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Biomedical subjects

R J Hawker

Publications and source records attributed to R J Hawker.

At least 19 recordsLinked to original sources
PubMed1998

Inhibition of phenolsulphotransferase by salicylic acid: a possible mechanism by which aspirin may reduce carcinogenesis.

BACKGROUND: Recent epidemiological evidence has shown that chronic use of aspirin decreases susceptibility to bowel cancer. Animal studies have shown that sulphotransferase inhibitors coadministered with sulphation activated carcinogens dramatically reduce the incidence of cancer. AIMS: To investigate the effect of the main aspirin breakdown product, salicylic acid, on the P and M isoforms of phenolsulphotransferase from human platelets and colonic mucosa. METHODS: Platelets were obtained from healthy blood donors and isolated within 24 hours after donation. Samples of colonic mucosa were obtained at resection for non-malignant disease. Phenolsulphotransferase activity was measured in cellular homogenates using a standard radiolabelling assay. RESULTS: Salicylic acid consistently and selectively inhibited the P form of phenolsulphotransferase at subtherapeutic concentrations in both tissue samples. A 50% inhibition of sulphation by the P phenolsulphotransferase occurred at salicylic acid concentrations of about 40 and 130 microM in platelets and bowel mucosa respectively. M phenolsulphotransferase was virtually unaffected by salicylic acid up to a concentration of 1.5 mM (the therapeutic plasma concentration for salicylates when treating rheumatoid arthritis is about 1-2 mM). CONCLUSION: The action of salicylic acid on P phenolsulphotransferase, by preventing the excessive activation of carcinogens, is a possible additional pathway by which aspirin can reduce cancer risk.

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PubMed1997

Citrate metabolism by human platelets.

As part of a study on the utilization of substrates by platelets in defined media the metabolism of citrate was measured, since citrate is a common anticoagulant of nearly all such media, and is also an intermediate of oxidative metabolism. Human platelets transferred from plasma to an artificial medium by gel filtration, were incubated with [14C]citrate at 22 degrees C and labelled carbon dioxide produced was measured during short-term incubations of 2 h. Citrate (1 mM) was oxidized to carbon dioxide at low (0.3 nmol per 10(9) platelets h-1) but significant rates, and the oxidation was decreased by the presence of an alternative substrate (acetate) in the medium. There was, however, no significant conversion of citrate to glycogen. It was calculated that under normal storage conditions of platelet concentrates for transfusion purposes, the amount of citrate used cannot decrease citrate concentrations sufficiently to bring about platelet activation.

Blood Platelets↗
PubMed1996

Use of prostaglandin E1 during preparation of platelet concentrates.

A paired study in 10 autologous volunteer donors was undertaken to investigate the efficacy of adding prostaglandin E1 (PGE1) in vitro during routine platelet concentrate (PC) production. After 5 days storage, PCs prepared with PGE1 were compared with control PCs. In vivo platelet recovery, survival and biodistribution were determined following autologous infusion of indium-111 labelled platelets into volunteers, together with the in vitro evaluation of platelet function and biochemistry. PGE1 facilitated easier and faster platelet resuspension following centrifugation. After storage there were few significant in vitro differences between PCs prepared with PGE1 and control PCs. The artifactual leucocyte concentration was significantly lower in the presence of PGE1, suggesting less platelet aggregates had been formed during storage and beta-thromboglobulin release was significantly reduced by PGE1, 14.0 +/- 6.0 micrograms per 10(9) platelets compared with 22.3 +/- 9.8 micrograms per 10(9) platelets in control PCs, (P < 0.01), indicating PGE1 reduced both platelet aggregation and activation probably at the initial preparation stage, known to produce the greatest trauma. Initial in vivo platelet recovery for PCs prepared with PGE1 was similar to that of control PCs, 41.1 +/- 12.5% vs. 44.4 +/- 8.0%, respectively, and there were no differences in organ distribution at 24 h. However, in vivo multiple hit survival was reduced in the presence of PGE1, 5.8 +/- 1.6 days compared with 6.9 +/- 1.4 days in control PCs (P < 0.05). Despite the ability of PGE1 to facilitate platelet resuspension and inhibit platelet aggregation and activation during preparation of the PCs, the reduced in vivo survival time may preclude the use of PGE1 during routine PC preparation.

