Aversion to xenotransplantation.
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Animals↗
Biomedical subjects
J F Thompson
Publications and source records attributed to J F Thompson.
Transcriptional modulators affect in vivo protein binding to the low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase promoters.
Treatment of HepG2 cells with known effectors of low density lipoprotein receptor (LDLR) gene expression altered the in vivo pattern of protein-DNA interactions in the promoter. The observed changes are consistent with proteins binding in vivo to the sterol regulatory element (SRE), to Sp1-like sites, as well as to other regions. Protein bound to the SRE in all conditions, but the nature of the dimethyl sulfate reactivity changed depending on the physiological state of the cell. Hypermethylation within the SRE of the low density lipoprotein receptor promoter was observed when cells were treated with cholesterol synthesis inhibitors, insulin, or phorbol 12-myristate 13-acetate, suggesting that the SRE regulates this promoter through sterol-independent as well as sterol-dependent mechanisms. No significant changes were observed in binding to the Sp1-like sites, suggesting that differential binding to these sites does not play a role in altered transcription levels. Analysis of the 3-hydroxy-3-methylglutaryl coenzyme A reductase promoter also revealed protections that varied in a cell type-specific manner. Binding to the 3-hydroxy-3-methylglutaryl coenzyme A reductase SRE and putative nuclear factor 1 sites could be observed but varied little in different physiological conditions.
Base Sequence↗
Clinical and experimental studies of intraoperative autotransfusion using a new filtration device.
The Haemocell S-350 device has recently been introduced for intraoperative autotransfusion. The system uses a novel membrane filter to process shed blood. In the first part of this study a 0.2-micron pore size filter was used in a randomized trial comparing the use of autotransfusion (n = 8) with bank blood controls (n = 9) during aortic reconstruction. This part of the trial was abandoned because of unexpected non-surgical bleeding. Bank blood requirements fell from a median of 3.0 (range 0.0-9.0) units to 1.5 (range 0.0-7.0) units when autotransfusion was used, but these patients had a greater perioperative blood loss (1791 (range 932-3104) versus 1140 (range 440-3840) ml). There was evidence of postoperative heparin excess with an activated partial thromboplastin time ratio of 1.3 (range 0.9-3.0) versus 1.0 (range 1.0-1.2) in controls and an activated clotting time of 206 (range 143-280) versus 137 (range 107-142) s. This was confirmed by raised plasma heparin levels and a prolonged thrombin time normalized by protamine. To improve performance a 0.6-micron pore size filter was studied in ten patients. Filtration efficiency doubled from 19 to 38 per cent. Electron micrographs demonstrated better filter clearance, but 44 per cent of the original concentration of heparin remained in the reinfusate. The S-350 device may be an attractive alternative to centrifugation for intraoperative autotransfusion but, until efficiency is improved, it should only be used for cardiovascular surgery when excess heparin can be reversed with protamine.
Aortic Aneurysm, Abdominal↗
Music in the operating theatre.
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Anesthesiology↗
Prediction of potential metastatic sites in cutaneous head and neck melanoma using lymphoscintigraphy.
BACKGROUND: The technique of lymphoscintigraphy may allow a more selective approach to the management of clinically negative neck nodes among patients with cutaneous head and neck melanoma. PATIENTS AND METHODS: A group of 97 patients with cutaneous head and neck melanoma had preoperative lymphoscintigraphy using intradermal injections of technetium 99m antimony trisulfide colloid to identify sentinel nodes. Fifty-one patients were eligible for clinical analysis after initial definitive treatment by wide excision only (n = 11), wide excision and elective dissection of the neck (n = 19) or axilla (n = 1), or wide excision and a sentinel node biopsy procedure (n = 20). RESULTS: Sentinel nodes were identified in 95 of 97 lymphoscintigrams, and 85% of patients had multiple sentinel nodes. In 21 patients (22%), sentinel nodes were identified outside the parotid region and the 5 main neck levels, mostly in postauricular nodes (n = 13). Lymphoscintigrams were discordant with clinical predictions in 33 patients (34%). Lymph nodes were positive in 4 elective dissections and 4 sentinel node biopsies. Among 16 patients evaluable after wide excision and a negative sentinel node biopsy, 4 patients subsequently developed metastatic nodes; however, confident identification of all nodes marked as sentinel nodes on lymphoscintigraphy was not achieved at the original biopsy procedure in 3 of these patients. CONCLUSIONS: Lymphoscintigraphy and sentinel node biopsy are more difficult to perform in the head and neck than in other parts of the body. The reliability of sentinel node biopsy based on lymphoscintigraphy may be improved by identifying and marking all nodes that are considered to receive direct lymphatic drainage from the primary melanoma, and by use of a gamma probe intraoperatively.
