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Biomedical subjects

A Barrett

Publications and source records attributed to A Barrett.

At least 91 records · Page 5Linked to original sources
PubMed1989

Results of the United Kingdom Children's Cancer Study Group's malignant germ cell tumor studies.

The United Kingdom Children's Cancer Study Group's malignant germ cell tumor studies were undertaken to establish standard protocols for investigating, staging, and treating children, and to study the efficacy of new drug combinations and the value of serial measurement of serum alphafetoprotein (AFP) and human chorionic gonadotrophin (HCG). Boys with Stage I testicular tumors were treated by orchidectomy alone, whereas, after appropriate surgery, chemotherapy was recommended for children with more advanced testicular tumors or with tumors at other sites. From 1979 to 1987, 126 children aged 0 to younger than 16 years with malignant germ cell tumors were registered. They were similar to patients in other large pediatric series with respect to sites of origin, age at presentation in relationship to primary site, histology, female predominance for sacrococcygeal site, and presence of associated malformations (present in 17%). Serum AFP was measured in 123 patients and was elevated in 115, whereas HCG was raised in 19 of 77. Monitoring by serial AFP measurement proved valuable in assessing response to therapy and in early detection of tumor recurrence. When treatment results were assessed in February 1988, 101 of 122 patients were alive (four who received nonprotocol chemotherapy were excluded). Forty-four patients had been cured by surgery alone (41 with testicular tumors, two with ovarian tumors, and one with sacrococcygeal tumor). All of the remaining 78 children received chemotherapy. The initial low dose vincristine, actinomycin, and cyclophosphamide (LDVAC) regimen proved ineffective, actuarial survival at 5 years followup being 8% (12 patients), and a regimen of cisplatin, vinblastine, and bleomycin (PVB) caused unacceptable toxicity, with actuarial survival at 5 years follow-up being 67% (nine patients). Five-year actuarial survival was 87% for 17 children given high dose VAC with or without doxorubicin and 84% for 33 given bleomycin, etoposide, and cisplatin (BEP). All 7 children given various combinations of these regimens survived. Excluding the 12 LDVAC cases, patient survival by site was as follows: testis (59 patients, 100%); vagina, uterus, and prostate (four patients, 100%); ovary (25 patients, 88%); thorax (five patients, 40%), and other (four patients, 67%). Similarly, patient survival by stage was Stage I (62,97%), Stage II (14,86%); Stage III (18,83%); and Stage IV (16,72%). Survival by histology was analysed only in cases for which histologic review had been done the LDVAC cases were excluded.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1989

The place of surgery in the management of germ cell tumours in childhood.

Because of their rarity and the availability of effective, if toxic, treatment, germ cell tumours should be managed by a team familiar with their behaviour and response to therapy. Treatment decisions from the time of presentation onwards should be made by surgeon and oncologist together, and, where the diagnosis is made unexpectedly after emergency surgery, early consultation is necessary to establish the best approach to treatment for that individual patient. Mutual recognition of the possibilities and problems of each modality of treatment will lead to their use together in the most effective way.

Child↗
PubMed1989

Evidence for two types of spatial representations: hemispheric specialization for categorical and coordinate relations.

Analyses of human object recognition abilities led to the hypothesis that 2 kinds of spatial relation representations are used in human vision. Evidence for the distinction between abstract categorical spatial relation representations and specific coordinate spatial relation representations was provided in 4 experiments. These results indicate that Ss make categorical judgments--on/off, left/right, and above/below--faster when stimuli are initially presented to the left cerebral hemisphere, whereas they make evaluations of distance--in relation to 2 mm, 3 mm, or 1 in. (2.54 cm)--faster when stimuli are initially presented to the right cerebral hemisphere. In addition, there was evidence that categorical representations developed with practice.

Adult↗
PubMed1988

Strategies for systemic radiotherapy of micrometastases using antibody-targeted 131I.

A simple analysis is developed to evaluate the likely effectiveness of treatment of micrometastases by antibody-targeted 131I. Account is taken of the low levels of tumour uptake of antibody-conjugated 131I presently achievable and of the "energy wastage" in targeting microscopic tumours with a radionuclide whose disintegration energy is widely dissipated. The analysis shows that only modest doses can be delivered to micrometastases when total body dose is restricted to levels which allow recovery of bone marrow. Much higher doses could be delivered to micrometastases when bone marrow rescue is used. A rationale is presented for targeted systemic radiotherapy used in combination with external beam total body irradiation (TBI) and bone marrow rescue. This has some practical advantages. The effect of the targeted component is to impose a biological non-uniformity on the total body dose distribution with regions of high tumour cell density receiving higher doses. Where targeting results in high doses to particular normal organs (e.g. liver, kidney) the total dose to these organs could be kept within tolerable limits by appropriate shielding of the external beam radiation component of the treatment. Greater levels of tumour cell kill should be achievable by the combination regime without any increase in normal tissue damage over that inflicted by conventional TBI. The predicted superiority of the combination regime is especially marked for tumours just below the threshold for detectability (e.g. approximately 1 mm-1 cm diameter). This approach has the advantage that targeted radiotherapy provides only a proportion of the total body dose, most of which is given by a familiar technique. The proportion of dose given by the targeted component could be increased as experience is gained. The predicted superiority of the combination strategy should be experimentally testable using laboratory animals. Clinical applications should be cautiously approached, with due regard to the limitations of the theoretical analysis.

