Translocation (11;11)(p13- p15;q23) in a child with therapy-related acute myeloid leukemia following chemotherapy with DNA-topoisomerase II inhibitors for Langerhans cell histiocytosis

We report a new case of therapy-related acute myeloid leukemia in a child with Langerhans cell histiocytosis. This patient was previously treated with a protocol of multidrug chemotherapy, containing a relatively low dose of etoposide (total dose of 900/m(2)). Twenty-six months after the end of the therapy, the patient returned to the hospital with fever and anemia. The white blood cell count was 53 x 10(9)/L. The bone marrow examination showed massive infiltration with French-American-British acute myeloid leukemia classification M4 blast cells. The patient did not respond to an intensive treatment with high dose ARA-C and idarubicin. He died 6 months later. The cytogenetic abnormality of the blast cells was a t(11;11)(p13 -15;q23), that has not been described before in a secondary leukemia case.     

Multivariate Base Rates of Low Scores on Tests of Learning and Memory among Spanish-Speaking Children

ABSTRACT

To determine the prevalence of low scores on two neuropsychological tests commonly used to evaluate learning and memory in children. 6,030 healthy children from 10 countries in Latin America and Spain were administered Rey–Osterrieth Complex Figure (ROCF) and the Test de Aprendizaje y Memoria Verbal–Infantil (TAMV-I). Results showed that low scores are common when multiple neuropsychological outcomes (tests and/or scores) are evaluated in healthy individuals. Clinicians should consider the higher probability of low scores in a given individual when evaluating learning and memory using various sets of scores to reduce false-positive diagnoses of cognitive deficits in pediatric populations.     

Infection of immunodeficient horses with Sarcocystis neurona does not result in neurologic disease

Equine protozoal myeloencephalitis is a progressive neurologic disease of horses most commonly caused by infection with the apicomplexan parasite Sarcocystis neurona. Factors affecting neuroinvasion and neurovirulence have not been determined. We investigated the pathogenesis of infection with S. neurona in horses with severe combined immune deficiency (SCID). Two immunocompetent (IC) Arabian horses and two Arabian horses with SCID were infected orally with 5 x 10(5) sporocysts of S. neurona. Four IC horses and one SCID horse were infected intravenously (i.v.) with 5 x 10(8) merozoites of the WSU-1 isolate of S. neurona. Despite prolonged parasitemia and persistent infection of visceral tissues (skeletal muscle, cardiac muscle, lung, liver, and spleen) as demonstrated by PCR and culture, SCID horses did not develop neurologic signs after oral or i.v. infection. S. neurona was undetectable in the neuronal tissues of SCID horses by either PCR, immunohistochemistry, or culture. In contrast, although parasitemia was undetectable in orally infected IC horses and of only short duration in i.v. infected IC horses, four of six IC horses developed neurologic signs. S. neurona was detectable by PCR and/or culture of neural tissue but not visceral tissue of IC horses with neurologic disease. Infected SCID horses are unable to clear S. neurona from visceral tissues, but the infection does not result in neurologic signs; in contrast, IC horses rapidly control parasitemia and infection of visceral tissues but frequently experience neuroinvasion and exhibit clinical signs of neurologic disease.     

Mediation of in vivo glucose sensor inflammatory response via nitric oxide release

In vivo glucose sensor nitric oxide (NO) release is a means of mediating the inflammatory response that may cause sensor/tissue interactions and degraded sensor performance. The NO release (NOr) sensors were prepared by doping the outer polymeric membrane coating of previously reported needle-type electrochemical sensors with suitable lipophilic diazeniumdiolate species. The Clarke error grid correlation of sensor glycemia estimates versus blood glucose measured in Sprague-Dawley rats yielded 99.7% of the points for NOr sensors and 96.3% of points for the control within zones A and B (clinically acceptable) on Day 1, with a similar correlation for Day 3. Histological examination of the implant site demonstrated that the inflammatory response was significantly decreased for 100% of the NOr sensors at 24 h. The NOr sensors also showed a reduced run-in time of minutes versus hours for control sensors. NO evolution does increase protein nitration in tissue surrounding the sensor, which may be linked to the suppression of inflammation. This study further emphasizes the importance of NO as an electroactive species that can potentially interfere with glucose (peroxide) detection. The NOr sensor offers a viable option for in vivo glucose sensor development.     

Comparing the effectiveness of home visiting paraprofessionals and mental health professionals delivering a postpartum depression preventive intervention: a cluster-randomized non-inferiority clinical trial

To determine whether pregnant women receiving the Mothers and Babies group–based intervention exhibited greater depressive symptom reductions and fewer new cases of major depression than women receiving usual community-based services, and to examine whether groups run by paraprofessional home visitors and mental health professionals yielded similar depressive symptom reductions and prevention of major depression. Using a cluster-randomized design, 37 home visiting programs were randomized to usual home visiting, Mothers and Babies delivered via home visiting paraprofessionals, or Mothers and Babies delivered via mental health professionals. Baseline assessments were conducted prenatally with follow-up extending to 24 weeks postpartum. Eligibility criteria were ≥ 16 years old, ≤ 33 gestation upon referral, and Spanish/English speaking. Depressive symptoms at 24 weeks postpartum was the primary outcome. Eight hundred seventy-four women were enrolled. Neither intervention arm was superior to usual care in decreasing depressive symptoms across the sample (p = 0.401 home visiting paraprofessional vs. control; p = 0.430 mental health professional vs. control). Post hoc analyses suggest a positive intervention effect for women exhibiting mild depressive symptoms at baseline. We have evidence of non-inferiority, as the model-estimated mean difference in depressive symptoms between intervention arms (0.01 points, 95% CI: −0.79, 0.78) did not surpass our pre-specified margin of non-inferiority of two points. Although we did not find statistically significant differences between intervention and control arms, non-inferiority analyses found paraprofessional home visitors generated similar reductions in depressive symptoms as mental health professionals. Additionally, Mothers and Babies appears to reduce depressive symptoms among women with mild depressive symptoms when delivered by mental health professionals. This trial is registered on ClinicalTrials.gov (initial post: December 1, 2016; identifier: NCT02979444).

