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Biomedical subjects

R M Lowenthal

Publications and source records attributed to R M Lowenthal.

89 records · Page 5Linked to original sources

The cryopreservation of leukaemia cells: morphological and functional changes.

Stored autologous haemopoietic cells may be used to repopulate the bone marrow of patients in the advanced stages of different leukaemias who have received cytotoxic drugs. We have used a continuous flow blood cell separator to collect peripheral blood leucocytes from patients with chronic granulocytic leukaemia (CGL) before treatment. We also collected bone marrow cells from patients with CGL and from patients with acute myeloid leukaemia in complete remission. The collected cells were frozen at I degree C per minute using dimethyl sulphoxide as cryoprotective agent and stored in liquid nitrogen. For reconstitution of frozen cells we found that the use of dextran II0 inhibited leucoagglutination. The viability and function of the reconstituted leucocytes were assessed by their morphological appearance, their capacity to phagocytose and kill Candida albicans organisms, their ability to reduce the dye nitroblue tetrazolium (NBT) in vitro and to incorporate tritiated thymidine into DNA and by the growth of colony forming units (CFUc) in agar culture. With this method of cryopreservation the phagocytic function of mature neutrophils is retained to some extent but their capacity to reduce NBT and their microbicidal activity are completely lost. In contrast CFUc may remain after storage for periods of at least 2 years.

Bone Marrow↗

Splenectomy for complications of chronic granulocytic leukaemia.

13 patients with chronic granulocytic leukaemia (C.G.L.) which was unsatisfactorily controlled underwent splenectomy. 3 out of 4 patients with hypersplenism did well, as did 5 out of 8 patients in whom the C.G.L. had undergone metamorphosis to a refractory phase. In a case of C.G.L. complicated by severe myelofibrosis the need for transfusion was reduced but survival was short. Splenectomy should be considered when C.G.L. in its chronic phase is complicated by hypersplenism, and may be considered as a part of the treatment after C.G.L. has undergone metamorphosis to a refractory phase. However, a favourable outcome is unlikely for patients over 65 years, and in the presence of coexistent illnesses, rapidly progressive metamorphosis to an acute phase, or severe bone-marrow failure from any cause. In C.G.L., elective splenectomy early in the chronic phase must be clearly distinguished from splenectomy performed at a later stage when the disease is not well controlled.

Adolescent↗

Recovery from Goodpasture's syndrome after immunosuppressive treatment and plasmapheresis.

A patient with Goodpasture's syndrome has recovered after treatment with immunosuppressive drugs (cyclophosphamide and prednisolone) and removal of circulating antibodies by plasma exchange. This was performed on seven occasions and seems to have hastened the decline in circulating antibody levels. Undertaken early in the course of the disease plasmapheresis could prove a useful addition to its therapy.

Adult↗

Granulocyte transfusions in treatment of infections in patients with acute leukaemia and aplastic anaemia.

By use of the continuous-flow blood-cell separator 137 bags of granulocyte-rich plasma were obtained from normal donors (59 bags) and patients with chronic granulocytic leukaemia (C.G.L.) (78 bags). Eighty-nine courses of granulocyte transfusion therapy consisting of 1 or more such bags were administered to forty-one ABO-compatible patients with acute leukaemia or aplastic anaemia, who had definite or probable infections that had failed to respond to antibiotics. The fever resolved after 67% of courses of transfusions of two or more bags but after only 24% of transfusions of single bags of granulocytes (p less than 0-01), and this result suggests that this form of treatment is in general effective. Granulocytes from C.G.L. and normal donors were equally effective, although transfusion reactions were commoner after C.G.L. cells (33% versus 12%, respectively, p less than 0-05). C.G.L. grafts, and probable graft-versus-host disease, occurred in three recipients of unirradiated C.G.L. cells. Recipients of normal cells whose fevers resolved received on average four times as many granulocytes per sq.m. as those fevers did not respond. No such difference was found when C.G.L. cells were used. The fever was more likely to resolve in recipients with established or clinically probable bacterial or fungal infections than in those with fever of uncertain cause. Fever was less likely to resolve in recipients with peripheral blood granulocyte counts before transfusion of greater than 1000 per mul. It is concluded that granulocyte transfusion therapy is a valuable advance in the management of infections in neutropenic patients.

Adolescent↗

Intensive leukapheresis as initial therapy for chronic granulocytic leukemia.

Intensive leukapheresis has been used as the initial treatment of chronic granulocytic leukemia (CGL) in six patients. The number of leukaphereses ranged from 3 in 7 days to 13 in 39 days (mean, 8 in 22 days). The procedures were well tolerated, and in all patients there was improvement in hematologic values, in most cases with considerable reduction in the peripheral leukocytosis and thrombocytosis and in the proportion of immature granulocytic cells in the circulation. Splenomegaly decreased considerably in the four patients who had more than four leukaphereses. Symptoms of sweating, malaise, and pain due to splenomegaly were rapidly relieved. Problems due to hyperuricemia did not occur, but four patients required blood transfusions for correction of anemia. This method of initial treatment of CGL appears to give more rapid relief of symptoms than does conventional chemotherapy; it incurs no risk of hyperuricemia and lessens that associated with thrombocytosis. In addition, large quantities of granulocyte-rich plasma are made available for the treatment of infections in neutropenic patients. Intensive leukapheresis deserves more widespread evaluation as the initial treatment of CGL.