Antibodies, Monoclonal↗
PubMed1988

Learning of a complex arithmetic skill in amnesia: evidence for a dissociation between compilation and production.

Two patients with severe amnesia following rupture of anterior communicating artery aneurysms were able to learn a complex algorithm for mentally squaring two-digit numbers. Although both patients learned the algorithm at a similar rate, one patient's improvement was accounted for by savings in the steps of the algorithm. The other patient, however, showed little improvement in the steps while performance of the whole algorithm improved dramatically. Neither patient showed savings in the Hebb Digit Span procedure. The results suggested a dissociation between amnesics in their capacity to learn the constituent "productions" or steps of a skill and their capacity to organize those productions into a single coherent act.

Adult↗
PubMed1988

International criteria for diagnosis, staging, and response to treatment in patients with neuroblastoma.

Neuroblastoma is one of the most common tumors in childhood. However, it often has been difficult to compare clinical and laboratory studies of this disease due to a lack of uniform criteria for diagnosis, staging, and response. An international group of conferees addressed each of these issues and reached a consensus. Specific criteria for making a diagnosis of neuroblastoma are defined. A new neuroblastoma staging system is proposed that takes into account the most important elements of current but incompatible systems. Finally, criteria for response to treatment are standardized. The criteria proposed herein represent an international consensus of essentially every major pediatric oncology group or organization in the United States, Europe, and Japan. The staging system should be referred to as the International Neuroblastoma Staging System, and the response criteria as the International Neuroblastoma Response Criteria. Implementation of these criteria will greatly facilitate the comparison of clinical and laboratory studies by different groups and countries. Furthermore, these criteria should serve as a foundation on which future modifications or improvements can be based.

Humans↗
PubMed1987

Vomiting associated with whole body irradiation.

A study has been made of the patterns of vomiting in 305 patients undergoing total body irradiation before bone marrow transplantation. Vomiting usually begins after a dose of 2 to 3 Gy has been given to the whole body and may persist for up to 12 hours from the start of treatment. There is a recurrence of vomiting after 2 to 5 days. It is infrequent in patients receiving fractionated radiation with fraction sizes of less than 2 Gy, and appears unrelated to cumulative dose after the threshold has been reached. The incidence of vomiting is reduced by limitation of patient movement during radiation and by sedation adequate to keep the patient asleep. It is increased by anxiety and there is a higher incidence in patients aged 10 to 40 than in those aged less than 10 years. Other drugs administered before total body irradiation may affect the incidence. Vomiting can be prevented completely in 50% of patients.

Age Factors↗
PubMed1987

Late effects of total body irradiation.

Late effects of chemo-radiotherapy conditioning before bone marrow transplantation (BMT) are being increasingly recognised in long-term survivors, particularly children. They can be divided into two categories: those affecting hormonal status and those affecting specific organ function. All women treated develop ovarian failure with low levels of beta-oestradiol and raised values of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). In males, raised FSH and LH values are found with normal testosterone levels but most patients have azoospermia. In children, puberty is usually but not invariably delayed by treatment but can be induced by appropriate hormone replacement. Compensated hypothyroidism was found in 6/30 children. Growth hormone secretion may be impaired especially if previous cranial irradiation has been given. In children, a reduction in sitting height has been observed. Cataract has occurred in 20% of children between 3 and 6 years after treatment. Two second tumours have been observed. No other major organ toxicities have been encountered.

Adult↗
PubMed1987

Cytogenetic follow-up studies of recipients of T-cell depleted allogeneic bone marrow.

Serial cytogenetic studies of bone marrow and blood cells were made in leukaemic patients who had received an allogeneic bone marrow graft from a donor of unlike sex. The donor marrow was treated with the monoclonal antibody Campath-1 before infusion. The persistence of a significant proportion of dividing recipient cells in marrow and blood was observed after grafting. These recipient cells showed evidence of radiation damage of both the stable and unstable types. More than one transient clone of chromosomally abnormal recipient cells was observed in three cases. The differences between the cytogenetic findings in patients receiving donor marrow from which T cells have been removed and those cases previously studied in our Leukaemia Unit who had received untreated donor marrow are discussed.

Adolescent↗
PubMed1986

Radiation damage in patients treated by total-body irradiation, bone marrow grafting, and cyclosporin.

