Repetitive analyses of P-glycoprotein in chronic myeloid leukaemia.

P-glycoprotein, a pump located in the plasma cell membrane, extrudes several clinically important drugs from the cell, and hence causes multidrug resistance. Reversing clinical drug resistance is possible by using agents that inhibit the activity of P-glycoprotein. We describe the results of sequential flow cytometric determinations of P-glycoprotein expression and activity in two patients suffering from acute lymphoblastic transformation of chronic myeloid leukaemia. Neither P-glycoprotein expression, nor its activity could be detected in the initial sample of the first patient. In the second patient, no P-glycoprotein expression was found at diagnosis. However, after chemotherapy containing P-glycoprotein substrates, a significant expression was found in both patients and the functional flow cytometric test was positive. In order to achieve an accurate selection of patients that might benefit from the clinical use of P-gp inhibitors, repeated analyses are indicated in each patient suffering from acute leukaemia, during the course of the illness.

Bone marrow necrosis.

BACKGROUND: In the medical community, little is known regarding bone marrow necrosis (BMN) as a clinicopathologic entity, although to the authors' knowledge it was described for the first time more than 50 years ago. To identify the rate of prevalence, the symptoms and signs, the underlying disease associations, and the usefulness of diagnostic procedures, an extensive literature search was made. METHODS: Only cases identified as extensive necrosis and diagnosed during life were selected. Two hundred forty cases met these criteria. RESULTS: Bone pain (75%) and fever (68.5%) were the most important symptoms, whereas anemia (91%) and thrombocytopenia (78%), associated with a leukoerythroblastic picture (51%), were the most frequent hematologic abnormalities. Nearly 50% of patients showed elevated lactate dehydrogenase and alkaline phosphatase levels. In 90% of the patients an underlying malignancy was identified. CONCLUSIONS: Bone marrow necrosis is caused by hypoxemia after failure of the microcirculation. Given the high rate of malignancy as an underlying disease association, an extensive search for neoplastic disease is justified whenever BMN is diagnosed. Pancytopenia and embolic processes are major complications that should be managed with supportive measures until effective treatment of the underlying disease has been administered. When necrosis resolves, repopulation of the bone marrow cavity with normal hematopoiesis is observed.

Effect of dilution, temperature, and preservatives on the long-term stability of standardized inhalant allergen extracts.

BACKGROUND: Although documented stability of allergens used for diagnosis is important, research in this area has been limited. Most studies on extract stability have been of limited duration and discrepancies have been reported between stability test results of in vivo and in vitro methods. OBJECTIVE: In this study we determined the stability of allergenic extracts, comparing the intracutaneous test and enzymallergosorbent test inhibition method and determining the effect of temperature, dilution, and preservatives. METHODS: Three formulations of timothy pollen, birch pollen, house dust mite (D. pteronyssinus) and cat dander extracts, as used for bronchoprovocation, skin prick testing and intracutaneous testing, were stored for 24 months at 6 degrees C. The influence of temperature on various formulations was determined using the enzymallergosorbent test inhibition technique during storage for up to 36 months. RESULTS: Most formulations were found to be stable for 24 (intracutaneous test) or 36 (enzymallergosorbent test inhibition) months at 6 degrees C. At 25 degrees C, most formulations showed a decrease in relative potency, which remained above the limit of 0.3 times the in-house-reference for the bronchoprovocation formulation of timothy pollen, birch pollen, and house dust mite and for the skin prick test formulation of cat dander. CONCLUSIONS: Cat dander was remarkably stable at 6 and 25 degrees C in glycerine and birch pollen was very susceptible to phenol. This destructive effect of phenol could be prevented by adding human serum albumin. The discrepancy between in vivo and in vitro tests reported by others was confirmed for house dust mite and timothy pollen.

GM-CSF and G-CSF in hematology and oncology.

The cloning of hematopoietic growth factors has allowed their application in clinical medicine. This review deals with clinical studies on GM-CSF and G-CSF in bone marrow insufficiency (primary or secondary to chemotherapy), myelodysplastic syndromes, AIDS and bone marrow transplantation.

Glutathione conjugation of 1,2-dibromo-1-phenylethane in rats in vivo.

The metabolism of 1,2-dibromo-1-phenylethane (DBPE) was studied in rats. Administration of DBPE orally, in doses of 0.25-1.25 mmol/kg (66-330 mg/kg), to male Wistar rats resulted in the excretion of a single mercapturic acid in urine. The methyl esters of three potential mercapturic acid metabolites were synthesized: N-acetyl-S-(2-oxo-2-phenylethyl)-L-cysteine methyl ester (O),N-acetyl-S-(2-hydroxy-1-phenylethyl)-L-cysteine methyl ester (I), and N-acetyl-S-(2-hydroxy-2-phenylethyl)-L-cysteine methyl ester (II). GC/MS analysis showed that the methyl ester of the excreted mercapturic acid was identical with II. Quantitative measurement of II in urine by GLC showed that, after 24 hr, excretion of the mercapturic acid was almost complete and amounted to 41% of the administered dose. At doses higher than 1.00 mmol/kg, the excretion no longer increased. Inhibition of the oxidative pathways by ip injection of 1-phenylimidazole resulted in an excretion decrease of about 40%. (Pre)treatment with diethyl maleate lowered the excretion of mercapturic acid by 30-60%. Glutathione conjugates synthesized from DBPE and styrene oxide were separated by HPLC. Both compounds can produce the same two pairs of diastereomers, viz. (R)- and (S)-(2-hydroxy-1-phenyl-ethyl)glutathione ((R)-1 and (S)-1), and (R)- and (S)-(2-hydroxy-2-phenylethyl)glutathione ((R)-2 and (S)-2). These could be separated in the order (R)-2, (R)-1, (S)-1, and (S)-2 within 20 min. This method was also applied to examine glutathione conjugates excreted in bile after DBPE administration.(ABSTRACT TRUNCATED AT 250 WORDS)

