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Biomedical subjects

John F Thompson

Publications and source records attributed to John F Thompson.

At least 37 records · Page 2Linked to original sources
PubMed2006

Surgical procedures for melanoma in public and private New South Wales hospitals, 2001-2002.

BACKGROUND: Evidence suggests that there is considerable variation in the types of procedures used to treat cancer. This variation may result in suboptimal or cost-ineffective care. The present study examined the variation in surgical treatment of melanoma before the establishment of a Melanoma Network that could promote more uniform high-quality care in New South Wales (NSW). The variations in the use of surgical procedures for melanoma by NSW Area Health Service of patient residence were examined. METHODS: Data in the Health Information Exchange of NSW Health collected on procedures carried out on patients with a diagnosis of melanoma in NSW public and private hospitals from 1 July 2001 to 30 June 2002 were examined. Data were aggregated by Area Health Services of patient residence. These data were compared with the numbers of new cases of melanoma notified to the NSW Central Cancer Registry in the same areas in 2001-2002. Excision of skin lesions, skin grafting and numbers and types of lymph node procedures were examined. RESULTS: During the study period, the Central Cancer Registry reported that there were 3085 notifications of melanoma, whereas hospital inpatient data recorded that 6864 procedures were carried out for patients with a melanoma diagnosis in NSW public and private hospitals. Sixty-seven per cent of procedures were carried out in private hospitals. A total of 852 skin grafting procedures were recorded. Of these, 60% were carried out in private hospitals. The average proportion of skin grafts associated with excisions in NSW was 30% (range, 0-53%). Eight hundred and fifty-eight lymph node procedures were recorded for 747 NSW residents. These were biopsies, excisions or both. Forty per cent were carried out in private hospitals. The average proportion of new cases of melanoma associated with a lymph node procedure in NSW was 28% (range, 0-47%). CONCLUSION: Most of the inpatient procedures for patients with melanoma were carried out in private hospitals. The proportions of new cases that underwent skin grafting after excision, or underwent lymph node dissection, varied more than fivefold from one Area Health Service to another. This may indicate variations in casemix, variations in clinical practice or both.

Hospitals, Private↗
PubMed2006

Contamination and decontamination of Doppler probes.

INTRODUCTION: Nosocomial infection occurs in 2-9% of patients undergoing vascular surgery and can lead to death, amputation or require complex revision surgery. Neck ties, pagers, stethoscopes and Doppler probes have been shown to carry pathogens. We measured bacterial colonisation of Doppler probes on a vascular unit and audited the effect of staff education at reducing this contamination. MATERIALS AND METHODS: Bacteriological culture swabs were taken from hand-held Doppler probes on the vascular surgical ward and clinic. There was no protocol for cleaning the Doppler probes, so manufacturers were contacted for their recommendations. The results of cultures were presented to nursing and medical staff, who were then asked to clean the probes with alcohol wipes after each use. After an interval of 1 week, bacteriological cultures from the same Doppler probes was repeated. RESULTS: Fifty bacteriological cultures were performed from 10 Doppler probes over a 4-week period. Thirteen (26%) cultures were positive for diphtheroids, coliforms, coagulase-negative staphylococci and skin flora. After staff education, 42 further swabs were taken from the same probes; two positive cultures were obtained with scanty growth of skin flora (chi2 P < 0.05). CONCLUSIONS: Staff education and simple cleaning significantly reduces the contamination of hand-held Doppler probes and may help prevent nosocomial infection.

Ambulatory Care↗
PubMed2006

Role of electrochemotherapy in the treatment of metastatic melanoma and other metastatic and primary skin tumors.

Electroporation is a novel therapeutic modality that uses pulsed electrical currents to enhance the uptake of drugs, vaccines and genes into cells, and has been used for over 20 years. Electroporation therapy using cytotoxic drugs is called electrochemotherapy. Electrochemotherapy has been studied in vitro, in vivo and in clinical trials. It is potentially useful for treating patients with metastatic tumors, such as melanoma, and even select primary tumors, such as head and neck squamous cell carcinomas and basal cell carcinoma. Various chemotherapeutic agents have been tested with electroporation therapy, but bleomycin and cisplatin are the two most widely used. The biological basis of electroporation therapy is outlined in this review and basic science studies and the limited clinical studies that have involved electrochemotherapy are reviewed. Particular focus is placed on trials involving melanoma, head and neck cancers and other primary and metastatic skin cancers.

