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Biomedical subjects

J M Thomas

Publications and source records attributed to J M Thomas.

At least 235 records · Page 13Linked to original sources
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

Minimize paperwork, maximize patient care.

A nursing system at McKennan Hospital in Sioux Falls, S.D., allows nurses to eliminate traditional care plans. The nursing intervention becomes the basic unit of work that drives all other documentation.

Computer Graphics↗
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

Carbon dioxide laser ablation of cutaneous metastases from malignant melanoma.

Multiple cutaneous and superficial subcutaneous metastases from malignant melanoma in 30 patients were treated palliatively by carbon dioxide laser ablation when lesions were to numerous, too large or recurring too rapidly for multiple local excisions. The number of lesions per patient ranged from three to 250 (median 30). Patients were treated under local or general anaesthetic and as day cases or inpatients. After a median follow-up interval of 8 months fewer than 1 per cent of lasered metastases have recurred locally. Sixteen patients have developed cutaneous metastases at other sites requiring further treatment. Approximately 2000 lesions have been treated on 64 occasions. Patients reported little or no pain after the operation and required only simple dry dressings. Wounds were completely healed in 2-6 weeks with good cosmetic results. This simple and effective treatment is becoming an alternative to isolated limb perfusion.

Carbon Dioxide↗
PubMed1991

Limitations of surgery in the treatment of retroperitoneal sarcoma.

A retrospective analysis was undertaken of 120 patients with retroperitoneal sarcoma referred to the Royal Marsden Hospital over a period of 20 years. The actuarial 5-year survival rate of all cases following referral was 29 per cent. On univariate and multivariate analysis the principal factors associated with an unfavourable prognosis were the presence of metastases, poor performance status at presentation, high tumour grade and incomplete excision of the primary tumour. The single most important factor affecting the ability to remove the primary tumour completely was multiple organ involvement. After apparently complete excision, however, the probability of local recurrence by 5 years was 85 per cent (95 per cent confidence interval 56-99). The prognosis of patients with retroperitoneal sarcoma is poor.

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

Primary soft tissue tumours of the pelvis causing referred pain in the leg.

Referred pain in the leg is occasionally due to a pelvic soft tissue tumour. Among 11 patients who presented this way, one had a lymphoma, one had a benign schwannoma, and nine had soft tissue sarcomas. Most patients had undergone a variety of procedures, including laminectomy, before the correct diagnosis was established. In five cases, an accurate diagnosis was obtained by needle biopsy. The lymphoma responded to chemotherapy, and the benign schwannoma was excised. Of the nine patients with soft tissue sarcoma, six underwent marginal/intracapsular excision, three receiving supplementary radiotherapy, and two were treated by nonsurgical means. Hindquarter amputation was technically impossible or inappropriate in these cases. All those with high-grade tumours have died or have metastases. Of four patients with low-grade tumours, three have exhibited only slow disease progression. Careful judgment and a precise histopathological diagnosis are required in planning treatment for patients with pelvic soft tissue tumours causing referred pain in the leg.

Adult↗
PubMed1991

Limb function following conservation treatment of adult soft tissue sarcoma.

Quality of life and limb function were studied in 54 patients who were disease-free 2 or more years after limb-conserving treatment for soft tissue sarcoma of the leg or pelvic girdle. Tumours of the thigh predominated (25 patients) and the mean tumour size was 9.9 cm. 41 patients had been treated with a combination of surgery and radiotherapy (29 with conventional and 12 with high dose), 12 with surgery alone and one with irradiation and intra-arterial doxorubicin. Only 15 patients had a normal range of movement in all lower limb joints and only 12 had normal power in all muscle groups; tumours of the lower leg were particularly unfavourable in this respect. Gait was normal in 42 patients but 8 required a walking aid and 4 a joint support. 16 had detectable lymphoedema but only 2 needed to wear compression hosiery. 35 patients still experienced pain at some time but only 6 required analgesia. However, when assessed by questionnaire for locomotion, grooming and home/leisure/vocational activities, 37 patients (68%) reported excellent function, and only 2 had moderate impairment. Function loss was most marked in leisure (25 patients) and vocational (8) activities, but was mild in 66% of cases. Multivariate analysis was carried out to determine the prognostic factors for poor limb function. The results suggested that overall functional score was predominantly determined by gait (P less than 0.001), muscle power or range of movement (P less than 0.001), with increasing age, female sex and the use of radiotherapy poor prognostic factors. Reduced muscle power or range of movement were the major factors determining gait (P less than 0.02) with the use of radiotherapy the significant prognostic factor for both in the conventionally treated group. Doses in excess of 60 Gy resulted in increased fibrosis and a worse functional outcome. Extent of surgery was not an independent prognostic factor for limb function, although univariate analysis suggested an association with range of movement in the conventionally treated group (P less than 0.025). Despite significant objective loss of range of movement and muscle power patients retain excellent limb function and quality of life following limb conserving treatment. For optimal function, radiotherapy should be given with small fractions to a dose not exceeding 60 Gy.

Adult↗
PubMed1991

Kidney allograft tolerance in primates without chronic immunosuppression--the role of veto cells.

Posttransplant infusion of specific donor bone marrow cells into ATG-treated recipients promotes long survival of allografts in the absence of immunosuppressive drug therapy. DBMC infusion also inhibits antidonor CTL activation in allograft recipients, a trend analogous to the veto phenomenon. The present studies investigated a hypothesis that veto activity in DBMC is involved in the induction of donor-specific unresponsiveness in rhesus monkey kidney transplant recipients given ATG and DBM. Normal monkey BMC were fractionated into subpopulations by depletion with mAbs and immunomagnetic beads. The unfractionated BMC and BMC subsets were tested for veto activity in in vitro MLR-induced CTL and for in vivo tolerance-promoting activity in ATG-treated monkey kidney transplant recipients. In MLR-induced CTL assays, BMC specifically suppressed CTL activity to PBL from the BMC donor. The suppression was mediated by a small population of BMC that expressed a CD2+, CD8+, CD16+, DR-, CD3-, CD38- phenotype. Results of in vivo studies showed a striking correlation with the in vitro results. ATG-treated recipients given either DR- DBMC or DR- CD3- DBMC infusions had significantly prolonged graft survival and a 40-50% incidence of long survivors over 150 days (P less than 0.001 vs. ATG controls). In contrast, in recipients given CD2- DBMC or DR- CD16- DBMC infusions, the tolerance-promoting effect of DBMC was absent, and there were no long-term survivors. The results also showed an association between long survival and suppressed in vivo antidonor CTL activity. Thus acute rejection and in vivo and in vitro antidonor CTL responses were suppressed by a minor subpopulation of DBMC with similar phenotypic markers. We suggest that a veto mechanism may control the induction phase of allograft tolerance in this model, providing a critical period of CTL silence to allow development of host immunoregulatory mechanisms necessary for maintaining graft tolerance.

Animals↗
PubMed1991

Metastatic melanoma of the orbit. A case report.

We report a metastatic cutaneous melanoma of the medial rectus muscle of the right orbit which presented with diplopia, exophthalmos and retrobulbar pain. Radioimmunoscintigraphy using melanoma-specific monoclonal antibody was used to confirm the diagnosis and to show the presence of disseminated disease in other areas. Effective palliation was achieved with external beam irradiation.

Antibodies, Monoclonal↗