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Biomedical subjects

J R Hobbs

Publications and source records attributed to J R Hobbs.

At least 55 records · Page 3Linked to original sources
PubMed1987

Treatment of Niemann-Pick disease type B by allogeneic bone marrow transplantation.

Allogenic bone marrow transplantation was carried out on a 3 year old girl with Niemann-Pick disease type B. Successful engraftment was achieved, and nine months after the procedure there was definite clearing of the sphingomyelin from the liver and pronounced clearing from the bone marrow. Any patient with Niemann-Pick disease type B complicated by early or severe hepatic impairment should be considered for bone marrow transplantation.

Bone Marrow Transplantation↗
PubMed1987

Beneficial effect of pre-transplant splenectomy on displacement bone marrow transplantation for Gaucher's syndrome.

2 patients with fast and 4 with medium varieties of Gaucher's syndrome were treated by displacement bone marrow transplantation to install a donor enzyme factory for life. Immunoprophylaxis was given to prevent host impairment of normal enzymes. 5 patients showed rapid and remarkable improvement and were leading fully active lives at 310-1207 days postgraft. Hypersplenism caused the death of 1 patient and a stormy time for another. Pre-transplant elective splenectomy hastened recovery.

Adolescent↗
PubMed1987

Differential effects of beta-endorphin fragments on human natural killing.

The endogenous opiate peptide, beta-endorphin, has two effects on human natural killing (NK). Preincubation of effector lymphocytes with between 10(-7) and 10(-11) M beta-endorphin increases NK. Preincubation with lower concentrations results in a reduction in NK. Endorphin peptides containing an unmodified N-terminal sequence, and which are known to bind only to opiate receptors, increase NK. Sequences reported to bind only to nonopiate receptors reduce NK.

Cytotoxicity, Immunologic↗
PubMed1987

Experience with bone marrow transplantation for inborn errors of metabolism.

Westminster experience had by 1973 evolved the concept of displacement bone marrow transplantation and extended the donors from matched siblings to other family and unrelated donors. The principles of its use to install donor bone marrow as a component factory for the life of the recipient, together with the importance of immunoprophylaxis are detailed. Satisfying correction has been achieved for 48 previously fatal genetic diseases, partial correction for another 5 with failure for 3 diseases. Displacement bone marrow transplantation is not a panacea, but could be applied to about 7% of known inborn errors, devising in vitro tests which can predict in vivo donor effects, especially since some 80% of our patients are not found in known families and could not have been prevented.

Bone Marrow Transplantation↗
PubMed1987

Regression of the radiological changes of Gaucher's disease following bone marrow transplantation.

Seven children with Type I Gaucher's disease have been treated with bone marrow transplantation (BMT). One patient died from the complications of BMT. In five patients computed tomography (CT) of the femora showed initially high attenuation in the marrow, returning towards normal after successful BMT. One of these patients also showed clearing of pulmonary infiltrates following treatment. In the first patient in the series no pre-transplant CT measurements were carried out but plain radiographs have demonstrated a return to normal shape of her femora 21/2 years after BMT. It is hoped that CT of the marrow cavities may provide a simple, non-invasive method for monitoring progress following BMT.

Adolescent↗
PubMed1986

Multiwell cap assay: a simple objective method for the assessment of leukocyte locomotion in vitro.

A simple method for evaluating leukocyte locomotion in vitro has been developed and validated for several chemoattractants. The multiwell cap assay (MWCA) comprises chambers constructed from readily available disposable plastics and is quickly assembled, permitting large experimental protocols. Leukocytes which have migrated through a micropore filter are recovered and counted electronically yielding a precise, objective result. Coefficients of variation are approximately 6%.

Chemotaxis, Leukocyte↗
PubMed1986

Prediction and prevention of relapse of acute lymphoblastic leukaemia after bone marrow transplantation.