     

Peritransplant use of ultraviolet-B irradiation (UV-B) therapy is detrimental to allogeneic stem cell transplantation outcome.

Whole-body UV-B phototherapy has been used for the treatment of graft-versus-host disease (GVHD) of the skin and has systemic immunosuppressive and tolerogenic effects. We hypothesized that whole-body UV-B therapy would improve donor engraftment and decrease the incidence and severity of GVHD that is associated with decreased intensity allogeneic hematopoietic stem cell transplantation. This study tested the feasibility of using UV-B phototherapy that was initiated before grafting and continued until engraftment to determine its effect on transplantation outcome. Eight patients (median age, 55.5 years; range, 32-65 years) with hematologic malignancies were included. Allogeneic peripheral blood stem cells were obtained from matched related (n=5) or matched unrelated (n=3) donors. Conditioning regimen was fludarabine 30 mg/m2 intravenously for 5 days, cyclophosphamide 1 g/m2/d intravenously for 2 days, and equine antithymocyte globulin 30 mg/kg/d for 2 days. GVHD prophylaxis included cyclosporine, methylprednisolone, and escalating doses of narrowband UV-B (311 nm) according to skin tolerance, 3 days a week, from 10 days before to 28 days after transplantation. The conditioning regimen and the UV-B therapy were well tolerated. Two patients received all 14 prescribed UV-B treatments (cumulative doses of 2000 and 3260 mJ/cm2, respectively) and 6 patients received 8 to 13 treatments with a cumulative dose range of 528-3465 mJ/cm2. There was a rapid decrease in epidermal CD1a+ cells by day of transplantation. Myeloid engraftment was rapid. One patient had secondary engraftment failure at 3 months and another had mixed chimerism at day 100. Seven of 8 patients developed severe acute GVHD (grade III, n=5; grade IV, n=2). Six had skin involvement, 5 had gastrointestinal involvement, and 1 had liver involvement. Four patients died (2 from sepsis, 1 from acute GVHD, and 1 from chronic GVHD). Four patients are alive (130-287 days), 3 with extensive chronic GVHD. We conclude that extended peritransplant UV-B therapy at the standard minimally erythemogenic dose is detrimental to the outcome of allogeneic stem cell transplantation. It is unclear how UV-B at this immunsuppressive dose might have altered skin and systemic cytokine and immune cell compositions in the host and increased GVHD- and treatment-related mortalities. Different UV-B dose and schedules should be further explored. However, although other phototherapeutic modalities may be effective against GVHD, extended UV-B therapy should not be used during early phases of decreased conditioning allogeneic transplantation.     

Familial translocation t(10;14) (q26.1;q32.3): report of three offspring with 10q deletion and 14q duplication

We describe two brothers and a cousin with common clinical features, including mild mental retardation, motor delays, hypotonia with truncal ataxia, esotropia, and mild facial and hand dysmorphia. The initial routine chromosome study failed to detect any abnormality in the proband. Based on a high index of clinical suspicion, high-resolution chromosome studies were performed on the proband's parents. A small reciprocal translocation t(10;14) (q26.1;q32.3) was detected in the father. The breakpoint on the derivative chromosome 14 was further placed telomeric to the immunoglobulin heavy-chain gene cluster at the band q32.33 by fluorescence in situ hybridization. Studies of the proband and two affected paternal cousins revealed that each had inherited the same derivative chromosome 10 from their carrier parents. This unbalanced karyotype resulted from an adjacent-1 segregation of the 10;14 translocation.     

Regulation of human natural killer (NK) cell function: Induction of killing of an NK-resistant renal carcinoma cell line

Natural killer (NK)-like activity against a renal carcinoma cell line, Cur, was assessed. There was no spontaneous killing of Cur cells by human peripheral blood mononuclear cells in 4-hr assays. Cur killing was observed in 18-hr assays, but the magnitude of killing was variable and always markedly less than that against K562. Cur killing was mediated by a nonadherent, nonphagocytic lymphocyte, the activity of which could be modulated both positively and negatively by monocytes or their products. Preincubation of effectors with monocyte supernatant, interleukin 1 (IL-1), -interferon (IFN), or interleukin 2 (IL-2) greatly increased the magnitude of Cur killing and accelerated the kinetics of lysis. The addition of prostaglandin E₂ (PGE₂) duringin vitro activation of NK by IL-2 profoundly inhibited subsequent Cur lysis, whereas only minimal inhibition of K562 lysis was noted. However, following activation with IL-2, lysis of Cur targets was less sensitive to the inhibitory effects of PGE₂. Removal of Leu 11b(+), OKM1(+), orl-leucylleucine methyl ester-sensitive cells markedly decreased both Cur and K562 lysis. Moreover, CD16(+) cells purified with the fluorescence-activated cell sorter were found to mediate Cur killing. Whereas Cur and K562 lysis is mediated by phenotypically similar effector cells, the present studies demonstrate that the cytotoxic functions defined by the ability to lyse these two targets differ in response to a variety of immunoregulatory stimuli.