Biomedical subjects

C Hesdorffer

Publications and source records attributed to C Hesdorffer.

27 records · Page 2Linked to original sources

PubMed1990

Efficient gene transfer in live mice using a unique retroviral packaging line.

Irradiated mice were transplanted with cells containing a foreign gene to evaluate gene transfer and expression as a model for gene therapy. Using a uniquely safe and efficient retroviral packaging line developed in this laboratory (GP + E86), we demonstrate efficient and safe long-term transfer of the neomycin resistance (neoR) gene into mice. By infusing cells obtained from spleen colonies of primary post-transplant mice marked with the neoR gene into irradiated recipients, secondary and tertiary generations of recipient mice were produced. There was very low reconstitution activity of single stem cells in these successive generations of mice. We conclude that many more than one stem cell is necessary for successful long-term bone marrow transplantation in mice, presumably as a result of the relatively low frequency of stem cell cycling.

Animals↗

PubMed1990

Retroviral gene transfer using safe and efficient packaging cell lines.

One of the requirements for the use of retroviral vectors in human gene therapy is a packaging cell line which is incapable of producing replication-competent virus and which produces high titers of replication-deficient vector virus. Wild-type virus may be produced through recombinational events between the helper virus and a retroviral vector. We have constructed an ecotropic packaging cell line, GP + E-86, and an amphotropic packaging cell line, GP + envAm12, in which the viral gag and pol genes are on one plasmid and the viral env gene is on another plasmid. Both plasmids contain deletions of the packaging sequence and the 3' LTR. The fragmented helper virus genomes, when introduced into 3T3 cells, produce titers of retrovirus which are comparable to the titers produced from packaging cells containing the helper virus genome on a single plasmid. We have found no evidence for the generation of wild-type retrovirus using the GP + E-86 and GP + envAm12 packaging lines, either alone or in combination with the N2 retroviral vector. We also show that these packaging cell lines can be used to transfer the neoR gene of the N2 vector into mouse hematopoietic cells, followed by successful (48-52%), long-term (up to 200 days) transplantation into irradiated recipients. These results indicate that these packaging lines are safe and efficient for use in experiments designed for murine (using GP + E-86) and human (using GP + envAm12) gene therapy.

Animals↗

PubMed1987

Metastases of prostate cancer to breast. A case report.

A case of carcinoma of the prostate metastasising to the breast and mimicking breast cancer in a male is presented. The possibility of this diagnosis should always be considered. The usefulness of cytochemical staining for prostate-specific acid phosphatase is illustrated.

Adenocarcinoma↗

PubMed1987

Breast cancer in men. Clinical features, hormone receptor status, and response to therapy.

Stage, estrogen receptor status, treatment and survival of 29 men with breast cancer attending the Breast Clinic of the Johannesburg Hospital between 1976 and 1985 are reviewed. Most patients had locoregionally advanced disease at presentation. Estrogen receptors (ER) were detected in significant concentration in 15/23 (65%). Local control was achieved in the majority, 19/26 (73%), by either surgery or radiation therapy alone or by combined modality treatment. Fifteen of 23 patients tested (65%) were ER-positive (greater than 10 fmol/mg protein). For patients with metastatic disease hormone receptor status was predictive of response to hormonal manipulation. Tamoxifen was the most acceptable and frequently used form of hormone therapy with 7/12 patients responding. Combination chemotherapy gave a response rate comparable to that seen in women with breast cancer.

Adult↗

PubMed1986

The use of mitoxantrone plus cyclophosphamide as first-line treatment of metastatic breast cancer.

Thirty-two patients with metastatic breast cancer who had not received prior chemotherapy for metastatic disease were entered into a trial of mitoxantrone 12 mg/m2 plus cyclophosphamide 600 mg/m2 given at three weekly intervals. Thirty-one patients are eligible for assessment. Response was seen in 65% (4/31 complete regression; 16/31 partial regression). Median duration of response was 6 months and median duration of survival was 10 months. Mitoxantrone + cyclophosphamide appears to be an active combination in treatment of metastatic breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1985

Serum ferritin and Hodgkin's disease.

