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Biomedical subjects

P W Saunders

Publications and source records attributed to P W Saunders.

18 recordsLinked to original sources

Model for assessment of endothelial cell function and viability using the MTT dye test and [3H].

OBJECTIVES: To establish a reproducible in vitro model for evaluating endothelial cell function in clinical disease states. DESIGN: A prospective study of human umbilical vein endothelial cells (HUVEC) isolated and cultured. SETTING: Department of Haematology, University of Yaounde I, Cameroon and Department of Medicine University of Newcastle-upon-Tyne, England. RESULTS: The optimum initial cell seeding concentration, for maximal conversion of the formazan dye was 40 x 10(3) cells/well, after 24 hours incubation. At concentrations above 40 x 103 cells/well some inhibition of dye conversion occurred. The conversion of formazan dye was directly proportional to cell numbers for the first 48 hours only, at all cell concentrations. Thereafter, cell metabolism appeared to be inhibited. Third passage endothelial cells (ECs) were exposed to a range of lipopolysaccharide (LPS) concentrations for one and 24 hours, prior to performing the MTT dye test. Dye conversion was observed after one hour at even the lowest concentration of LPS (0.1 microgram/ml), to 49.9% +/- 5.6% of unperturbed control EC, with 10 x 10(3) initial seeding numbers. After 24 hours perturbation a small but statistically significant further inhibition was observed. [3H] thymidine incorporation studies indicated that the lowest LPS concentration tested (0.1 microgram/ml) had a stimulatory effect on DNA synthesis at the higher cell concentration (20 x 10(3) cells/well). In the range of 1 to 100 micrograms/ml of the LPS tested, there was increased DNA synthesis at all cell numbers. CONCLUSION: The model may be used to monitor the effects of other agents which are known to, or could be associated with, alterations in endothelial cell function and will serve in mimicking clinical situations including hyper coagulable states.

Cell Culture Techniques↗

Spinal stabilisation in plasma cell disorders.

Five patients with plasma cell disorders and vertebral body lesions who presented with severe localised back pain associated with spinal instability are described. They underwent a total of six surgical spinal stabilisation procedures with excellent symptomatic relief. Spinal stabilisation was performed at presentation in 1 patient with a cervical spine lesion, and at sites of previously irradiated disease or recurrent disease in the other 4 patients. Stabilisation was achieved using various internal fixation techniques, and in 2 cases external fixation was obtained with a halo brace. The procedures were performed with minimal operative morbidity, and resulted in good symptom control. Spinal instability should be considered as a cause of severe localised back pain exacerbated by movement in patients with plasma cell disorders and vertebral body lesions. Operative spinal stabilisation should be considered as part of their management.

Aged↗

Longstanding proliferation of CD3 negative large granular lymphocytes preceding the development of high grade non-Hodgkin's lymphoma.

A patient with a persistent CD3 negative large granular lymphocyte (LGL) proliferation with immunophenotypic and functional characteristics of natural killer cells is described. The LGL proliferation persisted and six years after diagnosis the patient developed a high grade B cell non-Hodgkin's lymphoma. Molecular studies demonstrated clonal B cell populations in the peripheral blood, distinct from that identified in the lymphoma, both at presentation with non-Hodgkin's lymphoma and at complete remission following combination chemotherapy. It is postulated that T cell dysregulation associated with the CD3 negative LGL proliferation may have led to B cell dysfunction and loss of normal B cell control, with the subsequent development of a clonal B cell lymphoproliferative disorder.

Adult↗

Alveolar rhabdomyosarcoma infiltrating bone marrow at presentation: the value to diagnosis of bone marrow trephine biopsy specimens.

AIMS: To describe the histological appearances of bone marrow infiltrated with rhabdomyosarcoma at presentation and to determine their value in establishing the diagnosis. METHODS: Patients presenting over seven years in the northern health region of England with rhabdomyosarcoma were studied. Bone marrow aspirates and trephine biopsy specimens taken at presentation were examined. RESULTS: Seven of 32 patients with rhabdomyosarcoma had bone marrow infiltration, resulting in marrow failure in all cases, at diagnosis. The diagnosis was established in these seven by the typical cytological appearances and immunophenotype of the infiltrating cells (all seven patients) and cytogenetic abnormalities (three patients). Histological examination of the bone marrow showed a pseudoalveolar pattern with fibrous septal bands, enlarged vascular channels, and lack of cohesion of the tumour cells within the subdivided aggregates in all seven. In four cases multinucleate giant cells, often with peripherally sited nuclei, were found. CONCLUSIONS: These histological features of infiltrated marrow are so characteristic that the diagnosis of alveolar rhabdomyosarcoma can be made, or at least suspected, in many cases even without recourse to technically difficult and expensive further investigations. Bone marrow biopsy should be a routine part of the investigation of patients with bone marrow failure and will be of particular value in the diagnosis of those with disseminated alveolar rhabdomyosarcoma.

