Transient myeloproliferative disorder in a newborn with Down syndrome

This is the report of a newborn with Down syndrome diagnosed with transient myeloproliferative disorder (TMD) that required chemotherapy on the first day of life. Children with Down syndrome have a 10- to 20-fold increased risk of developing TMD. TMD is characterized by an uncontrolled proliferation of myeloblasts in the infant's peripheral blood and bone marrow. In most instances, this unique disorder has the ability to spontaneously "turn off" the overproliferation and enter a state of remission. Only supportive care is recommended for TMD during the first months of life unless the clinical condition requires intervention. As more cases of this baffling disorder are presented, it is important to share our experience to aid in management and diagnosis.     

Prevention of crystalline silica-induced inflammation by the anti-malarial hydroxychloroquine

Objectives: Inhalation of crystalline silica (cSiO₂) remains a significant occupational hazard and may lead to the development of silicosis. When cSiO₂ particles are phagocytized by alveolar macrophages, they cause disruption of the lysosomal membrane which results in cell death. There are currently no pharmaceutical treatments directed at this mechanism of disease; however, many existing pharmaceuticals, such as hydroxychloroquine (HCQ), become sequestered in the lysosome through an ion-trapping mechanism. The objective of this research was to determine whether HCQ can prevent cSiO₂-induced toxicity by blocking LMP in alveolar macrophages.

Materials and methods: This study assessed the ability of in vitro treatment with HCQ to block toxicity and lysosomal membrane permeability in cSiO₂-exposed mouse bone-marrow derived macrophages. Additionally, C57Bl/6 mice were treated with HCQ by oral gavage before cSiO₂ exposure, and the ability of HCQ to prevent lung injury and inflammation was assessed.

Results: In vitro studies demonstrated that HCQ attenuated activation of the NLRP3 inflammasome and blocked LMP. Mice treated with HCQ in vivo showed a modest trend towards decreased cSiO₂-induced toxicity. Ex vivo culture of alveolar macrophages collected from cSiO₂-treated mice showed significantly less NLRP3 inflammasome activation after in vivo exposure to HCQ.

Conclusions: Our findings suggest that hydroxychloroquine blocks LMP and can significantly decrease cSiO₂-induced toxicity in vitro. HCQ may be a promising treatment for prevention of cSiO₂-induced lung damage.     

Extracorporeal shock wave lithotripsy in the renal transplant patient: a case report and review of literature

Renal allograft lithiasis is a rare complication of renal transplantation, which in the past has required various invasive procedures for adequate stone fragmentation and dissolution. Noninvasive techniques such as extracorporeal shock wave lithotripsy (ESWL) can now be extended to the renal transplant patient. Five cases have been previously reported in which ESWL was used effectively for dissolution of renal allograft calculi. We now report a 6th case in which a calculus, initially identified 2 weeks after renal transplantation, was effectively fragmented 3 years later using ESWL. Based on our experience and the reviewed composite experience in the literature, ESWL is a safe therapy for renal allograft calculi.     

Genotypic correlates of a virologic response to stavudine after zidovudine monotherapy

To assess whether the incidence of invasive cervical cancer (ICC) has changed as a result of highly active antiretroviral therapy (HAART), we conducted a prospective cohort study on the incidence of ICC before and after the introduction of HAART among Italian women with a known duration of HIV infection. We estimated the incidence per 1000 person years of ICC as a first AIDS-defining disease for the periods 1981 through 1991, 1992 through 1995, and 1996 through 1998. We also estimated the incidence of other first AIDS-defining diseases. Kaplan-Meier and Cox models were applied to compare the periods 1981 through 1995 and 1996 through 1998 in terms of cumulative incidence and relative hazards (RHs). The analysis included 483 women (median follow-up: 7 years). In the period 1981 through 1995, a trend of increase was observed in the incidence of ICC and other AIDS-defining diseases; this trend has continued only for ICC, whereas the incidence of other AIDS-defining diseases has decreased since 1996. Compared with 1981 through 1995, the RH of ICC for 1996 through 1998 was 7.41 (95% confidence interval [CI]: 1.21--45.44); when adjusting for age at HIV seroconversion, the RH decreased to 4.75 (95% CI: 0.80--28.24). It remains to be determined whether the continued increase in ICC incidence after the introduction of HAART is attributable to a decreasing competitive mortality from other AIDS-defining diseases among HIV-infected women.     

The Africa Center for Biostatistical Excellence: a proposal for enhancing biostatistics capacity for sub‐Saharan Africa

Sub‐Saharan Africa has a shortage of well‐trained biomedical research methodologists, in particular, biostatisticians. In July 2014, a group of biostatisticians and researchers from the region attended a brainstorming workshop to identify ways in which to reduce the deficit in this critical skill. The workshop recognized that recommendations from previous workshops on building biostatistics capacity in sub‐Saharan Africa had not been implemented. The discussions culminated with a proposal to setup an Africa Center for Biostatistical Excellence, a collaborative effort across academic and researcher institutions within the region, as a vehicle for promoting biostatistics capacity building through specialized academic masters programs as well as regular workshops targeting researchers. Copyright © 2015 John Wiley & Sons, Ltd.     

The impact of age, temperature, and parasite density on treatment outcomes from antimalarial clinical trials in Kampala, Uganda

Antimalarial drug treatment policy in sub-Saharan Africa is generally guided by the results of clinical drug efficacy studies in patients with uncomplicated Plasmodium falciparum malaria. The selection criteria used to enroll these patients often vary and may have a significant impact on treatment outcomes. In Kampala, Uganda, we investigated the impact of age, baseline temperature, and pre-treatment parasite density on estimates of treatment efficacy using a statistical modeling approach in 2,138 patients enrolled in six clinical trials involving seven different treatment regimens. Decreasing age, increasing temperature, and increasing parasite density were all independent predictors of an increased risk of treatment failure across all treatment groups. Compared with an unrestrictive approach to subject selection, enrolling only patients fulfilling selection criteria recommended by the World Health Organization (age < 5 years old, documented fever, and parasite density < 200,000/microL) increased the risk of treatment failure by 25-60% for the different treatment regimens. Caution should be taken when comparing results from drug efficacy studies with different subject selection criteria.