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Biomedical subjects

J M Thomas

Publications and source records attributed to J M Thomas.

At least 19 recordsLinked to original sources
PubMed1992

Metastasectomy.

The literature on metastasectomy abounds in anecdote and retrospective studies of non-randomized patients. In this paper, the published evidence concerning the efficacy of metastasectomy in the lung, liver, brain, gastrointestinal tract and omentum is reviewed to formulate practical recommendations for patient selection and treatment. At some sites metastasectomy can be recommended with little hesitation for more widespread application, but surgery for liver metastases should still be regarded with some reservation.

Adult↗
PubMed1992

Early T-cell defects in pre-type 1 diabetes.

Alterations of lymphocyte subsets have been recently reported in pre-type 1 diabetes but the relation with other immunological markers, in particular islet cell antibodies (ICA), is still unknown. In the present study, we have investigated prospectively changes of lymphocyte subsets in 86 first-degree relatives of patients affected by type 1 diabetes and correlated such modifications with ICA titres. Among individuals with persistent ICA, 8 had ICA titres of more than 20 JDF units, 14 had ICA titres between 5 and 20 JDF units and 64 had ICA titres between 0 and 5 JDF units. First-degree relatives with ICA titres of more than 20 JDF units had significantly decreased proportions of CD3 cells. This reduction was predominantly in the CD4 subset, giving rise to a decreased CD4/CD8 lymphocyte ratio. Those with ICA titres between 5 and 20 JDF units showed abnormalities in both CD3 and CD4 lymphocytes, but not in CD4/CD8 lymphocyte ratio. Further characterization of the CD4 cell subset was performed using three other monoclonal antibodies, CD45RO (UCHL1), CD45RA and CD29, phenotyping memory T-cells, the inducer cells of suppressor function and helper-inducer cells, respectively. The proportions of total CD45RO and CD45RA were not significantly different among first-degree relative with distinct ICA titres in a cross-sectional study, whereas a trend towards a reduced proportion of CD4/CD45RA cells was observed. The longitudinal study demonstrated that individuals potentially susceptible to the development of type 1 diabetes and who possess high titres of ICA have impairment of CD4/CD8 lymphocyte ratio, mainly due to a reduction in the CD4 subset.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1992

Prolonged activation of inhibitory somatostatin receptors increases adenylate cyclase activity in wild-type and Gs alpha-deficient (cyc-) S49 mouse lymphoma cells.

Many cells develop enhanced adenylate cyclase activity after prolonged exposure to drugs that acutely inhibit the enzyme and it has been suggested that this adaptation may be due to an increase in Gs alpha. We have treated wild-type and Gs alpha-deficient cyc- S49 mouse lymphoma cells with a stable analogue (SMS 201-995) of the inhibitory agonist somatostatin. After incubation with SMS for 24 h, the forskolin-stimulated cAMP synthetic rate in intact cyc- cells was increased by 76%, similar to the increase found in the wild-type cells. Forskolin-stimulated adenylate cyclase activity in the presence of Mn2+ was also increased in membranes prepared from SMS-treated cyc- cells; however, guanine nucleotide-mediated inhibition of adenylate cyclase activity was not changed despite a small decrease in inhibitory Gi alpha subunits detected by immunoblotting. Pretreatment of cyc- cells with pertussis toxin prevented SMS from inducing the enhancement of forskolin-stimulated cAMP accumulation in intact cells. After chronic incubation of cyc- cells with SMS, exposure to N-ethylmaleimide, which abolished receptor-mediated inhibition of cAMP accumulation, did not attenuate the enhanced rate of forskolin-stimulated cAMP synthesis compared to N-ethylmaleimide-treated controls. These results with cyc- cells demonstrate that an adaptive increase in adenylate cyclase activity induced by chronic treatment with an inhibitory drug can occur in the absence of expression of Gs alpha.

Adenylyl Cyclases↗
PubMed1992

Adaptive increase in adenylyl cyclase activity in NG108-15 and S49 cells induced by chronic treatment with inhibitory drugs is not due to a decrease in cyclic AMP concentrations.

NG108-15 neuroblastoma x glioma hybrid cells and S49 lymphoma cells exhibit an enhancement in adenylyl cyclase activity after chronic treatment with receptor agonists that acutely inhibit the enzyme. Using agonists that activate five distinct inhibitory receptors in NG108-15 cells, we have found that there is a correlation between the extent of acute inhibition of prostaglandin E1 (PGE1)-stimulated cAMP accumulation and efficacy for induction of enhanced PGE1 stimulation of cAMP accumulation after chronic treatment and withdrawal. Chronic treatment with dideoxyadenosine, which acutely inhibits adenylyl cyclase activity by a mechanism independent or cell surface receptors or pertussis toxin-sensitive G proteins, did not induce enhanced PGE1 stimulation of cAMP accumulation in NG108-15 cells or forskolin stimulation of cAMP accumulation in S49 cells. While control basal cAMP concentrations were acutely decreased by carbachol in NG108-15 cells and by somatostatin in S49 cells, when the cAMP concentrations were maintained above the control basal values with a phosphodiesterase inhibitor, chronic treatment with these inhibitory drugs nonetheless resulted in enhanced cAMP responses in both NG108-15 and S49 cells. These results provide evidence that the initial decrement in cAMP concentrations caused by inhibitory drug is not the requisite signal for inducing the subsequent sensitization of adenylyl cyclase in NG108-15 and S49 cells but that activation of a pertussis toxin-sensitive G protein is involved in the development of this important adaptation.

