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Biomedical subjects

J F Thompson

Publications and source records attributed to J F Thompson.

At least 109 records · Page 6Linked to original sources

Lymphatic drainage from the skin of the back to retroperitoneal and paravertebral lymph nodes in melanoma patients.

BACKGROUND: Preoperative lymphoscintigraphy (LS) with 99mTc antimony sulphide colloid is now part of the routine management of patients with intermediate thickness melanoma at the Sydney Melanoma Unit. Over a 13-year period, 1375 patients have been examined using LS, and we have observed many unusual lymphatic drainage pathways, including direct drainage through the body wall to retroperitoneal and paravertebral lymph nodes from the skin of the back. The aim of this study was to determine the incidence of such drainage in the 542 patients who had primary melanoma sites on the posterior trunk. METHODS: The lymphoscintigrams performed on these patients were examined for the presence of direct lymphatic drainage through the posterior body wall to sentinel nodes in the retroperitoneal and paravertebral regions. RESULTS: Lymphatic drainage directly through the body wall to such lymph nodes occurred in 14 of these 542 patients. CONCLUSIONS: Preoperative knowledge of the presence of this lymph drainage pattern may influence surgical management, and follow-up investigations in these patients can be tailored to ensure that the relevant areas are examined with anatomic imaging or F18-FDG PET scans.

Back↗

Demonstration of second-tier lymph nodes during preoperative lymphoscintigraphy for melanoma: incidence varies with primary tumor site.

BACKGROUND: Preoperative cutaneous lymphoscintigraphy (LS) to identify sentinel (first-tier) lymph nodes was performed in 250 consecutive melanoma patients before wide local excision only or wide local excision with sentinel node biopsy. METHODS: The location of the sentinel nodes was marked on the overlying skin in all patients. Whether or not tracer was present in second-tier lymph nodes on the delayed scans was recorded for each patient and related to the lesion site at which the tracer had initially been injected. For 100 consecutive patients the rate of tracer movement through the lymphatic channels was compared to the incidence of second-tier drainage. RESULTS: Second-tier nodes were visualized in all patients with melanomas on the leg and thigh, and in almost all patients with melanomas on the forearm and hand, but were seen less often in patients with more centrally located melanomas. There was a significant correlation between the rate of lymph flow and the incidence of demonstrable second-tier drainage. CONCLUSION: The results suggest that the physiology of the lymphatic system varies depending on the origin of the lymphatic vessel. These findings have important implications for application of the sentinel node biopsy technique in individual patients.

Antimony↗

Analysis of histopathological factors associated with prolonged survival of 10 years or more for patients with thick melanomas (> 5 mm).

AIMS: Although tumour thickness is the best predictor of melanoma prognosis in patients with localized cutaneous melanoma, prolonged survival occasionally occurs in patients with thick melanomas (> 5 mm). This study examined histological features which were associated with long-term survival. METHODS AND RESULTS: Forty-two patients with thick, vertical growth phase melanomas surviving 10 years or more after diagnosis were matched by clinical stage of disease, sex, age and anatomical site of the primary lesion with 42 patients with similar characteristics who died from their disease within 3 years of diagnosis. Fourteen histological factors were assessed in both groups. Tumours with spindle cell and Spitz-like cell populations and those with low mitotic activity were significantly more frequently observed in long-term survivors. There was also a significant excess of melanomas exhibiting desmoplasia and those lacking vascular invasion in the long-term survivors. CONCLUSIONS: These findings suggest that it may be useful to modify the current cutaneous melanoma classification on the basis of unusual cytological characteristics (as discussed at the recent 4th World Conference on Melanoma).

Adolescent↗

Decreased citrate improves iron availability from infant formula: application of an in vitro digestion/Caco-2 cell culture model.

