PubMed Health⌕ Search

Biomedical subjects

D R Norfolk

Publications and source records attributed to D R Norfolk.

At least 55 records · Page 3Linked to original sources

Cell surface expression of beta 2-microglobulin (beta 2m) correlates with stages of differentiation in B cell tumours.

Cell surface beta 2-microglobulin (beta 2m) densities of malignant B cells were determined by enzyme immunoassay in 97 cases of immunologically defined lymphoproliferative disease. Absolute beta 2m densities were found to depend on disease category with the lowest levels found on cells from chronic lymphocytic leukaemia (mean = 5.6 ng/10(6) cells, n = 27); atypical chronic lymphocytic leukaemia (mean = 5.9 ng/10(6) cells, n = 8); and prolymphocytoid chronic lymphocytic leukaemia variant (mean = 6.0 ng/10(6) cells, n = 16). beta 2m densities for B non-Hodgkin's lymphoma (n = 14) and B prolymphocytic leukaemia (n = 17) cases were 8.1 and 10.0 ng/10(6) cells, respectively, and the highest densities were found on cells from "late-B cell" tumours (mean = 14.3 ng/10(6) cells). Plasma cells from cases of Ig secreting tumours expressed unexpectedly low beta 2m densities (mean = 9.3 ng/10(6) cells; n = 6).

B-Lymphocytes↗

Changes in plasma beta 2 microglobulin concentrations after allogeneic bone marrow transplantation.

Plasma concentrations of beta 2 microglobulin (B2M), the light chain of the class I major histocompatibility complex, were measured serially in 26 patients undergoing allogeneic bone marrow transplantation (BMT). The concentrations fell after conditioning treatment, and recovered when the marrow was transplanted. Bacterial infection did not influence B2M concentration, but nine of 22 episodes of acute graft versus host disease were associated with raised concentrations. Increased plasma B2M concentrations were also a feature of eight episodes of chronic graft versus host disease, and these fell after treatment. Reactivation of herpes simplex, varicella zoster, or cytomegalovirus infections were also accompanied by raised B2M concentrations. Three patients with cytomegalovirus pneumonitis had high concentrations of plasma B2M, the rise starting between five and 22 days before onset of symptoms. Although it is non-specific, serial measurement of plasma B2M in patients undergoing BMT may be clinically useful in monitoring chronic graft versus host disease.

Adolescent↗

Serum enzyme concentrations in untreated acute myeloid leukaemia.

Serum concentrations of lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (HBD), phosphohexose isomerase (PHI), leucine aminopeptidase (LAP), beta-glucuronidase (beta-gluc) and angiotensin-converting enzyme (ACE), were measured in 107 cases of untreated acute myeloid leukaemia which were classified by morphological, immunological and cytochemical criteria. The results show that serum LDH was increased in most cases, irrespective of leukaemic subtype, serum PHI and LAP were significantly higher in monocytic variants and serum beta-gluc and ACE levels were generally within normal limits. In addition, significant (p less than 0.05) relationships were found between serum LDH, PHI, LAP and beta-gluc concentrations and the numbers of circulating leucocytes.

Glucose-6-Phosphate Isomerase↗

Changes in plasma fibronectin during donor apheresis and therapeutic plasma exchange.

Changes in plasma levels of the opsonic glycoprotein fibronectin were studied during machine apheresis in 32 healthy plasma donors and 18 patients undergoing a total of 86 therapeutic plasma exchanges. Donation of 500 ml of plasma at 3-monthly intervals produced a 10% immediate decrease in plasma fibronectin with no evidence of a long-term affect on levels of this protein. One plasma volume exchange with fibronectin-poor plasma protein fraction produced subnormal plasma fibronectin levels in 98% of post-exchange samples. Efficiency of exchange was significantly lower in patients with paraproteinaemia, probably reflecting increased plasma volume in such patients. Daily plasma exchange produced progressive depletion of plasma fibronectin (index of recovery 0.68) whereas levels were maintained close to the initial value with longer exchange intervals, except in the more severely ill patients. Reduction of plasma fibronectin by plasma exchange may increase susceptibility to infection and reduce the efficacy of this procedure when the object of exchange is to reverse reticuloendothelial blockade.

Adult↗

Changes in plasma fibronectin during allogeneic bone marrow transplantation.

Plasma fibronectin concentrations were measured serially in nine patients undergoing allogeneic bone marrow transplantation. Concentrations were reduced by conditioning treatment and episodes of bacterial infection. Acute graft versus host disease may exacerbate or prolong this process. Reduced plasma fibronectin concentrations impair the function of the mononuclear phagocyte system and the maintenance of capillary endothelial integrity and may thus contribute to the morbidity and mortality in patients undergoing bone marrow transplantation.

Adolescent↗

Evaluation of serum beta 2-microglobulin as a prognostic indicator in myelomatosis.