Adaptation, Biological↗
PubMed1992

Benign mimics of soft tissue sarcomas.

We reviewed all new patients referred for treatment to the Sarcoma Unit at the Royal Marsden Hospital with a clinical diagnosis of soft tissue sarcoma (STS) during the course of 1 year (1989-1990). Of 118 patients, 65 (55.1%) had primary STS, 26 (22.0%) had recurrent STS, 19 (16.1%) had benign soft tissue tumours and eight (6.8%) had malignant tumours other than STS involving soft tissues and presenting clinically as soft tissue tumours. All patients underwent CT scanning which was used to assist diagnosis, assess operability or for radiotherapy planning. The CT findings of the benign lesions, all clinically suspicious of sarcoma, are discussed. The role of CT in the identification and management of these cases is emphasized.

Arteriovenous Malformations↗
PubMed1992

Preoperative radiotherapy for initially inoperable extremity soft tissue sarcomas.

The results and complications of a combination of preoperative radiotherapy and surgery in the treatment of 70 patients with large or fixed extremity soft tissue sarcomas are reported. Sixty-one patients were referred with a primary tumour and 9 had recurrences. Thirty-three patients had tumours in the thigh and 38 tumours were fixed to neighbouring structures. The mean preoperative dose was 53 Gy (range 21-75). Eleven patients received a postoperative boost to tumour site. Four patients received preoperative intra-arterial Adriamycin. Overall, 42 patients (60%) responded to the radiotherapy, 4 with complete tumour resolution. Eighty per cent of those receiving greater than or equal to 60 Gy responded and a significant correlation between 2 Gy equivalent dose and response was demonstrated (P less than 0.005). The degree of tumour necrosis was increased in 23 of 52 evaluable patients following radiotherapy, although there was no correlation with dose or clinical response. There have been eight local recurrences and 17 deaths after a median follow-up of 2 years. Tumour size less than 10 cm was the only significant factor in the development of local recurrence (P = 0.04). Thirty-six patients developed immediate postoperative complications: 9 major (13%), 13 moderate (19%) and 14 minor (20%). Increasing patient age was the only significant independent factor for the development of complications (P = 0.015). Preoperative radiotherapy will usually permit limb conservation of extremity sarcomas which otherwise would be inoperable or require amputation. However, the increased incidence of wound complications in older patients demands meticulous technique.

Adolescent↗
PubMed1992

The diagnosis of soft tissue tumours.

We prospectively analysed methods of diagnosis in 118 patients referred for definitive treatment with documented or presumed soft tissue sarcoma (STS). Of 65 patients with primary STS, 54 were biopsied before referral. Of these, 5 (9%) were biopsied by Tru-cut biopsy, 17 (32%) by incisional biopsy and 32 (59%) by excisional biopsy. The remaining 11 patients with primary STS, referred without biopsy, were all diagnosed by Tru-cut biopsy. An additional eight patients suspected of having STS were referred without biopsy and were found to have malignant tumours other than STS involving soft tissue by Tru-cut biopsy. Nineteen patients were proved to have benign soft tissue tumours; in 13 presumed to have STS, the diagnosis was unknown at referral. In four of these, biopsy was inappropriate. Of nine submitted to Tru-cut biopsy, an unequivocal diagnosis was made in 5 (56%) and incisional biopsy was required in the other four. Therefore, paradoxically, benign soft tissue tumours may be more difficult to diagnose with Tru-cut biopsy than malignant tumours. This study confirms the high degree of accuracy of Tru-cut biopsy in diagnosing malignant soft tissue tumours and highlights the disadvantages of open biopsy techniques.

Adolescent↗
PubMed1992

Radical axillary dissection in the staging and treatment of breast cancer.

The results of 237 radical axillary dissections undertaken by one surgeon in patients with breast cancer were reviewed to evaluate the role of this procedure in staging and treatment. The accuracy of physical examination in detecting axillary metastases was 68%. With a policy of enforced shoulder immobilisation for 10 days postoperatively, the incidence of postoperative wound complications was 8%. There have been three axillary recurrences during a median follow-up period of 44 months (range 6-97 months). Late complications were assessed in 50 patients followed up for greater than 12 months. While eight patients complained of constant swelling of the arm, only three had a difference in arm circumference of greater than 3 cm and only one had persistent limitation of shoulder abduction. Radical axillary dissection ensures accurate clinical staging and provides excellent local control with few complications and without the need for axillary irradiation.