Adolescent↗
Lymphatic drainage from peri-umbilical skin to internal mammary nodes.
While performing lymphoscintigraphy to define draining lymph node groups and sentinel nodes in patients with melanoma, the authors have discovered a new lymphatic channel in two patients with tumors in the peri-umbilical area. This channel passes over the right costal margin to an interval node before passing toward the midline, where it passes through the chest wall to reach the internal mammary lymph node chain. Appreciating the possible presence of this channel in patients with periumbilical lesions has important implications for the surgical management and follow-up of these patients.
Antimony↗
Sentinel lymph node status as an indicator of the presence of metastatic melanoma in regional lymph nodes.
The value of elective lymph node dissection (ELND) for melanoma patients with clinically uninvolved regional nodes remains controversial. However, it has been proposed that selective 'sentinel' lymph node biopsy reliably identifies individuals with micrometastases, who are most likely to benefit from full ELND. The aim of this study was to confirm that metastatic melanoma cells travelling in lymphatics do not bypass the sentinel node. After preoperative lymphoscintigraphy and intraoperative injection of blue dye around the primary melanoma site, sentinel node biopsy was performed in 118 melanoma patients for whom full ELND was planned as part of their definitive surgical treatment. A confidently identified sentinel node was tumour positive in 22 out of 105 regional lymph node fields (21%). In 18 cases the sentinel node was the only node found to be involved and in four cases, additional nodes were positive. In two other patients a positive node was found when the sentinel lymph node had been negative. However, in each case an avoidable error of technique had occurred and definite blue staining indicated that the positive node was in fact another sentinel node. This study thus confirms that sentinel lymph node status reliably indicates whether metastatic melanoma is present in regional lymph nodes.
Adolescent↗
The identification of potential cadaveric organ donors.
Most Australian transplantation programs are severely restricted in their activities by a limited availability of cadaveric donor organs. To investigate possible reasons for this problem, an audit was undertaken over three 12-month periods of all deaths in 13 hospitals in New South Wales and the Australian Capital Territory. From 7406 deaths, 271 patients were classified as having been realistic, medically suitable potential donors. Of these, only 60 (22%) became actual donors. In the other 211 patients, donation did not occur because of unsuccessful resuscitation (30%), permission refusal by relatives (34%), and failure to identify or support the potential donors (36%). If the impediments to organ donation which were identified in this study could be overcome, allowing a greater number of potential donors to become actual donors, the chronic shortage of cadaveric donor organs for transplantation could be at least partly relieved.
Brain Death↗
Obtaining consent for organ donation in nine NSW metropolitan hospitals.
Organ donation rates vary markedly around the world. In an attempt to analyse why some patients' families are not asked about organ donation, the case notes of 6080 patients who died over a twelve-month period from April 1991 to March 1992 in nine hospitals in Sydney, NSW, were studied. Irreversible coma occurred in 515 patients. Of these, 177 were considered to be potentially brain dead donors, 126 of whom had a formal diagnosis of brain death. The clinicians caring for the patients at the time of death were asked at follow-up about the reasons for not considering donation, or the reasons for family refusal. Consent to proceed to organ donation was requested in 112 cases (49 donated and 63 refused) and not requested in 65. Analysis of the proportions asked and consenting in each hospital revealed no correlation. Half of the families refusing gave no reason (24/50) while eleven gave religious or cultural reasons, and six expressed a desire to prevent mutilation of the body as their primary reason for not consenting. There was universal failure to gain consent from families when the patient was not in an Intensive Care Unit. Analysis of those patients of whom consent was not sought showed that they died more quickly after admission, were older and died from causes other than trauma or intracranial haemorrhage. The odds of the family being asked dropped by about half as the age increased from one group to the next.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Can cadaveric organ donation rates be improved?