We have applied an in vitro digestion/Caco-2 cell culture model to the assessment of iron availability from human milk and a generic cow's milk-based infant formula. Experiments were designed to determine the availability of iron from human milk relative to infant formula and whether known promoters of iron absorption would increase Caco-2 cell iron uptake and availability from the infant formula. In addition, we sought to determine if decreasing the citrate concentration in the infant formula would increase the iron uptake. Although approximately twice as much iron was in solution from digests of the infant formula relative to that of human milk, smaller or equal amounts of iron were taken up from the infant formula relative to the human milk digest. These results are qualitatively similar to in vivo studies. Addition of known iron uptake promoters to infant formula did not enhance Caco-2 cell iron uptake from the infant formula digest, indicating that the iron in the infant formula existed predominantly in a tightly bound unavailable form(s). Enzymatic pretreatment of the infant formula with citrate lyase and oxalacetate decarboxylase decreased the citrate concentration by 67% and resulted in a 64% increase of iron in solution, which corresponded to a 46% increase in the cell iron uptake. Iron uptake from the "low citrate" formula plus cysteine was 102% greater relative to the nontreated formula. The results indicate that too much citrate can reduce iron uptake, particularly if it is present at concentrations greater than promoters such as ascorbic acid and cysteine.

Animals↗

Exclusive lymphatic drainage from a melanoma on the back to intraabdominal lymph nodes.

Preoperative lymphoscintigraphy with Tc-99m antimony sulphide colloid was performed for a patient with a cutaneous melanoma on the left back. There was direct lymphatic drainage to retroperitoneal and paravertebral nodes but no drainage whatsoever to the axillary, inguinal, or triangular intermuscular space node fields, which would normally be expected to drain this area of the skin. Any attempt at sentinel lymph node biopsy in the axilla, groin, or triangular intermuscular space would have failed in this patient.

Abdomen↗

Variability of cutaneous lymphatic flow rates in melanoma patients.

Preoperative lymphoscintigraphy was performed in 198 consecutive patients with cutaneous melanoma prior to their definitive surgical treatment. After intradermal injection of antimony sulphide colloid labelled with technetium-99m, lymphatic flow rates were measured in each patient and found to vary according to the location of the primary tumour. The fastest flow rates occurred from melanoma sites on the distal limbs, particularly the lower limbs. The slowest flow rates were from the head and neck region and the proximal limbs, especially the upper arms and shoulders. Lack of flow in the early dynamic images occurred most commonly for tumours on the upper arms and shoulders. These results can be used to optimize the timing of blue dye injection prior to surgery and may influence the sentinel node biopsy method to be used in individuals who show no early drainage.

Antimony↗

Cadaveric liver procurement using aortic perfusion only.

BACKGROUND: To test the effectiveness of a simpler surgical technique for cadaveric liver procurement for liver transplantation, a prospective randomized study was carried out between August 1994 and December 1995, to compare aortic perfusion only (APO) for flush-preservation of the liver with the conventional combined aortic and portal perfusion (APP) technique. METHODS: Forty multiple organ donors were enrolled with 20 in each arm of the trial. Donor parameters (age, bodyweight, liver function tests), surgeons performing the operations, the involvement of other procurement teams and the total ischaemic times were similar in the two groups. The liver recipients had a wide range of native liver pathology but were of similar age, sex and bodyweight in the two groups. RESULTS: The mean procurement operation times for the APO and APP groups were 126.7+/-38.6 and 137.8+/-55.9 min, respectively (P=ns). The perfusion took longer to complete in the APO group (10.2+/-1.7 vs 7.2+/-1.4 min (APP), P < 0.001). The liver temperature fell to its lowest level (12.5+/-3.4 degrees C (APO) vs 11+/-3 degrees C (APP), P=ns) in a similar time (11.9+/-3.8 min (APO) vs 9.3+/-3.4 mins (APP), P=ns). There was no graft primary non-function or graft arterial injury in either group. There was no significant difference between the APO and APP initial graft outcomes. The 3-month patient survival rate was identical in the two groups (95%); 81% of renal grafts from the APO donors functioned well from the time of transplantation as did 76% of those from APP donors. CONCLUSIONS: It is concluded that the APO procurement technique produces equivalent results to those achieved with the APP method. The simplicity of the APO technique makes it the preferred technique.

Adult↗

Treatment of large, persistent lymphocoeles using an argon beam coagulator and talc.

