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Biomedical subjects

D L Mollin

Publications and source records attributed to D L Mollin.

At least 19 recordsLinked to original sources
PubMed1986

Megaloblastic anaemia due to vitamin B12 deficiency caused by small intestinal bacterial overgrowth: possible role of vitamin B12 analogues.

Megaloblastic anaemia due to bacterial overgrowth of the small intestine is due to vitamin B12 malabsorption. This report describes a patient with bacterial overgrowth of the small intestine who had megaloblastic anaemia and malabsorption of vitamin B12, but persistently normal levels of serum vitamin B12 and normal serum and red cell folate levels. However, there was evidence of vitamin B12 deficiency as shown by an abnormal deoxyuridine suppression test and by the response to treatment with physiological doses of vitamin B12. A relative increase in biologically inactive vitamin B12 analogues may be the explanation for the normal vitamin B12 level in this patient.

Aged↗
PubMed1985

Absent ileal uptake of IF-bound vitamin B12 in vivo in the Imerslund-Grasbeck syndrome (familial vitamin B12 malabsorption with proteinuria).

A Syrian family is described with three children who had inherited selective vitamin B12 malabsorption associated with proteinuria. (Imerslund-Grasbeck syndrome). Although inherited the defect was apparently not present at birth. A third child had less severe vitamin B12 malabsorption, was not vitamin B12 deficient and had no proteinuria. Studies on two of the affected children with subcellular fractionation of the uptake of radioactive vitamin B12 by ileal tissue in vivo indicate a defect in the ileal receptors for IF-bound vitamin B12. These findings are different from the single in vitro experiment on a patient with this condition that has been previously reported.

Adolescent↗
PubMed1985

Investigations into the effect of nitrous oxide anaesthesia on folate metabolism in patients receiving intensive care.

Anaesthesia with nitrous oxide inactivates vitamin B12 and impairs DNA synthesis in bone marrow cells. The secondary development of folate deficiency may prolong the recovery from these abnormalities in some seriously ill patients. This was investigated, using the deoxyuridine (dU) suppression test, in 48 patients admitted to an Intensive Care Unit (ICU). On admission to the ICU, following nitrous oxide anaesthesia, the pattern of correction of the abnormal dU-suppression tests was typical of that seen in vitamin B12 deficiency; 3 days later the pattern had changed to that usually seen in folate deficiency. During the same period the serum folate levels fell to subnormal values. Further evidence for the development of folate deficiency was provided by treatment with physiological amounts of folic acid which accelerated the recovery of the bone marrow abnormalities present after nitrous oxide anaesthesia. Urinary folate excretion was measured by radioassay, and increased following anaesthesia with nitrous oxide, however, this was insufficient by itself to explain the development of folate deficiency.

Adolescent↗
PubMed1982

Incidence and pathogenesis of acute megaloblastic bone-marrow change in patients receiving intensive care.

The incidence and pathogenesis of acute megaloblastic bone-marrow change and of abnormalities in DNA synthesis, as assessed with the deoxyuridine(dU) suppression test, have been investigated in a prospective study of 70 seriously ill patients admitted to an intensive-care unit. On admission megaloblastic bone-marrow change was present in 22 patients, 18 of whom had been anaesthetised with nitrous oxide for 2-6 h during surgical procedures before admission. 16 of these 18 patients died, compared with 7 of 22 patients in whom haemopoiesis remained normoblastic despite receiving equivalent amounts of nitrous oxide. An abnormal dU-suppression test developed only in patients who had received nitrous oxide; on admission an abnormal dU-suppression test was found in 39 of the 42 patients tested who had been exposed to the anaesthetic. The abnormality produced in the dU-suppression test by nitrous oxide in patients admitted to the intensive-care unit was more severe and recovery was slower than the abnormality seen in patients undergoing cardiac-bypass surgery. During the recovery period from the effects of nitrous oxide the pattern of correction of the dU-suppression test changed from that of vitamin-B12 deficiency to folate deficiency.

Adolescent↗
PubMed1982

Recurrent thrombocytopenia, erythroid hypoplasia and sideroblastic anaemia associated with hypothermia.

A distinct and previously undescribed haematological picture was noted in three patients with hypothermia. During hypothermia there was anaemia with reduced normoblastic erythropoiesis, marked sideroblastic change and thrombocytopenia in the presence of a normal number of megakaryocytes. In two patients as the body temperature returned to normal these changes were slowly reversed. Evidence both from observations in patients and from animal experiments is given why the haematological changes are due to the hypothermia.

Adult↗
PubMed1981

Severe megaloblastic bone marrow change associated with unsuspected mild vitamin B12 deficiency.

Two patients are reported who developed peripheral blood abnormalities and marked megaloblastic bone marrow change within eleven days of cardiac bypass surgery. The patients were shown to have unsuspected mild vitamin B12 deficiency due to Addisonian pernicious anaemia. The megaloblastic changes were presumed to be precipitated by the increased demand for erythrocytes and platelets after surgery.

Anemia, Pernicious↗
PubMed1980

Hydrolysis of pyridoxal-5'-phosphate in plasma in conditions with raised alkaline phosphate.

Hydrolysis of pyridoxal phosphate in plasma was demonstrated in patients with liver disease and other conditions with raised alkaline phosphatase, and this usually closely paralleled the alkaline phosphatase level, whether of liver or bone origin. The endogenous plasma pyridoxal phosphate was inversely related to the alkaline phosphatase, and plasma hydrolysis of pyridoxal phosphate may at least in part be responsible. Very large doses of vitamin B6 may be necessary to compensate for this hydrolysis.

Alkaline Phosphatase↗
PubMed1980

Interlaboratory comparison of serum vitamin B12 assay.

