A retrospective study on chemical and radioactive synovectomy in severe haemophilia patients with recurrent haemarthrosis

Between 1970 and 1994, 116 chemical and 90 radioactive synovectomies were performed in 107 patients with severe haemophilia and two with type 3 von Willebrand's disease. The products used were osmic acid (OA) in 100 cases, 90-Yttrium in 35 cases, 186-Rhenium in 48, 169-Erbium in two, hexacetonide triamcinolone in 16 and radioactive gold in five cases. The use of radioactive colloids is not allowed in France in patients under 15 years of age. Twenty-nine patients had more than one synovectomy per joint. All patients were evaluated for 6 months post-synovectomy, using both a clinical and a radiological score. Six months after synovectomy, a good or excellent result was obtained for 81% of the joints treated with isotopes, compared with 44% of those treated with OA, P<0.001. This superiority of isotopes over osmic acid was still observed after 6 months for the 89 joints that were re-evaluated, with follow-up ranging from 1 to 9 years. It was possible to calculate a radiological score in 84 cases. With OA the best results were from the joints with the lowest scores pre-synovectomy (<7). No correlation could be established between the clinical and the radiological scores, due to the small size of the sample. In summary: (1) chemical and radioactive synovectomy are simple and safe procedures for haemophilic arthropathy, (2) in our series, after 6 months the efficacy of isotopic synovectomy was greater than that of chemical synovectomy, and this benefit seems to persist after 6 months, and up to 9 years in the group of patients with longer-term follow-up.     

Detection and viability of tumor cells in peripheral blood stem cell collections from breast cancer patients using immunocytochemical and clonogenic assay techniques [see comments]

Although peripheral blood stem cell collections (PBSC) are thought to have less tumor involvement than bone marrow (BM), the incidence of circulating tumor cells in patients with breast cancer has not been widely investigated. We prospectively investigated the incidence and viability of tumor cell involvement in PBSC and BM collections from breast cancer patients undergoing high-dose chemotherapy/hematopoietic stem cell transplantation. Paired samples of PBSC and BM from 48 patients were analyzed using an immunocytochemical technique that detects one epithelial-derived tumor cell per 5 x 10(5) mononuclear cells. Immunostained tumor cells were detected in 9.8% (13/133) PBSC specimens from 9/48 (18.7%) patients and in 62.3% (38/61) BM specimens from 32/48 (66.7%) patients, a significantly higher rate than in PBSC (P < .005). The geometric mean concentration of tumor cells in contaminated PBSC specimens was 0.8/10(5) mononuclear cells (range 0.33 to 2.0/10(5)) compared with 22.9/10(5) mononuclear cells in BM (range 1 to 3,000/10(5), P < .0001). In culture experiments, clonogenic tumor colonies grew in 21/26 immunocytochemically positive specimens. No tumor colony growth was detected in 30/32 immunocytochemically negative specimens. Immunocytochemical detection of tumor involvement in BM and PBSC correlated significantly with in vitro clonogenic growth (P < .0001). We conclude that PBSC contain fewer tumor cells than paired BM specimens from patients with advanced breast cancer and that these tumor cells appear to be capable of clonogenic growth in vitro.     

In vivo biologic effects of PIXY321, a synthetic hybrid protein of recombinant human granulocyte-macrophage colony-stimulating factor and interleukin-3 in cancer patients with normal hematopoiesis: a phase I study

PIXY321 is a novel fusion protein of recombinant human granulocyte- macrophage colony-stimulating factor and interleukin-3 that exhibits biologic effects of both its parent cytokines in vitro and in preclinical studies. To evaluate the clinical safety and hematopoietic effects of this hybrid cytokine, PIXY321 was administered by subcutaneous injection twice daily at doses of 25 to 1,000 micrograms/m2/day over 14 days to 24 patients with sarcoma before chemotherapy as part of a phase I trial. The treatment was associated with significant increases in white blood cell, neutrophil, platelet, and reticulocyte counts (all P < .001). The increase in neutrophil count was dose-related and was seen during treatment with the cytokine, whereas the increase in platelet count was gradual and peaked after the cessation of the cytokine treatment and was not clearly dose related. PIXY321 treatment also increased bone marrow (BM) cellularity and the percentage of BM cells in S phase (P < .001). In addition, there was a significant increase in the number of CD34+ cells and committed and multipotential progenitors in the peripheral blood. The ex vivo expansion capacity of peripheral blood and BM progenitor cells was preserved after the in vivo treatment with PIXY321. The treatment was well tolerated, with the most common side-effect being injection site reactions. The results of this study show the biologic and clinical activity of a genetically engineered fusion molecule of two hematopoietic cytokines in humans with normal hematopoietic function.     