Results of bone marrow transplantation (BMT) in 63 adults and children with ALL transplanted in the 5-year period 1979-83 were analysed. Twenty-one patients (33%) relapsed, 25% of the group died in relapse and 19% died from complications of BMT. The actuarial disease-free survival at 6 years was 38%. Relapse after BMT could be predicted by standard prognostic diagnostic features such as age, sex, cell type and presenting blast cell count. Patients transplanted in first remission selected for their poor prognosis had a lower relapse risk than a similar group of poor prognosis patients transplanted in second or subsequent remission (P less than 0.05). Relapse following second and subsequent remission BMT was predicted by a score based on standard prognostic features or by the pace of the disease: patients with an interval of less than 2 years between diagnosis and first relapse having a 15% actuarial disease-free survival, compared with 81% for patients with an interval greater than 2 years (P less than 0.001). These results emphasize that ALL is a heterogeneous disease and establishes the importance of determining relapse risk when selecting BMT and other treatment schedules for ALL patients.

Acute Disease↗
PubMed1986

Total and allergen-specific IgE in relation to allergic response pattern following bone marrow transplantation.

Total and allergen-specific serum IgE were measured in relation to allergic response pattern before and after bone marrow transplant (BMT) in seven sibling donor/recipient pairs. Two non-atopic recipients developed persistently raised total serum IgE levels but no apparent allergic response after BMT from non-atopic donors; three non-atopic recipients showed raised total serum IgE after BMT, with allergen-specific IgE to the same allergens as their respective atopic donors. A penicillin-tolerant recipient showed clinical sensitivity and specific IgE to penicillin after BMT from a penicillin-sensitive donor, but with this case both donor and recipient showed raised serum IgE levels. One atopic recipient showed decreased total IgE after BMT from a mildly atopic donor. These allergic response patterns could occur as a result of repopulation in the recipient with IgE-specific T lymphocytes having similar regulatory influences as in the donor. The pattern of acquired responses would also be consistent with reconstitution by primed B lymphocytes of donor origin.

Adolescent↗
PubMed1986

Engraftment rates related to busulphan and cyclophosphamide dosages for displacement bone marrow transplants in fifty children.

The use of busulphan and cyclophosphamide permitted engraftment in 44 of 49 children receiving 'displacement' bone marrow transplants. Three patients who received T-cell-depleted marrow cells from HLA-haploidentical donors failed to engraft and other graft failures were due to inadequate induction dosage. Our standard schedule comprises busulphan 80 mg/m2/day x 4 days (adjusted if necessary to a minimum of 4 mg/kg/day or a maximum of 5 mg/kg/day) followed by cyclophosphamide 2 g/m2/day x 4 days but reduced so as not to exceed 75 mg/kg/day, a maximum dose preferred for patients with full marrows (e.g. those with thalassaemia major). Of 21 recipients of mixed lymphocyte culture (MLC)-negative donor marrow cells with full engraftment at 100 days, there were three late rejections. Of patients transplanted with marrow from MLC-positive donors, one had late rejection after cyclosporin A toxicity had necessitated withdrawal of the drug at day + 146 but six other patients, whose cyclosporin A was stopped routinely 1 year, remain well with full grafts. Ten patients died as a result of graft-versus-host disease. We are therefore exploring new approaches to T-cell depletion and storing autologous marrow for use in the event of graft failure. If necessary, a second transplant with busulphan and cyclophosphamide is best performed at 3 months after full recovery of the host. We conclude that elective transplants can be performed successfully in children with normal immune function without the need for irradiation.

Bone Marrow↗
PubMed1986

Busulphan and cyclophosphamide cause little early toxicity during displacement bone marrow transplantation in fifty children.

Fifty children were induced with busulphan and cyclophosphamide before bone marrow transplantation. Our standard dose of cyclophosphamide was 2 g/m2 daily for 4 days, but this dosage was reduced if necessary so as not to exceed 75 mg/kg/day. A basal pulse rate that increased by more than 20 beats/min or a reduction in ECG voltage were indications for stopping cyclophosphamide. As a consequence, the fourth dose of cyclophosphamide was omitted for four children. One child died of cardiac arrest related to cyclophosphamide. We used busulphan at a dosage of 4 mg/kg/day for 4 days; neither 'busulphan lung' nor veno-occlusive disease occurred in any patient. The use of busulphan and cyclophosphamide did not guarantee freedom from interstitial pneumonitis, but this seemed to be related rather to the nature of prior treatment and the cytomegalovirus antibody status of the patient. Thus, we have developed a safe chemotherapy schedule for transplantation that avoids the need for radiotherapy and can, if necessary, be repeated after a 3-month interval.

