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Biomedical subjects

J K Rees

Publications and source records attributed to J K Rees.

54 records · Page 3Linked to original sources

Long survival in acute myelogenous leukaemia: an international collaborative study.

A group of 82 adult patients with acute myelogenous leukaemia had survived in continuous first remission for more than three years was studied. These long-surviving patients were being treated at 12 referral centres in Europe and the USA, and they were compared with other patients with acute myelogenous leukaemia from 10 of these centres. There was no clear difference in the amount of induction chemotherapy or the time taken to achieve remission. Immunotherapy was not found to improve chances of long-term survival. The 82 patients were also compared with a group of 115 patients who had no appreciable difference in the number of blood or marrow myeloblasts between these two groups at presentation, but the long survivors had significantly higher initial platelet counts and were slightly younger. The long survivors also tended to have a lower total white cell count at presentation and lower granulocyte counts; there was no obvious explanation for these differences. Eight of the 82 patients relapsed from three to four years after remission and two (of 69 patients) after four to five year. Thereafter relapse was rare, and it seems likely that some of the 40 patients who have survived for five years or more are cured.

Adolescent↗

The association of eosinophilia with lymphoblastic leukaemia or lymphoma: a study of seven patients.

Seven patients with hypereosinophilia in association with a lymphoblastic malignancy are described. The eosinophilia preceded or was present at diagnosis in all patients. Eosinophil counts fell during complete remission but rose significantly before or during relapses in five patients. Hypogranular and sometimes Pelger-eosinophils were seen in five cases. Surface and enzyme markers defined the malignancy in six cases as common-ALL (three), T-ALL (two) and T-lymphoblastic lymphoma (one). Although a diagnosis of eosinophilic leukaemia or acute myeloid leukaemia with eosinophil differentiation was considered in three patients, cytochemical and ultrastructural studies failed to show any evidence of myeloid differentiation in the blast cells. The bone marrow karyotype was normal in the four patients studied. All seven patients had one or more relapses and six died 6-62 months from diagnosis. Severe complications of the hypereosinophilic syndrome developed in one patient. As T-lymphocytes have been shown to be involved in the induction of eosinophilia in rodents, it is suggested that the hypereosinophilia in these patients was induced by eosinopoietic stimuli produced by lymphoblasts.

Adolescent↗

Correlation of serum IgD level with clinical and histologic parameters in Hodgkin disease.

The concentration of serum IgD was measured in 100 patients with Hodgkin disease; 65 had 3--50-fold increases in IgD levels. Several parameters were found to influence serum IgD concentration: IgD level in older patients (greater than 50 yr) was significantly lower than in the younger patients (P less than 18 yr). IgD concentration was significantly higher in splenectomized than in nonsplenectomized patients (p less than 0.005). Therapy was found to depress IgD concentration, which fell to a value significantly lower than in untreated patients (p less than 0.05). An interesting correlation was found between IgD levels and histologic type of the disease, lower levels being preferentially associated with the lymphocyte predominance type and higher with the lymphocyte dipletion type. The logarithms of the means of these two groups were significantly different from the overall mean of the disease (p less than 0.05 and p less than 0.0005, respectively). Mixed cellularity and nodular sclerosing showed intermediate values.

Aging↗

Treatment of acute myeloid leukaemia with a triple cytotoxic regime: DAT.

Twenty patients with acute myeloid leukaemia (AML) were treated with a combination of chemotherapy which included daunorubicin, cytosine arabino-side and 6-thioguanine (DAT). The complete remission rate was 85% and was achieved, in responsive cases, after an average of 2 courses of therapy. Patients remained in hospital for an average of 37.5 days during remission-induction therapy and 3.7 days per month thereafter. The median remission period was 48 weeks and median survival was 70 weeks. A disappointing feature was the high relapse rate. This feature of the results re-affirms the need for a more effective form of remission therapy.

Adolescent↗

Aneurysm of the membraous septum in ventricular septal defect.

An aneurysm of the membranous septum was found frequently in patients with ventricular septal defect; although appearance at catheterization during infancy was not common, aneurysms were detected in about half of the patients older than 2 years of age. A significant decrease in the left-to-right shunt occurred with the development of an aneurysm, but progression to complete spontaneous closure was not seen in any patient. In three older patients, an aneurysm of the membranous septum "disappeared" with time, even though complete spontaneous closure had not occurred.

Child↗

Calciphylaxis in man.

A patient with renal failure developed widespread calcification in the thighs after the injection of iron-dextran (Imferon). This is considered as an example of calciphylaxis, a process in which calcium is laid down in parts of the body following the administration of a "challenger." Iron-dextran is a known challenger, and should be used with caution in uraemic subjects, who may be sensitized by high serum parathyroid hormone levels. Contributing factors may have been a high calcium/phosphate product, steroids, and the patient's immobility.

Adult↗

Retinoic acid alone and in combination with cytosine arabinoside induces differentiation of human myelomonocytic and monoblastic leukaemic cells.

