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J M Thomas

Publications and source records attributed to J M Thomas.

At least 145 records · Page 8Linked to original sources
PubMed1998

The effect of anti-CD3-immunotoxin on T lymphocyte function in vitro.

Recent advances in the design of immunotoxins (IT) have yielded significant improvements. FN18-CRM9, a construct of anti-CD3 epsilon mAb FN18 and mutated diphtheria toxin CRM9 has exhibited high specificity, low systemic toxicity and unusual efficacy compared to previous iterations of immunotoxins. Others and we have examined this anti-CD3-IT for the purpose of inducing immunological tolerance through selective ablation of T cells in rhesus macaques and have obtained encouraging results. In order to characterize its mode of action, we have examined its effects on peripheral blood and lymph node T cell killing in vitro. We have studied the cytotoxic mechanism induced by this anti-CD3-IT as well as its effects on proliferation, phenotypic changes and cytokine production (IL2, IFN gamma and TNF alpha). The results indicate that anti-CD3-IT was highly specific for T cell killing at doses as low as 1 x 10(6) micrograms/ml and showed a maximal effect at 48 h after exposure. The toxicity was restricted to T cells, as B cells and other bystander cells were spared. This immunotoxin was shown to induce T cell apoptosis, as assessed by TUNEL assay, DNA content and cytotoxicity. Fas expression was upregulated on T cells within 24 h after in vitro exposure to anti-CD3-IT, suggesting an early T cell activation phase prior to T cell death. T cell killing was manifest as an early cell cycle arrest at the G1/S phase transition, which appeared to virtually eliminate the production of cytokines. These findings corroborate the temporal, specificity and quantitative patterns for anti-CD3 immunotoxin administration previously observed in vivo.

Animals↗
PubMed1998

Reliability of the Terry: a mental health cartoon-like screener for African-American children.

Test-retest reliability and internal consistency of the Terry, a cartoon-based child mental health screener developed for African-American children, were measured in 36 boys (age 5 1/2 to 13) in a test-retest design. Reliability of the diagnosis (0.70 < or = k < or = 0.75) was good for ADHD, ODD, CD, and OAD, and excellent for MDD and SAD. Because of low base-rate, no kappa value was calculated for SPh. Both test-retest agreement, and reliability of the symptom scale (0.75 < or = ICC < or = 0.80) were very good for all 7 diagnoses. Internal consistency according to symptom scale (0.78 < or = Cronbach alpha < or = 0.90), was moderate for OAD, good for SPh, MDD, SAD, CD, and ODD, and excellent for ADHD. The Terry is a culturally-sensitive questionnaire with good reliability.

Adolescent↗
PubMed1998

An essential role for Fas ligand in transplantation tolerance induced by donor bone marrow.

Medawar and co-workers originally demonstrated that injection of donor bone marrow (DBM) into immuno-incompetent neonatal rodents could induce tolerance to grafts from animals of the same strain as the bone marrow donor. Induction of tolerance in this manner can also be accomplished in mature mice, dogs and monkeys if the resident T-cell populations in the recipient are depleted by a polyclonal antithymocyte globulin or an anti-T cell immunotoxin. The molecular mechanisms by which bone marrow cells mediate the induction of tolerance remain uncertain. Here we examined a well-established adult mouse model of antithymocyte globulin and DBM treatment and show that expression of functional Fas ligand (FasL, also CD95L) on the injected bone marrow cells is required for tolerance induction. The results indicate that a state of microchimerism per se is insufficient for the induction of tolerance in T cell-depleted transplant recipients. Moreover, the results are consistent with the hypothesis that tolerance induced by DBM involves an apoptotic process leading to deletion of graft-reactive cells.

Animals↗
PubMed1998

Summary of the practice parameters for the psychiatric assessment of infants and toddlers (0-36 months). American Academy of Child and Adolescent Psychiatry.

This summary describes the psychiatric assessment of infants and toddlers (0-36 months) and supports the growth of infant and toddler psychiatry, a rapidly developing field. Infants and toddlers are brought to clinical attention because of concerns about emotional, behavioral, relational, or developmental difficulties. It is axiomatic that the infant or toddler must be understood evaluated and treated within the context of the family. A perspective that is developmental relational, and multidimensional and that borrows from the knowledge of multiple disciplines is essential. Collaborative efforts support the urgent need and incomparable opportunity to understand and to intervene early and preventively with young children and their families.

