Biomedical subjects
J F Thompson
Publications and source records attributed to J F Thompson.
Adjuvant radiotherapy following neck dissection and parotidectomy for metastatic malignant melanoma.
BACKGROUND: Regional recurrence remains a problem in the management of patients with metastatic malignant melanoma in the cervical lymph nodes and parotid. In this study, the influence of the number of positive nodes, extracapsular spread, and the use of adjuvant radiotherapy on regional control and survival were analyzed. METHODS: A non-randomized, prospectively documented series of 143 patients with histologically positive nodes in the neck or parotid was analyzed. There were 152 dissected necks or parotids: 45 of these received postoperative radiotherapy, 6 x 5.5 Gy fractions over 3 weeks; 107 were not irradiated. RESULTS: The regional recurrence rate was 6.5% in the irradiated group, compared with 18.7% in the non-irradiated group (p = .055). The irradiated group, however, had more extensive nodal involvement than the non-irradiated group: 65% had two or more positive nodes, and 48% had extracapsular spread, compared with 40% and 19%, respectively, in the non-irradiated group. Survival was significantly worse when there was extracapsular spread (p < .05) or multiple node involvement (p < .01). By multivariate analysis, the use of adjuvant radiotherapy was associated with a trend toward improved regional control (p = .065), but survival was not improved. CONCLUSIONS: Adjuvant radiotherapy was associated with improved control of metastatic malignant melanoma in the neck and parotid; however, statistical significance was not reached. A prospective trial should be supported to clarify this question.
Cytoskeletal association of epidermal growth factor receptor and associated signaling proteins is regulated by cell density in IEC-6 intestinal cells.
Epidermal growth factor (EGF) mediates a variety of physiologic responses in rat intestine. EGF receptor (EGFR) responsiveness to EGF is mediated by the surface expression of high affinity EGFR, which is associated with the cytoskeleton (CSK). EGFR signal transduction appears to be mediated by the CSK association of EGFR and related signaling proteins. In the nontransformed intestinal cell line IEC-6, expression of EGFR, Src homology and collagen protein (SHC), phospholipase C gamma 1 (PLC gamma), and their tyrosine phosphorylation in response to EGF was assayed by immunoblot. The distribution of EGFR and tyrosine-phosphorylated EGFR was regulated by cell density. At confluence, EGFR and tyrosine-phosphorylated EGFR were predominantly associated with the Triton X-100-insoluble CSK at confluence, while predominantly Triton X-100-soluble at subconfluence. PLC gamma was predominantly soluble at both states of confluence. Confluent but not subconfluent IEC-6 cells demonstrated a cascade of EGF-mediated events consisting of a transient CSK association of PLC gamma with EGFR, a brief expression of tyrosine-phosphorylated PLC gamma, a brief increase in PLC gamma CSK association, and a prolonged soluble association of PLC gamma with the EGFR. EGF led to an increase in the CSK association of SHC at both states of confluence and was greater at confluence. EGFR association with SHC was primarily soluble at subconfluence, while at confluence EGFR association was markedly increased and predominantly in the CSK. Thus, cell density regulates the CSK association of the EGFR and its ability to associate and activate signaling pathways in intestinal cells.
Melanoma of the nose.
BACKGROUND: Melanoma of the nose is rare and management guidelines are poorly defined. In the past, excision margins have often been much narrower than for melanoma elsewhere. METHODS: The study was a retrospective clinicopathological study of 34 patients with cutaneous melanoma of the nose treated in a single unit. RESULTS: Desmoplastic neurotropic melanoma and lentigo maligna melanoma were the most common histological tumour types. Local recurrence occurred in eight patients, and in six cases appeared to be a result of inadequate excision margins. Regional lymph node metastases were associated with a very poor prognosis. CONCLUSION: Adequate surgical excision is the mainstay of successful treatment for melanoma of the nose. Excision margins for nasal melanoma should not be any less than for melanoma elsewhere. Careful planning is required, not only to gain local disease control and the best chance of cure, but also to achieve functionally and aesthetically acceptable results. Excision margins need not be compromised in view of the variety of local flaps that can be employed to close the primary defect.