BACKGROUND: Lymphocoele formation can be a troublesome surgical complication after lymph node dissection and mobilization of large skin flaps. Occasionally, lymphocoeles persist for prolonged periods despite repeated aspiration. Treatment by sclerotherapy has been recommended, but this requires a prolonged treatment time and often causes intense pain. METHODS: The technique used to treat large, persistent lymphocoeles involved 'painting' the lymphocoele wall with an argon beam coagulator after evacuating its contents. Sterile talc was then distributed liberally through the cavity, a closed suction drain placed and the wound closed. RESULTS: The procedure was completely successful in each of the four patients treated. After a mean follow-up period of 11 months (range 6-15 months) no lymphocoele recurrence has occurred. CONCLUSIONS: Use of an argon beam coagulator and talc reliably achieves rapid, definitive obliteration of large, persistent lymphocoeles.

Aged↗

Prophylactic isolated limb perfusion for localized, high-risk limb melanoma: results of a multicenter randomized phase III trial. European Organization for Research and Treatment of Cancer Malignant Melanoma Cooperative Group Protocol 18832, the World Health Organization Melanoma Program Trial 15, and the North American Perfusion Group Southwest Oncology Group-8593.

PURPOSE: Patients with primary cutaneous melanoma > or = 1.5 mm in thickness are at high risk of having regional micrometastases at the time of initial surgical treatment. A phase III international study was designed to evaluate whether prophylactic isolated limb perfusion (ILP) could prevent regional recurrence and influence survival. PATIENTS AND METHODS: A total of 832 assessable patients from 16 centers entered the study; 412 were randomized to wide excision (WE) only and 420 to WE plus ILP with melphalan and mild hyperthermia. Median age was 50 years, 68% of patients were female, 79% of melanomas were located on a lower limb, and 47% had a thickness > or = 3 mm. RESULTS: Median follow-up duration is 6.4 years. There was a trend for a longer disease-free interval (DFI) after ILP. The difference was significant for patients who did not undergo elective lymph node dissection (ELND). The impact of ILP was clearly on the occurrence-as first site of progression - of in-transit metastases (ITM), which were reduced from 6.6% to 3.3%, and of regional lymph node (RLN) metastases, with a reduction from 16.7% to 12.6%. There was no benefit from ILP in terms of time to distant metastasis or survival. Side effects were higher after ILP, but transient in most patients. There were two amputations for limb toxicity after ILP. CONCLUSION: Prophylactic ILP with melphalan cannot be recommended as an adjunct to standard surgery in high-risk primary limb melanoma.

Adolescent↗

Novel lactone compounds from Mortierella verticillata that induce the human low density lipoprotein receptor gene: fermentation, isolation, structural elucidation and biological activities.

Among methods of controlling hypercholesterolemia and hyperlipidemia is the direct stimulation of hepatic low density lipoprotein (LDL) receptors. Two novel lactone compounds, CJ-12,950 and CJ-13,357, containing and unusual oxime moiety, were isolated from a zygomycete Mortierella verticillata. These lactones are potent inducers of the LDL receptor gene in vitro, that enhanced LDL receptor expression in human hepatocytes 2-fold at 100 nM.

Cell Culture Techniques↗

Attitudes to xenotransplantation: scientific enthusiasm, assumptions and evidence.

The use of xenografts could relieve the chronically inadequate supply of human organs for transplantation, but doubts have been expressed about the general acceptability of transplanting animal organs into human. Some researchers and clinicians have chosen to ignore negative attitudes towards clinical xenotransplantation, assuming that people will automatically embrace this new technology when it becomes available. A review of eight studies of attitudes to xenotransplantation did not reveal overwhelming support for it. Particularly negative views were expressed by acute care nurses. Primates have been the donors of choice in clinical xenotransplantation to date, but their continued use is a highly contentious option; the preferred animal donor is now clearly the pig. Animal farming for xenotransplantation is generally regarded as acceptable since animals provide food for man and are an accepted source of items for human use such as heart valves and insulin. Open debate about xenotransplantation must now take place, and present attitudes may change as a result of this. However, it remains to be seen whether xenografts will be widely accepted and used, and the extent to which the chronic shortage of organs for transplantation will thereby be alleviated.

Animal Rights↗

Sequencing of the cholesteryl ester transfer protein 5' regulatory region using artificial transposons.

