopenic purpura in children.

OBJECTIVE: Previous reports suggest an association between inflammatory bowel disease (IBD) and immune thrombocytopenic purpura (ITP) in adults. To date, only five children with both diseases have been described. The aim of the study was to describe the characteristics of children with IBD and ITP. METHODS: Cases were obtained from the pediatric gastroenterology community by means of the pediatric gastroenterology internet bulletin board in June 1999. Eight cases were submitted from seven medical centers. Medical records were reviewed by two pediatric gastroenterologists and a pediatric hematologist. RESULTS: The age range of the patients was 2.1 to 16.5 years, with a mean age of 9.6 +/- 5.2 years. Four children had ulcerative colitis, three had Crohn disease, and one had indeterminate colitis. All had colonic involvement of IBD. Of eight patients, three had IBD first, three had ITP first, and two had both simultaneously. At ITP diagnosis, platelet count was less than 10,000/mL in five children, 17,000/mL in one child, and 50,000 to 60,000/mL in two children. Of the three children diagnosed with ITP first, two initially had rectal bleeding at the time of ITP diagnosis. Bone marrow evaluations, performed in six of eight children, were consistent with ITP. Six of the eight children had chronic ITP, including three children who were 5 years of age or younger. Therapy for ITP included steroids (n = 6), intravenous immunoglobulin (n = 6), Rh o (D) intravenous immunoglobulin (n = 2), and splenectomy (n = 1). CONCLUSIONS: The authors describe the largest pediatric case series of children with IBD and ITP. More than 50% of the children had the chronic form of ITP. Most patients responded to conventional therapy for ITP and IBD.

Adolescent↗
PubMed2001

Pharmacokinetics and pharmacodynamics of melphalan in isolated limb infusion for recurrent localized limb malignancy.

Isolated limb infusion (ILI) is an attractive, less complex alternative to isolated limb perfusion (ILP). It has a lower morbidity in treating localized recurrences and in transit metastases of the limb for tumours such as melanoma, Merkel cell tumour and Kaposi's sarcoma, allowing administration of high concentrations of cytotoxic agent to the affected limb under hypoxic conditions. Melphalan is the preferred cytotoxic agent for the treatment of melanoma by ILP or ILI. We report pharmacokinetic data from 12 patients treated by ILI for tumours of the limb in Brisbane. The kinetics of drug distribution in the limb was calculated using a two-compartment vascular model, where both tissue and infusate act as well-stirred compartments. Analysis of melphalan concentrations in the perfusate during ILI showed good agreement between the values measured and the concentrations predicted by the model. Recirculation and wash-out flow rates, tissue concentrations and the permeability surface area product (PS) were calculated. Correlations between the PS value and the drug concentrations in the perfusate and tissue were supported by the results. These data contribute to a better understanding of the distribution of melphalan during ILI in the limb, and offer the opportunity to optimize the drug regimen for patients undergoing ILI.

Aged↗
PubMed2001

Saturable dose-response relationships for melphalan in melanoma treatment by isolated limb infusion in the nude rat.

Nude rats bearing melanomas on their hindlimbs were treated by isolated limb infusion (ILI) with increasing doses (7.5-400 microg/ml) of melphalan. The response of tumours to treatment at the end of the observation period was graded, according to diameter, as complete response (CR), partial response (PR), no change (NC) or progressive disease (PD). No linear relationship between the dose of melphalan and the tumour response was observed. All doses above a threshold of 15 microg/ml achieved a PR or CR. The achievement of CR was not related to increased dose. Two major implications arise from this work. Firstly, the typically two- to three-fold increase in cytotoxic drug concentration given in high dose chemotherapy compared with standard drug concentration may not be sufficient to produce the expected increase in tumour response and possibly survival, and the controversial results of high dose chemotherapy in different studies may thus be explained. Secondly, since an increase in melphalan dose above a certain threshold does not greatly increase tumour response, the use of combination therapies would seem to be more likely to be effective than increased chemotherapeutic drug doses in achieving better tumour responses.

Animals↗
PubMed2001

Lymphatic mapping and sentinel node biopsy for melanoma.

Worldwide experience has now confirmed that the histological status of sentinel nodes (SNs) accurately reflects the status of regional lymph nodes in patients with melanoma. Preoperative lymphoscintigraphy has proved to be invaluable in identifying SNs and in demonstrating unusual lymphatic drainage pathways. Greatest accuracy at the time of surgery is achieved using both blue dye injection and a gamma-probe. Close cooperation between surgeons, nuclear medicine physicians and pathologists is required if the SN biopsy technique is to be reliable. The results of clinical trials will demonstrate whether SN biopsy has any therapeutic value. It is already clear, however, that SN examination provides very accurate staging, and SN biopsy is therefore essential for all melanoma patients entering adjuvant therapy trials.

