Tissue deficiency of vitamin B12 and folate results in an increase in serum homocysteine (sHcy). We have measured sHcy in patients with reduced serum vitamin B12 and/or red cell folate (RCF) to determine its usefulness as a discriminant for the diagnostic interpretation of reduced vitamin levels. Of 3846 patients who had serum vitamin B12 and RCF assayed, 335 (9%) had reduced vitamin levels. Multivariate analysis showed a significant association between sHcy and serum creatinine (p = 0.0001), positive intrinsic factor (IF) antibody or neutrophil hypersegmentation (NHS) (p = 0.001), increased MCV (p = 0.014) and low RCF (p = 0.025) but no relationship with the level of serum vitamin B12 or haemoglobin. After censoring the patients with renal impairment (n = 54), the distribution of the remaining 72 patients with elevated sHcy was 37/151 (25%) with low serum vitamin B12 with or without low RCF and 35/130 (27%) with low RCF alone. sHcy correctly identified response to vitamin therapy in 33/35 (94%) patients who had adequate parameters to assess response. The positive predictive values of IF antibody/NHS, macrocytosis and/or low RCF for elevated sHcy were 100% and 34% respectively. Twenty-four percent of patients with a low serum vitamin B12 and elevated sHcy had no abnormal haematologic parameters as determined by the routine laboratory staff. These data suggest that the usefulness of measuring sHcy in a routine diagnostic setting is limited and a careful review of the peripheral blood for macrocytosis and NHS plus determination of RCF may be a more cost-effective process than sHcy assay in most instances to determine the presence of tissue deficiency.

Adult↗

PubMed1993

Preoperative autologous blood donation. Linkage of the public and private hospital sectors.

OBJECTIVE: To evaluate the safety and efficacy of a preoperative autologous blood donation (PABD) program with liberal patient exclusion criteria. DESIGN: Prospective patient accrual from September 1990 to May 1992. SETTING: A PABD program in a public tertiary care hospital linked with a specialist orthopaedic practice in a private hospital. PATIENTS: One hundred and twenty patients consecutively scheduled for orthopaedic surgery were referred for PABD. There were 77 women (median age, 63 years) and 43 men (median age, 62 years). One-third of patients were 70 or more years old. Coexistent medical disease, mainly cardiovascular, was present in 46% of patients and 3% were excluded because of coexisting morbidity. Total hip or total knee replacement was performed in a private hospital with intraoperative or postoperative blood salvage in 37% of the patients. OUTCOME MEASURES: Adverse effects of PABD, autologous blood collected and used and homologous blood transfused. RESULTS: One hundred and sixteen patients donated 267 units of autologous blood. In 70 patients undergoing total hip replacement, 78% donated three and 20% donated two units, with 95% of autologous blood being used. In 38 patients undergoing total knee replacement, 42% donated two units and 55% donated one unit, with 87% of autologous blood being transfused. Seventy-eight per cent of all patients only received autologous blood. In the remaining patients, homologous blood use was confined to two units or less in 80%. Hypotensive episodes associated with phlebotomy occurred in 3% of patients, and 13% of patients had preoperative haemoglobin levels ranging from 85-100 g/L without adverse clinical effects. CONCLUSION: A hospital-based PABD program with less strict patient exclusion criteria does not prejudice the clinical status of the donors. Its linkage to private hospitals can significantly reduce the use of homologous blood in selected elective surgery.

Adult↗

PubMed1993

Common expression of the multidrug resistance marker P-glycoprotein in B-cell chronic lymphocytic leukaemia and correlation with in vitro drug resistance.

