Noninvasive Assessment of Neurodevelopmental Disorders after In Utero Irradiation in Mice: An In Vivo Anatomical and Diffusion MRI Study.

In utero exposure to ionizing radiation can lead to cerebral alterations during adulthood. Using anatomical magnetic resonance imaging (MRI), it is possible to assess radiation-induced structural brain damage noninvasively. However, little is currently known about microstructure alterations in brain tissue. Therefore, the goal of this study was to establish, based on an original and robust pipeline of MRI image analysis, whether the long-term effects of in utero radiation exposure on brain tissue microstructure could be detected noninvasively. Pregnant C57BL/6N mice received a single dose of 1 Gy on gestation day 14.5, which led to behavioral impairments in adults. At 3 months old, in vivo MRI data were acquired from in utero irradiated and nonirradiated male mice. An MRI protocol was designed to assess the effects of radiation on the parameters of brain volume, non-Gaussian diffusion (ADC0, kurtosis and signature index) and anisotropic diffusion (fractional anisotropy and mean, axial, radial diffusivities and anisotropic signature index) in 10 key cerebral structures defined using an in-house atlas of the mouse brain. Based on the relative amplitude of these anatomical and microstructural changes, maps of the radiosensitivity of the brain to in utero irradiation were created. We observed microcephaly in irradiated mice with noticeably larger volume changes in the cortex and the corpus callosum. We also observed significantly lower ADC0, anisotropy fraction (sFA), radial diffusivity (sRD), as well as signature index (S-index and SI3) values, which are original markers sensitive to tissue microstructure alterations. All these changes together are in favor of a decreased cellular "imprint" and in some regions a reduced density in myelinated axons. A reduction in the number and complexity of myelinated axons was further revealed by myelin basic protein immunostaining. Combining anatomical and diffusion MRI is a promising approach to noninvasively investigate the radiosensitivity of local brain areas in adult mice after in utero irradiation in terms of microstructure.

Influence of eNOS gene polymorphism on cardiometabolic parameters in response to physical training in postmenopausal women.

The health-promoting effects of exercise training (ET) are related to nitric oxide (NO) production and/or its bioavailability. The objective of this study was to determine whether single nucleotide polymorphism of the endothelial NO synthase (eNOS) gene at positions -786T>C, G894T (Glu298Asp) and at the variable number of tandem repeat (VNTR) Intron 4b/a would interfere with the cardiometabolic responses of postmenopausal women submitted to physical training. Forty-nine postmenopausal women were trained in sessions of 30-40 min, 3 days a week for 8 weeks. Genotypes, oxidative stress status and cardiometabolic parameters were then evaluated in a double-blind design. Both systolic and diastolic blood pressure values were significantly reduced after ET, which was genotype-independent. However, women without eNOS gene polymorphism at position -786T>C (TT genotype) and Intron 4b/a (bb genotype) presented a better reduction of total cholesterol levels (-786T>C: before = 213 ± 12.1, after = 159.8 ± 14.4, Δ = -24.9% and Intron 4b/a: before = 211.8 ± 7.4, after = 180.12 ± 6.4 mg/dL, Δ = -15%), and LDL cholesterol (-786T>C: before = 146.1 ± 13.3, after = 82.8 ± 9.2, Δ = -43.3% and Intron 4b/a: before = 143.2 ± 8, after = 102.7 ± 5.8 mg/dL, Δ = -28.3%) in response to ET compared to those who carried the mutant allele. Superoxide dismutase activity was significantly increased in trained women whereas no changes were observed in malondialdehyde levels. Women without eNOS gene polymorphism at position -786T>C and Intron 4b/a showed a greater reduction of plasma cholesterol levels in response to ET. Furthermore, no genotype influence was observed on arterial blood pressure or oxidative stress status in this population.

Influence of eNOS gene polymorphism on cardiometabolic parameters in response to physical training in postmenopausal women