Serum beta 2-microglobulin (beta 2-m) is frequently increased in patients with myelomatosis. The possibility that it could provide a biochemical indicator of prognosis was tested in a group of 129 patients from 3 centres, all serum analyses being carried out in one laboratory by radioimmunoassay. A strong association between the pretreatment serum beta 2-m level and survival was demonstrated, the data for the 2 main subgroups being very similar. In further detailed analyses of 64 patients, serum beta 2-m proved to be a stronger indicator of prognosis than current "standard" clinical and laboratory data, including stage determined by the method of Durie and Salmon and the combination of haemoglobin level and blood urea. The association between serum beta 2-m and survival remained close after treatment as indicated by the findings at one year. The serum beta 2-m in myeloma reflects the tumour mass and also reduced glomerular filtration when renal failure supervenes. It is concluded that the serum beta 2-m is a powerful prognostic indicator in myelomatosis and of considerable value in the investigation of patients with the disease.

Beta-Globulins↗

Plasma fibronectin in myeloproliferative disorders and chronic granulocytic leukaemia.

A significant reduction of plasma fibronectin levels was found in polycythaemia vera and myelofibrosis, the lowest levels being found in patients with marked splenomegaly. Plasma fibronectin concentration was normal in essential thrombocythaemia, and only modest reduction was seen in chronic granulocytic leukaemia in either controlled chronic phase or blast cell crisis. In a patient with myelofibrosis, the plasma fibronectin rose from less than 100 mg/l to 177 mg/l after splenectomy. Possible explanations include increased consumption of plasma fibronectin in the expanded mononuclear phagocyte system present in the liver and spleen, reduced hepatic synthesis, and the clearance of circulating immune complexes. Low plasma fibronectin concentrations may increase susceptibility to infection.

Adult↗

Serum beta-2-microglobulin in disorders of myeloid proliferation.

Serum beta-2-microglobulin (beta 2-m) was measured on 182 samples from 98 patients with diseases characterized by proliferation of predominantly non-lymphoid marrow elements. Raised levels were found in myeloproliferative disorders, chronic granulocytic leukaemia, acute myeloid leukaemia and in many patients with myelodysplastic syndromes. The most striking elevation was seen in acute and chronic myelomonocytic leukaemia. These raised serum levels are probably derived from increased cell turnover, and it is suggested that cells of monocyte-macrophage series are particularly high producers of beta 2-m.

Anemia, Aplastic↗

Pernicious anaemia and hypogammaglobulinaemia in a patient with severe infantile kyphoscoliosis.

A 27-year-old man with severe infantile kyphoscoliosis suffered from recurrent respiratory tract infections during childhood and early adult life. He deteriorated and was found to have pernicious anaemia and common variable immunodeficiency with hypogammaglobulinaemia and impairment of cell-mediated immunity. Marked clinical improvement has followed the institution of effective gamma-globulin replacement.

Adult↗

Pulsed high dose oral prednisolone in relapsed or refractory multiple myeloma.

Seventeen unselected patients with relapsed or refractory multiple myeloma were treated with oral prednisolone 60 mg per m2 for five consecutive days with nine-day treatment-free intervals. Of the fourteen patients who completed at least six courses of treatment there were five good responses (Chronic Leukemia-Myeloma Task Force Criteria), five partial responses and four failures. Median survival (all seventeen patients) was between 19 and 20 months. Eight patients achieved plateau phase (median duration 9 months). Eleven patients showed improved performance status and four became free of transfusion support. The commonest side-effect was bacterial pulmonary infection. Peptic ulceration occurred in two patients despite prophylactic ranitidine. Other steroid-related side-effects were mild and well tolerated. This study provides further evidence for the efficacy of higher dose steroid regimens in relapsed or refractory myelomatosis and confirms that durable remissions may be achieved. Responders show a gratifying improvement in quality of life and are spared the many toxicities of combination cytotoxic chemotherapy. Further studies of high dose steroid regimens in first-line therapy, especially in patients with bone marrow suppression, are clearly merited.

Adult↗

Ifosfamide and mitoxantrone (I-M) in relapsed and refractory high grade non-Hodgkin's lymphoma and Hodgkin's disease.

Fifty-five patients, initially diagnosed as having advanced high grade non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) refractory to first-line treatment or in relapse, were treated with ifosfamide 6 g/m2, infused over 48 h, followed by mitoxantrone 12 mg/m2. The regimen repeated at three-weekly intervals. Of 32 patients with NHL evaluable for response, 10 (31 per cent) achieved complete remission and five partial remission, giving an overall response rate of 47 per cent. Two patients subsequently went on to bone marrow transplant (BMT)--one allogeneic and the other autologous. Of 17 patients with HD evaluable for response, six (35 per cent) achieved complete remission and six partial remission, giving an overall response rate of 71 per cent. Two of this group also went on to BMT (both autografts). The principal toxicity was neutropenia, though central nervous system changes were observed in 10 patients. Given the need to offer alternative treatment of patients in these categories, this combination (I-M) is clearly of value in relapsed patients especially where therapeutic options are limited because of previous multi-drug treatment.

Adolescent↗