The expression of P-glycoprotein (Pgp), which is associated with multidrug resistance (MDR), was investigated in 20 B-cell chronic lymphocytic leukaemia (B-CLL) patients by flow cytometry using two Pgp-specific monoclonal antibodies (mAb), MRK-16 which recognizes an extracellular epitope, and JSB-1 which recognizes an intracellular epitope. Sixteen (80%) patients were positive with MRK-16 whereas all patients were positive with JSB-1. The proportion of Pgp-positive lymphocytes from each patient sample varied from 2-94% for MRK-16 and 20-93% for JSB-1. There was no correlation between the level of positivity and disease stage or treatment history. In vitro drug resistance to vincristine (VCR) and doxorubicin (DOX) was determined by the colorimetric MTT assay. All patients were resistant to one or both drugs being consistent with the expression of Pgp. There was no correlation between the level of resistance and disease stage or drug treatment. We investigated the expression of Pgp in the normal counterpart of the B-CLL cells, CD5+CD19+ B-lymphocytes. A minor subpopulation (3%) of CD5+CD19+ lymphocytes isolated from normal controls expressed Pgp suggesting that these cells may be the potential precursors to the B-CLL cell. We conclude that Pgp expression and drug resistance are inherent characteristics of the B-CLL lymphocyte.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1991

Treatment of acute promyelocytic leukaemia relapsing after allogeneic bone marrow transplantation with all-trans-retinoic acid: suppression of the leukaemic clone.

We describe the clinical experience of a male patient with acute promyelocytic leukaemia, relapsing after sex-mismatched allogeneic bone marrow transplantation and treated with all-trans-retinoic acid. Resolution of the coagulopathy was observed by day 7 of therapy. A complete remission was achieved by day 47 after a period of pancytopenia, dysplastic myeloid maturation and bone marrow hypocellularity with necrosis and fibrosis. Serial cytogenetic analyses revealed a progressive loss of the male leukaemic clone [46XY,t(15;17)] and emergence of normal female (donor) cells [46XX] which became completely dominant with remission. Adverse effects of all-trans-retinoic acid included bone pain and a prominent leucocytosis requiring leukaphereses and hydroxyurea therapy. All-trans-retinoic acid can induce complete remission of recurrent acute promyelocytic leukaemia following bone marrow transplantation. The data suggest that remission is due to differentiation and suppression of the leukaemic clone while allowing repopulation of the marrow with non-malignant cells.

Adult↗

PubMed1991

Hematological, biochemical and bone scan findings in patients with marrow carcinoma.

The peripheral blood hematological and biochemical parameters in 60 patients with marrow involvement with carcinoma are described. In all patients the hematologic findings were of anemia (46%), thrombocytopenia (36%), leukocytosis (28%) and leukoerythroblastosis (22%). Elevated serum lactate dehydrogenase (sLDH) and alkaline phosphatase (sALP) occurred in 78% of patients and hypercalcemia in 28% and these abnormal biochemical parameters occurred more frequently with marrow fibrosis. In patients with small cell carcinoma of lung (SCCL) the sLDH was normal in 24% and sALP in 32% and abnormal hematological findings or a raised sLDH occurred more frequently with liver involvement. Bone scan was positive in 49% of patients and the hematological and biochemical parameters in these patients were similar to those of patients with a normal scan. Ten percent of patients with SCCL and marrow involvement had both a normal sLDH and bone scan.

Alkaline Phosphatase↗

PubMed1989

Red cell ferritin and iron overload in heterozygous beta-thalassemia.

Red cell ferritin was evaluated in 101 individuals with heterozygous beta-thalassemia to determine its clinical utility as an index for iron deficiency or overload in these subjects. The mean red cell ferritin for the total population was elevated threefold and showed a significant correlation with transferrin saturation, plasma ferritin, and HbA2 levels. Five of six subjects with reduced red cell ferritin had associated iron deficiency; a further five had iron deficiency and normal red cell ferritin. Normal red cell ferritin occurred in 51 subjects, and 44 had increased values. In the elevated red cell ferritin group, 21 individuals had associated normal plasma ferritin, and 23 had increased plasma ferritin. Only in the latter group was red cell ferritin significantly correlated with transferrin saturation and plasma ferritin. Ten individuals had a red cell ferritin greater than or equal to 150 attogram/cell, and liver biopsy performed in four showed grades II to IV iron overload. A clinical feature of subjects with both increased red cell and plasma ferritin levels was a high incidence of inappropriate iron administration. These findings suggest that red cell ferritin, particularly when combined with plasma ferritin, is a useful parameter for determining potential iron overload in individuals with heterozygous beta-thalassemia.

Adolescent↗