Adenosine Triphosphate↗
PubMed1995

A comparative study of platelets stored in polyvinyl chloride containers plasticised with butyryl trihexyl citrate or triethylhexyl trimellitate.

Platelet concentrates (PCs), stored for 5 days in PL 2209, a new polyvinyl chloride (PVC) storage container plasticised with butyryl trihexyl citrate, were compared with those stored in PL 1240, a PVC platelet container plasticised with triethylhexyl trimellitate. In part 1 of the study, pooled platelet-rich plasma (PRP) was aliquoted into each type of pack and pH, pCO2, pO2, hypotonic shock response, aggregation responses, lactate, glucose and ATP concentrations, and lactate dehydrogenase and beta-thromboglobulin release were compared at days 1, 3 and 5. In part 2, 12 volunteers gave a unit of blood on two separate occasions and PCs produced by the PRP method were stored in PL 2209 or PL 1240 for 5 days before autologous reinfusion of a 111In-labelled sample. In vitro results demonstrated that PL 2209 was more gas permeable than PL 1240. In part 2 of the study, at day 5, pCO2 was 3.13 +/- 0.62 versus 5.14 +/- 0.69 (p < 0.001), whilst pO2 was not significantly different for PL 2209 versus PL 1240, respectively. pH was better maintained in PL 2209 than in PL 1240 (7.38 +/- 0.13 vs. 7.24 +/- 0.10, respectively, p < 0.01) after storage for 5 days. These results were confirmed by those from part 1. In vivo data were similar for PC stored in the two plastics with a multiple-hit recovery of 40.9 +/- 12.1% for PL 2209 and 37.4 +/- 11.3% for PL 1240, and a multiple-hit survival of 4.89 +/- 1.20 days and 5.28 +/- 2.06 days for PL 2209 and PL 1240, respectively. gamma-Camera imaging of volunteers showed similar biodistribution of radiolabelled platelets stored in each container. These results demonstrate that PL 2209 is a suitable container for storage of PCs for 5 days.

Benzoates↗
PubMed1994

Paired in vivo and in vitro comparison of apheresis and "recovered" platelet concentrates stored for 5 days.

Using a paired study, in vivo and in vitro characteristics of apheresis platelets collected on a cell separator and single-donor whole-blood (recovered) platelets via platelet-rich plasma (PRP) were compared after storage for 5 days in similar plastic containers. Autologous platelets from each of 12 volunteers were labeled with 111Indium after storage and reinjected. There was no significant difference in circulating recovery between platelets prepared by the two methods, and only one of five models of survival showed a significant difference. Hypotonic shock recovery was significantly better in apheresis than recovered platelets (57.0% and 32.4%, respectively), whilst aggregation to ADP at 3.2 microM and 32 microM was significantly higher in recovered than in apheresis platelets (17.0% and 45.2% versus 7.8% and 32.9%, respectively). Lactate dehydrogenase (LDH) content was significantly higher in recovered platelets (143.3 versus 77.1 IU/10(11) platelets), but LDH release was similar (15.0% cf. 12.6%). There was no significant difference between the two platelet preparations for platelet concentration, pH, aggregation with the calcium ionophore A23187 or collagen plus epinephrine, or ATP content or release. beta-TG release was lower in apheresis platelets. Neither product was consistently better than the other for the parameters tested, but apheresis platelets have the advantage of lower donor exposure to the patient.

Adenosine Triphosphate↗
PubMed1994

Effect of agitation on the quality of platelet concentrates.

Platelet concentrates (PCs) were stored for 4 days at 22 degrees C in 400 ml second-generation (PL1240) platelet packs with either constant agitation, manual mixing once every 24 h or without agitation at any time. After 4 days storage, in vivo recovery, survival and biodistribution were determined following indium-111 labelling of platelets and infusion into autologous volunteers. In vitro assays of platelet function and biochemistry were likewise carried out after 4 days storage. The PCs stored without agitation had significantly lower in vivo recoveries, pH and aggregation responses to ionophore A23187 and a combination of collagen and epinephrine and significantly higher beta-thromboglobulin and indium-111 release than the agitated PCs. The manually mixed PCs were not significantly different from the constantly agitated PCs. PCs mixed simply once every 24 h remained viable with active oxidative phosphorylation and a pH above 6.74 in all but 1 case indicating that PCs stored at 22 degrees C for up to 4 days with only intermittent mixing are satisfactory for transfusion. A change from constant agitation would reduce capital costs in mixing equipment and simplify the transport of PCs from the transfusion centre to small hospital blood banks.