The effect of retinoic acid (RA) alone and in combination with cytosine arabinoside (Ara-C) on differentiation of fresh human myeloid leukaemic cells from patients with AML was studied. Cells from six patients: three with acute myelomonocytic leukaemia AMMoL and three with acute monoblastic leukaemia AMoL with a percentage of blasts greater than 70, were treated in an in vitro primary suspension culture with retinoic acid (10(-7) M), cytosine arabinoside (100 ng/ml) or both in combination. Non-adherent mononuclear cells were seeded at a concentration of 5 x 10(5) cells/ml in RPMI 1640 culture medium supplemented with 20 per cent fetal bovine serum and 10 per cent (PHA-LCM) phytohaemagglutinin leucocyte conditioned medium and incubated for 6 days at 37 degrees C in a humidified incubator containing 5 per cent CO2 in air. Morphological and functional differentiation into terminal mature elements was induced in all leukaemia cells of the six patients following exposure to the combination of both agents. These results suggest the potential usefulness of the combination of a differentiating agent (retinoic acid) and an antileukaemic drug (cytosine arabinoside) in the treatment of acute myeloid leukaemias: AMMoL and AMoL. This combination warrants a clinical trial.

Adult↗

Triple combination of retinoic acid + low concentration of cytosine arabinoside + hexamethylene bisacetamide induces differentiation of human AML blasts in primary culture.

Differentiation induction therapy provides an alternative therapeutic approach for patients with acute myeloid leukemia (AML) who are either unsuitable for or unresponsive to conventional cytotoxic chemotherapy. The effect of a triple combination of retinoic acid (RA) + low concentration of cytosine arabinoside (Ara-C) + hexamethylene bisacetamide (HMBA) on differentiation of blasts from 24 AML patients was studied. Non-adherent mononuclear cells were seeded at a concentration of 5 x 10(5) cells per ml in 24-well tissue culture plates containing RPMI 1640 culture medium with 20 per cent fetal calf serum and 10 per cent 5637-conditioned medium and incubated with 10(-6) M retinoic acid, 10(-6) M cytosine arabinoside and/or 2 mM hexamethylene bisacetamide for six days at 37 degrees C in a humidified incubator under 5 per cent CO2. Morphological, cytochemical and functional differentiation into mature cells were induced in blasts from 22 out of the 24 AML patients following exposure to the triple combination of 10(-6) M RA + 10(-6)M Ara-C + 2 mM HMBA in primary culture. These effective results justify a clinical trial of such triple combination for AML patients who are either unsuitable for or unresponsive to conventional cytotoxic chemotherapy.

Acetamides↗

The relation between hypocholesterolemia and degree of maturation in acute myeloid leukemia.

Plasma cholesterol concentrations were determined in 83 acute myeloid leukemia patients. Mean plasma cholesterol concentration (+/- S.D.) at the time of diagnosis was 2.91 mmol/L (+/- 1.13). The percentage of AML patients having hypocholesterolemia was 90.4 per cent. The lowest cholesterol levels were observed in the poorly differentiated FAB subtypes of acute myeloid leukaemia: AMyL(M1) and AMoL(M5a). The results showed that the initial hypocholesterolemia in acute myeloid leukemia is significantly related to the degree of both cytological and cytochemical maturation of leukemic blast cells at diagnosis. The degree of maturation at diagnosis has been shown to be related to prognosis in favour of more differentiated subtypes of acute myeloid leukemia. Also, hypocholesterolemia has been shown in several epidemiological studies to be related to an increased mortality from human cancer. Therefore, the degree of maturation may serve as a link between hypocholesterolemia and the increased mortality from human cancer.

Adult↗

Triple combination of retinoic acid+aclacinomycin A+ dimethylformamide induces differentiation of human acute myeloid leukaemic blasts in primary culture.

Differentiation induction therapy provides unalternative for treatment of acute myeloid leukaemia (AML) patients who are either unsuitable for or unresponsive to conventional cytotoxic chemotherapy. The effect of a triple combination of retinoic acid(RA)+aclacinomycin A (ACM)+dimethylformamide (DMF) on differentiation of blasts from 24 AML patients was studied. Non-adherent mononuclear cells were seeded at a concentration of 5 x 10(5) cells/ml in 24-well tissue culture plates containing RPM11640 culture medium with 20% fetal calf serum and 10% 5637-conditioned medium and incubated with 10(-6) M retinoic acid, 80nM aclacinomycin A and/or 100mM dimethylformamide alone and in combinations with each other for six days at 37 degrees C in a humidified incubator under 5% CO2. Morphological, cytochemical and functional differentiation into mature cells were induced in blasts from 22 out of the 24 AML patients after exposure to the triple combination of 10(-6)M RA+80nM ACM+100mM DMF for 6 days in primary culture. These highly effective results justify a clinical trial of this triple combination for AML patients who are either unsuitable for or unresponsive to conventional cytotoxic chemotherapy.

Aclarubicin↗