Unilateral striatal lesions in the cat disrupt well-learned motor plans in a GO/NO-GO reaching task.
We examined the changes in learned and spontaneous motor behavior after a unilateral excitotoxin lesion of the neostriatum. Cats were trained to perform a sensory-cued GO/NO-GO reaching task. Success rate, reaction time, movement speed and kinematic patterns were used to characterize motor system properties. In addition, motor properties before and after the lesion were compared by clinical neurological examinations and video tape observations of free-range behavior. We found that in normal animals motor performance in the task was fluent, highly automatic and skillful with consistent patterns from trial to trial and day to day. The striatal lesion resulted in a marked impairment in the animals' ability to perform the automatic response to the sensory cues in the motor task. In contrast, sensorimotor behavior in contexts apart from the task was altered minimally, with changes that were often difficult to detect. The animals recovered their ability to perform the task gradually, although they never reached prelesion performance levels in up to 24 weeks of evaluation. The animals had difficulty making reaching movements in GO trials and, in NO-GO trials failures to withhold movements were more frequent. Failures were due to a specific inability to execute previously well-learned movements in response to cues and not to an inability to recognize and interpret the cues. The lesion effects were restricted to the automatic motor response to the learned cues, as the animals could make reaching movements to the target without obvious impairment in response to novel stimuli. They also made similar spontaneous movements apart from the motor task that appeared to be unimpaired. The unique motor style and strategies that characterized the behavior of individual animals prior to the lesion were still evident after the lesion, even though they were superimposed on lower success rates and slower movement speeds. Our findings suggest that the basal ganglia facilitate the fluent and rapid execution of sequences of well-learned sensorimotor behavior, but the representations of motor plans are not stored in the basal ganglia.
Advantages of polytetrafluoroethylene arteriovenous loops in the thigh for hemodialysis access.
BACKGROUND: The upper thigh is an alternative but infrequently used site to the forearm for placement of subcutaneous polytetrafluoroethylene (PTFE) arteriovenous conduits in patients requiring hemodialysis for end stage renal failure. This site has the great advantage of easier accessibility for self-cannulation. METHODS: The outcome was reviewed for 74 PTFE loops placed in 61 patients between 1985 and 1991. RESULTS: Mean loop survival time was 99.8 weeks (SD 78.0) when patients with early failure (<1 week), and those patients whose loops functioned adequately until transplantation or death were excluded. Infection occurred in 12 of 74 loops. CONCLUSIONS: Thigh PTFE loops provide satisfactory medium- to long-term vascular access for hemodialysis although, like all other forms of access currently available, they fall short of the ideal for prolonged dialysis.
Lymphatic mapping and selective lymphadenectomy for melanoma: not yet standard therapy.
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Contralateral groin node metastasis from lower limb melanoma.
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Intramedullary spinal cord metastasis from carcinoma of the lung: detection by positron emission tomography.
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Single-dose isotope injection for both preoperative lymphoscintigraphy and intraoperative sentinel lymph node identification in melanoma patients.
For patients with melanoma the 'sentinel' lymph node biopsy technique, although simple in concept, has the potential to provide misleading information if great care is not taken to ensure accurate sentinel node (SN) identification. The method initially reported involved lymphatic mapping by injection of blue dye around the primary melanoma site. Preoperative lymphoscintigraphy was subsequently shown to improve both the speed and accuracy of SN identification. More recently, intraoperative use of a hand-held gamma probe has been recommended, and it is likely that maximum reliability of SN biopsy will be achieved if all three manoeuvres are undertaken. As originally described, use of a gamma probe intraoperatively followed injection of tracer a short time before the surgical procedure. We report a simpler method of confirming SN identity with a gamma probe, using residual activity in the node following lymphoscintigraphy the previous day. In 21 patients close concordance with preoperative lymphoscintigram results and intraoperative findings after blue dye injection confirmed the reliability of the technique. Avoiding the need for repeat isotope administration on the day of surgery simplifies logistics, reduces costs, minimizes inconvenience and radiation dose for patients, and eliminates potential health and safety problems for operating theatre staff.
