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Biomedical subjects

J M Thomas

Publications and source records attributed to J M Thomas.

At least 163 records · Page 9Linked to original sources

Lymphoma presenting as an intramuscular mass.

BACKGROUND: Resection of an intramuscular mass without tissue diagnosis can lead to unnecessary surgery. METHOD: During a 4.5-year period 19 previously healthy patients referred with an undiagnosed soft tissue tumour were found to have intramuscular non-Hodgkin's lymphoma. In seven patients this was the only focus of disease (Stage IE). Patients were treated with chemotherapy or radiotherapy alone or in combination. RESULTS: After mean follow-up of 43 months all of the patients with stage IE lymphoma are alive and disease free. CONCLUSION: Primary intramuscular non-Hodgkin's lymphoma has a good prognosis. The importance of a tissue diagnosis by needle core biopsy is emphasized.

Adolescent↗

Use of the carbon dioxide laser to manage cutaneous metastases from malignant melanoma.

Between October 1988 and November 1994, 100 patients with cutaneous metastases from malignant melanoma were treated by carbon dioxide laser ablation under local or general anaesthesia as appropriate. There were minimal postoperative complications and most wounds healed within 6 weeks. A total of 34 of the 53 patients in this series with stage IIIa disease were controlled with four or fewer laser ablations during the first year from presentation. This technique provides a simple effective alternative to hyperthermic isolated limb perfusion with melphalan. Patients with disease not controlled by laser can be considered for isolated limb perfusion.

Adult↗

The management of retroperitoneal soft tissue sarcomas.

Over a 5-year period, all retroperitoneal soft tissue sarcomas (119) referred to the Royal Marsden Hospital, London, U.K., were recorded prospectively on a database and managed with a consistent treatment policy. On multivariate analysis, the significant factors responsible for determining prognosis were grade and completeness of excision. Despite improvements in surgical clearance rates (nearly 50% completely excised in this series), the prognosis was poor with 2- and 5-year survival rates of 53 and 20%, respectively. Further improvements in survival rates will depend on better adjuvant treatment.

Adolescent↗

Hindquarter amputation for lymphangiomatosis.

We describe the presentation of a 16-year-old boy with locally advanced lymphangiomatosis affecting the left thigh and groin. This is a difficult disease to both diagnose and treat, and one in which radical surgery may be necessary to effect a cure or even palliation. In this case, hindquarter amputation allowed a previously wheelchair-bound teenager to mobilize unaided.

Adolescent↗

Sonographic abnormalities of the thyroid gland following radiotherapy in survivors of childhood Hodgkin's disease.

The aims of this study were as follows. (1) To demonstrate the spectrum, frequency and changes on follow-up of sonographic abnormalities in the thyroid gland of survivors of Hodgkin's disease who had received radiotherapy to the neck in childhood. (2) To compare the sonographic findings with clinical examination and radionuclide imaging. (3) To investigate the association between the presence or absence of focal sonographic abnormalities with age at radiotherapy, the interval from radiotherapy, the presence of a raised thyroid stimulating hormone (TSH) and the length of time the TSH had been raised. 46 patients were scanned prospectively and rescanned at 6-18 months. The mean age at first sonography was 22.7 years, the median age at radiotherapy was 12.5 years, and the median interval post-radiation was 10.3 years. Sonographic abnormalities were seen in all 46 patients. 45 had diffuse atrophy and 30 had focal sonographic abnormalities. 18 patients developed new focal sonographic abnormalities on follow-up. Focal sonographic abnormalities were more commonly associated with longer duration of a raised TSH. Two patients had thyroid carcinoma. Sonographic abnormalities of the thyroid are common in patients following neck radiotherapy in childhood. Focal abnormalities are usually associated with a longer duration of raised TSH.

Adolescent↗

Isoform-specific sensitization of adenylyl cyclase activity by prior activation of inhibitory receptors: role of beta gamma subunits in transducing enhanced activity of the type VI isoform.

