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Biomedical subjects

P Reizenstein

Publications and source records attributed to P Reizenstein.

At least 253 records · Page 14Linked to original sources
PubMedDate not supplied

Absent clinical effects of retinoic acid and isoretinoin treatment in the myelodysplastic syndrome.

Ten patients with the myelodysplastic syndrome (eight with anemia, two with granulocytopenia, four with thrombocytopenia) were given etretinate (ER) and retinoid acid (RA). No correlation was seen between the RA effect in vitro and its clinical effect. No effect was seen of the ER-treatment or of the RA-treatment on anemia, thrombocytopenia or the abnormal karyotype seen in three patients. In three of eight patients given RA a decreased blast cell percentage in the bone marrow was seen, and in two of these there was also a normalization of the in vitro bone marrow cell colony formation. We found no clinical effect of ER and only a minimal one of RA.

Bone Marrow↗
PubMedDate not supplied

Iron metabolism in porphyria cutanea tarda.

The iron metabolism has been studied in 11 patients with porphyria cutanea tarda. Despite significantly increased amounts of iron in the serum and liver, the porphyria patients absorb not less but significantly more radioiron than normal controls. Whereas phlebotomy-induced iron deficiency stimulates the absorption in controls, no further stimulation is found in the porphyria patients. The plasma iron turnover is high in the porphyria patients, and some of this iron is probably deposited in the liver. The relationship between the high iron absorption, high plasma iron turnover, high liver iron, liver damage and uroporphyrin production in the liver is discussed. It is suggested that two concurrent genetic defects may cause porphyria cutanea tarda, one in iron absorption and one in porphyrin synthesis by damaged liver cells. The absorption of inorganic iron was higher than that of hemaglobin iron. The possible damage which fortification with inorganic iron could cause to the very small group of porphyria patients is discussed.

Adult↗
PubMedDate not supplied

Quality and efficiency in a Swedish hospital and rural medical centre. Alternative methods of quality assurance.

Attitude studies of patients, their relatives, and sometimes even widows or widowers suggest that about 80 per cent of a small sample of Swedish in-patients are satisfied. However, the discontinuity of patient-staff relations in 69 per cent of out-patients is disturbing. There is a possibility that medical quality in the Swedish non-fee-for-service system is affected negatively by staff inactivity, which could explain slow diagnoses, long median durations of stay, and high cost. A tentative but comprehensive study indicates a theoretical efficiency increase in a large Swedish hospital of about 40, and a realistic increase of about 10 per cent. In the author's view, present attempts at cost reduction rarely achieve an efficiency increase, but they may reduce medical quality. The absence of quality assurance in parallel with cost reduction is criticized, and a WHO recommendation is proposed.

Cost-Benefit Analysis↗
PubMedDate not supplied

Can verapamil induce second response in patients refractory to vincristine?

Verapamil (240 mg daily orally) was tested in a phase II trial to restore vincristine sensitivity in 9 patients with myeloma, chronic lymphatic leukemia and immunocytoma. These tumors were selected because treatment response and tumor progression can easily be ascertained with the help of electrophoresis and marrow studies, blood counts and lymph node examination. All patients were clinically refractory to vincristine-cytoxan-prednisolone combinations, to which adriamycin had been added in 2 patients. One patient was refractory to adriamycin, VM 26, and prednisone. In 2/9 patients a side effect-free second response lasting 5-10 months was observed, with a doubtful response in two additional patients. It is suggested that occasional clinical responses can be seen, despite the fact that in vitro the mean verapamil concentration required to affect vincristine efflux from malignant lymphocytes in 5 mumols/1 and the mean in vivo serum concentration only 1 mumole. Hypothetically, the clinical response can be explained by an overlapping in some patients of an unusually high serum concentration with an unusually low verapamil requirement.

Drug Resistance↗
PubMedDate not supplied

Serum lipid-bound sialic acid as a tumoral marker in minimal residual tumors.

The lipid-associated sialic acid (LASA) level in serum was increased in 663 out of 794 patients (83.5%) of which 55.1% were CEA negative. There were 16.5% LASA (possibly false) negative, CEA positive patients. There were 24.1% false positives in 116 patients without malignant tumors. In manifest prostatic carcinoma 94.2% of the LASA values but only 36.5% of the prostatic acid phosphatase values were increased. Similarly, in breast and pulmonary carcinoma, LASA was more sensitive than CEA. In 499 patients with minimal residual disease, 203 (41.5%) were LASA-negative, of which 180 were CEA-negative. Out of 180 LASA positive patients, 70 have relapsed, as have 70 out of 219 patients with increases in both LASA and CEA. The sensitivity of LASA (87%) in lymphoma was higher than that of the erythrocyte sedimentation rate (53.3%), of C-reactive protein (51.2%), serum copper (64.7%) and of six other markers.

Biomarkers, Tumor↗
PubMedDate not supplied

Adjuvant treatment of minimal residual tumors. A comparison of chemotherapy and immunotherapy.