Hand-held Doppler as a screening test in primary varicose veins.
BACKGROUND: Hand-held Doppler is in common use for evaluating varicose veins, but its accuracy in identifying the exact sites of venous reflux is inferior to that of duplex scanning. It has been suggested that duplex should be used to investigate all varicose veins, but this is currently impractical, and should be unnecessary if hand-held Doppler examination were shown to be an adequate screening test. METHODS: Eighty-five patients (122 legs) with primary varicose veins were evaluated using a hand-held Doppler in the outpatient clinic, according to a protocol. Patients then had venous duplex imaging. RESULTS: Different methods of assessing the long saphenous vein (LSV) (tourniquet and tapping tests, and examination at and below the groin) had similar sensitivities for detecting reflux (75-86 per cent), and together detected 91 per cent of cases. Six of the nine missed had a competent saphenofemoral junction, and five had low-velocity reflux. Hand-held Doppler assessment missed 11 cases of popliteal fossa reflux; only four involved the short saphenous vein (SSV), and most had low-velocity popliteal vein reflux. CONCLUSION: Hand-held Doppler examination missed LSV or SSV incompetence in 11 per cent of legs, but these included cases with short-duration and low-velocity reflux of dubious clinical importance.
Latex allergy: an emerging clinical and occupational health problem.
Allergy to latex products has become a problem of increasing dimensions, affecting both patients and health-care professionals. Certain high-risk groups and sources of latex exposure have been identified. The clinical manifestations vary from contact eczema through a range of allergic syndromes including life-threatening anaphylaxis. An understanding of the clinical and immunological features of latex allergy provides the basis of therapeutic and preventive strategies. Latex allergy is also becoming a major occupational health issue.
Cutaneous melanoma in childhood: incidence and prognosis.
The incidence and prognosis of cutaneous melanoma in children under 13 years of age has always been difficult to assess. The main reasons for this difficulty include the rarity of melanoma in children, referral biases from investigating institutions, changing conceptions in the histological diagnosis of true melanoma, and the lack of large enough study groups with sufficient follow-up to estimate 10-year survival rates. The present study documents 32 cases of childhood cutaneous melanoma drawn from the records of two large referral centres in New South Wales, Australia: the Sydney Melanoma Unit and the Newcastle Melanoma Unit in order to demonstrate some of the difficulties in the assessment of incidence and prognosis in children.
Giant infiltrating lipoma of the thigh causing sciatica.
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Increased C/EBP in fetal rat small intestine precedes initiation of differentiation marker mRNA synthesis.
Morphogenesis, initiation of differentiation marker gene expression, and their correlation with CCAT/enhancer binding protein (C/EBP) expression were analyzed in the developing fetal rat small intestine. Expressions of mRNAs for lactase-phlorizin hydrolase (LPH), intestinal alkaline phosphatase (IALP), carbamoyl-phosphate synthetase (CPS), and three isoforms of C/EBP were simultaneously determined by Northern blot analysis from 15 to 19 days of gestation. At 17 days of gestation, prior to villus formation as demonstrated by light and electron microscopy, only CPS and C/EBPalpha, -beta, and -delta expression could clearly be detected. Both LPH and IALP mRNA were definitely detectable in proximal and middle intestine on day 18, as soon as the stratified epithelium of the early intestine had been transformed into a single layer of columnar epithelium lining villi. This distribution was confirmed by in situ hybridization for LPH mRNA. During the period of transformation when the columnar epithelium and villi were forming, no LPH or IALP mRNA was detectable in the immature distal one-third of the fetal intestine. Preceding villus morphogenesis, immunostaining demonstrated nuclear localization of C/EBPalpha protein in intestinal epithelial cells, with continued expression in all enterocytes through 19 days of gestation. Enhanced expression of C/EBPalpha mRNA and protein began 24 h prior to the initiation of the differentiation markers, suggesting that it may play a role in regulation of fetal intestinal differentiation.