There are many reasons why potential cadaveric organ donors may fail to become actual donors. These include permission refusal by the next of kin, incorrect assumptions about medical suitability and, occasionally, an excessive workload in the intensive care unit. Some potential donors currently regarded in Australia as "unrealistic" might become actual donors if attitudes were to change towards ventilation of patients with a clearly hopeless prognosis who have expressed a wish to be organ donors. "Required request" legislation ignores the wishes of the potential donor and "presumed consent" laws also present some ethical difficulties, but a suggested "required response" process could ensure that an individual's wishes concerning organ donation would be known and able to be carried out after death. For the present, however, it is clear that operating within existing Australian legislation and abiding by currently accepted codes of practice, we can still find considerable scope for improving cadaveric organ donation rates.
Age Factors↗
Mammary lymphoscintigraphy in breast cancer.
UNLABELLED: Lymphoscintigraphy has previously been used to define lymph drainage patterns and locate sentinel lymph nodes, prior to surgery, in patients with cutaneous melanoma. The aim of this study was to apply this technique to patients with breast cancer using intramammary injections placed around the primary tumor in the breast. METHODS: Lymphoscintigraphy using 99mTc-labeled antimony sulphide colloid was performed in 34 patients with a suspected primary breast cancer. Images were recorded immediately and at 2.5 hr using a LFOV digital gamma camera. Sentinel lymph node location was marked when possible. RESULTS: Lymphatic drainage patterns were successfully recorded in all but three patients. Lymph drainage was to the axillary, internal mammary, supraclavicular and, in one patient, infraclavicular node fields in various combinations but always on the same side of the body as the breast tumor. There was unexpected drainage across the center line of the breast to axillary or internal mammary nodes in 32% of patients with inner or outer quadrant lesions. Direct drainage to supraclavicular or infraclavicular nodes occurred in 20% of upper quadrant lesions. Drainage to the ipsilateral axilla occurred in 85% of patients, where a single sentinel node was seen in all cases. CONCLUSION: Intramammary lymphoscintigraphy can be used to define the lymphatic drainage patterns of individual breast cancers. The surface location of sentinel lymph nodes in the draining node fields can be marked and in the axilla their depth can be measured. It should therefore be possible to use lymphoscintigraphy, along with a blue dye injection technique or the gamma probe at surgery, to locate sentinel lymph nodes in patients with breast cancer.
Antimony↗
Elective lymph node dissection.
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Elective Surgical Procedures↗
Elective lymph node dissection in patients with primary melanoma of the trunk and limbs treated at the Sydney Melanoma unit from 1960 to 1991.
BACKGROUND: The value of elective lymph node dissection (ELND) in melanoma remains controversial. Published prospective and retrospective studies can be criticized, and results from two ongoing randomized trials are not yet available. A previous retrospective review from the Sydney Melanoma Unit (SMU) showed apparent survival benefit from ELND, especially in tumors of intermediate thickness. STUDY DESIGN: We undertook a retrospective analysis of all patients treated at the SMU since 1960 for melanoma of the trunk or limbs measuring 1.5 mm or more in thickness, without clinical lymph node metastases, whose definitive wide excision (WE) with or without ELND was performed at the SMU within 60 days of initial diagnosis. RESULTS: There were 1,278 patients who fulfilled these criteria. Of these, 845 (66 percent) were treated with ELND and the remaining 34 percent were treated with WE alone. The median follow-up period was 58 months. Patients with thicker tumors and younger age more commonly underwent ELND. Among patients with thinner tumors, males underwent ELND more commonly than females. A multivariate proportional hazard model of melanoma-specific survival stratified by tumor thickness was chosen to allow for the imbalances between the two groups. With or without allowance for covariates, no benefit from ELND was found in the whole group or any subset. In contrast to previous studies from the SMU, we deliberately excluded from the present study patients referred only after WE with or without ELND elsewhere, because these might have been a selectively biased poor prognostic group. CONCLUSIONS: This study does not indicate a benefit from ELND for melanomas of the trunk or limbs measuring over 1.5 mm in thickness.
Female↗
Malignant melanoma of the toenail apparatus.
