HLA class-I and -II antigens in chronic idiopathic autoimmune thrombocytopenia

Summary We studied MHC class-I and -II phenotypes in adult Caucasian patients with chronic idiopathic autoimmune þrombocytopenia (cAITP). Forty-five patients (median age 51 years, range 21–78 years) with a median disease duration of 7 years (range 2–26 years) were phenotyped for HLA-A, -B, -C by the standard lymphocytotoxicity test, HLA-DR and-DQ by restriction fragment-length polymorphism (RFLP), and-DP by oligonucleotide typing. Antiplatelet antibodies directed against glycoproteins Ib/IX and IIb/IIIa were determined by monoclonal antibody-specific immobilization of platelet antigens (MAIPA). The comparison of antigen frequencies of the whole group of patients with healthy controls revealed no significant difference for any of the MHC class-I or class-II specificities (p>0.05). Patients were then divided into groups based on (a) their response to therapy, and (b) on whether they did or did not have detectable anti-platelet antibodies (n=16 versusn=29). All patients with a poor response to splenectomy carried the HLA-DPB1*0402 phenotype. The HLA-DPB1*1501 allele was found only among patients with detectable antiplatelet antibodies. These differences were not significant after correction for the number of tested antigens, however. Our data suggest that there is no association between MHC class-I/II alleles and adult cAITP or subgroups thereof.     

Spinal metastases mimicking low back pain of mechanical origin: a case report

Spinal malignancies are an essential consideration when a patient presents to a chiropractic office with back pain. This single case report exemplifies the importance of patient presentation and physical examination findings. We must also consider the rationale for x-raying patients on an individual case basis. Textbook cases do not always exist and special diagnostic tests do not always provide a definitive diagnosis of underlying pathology. Even though history and examination findings suggest a routine diagnosis, continual re-evaluation and recognition of the need to change the diagnosis on occasion is extremely important. The patient should not only be thoroughly evaluated upon initial presentation, but also each time they present for treatment. The decision to x-ray a patient is considered important. X-ray examination can be used to confirm a diagnosis or to rule out potential pathologies, and not necessarily done as a routine screening procedure.A case report is presented in which the pathologic signs were not evident on plain film x-rays upon initial presentation.     

Parameters influencing FVIII pharmacokinetics in patients with severe and moderate haemophilia A

In haemophilia A patients factor VIII (FVIII) recovery and half‐life can vary substantially. There are parameters known to modulate FVIII pharmacokinetics (PK), but they explain only about 34% of the variability. The aim of this study was to identify new parameters that influence FVIII PK and thus to expand the current knowledge. FVIII PK were determined in 42 haemophilia A patients (37 severe, 5 moderate) without inhibitor. Patients' characteristics and laboratory parameters were evaluated for an association with FVIII PK. We analysed plasma levels of low‐density lipoprotein receptor‐related protein 1 (LRP1) and protein C (PC) activity, which had been hypothesized to influence FVIII activity. Furthermore, four variations in intron 6 of the LRP1 gene, which had been shown to influence LRP1, were investigated. FVIII half‐life differed widely from 6.2 to 20.7 h, with a median of 10.0 h. Patients with blood group O had shorter FVIII half‐life compared to patients with non‐O blood group (median FVIII half‐life 9.0 h vs. 10.4 h, P = 0.018). Age was significantly associated with FVIII half‐life (r = 0.32, P = 0.035). Besides age, also VWF antigen (r = 0.52, P < 0.001) and blood group (r = ?0.37, P = 0.015) was associated with FVIII half‐life. No correlation was found with FVIII‐ or LRP1‐genotype, LRP1 or PC concentrations. Our data showed large differences in FVIII PK between individual patients and revealed age, blood group and VWF levels as important determining factors for FVIII half‐life. FVIII genotype or levels of LRP1 or PC had no influence on FVIII PK.     