Adolescent↗

In vitro colony forming cells and colony stimulating factor in chronic granulocytic leukaemia.

We have used the technique of human haemopoietic cell culture in agar to study the peripheral blood and bone marrow colony forming capacity of 23 patients with Ph(1) + ve chronic granulocytic leukaemia (CGL) before and after treatment. In comparison with normal controls the number of colony forming cells (CFC) is moderately increased (about three-fold) in the bone marrow and enormously increased in the peripheral blood of untreated patients. In the peripheral blood their number in general is related to the total leucocyte count. In patients whose blood counts have been restored to normal by the use of cytotoxic drugs the number of CFC in the peripheral blood is very greatly reduced. In the marrow of treated patients CFC are present in approximately normal numbers. When used as feeder layer sto support the culture of normal bone marrow cells, the peripheral blood leucocytes of untreated patients are a uniformly poor source of colony stimulating factor (CSF) and fractionation experiments suggest that this is not due merely to a relative scarcity of monocytes. After treatment the peripheral blood has normal CSF activity and this is associated with the monocytic cell component. The last data may be explained in either of two ways: it is possible that restoration of the blood of patients with CGL to normal values removes a homeostatic factor suppressing the formation of CSF by functionally normal monocytes, or alternatively treatment with cytotoxic drugs leads to the replacement of defective monocytes by a population of relatively normal CSF producing cells.

Adolescent↗

Toxicities of dextrans.

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Blood Specimen Collection↗

Chinese herbal arthritis cure and agranulocytosis.

Rheumatoid arthritis remains an incurable disease, and the patient who is unable to obtain relief from standard therapies will often turn to one of the many alternative treatments available. We report an episode of agranulocytosis which occurred in a patient with rheumatoid arthritis while he was taking a Chinese herbal preparation. We understand this preparation is readily obtainable by Australians.

Aged↗

Can cancer be cured by meditation and "natural therapy"? A critical review of the book You can conquer cancer by Ian Gawler.

There is a widespread belief that cancer is caused, at least in part, by aberrant mental processes. A corollary of this belief is that cancer may be cured by the application of the mind. These ideas are fostered in Australia by a popular book You can conquer cancer by Ian Gawler, a veterinary surgeon who attributes, at least in part, the development and subsequent cure of his own cancer to such processes. Critical examination of these beliefs finds evidence in their support to be lacking. None the less, many patients with cancer in this country follow the book's advice, often on the basis that it "at least can do no harm". While some patients may be aided to come to terms with their disease and to lead more fulfilling lives by taking up meditation and the positive approach to living that is described in the book, it also contains recommendations about orthodox treatments, life-style and diet which, if adopted uncritically, could be quite detrimental. The potentially harmful effects of accepting such unproved ideas about cancer need to be known more widely. Furthermore, because his ideas are making such an impact on the day-to-day treatment of cancer in this country, Gawler owes it to the community to justify, with evidence, his claims that by meditation patients with cancer may be enabled to achieve a cure of their disease in a way that is unattainable with orthodox medical treatment alone.

Attitude of Health Personnel↗

Oral idarubicin as treatment for advanced myelodysplastic syndrome.

BACKGROUND: The myelodysplastic syndromes (MDS) are a group of haemopoietic stem cell disorders of unknown cause, occurring predominantly in elderly patients. They have a high mortality due to deaths from complications of cytopenias or transformation to leukaemia. No effective treatment is known. Preliminary studies have identified idarubicin (IDA), an anthracycline drug that can be administered orally, as an agent with possible activity in MDS. METHODS: In a phase I-II study we administered oral IDA to 14 predominantly elderly patients (age range 40-79, median 74) with advanced forms of MDS, namely chronic myelomonocytic leukaemia (CMML) (one case), refractory anaemia with excess blasts (RAEB) (7 cases) or refractory anaemia with excess blasts in transformation (RAEB-t) (6 cases). IDA was given at a dose of 30 mg/m2 once each 2 weeks for 8 doses. RESULTS: There was one complete remission (CR) and one partial response (PR), for an overall response rate of 14%. Mean survival from time of initiation of therapy was 10.0 months (+/- 8.0 months [SD]; median, 7.0 months). 5 patients developed severe side-effects, including 3 with life-threatening infections, and there were two deaths from cytopenias during the drug therapy. CONCLUSIONS: In this small uncontrolled trial, the overall response rate and extent of toxicity seem similar to those reported for other forms of experimental therapy for MDS, such as low-dose cytosine arabinoside. Further evaluation of the drug's potential in this difficult condition may be warranted.

Administration, Oral↗