The health-promoting effects of exercise training (ET) are related to nitric oxide (NO) production and/or its bioavailability. The objective of this study was to determine whether single nucleotide polymorphism of the endothelial NO synthase (eNOS) gene at positions -786T>C, G894T (Glu298Asp) and at the variable number of tandem repeat (VNTR) Intron 4b/a would interfere with the cardiometabolic responses of postmenopausal women submitted to physical training. Forty-nine postmenopausal women were trained in sessions of 30-40 min, 3 days a week for 8 weeks. Genotypes, oxidative stress status and cardiometabolic parameters were then evaluated in a double-blind design. Both systolic and diastolic blood pressure values were significantly reduced after ET, which was genotype-independent. However, women without eNOS gene polymorphism at position -786T>C (TT genotype) and Intron 4b/a (bb genotype) presented a better reduction of total cholesterol levels (-786T>C: before = 213 ± 12.1, after = 159.8 ± 14.4, Δ = -24.9 percent and Intron 4b/a: before = 211.8 ± 7.4, after = 180.12 ± 6.4 mg/dL, Δ = -15 percent), and LDL cholesterol (-786T>C: before = 146.1 ± 13.3, after = 82.8 ± 9.2, Δ = -43.3 percent and Intron 4b/a: before = 143.2 ± 8, after = 102.7 ± 5.8 mg/dL, Δ = -28.3 percent) in response to ET compared to those who carried the mutant allele. Superoxide dismutase activity was significantly increased in trained women whereas no changes were observed in malondialdehyde levels. Women without eNOS gene polymorphism at position -786T>C and Intron 4b/a showed a greater reduction of plasma cholesterol levels in response to ET. Furthermore, no genotype influence was observed on arterial blood pressure or oxidative stress status in this population.

Influence of naloxone and methysergide on the analgesic effects of low-level laser in an experimental pain model.

BACKGROUND AND OBJECTIVES: Although the mechanism of action of laser phototherapy (LPT) is not known, it is a promising analgesic method. The aim of this study was to evaluate whether the action of LPT depends on the activation of peripheral opioid or serotonergic receptors. METHOD: Inflammatory pain was induced through the injection of carrageenin in the left posterior paw of male Wistar rats. The InGaAIP visible laser diode (660 nm) with fluency of 2.5 J*cm(-2) was used. Von Frey filaments were used to analyze mechanical hyperalgesia. Animals were separated into five groups: Carrageenin; Laser (LPT); Non-coherent light; LPT + Naloxone; and LPT + Methysergide. RESULTS: Low-Level Laser phototherapy proved to be an effective analgesic method, while non-coherent light did not show a similar effect. The use of naloxone blocked the analgesic effect of LPT, while methysergide did not affect LPT-induced analgesia. CONCLUSIONS: According to the parameter used in this study, LPT produced analgesia. Analgesia induced by laser phototherapy is mediated by peripheral opioid receptors. Laser phototherapy does not seem to interact with peripheral serotonergic receptors.

Influência da naloxona e metisergida sobre o efeito analgésico do laser em baixa intensidade em modelo experimental de dor / Influence of naloxone and methysergide on the analgesic effects of low-level laser in an experimental pain model

JUSTIFICATIVA E OBJETIVOS: A fototerapia com laser (LPT) é um método analgésico promissor, embora seu mecanismo de ação não seja totalmente conhecido. O objetivo deste estudo foi avaliar se a ação da LPT é dependente da ativação de receptores opioides ou serotoninérgicos periféricos. MÉTODO: Foram utilizados ratos Wistar machos. A dor produzida foi de caráter inflamatório, através da injeção de carragenina na pata posterior esquerda dos ratos. O laser utilizado foi o Photon Lase III em meio ativo InGaAIP (660 nm), fluência de 2,5 J.cm-2. Analisou-se a hiperalgesia mecânica utilizando filamentos de von Frey. Os animais foram separados em cinco grupos: Carragenina; Laser (LPT); Luz não coerente; LPT + Naloxona e LPT + Metisergida. RESULTADOS: A fototerapia com laser em baixa intensidade mostrou-se um método analgésico eficaz, enquanto o emprego de fonte de luz não coerente não mostrou ter efeito analgésico. O uso de naloxona bloqueou o efeito analgésico do LPT; já o uso de metisergida não afetou a analgesia do LPT. CONCLUSÕES: A LPT nos parâmetros utilizados apresentou efeito analgésico. A analgesia da LPT é mediada por receptores opioides periféricos. A LPT parece não interagir com receptores serotoninérgicos periféricos.