Child Psychiatry↗
PubMed1998

Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever.

BACKGROUND: The role of viruses in the aetiology of both chronic fatigue syndrome (CFS) and depressive illness is uncertain. METHOD: A prospective cohort study of 250 primary care patients, presenting with glandular fever or an ordinary upper respiratory tract infection (URTI). RESULTS: The incidence of an acute fatigue syndrome was 47% at onset, after glandular fever, compared with 20% with an ordinary URTI (relative risk 2.3, 95% CI 1.3-4.1). The acute fatigue syndrome lasted a median (interquartile range) of eight weeks (4-16) after glandular fever, but only three weeks (2-4) after an URTI. The prevalence of CFS was 9-22% six months after glandular fever, compared with 0-6% following an ordinary URTI, with relative risks of 2.7-5.1. The most conservative measure of the incidence of CFS was 9% after glandular fever, compared with no cases after an URTI. A conservative estimate is that glandular fever accounts for 3113 (95% CI 1698-4528) new cases of CFS per annum in England and Wales. New episodes of major depressive disorder were triggered by infection, especially the Epstein-Barr virus, but lasted a median of only three weeks. No psychiatric disorder was significantly more prevalent six months after onset than before. CONCLUSIONS: Glandular fever is a significant risk factor for both acute and chronic fatigue syndromes. Transient new major depressive disorders occur close to onset, but are not related to any particular infection if they last more than a month.

Acute Disease↗
PubMed1998

Acquired ichthyosis, alopecia and loss of hair pigment associated with leiomyosarcoma.

Acquired ichthyosis is an important clinical finding; internal malignancy, systemic disease and medication are recognised associations. We present a 70-year-old lady with acquired ichthyosis and leiomyosarcoma, one of the less frequently associated malignancies. An additional unusual finding was generalised thinning and loss of pigment affecting her hair. Scalp biopsy showed histological evidence of ichthyosis. Following resection of the tumour the ichthyosis resolved and there was regrowth of darker hair.

Aged↗
PubMed1997

Preclinical studies of allograft tolerance in rhesus monkeys: a novel anti-CD3-immunotoxin given peritransplant with donor bone marrow induces operational tolerance to kidney allografts.

A major challenge in clinical transplantation today is to design a practical and effective protocol for tolerance induction compatible with cadaver organ transplantation. A preclinical rhesus monkey kidney allograft model using immediate peritransplant anti-CD3 immunotoxin (anti-CD3-IT) and donor bone marrow (DBM) is shown here to induce operational tolerance with prolonged graft survival in the absence of chronic immunosuppressive drugs. Bone marrow harvested from the kidney donor was depleted of mature alloantigen-presenting cells and T cells by removing DR(bright) cells and CD3(bright) cells, respectively. In outbred, major histocompatibility complex-incompatible donor-recipient pairs with high pretransplant mixed lymphocyte response and cytotoxic T lymphocyte precursor activity, four of six allografts survived for periods of 120 days to >1.5 years. Graft acceptance after peritransplant treatment followed robust elimination of both peripheral blood T cells and lymph node T cells. In most recipients given anti-CD3-IT and DBM infusion, anti-donor immunoglobulin G responses were completely inhibited. Microchimerism was observed in all recipients studied, including those not given DBM, but levels of microchimerism did not correlate with graft survival. Anti-CD3-IT induction in combination with modified DBM protocols such as the depletion of mature T cells and DR(bright) antigen-presenting cells may offer new opportunities to improve clinical tolerance protocols beyond those attempted in the clinic to date. Overall, these results with anti-CD3-IT show promise for development of cadaver transplant tolerance induction.

Animals↗
PubMed1997

Seasonality prevalence and incidence of depressive disorder in a general practice sample: identifying differences in timing by caseness.

A total of 2225 consecutive consulting general practice patients attending a North London Health Centre over the course of a year were screened and interviewed for the presence of psychiatric disorder using the GHQ and SADS; 196 patients suffering from RDC depressive disorders were identified and followed up for a further 12 months. A difference in prevalence incidence and recovery time was identified between major and minor depression. Various associations between season of onset and a range of variables were observed. Logistic modelling identified interactions between some of these variables some of which have not been explored in previous studies.