Adjuvant chemotherapy. The frequent 6 month complete remission induction chemotherapy is not discussed here. What is under debate at present is the prolonged maintenance or adjuvant chemotherapy, which in comparative trials with 5 year follow-up does not appear to improve survival prognosis in leukemia, myeloma, non-Hodgkin lymphoma or post-menopausal breast cancer. However, it may prolong the duration of the first remission. It is suggested that the sensitivity to chemotherapy might depend on cells being induced into the G2 or M phases by growth growth promotor(s), such as estrogens in breast carcinoma. Their presence before the menopause could explain why this neoplasia in this condition is one of the few tumoral diseases transitorily sensitive to adjuvant chemotherapy. Adjuvant immunotherapy is also under debate. Immunotherapy has been reported to give a significant improvement in remission duration and/or overall survival and/or survival after relapse in several tumors and in several trials. However, for almost every trial reporting a statistically significant effect there is one (or more) which shows no significant effect. Theoretically, immunotherapy has several advantages over chemotherapy. It may be effective in minimal residual disease if tumor cells are in the G0 phase. So-called kinetic refractoriness (see separate chapter in this volume) may not apply to immunotherapy. Finally, tumor cells appear to be more sensitive than normal cells to some cytotoxic mechanisms which form a part of the biological response to tumors.

Antineoplastic Agents↗
PubMedDate not supplied

Effect of verapamil in vitro and in vivo on the accumulation of vincristine in leukemic cells from patients with low malignant lymphoma.

The accumulation of vincristine in leukemic cells and normal mononuclear cells and the effect of verapamil on cellular drug accumulation were studied. Leukemic cells were isolated from 10 patients with chronic lymphocytic leukemia, immunocytoma and prolymphocytic leukemia. Normal mononuclear cells were collected from 3 healthy subjects. The cells were incubated with [3H]-vincristine and cellular drug accumulation was determined. The accumulation of vincristine differed nine-fold between patients. The presence of verapamil, 6.6 microM, during the incubation, increased drug accumulation by 150-550%. The effect increased with increasing verapamil concentrations up to 12-15 microM. The increased accumulation of vincristine caused by verapamil also led to increased in vitro cytotoxicity. However, neither the cellular accumulation of vincristine nor the effect of verapamil on drug accumulation was correlated with the clinical response to vincristine-containing treatment regimens. To study the clinical effect of verapamil on leukemic cell accumulation of vincristine, 4 patients were given verapamil, 120 mg three times orally. The plasma concentrations of verapamil after 3 days of treatment were lower than those required to enhance vincristine accumulation in vitro. In addition, norverapamil could also be detected in all patients. Before and at the end of the verapamil treatment period, blood from the patients was incubated with [3H]-vincristine and the leukemic cells then isolated. Verapamil treatment had no effect on the accumulation of vincristine in leukemic cells.

Aged↗
PubMedDate not supplied

Adjuvant chemotherapy and the kinetic refractoriness of minimal residual tumors.

If Skipper's exponential growth and 'log-kill' hypothesis is replaced by one assuming an S-shaped growth curve and a growth inhibition proportional to the product of the growth fraction and the tumor volume, little growth inhibition can be achieved in minimal tumors. This 'kinetic refractoriness' may explain why minimal residual tumors cannot be eradicated by adjuvant chemotherapy.

Antineoplastic Agents↗
PubMedDate not supplied

Survival, hospitalization and cause of death in 99 patients with the myelodysplastic syndrome.

Survival, causes of death and hospitalization have been studied in 99 patients with the myelodysplastic syndrome. The median survival of the patients was 702 days, and the 10 year actuarial survival only 10 per cent, which is not significantly better than the corresponding figures in the remission stage of AML. Although MDS-patients who developed acute leukemia had significantly (p less than 0.05) more platelets, they also had significantly (p less than 0.05) more major bleeding as a contributory cause of death than patients who did not develop leukemia. Bleeding seems to be diagnosed only in 12 per cent in vivo, whereas major bleeding is found at autopsy in 38 per cent of the patients. The patients who did not develop leukemia died significantly (p = 0.018) more often of cardiovascular causes. MDS patients spend one sixth of their remaining life in hospital, on an average. This is true both for those who develop leukemia and for those who do not. The terminal hospital stay lasts an average of 24 days, which is comparable to the figure for myeloma.

Follow-Up Studies↗
PubMedDate not supplied

Maturation asynchrony in leukemic cells. An abnormal combination of normal cell markers.

Multiple monoclonal antibodies and enzyme assays were used to study maturity markers (myelo-peroxidase) and immaturity markers (terminal transferase, HLA-2) in acute myeloid leukemia cells from 35 patients. In 8 of the patients, indications were found of an expression of maturity and immaturity markers on the same cells, here in called maturation asynchrony. It is suggested that the orderly appearance and disappearance of markers during the maturation of normal cells is disordered in malignant cells, and that single markers should be used with caution for the maturation classification of tumors. The simultaneous expression of maturity and immaturity marker by tumor cells could explain also why such cells can be recognized as abnormal even in the absence of tumor specific antigens.

Antibodies, Monoclonal↗
PubMedDate not supplied

Detection of TdT in AML blasts by immunological and biochemical techniques.

The cellular level of terminal deoxynucleotidyl transferase (TdT) was measured in blasts from patients with AML. Parallel determinations were made using an immunoassay and polymerizing reaction. There was a good correlation between the two techniques (r = 0.92) and detectable levels of the enzyme was found in approximately 50% of the cases. The TdT levels found in AML blasts were 1/10 - 1/100 of that reported for cells of lymphoid origin.

DNA Nucleotidylexotransferase↗