BACKGROUND AND OBJECTIVES: Although the mechanism of action of laser phototherapy (LPT) is not known, it is a promising analgesic method. The aim of this study was to evaluate whether the action of LPT depends on the activation of peripheral opioid or serotonergic receptors. METHOD: Inflammatory pain was induced through the injection of carrageenin in the left posterior paw of male Wistar rats. The InGaAIP visible laser diode (660 nm) with fluency of 2.5 J.cm-2 was used. Von Frey filaments were used to analyze mechanical hyperalgesia. Animals were separated into five groups: Carrageenin; Laser (LPT); Non-coherent light; LPT + Naloxone; and LPT + Methysergide. RESULTS: Low-Level Laser phototherapy proved to be an effective analgesic method, while non-coherent light did not show a similar effect. The use of naloxone blocked the analgesic effect of LPT, while methysergide did not affect LPT-induced analgesia. CONCLUSIONS: According to the parameter used in this study, LPT produced analgesia. Analgesia induced by laser phototherapy is mediated by peripheral opioid receptors. Laser phototherapy does not seem to interact with peripheral serotonergic receptors.

JUSTIFICATIVA Y OBJETIVOS: La fototerapia con láser (LPT) es un método analgésico promisorio, aunque su mecanismo de acción no se conozca en su totalidad. El objetivo de este estudio fue evaluar si la acción de la LPT es dependiente de la activación de receptores opioides o serotoninérgicos periféricos. MÉTODO: Se usaron ratones Wistar machos. El dolor generado fue de carácter inflamatorio, a través de la inyección de carragenina en la pata posterior izquierda de los ratones. El láser utilizado fue el GaIAsAl (660 nm), fluencia de 2,5 J.cm-2. Se analizó la hiperalgesia mecánica utilizando filamentos de von Frey. Los animales se dividieron en cinco grupos: Carragenina; Láser (LPT); Luz no coherente; LPT + Naloxona y LPT + Metisergida. RESULTADOS: La fototerapia con láser en baja intensidad demostró ser un método analgésico eficaz, mientras que el uso de la fuente de luz no coherente no demostró poseer ningún efecto analgésico. El uso de naloxona bloqueó el efecto analgésico del LPT, mientras que el uso de metisergida no afectó la analgesia del LPT. CONCLUSIONES: La LPT en los parámetros utilizados tuvo un efecto analgésico. La analgesia de la LPT es mediada por receptores opióides periféricos. La LPT parece que no interactúa con los receptores serotoninérgicos periféricos.

Cardiac complications in patients undergoing a reduced-intensity conditioning hematopoietic stem cell transplantation.

Reduced-intensity conditioning (RIC) extends hematopoietic stem cell transplants (HSCT) to elderly or debilitated patients who are not candidates for HSCT. The incidence and outcomes of cardiac complications have been reported following myeloablative HSCT. We assessed the incidence and outcomes of cardiac complications in 278 recipients of RIC from July 2000 to July 2006. All patients received conditioning with BU, fludarabine and TBI. Patients were evaluated from conditioning therapy until 100 days after HSCT. Median age was 56 years. Cardiac events were defined as either one or more of the following: arrhythmias, myocardial infarction or congestive heart failure. Twenty-five patients developed arrhythmias at a median of 3 days post transplant, in 19 patients hemodynamic compromise occurred and mechanical ventilation was required in 15 patients. The arrhythmias included atrial fibrillation (n=17), atrial flutter (n=6) and supraventricular tachycardia (n=2). Troponin was elevated in 12 out of 25 patients. The mean brain natriuretic peptide was 679. All patients converted to a normal rhythm by medical therapy at a median of 2 days. Recurrence of arrhythmia occurred in 76% of patients. Day 100 mortality was 40% in this group. A history of high-dose anthracycline treatment and a low ejection fraction were risk factors for the development of cardiac complications.

Reduced intensity versus full myeloablative stem cell transplant for advanced CLL.

CLL remains incurable with the standard therapy. Allogeneic hematopoietic stem cell transplant may be curative. We examined 50 patients with advanced CLL who underwent allogeneic HCT at the University of Michigan between 1996 and 2006. Twenty-one patients received reduced-intensity conditioning (RIC) and twenty-nine patients received full-intensity conditioning (FIC) consisting of CY, etoposide and BCNU (n=20) or BU and CY (n=9). RIC recipients were older than FIC recipients (median age 54 vs 51, P=0.009). There were no statistically significant differences between groups in terms of the number of earlier therapies or patients with adverse cytogenetics. There were more unrelated donors in the RIC group 62% than in the FIC group 31% (P=0.030). Despite their older age and greater use of URD, the 5-year overall survival (OS) rate was 63% in the RIC group as compared with 18% in the FIC group (P=0.006). The primary cause of inferior survival in the FIC recipients was TRM, which was twice as high at day 100 for the FIC group 27% compared with the RIC group 14% (P=0.005). The relapse rate was 15% regardless with the majority of relapses occurring after day 100. These results suggest a favorable outcome for advanced CLL who undergo a RIC regimen compared with FIC.