Bipolar Disorder↗
PubMed1997

The natural history and management of Merkel cell carcinoma of the skin: a review of 22 patients treated at the Royal Marsden Hospital.

Merkel cell carcinoma is a rare skin malignancy, which primarily affects the elderly. Currently, there is only limited data on the natural history of this condition and no consensus on its optimum management. We have reviewed the natural history and management of 22 patients with Merkel cell carcinoma, who were treated at the Royal Marsden Hospital between 1985 and 1994. The median age at diagnosis was 75 years (range 55-96), with the head and neck region being the most common site of disease (nine patients: 41%). Seventeen patients (77%) presented with skin disease, three (14%) with regional lymphadenopathy and two (9%) with metastatic disease. Of the Stage I patients, 41% developed local recurrence postoperatively at a median time to relapse of 12 months. Those with head and neck disease had the highest risk of local recurrence, which occurred in 62.5% of this group. Stage I patients also had a high risk of disease progression, with 53% developing regional lymphadenopathy or visceral metastases. The median survival for all disease stages was 47 months. The treatment of unresectable primary or recurrent disease with radiotherapy led to valuable long term control in four of nine patients treated. Six courses of chemotherapy were administered; one brief complete response was observed, occurring in a patient treated with cyclophosphamide, vincristine and doxorubicin. The data in this study confirms the predilection for the elderly and the aggressive nature of Merkel cell carcinoma, with only four of 17 Stage I patients remaining disease free. To clarify the role of adjuvant postoperative radiotherapy and to establish the appropriate use of chemotherapy in metastatic spread of this rare malignancy will require further studies with multicentre cooperation.

Aged↗
PubMed1997

Infantile (desmoid-type) fibromatosis of the parotid gland.

Infantile fibromatosis, one of the fibrous tumours of infancy and childhood, is a fibroproliferative lesion characterized by aggressive local invasion without any tendency to metastasize, the absence of cytological evidence of malignancy and a high rate of local recurrence when incompletely excised. We report a case of infantile (desmoid-type) fibomatosis in a seven-year-old girl arising from the deep lobe of the parotid gland that was treated by complete surgical excision with preservation of the facial nerve. The clinical features, pathology and treatment are briefly discussed.

Child↗
PubMed1997

The use of paediatric chemotherapy protocols at full dose is both a rational and feasible treatment strategy in adults with Ewing's family tumours.

BACKGROUND: Ewing's sarcoma and primitive neuroectodermal tumour (ES/PNET) are rare, limiting opportunities for therapy studies in adults. Chemotherapy regimens adapted from paediatric studies are often used for adults but concerns about poor outcome and treatment toxicity may adversely affect drug dose intensity. We present our experience using a paediatric protocol at full dose. PATIENTS AND METHODS: Records of 34 patients with ES/PNET who received the IVAD chemotherapy regimens were reviewed. Received drug dose intensity, toxicity and survival data were collected. RESULTS: Received dose intensity in 30 evaluable patients was 0.92 compared to the standard IVAD schedule. Myelosuppression was the major toxicity, 83% of patients experienced grade 4 neutropenia. There was no major renal or cardiac toxicity. In patients without metastases at presentation, five-year overall survival was 63% and progression free survival was 39%. Tumour burden at presentation was statistically significantly associated with survival (P = 0.002). The five-year survival rate of 80% in patients presenting with low volume non metastatic disease was equivalent to published paediatric series. CONCLUSIONS: Although the IVAD chemotherapy regimens are myelotoxic in adults, they can be given safely. We recommend that adults with ES/PNET should be included in current multicentre, multidisciplinary treatment studies directed at children.

Adolescent↗
PubMed1997

Practice parameters for the psychiatric assessment of infants and toddlers (0-36 months). American Academy of Child and Adolescent Psychiatry.

These practice parameters describe the psychiatric assessment of infants and toddlers (0-36 months) and support the growth of infant and toddler psychiatry, a rapidly developing field. Infants and toddlers are brought to clinical attention because of concerns about emotional, behavioral, relational, or developmental difficulties. It is axiomatic that the infant or toddler must be understood, evaluated, and treated within the context of the family. A perspective that is developmental, relational, and multidimensional and that borrows from the knowledge of multiple disciplines is essential. Collaborative efforts support the urgent need and incomparable opportunity to understand and to intervene early and preventively with young children and their families.

