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Biomedical subjects

J Pritchard

Publications and source records attributed to J Pritchard.

At least 181 records · Page 10Linked to original sources

The aniridia-Wilms' tumour association: molecular and genetic analysis of chromosome deletions on the short arm of chromosome 11.

We have analysed karyotypes and DNA from three patients with aniridia (congenital absence of irises) and Wilms' tumour. All three had constitutional deletions from the short arm of chromosome 11. The minimum region of overlap of the deletion involves a small region of band 11p13 presumed to contain the genetic loci responsible for both phenotypic abnormalities. Using cells from these patients, somatic cell hybrids with transformed mouse cells have been prepared. Individual subclones retaining either the deletion-11 chromosome or the normal chromosome 11, in addition to a variety of other human chromosomes, have been identified. The relative position of these breakpoints have been determined and the panel of hybrids has been used to map randomly-isolated 11p13 DNA sequences. The characterisation of these deletions has provided a useful panel of hybrids for random mapping strategies designed to identify the Wilms' and aniridia genes.

Cell Line↗

The biophysics of differential growth.

The intrinsic control of uniform and differential growth of plant cells can be traced to a small number of physical parameters. These are cell wall rheology, membrane and tissue hydraulic conductivity, and membrane and tissue solute transport. Water and solute effects are manifested as alterations in turgor pressure. Environmental and biochemical processes always channel their effects through one or more of these parameters. Technical developments such as the pressure probe and Instron tensiometer, together with a reappraisal of older techniques, are beginning to allow assessment of the relative roles of these factors. Although the importance of cell wall rheology is becoming increasingly apparent, there is still insufficient information to allow generalized conclusions regarding the role of turgor pressure in differential growth. This review considers attempts to correlate these parameters with observed anatomical growth patterns.

Biophysical Phenomena↗

'Debulking' surgery is unnecessary in advanced abdominal Burkitt lymphoma in Iraq.

In a previous study (Burkitt lymphoma study I, BL I) between 1982 and 1984, we used a multidrug rotating chemotherapy schedule, now known as 'GRAB', to treat 24 Iraqi children with non-localised BL (Murphy stages II, III and IV). At the time of reporting, actuarial survival was 50% (current actual survival 42%) and the major morbidity and mortality was not from resistant or relapsed lymphoma, but from complications of the tumour lysis syndrome, sepsis and early abdominal surgery. The study (BL II) reported here was carried out between 1984 and 1986; we used GRAB to treat 24 newly and consecutively diagnosed children with advanced Burkitt lymphoma but discouraged early 'debulking' surgery and paid special attention to supportive care during the first two weeks of treatment. As in BL I, no radiotherapy was used. Twenty patients (83.8%) attained complete remission: 17 (71%), including three of the seven stage IV patients, survive continuously disease-free at a median of 26 months (range 18-36 months) from diagnosis. We have previously pointed out that GRAB, without radiotherapy, may be especially suited for use in some developing countries. From this study we conclude that, with appropriate supportive care and minimal surgery, survival rates over 50% may be achieved. Our next studies are aimed at defining a 'good risk' group of patients, who may be curable without alkylating agents and a 'poor risk' group, who need more intensive therapy.

Abdominal Neoplasms↗

Peripheral T-cell lymphoma in childhood. A clinicopathological study of six cases.

A review of the pathological material from 42 children with non-Hodgkin's lymphoma seen over a 44 month period revealed 10 large cell tumours. Of these, six were classified as peripheral T-cell lymphoma, an entity rarely reported in childhood. Three patients were boys and three girls (median age 9.5 years), and extranodal presentation was a feature of two patients. Five had high-grade tumours; of these, three were classified as large cell anaplastic, Ki-1 positive and two as pleomorphic large cell. The remaining patient had a low-grade tumour of angioimmunoblastic type. T-cell subsets were examined in three cases and showed the following phenotypes: CD4-, CD8-; CD4+, CD8-; CD4-, CD8+. Three of the patients with high-grade tumours died, with a mean survival of 22 weeks. The remaining patients are alive and clinically disease-free for between 10 and 24 months after treatment.

Antibodies, Monoclonal↗

Monoclonal antibodies for detecting bone marrow invasion by neuroblastoma.

One hundred and sixty six bone marrow aspirates from children with abdominal neuroblastoma were independently examined for the presence of neuroblastoma cells by conventional haematological staining techniques and by indirect immunofluorescence using one or more of five monoclonal antibodies. Results using the two methods were evaluated by comparison with the results of bone marrow, bone and lymph node biopsy specimens taken at the same time, and in the light of the child's clinical course. One antibody, UJ13A, was found to have 98.5% specificity and 85.7% sensitivity, compared with sensitivities for conventional staining of 50% for aspirate alone and of aspirate or trephine biopsy specimen of 71.4%. The remaining antibodies UJ127/11, UJ223/8, UJ181/4 and UJ167/11, with specificities in the range 94-99%, were found to have sensitivities in the range 47-61%, lower than the sensitivity of conventionally stained aspirate or trephine biopsy specimen. Routine immunofluorescence staining with monoclonal antibody UJ13A should increase the sensitivity of detection of metastatic neuroblastoma.