Latex allergy: an emerging health hazard for operating theatre staff.
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Prospective randomized placebo-controlled trial of aprotinin for elective aortic reconstruction.
BACKGROUND: The serine protease antagonist, aprotinin, reduces perioperative blood loss in cardiac surgery and orthotopic liver transplantation. A pilot study suggested that the drug may also reduce bleeding during infrarenal aortic replacement; the aim was to confirm or refute this observation with a prospective, randomized, double-blind, placebo-controlled trial. METHODS: Some 136 patients were randomized to receive either aprotinin, given as a loading dose of 2 x 10(6) kallikrein inactivator (KI) units followed by 0.5 x 10(6) KI units/h or equal volumes of 0.9 per cent saline. After 80 patients had been randomized the infusion dose was doubled to ensure that plasma levels were similar to those seen in successful cardiac studies. Blood loss, coagulation and haematological parameters were recorded throughout surgery and for 7 days afterwards. Blood was transfused to maintain the haemoglobin level at 100 g/l. RESULTS: Four patients were withdrawn after randomization when found at laparotomy to be unsuitable for the planned reconstruction. The 30-day mortality rate was 4.5 per cent, with no excess complications in either group. Blood loss collected on swabs was reduced from 480 ml in placebo-treated patients to 379 ml with aprotinin (P = 0.014). Blood loss into suction drains in the first 24 h after operation was reduced from 295 to 205 ml in aprotinin-treated patients (P = 0.002). However, no significant reduction was found in intraoperative or total blood loss, or transfusion requirement. CONCLUSION: The small reduction in blood loss in patients treated with aprotinin demonstrated in this study does not support its use in routine elective aortic surgery.
Sialomucin complex, a heterodimeric glycoprotein complex. Expression as a soluble, secretable form in lactating mammary gland and colon.
Ascites 13762 rat mammary adenocarcinoma cells express abundantly on their cell surfaces a heterodimeric glycoprotein complex composed of a sialomucin ascites sialoglycoprotein (ASGP)-1 and a transmembrane subunit ASGP-2. The latter, which contains two epidermal growth factor-like domains, binds the receptor tyrosine kinase p185(neu), suggesting that the complex is bifunctional as well as heterodimeric. Immunoblot analyses using monoclonal antibodies prepared against the complex demonstrate high levels of expression in rat lactating mammary gland and colon. Immunolocalization studies with anti-ASGP-2 indicate that ASGP-2 is present in these two tissues in the apical regions of secretory epithelial cells. Both mammary gland and colon contain a soluble, secretable form of ASGP-2, which is not found in the ascites cells; milk and mammary gland also have the membrane form. Immunoblot analyses using a COOH-terminal-specific polyclonal antibody indicate that the soluble form of ASGP-2 is missing its COOH-terminal domains. Both the soluble and membrane forms of ASGP-2 are similar to the membrane-associated form from the 13762 adenocarcinoma with respect to Mr, antigenicity, and association with ASGP-1. The presence of ASGP-1 in milk suggests that it is a candidate for the uncharacterized high Mr milk mucin, MUCX. ASGP-2 expression is up-regulated in mammary gland during pregnancy, because it is undetectable in virgin and early pregnant rats but abundant in the gland from late pregnant and lactating animals. However, compared with the lactating mammary gland, the 13762 ascites cells overexpress ASGP-2 by more than 100-fold, which may contribute to their malignancy. These combined results indicate that sialomucin complex is a unique secreted product in the mammary gland and colon, whose behavior is different from that in the mammary ascites tumors, and which may play important roles in mammary and intestinal physiology.