Cardiac transplantation at Harefield Hospital.
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Biomedical subjects
Publications and source records attributed to C Reid.
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Urginea physodes (Jacq.) Bak., a species closely related to or possibly synonymous with U. pusilla, is described and its distribution given. Four bufadienolides were isolated from U. physodes and the approximated LD50 and cumulative effect of some of them determined in guinea pigs. The most toxic one proved to be mildly cumulative. Typical signs of acute cardiac glycoside poisoning, involving the locomotory, gastro-intestinal, respiratory and cardiac system, were seen in the field cases and/or were experimentally induced by the plant. Similar signs could also be induced by injecting the isolated bufadienolide, physodine A, to a sheep.
Ten patients with end-stage renal failure and anaemia (mean haemoglobin 6.1 g/dl, range 4.6-8.8 g/dl) on thrice-weekly haemodialysis were treated with human erythropoietin derived from recombinant DNA (rHuEPO). This was given as an intravenous bolus after each dialysis in rising doses within the range 3-192 IU/kg. All patients showed increases in reticulocyte numbers and haemoglobin concentration and after the first week of treatment none of the four previously transfusion-dependent patients needed further transfusions. In nine patients treated for 12 weeks haemoglobin rose to a mean of 10.3 g/dl, range 9.5 to 12.8 g/dl. Thereafter the dose of erythropoietin was adjusted to avoid a further rise in haemoglobin. During treatment one patient had an episode of hypertensive encephalopathy and two had clotting in their arteriovenous fistulas (complete in one). rHuEPO is an effective treatment for the anaemia of end-stage renal failure but longer-term observations are needed on the consequences of increasing the haematocrit.
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We assessed the diagnostic value of determinations of serum levels of immunoreactive erythropoietin in 90 patients referred for the investigation of a raised packed red-cell volume (hematocrit) and possible erythrocytosis (a red-cell volume greater than that predicted by weight, body-surface area, or both). The mean values for erythropoietin were 16 mIU per milliliter (range, 8 to 22) in patients with polycythemia rubra vera (n = 24), 30 mIU per milliliter (range, 14 to 123) in patients with secondary erythrocytosis (n = 12), 27 mIU per milliliter (range, 13 to greater than 400) in patients with erythrocytosis of unknown origin (n = 19), and 25 mIU per milliliter (range, 18 to 35) in normal controls (n = 25). The values in the patients with polycythemia rubra vera were lower than those in the other three groups (P less than 0.01, P less than 0.05, and P less than 0.0001, respectively). In subjects with an increased packed red-cell volume but without erythrocytosis (n = 35), the levels of serum erythropoietin were the same as those in normal controls. Among patients with erythrocytosis with an unknown cause, abnormally high serum erythropoietin levels were found in 3 of 19 subjects, and in 1 of these 3 the abnormality was intermittent. Thus, measurement of serum erythropoietin in a single sample may be misleading and may not have high discriminatory value in distinguishing between polycythemia rubra vera and secondary erythrocytosis. This assay is useful in identifying patients with secondary erythrocytosis who have inappropriate erythropoietin secretion.
Two cases of coexisting septic and crystalline joint disease are reported. In one patient polyarticular septic arthritis occurred simultaneously with gout and pseudogout. In a second patient septic arthritis preceded the appearance of calcium pyrophosphate dihydrate (CPPD) crystals in the joint fluid, supporting an earlier postulate that lysosomal enzymes released during sepsis lead to shedding of crystals from cartilage and synovium into the joint space. This sequence was demonstrated in a rat air pouch model of synovium, in which CPPD crystals embedded in facsimile synovial tissue were released after injection of pyogenic bacteria. Coexisting septic arthritis should always be considered when crystals are identified in inflamed joints, particularly in elderly patients with concurrent infections.
