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Biomedical subjects

C Forsyth

Publications and source records attributed to C Forsyth.

14 recordsLinked to original sources
PubMed2001

Abnormal dicentric chromosome with co-amplification of sequences from chromosomes 11 and 19: a novel rearrangement in a patient with myelodysplastic syndrome transforming to acute myeloid leukemia.

A 66-year-old man with a myelodysplastic syndrome transforming to acute myeloid leukemia showed a complex abnormal karyotype on bone marrow aspirate. An unbalanced dicentric translocation with a very long der(11) long arm-dic(11;19)(q25;p13.4)-was present. Fluorescence in situ hybridization studies utilised paints for chromosomes 11 and 19 as well as the locus specific probe MLL, localised to 11q23. The abnormal chromosome 11q contained 6 copies of intact MLL and 6 copies of chromosome 19 (unidentified) sequences. To our knowledge, gene co-amplification of chromosomes 11 and 19 sequences has not been reported before.

Acute Disease↗
PubMed1996

Rapid quantitation of mixed red cell populations using flow cytometry.

Methods are described for the identification and quantitation of mixed red cell populations using flow cytometry. Antibodies specific for a wide range of blood group antigens have been used and examples are given in which these analyses have proved to be of clinical use. These examples include monitoring of erythropoiesis following engraftment in allogeneic bone marrow transplant recipients and the detection of chimaeric states months or years after transplantation. The techniques involved are fast, simple and inexpensive.

Bone Marrow Transplantation↗
PubMed1996

Autologous red cell recovery and relapse of multiple myeloma after bone marrow transplantation: is this a graft-versus-myeloma effect?

We report a patient who, following an allogeneic bone marrow transplant for multiple myeloma, recovered autologous erythropoiesis which was rapidly followed by relapse of her multiple myeloma. We postulate that the loss of the graft (as demonstrated by loss of donor erythropoiesis) and subsequent relapse of the multiple myeloma may be support for the existence of a graft-versus-myeloma effect.

Adult↗
PubMed1995

Membrane-associated CD19-LYN complex is an endogenous p53-independent and Bc1-2-independent regulator of apoptosis in human B-lineage lymphoma cells.

CD19 receptor is expressed at high levels on human B-lineage lymphoid cells and is physically associated with the Src protooncogene family protein-tyrosine kinase Lyn. Recent studies indicate that the membrane-associated CD19-Lyn receptor-enzyme complex plays a pivotal role for survival and clonogenicity of immature B-cell precursors from acute lymphoblastic leukemia patients, but its significance for mature B-lineage lymphoid cells (e.g., B-lineage lymphoma cells) is unknown. CD19-associated Lyn kinase can be selectively targeted and inhibited with B43-Gen, a CD19 receptor-specific immunoconjugate containing the naturally occurring protein-tyrosine kinase inhibitor genistein (Gen). We now present experimental evidence that targeting the membrane-associated CD19-Lyn complex in vitro with B43-Gen triggers rapid apoptotic cell death in highly radiation-resistant p53-Bax- Ramos-BT B-lineage lymphoma cells expressing high levels of Bcl-2 protein without affecting the Bcl-2 expression level. The therapeutic potential of this membrane-directed apoptosis induction strategy was examined in a scid mouse xenograft model of radiation-resistant high-grade human B-lineage lymphoma. Remarkably, in vivo treatment of scid mice challenged with an invariably fatal number of Ramos-BT cells with B43-Gen at a dose level < 1/10 the maximum tolerated dose resulted in 70% long-term event-free survival. Taken together, these results provide unprecedented evidence that the membrane-associated anti-apoptotic CD19-Lyn complex may be at least as important as Bcl-2/Bax ratio for survival of lymphoma cells.

Animals↗
PubMed1994

Rapid detection of Rh(D)- or K-positive fetal red cells in chorion villus samples by a flow cytometric technique.

Rh(D)- and K-negative women who have become severely isoimmunized by pregnancy are at risk of fetal loss or damage in subsequent pregnancies. A flow cytometric method is described whereby the presence of Rh(D) or K antigen on fetal erythrocytes may be determined using chorion villus samples taken during the first trimester. This method has the advantage of speed and sensitivity with results being available within 2 h. Decisions as to management of the pregnancy or termination may thus be made with minimal delay.

Chorionic Villi Sampling↗
PubMed1994

Development of a flow cytometric test for the detection of D-positive fetal cells after fetomaternal hemorrhage and a survey of the prevalence in D-negative women.