Antibiotics, Antineoplastic↗
PubMed2005

Intralesional targeted alpha therapy for metastatic melanoma.

UNLABELLED: This paper reports the development and application of intralesional targeted alpha therapy (TAT) for melanoma, being the first part of a program to establish a new systemic therapy. RATIONALE: Labelling the benign targeting vector 9.2.27 with 213Bi forms the alpha-immunoconjugate (AIC), which is highly cytotoxic to targeted melanoma cells. OBJECTIVE: To investigate the safety and efficacy of intralesional AIC in patients with metastatic skin melanoma. FINDINGS: 16 melanoma patients were recruited. All the patients were positive to the monoclonal antibody 9.2.27. AIC doses from 50 to 450 mCi injected into lesions of different sizes resulted in massive cell death, as observed by the presence of tumour debris. The AIC was very effective in delivering a high dose to the tumour while sparing other tissues. There were no significant changes in blood proteins and electrolytes. There was no evidence of a human-antimouse-antibody reaction. Evidence of significant decline in serum marker melanoma-inhibitory-activity protein (MIA) at 2 weeks post-TAT was observed. CONCLUSIONS: Intralesional TAT for melanoma was found to be quite safe up to 450 mCi, and efficacious at a dose of 200 mCi. MIA, apoptosis and ki67 proliferation marker tests all indicated that TAT is a promising therapy for the control of inoperable secondary melanoma or primary ocular melanoma.

Aged↗
PubMed2005

Novel variants in human and monkey CETP.

Variation in CETP has been shown to play an important role in HDL-C levels and cardiovascular disease. To better characterize this variation, the promoter and exonic DNA for CETP was resequenced in 189 individuals with extreme HDL-C or age. Two novel amino acid variants were found in humans (V-12D and Y361C) and an additional variant (R137W) not previously studied in vitro were expressed. D-12 was not secreted and had no detectable activity in cells. C361 and W137 retained near normal amounts of cholesteryl ester transfer activity when purified but were less well secreted than wild type. Torcetrapib, a CETP inhibitor in clinical development with atorvastatin, was found to have a uniform effect on inhibition of wild type CETP versus W137 or C361. In addition, the level of variation in other species was assessed by resequencing DNA from nine cynomolgus monkeys. Numerous intronic and silent SNPs were found as well as two variable amino acids. The amino acid altering SNPs were genotyped in 29 monkeys and not found to be significantly associated with HDL-C levels. Three SNPs found in monkeys were identical to three found in humans with these SNPs all occurring at CpG sites.

Black or African American↗
PubMed2005

Melanoma metastases in regional lymph nodes are accurately detected by proton magnetic resonance spectroscopy of fine-needle aspirate biopsy samples.

BACKGROUND: Nonsurgical assessment of sentinel nodes (SNs) would offer advantages over surgical SN excision by reducing morbidity and costs. Proton magnetic resonance spectroscopy (MRS) of fine-needle aspirate biopsy (FNAB) specimens identifies melanoma lymph node metastases. This study was undertaken to determine the accuracy of the MRS method and thereby establish a basis for the future development of a nonsurgical technique for assessing SNs. METHODS: FNAB samples were obtained from 118 biopsy specimens from 77 patients during SN biopsy and regional lymphadenectomy. The specimens were histologically evaluated and correlated with MRS data. Histopathologic analysis established that 56 specimens contained metastatic melanoma and that 62 specimens were benign. A linear discriminant analysis-based classifier was developed for benign tissues and metastases. RESULTS: The presence of metastatic melanoma in lymph nodes was predicted with a sensitivity of 92.9%, a specificity of 90.3%, and an accuracy of 91.5% in a primary data set. In a second data set that used FNAB samples separate from the original tissue samples, melanoma metastases were predicted with a sensitivity of 87.5%, a specificity of 90.3%, and an accuracy of 89.1%, thus supporting the reproducibility of the method. CONCLUSIONS: Proton MRS of FNAB samples may provide a robust and accurate diagnosis of metastatic disease in the regional lymph nodes of melanoma patients. These data indicate the potential for SN staging of melanoma without surgical biopsy and histopathological evaluation.