Adolescent↗
PubMed1986

Cryoproteins.

Proteins producing phenomena after exposure to the cold are reviewed but concentrating mainly on those that can produce aggregates within the laboratory. From three large series the frequencies were I. Mixed Cryoglobulins (polyclonal 50 p. 100, monoclonal 18 p. 100); II. Monoclonal Cryoglobulin (25 p. 100); III. Cryofibrinogen (3 p. 100) and IV. Cold Agglutinins (polyclonal 2 p. 100, monoclonal 2 p. 100). Mixed cryoglobulins present with any of the features of immune complex disease, but with the onset of renal involvement, over 50 p. 100 of the patients are dead within 5 years. Monoclonal cryoglobulins present with flat lesions in dependent areas, most reflecting an underlying or impending malignant B-cell neoplasm. Cryofibrinogen, missed in heparinised samples, is associated with thrombophlebitis migrans and sometimes underlying cancer, especially of the pancreas. Cold agglutinins cause Raynaud's phenomenon and haemolytic anaemia and the blood must be centrifuged at 37 degrees C. Treatments are discussed and are certainly encouraging in about one-third of the patients.

Anemia, Hemolytic, Autoimmune↗
PubMed1985

Chylous effusions due to neuroblastoma resolved by intrapleural chlorambucil coupled to father's antibodies.

A 2-year-old boy presented with a stage IV neuroblastoma and, despite surgical reduction of the tumor mass followed by chemotherapy and radiotherapy, he developed bilateral chylous pleural effusions. These proved resistant to traditional methods of treatment but were resolved with minimal discomfort to the child by intrapleural injections of chlorambucil chemically bound to antibodies raised by immunizing his father with irradiated tumor cells.

Antibodies, Neoplasm↗
PubMed1985

[Bone marrow transplantation in the therapy of genetic diseases].

The technique of bone marrow transplantation (BMT) is now well established. Of now over 90 inborn errors of metabolism at least 45 have been treated by BMT. Among these some 35 have been proven to be curable by this procedure. The present paper reviews the respective literature and considers in particular the pertinent experiences of the Westminster Bone Marrow Transplantation Team.

Bone Marrow Transplantation↗
PubMed1985

Immunodeficiencies better treated by transplantation.

The correction of immunodeficiency requires T-cells, B-cells and antigen-presenting cells, all cooperating with each other in a balanced manner, and able to protect the tissues of the host from intracellular viral infections. Full B-cell function may require more than one genetic haplotype, and has only been achieved between host and donor cells when these are very well matched. Otherwise it has been necessary for the donor T- and B-cells to displace the host B-cells. In infants, displacement is better achieved using Busulphan rather than irradiation, (which also impairs the tolerising influence of the host thymus). Full correction has been achieved in 4 kinds of lymphopaenic SCID (+/- reticular dysgenesis or cartilage-hair dysplasia) without induction. For 16 other errors of lymphocyte function, displacement induction is preferred to ensure donor T-B-cell cooperation, although Cyclophosphamide alone has worked for matched sibling donors. For 9 other defects all expressed in phagocytes, which nevertheless occupy bone marrow space, displacement induction is essential. Elective transplants into fit hosts (e.g. no bronchiectasis) from matched sibling donors enabled 74 of 75 patients to leave hospital alive and well, with only 1 fatal acute GvHD. Currently, experienced teams can therefore consider another 20 diseases which might be better treated by bone marrow transplantation from matched siblings. In contrast, emergency transplants into unfit recipients produce only 60% survival. Transplants from donors sharing one genetic haplotype have reached 50% survival and there is room for improvement, but they are preferred to the use of unrelated donors or foetal tissues.

B-Lymphocytes↗