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Biomedical subjects

T A Splinter

Publications and source records attributed to T A Splinter.

84 records · Page 5Linked to original sources
PubMed1986

Phase I study of alpha-difluoromethylornithine and methyl-GAG.

alpha-Difluoromethylornithine (DFMO) is a potent inhibitor of the synthesis of putrescine (pu) and spermidine (sd) in some benign and malignant tissues. Intracellular deprivation of pu and sd has been shown to induce an enhanced uptake of polyamine-analogs such as methyl-GAG (MGBG). The purpose of this study was to investigate the tolerance and the toxicity of the combination of DFMO and MGBG. Thirty-six patients received 4 X 2 g of DFMO/day orally and every 2 weeks 250-500 mg/m2 of MGBG as a 2-hr infusion, starting on day 14. Besides the well known acute and late side-effects of methyl-GAG, dose-limiting toxicity consisted also of thrombocytopenia, leucopenia, dyspnea, hemolysis and jaundice. The maximal tolerated dose of MGBG for one course was 350 mg/m2 and for repeated courses 250 mg/m2, due to cumulative toxicity. Furthermore, after 8 weeks of continuous administration of DFMO 70% of the patients had a severe hearing loss, which was reversible after a treatment delay of 4-6 weeks. Since the hearing loss prohibited the continuous use of DFMO, two different schedules of intermittent DFMO-administration together with two different infusion periods of MGBG have been investigated in 15 patients. In none of these patients did hearing loss occur. The schedule of continuous administration of 4 X 2 g of DFMO/day orally for 21 days and 250 mg/m2 of MGBG as a 24-hr infusion on days 7, 14 and 21, repeated on day 42, was tolerated best. In 28 evaluable patients two partial remissions were seen. Pretreatment with DFMO significantly enhanced the toxicity of MGBG and the combination of both drugs produced side-effects not seen with either drug alone.

Adolescent↗
PubMed1986

Pharmacokinetic comparison of cisplatin in solution with common lyophilized cisplatinum (Platinol).

Total platinum kinetics were studied after the administration of two formulation products of cisplatin: the lyophilized form and a ready-to-use solution. Twelve patients received both preparations during two successive cycles in a randomized crossover study. Platinum concentrations in plasma and urine were measured by atomic absorption spectrometry. Data were analyzed by means of a mixed-effect analysis of variance. Areas under the concentration-time curves up to 96 h were increased (p = 0.026) and slopes of the elimination phase were decreased (p = 0.035) during cycle 2 when compared with cycle 1. However, no difference in these two parameters was observed when comparing the two formulations. Three-day urinary platinum excretion was not related to either the treatment cycle or the formulation used. Because of its convenience of use and reduced risk of aerosolization, the ready-to-use formulation seems preferable.

Aged↗
PubMed1985

Renal function, serum calcium and magnesium during treatment of advanced bladder carcinoma with cis-dichlorodiamineplatinum: impact of tumour site, patient age and magnesium suppletion.

In a group of ten patients, treated with cisplatin for advanced or metastatic urothelial cancer, renal function deteriorated in six. In a group of 28 patients, treated with cisplatin for tumours outside the urinary tract, renal function was impaired in 14 (50%). Renal function deterioration occurred more frequently in later life. Localization of the primary tumour in the urinary tract does not seem to predispose to renal function impairment. In contrast with reports in the literature, there was a significant decrease in serum calcium levels in spite of magnesium suppletion and normal serum magnesium levels. These calcium levels spontaneously returned to normal some months after the last treatment course with cisplatin.

Adult↗
PubMed1985

Evaluation of a radioimmunoassay for neuron specific enolase in small cell lung cancer.

A radioimmunoassay for neuron specific enolase (NSE), a marker of neuroendocrine differentiation, has been evaluated in small cell lung cancer (SCLC). In untreated patients 25/38 (68%) with localized SCLC had raised blood levels of NSE (greater than 13 ng ml-1), in extensive disease 34/39 (87%) patients had raised NSE levels. In patients with non-small cell lung cancer (NSCLC) the serum levels were raised in 16/94 (17%). In extensive tumours of non-pulmonary origin NSE levels were increased in 24/116 (20%) patients. Longitudinal studies indicated a good correlation between the response to chemotherapy and fall of NSE levels. Tumour progression was accompanied by a rising NSE in 25/29 patients, with doubling times of 7-90 days. In patients with progression with a normal NSE the recurrence was a NSCLC. Cerebral metastases occurring as the only recurrence during clinical complete remission were not accompanied by a rise of NSE. Serum NSE levels provides a valuable monitor for SCLC during and after chemotherapy.

Carcinoma, Small Cell↗
PubMed1985

Synchronous presentation of two primary bronchogenic carcinomas.

A 61-year-old man underwent chemotherapy for a small-cell undifferentiated lung cancer. During this treatment the primary tumour showed complete remission, whereas a lesion in the contralateral lung increased in size. This second tumour was found on cytological examination to be a moderately differentiated adenocarcinoma which was resected. Histological examination of the resected lung segment provided confirmation that this was a second primary bronchogenic carcinoma. The treatment of synchronous primary bronchogenic carcinomas is reviewed.