Biopsy, Fine-Needle↗
PubMed2005

A sentinel node biopsy does not increase the incidence of in-transit metastasis in patients with primary cutaneous melanoma.

BACKGROUND: It has been suggested that performing a sentinel node biopsy (SNB) in patients with cutaneous melanoma increases the incidence of in-transit metastasis (ITM). METHODS: ITM rates for 2018 patients with primary melanomas > or =1.0 mm thick treated at a single institution between 1991 and 2000 according to 3 protocols were compared: wide local excision (WLE) only (n = 1035), WLE plus SNB (n = 754), and WLE plus elective lymph node dissection (n = 229). RESULTS: The incidence of ITM for the three protocols was 4.9%, 3.6%, and 5.7%, respectively (not significant), and as a first site of recurrent disease the incidence was 2.5%, 2.4%, and 4.4%, respectively (not significant). The subset of patients who were node positive after SNB and after elective lymph node dissection also had similar ITM rates (10.8% and 7.1%, respectively; P = .11). On multivariate analysis, primary tumor thickness and patient age predicted ITM as a first recurrence, but type of treatment did not. Patients who underwent WLE only and who had a subsequent therapeutic lymph node dissection (n = 149) had an ITM rate of 24.2%, compared with 10.8% in patients with a tumor-positive sentinel node treated with immediate dissection (n = 102; P = .03). CONCLUSIONS: Performing an SNB in patients with melanoma treated by WLE does not increase the incidence of ITM.

Adolescent↗
PubMed2005

Outcome in 846 cutaneous melanoma patients from a single center after a negative sentinel node biopsy.

BACKGROUND: A negative sentinel node biopsy (SNB) implies a good prognosis for melanoma patients. The purpose of this study was to determine the long-term outcome for melanoma patients with a negative SNB. METHODS: Survival and prognostic factors were analyzed for 836 SNB-negative patients. All patients with a node field recurrence were reviewed, and sentinel node (SN) tissue was reexamined. RESULTS: The median tumor thickness was 1.7 mm, and 23.8% were ulcerated. The median follow-up was 42.1 months. Melanoma specific survival at 5 years was 90%, compared with 56% for SN-positive patients (P < .001). On multivariate analysis, only thickness and ulceration retained significance for disease-free and disease-specific survival. Five-year survival for patients with nonulcerated lesions was 94% vs. 78% with ulceration. Eighty-three patients (9.9%) had a recurrence. Twenty-seven patients developed recurrence in the regional node field, and in 22 of these, it was the first recurrence site. Six developed local recurrence, 17 an in-transit metastasis, and 58 distant disease. The false-negative rate was 13.2%. SN slides and tissue blocks were further examined in 18 patients with recurrence in the node field, and metastatic disease was found in 3 of them. CONCLUSIONS: This large, single-center study confirms that patients with a negative SNB have a significantly better prognosis than those with positive SNs. In those with a negative SNB, primary tumor thickness and ulceration are independent predictors of survival. Incorrect pathologic diagnosis contributed to only a minority of the false-negative results in this study.

False Negative Reactions↗
PubMed2005

CETP polymorphisms associated with HDL cholesterol may differ from those associated with cardiovascular disease.

To better understand the role of cholesteryl ester transfer protein (CETP) in cardiovascular disease, nine polymorphisms spanning the gene from the upstream promoter region to beyond the 3'UTR were genotyped in 2553 individuals from multiple ethnic groups and with different cardiovascular disease profiles. The frequency of four of these SNPs varied by 40-300% between Caucasians and African Americans. SNPs in each ethnic group fell into two haploblocks with significant linkage disequilibrium within each block. SNPs in the 5' haploblock were significantly associated with HDL cholesterol while SNPs in the 3' haploblock were, at best, only weakly associated with HDL-C. One SNP in the 3' haploblock (rs1800774 in intron 12) was highly associated with history of myocardial infarction even though it was not associated with HDL-C. This association was driven by the effect in Caucasian women where 11.9% of the women with no history of MI are homozygous for the less common allele while 23.7% of those with a history of MI share this genotype. In addition, this SNP was highly associated with BMI among Caucasians (p < 0.0001). The association of HDL-C with CETP genotype was found to be independent of smoking or alcohol consumption. These results replicate some earlier findings and also help to explain some of the apparent contradictions in the literature surrounding the role of CETP in modulating HDL-C and cardiovascular disease.