Axilla↗
PubMed1992

Knowing and practicing ethics.

The interrelationship between ethics and child and adolescent psychiatry is discussed, particularly as it relates to clinical practice. Three principles for ethical clinical practice are presented from a philosophical perspective and illustrated with two case vignettes. A formulation is reached that states that ethical theory parallels clinical theory.

Adolescent↗
PubMed1991

Factors influencing local recurrence and survival in patients with soft tissue sarcoma of the upper limb.

Fifty-one patients with soft tissue sarcoma of the upper limb were studied to identify risk factors for local recurrence and survival. More than half (53 per cent) of the patients referred had locally recurrent disease. The flexor aspect of the forearm was the most common site of origin. The majority of patients were managed by a combination of conservative surgery and radical radiotherapy. Wide or radical excision was achieved in 49 per cent of cases. One-third of patients required partial resection of bone or neurovascular structures; 75 per cent of them had presented with local recurrence after treatment elsewhere. Skin grafts and flap repairs were used more often in patients with local recurrence (P = 0.013) and 20 (74 per cent) of those referred with locally recurrent disease have had no further local relapse. The overall 5-year survival rate of 80 per cent (95 per cent confidence interval 61-90 per cent) supports a policy of conservative surgery. Factors associated with a lower survival rate were deep fixation, origin in the flexor aspect of the forearm, and previous local recurrence. Deep fixation was also associated with an increased risk of local recurrence. Referral to a specialist unit at the time of initial presentation may result in lower rates of local recurrence and may improve the survival rate.

Adolescent↗
PubMed1991

Persistent reduction of B virus (Herpesvirus simiae) seropositivity in rhesus macaques acquired for a study of renal allograft tolerance.

One hundred and two rhesus macaques were used in a study of renal allograft tolerance. Each animal was monitored serologically more than one time to determine its B virus (Herpesvirus simiae) antibody status. The follow-up period for some individuals was 3 years, extending from 1986 to 1989. The accumulated test results eventually provided an opportunity to retrospectively support a contention that a small research colony of rhesus macaques could become and remain B virus seronegative if the animals were housed individually, monitored periodically, acquired only if they were seronegative, and culled if they converted to positive status. It was also possible that the test results might disclose useful information about the influence of acute immunosuppression on the reliability of determining B virus antibody status by serologic methods, and help formulate guidelines for selecting donor-recipient pairs. A review of the serologic test results disclosed that antibody status before the initiation of experimental therapy, and subsequent seroreactivity, did not change throughout the experimental lifetime of 92 monkeys. The few exceptions were six juveniles that lost detectable antibody, and four other juveniles that converted to positive. Preliminary data suggested that total lymphoid irradiation (TLI) and splenectomy were associated with the loss of detectable antibody; however, further study is needed to establish the validity and significance of this association. No other unexpected or unexplained results were associated with concomitant periods of acute immunosuppression. The number of seropositive animals in the colony was reduced to three through attrition and culling by the end of 1989.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Decreased cyclic AMP degradation in NG 108-15 neuroblastoma X glioma hybrid cells and S49 lymphoma cells chronically treated with drugs that inhibit adenylate cyclase.

The increase in hormone-stimulated cyclic AMP accumulation observed in a variety of intact cells after chronic pretreatment with drugs that inhibit adenylate cyclase activity has been attributed to an increase in adenylate cyclase activity following withdrawal of the inhibitory drug. In NG 108-15 mouse neuroblastoma X rat glioma hybrid cells (NG cells) chronically treated with the muscarinic cholinergic agonist carbachol, we have found a significant decrease in the apparent degradation rate constant for cyclic AMP, in addition to an increase in the prostaglandin E1 (PGE1)-stimulated cyclic AMP synthesis rate in intact cells. In carbachol-pretreated NG cells that were stimulated with a maximally effective dose of PGE1, and that accumulated steady-state cyclic AMP concentrations fourfold or more higher than in control cells, the apparent rate constant for degradation was about 53% lower than the value for control cells. In carbachol-pretreated cells stimulated with a submaximal dose of PGE1 to yield a steady-state cyclic AMP concentration comparable to control cells, the apparent rate constant was 31% lower than the value for control cells. In S49 mouse lymphoma cells (S49 cells) chronically treated with an analog of the inhibitory agonist somatostatin, the first-order rate constant for cyclic AMP degradation in intact cells following isoproterenol stimulation was 29% lower than the value for control cells. Despite these changes in the kinetics of cyclic AMP degradation in intact NG cells and S49 cells, there was either no change or a minimal change (less than 10%) in phosphodiesterase activities assayed in extracts of cells chronically exposed to inhibitory drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