Adolescent↗

Myeloproliferative disease in children: a demographic study.

Over eight years, eight cases of childhood myeloproliferative disease were recognised in the northern region of England (population 3.1 million). Five were classic chronic myeloid leukaemia (CML) and the three others, forms of myeloproliferative disease. No case of juvenile CML was recognised. With the exception of CML, "adult" type myeloproliferative disease of children is underrepresented in the literature and its natural history remains unknown.

Adolescent↗

A survey of anti-platelet antibody detection--report of the UK Platelet and Granulocyte Serology Working Group, 1985.

In 1985, serum samples were distributed to 27 laboratories within the UK and Eire with the objective of determining the current state of anti-platelet antibody detection. The sera included five unknown samples for blind assessment and four well-characterized reference reagents. The laboratories involved used a wide range of different methods but the most commonly used techniques were the fluorescent antiglobulin test and the enzyme-linked immunosorbent assay. In the trial, all responding laboratories were able to detect potent anti-platelet alloantibodies but there was a 43% incidence of 'false positive' results with samples which had been designated as inert. There were no apparent differences in performance between assays using fluorescein- or enzyme-labelled antiglobulin reagents or between assays which utilized PFA-treated rather than untreated platelets.

Antibodies↗

Observations on the distribution of the Zwa (P1A1) antigen on fixed and unfixed platelets.

We have investigated the distribution of the Zwa antigen on unfixed platelets and platelets fixed in paraformaldehyde by examining thin sections of platelets by electron microscopy. Fixation of the platelets produces an even distribution of antigen around the surface membrane of the platelets. Unfixed platelets show clustering in some areas with other areas apparently free of antigen. In addition to this clustered antigen distribution, the unfixed platelets also show invaginations and vesicles containing antigen. The significance of these findings is discussed.

Antigens, Human Platelet↗

Splenunculectomy in thrombocytopenic purpura.

In six patients with thrombocytopenic purpura not cured by splenectomy platelets fell to less than 150 X 10(9)/l within six weeks of splenectomy. They 'failed to respond'. Two underwent splenunculectomy without improvement. Splenuculectomy offered little chance of improvement to published cases who failed to respond but may well be helpful after true relapse.

Child↗

Zwa antigen distribution on the human platelet: an electron microscope study using a colloidal gold labelled marker.

We present the application of a new technique for visualizing surface antigen distribution patterns on intact platelets, treated with anti Zwa antibody, using colloidal gold labelled anti-human immunoglobulin as a marker. Platelets from Zwa negative and from both heterozygous and homozygous Zwa positive individuals were examined for surface Zwa antigen distribution. Platelets fixed with paraformaldehyde show an even distribution of gold particles with a well-developed reticular pattern over their surfaces. Platelets heterozygous for Zwa shows considerable antigen variation, some platelets having similar quantities of antigen to, others much less than, homozygotes. The importance of platelet fixation prior to antigen demonstration by anti Zwa antibody and immunogold visualization is seen by the redistribution of antigen on unfixed platelets. It is suggested that this technique could be exploited to investigate the relationship between platelet surface antigens or structures and their functions.

Antibodies, Anti-Idiotypic↗

Common pulmonary vein atresia: Importance of immediate recognition and surgical intervention.

Common pulmonary vein atresia is a rare congenital anomaly; all four pulmonary veins drain into a common dilated chamber with no direct connections to the heart or systemic venous system. Since its first description in 1962, 16 cases have been reported. Only four patients were surgically managed and none survived. This communication presents the seventeenth reported case of common pulmonary vein atresia and the only patient whose anomaly was suspected early enough to demand immediate surgical management, with gratifying long-term success. The literature on the subject is reviewed and common features of the anomaly are emphasized to facilitate precise diagnosis, so that a futile search for a nonexistent communicating vein is avoided at the time of operation. This approach has led to the first successful surgical management of this otherwise fatal lesion.

Heart Atria↗