Blood Banks↗
PubMed1992

Platelet accumulation after laser angioplasty--a scintigraphic assessment.

Indium 111-labeled platelet scintigraphy was performed to evaluate platelet deposition in response to different levels of Nd:YAG laser/thermal energy. A dose-related increase in platelet deposition was observed. In clinical studies after laser-assisted balloon angioplasty, intense platelet deposition was observed in 2 patients who subsequently developed clinical arterial thrombosis. The pathogenesis of reocclusion appears, however, to be more complicated and ill understood. The authors suggest further extensive studies incorporating several parameters in the evaluation of the pathogenic factors involved in reocclusion after laser angioplasty. Such studies should also consider the role of arterial injury produced by the balloon catheter after laser-assisted balloon angioplasty.

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PubMed1990

Detection of arterial thrombosis after laser angioplasty by platelet scintigraphy.

Indium-111-labelled platelet scintigraphy was performed in two patients after laser-assisted balloon angioplasty. Both patients demonstrated a significant 'hot spot' at the angioplasty site 24 h after successful recanalisation with laser and balloon. Clinically apparent thrombosis of the recanalised arteries occurred 5 and 6 days after angioplasty in both patients. Laser-assisted balloon angioplasty leads to significant platelet deposition over recanalised segments of the artery, which may result in arterial thrombosis, as evident from the reports presented. Indium-111-labelled platelet scintigraphy emphasises the extent of trauma caused by laser and balloon angioplasty to the arterial wall.

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PubMed1989

Quantification of the leucocyte influx into rabbit ileal loops induced by strains of Salmonella typhimurium of different virulence.

Leucocyte influx into rabbit ileal loops, induced by strains of Salmonella typhimurium of different virulence, was assessed with 111Indium-labelled leucocytes. Strains fell into two groups on the basis of their leucotactic potential: "virulent" strains (which induced fluid secretion) caused a dose-dependent leucocyte influx; strains which did not induce fluid secretion failed to induce a significant leucocyte influx. Fluid secretion was never observed in the absence of leucocyte influx, but leucocyte influx per se did not induce fluid secretion. The phenotype of the challenge inoculum influenced fluid secretion; young log-phase organisms induced fluid secretion with a higher frequency than overnight cultures. These findings support earlier evidence implicating leucocytes in an interactive but not exclusive role in the genesis of salmonella-induced fluid secretion. They suggest, though do not prove, that interaction of leucocytes with the appropriate phenotype of organisms results in the release of a host-derived or bacterial secretagogue, or both. The bacterial factor may or may not be the antigen related to cholera toxin, described previously.

Animals↗
PubMed1987

Indium-111-labelled leucocytes in the diagnosis of abdominal abscess.

The extensive morbidity and mortality of intra-abdominal abscess is mainly due to the delay in a diagnosis. The diagnostic accuracy of 111In-labelled mixed leucocytes with gamma imaging has been investigated in 100 consecutive patients including 34 following surgery and 36 with inflammatory bowel disease. White cell scans were performed 24 h following injection of autologous 111In-labelled leucocytes and were compared with clinical outcome where abscess was only diagnosed when pus either discharged or was drained at operation. Gamma images detected 28 of the 30 abscesses with no false positives giving 93 per cent sensitivity and 100 per cent specificity. Loculi of pus were identified in 11 of the 36 patients with inflammatory bowel disease with no errors in interpretation. Inflammation was reported in 15 of the remaining 25 patients with known but not necessarily active inflammatory bowel disease. 111In-labelled leucocyte imaging provides a rapid, safe and precise method for detecting intra-abdominal abscess even in the presence of inflammatory bowel disease.

Abscess↗
PubMed1987

Splenic platelet-sequestration following routine blood transfusion is reduced by filtered/washed blood products.