Fixed-dose single administration of Pegfilgrastim vs daily Filgrastim in patients with haematological malignancies undergoing autologous peripheral blood stem cell transplantation

Infectious complications are frequent events in patients undergoing high-dose cytotoxic chemotherapy with subsequent autologous peripheral blood stem cell transplantation (PBSCT). To evaluate whether a single subcutaneous injection of pegfilgrastim (6 mg) is as safe and effective as daily filgrastim (5 mug/kg/day), 60 consecutive autologous stem cell transplantations performed for various haematological malignancies have been analysed. In total, 24 patients undergoing 30 consecutive PBSCT received a single subcutaneous injection of 6 mg pegfilgrastim on day 5 after transplantation and were compared retrospectively with 30 patients receiving 5 mug/kg/day of filgrastim starting from day 7 post transplantation. The mean duration of grade 4 neutropenia in the pegfilgrastim and filgrastim groups was 8.3 and 9.5 days, respectively (P=0.047). The results of the two groups were not significantly different for incidence of febrile neutropenia and toxicity profile. However, duration of febrile neutropenia (1.6 vs 3.0 days) and total days of fever (1.73 vs 4.1) were different (P=0.017 and 0.003, respectively), favouring the pegfilgrastim arm. Consequently, a higher incidence of transplants with documented infectious complications associated with the filgrastim group could be observed (56 vs 26%) (P=0.02). A single injection of pegfilgrastim administered at day 5 post transplant shows comparable safety and efficacy profiles to daily injections of filgrastim.     

Expression of inducible nitric oxide synthase in muscle flaps treated with ischemic postconditioning

Background/Objective

Preconditioning has been considered promising for the treatment of ischemic flaps. In this study, the therapeutic effect of postconditioning was compared with that of preconditioning during ischemia/reperfusion (I/R) injury, and a role of inducible nitric oxide synthase (iNOS) in postconditioning treatment was also explored.

Methods

Sixty rats were randomly divided into four groups with 15 rats in each group. Ischemic injury was induced in a rat’s gracilis muscle flap model. Preconditioning and postconditioning were performed respectively on the flaps in the pre-con group and the post-con group. No treatment was given to the flaps in the control group, and flaps without I/R injury were used as a sham control. Muscle viability ratio, histology, and gene expression of iNOS were examined at different time intervals (3, 12, and 18 h).

Results

A significantly higher survival ratio was observed in both the pre-con group (78.98 ± 3.39, 62.74 ± 3.7, and 54.42 ± 4.45 %) and the post-con group (77.42 ± 4.14, 59.74 ± 6.67, and 49.52 ± 4.13 %) than the control group (45.22 ± 3.69, 42.44 ± 3.76, and 33.2 ± 3.29 %) at 3, 12, and 18 h postoperatively (P < 0.05). There was no statistical difference between the pre-con group and the post-con group (P > 0.05). Histological examination showed delayed and attenuated tissue damage in both the pre-con group and the post-con group when compared to that of the control group. A higher expression of iNOS was observed in both the pre-con group and the post-con group than the control group and the sham group (P < 0.05).

Conclusions

Significant improvement of flap survival could be achieved by both preconditioning and postconditioning treatments; however, better protection could be provided by preconditioning. The higher expression of iNOS may play an important role in the therapeutic effect of postconditioning during I/R injury.     

On the interaction of rabbit antithrombin III with the luminal surface of the normal and deendothelialized rabbit thoracic aorta in vitro

Pure rabbit antithrombin III was isotope labeled (with 125I or 3H) by two different methods; neither procedure caused a loss of antithrombin activity although both methods affected the affinity of the protein for Sepharose-heparin. From segments from freshly excised rabbit aorta, the uptake of isotope-labeled antithrombin III by the endothelium was rapid and saturable, although relatively small compared to the uptake of thrombin; binding of 3H-antithrombin III to the endothelium resembled that of 125I-antithrombin III. Transendothelial passage of antithrombin III into the subendothelial layers (intima-media) was slow and progressive. Endothelium binding was not affected by pretreating the vessel with either heparin, thrombin, or glycosaminoglycan-specific enzymes. Endothelium-bound antithrombin III was not selectively displaced by either heparin or thrombin. In contrast, endothelium-bound thrombin was rapidly dislodged by antithrombin III as a thrombin- antithrombin III complex. The surface of the deendothelialized aorta (ie, subjected to a balloon catheter) bound antithrombin III avidly. Pretreatment of the deendothelialized vessel with glycosaminoglycan- specific enzymes, particularly heparitinase, decreased intima-media binding by up to 80%. 125I-antithrombin III, when bound to the deendothelialized vessel surface, was actively displaced by either heparin, thrombin, or by unlabeled antithrombin III. The relatively poor binding of antithrombin III compared with that of thrombin by the endothelium in vitro supports an earlier proposal (Lollar P, Owen WG: J Clin Invest 66:1222-1230, 1980) that thrombin bound to high-affinity sites, possibly pericellular proteoglycan, of the endothelium is inactivated by plasma antithrombin III in vivo. Such a situation probably holds for large arteries at least.