Humans↗
PubMed2001

The Sydney Melanoma Unit experience of sentinel lymphadenectomy for melanoma.

Commenced in 1992, a validation study involving 118 patients who underwent sentinel lymphadenectomy, then immediate complete regional node dissection, confirmed that the histological status of sentinel nodes (SNs) accurately reflects the status of regional nodes. Preoperative lymphoscintigraphy was found to be valuable in determining the number and position of SNs and demonstrated several previously unsuspected lymphatic drainage pathways. The greatest accuracy was achieved by using both blue dye and a gamma probe (to detect radioactivity in SNs after lymphoscintigraphy the previous day). In experience to date, SN positivity has been related to primary tumor thickness (<1.5 mm, 5%; 1.5-3 mm, 14%; >3 mm, 24%). In 827 patients, with a median follow-up of 37 months, recurrence (at any site) has occurred in 47% of SN-positive patients but only 12% of SN-negative patients. Already 30% of SN-positive patients have died of melanoma, but only 6% of SN-negative patients. Although sentinel lymphadenectomy provides accurate staging and important prognostic information, its therapeutic significance has yet to be determined in clinical trials.

Australia↗
PubMed2001

Factors influencing the early outcome of major lower limb amputation for vascular disease.

A consecutive series of 349 primary lower limb amputations for vascular disease, done during 1992-1998, were reviewed for amputation level, revision, complications and death, seeking associations with the American Society of Anesthesiology (ASA) grade and pre-operative co-morbidities of patients. Attempted revascularisation, and seniority of surgeon supervising the amputation were also examined for their possible influence on outcome. There were 312 patients (163 male) aged 39-92 years (median, 76 years). The majority of patients were ASA 3 or 4 (76%), and ASA 4 was associated with increased mortality (P < 0.01). Limiting heart problems (P < 0.01) and 'general frailty' (P < 0.001) also carried significantly higher risks of death, but limiting chest problems, dementia, and diabetes mellitus did not. There was no significant association between attempts at revascularisation at any time before amputation, and amputation level or the need for revision. There were no differences between consultants, registrars, and senior house officers (most senior surgeon) for any outcome measure. This study documents the medical status of amputees more clearly than usual, and demonstrates the effect of co-morbidity on the substantial mortality of these patients. The results support an aggressive policy of attempted revascularisation, and show that properly trained junior surgeons obtain satisfactory results.

Adult↗
PubMed2000

Overexpression of eotaxin and the CCR3 receptor in human atherosclerosis: using genomic technology to identify a potential novel pathway of vascular inflammation.

BACKGROUND: Unstable atherosclerotic lesions typically have an abundant inflammatory cell infiltrate, including activated T cells, macrophages, and mast cells, which may decrease plaque stability. The pathophysiology of inflammatory cell recruitment and activation in the human atheroma is incompletely described. METHODS AND RESULTS: We hypothesized that differential gene expression with DNA microarray technology would identify new genes that may participate in vascular inflammation. RNA isolated from cultured human aortic smooth muscle cells treated with tumor necrosis factor-alpha (TNF-alpha) was examined with a DNA microarray with 8600 genes. This experiment and subsequent Northern analyses demonstrated marked increases in steady-state eotaxin mRNA (>20 fold), a chemokine initially described as a chemotactic factor for eosinophils. Because eosinophils are rarely present in human atherosclerosis, we then studied tissue samples from 7 normal and 14 atherosclerotic arteries. Immunohistochemical analysis demonstrated overexpression of eotaxin protein and its receptor, CCR3, in the human atheroma, with negligible expression in normal vessels. Eotaxin was predominantly located in smooth muscle cells. The CCR3 receptor was localized primarily to macrophage-rich regions as defined by immunopositivity for CD 68; a minority of mast cells also demonstrated immunopositivity for the CCR3 receptor. CONCLUSIONS: Eotaxin and its receptor, CCR3, are overexpressed in human atherosclerosis, suggesting that eotaxin participates in vascular inflammation. These data demonstrate how genomic differential expression technology can identify novel genes that may participate in the stability of atherosclerotic lesions.

Actins↗
PubMed2000

Crystal structure of human squalene synthase. A key enzyme in cholesterol biosynthesis.