The mean fall in the platelet count following 23 routine transfusions of 3-5 units packed cells for anaemia was 32.5%. This was significantly reduced to 12.5% in 15 similar transfusions through a 40 microns microaggregate filter (P less than 0.01) and to 4.6% following five transfusions through a polyester fibre filter (P less than 0.005). In 10 transfusions with frozen or polyester fibre filtered, washed red cells, the decrease in platelet count was 4.2% (P less than 0.001). A study of 111In-oxine labelled autologous platelets in nine patients indicated that the fall in platelet count was due to increased splenic sequestration. Since thrombocytopenia following routine transfusion is reduced by procedures which filter the packed cells, the decrease in platelets is probably caused by their adherence to infused microaggregate debris causing their premature removal from the circulation. Patients with preexisting thrombocytopenia who receive red cell transfusions for anaemia, should therefore receive blood products depleted of microaggregate debris in order to avoid exacerbation of thrombocytopenia and haemorrhagic complications.

Anemia↗
PubMed1986

Clinical experience with 99mTc-hexamethylpropylene-amineoxime for labelling leucocytes and imaging inflammation.

Hexamethylpropylene-amineoxime (HMPAO) forms a lipid-soluble neutral complex with 99mTc which is rapidly incorporated into leucocytes in vitro. In six patients with suspected or known inflammatory disease, a "mixed" leucocyte suspension isolated from 85 ml blood anticoagulated with acid-citrate-dextrose was labelled by 99mTc-HMPAO with a mean efficiency of 47% (SE2%), of which 78% (3) was taken up by granulocytes. Activity eluted more rapidly from other cell types in vitro than from granulocytes, which remained firmly labelled. Mean initial biodistribution of the label and granulocyte recovery in blood of 32% (8) at 30-40 min showed that the granulocytes were not significantly activated during labelling. All six patients were positive for inflammatory disease, as early as 30 min in five patients and at 3 h in the sixth; they all remained positive at 20-24 h. Four patients also received 111In-labelled "pure" granulocytes. In terms of detail, the 99mTc images were comparable or superior to the 111In images.

Adult↗
PubMed1985

111-Indium platelets in monitoring pancreatic allografts in man.

A technique for monitoring pancreatic allografts in man is presented. The method utilizes 111-indium labelled autologous platelets and provides quantitative and qualitative analysis of uptake of the tracer by the graft. Five patients without any significant accumulation of radiolabelled platelets in their transplants had an uneventful recovery and left hospital with satisfactory graft function. The three patients who suffered graft failure showed abnormal uptake of the tracer. This presented as a diffuse platelet accumulation within the transplanted pancreas in the case of acute rejection, or as a focal accumulation in two cases of venous thrombosis. Minor complications such as perigraft haematoma can also be diagnosed using this technique. We suggest that 111-indium labelled platelets provide a valuable diagnostic aid in the management of pancreatic transplant recipients.

Adolescent↗
PubMed1985

Indium leucocyte imaging in true pyrexia of unknown origin.

A patient with pyrexia of unknown origin (PUO) was investigated for a focal infection using autologous indium-labelled leucocytes. Only one site of increased activity was observed; this was asymptomatic and subsequently proved to be an infected nasal sinus. This case highlights the necessity, in PUO investigations, of carrying out whole-body imaging rather than just investigating the areas with presenting symptoms.

Aged↗
PubMed1984

Platelet survival, atherosclerotic intermittent claudication and ticlopidine.

Platelet survival times were measured twice within 6 months using autologous 111-Indium-labelled platelets in 13 male patients diagnosed as stable intermittent claudicants. Linear, exponential, weighted mean and gamma function (multiple-hit) analyses were carried out on the data. Of these methods, exact mathematical models such as linear and exponential are unsuitable for the comparison of curves which may alter with treatment or disease progression. Weighted mean platelet survival correlated (r = 0.96) with platelet survival calculated by the precision reference method of analysis, gamma function. Statistics were expressed from gamma function analyses unless otherwise stated. Severity of claudication was measured by doppler; the ratio of brachial to mean ankle pressures was directly related to platelet survival (r = 0.84). In 7 patients, where duration of claudication was greater than 5 years, platelet survival was significantly reduced (P less than 0.02) compared with 6 newly diagnosed claudicants of less than 18 months duration. Six randomly selected patients were treated with 250 mg b.d. ticlopidine during one of the study periods. Ticlopidine significantly increased platelet survival (P less than 0.02) in all patients irrespective of disease duration or severity. The involvement of platelets in atherosclerosis observed in these claudicants, can be reduced by therapy with ticlopidine, however, the lack of clinical improvement following long-term drug treatment only confirms the platelet's secondary role in this disabling disease.

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