Black or African American↗
PubMed2005

Cholesteryl ester transfer protein variants have differential stability but uniform inhibition by torcetrapib.

Cholesteryl ester transfer protein (CETP) is an important modulator of high density lipoprotein cholesterol in humans and thus considered to be a therapeutic target for preventing cardiovascular disease. The gene encoding CETP has been shown to be highly variable, with multiple single nucleotide polymorphisms responsible for altering both its transcription and sequence. Examining nine missense variants of CETP, we found some had significant associations with CETP mass and high density lipoprotein cholesterol levels. Two variants, Pro-373 and Gln-451, appear to be more stable in vivo, an observation mirrored by partial proteolysis studies performed in vitro. Because these naturally occurring variant proteins are potentially present in clinical populations that will be treated with CETP inhibitors, all commonly occurring haplotypes were tested to determine whether the proteins they encode could be inhibited by torcetrapib, a compound currently in clinical trials in combination with atorvastatin. Torcetrapib behaved similarly with all variants, with no significant differences in inhibition.

Adult↗
PubMed2005

Expression and localization of Muc4/sialomucin complex (SMC) in the adult and developing rat intestine: implications for Muc4/SMC function.

Muc4/sialomucin complex (SMC) is a high molecular mass heterodimeric membrane mucin, encoded by a single gene, and originally discovered in a highly metastatic ascites rat mammary adenocarcinoma. Subsequent studies have shown that it is a prominent component of many accessible and vulnerable epithelia, including the gastrointestinal tract. Immunoblot and immunofluorescence analyses demonstrated that Muc4/SMC expression in the rat small intestine increases from proximal to distal regions and is located predominantly in cells at the base of the crypts. These cells were postulated to be Paneth cells, based on their location, morphology, and secretory granule content. Immunohistochemistry indicated the presence of Muc4/SMC in these granules. Muc4/SMC expression was higher in the rat colon than small intestine and was abundantly present in colonic goblet cells, but not in goblet cells in the small intestine. Immunohistochemistry also suggested the presence of MUC4 in human colonic goblet cells. Biochemical analyses indicated that rat colonic Muc4/SMC is primarily the soluble form of the membrane mucin. Analyses of Muc4/SMC during development of the rat gastrointestinal tract showed its appearance at embryonic day 14 of the esophagus and at day 15 at the surface of the undifferentiated stratified epithelium at the gastroduodenal junction, then later at cell surfaces in the more distal regions of the differentiated epithelium of the small intestine, culminating in expression as an intracellular form in the crypts of the small intestine at about day 21. Limited expression in the colon was observed during development before birth at cell surfaces, with expression as an intracellular form in the goblet cells arising during the second week after birth. These results suggest that membrane mucin Muc4/SMC serves different functions during development of the intestine in the rat, but is primarily a secreted product in the adult animal.

Age Factors↗
PubMed2005

Selective sentinel lymphadenectomy: progress to date and prospects for the future.

The sentinel node (SN) concept was clearly outlined by Virchow in the mid-nineteenth century, and Braithwaite used the term "glands sentinel" in 1923. However, it was not until Morton, Cochran et al. published their landmark report in 1992 that the clinical relevance of the SN was fully appreciated. Since then, the validity of the concept has been confirmed in studies undertaken at a number of centers worldwide. It has become clear that SN status accurately reflects the status of the entire regional node field, not only in patients with melanoma but also in those with breast cancer and a wide range of other primary malignancies. New insights into lymphatic anatomy have been gained by preoperative lymphoscintigraphy, and the original blue dye mapping technique for SN identification has been supplemented by intraoperative use of a hand-held gamma probe to identify radioactivity in colloid particles injected at the primary tumor site. It has become clear that all three methods are required to achieve optimal accuracy of SN identification. Although SN assessment provides very important prognostic information, the results of randomized trials must be awaited to determine whether selective sentinel lymphadenectomy, with full regional node dissection if a positive SN is found, is of any therapeutic value. It is possible that SN positivity is merely a marker of disease that has the potential for hematogenous dissemination and systemic metastasis. As follow-up times extend, reported false-negative SN rates are increasing, and ways to reduce these false-negative rates are therefore being actively sought. Attempts are being made to increase the accuracy of SN identification, and to confirm true SN identity both at the time of surgery and retrospectively. The ultimate objective is to develop minimally invasive and even non-invasive methods of SN assessment, Proton magnetic resonance spectroscopy is one technique that might make it possible to achieve this goal, and avoid the present morbidity and cost of operative SN removal.

