Biomedical subjects

T Rasmussen

Publications and source records attributed to T Rasmussen.

131 records · Page 8Linked to original sources

PubMedDate not supplied

Mobilisation of tumour cells along with CD34+ cells to peripheral blood in multiple myeloma.

BACKGROUND: Cells belonging to the malignant clone are found in the peripheral blood in myeloma patients. In order to minimise the content of tumour cells in the stem cell product it is crucial to perform stem cell harvest at a time when tumour cells in the peripheral blood are at a minimum. OBJECTIVE: The aim of the study was to compare the mobilisation kinetics of normal CD34+ cells and myeloma plasma cells during mobilisation with either G-CSF alone or high-dose cyclophosphamide (HDCy) plus G-CSF. DESIGN AND METHODS: Morning blood samples were drawn each day during mobilisation from start of G-CSF or HDCy and to the end of leukapheresis, and were analysed by flow cytometry for content of CD34+ cells and myeloma plasma cells (CD38+ + CD45-). Tumour cells were also estimated by a patient-specific real-time polymerase chain reaction (PCR) method based on the 5' nuclease TaqMan technology. RESULTS: Flow cytometry data from 16 patients showed concomitant mobilisation of CD34+ cells and myeloma plasma cells. Seven patients were mobilised twice; first with G-CSF alone and then with HDCy plus G-CSF. There was no difference between the two mobilisation regimens regarding tumour cell mobilisation kinetics. Real-time PCR was performed in one patient and confirmed the mobilisation of tumour cells at the time when CD34+ blood cells were at a maximum. CONCLUSIONS: Tumour cells are mobilised to the peripheral blood at the same time as CD34+ cells in multiple myeloma patients after priming with both G-CSF alone and HDCy in combination with G-CSF.

Adult↗

PubMedDate not supplied

Frequency and prognostic relevance of cyclin D1 dysregulation in multiple myeloma.

OBJECTIVE: Cyclin D1 dysregulation has been found with varying frequencies in multiple myeloma (MM) and has been suggested to be associated with a poor prognosis. The aim of this study was to investigate the frequency of cyclin D1 dysregulation in patients being treated for MM and to test whether cyclin D1 dysregulation is a prognostic factor for MM patients. METHODS: To achieve the above aims we designed a highly sensitive and reproducible real-time reverse-transcription polymerase chain reaction (RT-PCR) assay for quantitation of cyclin D1 mRNA. Using this assay, 110 diagnostic bone marrow (BM) samples from patients with MM were screened for cyclin D1 dysfunction. RESULTS: The real-time assay was able to detect the presence of 0.01% cyclin D1 positive cells allowing a safe detection in MM BM samples. In 42% (46/110) of MM BM samples a greater-than-or-equals 3-fold increase in cyclin D1 mRNA was observed compared to the cyclin D1 level in normal BM. In the remaining group of MM patients the cyclin D1 mRNA levels were comparable to normal donors. Follow-up of 76 MM patients showed no significant (P = 0.35) difference in survival between cyclin D1 positive and negative MM patients. In addition, cyclin D1 dysregulation did not correlate with known prognostic factors. CONCLUSION: The developed real-time RT-PCR assay for detection of cyclin D1 mRNA levels offers a fast and safe screening for cyclin D1 dysfunction. When a large cohort of MM patients was screened, the cyclin D1 gene was found to be frequently dysregulated, but there was no significant correlation to survival or known prognostic parameters.

Adult↗

PubMedDate not supplied

Surgical treatment of children with medically intractable frontal or temporal lobe epilepsy: results and highlights of 40 years' experience.

Etiologic, pathologic, and clinical features of possible prognostic significance were studied in 118 children who underwent frontal or temporal lobe epilepsy surgery at the Montreal Neurological Institute (MNI) between 1940 and 1980 (excluding tumor cases). Mean age of seizure onset was 5.1 years (range 0-12 years), mean age at operation was 11.7 years (range 0.6-15 years), and median duration of follow-up was 15 years (range 2-31 years). Thirteen of 45 frontal surgery patients and 43 of 73 temporal surgery patients had an excellent outcome. In the frontal surgery group, this was restricted almost entirely to patients with an established etiology, particularly if this included a circumscribed resectable structural abnormality. In the temporal surgery group, a history of early, prolonged febrile seizures was usually associated with good outcome, unless there was additional evidence of extratemporal epilepsy. In the entire series, the presence of a nonresectable structural lesion or secondarily generalized seizures was associated with a poor outcome.

Child↗

PubMedDate not supplied

Reevaluation of surgical failures and the role of reoperation in 39 patients with frontal lobe epilepsy.

Between 1929 and 1980, 284 patients with refractory nontumoral frontal lobe epilepsy (FLE) underwent operation at the Montreal Neurological Institute (MNI). We studied 39 patients (14%) who required reoperation. Mean age at the time of first operation was 18 years and at reoperation was 22 years. Clinical manifestations were similar to those of patients with "a pure culture of frontal lobe epilepsy" as reported by Rasmussen in 1983. At the time of first operation, large epileptogenic zones were noted in most patients. Resection was confined to the frontal lobe. Continuing seizure activity was due to residual areas of epileptogenesis, and reoperation with more extensive resection of cortex increased the number of seizure-free patients. Twenty-six patients underwent further frontal resection, and in 13 surgical removal was extended to the temporal lobe. Residual electrocorticographic (ECoG) spiking was documented in 15 of 23 (65%) of the reoperated patients. Thirty-five patients were followed for periods ranging from 4 to 46 years. One fifth became seizure-free, and 31% had significant seizure reduction. Thus, half of these patients had a good result. Patients with residual postexcision ECoG spiking had poor outcomes and evidence of large epileptogenic zones. None of the patients who underwent frontotemporal resections became seizure-free. Reoperation should be considered if initial resection does not lead to a satisfactory result and may convert an initial failure into a good surgical result.

Adolescent↗

PubMedDate not supplied

The presence of circulating clonal CD19+ cells in multiple myeloma.

Multiple myeloma (MM) is a B-cell malignancy characterized by the expansion of mature plasma cells (PC) localized in the bone marrow (BM). Several studies have identified circulating clonotypic CD19+ cells at a differentiation stage preceding the PC. The level of circulating clonotypic CD19+ cells is highly variable but generally low. Circulating clonotypic cells respond well to induction therapy, although a small subset within the CD19 compartment is resistant even to high-dose chemotherapy. The clonal CD19+ cells represent an ongoing differentiating population ranging from memory B-cells to plasmablasts. However, a clonal relationship gives no proof of malignant potential, and whether or not clonotypic precursor cells are involved in the disease process is a subject of intense debate. Translocations involving the immunoglobulin locus (14q32) are an early non-transforming event common to both monoclonal gammopathy of undetermined significance (MGUS) and MM introduced at the memory B-cell level. At the plasmablast stage, a phenotypic transformation occurs with downregulation of CD19 and upregulation of myeloma specific markers such as CD56, CD117 and CD28. Translocations involving the isotype-switch machinery and the introduction of tumor-specific markers at the plasmablast stage suggest that the clonal CD19+ memory B-cells and CD19+ plasmablasts are non-malignant, but immortalized relatives that gave rise to myeloma. A final proof of the malignant potential of CD19+ clonotypic cells might await the identification of the molecular events causing the transformation in myeloma.

Antigens, CD19↗