The bone marrow (BM) and peripheral blood (PB) from 63 patients were assessed for the presence of chromosomal aberrations after bone marrow transplantation (BMT) following total body irradiation (TBI) for leukemia. Forty-one patients showed no abnormalities in either BM or PB, and 22 had aberrations in either BM or PB or both. Only stable aberrations were found in the BM, but both stable and unstable abnormalities were present in the PB, the majority showing only unstable aberrations. Among the 25 patients who had a leukemic relapse, clonal chromosomal abnormalities were found in the BM of 12 out of the 16 cases for whom marrow was studied at the time of the relapse. A statistically significant negative correlation between leukemic relapse and graft versus host disease (GvHD) was found, but the relationships between chromosome damage and leukemic relapse, GvHD, and the pretransplant radiation dose and between the radiation dose and both leukemic relapse and GvHD were not significant.

Adolescent↗
PubMed1986

Intracardiac metastases from malignant teratoma of the testis.

Cisplatin-based chemotherapeutic regimens are highly successful at controlling testicular teratomas, returning tumor markers to normal in 76% of patients. However, bulky residual disease persists in 24%, and surgical excision of these deposits is becoming increasingly common. This approach is justified, because the histologic characteristics of such deposits gives valuable prognostic information, allowing a decision to be made regarding additional therapy, and relapse of apparently stable disease may occur. Excision of residual bulky disease may be achieved safely. We have recently successfully excised an intracardiac metastasis in a patient with no demonstrable extrathoracic disease and normal serum marker levels.

Adult↗
PubMed1984

Influence of proteinase inhibitors on glucocorticoid receptor binding.

The influence of several proteinase inhibitors on rat liver cytosolic glucocorticoid receptor binding to [3H]triamcinolone acetonide has been investigated. E-64 (36 microM), an active-site directed cysteine proteinase inhibitor, significantly (about 40%) inhibited receptor binding. Tos-Lys-CH2Cl (1-2 mM) and Tos-Phe-CH2Cl (1-2 mM) also depressed receptor binding (20-67%). Interestingly, 5 mM dithiothreitol was able to prevent Tos-Lys-CH2Cl and Tos-Phe-CH2Cl effects, but had no apparent influence on E-64 action. A degree of proteinase inhibitor specificity was indicated by the lack of effect of several other proteinase inhibitors such as diisopropylfluorophosphate (1 mM), phenylmethylsulfonyl fluoride (1-2 mM), soybean trypsin inhibitor (1-2 mg/ml), tissue inhibitor of metalloproteinase (3.8 U/ml), cystatin (4-8 microM), and phosphoramidon (20-40 microM). These results suggest that thiol reactive proteinase inhibitors block glucocorticoid receptor binding, and that E-64 may prove to be a useful chemical probe in studying glucocorticoid receptor interaction.

Animals↗
PubMed1984

Chemotherapy and irradiation in childhood Hodgkin's disease.

Eighty children aged less than 16 years with newly diagnosed Hodgkin's disease were treated between 1974 and 1982. Complete remission occurred in 95%, with actuarial five year overall survival of 94%, and relapse free survival of 82%: median follow up was 4.8 years. Sixty one children were staged clinically while 19 had staging laparotomies before treatment. Most received combined modality treatment with Ch1VPP chemotherapy (chlorambucil, vinblastine, procarbazine, and prednisolone) followed by irradiation of initial bulk disease. Nodular sclerosis predominated in both sexes, accounting for 60% of the total. Girls with stage IV disease, nodal sclerosis histology, and bulky mediastinal masses had a relatively poor prognosis. Ten children have relapsed, and three prolonged (6 to 7 years) second remissions have been observed. Four died of disease, and one from infection. Clinical staging, avoiding splenectomy, reduced the risk of serious infections. Our current policy is to treat stage IA disease with local irradiation and all other stages with chemotherapy, adding irradiation for bulky mediastinal disease.

Adolescent↗
PubMed1983

Mismatched family donors for bone-marrow transplantation as treatment for acute leukaemia.

35 patients were treated for acute myeloid leukaemia or acute lymphoblastic leukaemia with allogeneic bone-marrow grafts from a parent, child, or sibling who was mismatched at the major histocompatibility complex (MHC). 11 of these patients are alive at least 6 months after grafting, 5 of them after more than 2 years. Of the 15 patients aged under 20 at the time of the graft, 8 are alive and well 6 months to 3 years later. Cyclosporin A was given to all patients after grafting. 1 patient died of acute graft-versus-host disease and in 2 other cases this was a major factor in their death. Graft failure caused the death of 2 patients. 4 patients died of recurrent leukaemia. A fatal complication in 12 patients was pulmonary oedema, often associated with convulsions, intravascular haemolysis, and renal failure. Some of these patients had viral or bacterial infections, but in the majority the syndrome was not associated with demonstrable infection. This syndrome, in which the essential lesion appears to be vascular, was much more common in recipients of mismatched than matched grafts. 3 others died from lung disease in which infection was a factor.

Acute Disease↗