An association between mastocytosis and monoclonal gammopathy is a relatively rare but well recognized clinical finding. In the majority of cases, however, overt myeloma or lymphoma is not detectable ...morphologically. Here we describe the case of a 51 year-old male patient first presenting with paresis of the right facial nerve and the serological finding of IgM kappa paraproteinemia. The patient did not have organomegaly, lytic bone lesions, or urticaria pigmentosa-type skin lesions. Histological examination of a trephine biopsy specimen revealed the unusual coexistence of plasma cell myeloma and mastocytosis. Immunohistochemically, plasma cells were found to exhibit a monotypic staining for Ig heavy chain mu and Ig light chain kappa, thus confirming their neoplastic nature. Mast cells showed prominent spindling and formed dense multifocal infiltrates, thus enabling the diagnosis of bone marrow mastocytosis. Immunohistochemically, mast cells expressed tryptase, chymase, and KIT (CD117). In addition, aberrant expression of CD25 on mast cells was detected, confirming the coexistence of a neoplastic mast cell-proliferative disorder. According to the WHO proposal for classification of hematopoietic malignancies, this unique case, showing the association of two very rare haematologic neoplasms, can therefore best be referred to as bone marrow mastocytosis associated with IgM kappa plasma cell myeloma (SM-AHNMD).
We conducted a phase I/II trial of 5-fluorouracil (5-FU)/folinic acid (FA) and alpha-2b interferon (IFN) in 43 previously untreated patients with measurable metastatic colorectal cancer. Patients had ...disease progression prior to therapy consistent of 5-FU 500 mg/m2 (level A) or 600 mg/m2 (level B) as starting dose administered as a 2-hour infusion, FA 200 mg/m2, and alpha-2b IFN 5MU/m2 subcutaneously. All drugs were given on days 1 to 5 and cycles were repeated after 3 to 4 weeks. The aim of the study was to define the maximal tolerable dose (MTD) of 5-FU for this schedule. In the absence of toxicity above MTD, defined as diarrhea and mucositis of World Health Organization grade 2 and leukopenia of World Health Organization, grade 3 5-FU was increased in increments of 100 mg/m2 for further cycles. Twenty-four patients were started on level A; 18 were started on level B. Forty-two patients were evaluable for toxicity, 32 for response. Three of 32 patients achieved a partial response; in 22 of 32 patients, tumor stabilization occurred. Forty percent of patients started on level A developed grade 2 diarrhea; 28% of patients developed grade 2 or 3 mucositis. Of 18 patients on level B, two patients experienced grade 4 mucositis (11%) and grade 3 or 4 diarrhea (11%). One drug-related death in the presence of sepsis occurred. Due to 11% of patients with grade 4 toxicity when started on 600 mg/m2 5-FU and 40% of patients with grade 2 diarrhea when started on level A, MTD as starting dose for 5-FU is 500 mg/m2 as a 2-hour infusion when used in combination with FA and IFN on a day 1 to 5 active schedule. We observed a wide range of 5-FU dose tolerated by individual patients. While some patients experienced severe, mainly gastrointestinal, toxicity on lower levels of 5-FU, others tolerated much higher 5-FU doses (11 patients, 700 mg/m2; 5 patients, 800 mg/m2; and one patient, 900 mg/m2). Our data suggest that double modulation of 5-FU by FA and IFN may not be superior to modulation of 5-FU with either drug alone.
Platelet factor 3 activity is usually determined by the Stypven method in which factor Xa generation is measured indirectly. The determination is dependent on factors I, II, V, X in the test sample. ...A coagulation assay for platelet factor 3, which measures the thrombin generation promoted by platelet factor 3, is presented. The test depends on platelet factor 3 only, because factors II, Xa, V, fibrinogen and Ca++ are added in excess. The usability of the new method is shown by platelet factor 3 determinations in patients with various platelet diseases, after ingestion of aspirin and in samples of platelet concentrates before and after storage.
A time-saving and sensitive high resolution method for the analysis and identification of platelet glycoproteins using nonradioactive compounds has been developed. Platelet proteins (50 micrograms) ...of normal subjects were separated by isoelectric focusing and SDS-PAGE. Proteins were either stained with silver or electroblotted onto nitrocellulose. Nitrocellulose blots were treated with the following biotinylated lectins: Abrus precatorius lectin, concanavalin A, Lens culinaris lectin, or wheat germ agglutinin. Staining was achieved by avidin-biotin-coupled peroxidase using 4-chloro-1-naphthol as the substrate. A rapid overview of platelet glycoproteins may be obtained by applying all the lectins to a single blot.
Aggregation of platelets by fibrils formed from collagens type I, II and III could be inhibited by coating the fibrils with anti-collagen antibodies or Fab fragments. Similar results were obtained in ...a clot-retraction assay. Inhibition was achieved with stoichiometric amounts of antibodies and was specific for each type of collagen. Aggregation caused by a mixture of type-I and -III collagens could only be inhibited by a mixture of antibodies against both collagens. The data show that each interstitial collagen is capable of interacting with platelets and do not support the concept of an outstanding activity of type-III collagen.
In a pilot study 16 patients with advanced inoperable stomach cancer were treated with Etoposide, Adriamycin, Cisplatin. The recommended dose for phase II studies was established and first therapy ...results are presented. Two of 16 patients responded with complete remissions and 8 with partial remissions. The recommended dose schedule for phase II studies is: Adriamycin 20 mg/m2 i.v. day 1 + 7; Cisplatin 40 mg/m2 i.v. day 2 + 8; Etoposide 120 mg/m2 i.v. day 4, 5, 6, every four weeks.
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