Many different types of cells develop increased adenylyl cyclase activity (sensitization) on prior treatment with drugs such as opiates that acutely inhibit the enzyme. We found that human embryonic kidney (HEK) 293 m2 cells, which express the inhibitory m2 muscarinic cholinergic receptor, exhibit a large increase in forskolin-stimulated cAMP synthesis when the cells are preincubated with the muscarinic agonist carbachol for > or = 5 min and forskolin stimulation is performed in the presence of the muscarinic antagonist atropine. To determine whether a specific isoform of adenylyl cyclase is susceptible to the adaptation induced by prior activation of inhibitory receptors, cells were transfected with expression vectors encoding adenylyl cyclase types I, II, and VI, representing three major groups of the adenylyl cyclase family. Preincubation of the cells with carbachol for 30 min resulted in a significant increase in prostaglandin E1-stimulated cAMP accumulation in cells expressing type VI, but not type I or type II, adenylyl cyclase. A similar selective increase in activity from type VI adenylyl cyclase was observed for prior treatment with the D2 dopamine agonist quinpirole and stimulation of cAMP synthesis with human chorionic gonadotropin in cells transfected with expression vectors coding for the cognate receptors. We next investigated whether beta gamma subunits play a role in the sensitization of type VI adenylyl cyclase activity; using expression of alpha tau to inhibit beta gamma-mediated effects, we found that the quinpirole-induced sensitization of type VI adenylyl cyclase was abolished. However, beta gamma subunits do not seem to directly activate type VI adenylyl cyclase, in contrast with their ability to directly activate the type II enzyme. Therefore, beta gamma subunits liberated after activation of inhibitory receptors seem to indirectly cause an increase in activity of type VI adenylyl cyclase. Indirect activation of the type VI enzyme by beta gamma subunits is a novel mechanism contributing to the sensitization of adenylyl cyclase.

Adenylyl Cyclases↗

Role of the C-terminal tail of the GLUT1 glucose transporter in its expression and function in Xenopus laevis oocytes.

Structural determinants for the glucose transport kinetics of the erythrocyte glucose transporter have not been established. In this work the role of the cytosolic carboxy-terminal tail in the expression and function of the human GLUT1 isoform in Xenopus oocytes was investigated. Oocyte plasma membrane expression of GLUT1 was a saturable function of the amount of mRNA injected. Transport activity increased as a linear function of the amount of immunoreactive transporter in the plasma membrane. Transport kinetics of human GLUT1 expressed in oocytes resembled those of human erythrocyte GLUT1. Addition of up to 31 extra amino acids to the carboxy-terminal tail of GLUT1 was without effect on its function in oocytes. Removal of the carboxy-terminal 21 amino acids also did not affect GLUT1 expression or transport kinetics in oocytes. Removal of the entire carboxy-terminal tail to Phe-450 resulted in a transporter that had moderately decreased plasma membrane expression compared to that of GLUT1. However, transport activity of this construct was less than 5% of that of GLUT1, and was associated with loss of its outward-facing inhibitor binding site. When the carboxy-terminal 29 amino acids of GLUT1 were replaced with the corresponding region of GLUT4, transporter expression in the plasma membrane and the transport Vmax fell to low levels, similar to those of native GLUT4. When the carboxy-terminal 29 or 73 amino acids of GLUT1 were swapped into the corresponding region of GLUT4, the transport Vmax markedly increased to about one-third to one-half that of GLUT1, although the affinity for substrate was halved. These results show that the carboxy-terminal tail of the GLUT1 is not critical for targeting of the protein to the plasma membrane, but that this region is an important determinant of transport function.

3-O-Methylglucose↗

The facilitating effect of one-DR antigen sharing in renal allograft tolerance induced by donor bone marrow in rhesus monkeys.

Infusion of donor bone marrow cells (DBMC), a long-standing, successful strategy for inducing tolerance in experimental rodent transplantation models, can promote long-term acceptance of life-sustaining renal allografts in rhesus monkeys with no maintenance immunosuppression. To investigate the immunological basis for heterogeneity in duration of long-term graft acceptance following infusion of the DR-/dim fraction of DBMC into RATG-treated rhesus monkeys, we examined the relationship of recipient-donor major histo-compatibility class I and II DR matching to the development of antidonor antibody-dependent cellular cytotoxicity (ADCC) and renal allograft survival. The findings indicate a requirement for sharing one DR allele to achieve long-term graft acceptance. The observed immunological consequence of DR sharing that correlated with functional graft tolerance in this model was the suppression of early antidonor ADCC+ IgG antibody responses. Significant associations were observed between graft survival and suppression of ADCC antibody (P < 0.0005), graft survival and DR sharing (P < 0.005), and DR sharing and suppression of ADCC (P < 0.02). Early antidonor ADCC antibody responses associated with failure to maintain graft tolerance and were most consistently directed to donor class I. The required one DR antigen sharing in DBMC-induced suppression of antidonor class I antibody suggests a restriction for recipient DR, implying critical regulation of a response to donor antigen presented on recipient cells. We hypothesize a DBMC tolerogenic mechanism in which presentation of donor class I peptide by a shared DR allele configuration allows a veto effect by DBMC. Thus DR sharing would allow DBMC veto cells to reduce clonal expansion elicited by both the direct and indirect antigen presentation pathways.