Abdominal Neoplasms↗

Chemotherapy as the initial treatment of spinal cord compression due to disseminated neuroblastoma.

During a 12-month trial period, all children attending the Hospitals for Sick Children, London, England, for management of spinal cord compression due to disseminated neuroblastoma were given chemotherapy as initial treatment rather than radiotherapy or laminectomy. Response to treatment was evaluated by a neurosurgeon as well as by oncologists. Four children were treated in this way and all made a full recovery of spinal cord function.

Antineoplastic Agents↗

Bronchoscopy for aspirated foreign bodies in children. Experience in 131 cases.

One hundred thirty-one children underwent rigid bronchoscopy under general anesthesia for suspected aspirated foreign bodies. There were 79 boys and 52 girls, with a mean age of 2.1 years. Physical examination showed decreased breath sounds (n = 130) and wheezing (n = 119) over the affected site. Chest roentgenograms were diagnostic or suggestive of aspirated foreign bodies in 127 cases (97%). Radiopaque lesions were noted on roentgenograms in ten cases. Four infants had a preoperative hypoxic arrest. Two patients had negative results of bronchoscopy (1.5%). Extraction of the aspirated foreign body was carried out at laryngoscopy in two patients and by forceps under direct vision at bronchoscopy in 97 patients. A Fogarty catheter was used in 12 cases. Postendoscopic complications included fever (n = 27), pulmonary infiltrate (n = 11), ventilatory support (n = 4), and pneumothorax (n = 2). Rigid bronchoscopy for aspirated foreign body in children is a safe, effective, and sometimes life-saving procedure. Morbidity is low and mortality is zero.

Bronchi↗

Cytogenetic changes in Wilms' tumors.

Cytogenetic analysis of 20 Wilms' tumors using short-term culture techniques were undertaken. Chromosome abnormalities were detected in all tumors. In 19 of 20 cases only minor karyotypic changes were observed within cells with near-diploid chromosome numbers; only one tumor was predominantly hyperdiploid. Rearrangements involving chromosome 1 were the most frequently observed abnormality (in 25%) and often resulted in partial or complete trisomy for the long arm. In 20% of the tumors, abnormalities involving chromosomes 11 and 16 were present. The only other chromosomes frequently involved in structural or numerical changes were #12, and #18. Two discrete tumor foci within the same kidney differed cytogenetically, suggesting an independent origin for each focus. No correlation could be made between specific chromosome abnormalities and tumor stage or histologic subtype. Although constitutional deletion of chromosome region 11p13 has frequently been reported to predispose to Wilms' tumor formation, only two tumors with deletions involving this region were observed. Chromosomes from tumors treated with chemotherapy prior to surgical removal and culture yielded findings similar to those in untreated tumor cells.

Child↗

Ifosfamide in previously untreated disseminated neuroblastoma. Results of Study 3A of the European Neuroblastoma Study Group.

A prospective study of the effectiveness of ifosfamide as a single agent in the management of previously untreated patients with Evans stage IV neuroblastoma was undertaken. Eighteen children aged more than 1 year were treated with ifosfamide (IFX) 3 g/m2 daily for 2 days immediately after diagnosis and 3 weeks later. Treatment was continued with combination chemotherapy using vincristine, cyclophosphamide, cisplatinum and etoposide (OPEC) or a variant. Mesna (2-mercaptoethane sulphonate) was given to all patients during IFX treatment to prevent urotoxicity. Eight of the 18 patients (44%) responded to IFX. Nine had greater than 66% reduction in baseline tumor volume. Of 15 evaluable patients with raised pre-treatment urinary catecholamine excretion, six (40%) achieved greater than 50% reduction in pretreatment levels. Two of 10 patients evaluable for bone marrow response had complete clearance. Toxicity was mild in all patients. Upon completing 'first line' therapy, only four patients (22%) achieved a good partial remission (GPR) or complete response (CR). Median survival was 11 months. There was a lower rate of attaining GPR and shortened median survival in patients receiving phase II IFX before OPEC or variant, compared to patients with similar pre-treatment characteristics treated with OPEC from diagnosis in an earlier study.

Antineoplastic Combined Chemotherapy Protocols↗

Pelvic rhabdomyosarcoma in children.

Twenty children with pelvic rhabdomyosarcoma treated between 1976 and 1983 are reviewed. The survival rate was 55% (11/20), with a bladder salvage rate of 54.5% among survivors. Systemic chemotherapy combined with radiotherapy and/or surgery was most effective in producing cure.

Adolescent↗