The results have been compared of microbiological and radioisotope dilution (RID) assay of serum vitamin B12 by participants in national interlaboratory trials in Britain. There was wide variation between the individual participants, especially marked in the L. leichmannii microbiological assay and in the RID methods, whereas excellent correlation, reproducibility, and recovery were obtained in reference laboratories by microbiological assay with both E. gracilis and L. leichmannii. In general, RID gave higher results than microbiological assay. The need for suitable reference sera is emphasised.

Biological Assay↗
PubMed1979

Inherited lack of transcobalamin II in serum and megaloblastic anaemia: a further patient.

We have studied a patient, unrelated to the patients previously described, with inherited lack of the vitamin B12 binding protein Transcobalamin II. Severe haematological abnormalities were found within a few weeks of birth and responded to treatment with both vitamin B12 and folic acid. He was maintained in partial remission with such treatment until adolescence, except for a time in early childhood when folic acid alone was given and he suffered severe neurological deterioration. A the age of 18 years he was admitted to hospital because of convulsions; the deoxyuridine suppression test showed intracellular deficiency of B12 despite a normal serum B12 and normal haemoglobin concentration. His serum failed to promote the uptake of radioactive B12 by bone marrow cells, and analysis of serum B12 binding proteins demonstrated the lack of Transcobalamin II. Treatment with injections of 1000 micrograms of B12 three times weekly corrected the abnormality shown in the deoxyuridine suppression test; following this treatment, together with changes in anticonvulsive therapy, he remains healthy without occurrence of further convulsions, and is haematologically normal.

Adult↗
PubMed1979

Abnormal red-cell metabolism of pyridoxine associated with beta-thalassaemia.

Red-cell conversion of pyridoxine to pyridoxal phosphate was studied in control subjects, and patients with heterozygous and homozygous beta-thalassaemia. In 7% of control subjects the rate of pyridoxine conversion was well below the range found in the other control subjects (5.0-8.6%, mean 6.5%/g Hb x 10(-2)) but in heterozygous beta-thalassaemia was below that range in 63% of the patients. The conversion rate was also slow or borderline in the majority of patients with severe transfusion-dependent homozygous beta-thalassaemia, in spite of the presence of some donor cells; but was normal, or fast as in other anaemias, in all but one patient with mild homozygous thalassaemia. There was a much higher incidence of a slow conversion rate in the parents of the severe homozygotes than in parents of the mild homozygotes, illustrating the familial pattern. This supports our view that the red-cell conversion rate of pyridoxine is an inherited characteristic, independent of thalassaemia. The cause of a reduced rate of pyridoxine conversion was investigated. The increase to a normal rate following riboflavin ingestion suggests a defect in the activity of the flavin mononucleotide (FMN)-dependent pyridoxine phosphate oxidase.

Adenosine Triphosphate↗
PubMed1979

Family studies of red-cell metabolism of pyridoxine in beta-thalassaemia.

Red-cell conversion of pyridoxine to pyridoxal phosphate was measured in 12 families with thalassaemia and 2 normal families. A strong familial pattern was demonstrated and the evidence suggested that the rate of red-cell conversion of pyridoxine is an independently inherited characteristic.

Erythrocytes↗
PubMed1978

Megaloblastic haemopoiesis in patients receiving nitrous oxide.

In a prospective study the incidence of megaloblastic change after ventilation with nitrous oxide for periods of up to 24 h has been determined and the cause of the altered D.N.A. synthesis studied with the deoxyuridine (dU) suppression test in 22 patients undergoing cardiac bypass surgery. 8 patients who received nitrous oxide and oxygen for 24 h had megaloblastic bone-marrow aspirates and abnormal dU suppression tests at the end of ventilation. 5 patients who received no nitrous oxide had normoblastic aspirates and normal dU suppression test. Of the remaining 9 patients, who received nitrous oxide during the operation only, 3 had abnormal dU suppression tests at 24 h. The abnormality revealed by the dU suppression tests was identical with that found in vitamin-B12 deficiency, but the patients' serum-B12 concentrations were normal. These results suggest that nitrous oxide interferes with the function of vitamin B12. Nitrous oxide oxidises vitamin B12 in vitro, and probably also in vivo when premixed 50% nitrous oxide and 50% oxygen mixture ('Entonox') is given.

Acute Disease↗
PubMed1978

Measurement of ferritin in serum by radioimmunoassay.

A method for the measurement of circulating ferritin concentrations by direct radioimmunoassay is presented. The method described is simple to operate, precise, and sensitive and is suitable for the routine diagnostic measurement of ferritin in either plasma or serum.

Bone Marrow↗
PubMed1977

A radioisotope dilution assay for unlabelled vitamin B12-intrinsic factor complex employing the binding intrinsic factor antibody: probable evidence for two types of binding antibody.

A new radioisotope dilution assay for vitamin B12-intrinsic factor complex is described. The method is based on the use of the binding type intrinsic factor antibody (the binding reagent), which when combined with the intrinsic factor-vitamin B12 complex (labelled ligand), is quantitatively adsorbed onto zirconium phosphate gel at pH 6.25. The new assay has been shown to provide a measure of intrinsic factor comparable with other intrinsic factor assays, but it has the important advantage of being able to measure the unlabelled vitamin B12-intrinsic factor complex (unlabelled ligand), and will, therefore, be valuable in the study of physiological events in the gastrointestinal tract. During the study, it was found that there is some evidence for a least two types of binding intrinsic factor antibody: One which combines preferentially with the intrinsic factor-vitamin B12 complex and one which combines equally well with this complex or with free intrinsic factor.

Antibodies↗