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Biomedical subjects

E J Fitzsimons

Publications and source records attributed to E J Fitzsimons.

At least 37 records · Page 2Linked to original sources
PubMed1990

The porphyrias.

The porphyrias are a group of metabolic disorders arising from defects in the haem biosynthetic pathway. Most forms are inherited as Mendelian autosomal dominant characters, but some are recessive and others acquired. There is a linked group of diseases, which are not porphyrias, but have in common alterations of haem biosynthesis. The haem biosynthetic pathway is now well understood and the molecular biology of its function and dysfunction in the porphyrias is currently an area of major investigation. The acute porphyrias are of most importance since attacks of these may be life-threatening. A variety of factors may precipitate these attacks including various drugs, alcohol, strict dieting or fasting and hormonal fluctuations. The non-acute porphyrias are largely dermatological conditions, which present clinically as cutaneous photosensitivity. The dermatological changes are brought about by the photosensitizing properties of circulating porphyrins. On the basis of this photoactivity, porphyrins are now being used, therapeutically, in the treatment of cancer.

Acute Disease↗
PubMed1990

The INR--a help or a hindrance to warfarin dosage?

We have examined the INR values of 128 warfarin patients obtained by four different techniques in common use in Scotland namely venous and capillary. Thrombotest and venous and capillary Prothrombin Time (PT). The PT INRs were carried out using Manchester Reagent thromboplastin. Discrepant INR values were obtained. The mean Manchester venous INR values were lower than those obtained by the other three methods (p less than 0.0001). This suggests that patient's dosed by reference to Manchester venous INR are liable to receive more warfarin than those dosed by the other methods.

Blood Coagulation Tests↗
PubMed1989

Discrepant INR values: a comparison between Manchester and Thrombotest reagents using capillary and venous samples.

The International Sensitivity Index (ISI) for different thromboplastin reagents is obtained by calibration against WHO reference preparations. It is hoped that calculation of the International Normalized Ratio (INR) from the ISI will permit accuracy and conformity in reporting laboratory assays of warfarin effect even across a range of different techniques. We have examined the INR values of 128 warfarin patients obtained by four different techniques in common use, namely venous and capillary Thrombotest and venous and capillary Manchester reagent. Discrepant INR values were obtained. The mean Manchester venous INR values were lower than those obtained by the other three methods (P less than 0.0001). This suggests that patients dosed by reference to Manchester venous INR are liable to receive more warfarin than those dosed by the other methods.

Animals↗
PubMed1988

5-Aminolaevulinic acid synthase activity in developing human erythroblasts.

5-Aminolaevulinic acid (ALA) synthase activity was measured in highly purified preparations of age-matched human erythroblasts. Enzyme activity in immature normoblasts was four-fold higher than that found in late orthochromatic normoblasts. ALA synthase activity in the immature erythroblasts in primary acquired sideroblastic anaemia (PASA) was reduced and remained unchanged during further erythroid differentiation. The pattern of erythroblast ALA synthase activity in two patients with congenital dyserythropoietic anaemia (CDA) and in one patient with beta-thalassaemia intermedia was similar to that found in PASA. This study has clearly demonstrated reduced erythroblast ALA synthase activity in PASA but has also found reduced enzyme activity in conditions in which ring sideroblasts are not prominent. This would suggest that haem synthesis is abnormal in PASA but that reduced erythroblast ALA synthase activity does not inevitably lead to ring sideroblast formation.

5-Aminolevulinate Synthetase↗
PubMed1988

Serum copper concentration as an index of lung injury in rats exposed to hemithorax irradiation.

Serum copper concentration was evaluated as an index of lung injury (monitored by lung prostacyclin production) with respect to the effects of time, dose, dose fractionation, and penicillamine dose modification in rats irradiated to the right hemithorax. Both lung PGI2 production and serum Cu concentration increased with increasing 60Co gamma-ray dose in animals sacrificed 2 or 6 months postirradiation, and the highest values for both responses were observed at the latter autopsy time. At 2 months postirradiation, the elevations in lung PGI2 production and serum Cu concentration also were spared similarly when total radiation doses were delivered in five equal daily fractions as compared to single doses. Finally, the ability of D-penicillamine to ameliorate the radiation-induced hyperproduction of PGI2 by rat lung was accompanied by an attenuation of the dose-dependent increase in serum Cu concentration at 2 months postirradiation in the drug-treated rats. In contrast, serum iron concentration was independent of time, dose, and penicillamine. At 2 months after irradiation, there also was a dose-dependent increase in lung hydroxyproline (collagen) content, the magnitude of which correlated closely with serum copper concentration in individual animals. Thus serum copper concentration is an accurate and minimally invasive index of lung injury in rats irradiated to the hemithorax and can predict lung hydroxyproline (collagen) content in individual irradiated rats.

Animals↗
PubMed1987

The isolation of cross-reactive monoclonal antibodies: hybridomas to streptococcal antigens cross-reactive with mammalian basement membrane.