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Nineteen patients with chronic heart failure participated in a double blind crossover trial of captopril and prazosin--two drugs with differing neuroendocrine effects--to determine whether neuroendocrine changes could explain clinical and haemodynamic responses to treatment. Patients were assessed before and after acute and long term (four weeks') treatment with each drug given in random order. Sixteen patients completed the study. During captopril haemodynamic improvement was maintained by inhibition of the renin-angiotensin system. Breathlessness was relieved in 15 patients and exercise capacity increased. During prazosin a reduction in systemic vascular resistance was maintained, but plasma renin activity and aldosterone and noradrenaline concentrations increased, fluid retention developed, and clinical benefit did not occur. These results suggest that clinical and haemodynamic responses to long term vasodilator treatment for chronic heart failure are related to neuroendocrine changes. In patients with chronic heart failure inhibition of the renin-angiotensin system results in clinical benefit, whereas inhibition of the alpha adrenergic system does not.
Gout and classical rheumatoid arthritis rarely coexist. We report a patient with strong evidence for both these diseases. Possible reasons for the negative correlation between these diseases are summarised. One hypothesis suggests inhibition of surface activity of monosodium urate crystals (MSU) by binding of rheumatoid factor (RF). This was studied with a purified monoclonal rheumatoid factor (mRF) with specificity for IgG. The mRF bound preferentially to MSU coated with IgG in contrast with the IgM control. Inhibition of the neutrophil chemiluminescence (CL) response to IgG-coated MSU was observed at concentrations of mRF that had no effect on the CL response to uncoated crystals. Neutrophil activation was not altered by coating crystals with an IgM control at the same concentration. These data suggest that RF may bind to antigenic determinants on exposed Fc of adsorbed IgG and block the interaction of crystal-bound IgG with Fc receptors. Although crystal coating by RF may modify the expression of gouty arthritis, it is unlikely to be the sole explanation for the dissociation between gout and RA.
Paresis afflicted 85 out of a flock of 770 young Merino ewes kept on old wheat lands in the western Cape during a period of drought. Many of the paretic ewes died. The vegetation was sparse and was dominated by Trachyandra divaricata. At necropsy, yellowish-brown discoloration of the grey matter throughout the brain and spinal cord and mild brown discoloration of the liver, renal cortex and lymph nodes were consistently seen. Light microscopical examination revealed abundant, yellowish-brown pigment granules in the cytoplasm of most of the larger neurons. Similar pigment also occurred in some non-nervous tissues. Shrinkage and loss of a few randomly scattered axons were observed in the white matter of the spinal cord in 2 sheep. Histochemical and ultrastructural features of the pigment were consistent with those of lipofuscin. T. divaricata failed to reproduce the condition when dosed to a sheep, but the paresis and pigmentation shown to be caused by the closely related plant, T. laxa, are strikingly similar. Trachyandra poisoning appears to be the first documented example in farm animals of an acquired lipofuscin storage disease involving nervous and non-nervous tissues for which a specific plant has been causally implicated.
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A mesenteric mass, histologically characterized as giant lymph node hyperplasia was found in an 18-yr-old man with at least 11 yr of growth retardation and anemia. The anemia was characterized by iron deficiency from selective malabsorption of iron, and by features of the anemia of chronic disorders. In contrast with a previous report, no inhibitor of erythropoietin was found and there was no abnormality of erythropoietin secretion. Resection of the mass was followed by rapid correction of the anemia and catch-up growth. The mass had histologic features of the hyaline vascular and plasma cell types of Castleman's disease with multinucleate giant cells probably of macrophage origin. Immunologic studies of the mass showed that the B lymphocytes were polyclonal and the T lymphocyte helper/suppressor cell ratio was normal, suggesting that giant lymph node hyperplasia is a local inflammatory reaction.
