Maintenance treatment of adults with chronic refractory immune thrombocytopenic purpura using repeated intravenous infusions of gammaglobulin [see comments]

Intravenous infusion of gammaglobulin (IVGG) has been extensively used in the treatment of immune thrombocytopenic purpura (ITP) in adults to acutely raise the platelet count but not as a maintenance therapy. This report describes the maintenance treatment of adults with chronic ITP using repeated infusions of 800 to 1,000 mg/kg of IVGG. Sixteen of 40 patients were able to discontinue all therapy after receiving between one and 15 infusions. Five patients achieved remission and 11 other patients became stable without therapy (SWT) maintaining a platelet count greater than 20,000/microL without bleeding. The average quantity of gammaglobulin received for all patients was 606 g per patient. Of the 30 patients who underwent but did not respond to splenectomy, 11 (37%) were able to discontinue all therapy by either achieving remission (5) or becoming SWT (6). None of the five patients who achieved remission did so after only the initial therapy; all first received between one and 12 maintenance infusions. The ten splenectomized patients who were unresponsive to IVGG also failed to subsequently respond to conventional therapy including immunosuppressive agents and androgens. No toxicity of IVGG was seen except for postinfusion headaches. IVGG is an effective although expensive maintenance therapy for adults with ITP and is useful in patients who have not responded to splenectomy.     

Ovary volume in young and premenopausal adults: US determination. Work in progress

Normal adult ovary volume determined by ultrasonography (US) is often stated to be less than 6 cm3. This is based on data from teenagers and young adults aged 12-20 years. Recently, the mean normal volume determined by US was reported to be considerably higher. We measured the volumes of 28 ovaries from 15 healthy young adults and found them to range as high as 13.84 cm3, with an average of 6.48 cm3.     

Staphylococcal alpha-toxin: a structure-function study using a monoclonal antibody

A monoclonal antibody (A-Tox-653.1) selected for its reactivity in a dot immunoblot assay with denatured staphylococcal alpha-toxin has been isolated and its capacity to block the hemolytic and lethal activities of alpha-toxin measured. In addition, 'reactivity with monomer, hexamer, 125I-monoiodinated and CNBr peptides of alpha-toxin was studied. In all cases the reactions of the monoclonal antibody were compared to those obtained with anti-alpha-toxin rabbit hyperimmune serum. We find that while both the monoclonal antibody and the rabbit antiserum react with all forms of alpha-toxin, only the rabbit antiserum blocks hemolytic or lethal activity. Further, the rabbit antiserum reacts with CNBr fragments IV, V ad VII, whereas the monoclonal antibody reacts only with the carboxy terminal CNBr peptide VII. We conclude that, in solution, the carboxy terminal segment of alpha-toxin is relatively free and reaction with the monoclonal antibody neither impedes its binding to the specific receptor on the membrane nor interferes with formation of the hexamer complex.     

p72syk protein tyrosine kinase: an early transducer of sIgG-triggered apoptotic signalling in human follicular lymphoma cells

Cross-linking of B cell antigen receptor (sIg) elicits different biological responses, including cell activation, proliferation, differentiation, anergy and cell death depending on the maturational stage of the cell. We established the tumor cell lines HF-1.3.4 and HF- 4-9 from two patients with follicular lymphoma. Both cell lines carry the characteristic t(14;18) chromosomal translocation and display constitutively overexpressed Bcl-2. HF-1.3.4 represents a mature B cell with sIgG and several somatic hypermutations in its Ig genes, while HF- 4-9 is a less mature B cell, expressing sIgM and only a few mutations in its Ig genes. Cross-linking of sIg with antibodies leads to apoptosis in HF-1.3.4 cells but not in HF-4-9 cells. Triggering of sIg induced, within seconds, identical tyrosine phosphorylation of p53/56lyn protein tyrosine kinase (PTK) and p55blk PTK in both of the cell lines; however, a prominent tyrosine phosphorylation and activation of p72syk PTK only in HF-1.3.4 cells. We conclude that p72syk PTK is of importance in relaying apoptotic signalling upon sIg cross-linking in the HF-1.3.4 cell line. Given the mature phenotype of the HF-1.3.4 cell line it serves as a model for the late negative selection during B cell ontogeny. Moreover, our results question the current concept that a constitutive overexpression of BcI-2 confers resistance to sIg ligation-induced apoptosis in lymphoma cells.      

Chemoattractant-mediated stimulation of the respiratory burst in human polymorphonuclear leukocytes may require appearance of protein kinase activity in the cells' particulate fraction

Low doses of aliphatic alcohols produce divergent effects on the function of chemoattractant receptors on human polymorphonuclear leukocytes (PMNs) since they enhance chemotaxis but inhibit stimulation of superoxide production by chemoattractants. As such, alcohols can provide useful pharmacologic tools to probe the mechanisms of stimulus- response coupling in leukocytes. A role for protein kinase C has been implicated in the activation of the respiratory burst in PMNs. Although the vast majority of this enzyme activity is located in the cytosolic fraction of unactivated PMNs, protein kinase C activity appears in the particulate fraction of the cells when they are stimulated to produce superoxide by either chemoattractants or by phorbol myristate acetate (PMA). Doses of the alcohols that selectively inhibited stimulation of superoxide production by chemoattractants also inhibited the appearance of protein kinase C activity as well as an undefined protein kinase activity in the particulate fraction of the cells. In contrast, the alcohols did not affect either the ability of PMA to stimulate the production of superoxide in PMNs nor the appearance of protein kinase activity in the cells' particulate fraction. PMA is known to bind and activate protein kinase C directly, thus bypassing receptor-mediated events. These data suggest that alcohols inhibit the stimulation of the respiratory burst by chemoattractants in PMNs by blocking the ability of receptor occupancy to induce the appearance of protein kinase activity in particulate fractions. These results moreover suggest that the appearance of protein kinase activity in the particulate fraction may be required for activation of the respiratory burst in PMNs.     

High-yield platelet concentrates attainable by continuous quality improvement reduce platelet transfusion cost and donor exposure

BACKGROUND: Donor exposure risk and cost in platelet transfusion practice can be limited by increasing the recovery of platelets from donor units. STUDY DESIGN AND METHODS: This study presents results of continuous quality improvement efforts in platelet production and compares the in vivo therapeutic efficacy of currently produced platelet concentrates (PCs) with that of apheresis platelets. Production quality improvement measures included optimization of instrument performance (rotor speed trials), process (massaging whole- blood units, using cup liners, limiting spin-expression time, and refining plasma expression technique), and staff (intensive training with observation and ongoing quality control data feedback). Corrected count increments and increments per kg were calculated for transfusions of 4 pooled PCs and apheresis platelets over a 30-day period. RESULTS: The mean number of platelets per PC increased from 5.5 × 10(10) in 1975 to 9.69 × 10(10) in 1994. The mean platelet dose was 3.78 × 10(11) for 4 PCs and 4.17 × 10(11) for apheresis platelets. A total of 34 pooled PCs and 17 apheresis platelets was transfused to 21 patients. The mean increment, the increment per kg, and the corrected count increment were, respectively, 31 × 10(3) per microL, 4.8 × 10(2) per microL, and 14,700 for 4 PCs and 35.4 × 10(3) per microL, 5.4 × 10(2) per microL, and 14,700 for apheresis platelets. Differences were not significant. CONCLUSION: Therapeutic efficacy comparable to that of apheresis platelets can be obtained with 4 high-yield PCs.