Based upon the assumption that post-streptococcal sequelae are the result of cross-reactive antibodies, hybridomas were prepared from the spleens of mice immunized with Group A type 12 streptococcal cell membranes (SCM) specifically to screen for such cross-reactive antibodies. One fusion produced a cell population displaying antibodies reactive to both SCM and glomerular basement membrane (GBM) antigens as demonstrated by ELISA technique. Ascites produced by this cell population also showed reactivity to lung basement membrane (LBM). Limiting dilution procedures have produced 15 monoclonal hybrids with both anti-SCM and anti-GBM activity. Confirmation of the cross-reactive and monoclonal nature of the antibody was accomplished by both direct and indirect competitive ELISA. These observations have established that unique cross-reactive antibody-secreting hybrid cells with reactivity to both SCM and basement membrane (BM) antigens can be isolated by standard cloning procedures.

Animals↗
PubMed1986

Measurement of 5-aminolevulinic acid synthase activity in whole and fractionated human bone marrow: effect of myeloid cell lysis by monoclonal antibody.

A sensitive radiochemical assay for the measurement of bone marrow and erythroblast 5-aminolevulinic acid (ALA) synthase (EC 2.3.1.37) was developed and optimized with respect to sample preparation and reagent concentration. Succinylacetone (4,6-dioxoheptanoic acid) was used to prevent ALA utilization during the incubation period. Sample purification on a Sep-Pak cartridge (Waters Associates) followed by reverse-phase high-performance liquid chromatography (HPLC) allowed rapid isolation of pure ALA-pyrrole, free from radioactive succinate and other contaminants. ALA synthase activity was measured in unfractionated bone marrow and in samples from which myeloid cells had been removed by monoclonal antibody-mediated cell lysis. Myeloid-derived ALA synthase was calculated and found to contribute approximately half of the total unfractionated marrow enzyme activity. This suggests that results from previous studies using unfractionated bone marrow which have assumed that myeloid cells are an insignificant source of ALA synthase require reappraisal.

5-Aminolevulinate Synthetase↗
PubMed1984

Acute hypoferremia following cardiac surgery.

Serum iron concentration, temperature, white blood count, and weight were reviewed throughout hospitalization in 13 patients who underwent open-heart surgery for valvular replacement and 43 who required coronary artery bypass grafting. Serum iron concentration climbed from an admission average of 91.1 micrograms/100 ml +/- 44.0 to 124.3 micrograms/ml +/- 40 within 12 hours of surgery and then rapidly dropped to 29.0 micrograms/100 ml +/- 20.1 within 18 hours of surgery. Serum iron levels remained less than one half of admission values throughout hospitalization (2 weeks). Temperature increased from 98.6 F +/- 0.5 before surgery to 101.1 F +/- the night of surgery, remaining mildly elevated until 14 days following surgery. White blood count jumped from admission levels of 7.1 X 10(3) +/- 1.8 to 15.2 X 10(3) +/- 5.8 within 6 hours of operation. Preoperative levels were again reached 5 days following operation. Patient weights averaged 73.9 kg +/- 14.6 on admission increasing to 78.6 kg +/- 10.4 on the day following surgery. Only hypoferremia persisted beyond discharge into the anabolic phase of recovery. Stress-induced hypoferremia following operation runs a different time course than fewer, leukocytosis, or weight gain and thus must be mediated by a different mechanism.

Body Temperature↗
PubMed1984

Values for some serum analytes in high-risk infants, two days postpartum.

Using a continuous-flow (Technicon SMAC) analyzer, we measured the concentration of 20 analytes in capillary blood sera from 149 neonates in an intensive-care unit. Included were term and pre-term babies, both groups with and without asphyxia. The values obtained, especially for those enzymes and analytes that are related to renal function, offer baseline data against which the effect of therapeutic and physiological changes can be evaluated.

Apgar Score↗
PubMed1983

Changes in serum iron and leukocyte count associated with open-heart surgery.

Rapid and pronounced changes in serum iron concentration and leukocyte count in association with open-heart surgery were observed in each of 58 patients. We examined the temporal aspects of these alterations. An initial increase in Fe concentration from a mean of 0.94 mg/L before surgery to 1.20 mg/L was observed within 6 h of the start of surgery. Decreased Fe concentration, a phenomenon previously associated with physiologically stressful events, became apparent 12 h after surgery, by which time the mean Fe concentration had declined to 0.26 mg/L. An increase in the mean leukocyte count, from 7.1 to 15.2 X 1000/mm3 was observed within 6 h of the start of surgery. An increase in ferritin concentration in serum was concurrent with decreased iron concentration.

Cardiac Surgical Procedures↗
PubMed1980

Rapid drop in serum iron concentration in myocardial infarction.

Two hundred one patients admitted to the Coronary Care Unit had repeated serum iron determinations. There was a rapid (within 24 to 48 hours), pronounced decrease (mean = 64%) of the serum iron concentration in 87% of the 112 patients who had a diagnosis of acute myocardial infarction. Seventy-nine per cent of the 89 patients who did not have an acute myocardial infarction did not have a drop in serum iron concentration. This suggests an association between myocardial infarction and rapid decrease in serum iron concentration.

Creatine Kinase↗