Outcomes after auto-SCT in African Americans with multiple myeloma.

To study the impact of auto-SCT on the outcomes in African Americans (AA) with multiple myeloma (MM), we evaluated 101 consecutive AA patients who underwent auto-SCT. The median PFS and OS were 15.6 and 50.8 months, respectively. The median OS from diagnosis was 60 months. Traditional pre and post transplant prognostic variables earlier examined in Caucasian Americans (CA), including beta-2 microglobulin (B2M), chromosome 13 deletion, CR status after auto-SCT, gender, stage, Ig subtype, time to transplant, number of prior regimens and presence of lytic lesions, were not predictive of improved PFS or OS on univariate analysis. Age, lower CD34 cell dose infused, history of palliative radiation therapy (XRT) prior to auto-SCT and refractory disease at the time of auto-SCT were predictive of inferior PFS. History of palliative XRT was the only predictive factor of inferior PFS and OS after auto-SCT on multivariate analysis. In conclusion, MM in AA tends to relapse early after auto-SCT. It is unclear whether early relapses impact OS. Common prognostic peritransplant variables known in CA with MM may not be applicable to AA with MM.

Mycobacterium chelonae necrotizing pneumonia after allogeneic hematopoietic stem cell transplant: report of clinical response to treatment with tigecycline.

We present a case of progressive Mycobacterium chelonae ssp. chelonae necrotizing pneumonia after hematopoietic stem cell transplantation (HSCT) in the presence of chronic graft-versus-host disease. The patient failed to respond to standard combination therapy with multiple agents and developed resistance to most drugs over the course of treatment. Tigecycline, a new glycylcycline antimicrobial agent with in vitro activity against M. chelonae, was then used with a clinical response to treatment. To our knowledge, this is the first reported case demonstrating tigecycline to have a degree of clinical effectiveness to treat refractory pulmonary infection with M. chelonae in an HSCT recipient.

High-dose chemotherapy and adoptive immunotherapy in the treatment of recurrent pediatric brain tumors.

Pediatric patients with recurrent brain tumors have a poor prognosis and limited therapeutic options. We investigated the use of high-dose chemotherapy with adoptive immunotherapy for recurrent brain tumors. Three pediatric patients with recurrent brain tumors received high-dose chemotherapy. This was followed by adoptive transfer of ex-vivo expanded T-cells. The T-cells were generated from peripheral blood after immunization with autologous cancer cells. The objectives of this study included (1) establishing the safety and feasibility of this potential treatment, (2) measuring changes in immune response after high-dose chemotherapy and adoptive immunotherapy, and (3) determining whether adoptive immunotherapy would be able to translate into a clinical response. Immune function was tested in all patients at the time of enrollment into the study. Humoral responses to recall antigens delayed-type hypersensitivity (DTH) were intact in all patients. After immunizing patients with autologous cancer cells, peripheral blood lymphocytes were harvested and activated with anti-CD3, expanded in-vitro, and infused post-autologous transplant. Patients received at least three doses of the vaccine, each consisting of an intradermal administration near a draining lymph node at biweekly intervals. Toxicity was limited and well tolerated in all patients. All three patients showed a tumor-specific immune response by serial imaging. Responses were durable at 16, 23, and 48 months, respectively.

Non-bacterial infections in allogeneic non-myeloablative stem cell transplant recipients.

Data on non-bacterial infections during allogeneic non-myeloablative hematopoietic stem cell transplantation (HSCT) are widely different. We evaluated data on 48 consecutive patients who received a conditioning regimen with fludarabine and cyclophosphamide (73%) or fludarabine and total body irradiation (27%) and then underwent allogeneic non-myeloablative HSCT. Cytomegalovirus (CMV) infection was common and occurred in 48% of patients; 3 patients developed CMV disease, and all survived. CMV reactivation was found to be common with both conditioning regimens in our patient population. Invasive aspergillosis occurred in 4 patients (8%) and 3 died. Other serious non-bacterial infections were uncommon. Review of the available literature on non-myeloablative HSCT suggests that the frequency and type of opportunistic infections vary considerably.

Nonhomogeneous immunostaining of hyaline membranes in different manifestations of diffuse alveolar damage.

