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Biomedical subjects

M R Halie

Publications and source records attributed to M R Halie.

At least 73 records · Page 4Linked to original sources

Hypothyroidism leads to more small-sized platelets in circulation.

The effect of induced hypothyroidism on platelet count and platelet volume distribution was studied in twelve athyreotic patients. After a two weeks withdrawal of triiodothyronine supplementation, platelet count and the ratio between platelet and red cell count were increased in all patients. Furthermore, mean platelet volume was declined and platelet distribution width was risen. Thus, hypothyroidism appears to increase the number of circulating platelets, especially the smaller ones.

Adult↗

Urinary polyamines and their metabolites during new combination chemotherapeutic treatments of high grade non-Hodgkin lymphoma.

Nineteen patients with non-Hodgkin lymphoma of unfavourable histology (15 high grade and 4 intermediate grade) were treated with two new combination chemotherapeutic schemes. Except for one all were partial (8) or complete (10) responders to treatment. Polyamines were measured in every spontaneously voided urine sample. Pretherapeutically all (11) stage III and IV patients had borderline or increased urinary putrescine (Pu) and sum of isoputreanine, spermidine and spermine (sigma Isoputr,Sd,Sp), except for the non-responder. Except for one, all (8) stage I and II patients had normal urinary Pu and sigma Isoputr,Sd,Sp. Posttherapeutically patients with pretherapeutically increased sigma Isoputr,Sd,Sp returned to normal (5), borderline (2), or slightly increased (3) levels. The post-therapeutic achievement of normal or borderline sigma Isoputr,Sd,Sp was not necessarily connected with accomplishment of complete remission. From the start of therapy until clinical restaging, partially or completely responding stage III and IV patients excreted 5-234 mmol sigma Isoputr,Sd,Sp per mol of creatinine above the mean normal value plus 2 SD. For stage I and II patients and the clinical non-responder this parameter amounted to 0-5 mmol/mol of creatinine. Peaks in urinary Pu and sigma Isoputr,Sd,Sp follow-up curves were related in time to the administration of chemotherapeutics. For responding stage III and IV patients the rate of the decrease of sigma Isoputr,Sd,Sp levels paralleled the clinically observed rate of tumour load reduction. This study suggests that notably for non-Hodgkin lymphoma patients with high tumour loads the constant monitoring of polyamines can provide information on pretherapeutic spontaneous tumour cell loss, the efficacy of chemotherapeutic combinations, the kinetics-, and (within certain limitations) the extent of therapeutically induced tumour cell death.

Adolescent↗

Lymphocyte subpopulations in peripheral blood and bone marrow in patients with idiopathic myelofibrosis.

In 8 patients with idiopathic myelofibrosis (IM) T and B cells were studied in view of the possibility that immunological dysfunctions are involved in initiating or contributing to the bone marrow fibrosis. In peripheral blood the absolute numbers of E-SRBC and OKT3+ lymphocytes were significantly reduced; in addition a significant decline was observed in the proportion and absolute numbers of OKT8+ cells, resulting in a reversed Leu-3a/OKT8 ratio. An impaired B cell function was observed in 4 of the 8 patients, characterized by a disturbed in vitro pokeweed mitogen stimulated immunoglobulin synthesis and low serum immunoglobulin levels. Immuno-histological studies of the bone marrow demonstrated a scarcity of T cells but normal numbers of B cells. However, no correlation was noted between the observed deviations of B and T cells and the degree of bone marrow fibrosis determined by means of bone marrow histology and serum procollagen-III levels. These data are not sufficient to support the hypothesis that immunological changes in IM are primarily involved in the process of bone marrow fibrosis.

Adult↗

Acute nonlymphocytic leukemia 5 years after treatment with cisplatin, vinblastine, and bleomycin for disseminated testicular cancer.

The combination of cisplatin, vinblastine, and bleomycin (PVB) was used to treat a 25-year-old man for disseminated testicular germ cell cancer, leading to a complete remission. Acute nonlymphocytic leukemia (ANLL), resistant to chemotherapy, developed 5 years later. The secondary nature of this ANLL was corroborated by the detection of nonrandom chromosomal aberrations in bone marrow cells of chromosomes, 7, 5, and 3. This is one of the first reports of possible leukemogenic activity of PVB treatment when applied without additional irradiation or alkylating agents.

Acute Disease↗

In vitro function of radiocolloid-labelled monocytes.