We have isolated and sequenced genomic clones encompassing more than 5 kb of the 5' flanking region of the cholesteryl ester transfer protein gene. This region contains multiple Alu repeats, a Mermaid repeat, and an extensive GA repeat, which made sequencing exceedingly difficult. To circumvent the problems that these repeats posed to traditional sequencing methodologies, we employed a novel transposon-facilitated technique, which greatly simplified sequencing of regions that had been difficult to accomplish otherwise. We utilized the artificial transposon, AT-2, a Bluescript derivative containing the dhfr gene and unique primer sites at both ends of the insertion DNA. Integration of the transposon occurred efficiently and covered the entire region of interest. Analysis of the sequence indicates a number of potential regulatory factor binding sites upstream of the previously characterized minimal promoter. The 5.7-kb regulatory region confers significant transcriptional activation in a conditionally transformed mouse hepatocyte line as compared to a minimal 137-bp promoter fragment. In addition, a tetranucleotide repeat of variable length that may provide a useful genetic marker has been identified 2 kb upstream of the CETP transcriptional start site.

Animals↗

Mutation of a protease-sensitive region in firefly luciferase alters light emission properties.

Luciferase (EC 1.13.12.7) from the North American firefly, Photinus pyralis, is widely used as a reporter enzyme in cell biology. One of its distinctive properties is a pronounced susceptibility to proteolytic degradation that causes luciferase to have a very short intracellular half-life. To define the structural basis for this behavior and possibly facilitate the design of more stable forms of luciferase, limited proteolysis studies were undertaken using trypsin and chymotrypsin to identify regions of the protein whose accessible and flexible character rendered them especially sensitive to cleavage. Regions of amino acid sequence 206-220 and 329-341 were found to be sensitive, and because the region around 206-220 had high homology with other luciferases, CoA ligases, and peptidyl synthetases, this region was selected for mutagenesis experiments intended to determine which of its amino acids were essential for activity. Surprisingly, many highly conserved residues including Ser198, Ser201, Thr202, and Gly203 could be mutated with little effect on the luminescent activity of P. pyralis luciferase. One mutation, however, S198T, caused several alterations in enzymatic properties including shifting the pH optimum from 8.1 to 8.7, lowering the Km for Mg-ATP by a factor of 4 and increasing the half-time for light emission decay by a factor of up to 150. While the S198T luciferase was less active than wild type, activity could be restored by the introduction of the additional L194F and N197Y mutations. In addition to indicating the involvement of this region in ATP binding, these results provide a new form of the enzyme that affords a more versatile reporter system.

Amino Acid Sequence↗

Frequency and duration of remission after isolated limb perfusion for melanoma.

OBJECTIVE: To examine the frequency and duration of complete remission for locally recurrent and metastatic limb melanoma after isolated limb perfusion (ILP) with cytotoxic agents. DESIGN: A case series of 114 consecutive therapeutic ILPs performed between April 1984 and April 1994 and a review of previously published studies. SETTING: A tertiary referral center for melanoma treatment, located at a university teaching hospital. RESULTS: Of 111 assessable ILPs, 81 (73%) resulted in complete limb tumor remission and 14 (13%) resulted in partial remission (defined as a reduction in size of tumor deposits by > 50%). Complete remission was maintained in 37 (46%) of the 81 cases without any further treatment (median follow-up, 33 months; range, 8-112 months). Of the other 44 cases, disease subsequently recurred in the perfused limb (median time to recurrence, 9.5 months; range, 2-65 months). In 19 of these cases, however, the limb was again disease free at last follow-up after local surgery (12 cases) or a repeat ILP (7 cases). Overall, complete locoregional control was achieved after 50% of assessable ILPs, and a long-term disease-free state in the limb was achieved, with or without further treatment, in 56 (69%) of the 81 cases in which an initial complete remission occurred. For 743 therapeutic ILPs undertaken in 12 series previously reported in the literature, an initial complete remission was reported in 50% of these cases and partial remission in 32%. CONCLUSION: Therapeutic ILP is an effective form of treatment for patients with recurrent and metastatic limb melanoma, achieving short- and long-term results that are superior to those achievable by any other form of treatment currently used.

Adult↗