The PFA‐100® does not predict delta‐granule platelet storage pool deficiencies

Summary.  There are no published reports investigating the ability of the platelet function analyzer (PFA‐100^®) to detect the presence of delta‐granule platelet storage pool deficiencies (δ‐PSPD), a common mild bleeding disorder. Prior studies of the PFA‐100^® and congenital platelet disorders have been limited by small numbers of patients with a variety of disorders. We examined PFA‐100^® results in a large paediatric patient population diagnosed specifically with δ‐PSPD, and determined the relationship between PFA‐100^® and platelet electron microscopy (the gold standard for diagnosis). This study is a retrospective review of patients <19 years of age diagnosed with δ‐PSPD at Nationwide Children’s Hospital from 2008 to 2010. To examine the correlation between PFA‐100^® and average number of granules per platelet we used Spearman’s Rho as a non‐parametric measure of dependence. A total of 105 patients diagnosed with δ‐PSPD were included, of which 99 patients underwent PFA‐100^® testing. Of those tested 46% had at least one abnormal closure time, whereas 16% had abnormal results for both cartridges. We found no statistical correlation between C‐EPI closure time and average number of granules per platelet (ρ= ?0.0095, P‐value = 0.9328), nor between C‐ADP closure time and the average number of granules (ρ = 0.0315, P‐value = 0.7798). The PFA‐100^®, a widely used screening test for suspected bleeding disorders, did not correlate with presence or severity of δ‐PSPD as determined by platelet electron microscopy. When evaluating patients with suspected bleeding disorders, PFA‐100^® alone cannot be used to rule out the presence of a δ‐PSPD.     

Reasons for enhanced activity of doxorubicin on co-delivery with octa(3-aminopropyl)silsesquioxane

This paper presents results of spectroscopic (NMR, FTIR, fluorescence), Q-TOF mass spectrometry and Z-potential analyses of interactions between octa(3-aminopropyl)silsesquioxane hydrochloride (POSS-NH₂·HCl) and anticancer drug – doxorubicin hydrochloride. These studies aimed at explanation of the enhanced activity of doxorubicin on co-delivery with POSS-NH₂. The results point to the formation of active complexes via ionic interactions between the ammonium chloride groups of silsesquioxane and the drug, and not, as suggested earlier, via NH⋯N hydrogen bonding. It has also been shown that the main driving force for the formation of the complexes can be strengthened by π–π stacking and hydrogen bonds. The experimental results are supported by quantum mechanical calculations. This work has proven that co-delivery with POSS offers a potentially advantageous and simple approach for improved efficacy in chemotherapy, avoiding often complicated synthesis of conjugates, involving covalent bonding between drug, nanocarrier and targeting agents.

The interaction between polyhedral oligomeric silsesquioxane (POSS) and doxorubicin, leading to formation of active complexes involving POSS functional aminopropyl groups and anthracycline functional groups.     

Laparoendoscopic single-site (LESS) varicocelectomy with reusable components: comparison with the conventional laparoscopic technique

Background

This study aimed to compare laparoendoscopic single-site varicocelectomy (LESSV) with multiport laparoscopic varicocelectomy (MLV) in terms of intraoperative parameters and postoperative outcomes.

Methods

A retrospective case–control study investigated 10 male adolescents and 89 adults who underwent either LESSV or MLV at the authors’ center. The reusable X-Cone single port was inserted transumbilically. A 5-mm 30° telescope was used together with a straight and a prebent laparoscopic instrument. The MLV procedure was performed using two 5-mm ports and one 10-mm port.

Results

Between January 2009 and November 2012, 20 patients underwent LESSV and 79 patients underwent MLV. The demographic data were comparable between the two groups. The mean operating time was 59.1 ± 15.5 min for LESSV and 51.2 ± 14.4 min for MLV (P = 0.04). In the LESSV group, no conversion to MLV was necessary. The hospital stay was 1.6 ± 0.7 days in the LESSV group versus 1.8 ± 0.5 days in the MLV group (P = 0.17). The postoperative pain scores did differ between the two groups. By day 2, significantly more patients in the LESSV group than in the MLV group fully recovered their normal physical activity (P = 0.02). Comparison of pre- and postoperative values showed relief of testicular pain and improvement of semen parameters for the majority of the patients. The overall incidence of complications was distributed equally between the two groups as follows: paresthesia of the upper thigh (8 %), wound infection (5 %), epididymitis (3 %) and hydrocele (4 %). All the patients in the LESSV group were fully satisfied with their cosmetic results compared with only 76 % of the patients in the MLV group (P = 0.01).

Conclusions

The LESSV procedure performed with the reusable X-Cone is as safe and efficient as MLV. After LESSV, the parameters measuring postoperative patient satisfaction are significantly improved. Given its reusable components, including prebent laparoscopic instruments, the X-Cone platform is a cost-effective alternative to disposable or homemade single ports.     

Dynamic changes of B‐cell compartments in kidney transplantation: lack of transitional B cells is associated with allograft rejection

B cells play an important role in the immune responses which affect the outcomes of kidney allografts. Dynamic changes of B‐cell compartments in clinical kidney transplantation are still poorly understood. B‐cell subsets were prospectively monitored using flow cytometry for 1 year in 98 kidney transplant recipients. Data were correlated with immunosuppression and clinical outcomes. An increase in the total population of B lymphocytes was observed during the first week after transplantation. The level of IgM^highCD38^highCD24^high transitional B cells reduced significantly up until the third month, with partial repopulation in the first year. Lower numbers of transitional B cells in the third month were associated with higher risk of graft rejection. IgM⁺IgD⁺CD27^? naive B cells did not change within follow‐up. IgM⁺CD27⁺ nonswitched memory B cells and IgM^?CD27⁺ switched memory B cells increased on post‐operative day 7. IgM^?CD38^highCD27^high plasmablasts showed similar kinetics during the first post‐transplant year, similar to transitional B cells. In conclusion, sensitized kidney transplant recipients as well as those with either acute or chronic rejection within the first post‐transplant year exhibited lower levels of transitional B cells. Therefore, these data further support the hypothesis that transitional B cells have a protective role in kidney transplantation.     

Investigating the human immunodeficiency virus type 1-infected monocyte-derived macrophage secretome

Mononuclear phagocytes (bone marrow monocyte-derived macrophages, alveolar macrophages, perivascular macrophages, and microglia) are reservoirs and vehicles of dissemination for the human immunodeficiency virus type-1 (HIV-1). How virus alters mononuclear phagocyte immunoregulatory activities to complete its life cycle and influence disease is incompletely understood. In attempts to better understanding the influence of virus on macrophage functions, we used one-dimensional electrophoresis, and liquid chromatography tandem mass spectrometry to analyze the secretome of HIV-1-infected human monocyte-derived macrophages. We identified 110 proteins in culture supernatants of control (uninfected) and virus-infected cells. Differentially expressed cytoskeletal, enzymes, redox, and immunoregulatory protein classes were discovered and validated by Western blot tests. These included, but were not limited to, cystatin C, cystatin B, chitinase 3-like 1 protein, cofilin-1, l-plastin, superoxide dismutase, leukotriene A(4) hydrolase, and alpha-enolase. This study, using a unique proteomics platform, provides novel insights into virus-host cell interactions that likely affect the functional role of macrophages in HIV disease.