Human monocytes in a mononuclear cell suspension were labelled specifically using 111In-Fe-colloid, with the ultimate goal of using them for monocyte kinetic studies in haematological malignancies. In order to examine the function of the labelled monocytes, in vitro function tests were performed on cell suspensions containing labelled or non-labelled monocytes. These tests were: phagocytosis of opsonized zymosan particles and ability of monocytes to mature into macrophages when cultured in glass tissue chambers. There were no significant differences in in vitro function between labelled and non-labelled monocytes. Cell viability was always greater than 90%. During culture, a rapid loss of monocyte-bound radioactivity took place. We conclude that the labelling procedures do not interfere with subsequent in vitro cell function. However, because of the rapid loss of cell bound radioactivity in vitro, monocytes labelled by this method do not seem suited for long-term studies in vivo.

Colloids↗

Effect of intestinal flora modulation by oral polymyxin treatment on hemopoietic stem cell kinetics in mice.

After oral treatment with polymyxin for only 1 day, fecal aerobic gram-negative bacteria were found completely suppressed in C3H/Law mice. Complete suppression of aerobic gram-negative bacteria was accompanied by a reduction of the fecal endotoxin concentration from 100 to 10 micrograms endotoxin per gram of feces as measured with the Limulus amebocyte lysate assay. Oral administration of polymyxin affected hemopoietic stem cell kinetics at different stages. The kinetic behavior of hemopoietic stem cells was determined as the in vivo sensitivity to the S phase specific cytostatic drug hydroxyurea. The hydroxyurea kill of bone marrow spleen colony-forming cells diminished not significantly (p less than 0.10) from 14 to 4% after 2 days of polymyxin treatment. Already after 1 day of treatment the hydroxyurea kill of bone marrow progenitor cells forming granulocyte-macrophage colonies in vitro decreased from 29 to 7% (p less than 0.05). It took 8 days of treatment before the hydroxyurea kill of splenic granulocyte-macrophage colonies was found reduced from 53 to 14% (p less than 0.001). The decreased susceptibility of hemopoietic stem cells to hydroxyurea during polymyxin treatment appears to argue for a role of intestinal aerobic gram-negative bacteria in the regulation of hemopoiesis, probably mediated by endotoxin.

Administration, Oral↗

Retinoic acid as antileukemic therapy in a patient with acute promyelocytic leukemia and Aspergillus pneumonia.

A patient with acute promyelocytic leukemia (APL) and laboratory evidence of fibrinolysis who could not be treated with aggressive cytostatic regimens because of Aspergillus pneumonia was treated with cis-retinoic acid (RA), a substance that can induce differentiation and maturation of APL cells. After seven weeks of daily oral treatment, he went into complete remission, and signs of coagulopathy disappeared. Meanwhile, the Aspergillus pneumonia could be treated adequately. Based on the experience in this single patient, RA deserves further evaluation in the treatment of APL.

Adult↗

Simultaneous gas-chromatographic determination of free and acetyl-conjugated polyamines in urine.

A capillary gas-chromatographic method with nitrogen-phosphorus detection is used to determine simultaneously urinary 1,3-diaminopropane, monoacetyl-1,3-diaminopropane, putrescine, monoacetylputrescine, cadaverine, monoacetylcadaverine, spermidine, N1-acetylspermidine, N beta-acetylspermidine, spermine, N1-acetylspermine, isoputreanine, N-(3-aminopropyl)pyrrolidin-2-one, and putreanine. The compounds are isolated by adsorption onto silica and converted into their methyl-heptafluorobutyryl derivatives. We give quality-control data and age-dependent "normal" values for urinary excretion of these analytes from 51 apparently healthy control subjects. Normal values for 31 adults are compared with those reported in the literature. Monoacetyl-1,3-diaminopropane and N1-acetylspermine are identified by mass fragmentography. We applied the method to monitor chemotherapeutic treatment of a patient with advanced non-Hodgkin's lymphoma; we identified by mass spectrometry N1,N12-diacetylspermine in this patient's urine.

Acetylation↗

Mass fragmentographic identification of polyamine metabolites in the urine of normal persons and cancer patients, and its relevance to the use of polyamines as tumour markers.

The mass fragmentographic identification of N-(2-carboxyethyl)-4-amino-n-butyric acid, N-(3-aminopropyl)-N1-(2-carboxyethyl)-1,4-diaminobutane, N,N1-bis(2-carboxyethyl)-1,4-diaminobutane, and delta-aminovaleric acid in acid-hydrolysed urines of a normal person and two cancer patients is described. A previous study, in which the metabolic fate of intraperitoneally injected polyamines in rats was investigated, revealed that these compounds should be considered as non-alpha-amino acid metabolites of the naturally occurring polyamines. Quantification of polyamines and their non-alpha-amino acid metabolites by gas chromatography with nitrogen--phosphorus detection showed that, relative to the parent polyamines, humans normally excrete higher quantities of polyamine catabolites in urine than rats, suggesting that humans catabolize polyamines more efficiently. As illustrated by the follow-up of the concentrations of polyamines and their catabolites in the urine of a patient with high-grade non-Hodgkin lymphoma during chemotherapy, the catabolic pressure on polyamines may be considerably increased during neoplastic diseases, since an even higher proportion of oxidized polyamine metabolites was observed. It is therefore suggested that the additional measurement of the circulating concentrations of polyamine-degrading enzymes is of importance for the correct interpretation of polyamine (metabolite) determinations for oncological purposes.