Catecholamine turnover rates in discrete hypothalamic areas and associated changes in median eminence luteinizing hormone-releasing hormone and serum gonadotropins on proestrus and diestrous day 1

We have correlated catecholamine [CA; i.e. norepinephrine (NE), dopamine (DA), and epinephrine (E)] turnover rates in discrete hypothalamic nuclei and in the median eminence (ME), with concentration changes in ME LHRH and serum LH, FSH, PRL, estradiol, and progesterone levels at various times during proestrus and diestrous day 1 in 4-day cyclic rats. CA concentrations were measured with a radioenzymatic assay at 0, 60, and 120 min after ip injection of 400 mg/kg alpha-methyl-p-tyrosine, and rate constants and turnover rates were calculated. In a separate assay NE, DA, and E were separated by two-dimensional thin layer chromatography, and concentrations and turnover rates of CAs were calculated. The microdissected hypothalamic nuclei examined for NE turnover rates included the medial preoptic nucleus (MPN), suprachiasmatic nucleus (SCN), arcuate nucleus (AN), and ME. DA turnover rates also were measured in the MPN, ME, and AN. ME LHRH and serum hormone concentrations were measured by RIA. Between 0900--1200 h, proestrous serum estradiol was elevated, but other serum hormones were basal, and CA turnover rates in the brain were low. However, ME LHRH concentrations increased significantly between 0900--1200 h on proestrus. Between 1200--1500 h, serum LH, FSH, PRL, and progesterone levels increased and ME LHRH levels declined significantly; during this time interval (1200--1400 h), a significant rise in ME NE and DA turnover rates occurred. Between 1500--1700 h on proestrus, while serum gonadotropins were still rising toward peak concentrations, increased ME NE turnover rates were maintained, but increased NE turnover rates also were evident in MPN, SCN, and AN. During this same time interval (1500--1700 h), a marked decline in ME and AN DA turnover rates occurred, although such rates remained unchanged within the MPN. There were no corresponding changes in MPN E turnover rates at any of the time intervals studied. The increased turnover rates of ME NE coupled with the concomitant decline in ME LHRH levels and the rise in plasma LH and FSH levels suggest that increased NE release may be important in initiating preovulatory LH and FSH surges. These changes in brain neurotransmitters and serum hormones are not the result of a diurnal rhythm, since corresponding changes in CA turnover rates or serum gonadotropins did not occur between 0900--1100 h and 1500--1700 h diestrous day 1.     

Human platelets exert cytotoxic effects on tumor cells

Monocytes are thought to play a role in host resistance to tumor cell growth in animals and humans. In addition, platelets are known to be involved in tumor metastases. To investigate the interaction of these two cell types and their effect on tumor cells, human monocytes and platelets were examined using an in vitro monocyte-tumor cell cytotoxicity assay. Monocytes alone resulted in 32% +/- 1.5 (mean +/- SEM) tumor cell kill. When platelets were added to monocytes in a 1:1 ratio, an increase in cytotoxicity to 61% +/- 3.2 was observed. The cytotoxicity noted when platelets were added to a fixed number of monocytes and tumor cells was dependent on the number of platelets added. A decrease in cytotoxicity from 32% +/- 1.5 to 12% +/- 2.3 was observed when contaminating platelets were removed from monocyte preparations. Platelets added to tumor cells in the absence of any monocytes were also toxic, resulting in a maximum kill of 95% at a 4:1 platelet/tumor cell ratio. Secreted products of freshly isolated platelets may be responsible for much of the observed cytotoxicity, since supernatants from the platelets were toxic for tumor cells. Platelets pretreated with a cyclooxygenase inhibitor (ASA) or a lipoxygenase inhibitor had decreased cytotoxicity compared with untreated platelets. Our results indicate that products of platelet arachidonate metabolism are toxic for tumor cell lines. They also suggest that the role of the platelet must be considered when studying monocyte-tumor cell cytotoxicity.     

Hairy cell leukemia and myelomatosis: chance association or clinical manifestations of the same B-cell disease spectrum

We describe three patients who had typical features of hairy cell leukemia (HCL) and multiple myeloma (MM) at the same time. In two, both diagnoses were made within a short period of time, and in the third, HCL had been present for 2 yr before the appearance of a paraprotein, bone lesions, and plasma-cell infiltrates established the diagnosis of MM. Although this association has not been previously reported, cases of HCL with osteolytic lesions or a paraprotein band have been described. The cases described may represent clinical manifestations of closely related disorders arising from divergent differentiation from a common B-cell precursor rather than a chance association.     

Coeliac axis thrombosis associated with the combined oral contraceptive pill: a rare cause of an acute abdomen

We report a case of coeliac axis thrombosis and splenic infarction presenting in a girl of 14 years who had been on the oral contraceptive pill (OCP), Marvelon (ethinyloestradiol 30 μg plus desogestrel 150 μg, Organon, Cambridge, UK), for 3 weeks. She had no other risk factors for thrombo-embolism. Diagnosis was made with duplex Doppler ultrasound and confirmed with dynamically-enhanced comput‐ed tomography and magnetic resonance angiography, thus avoiding the need for percutaneous arteriography. Though mesenteric thrombo-embolic disease is recognised in association with use of the combined OCP, it has not previously been reported to affect the coeliac axis. Paediatricians and surgeons should be aware of the risks to young girls on the OCP, and consider it in their differential diagnosis of the acute abdomen. Accepted: 4 April 1997