A sensitive test for the presence of D-positive fetal red blood cells (RBCs) in the maternal circulation of D-negative women has been developed. It was used to investigate the possibility that the occasional failure in preventing alloimmunization might be due to the administration of inadequate amounts of prophylactic anti-D Rh immune globulin. The standard dose in Australia contains 125 microg of antibody, and can suppress immunization by an estimated 6 mL of packed D-positive RBCs. A fetomaternal hemorrhage (FMH) of this volume is detectable in the maternal circulation as approximately 0.25 percent of the total RBCs. Our test utilizes a commercially available human monoclonal IgG anti-D that has been biotinylated and used with a dye-conjugated streptavidin. Flow cytometry is used to quantitate fluorescing D-positive RBCs. To date, 2,288 tests have been performed on blood samples from D-negative women attending local antenatal clinics or at the time of delivery. Evidence for an FMH has been obtained in six cases (0.26%). In one case, the FMH was only 0.1 percent, and in another (confirmed by the Kleihauer-Betke method), fetal cells constituted only 0.2 percent. Additional Rh immune globulin was not given to these patients. In the other four cases, the D-positive fetal cells were estimated to be 0.7,0.5,0.5, and 0.4 percent, and additional prophylactic Rh immune globulin was administered. Although the prevalence of FMH is low, screening D- negative women at risk of alloimmunization has proved to be simple, fast, and inexpensive.

Journal Article↗
PubMed1993

Synaptic degeneration is the primary neuropathological feature in prion disease: a preliminary study.

The range of neuropathology found in cases of prion disease is considerable. The pathology present in dendrites and axons is associated with a marked loss of spines and synaptic contacts. It is probable that this loss underlies the functional and neurological deficits in the disease. Immunocytochemical re-examination of 2 cases of inherited disease with a 144 bp prion gene insertion with no characteristic pathology (i.e. spongiform change, astrocytosis and gliosis), together with 3 typical cases of prion disease (CJD), with antibodies to synaptophysin and synaptic protein demonstrated the presence of synaptic "plaque-like" lesions throughout the temporal cortex and cerebellum. In addition, examining the tissue by image analysis demonstrated a greater than 30% reduction in the relative synaptic index in all the prior disease cases when compared with controls. Synaptic disorganization and/or loss is a fundamental and constant feature of prion disease, irrespective of the presence or absence of spongiform change, neuronal loss and severe gliosis. Assessment of the extent and location of synaptic deficits might produce a more accurate documentation of the degree of neuronal disorganisation occurring during the course of prion disease.

Adult↗
PubMed1992

Severe vascular adverse effects with thrombocytopenia and renal failure following emetogenic chemotherapy and ondansetron.

During late 1991, a series of severe adverse events involving thrombocytopenia, renal insufficiency and thrombotic episodes was observed in patients receiving emetogenic chemotherapy. Two patients died, one of renal failure and one of cerebral haemorrhage in the presence of thrombocytopenia. Other severe side effects included thrombosis of the aorta causing paraplegia and multifocal cerebral infarctions. Common exposure features included the use of ondansetron and dexamethasone as antiemetics, and in most of the cases high dose (100 mg/M2 or more) cisplatin. Retrospective review of a series of patients treated with similar cytotoxic regimens for similar diseases before the use of ondansetron revealed no similar adverse effects, but no substantial differences were observed in renal function or haematologic toxicity in the two groups overall. Sporadic adverse vascular events have been observed before the use of ondansetron. The mechanism remains unknown, and it is not clear whether ondansetron was a factor in the unusual incidence of such events in the present series.

Adult↗
PubMed1987

The management of .22 caliber gunshot wounds of the brain: a review of 49 cases.

We analyzed the charts and CT scans of 49 cases of civilian .22 caliber gunshot wounds of the brain admitted to the University of Alberta and Royal Alexandra Hospitals between 1975 and 1985. The average age of the patients was 30 years, 88% were males, 88% were suicide attempts. There were no deaths among patients with an initial coma score above 12 whereas the mortality rate was 85% for those admitted with a score of 7 or less. All those with fixed pupils on admission died. The overall mortality rate of 61% is comparable to that of other series of civilian gunshot wounds including those in which more aggressive surgical management was undertaken. We recommend that no treatment be given those cases with an admission coma score of 3 and/or fixed pupils and that simple scalp wound debridement be employed with those having a coma score of 7 or less. Tract exploration and retrieval of bullet fragments is not indicated, as retained fragments carry a very low incidence of complications (e.g. abscess formation). In patients in good condition (GCS greater than or equal to 12) the management of intracranial hematomas should be independent of their etiology and approached aggressively.

Adolescent↗