Amino Acids↗

T cells in patients with chronic T gamma lymphocytosis: morphology, cytochemistry, ultrastructure and immunological characteristics.

We have studied the morphology and cytochemistry in relation to the immunological phenotyping and functional properties of T cells from eight patients with chronic T gamma lymphocytosis. At the light microscopic level the morphology of the patients' lymphocytes was similar to that described for large granular lymphocytes. Ultrastructurally, a division into two groups could be made on differences in the amount of cytoplasm and the location and the more irregular form of the nuclei. The lymphocytes of one group (five patients) had in common the phenotype Fc gamma +, T3 +, T4 -, T8 +, Ia -, M1 - and demonstrated (with the exception of one patient) the same functions: presence of K-cell activity, absence of NK, helper and suppressor cell activities. In the other group (three patients), the lymphocytes of one patient showed the same phenotype and functions as those indicated above. The other two patients both lacked the T8 antigen on their lymphocytes but were different with regard to other surface markers. In addition, their cells were functionally identical: both demonstrated NK- and K-cell activity. Thus in this group of eight patients with chronic T gamma lymphocytosis, the immunological and functional subdivision paralleled in part a morphological division at the ultrastructural level.

Acid Phosphatase↗

Faecal endotoxin and activity of the gut-associated lymphoid tissue in patients with malignant (B-cell) lymphoma.

On the basis of previously obtained evidence that Gram-negative bacteria may influence the activity of leukaemia, a study of the composition of the flora, the immune stimulation by the Gram-negative bacteria and the endotoxin concentration in faeces was conducted in patients with low-grade malignant B-cell lymphoma as well as in patients with acute leukaemia. In these patients it was investigated whether the number of facultative anaerobic Gram-negative bacteria in the faeces correlated with endotoxin concentration. In addition, IgA coating of Gram-negative bacteria in the faeces was determined and the titre of circulating antibodies to endogenous Enterobacteriaceae species from the faeces of the corresponding patient was studied. No clear difference was found to exist in the percentage of IgA-coated Gram-negative bacteria in the faeces and in the circulating antibody titres to endogenous Enterobacteriaceae between healthy control persons, lymphoma patients and patients with acute leukaemia. Antimicrobial treatment to establish selective decontamination (SD) of Enterobacteriaceae species from the digestive tract did cause a significant decrease in the faecal endotoxin concentration in a subset of patients treated for SD with polymyxin.

Acute Disease↗

Stability of azure B-eosin Y staining solutions.

The stability of azure B-eosin Y staining solutions of varying composition and of a routine May Grunwald Giemsa (MGG) stain were studied by analysis of the density histogram of white blood cells obtained by an image analysis computer. The stability appeared to be variable and depended on the concentration of the dyes, the molarity of the buffer solutions and the presence of dimethylsulfoxide (DMSO) as a stabilizer. Although most staining solutions including the routine MGG stain showed marked loss of staining capacity soon after preparation, it was possible to obtain an azure B-eosin Y mixture with very satisfactory staining properties which did not decrease during 8 h after its preparation.

Azure Stains↗

Technique of labeling monocytes with 111In-Fe colloid for use in humans.

In order to follow monocyte kinetics in hematologic malignancies by means of radioactive labeling, three conditions are necessary: (a) no loss of monocytes during separation, (b) specific labeling of monocytes, and (c) normal functional capacities of the labeled monocytes. In this report a method is described that fulfills the first two conditions and can be executed with maintenance of sterility. Cell labeling was performed using a mononuclear cell suspension consisting of monocytes (20%-50%), lymphocytes (50%-80%), and with minor contamination by granulocytes, thrombocytes, and erythrocytes. This cell suspension was obtained by centrifugation of a leukocyte suspension on a gradient of 16% wt/vol and 22% wt/vol human serum albumin solutions. The recovery of monocytes with this enrichment method approached 100%. Monocytes were labeled by endocytosis of 111In-Fe colloid; monocytes were labeled significantly higher than lymphocytes (P less than 0.001) and granulocytes (P less than 0.01) (Wilcoxon's two-sample test). Cell viability after labeling was greater than 90%.

Autoradiography↗