While the hemodynamic effects of hydroxyethyl starch (HES) have been reported, the effect of this material upon extravascular lung water (EVLW) has not been investigated. Twenty mongrel dogs were subjected to both an oleic acid-induced lung injury and a 2-h period of hemorrhagic shock (MAP = 40 mm Hg). After reinfusion of shed blood, 5 dogs in each of 4 groups were given either 0.5 L of lactated Ringer's solution or 0.5 L of 5% albumin, 6% dextran 75, or 6% HES. Lactated Ringer's solution was then given in sufficient quantity to keep the wedge pressure (WP) at 12-15 mm Hg and PaO2, P(A-a)O2, cardiac index (CI) and oxygen delivery were determined. EVLW was measured by thermal-green dye double-indicator technique with an Edwards Lung Water Computer (American Edwards Laboratories, Santa Ana, CA). Mean baseline EVLW was 6.9 +/- 0.3 ml/kg. Mean EVLW rose to 11.5 +/- 1.9 ml/kg after oleic acid. One h after reinfusion, EVLW increased to 40.5 +/- 4 ml/kg in the dogs given only lactated Ringer's solution and to 39.5 +/- 1.5 ml/kg in the dextran group. EVLW was 25.5 +/- 3 ml/kg in the HES dogs, and 29.5 +/- 2 ml/kg in the group given albumin. Differences between albumin and lactated Ringer's solution and between the HES and lactated Ringer's groups were significant (p less than 0.02 and p less than 0.05). Measurements of oxygen, ventilation, CI, and oxygen delivery were not significantly different between the albumin and HES subjects.
We reviewed the M-mode and two-dimensional echocardiograms of 100 consecutive patients with rheumatic heart disease. All were subsequently studied by cardiac catheterization and angiography. In four patients, cardiac catheterization showed tricuspid stenosis (average mean diastolic gradient 6.2 mm Hg), which was confirmed during cardiac surgery. M-mode echocardiography showed a diminished EF slope in 12 patients (mean 26 mm/sec), including the four patients with tricuspid stenosis. Seven of the eight patients without tricuspid stenosis had significant pulmonary hypertension; the reasons for the diminished EF slope in the other patient could not be identified. Tricuspid stenosis was diagnosed in four patients from two-dimensional echocardiograms on the basis of diastolic doming and restricted leaflet motion of the tricuspid valve. These four patients were the same patients in whom tricuspid stenosis was diagnosed by cardiac catheterization. We conclude that two-dimensional echocardiography is useful in the diagnosis of tricuspid stenosis.
Transmission electron micrographs of unactivated platelets, adenosine diphosphate-induced platelet aggregates and thrombin-induced platelet clots, prepared using a tannic acid fixative/stain, reveal characteristic lamellar bodies. These lamellar bodies are seen more frequently in the clots. The lower limit of the dark band periodicity in the lamellar bodies is between 4 . 4 and 5 . 0 nm, and the layers are thought to be composed of phospholipid, probably phosphatidyl choline. Analogies are drawn between the lamellar bodies of platelets and the concentric laminar organelles present in Type II pneumocytes (dust cells) which show similar ultrastructural characteristics when treated with the tannic acid fixative/stain.
Peritoneal adhesions were induced in 250 female Wistar rats by the excision and closure of a right lower quadrant parietal peritoneal defect. After closure of the defect each rat was randomly allocated to one of five treatment groups: A, control with no instillate; B, control with Ringer solution; C, noxythiolin 0.5 per cent solution; D, noxythiolin 1 per cent solution; E povidone-iodine/PVP solution. Two millilitres of the appropriate solution were injected into the peritoneal cavity just before closure of a standard 4-cm midline incision. Assessment of adhesion formation was made at 1 week in ignorance of the treatment group. Noxythiolin 1 per cent was more effective than Ringer solution and noxythiolin 0.5 per cent in reducing the mean number of adhesions (P less than 0.05) but was inferior to povidone-iodine/PVP (P less than 0.05). Povidone-iodine/PVP solution significantly reduced the number of adhesions compared with the four other groups. In addition, it significantly reduced the mean length of attachment of each adhesion compared with the two control groups (P less than 0.001).
Glucose phosphate isomerase (GPI) deficiency with severe haemolysis and hydrops fetalis was found in the first child of unrelated, healthy Caucasian parents. The child died at 3 hours. Both parents were found to have 50% of normal red cell GPI activity and qualitative tests on their red cells and white cells showed that each was heterozygous for a different GPI variant allele associated with enzyme deficiency. Tests on the placenta showed that the propositus was a 'compound' heterozygote. Examination of amniotic cells obtained by amniocentesis on the mother at 28 weeks in her second pregnancy led to the prenatal diagnosis of GPI deficiency. This second child, a 'compound' heterozygote at the GPI locus indistinguishable from the first, was successfully treated by immediate exchange transfusion and subsequent blood transfusions.