Pentostatin in the treatment of hairy-cell leukemia

Pentostatin (2'-deoxycoformycin; Nipent), a potent inhibitor of adenosine deaminase, is a purine nucleoside analogue that is highly effective in the treatment of hairy-cell leukemia. This agent is capable of inducing durable complete remissions in the majority of patients, and is capable of re-inducing a complete remission in many of the patients who have relapsed. Pentostatin appears to have changed the natural history of this disease. Long-term follow-up studies suggest that patients with hairy-cell leukemia who are induced into complete remission have a projected survival comparable to age-matched controls. While purine nucleoside analogues induce profound T-cell dysfunction and longstanding immunosuppression, the incidence of secondary malignancies is apparently not increased. Infections still pose a threat to these patients, and effective strategies for treating this disease that do not further compromise the immune system are needed. Patients with this disease should be encouraged to participate in ongoing clinical trials to better define the optimal treatment regimen. New studies should explore the combination of pentostatin and rituxan in treating the typical form of hairy-cell leukemia, and the incorporation of new agents for those with the rare variant form of this disease.     

Quantitative differences in CD45 expression unmask functions for CD45 in B-cell development, tolerance, and survival

The receptor-like tyrosine phosphatase CD45 positively regulates antigen receptor signaling by dephosphorylating the inhibitory tyrosine of the src family kinases. CD45-deficient mice fail to fully unmask the role of CD45 in B cells because of the expression of a partially redundant tyrosine phosphatase, CD148. However, mice that are doubly deficient in CD45 and CD148 exhibit a very early block in B-cell development, thereby obscuring later roles for CD45. To overcome these limitations, here we take advantage of an allelic series of mice in which CD45 expression is titrated broadly (0-180%). Although high expression of CD45 inhibits T-cell receptor (TCR) signaling, we show that CD45 plays a purely positive regulatory role during B-cell receptor (BCR) signaling. In concert with exaggerated BCR signaling, increasing CD45 expression drives enhanced receptor editing in the bone marrow and profound loss of follicular and marginal zone B cells in the spleen. In the context of the IgHEL/sHEL model of B-cell tolerance, such high CD45 expression transforms anergy into deletion. Unexpectedly, elimination of the autoantigen sHEL in this model system in order to block clonal deletion fails to rescue survival of mature B cells. Rather, high CD45 expression reduces B-cell activating factor receptor (BAFFR) expression and inhibits B-cell activating factor (BAFF)-induced B-cell survival in a cell-intrinsic manner. Taken together, our findings reveal how CD45 function diverges in T cells and B cells, as well as how autoreactive B cells are censored as they transit development.     

Is flapless implant surgery a viable option in posterior maxilla? A review

This article reviews the literature on the outcome of flapless surgery for dental implants in the posterior maxilla. The literature search was carried out in using the keywords: flapless, dental implants and maxilla. A hand search and Medline search were carried out on studies published between 1971 and 2011. The authors included research involving a minimum of 15 dental implants with a follow-up period of 1 year, an outcome measurement of implant survival, but excluded studies involving multiple simultaneous interventions, and studies with missing data. The Cochrane approach for cohort studies and Oxford Centre for Evidence-Based Medicine were applied. Of the 56 published papers selected, 14 papers on the flapless technique showed high overall implant survival rates. The prospective studies yielded 97.01% (95% CI: 90.72-99.0) while retrospective studies or case series illustrated 95.08% (95% CI: 91.0-97.93) survival. The average of intraoperative complications was 6.55% using the flapless procedure. The limited data obtained showed that flapless surgery in posterior maxilla areas could be a viable and predictable treatment method for implant placement. Flapless surgery tends to be more applicable in this area of the mouth. Further long-term clinical controlled studies are needed.     

Electrodeposited nickel–graphene nanocomposite coating: effect of graphene nanoplatelet size on its microstructure and hardness

In this study, the effect of graphene nanoplatelet (GNP) size on the microstructure and hardness of the electrodeposited nickel–graphene nanocomposite coatings were investigated. GNPs with different sizes were prepared by using a high energy ball milling technique. The experimental result revealed the high energy ball milling technique could reduce the size, increase the surface area, and improve the dispersion ability of GNPs. The microstructure, hardness, and components of the nanocomposite coatings were greatly affected by GNP sizes. The highest microhardness was measured to be 273 HV for the nanocomposite coatings containing 5 h-milled GNPs, which is increased up to ∼47% compared to pristine Ni coating. The enhancement in the hardness is attributed to the uniform dispersion of the small GNP sizes inside the Ni matrix and the Ni grain size reduction when using milled GNPs.

The effect of graphene nanoplatelet size on the microstructure and hardness of electrodeposited nickel–graphene nanocomposite coatings was investigated.     

Vitamin B12 Deficiency in Infancy: The Case for Screening

The classic principles put forth by Wilson and Jungner are often applied to determine the suitability of a condition for universal newborn screening. The three cases described here portray the harmful effects of vitamin B₁₂ deficiency in infancy. The challenges and opportunities of early recognition and treatment are highlighted. Screening newborns would allow early detection and prevention of severe neurological damage in vitamin B₁₂‐deficient infants and enable diagnosis of unrecognized maternal pernicious anemia in asymptomatic mothers. However, lack of standardized methodology and screening cutoffs present challenges to the use of current tandem mass spectrometry technologies for screening.