The haemoglobin, serum iron, transferrin saturation, serum ferritin, erythrocyte sedimentation rate (ESR), splenic weight and non-haem iron concentration in the marrow, liver and spleen were measured prior to treatment in 35 patients with Hodgkin's disease who underwent staging laparatomy. The Hb, serum iron and transferrin saturation showed a significant decrease with increasing stage of the disease. In contrast, there was a significant increase in the serum ferritin, ESR, splenic weight and in all the tissue non-haem iron concentrations. The calculated total iron content of the body remained relatively constant throughout at about 2 g but with increasing stage there was an internal redistribution of iron, with a progressive drop in Hb iron and a reciprocal rise in storage iron, especially in the liver. Serum ferritin concentrations, which rose with progression of the disease, were inappropriately high in relation to the size of body stores at all stages but especially in patients with 4B disease and hepatic involvement. It was concluded that the serum ferritin concentrations are raised for several reasons in Hodgkin's disease. They reflect an increase in body iron stores, ferritin's role as an 'acute phase' protein in the inflammatory response and hepatic damage in patients with advanced disease.

Blood Sedimentation↗

PubMed1984

The value of pleural fluid carcinoembryonic antigen estimation in the diagnosis of malignant tumours of the pleural cavity.

Measurement of pleural fluid and blood carcinoembryonic antigen (CEA) concentrations as well as estimations of pleural fluid protein, lactic acid dehydrogenase and sugar levels were carried out in 45 patients with pleural effusions in order to determine the value of these biochemical parameters in the diagnosis of malignant tumours involving the pleural space. The study population included individuals with epithelial and non-epithelial malignant tumours involving the pleural cavity as well as patients with inflammatory effusions and patients with transudates due to cardiac, renal or hepatic disease. Pleural fluid CEA content was the single most useful measurement in distinguishing epithelial malignant tumours from other causes of pleural effusion. In addition, the pleural fluid CEA/blood CEA ratio was greater than 1 in most patients with epithelial cancer of the pleural space, suggesting that local production of CEA is responsible for elevated values in the pleural fluid.

Carcinoembryonic Antigen↗

PubMed1984

Vitamin B12 levels in the prolonged use of sodium nitroprusside.

Long-term (greater than 48 h) sodium nitroprusside (SNP) infusion significantly reduced cobalamin (vitamin B12) levels in 23 patients treated in a CCU after myocardial infarction. There was no evidence of vitamin B12 deficiency or SNP toxicity. Low vitamin B12 levels should not limit the use of SNP, because prolonged infusion of SNP at maximum doses of 2.5 micrograms/kg X min did not adversely affect hemodynamic stability.

Blood Pressure↗

PubMedDate not supplied

Phase I/II study of tandem cycles of high-dose chemotherapy followed by autologous hematopoietic stem cell support in women with advanced ovarian cancer.

The objectives of this study were to investigate the tolerability of a novel high-dose chemotherapy (HDC) regimen with peripheral blood progenitor cell (PBPC) support in patients with pretreated advanced ovarian cancer and to determine the maximum-tolerated dose (MTD) of topotecan in this setting. Advanced ovarian cancer patients previously treated with platinum-based first-line therapy were enrolled. After PBPC mobilization and harvesting, patients received three consecutive cycles of HDC with PBPC support. Cycle 1 was carboplatin area under the concentration curve 20 and paclitaxel 250 mg/m(2). Cycle 2 was topotecan starting at 5 mg/m(2), dose escalated in 2 mg/m(2) increments, and etoposide 600 mg/m(2). Cycle 3 was thiotepa 500 mg/m(2). After each cycle, PBPCs were infused. Granulocyte colony stimulating factor (5 microg/kg/day) was administered until neutrophil recovery occurred. Seventeen patients were enrolled; all were safety evaluable. The most common nonhematologic toxicity was grade 3 mucositis (44%). Engraftment of PBPCs was successful in all patients after each cycle, and no treatment-related deaths occurred. Of 14 patients with measurable disease, 5 (36%) had complete responses, 2 (14%) had partial responses, and 4 (29%) had stable disease. The median progression-free and overall survivals were 7 and 18 months, respectively. The MTD of topotecan was not reached. The tolerability and activity of this regimen in patients with advanced ovarian cancer warrant further investigation.

Adult↗