Child Psychiatry↗
PubMed1997

Soft tissue tumours.

Any soft tissue swelling beneath the deep fascia should be considered a sarcoma until proven otherwise. As the most important factor in the primary treatment of these cancers is the adequacy of the primary surgical resection, it is vital to diagnose these malignant tumours pre-operatively. The modern treatment of soft tissue sarcomas may involve all modalities, but the most important aspect of treatment of a primary localised sarcoma is wide excisional surgery preserving limb function. Radiotherapy is a vital adjunct in high-grade tumours, or in tumours whose resectability is limited either by size or anatomical proximity to vital structures. Apart from a few chemosensitive sarcomas, the role of chemotherapy is limited to treatment of metastatic disease where documented response rates are no greater than 30%. As 50% of patients with high-grade sarcomas will die from metastatic disease, improvements in survival rates will only come from improvements in response to systemic therapy. No controlled trials have shown any survival benefit for adjuvant chemotherapy, although a recent meta-analysis of published data has shown a trend to increased survival at two years. Multicentre randomised trials are ongoing. The prognosis of these lesions is highly variable, but is intimately related to the anatomical site (i.e., resectability), and also the grade and size of the tumour.

Combined Modality Therapy↗
PubMed1997

Ewing's sarcoma and primitive neuroectodermal tumor in adults: are they different from Ewing's sarcoma and primitive neuroectodermal tumor in children?

PURPOSE: To determine whether age at diagnosis influences the behavior of Ewing's sarcoma and primitive neuroectodermal tumor (PNET). PATIENTS AND METHODS: We reviewed the clinical features, treatment, and outcome of 59 consecutive patients with Ewing's sarcoma and PNET treated on the Adult Sarcoma Unit at our institution from 1980 to 1995. RESULTS: The 37 male and 22 female patients had a median age of 24 years. Lower limb was the most common primary tumor site. Fifteen patients had nonmetastatic tumor less than 100-mL volume, 27 had nonmetastatic disease greater than 100-mL volume, and 17 had evidence of metastatic disease at presentation. The origin of the primary tumor was soft tissue in 28 cases, bone in 30, and uncertain in one. The Kaplan-Meier estimate of 5-year overall survival (OS) in all patients was 38% and of progression-free survival (PFS), 27%. When patients with metastatic disease at presentation were excluded, these figures increased to 52% and 34%, respectively. Bulk of disease at presentation and response to primary treatment were statistically highly significant predictors of both PFS and OS. Age and tissue of origin of the tumor did not influence outcome. CONCLUSION: The behavior of Ewing's sarcoma and PNET in adults is no different from its behavior in children. We feel the way forward in the treatment of adults with Ewing's sarcoma and PNET is for them to be included in the current multicenter trials of multidisciplinary treatment directed at children.

Adolescent↗
PubMed1997

Esophagogastroduodenoscopy training in family practice residency program.

BACKGROUND AND OBJECTIVES: Esophagogastroduodenoscopy (EGD) is a procedure that has been gaining interest among family physicians. To determine the extent of EGD training at family practice residences, we surveyed all US family practice residency directors. METHODS: In late 1994, we mailed a questionnaire to the residency directors of all ACGME-accredited family practice residency programs. RESULTS: A total of 359 programs responded to the questionnaire (87.7%). Eighty-seven (24.2%) programs reported that their residents receive training to perform EGD. At the majority of these programs, residents perform 10 or less EGDs during their residency experience. Programs on the East and West coasts were less likely to provide this training than were programs in other regions of the country. Residents at programs in the South performed significantly more EGDs than did residents in programs in other regions. Southern residents also were more likely to perform these procedures in family practice centers rather than gastroenterology (GI) labs. Those programs whose residents perform more than 25 EGDs were more likely to have family physicians as trainers of this procedure and also were more likely to offer this training at family practice centers instead of GI labs. CONCLUSIONS: EGD training is now offered by a relatively large number of family practice residency programs. However, concern could be raised as to whether these programs provide adequate quantitative experience. Strong regional differences were noted in the availability of this training.

Endoscopy, Digestive System↗