Adenocarcinoma↗
PubMed1979

Capping of surface immunoglobulin on 'hairy cells' is independent of energy production.

Capping, independent of metabolic energy, of surface immunoglobulin (S-Ig) on 'Hairy cells' from patients with Hairy cell leukaemia (HCL) is described. As controls leukaemic cells from a patient with a prolymphocytic leukaemia (PLL) and blood lymphocytes from healthy individuals were used. The specificity of the energy-independent capping of the HCL-cells as compared to the controls was tested by incubation of the cells at 4 degrees C in the presence of 0.1 M sodium azide with different FITC-labelled ligands. In order to find an explanation for this phenomenon, the influence of cytochalasin B, colchicine and the combination of both drugs on capping of S-Ig and concanavalin (Con-A)-receptors at 37 degrees C was investigated. Furthermore the effect of Con A on S-Ig capping and vice versa was studied. The results show that only S-Ig on HCL cells could form caps at 4 degrees C in the presence of sodium-azide. Cytochalasin B alone induced a strong inhibition of Con A capping on all 3 cell types, whereas S-Ig capping was unaffected. Colchicine alone had practically no effect. Anti-Ig inhibited subsequent patch and cap formation with Con A on both HCL cells and PLL cells, whereas Con A caps and patches were redistributed by anti-Ig on PLL cells, but not on HCL cells. Conversely, Con A could link S-Ig to other receptors, leading to inhibition of S-Ig capping at 4 degrees C on HCL cells and to co-capping of S-Ig at 37 degrees C on both cell types. In addition Con A induced redistribution of S-Ig caps. The combination of co-capping of S-Ig by Con A, followed by redistribution of the caps by FITC-anti-Ig simulated inhibition of S-Ig capping by Con A on PLL cells. The major conclusions are: in some cases inhibition of capping may actually be caused by redistribution of caps; the energy-independent capping cannot be explained by free diffusion of S-Ig in the membrane through lack of any connexion with receptor-mobility regulating systems. It is proposed that the energy requirement of capping is needed to inactivate a specific mechanism,w which restrains receptor mobility and which is non-operative in HCL cells.

Adult↗
PubMed1978

Surface markers and functional properties of non-Hodgkin's lymphoma cells in relation to histology.

Cells from 32 adult patients with non-Hodgkin's lymphoma were studied with respect to surface markers and functional properties in short-term culture. Twenty-six lymphomas were of B-cell origin, including all nodular and diffuse lymphocytic lymphomas. Three tumors were of T-cell origin (one histiocytic lymphoma and two undifferentiated lymphomas). In the remaining three cases (histiocytic lymphomas) the immunological nature of the tumor cells could not be determined. All reactivity to mitogenic stimuli of cells from B-cell lymphomas was due to residual normal T cells. In follicular lymphocytic lymphomas more reactive T cells prevailed among the malignant B cells than in diffuse lymphocytic lymphomas. Heterogeneity among B-cell lymphomas was indicated by differences in intensity of fluorescence with anti-Ig reagents and in stimulatory capacity in mixed lymphocyte culture. T-cell lymphomas were characterized by high percentages of T cells together with impaired responses to stimuli. The results of immunological studies correlated well with the histological classifications of Rappaport, Lukes and Lennert.

Adult↗
PubMed1978

CLL and diffuse histiocytic lymphoma in one patient: clonal proliferation of two different B cells.

A case report is presented of a 77-year-old woman suffering from a composite lymphoma, known as Richter's Syndrome, consisting of chronic lymphocytic leukaemia (CLL) and diffuse histiocytic lymphoma. Light-microscopic investigation revealed the presence of CLL cells in the blood and bone marrow and a combination of CLL cells and large immunoblastic cells in the lymph node. Immunological investigation showed that both malignant cell types were B cells. The CLL cells carried a monoclonal surface immunoglobulin (S-Ig) micron lambda, and the immunoblastic cells had a monoclonal S-Ig micron K. These findings indicated that both clonal lymphoproliferative diseases were probably derived from different tumour stem cells.

Aged↗
PubMed1975

Tubuloreticular structures in human lymphoid cell lines. A cell biological study.

Human lymphoid cell lines were studied as an experimental model for the spontaneous or induced occurrence of tuburloreticular structures (TRS). It was possible to induce TRS after culturing the EB-3 cell line with 20 mug/ml bromodeoxyuridine (BrUdR) during 96 h. Starvation, culturing at lower temperature (32 degrees) or inhibition of DNA synthesis did not give rise to the production of TRS. The response to BrUdR could be blocked with 60 mug/ml thymidine but not with 60 mug/ml deoxycytidine. The addition of 5 mug/ml cytarabine or the removal of BrUdR at different times resulted in inhibition of TRS induction, indicating that BrUdR had to be incorporated into DNA during at least 48 h. After incorporation, neither the presence of BrUdR nor DNA synthesis was necessary for the production of TRS. These experiments and the finding that in the cell line IHTC-33, which does not produce Epstein-Barr virus associated antigens, TRS were spontaneously present, exclude a correlation between TRS and these antigens. However, the induction of TRS by BrUdR may be related to the activation of another (latent) virus.

Antigens, Viral↗