Monoclonal antibodies to human platelet glycoprotein IIb beta that initiate distinct platelet responses

Hybridomas secreting monoclonal antibodies (MoAbs) to human platelet membrane glycoprotein IIb (GPIIb) were prepared by fusing cells of a mouse myeloma line to spleen cells from a BALB/c mouse immunized with purified GPIIb. Six of the hybridomas secreted MoAbs that recognized epitopes on the 23,000-dalton, disulfide-linked subunit of GPIIb, GPIIb beta. All six of these MoAbs agglutinated platelets in the absence of calcium. The agglutination titers of three of the MoAbs, however, were enhanced between 2 and 6 log2 dilutions when titrated in the presence of mmol/L of calcium. The enhancement in titer was the result of MoAb- induced platelet activation followed by platelet aggregation, a reaction that could also be initiated by the monovalent Fab fragments prepared from one of the MoAbs. The MoAbs did not significantly agglutinate platelets from patients with Glanzmann's thrombasthenia, confirming biochemical evidence that there is a paucity of GPIIb beta in the membranes of these cells. Our results show that MoAbs to epitopes on GPIIb beta initiate distinct platelet responses; therefore, they should be useful for studying the ways in which regions of surface glycoproteins are involved in platelet-platelet interactions. In addition, these reagents may prove of value in diagnosing and typing patients with Glanzmann's thrombasthenia.     

Internal mammary artery and vein: recipient vessels for free tissue transfer to the head and neck in the vessel-depleted neck

BACKGROUND: Microvascular free tissue transfer is a standard reconstructive option for postablative defects of the head and neck. However, the success of this surgery requires suitable recipient vessels in the cervical region. This form of reconstruction can be particularly challenging in the vessel-depleted neck. While the internal mammary artery and vein (IMA/V) have been used extensively in breast reconstruction, there are few reports describing their use in head and neck reconstruction. We report the first case series of the use of the internal mammary vessels for head and neck microvascular reconstruction. METHODS: We reviewed 5 cases of free tissue transfers to the head and neck in which extensive prior treatment precluded the use of more traditional recipient vessels in the neck or upper chest. RESULTS: A variety of free flaps were transferred for different reconstructive problems which included: chin/lower lip (n = 2), closure of widely patent tracheoesophageal puncture sites (n = 2), and pharyngoesophageal reconstruction following staged repair of a severe stenosis (n = 1). The radial forearm free flap was transferred in 4 patients and the rectus abdominus free flap in 1 patient. The IMA/V on the right side was prepared in all cases. All free flaps were successfully revascularized without the need for vein grafts and without the need for any microvascular revision procedures. CONCLUSION: The internal mammary artery and vein provide reliable, easily accessible recipient vessels for microvascular reconstruction in the vessel-depleted neck. The selection of free flap donor sites with long donor vessels facilitates the microvascular repair.     

Sera from patients with heparin-induced thrombocytopenia generate platelet-derived microparticles with procoagulant activity: an explanation for the thrombotic complications of heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia is characterized by moderate thrombocytopenia and thrombotic complications, whereas quinine/quinidine-induced thrombocytopenia usually presents with severe thrombocytopenia and bleeding. Using flow cytometry and assays of procoagulant activity, we investigated whether sera from patients with these immune drug reactions could stimulate normal platelets to generate platelet-derived microparticles with procoagulant activity. Sera or purified IgG from patients with heparin-induced thrombocytopenia stimulated the formation of platelet-derived microparticles in a heparin-dependent fashion. Further studies showed that heparin-induced thrombocytopenia sera also produced a marked increase in procoagulant activity. In contrast, sera from patients with quinine- or quinidine-induced thrombocytopenia did not generate platelet-derived microparticles nor generate increased procoagulant activity. However, quinine/quinidine-induced thrombocytopenia sera produced a significant increase in the binding of IgG to platelets in a drug-dependent fashion, whereas sera from patients with heparin-induced thrombocytopenia demonstrated no drug-dependent binding of IgG to platelets. We also observed increased levels of circulating microparticles in patients with acute heparin-induced thrombocytopenia compared with control patients. Our observations indicate that the generation of procoagulant platelet-derived microparticles in vivo is a plausible explanation for the thrombotic complications observed in some patients with heparin-induced thrombocytopenia.     

Allogeneic marrow transplantation in patients with chronic myeloid leukemia in the chronic phase: a randomized trial of two irradiation regimens

A randomized trial was performed to compare two regimens of total body irradiation in patients with chronic myeloid leukemia treated by allogeneic marrow transplantation while in the chronic phase. All patients received cyclophosphamide 120 mg/kg followed by total body irradiation and marrow from HLA-identical siblings. Cyclosporine and methotrexate were used for prophylaxis against acute graft-versus-host disease. Fifty-seven patients were randomized to receive 2.0 Gy fractions of irradiation daily for 6 days and 59 were randomized to receive 2.25 Gy fractions daily for 7 days. The probabilities of relapse at 4 years were 0.25 for the 12.0 Gy group and 0.00 for the 15.75 Gy group (P = .008). The actuarial probabilities of survival and relapse-free survival at 4 years were 0.60 and 0.58 among the patients who received 12.0 Gy compared with 0.66 and 0.66 for those who received 15.75 Gy. The 4-year probabilities of transplant-related mortality were 0.24 and 0.34 respectively (P = .13) while the probability of moderate to severe acute graft-versus-host disease was 0.33 for the 12.0 Gy group and 0.44 for the 15.75 Gy group (P = .15). The lower relapse probability in the patients receiving the higher dose of total body irradiation did not result in improved survival because mortality from causes other than relapse was increased.     

Bortezomib,Melphalan, and Prednisone (VMP) Regimen for Multiple Myeloma

The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr, President, Oncology Pharmacy Services, Inc., 4201 Wilson Blvd #110-545, Arlington, VA 22203, e-mail: ten.tsacmoc@cvSxRcnO; or J. Aubrey Waddell, Professor, University of Tennessee College of Pharmacy; Oncology Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander Parkway, Maryville, TN 37804, e-mail: ten.retrahc@ruofddaw.Regimen name: VMPOrigin of name: VMP is an acronym for the 3 drugs (bortezomib [Velcade], melphalan, and prednisone) in the regimen.     

Change in Alcohol Use Based on Self-Report and a Quantitative Biomarker,Phosphatidylethanol, in People With HIV

AIDS and Behavior - The timeline followback (TLFB) takes more resources to collect than the Alcohol Use Disorder Identification Test (AUDIT-C). We assessed agreement of TLFB and AUDIT-C with the...