Animals↗

Malignant epithelial parotid tumours: a rational treatment policy.

Formal parotidectomy was undertaken in 271 patients by one surgeon over 11 years. Forty patients were treated for malignant salivary tumours (nine were recurrent). Low-grade tumours (45 per cent) were treated by surgery alone, untreated high-grade tumours (55 per cent) by surgery and radiotherapy, before or after operation, depending on clinical findings. The aims of surgery were to obtain tumour clearance, to preserve the facial nerve if possible, and to perform radical neck dissection for palpable malignant lymphadenopathy proven cytologically and for high-grade tumours when intraoperative jugulodigastric lymph node biopsy confirmed metastasis. Four patients sustained facial weakness as a result of surgery. At a median of 46 months follow-up two patients had developed local recurrence. Eleven patients with high-grade but none with low-grade tumours died from metastases. Patients with high-grade lesions with facial weakness from malignant infiltration and those with lymphatic metastasis have a significantly worse prognosis than those without. Locoregional control of parotid cancers can be achieved by formal parotidectomy and selective irradiation without routine sacrifice of the facial nerve.

Adolescent↗

Dominant lethal studies in male mice after exposure to a 50 Hz magnetic field.

The potential mutagenicity of power frequency magnetic fields was investigated using a dominant lethal assay in mice. A total of 42 male mice were exposed for 8 weeks to a 50 Hz sinusoidal magnetic field at 10 mT (rms) and 47 males acted as simultaneous cage controls. Each male was subsequently mated with two females on weeks 1, 3, 5, 7, and 9 post-exposure. The numbers of pregnant females, corpora lutea, and live and dead implants were recorded. Multiple logistic regression analyses examined the effects of exposure on pregnancy rate, pre-implantation survival and post-implantation survival. There were no statistically significant differences in overall response between exposed and control groups, nor was there any significant effect of exposure in any post-exposure week. Thus, exposure to power frequency magnetic fields at 10 mT for the approximate period of spermatogenesis did not appear to induce dominant lethal mutation in the germ cells of male mice.

Animals↗

Duodenal leiomyosarcoma as a cause of retroperitoneal sepsis.

The case of a patient with a duodenal leiomyosarcoma presenting with sepsis is presented. The necrotic centre of the tumour communicated with the lumen of the duodenum without causing duodenal obstruction. Resection of the duodenum with tumour offers the only chance of cure.

Duodenal Neoplasms↗

The existence of a fatigue syndrome after glandular fever.

This prospective cohort study was designed to test whether a distinct fatigue syndrome existed after the onset of glandular fever. Two hundred and fifty primary care patients, with either glandular fever or an ordinary upper respiratory tract infection (URTI) were interviewed three times in the 6 months after the clinical onset of their infection. At each interview a standardized psychiatric interview was given and physical symptoms were assessed. There were 108 subjects with and Epstein-Barr virus (EBV) infection; 83 subjects had glandular fever not caused by EBV and 54 subjects had an ordinary URTI. Five subjects were excluded because they had no evidence of an infection. Principal components analyses of symptoms supported the existence of a fatigue syndrome, particularly in the two glandular fever groups. The addition of symptoms not elicited by the standard interviews gave the full syndrome. This included physical and mental fatigue, excessive sleep, psychomotor retardation, poor concentration, anhedonia, irritability, social withdrawal, emotional lability, and transient sore throat and neck gland swelling with pain. A fatigue syndrome probably exists after glandular fever.

Animals↗

The validity and reliability of the fatigue syndrome that follows glandular fever.

The validity and reliability of an empirically defined fatigue syndrome were tested in a prospective cohort study of 245 primary care patients, with glandular fever or an upper respiratory tract infection. Subjects were interviewed three times in the 6 months after onset. Subjects with the empirically defined fatigue syndrome were compared with those who were well and those who had a psychiatric disorder. The validity of the fatigue syndrome was supported, separate from psychiatric disorders in general and depressive disorders in particular. Only 16% of subjects with the principal component derived fatigue factor also met criteria for a psychiatric disorder (excluding pre-morbid phobias). Compared with subjects with psychiatric disorders, subjects with the operationally defined fatigue syndrome reported more severe physical fatigue, especially after exertion, were just as socially incapacitated, had fewer mental state abnormalities, and showed little overlap on independent questionnaires. A more mild fatigue state also existed. Both fatigue syndrome and state were more reliable diagnoses over time than depressive disorders. The empirically defined syndrome probably is a valid and reliable condition in the six months following glandular fever.

Cohort Studies↗