Squalene synthase catalyzes the biosynthesis of squalene, a key cholesterol precursor, through a reductive dimerization of two farnesyl diphosphate (FPP) molecules. The reaction is unique when compared with those of other FPP-utilizing enzymes and proceeds in two distinct steps, both of which involve the formation of carbocationic reaction intermediates. Because FPP is located at the final branch point in the isoprenoid biosynthesis pathway, its conversion to squalene through the action of squalene synthase represents the first committed step in the formation of cholesterol, making it an attractive target for therapeutic intervention. We have determined, for the first time, the crystal structures of recombinant human squalene synthase complexed with several different inhibitors. The structure shows that SQS is folded as a single domain, with a large channel in the middle of one face. The active sites of the two half-reactions catalyzed by the enzyme are located in the central channel, which is lined on both sides by conserved aspartate and arginine residues, which are known from mutagenesis experiments to be involved in FPP binding. One end of this channel is exposed to solvent, whereas the other end leads to a completely enclosed pocket surrounded by conserved hydrophobic residues. These observations, along with mutagenesis data identifying residues that affect substrate binding and activity, suggest that two molecules of FPP bind at one end of the channel, where the active center of the first half-reaction is located, and then the stable reaction intermediate moves into the deep pocket, where it is sequestered from solvent and the second half-reaction occurs. Five alpha helices surrounding the active center are structurally homologous to the active core in the three other isoprenoid biosynthetic enzymes whose crystal structures are known, even though there is no detectable sequence homology.

Alkyl and Aryl Transferases↗
PubMed2000

Early discharge and postnatal depression: a prospective cohort study.

OBJECTIVES: To determine whether women discharged from hospital < or = 72 hours after childbirth (early discharge) were at greater risk of developing symptoms of postnatal depression during the following six months than those discharged later (late discharge), their reasons for early discharge and their level of postnatal support. DESIGN AND SETTING: Population-based, prospective cohort study with questionnaires at Day 4, and at 8, 16 and 24 weeks postpartum, conducted at all birth sites in the Australian Capital Territory (ACT). PARTICIPANTS: Women resident in the ACT giving birth to a live baby from March to October 1997. MAIN OUTCOME MEASURE: A score > 12 on the Edinburgh Postnatal Depression Scale (EPDS). RESULTS: 1295 (70%) women consented to participate; 1193 (92%) were retained in the study to 24 weeks and, of these, 1182 returned all four questionnaires. Of the 1266 women for whom length-of-stay data were available, 467 (37%) were discharged early and 799 (63%) were discharged late. There were no significant differences between the proportion of women discharged early who ever scored > 12 on the EPDS during the six postpartum months and those discharged late (17% v. 20%), even after controlling for other risk factors (adjusted OR, 0.67; 95% CI, 0.44-1.01). Of women discharged early, 93% had at least one postnatal visit at home from a midwife and 81% were "very satisfied" with the care provided. Most women (96%) reported they had someone to help in practical ways. CONCLUSIONS: Women discharged early after childbirth do not have an increased risk of developing symptoms of postnatal depression during the following six months.

Adult↗
PubMed2000

A new American Joint Committee on Cancer staging system for cutaneous melanoma.

The Melanoma Staging Committee of the AJCC has proposed major revisions of the melanoma TNM and stage grouping criteria. The committee members represent most of the major cooperative groups and cancer centers worldwide with a special interest in melanoma; the committee also collectively has had clinical experience with over 40,000 patients. The new staging system better reflects independent prognostic factors that are used in clinical trials and in reporting the outcomes of various melanoma treatment modalities. Major revisions include 1) melanoma thickness and ulceration, but not level of invasion, to be used in the T classification; 2) the number of metastatic lymph nodes, rather than their gross dimensions, the delineation of microscopic versus macroscopic lymph node metastases, and presence of ulceration of the primary melanoma to be used in the N classification; 3) the site of distant metastases and the presence of elevated serum LDH, to be used in the M classification; 4) an upstaging of all patients with Stage I,II, and III disease when a primary melanoma is ulcerated; 5) a merging of satellite metastases around a primary melanoma and in-transit metastases into a single staging entity that is grouped into Stage III disease; and 6) a new convention for defining clinical and pathologic staging so as to take into account the new staging information gained from intraoperative lymphatic mapping and sentinel lymph node biopsy. The AJC Melanoma Staging Committee invites comments and suggestions regarding this proposed staging system before a final recommendation is made.

Biopsy↗