BACKGROUND: Subungual melanoma is an unpredictable and aggressive tumor with a propensity to metastasize widely. Because it is an uncommon condition, statistical analysis of its behavior patterns is difficult, factors that determine its prognosis are unclear, and optimal management is ill defined. STUDY DESIGN: A detailed review was undertaken of the clinical and histologic features of subungual melanomas arising from the toenail apparatus in 25 patients treated at the Sydney Melanoma Unit during a 40-year period. Treatment and outcomes were analyzed. RESULTS: Most of the lesions were situated on the great toe in elderly patients of Anglo-Celtic extraction. Antecedent trauma to the toe was frequently reported and delayed diagnosis was usual. There was great variation in Breslow thickness and Clark's level, but these indices were found to have less prognostic significance than for other forms of cutaneous melanoma. CONCLUSIONS: The treatment of subungual melanoma of the toenail apparatus is primarily surgical, by amputation at or proximal to the metatarsophalangeal joint. Even if there is no clinical evidence of metastatic disease in regional lymph nodes, radical node dissection is desirable. The condition is most appropriately managed at a specialist center.
Adult↗
Protein binding to the low density lipoprotein receptor promoter in vivo is differentially affected by gene activation in primary human cells.
Protein-DNA interactions within a region of the LDL receptor promoter involved in sterol-mediated feedback repression of transcription were examined using in vivo genomic footprinting with dimethylsulfate (DMS). A broad region of protein-DNA contacts spanning from repeat 1 to beyond the transcription start sites was observed in primary cultures of human skin fibroblasts and hepatocytes. Hypermethylation of guanine -59 within the sterol regulatory element-1 (SRE-1, repeat 2) occurred within a 4.0 h incubation of fibroblasts with media containing lipoprotein-deficient serum (LPDS) and cholesterol synthesis inhibitors. Methylation of this residue was reduced to control levels within 2.0 h after the addition of a mixture of 25-hydroxycholesterol and mevalonic acid. The time-dependent changes in DMS-reactivity of guanine -59 induced by the cholesterol synthesis inhibitors or oxysterols were paralleled by alterations in LDL receptor mRNA. In contrast to the results with fibroblasts, neither cholesterol synthesis inhibitors nor oxysterols produced consistent effects on the DMS-reactivity of guanine -59 in hepatocytes despite induction or repression of LDL receptor mRNA in these cells. Interestingly, no other changes in the protection pattern over repeats 1, 2, and 3 were apparent in either fibroblasts or hepatocytes. These results demonstrate that hypermethylation of guainine -59 within the SRE-1 is positively associated with activation of LDL receptor gene transcription in skin fibroblasts. Furthermore, the absence of demonstrable changes in DMS-reactivity of other purines within this region suggests that the LDL receptor promoter is poised to activate transcription with only minimal changes of protein binding to the proximal promoter in vivo.
Base Sequence↗
Survival superiority of females with melanoma.
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Female↗
Pharmacodynamics of heparin in vascular surgery.
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Blood Coagulation↗
Developmental regulation of epidermal growth factor receptor kinase in rat intestine.
BACKGROUND/AIMS: Intraluminal epidermal growth factor (EGF) may regulate intestinal growth and function. The ontogeny, localization, and phosphorylation of the EGF receptor in rat small intestine were studied. METHODS: EGF-receptor phosphorylation was assayed by antiphosphotyrosine Western blot after EGF administration in vivo and EGF incubation to everted sacs in vitro. EGF-receptor abundance and localization were assayed by Western blot and immunofluorescence using anti-EGF-receptor antibodies. RESULTS: In vivo, orogastric EGF enhanced EGF-receptor phosphorylation in newborn rat jejunum and liver. However, intraluminal EGF had no effect on EGF-receptor phosphorylation in adult intestine or liver. In vitro, mucosal EGF stimulated a fourfold increase in EGF-receptor phosphorylation in suckling jejunum but not in weanling or adult jejunum. In Western blot, EGF-receptor abundance was similar in 22-day-old fetal, 8-day-old suckling, and adult jejunum. In both crypt and villus, EGF-receptor was localized to the basolateral membrane but not to the apical membrane in fetal, suckling, and adult jejunum. CONCLUSIONS: Mucosal EGF stimulates EGF-receptor phosphorylation in immature but not in mature intestine. These differences are not explained by EGF-receptor abundance or localization and suggest that the greater mucosal permeability of the immature gut may allow EGF to bind to the EGF-receptor in the basolateral membrane to mediate its effects in suckling rat intestine.
Animals↗