A chromosomal profile of polycythemia vera.

One hundred four patients with a diagnosis of polycythemia vera and a variable period of follow-up had one or more cytogenetic investigations. Chromosome abnormalities were found in 13% of untreated patients, in 56% of cases treated with radioactive phosphorus (32P) or cytotoxic drugs, and in 85% of patients in which transformation of the disease had occurred. Nonrandom chromosome abnormalities found before treatment included +8, +9, 13q-, 20q-; their prognostic value is little, as they are often associated with longstanding, stable disease. In contrast, 5q- anomaly and the appearance of subclones in patients with an abnormal karyotype were found to be poor prognostic signs, as they are usually coincidental with evolution of the disease to myelofibrosis or leukemia. Chromosomally two patterns of acute leukemia were observed in polycythemia vera patients. The first type resembles de novo acute leukemia, in that the clinical and cytologic characteristics of the disorder are easily defined by FAB criteria and the chromosome changes compatible with the types usually found in those conditions. In the second type, assignment to a FAB morphologic subgroup was more difficult, myelodysplastic changes were often present, and the karyotype showed complex abnormalities frequently involving chromosomes #5 and #7. All these features suggest the occurrence of secondary leukemia.

Interstitial 9q- deletions in hematologic malignancies.

Sixteen patients with interstitial deletions of the long arm of chromosome #9 (9q-). were studied. From our observations and the findings of ten other cases in the literature, it can be deduced that the anomaly is almost exclusively found in myeloproliferative disorders and that it rarely occurs as the sole anomaly; however, in more than one-third of the cases, it was associated with a t(8;21) and occurred as a secondary event. The deletion appears to be interstitial, the breakpoints are somewhat variable, and the region carrying the abl oncogene was never involved.

Anomalies of the long arm of chromosome 11 in human myelo- and lymphoproliferative disorders. I. Acute nonlymphocytic leukemia.

In a series of 365 consecutive ANLL cases of which 45.1% had abnormal karyotypes, 13 cases were detected with a structural abnormality of the long arm of chromosome 11. Besides one isochromosome 11q, there were six deletions and six translocations. Of these 12 patients, seven had acute monocytic leukemia (FAB-type M5), two had an M4, two had an M2, and one case of secondary leukemia had an M3-like disorder. Similar results with regard to the type of leukemia were obtained upon analysis of 41 cases of ANLL with an 11q anomaly described in the literature. This study confirms that a high proportion of acute monocytic leukemias and a lesser proportion of acute myelomonocytic leukemias are characterized by an 11q anomaly, mostly involving bands q22 and/or q23. Acute monocytic leukemia with an 11q structural anomaly appears to have a poor prognosis.

Puncture of thoracic lesions under sonographic guidance.

Thirty-six punctures of thoracic lesions have been performed with a compound B-scanner or a real-time linear-array scanner for guidance. Twenty-three fluid collections were punctured and aspiration biopsies were performed on 13 echogenic lesions. All the punctures were successful at the first attempt. No complications occurred. The results confirm the usefulness of sonography for guiding punctures of thoracic fluid effusions and solid masses. Usually a static B-scanner is sufficient, but when masses are small or surrounded by vital structures puncture may be controlled by a real-time scanner.

A novel alkaline phosphatase isozyme in 4 patients with acute non-lymphocytic leukemia: its nature, origin and clinical significance.

A novel alkaline phosphatase (AP) isozyme has been observed in the serum of 4 patients suffering from acute non-lymphocytic leukemia (ANLL). It resembled the AP of liver/bone origin in most physico-chemical characteristics, but particular electrophoretic characteristics in agar and starch gel and a distinct molecular weight gave this novel AP isozyme its unique character. Its leukemic origin has been demonstrated by isolation from peripheral blood and bone and bone marrow blasts. The appearance of the novel AP isozyme in the patients' sera appeared to be an ominous sign as, in all four, it shortly preceded death. In patients it may have contributed to the observed resistance towards thioguanine therapy.

Pseudomyxoma peritonei. Report of a case with extraperitoneal metastasis and invasion of the spleen.

The findings in a patient with pseudomyxoma peritonei, probably of appendicular origin, are reported. As a rule, pseudomyxoma peritonei remains limited to the peritoneal cavity, but in this case, dissemination occurred to the right pleural cavity and to the pericardium. In addition, invasion of the spleen (to our knowledge, nor previously described) was noted.