Forecasting↗
PubMed2005

Role of lymphoscintigraphy for selective sentinel lymphadenectomy.

An essential prerequisite for a successful sentinel node biopsy (SNB) procedure is an accurate map of the pattern of lymphatic drainage from the primary tumor site. The role of lymphoscintigraphy (LS) in SNB is to provide such a map in each patient. This map should indicate not only the location of all sentinel nodes but also the number of SNs at each location. Such mapping can be achieved using 99mTc-labeled small particle radiocolloids, high-resolution collimators with minimal septal penetration, and imaging protocols that detect all SNs in every patient regardless of their location. This is especially important in melanoma patients, since high-quality LS can identify the actual lymphatic collecting vessels as they drain into each SN. The SN is not always found in the nearest node field and is best defined as "any lymph node receiving direct lymphatic drainage from a primary tumor site." Reliable clinical prediction of lymphatic drainage from the skin or breast is not possible. Patterns of lymphatic drainage from the skin are highly variable from patient to patient, even from the same area of the skin. Unexpected lymphatic drainage has been found from the skin of the back to SNs in the triangular intermuscular space and in some patients through the posterior body wall to SNs in the para-aortic, paravertebral, and retroperitoneal areas. Lymphatic drainage from the head and neck frequently involves SNs in multiple node fields, and can occur from the base of the neck up to nodes in the occipital or upper cervical areas or from the scalp down to nodes at the neck base, bypassing many other node groups. Lymphatic drainage from the upper limb can be directly to SNs above the axilla. Drainage to the epitrochlear region from the hand and arm is more common than was previously thought as is drainage to the popliteal region from the foot and leg. Interval nodes, which lie along the course of a lymphatic vessel between a melanoma site and a recognised node field, are not uncommon especially on the trunk. Drainage across the midline of the body is quite frequent on the trunk and in the head and neck region. In breast cancer, although dynamic imaging is usually not possible, an early postmassage image will also often visualize the lymphatic vessels leading to the SN allowing them to be differentiated from any second tier nodes. Small radiocolloid particles are also needed to achieve migration from peritumoral injections sites and LS allows accurately detection of SNs outside the axilla, which occur in about 50% of patients. These nodes may lie in the internal mammary chain, the supraclavicular region, or the interpectoral region. Intramammary interval nodes can also be SNs in some patients. The location of the cancer in the breast is not a reliable guide to lymphatic drainage, since lymph flow often crosses the center line of the breast. Micrometastatic disease can be present in any SN regardless of its location, and for the SNB technique to be accurate all true SNs must be identified and removed in every patient. LS is an important first step in ensuring that this goal is achieved.

Breast Neoplasms↗
PubMed2005

In vivo and ex vivo proton MR spectroscopy of primary and secondary melanoma.

In vivo magnetic resonance (MR) spectroscopy at 1.5T was performed on a large polypoid cutaneous melanoma, and two enlarged lymph nodes containing metastatic melanoma, from three patients. Spectra were acquired in vivo from voxels wholly within the primary tumour or secondary lymph node and were thus uncontaminated by signals from adjacent tissue. Tissue biopsies taken after resection of primary tumours and secondary lymph nodes were examined by 8.5T magnetic resonance spectroscopy (MRS) and the results compared with the in vivo spectra, and with spectra from normal skin and a benign skin lesion. There was good agreement between the dominant features of 1.5T spectra acquired in vivo and 8.5T spectra acquired from resected tissue. However, less intense resonances observed at 8.5T in malignant biopsy tissue were not consistently observed at 1.5T in vivo. In vivo spectra from primary and metastatic melanoma showed high levels of choline metabolites. An intense lactate resonance was also present in the in vivo spectrum of primary melanoma. All 8.5T spectra of biopsies from primary and secondary melanoma showed high levels of choline metabolites and lactate, and additional resonances consistent with elevated levels of taurine, alanine, lysine, and glutamate/glutamine relative to normal and benign tissue. Elevated levels of choline, lactate, taurine, and amino acids appear to be clinically useful markers for identifying the pathology of primary and metastatic melanoma.

Adult↗