PURPOSE: To determine the nature of hyaline membranes in different manifestations of diffuse alveolar damage, [pulmonary and extrapulmonary acute respiratory distress syndrome], and idiopathic [acute interstitial pneumonia]. MATERIALS AND METHODS: Pulmonary specimens were obtained from 17 patients with acute respiratory distress syndrome and 9 patients with acute interstitial pneumonia. They were separated into 3 different groups: (a) pulmonary diffuse alveolar damage (pDAD) (n = 8), consisting only of pneumonia cases; (b) extrapulmonary diffuse alveolar damage (expDAI) (n = 9), consisting of sepsis and septic shock cases; and (c) idiopathic diffuse alveolar damage (iDAD) (n = 9), consisting of idiopathic cases (acute interstitial pneumonia). Hyaline membranes, the hallmark of the diffuse alveolar damage histological pattern, were examined using various kinds of antibodies. The antibodies used were against surfactant apoprotein-A (SP-A), cytokeratin 7 (CK7), cytokeratin 8 (CK8), alpha smooth muscle actin (alpha-SMA), cytokeratin AE1/AE3 (AE1/AE3), and factor VIII-related antigen (factor VIII). RESULTS: Pulmonary diffuse alveolar damage showed the largest quantity of hyaline membranes (12.65% +/- 3.24%), while extrapulmonary diffuse alveolar damage (9.52% +/- 3.64%) and idiopathic diffuse alveolar damage (7.34% +/- 2.11%) showed intermediate and lower amounts, respectively, with the difference being statistically significant between pulmonary and idiopathic diffuse alveolar damage (P < 0.05). No significant difference was found for hyaline membranes Sp-A immunostaining among pulmonary (15.36% +/- 3.12%), extrapulmonary (16.12% +/- 4.58%), and idiopathic (13.74 +/- 4.20%) diffuse alveolar damage groups. Regarding factor VIII, we found that idiopathic diffuse alveolar damage presented larger amounts of immunostained hyaline membranes (14.12% +/- 6.25%) than extrapulmonary diffuse alveolar damage (3.93% +/- 2.86%), with this difference being statistically significant (P < 0.001). Equally significant was the difference for progressive decrease of cytokeratin AE1/AE3 immunostaining in hyaline membranes present in the extrapulmonary diffuse alveolar damage (5.42% +/- 2.80%) and idiopathic diffuse alveolar damage (0.47% +/- 0.81%) groups (P < 0.001). None of the groups stained for cytokeratin CK-7, CK-8, vimentin, or a anti-smooth muscle actin. CONCLUSIONS: This study showed that only the epithelial/endothelial components (SP-A, factor VIII, and AE1/AE3) of the alveolar/capillary barrier are present in hyaline membranes formation in the 3 groups of patients with diffuse alveolar damage. The significant difference in the expression of factor VIII-related antigen and cytokeratin AE1/AE3 in the expDA versus iDAD groups as well as the significant difference in the amount of hyaline membranes present in the pDAD versus iDAD groups are suggestive of a local and specific lesion with different pathways (direct, indirect, or idiopathic), depending on the type of diffuse alveolar damage.

Nonhomogeneous immunostaining of hyaline membranes in different manifestations of diffuse alveolar damage / Imunomarcação não homogênea das membranas hialinas na sindrome da angustia respiratório do adulto pulmonar, extrapulmonar e idiopática

PURPOSE: To determine the nature of hyaline membranes in different manifestations of diffuse alveolar damage, [pulmonary and extrapulmonary acute respiratory distress syndrome], and idiopathic [acute interstitial pneumonia]. MATERIALS AND METHODS: Pulmonary specimens were obtained from 17 patients with acute respiratory distress syndrome and 9 patients with acute interstitial pneumonia. They were separated into 3 different groups: (a) pulmonary diffuse alveolar damage (pDAD) (n = 8), consisting only of pneumonia cases; (b) extrapulmonary diffuse alveolar damage (expDAI) (n = 9), consisting of sepsis and septic shock cases; and (c) idiopathic diffuse alveolar damage (iDAD) (n = 9), consisting of idiopathic cases (acute interstitial pneumonia). Hyaline membranes, the hallmark of the diffuse alveolar damage histological pattern, were examined using various kinds of antibodies. The antibodies used were against surfactant apoprotein-A (SP-A), cytokeratin 7 (CK7), cytokeratin 8 (CK8), alpha smooth muscle actin (a-SMA), cytokeratin AE1/AE3 (AE1/AE3), and factor VIII-related antigen (factor VIII). RESULTS: Pulmonary diffuse alveolar damage showed the largest quantity of hyaline membranes (12.65 percent ± 3.24 percent), while extrapulmonary diffuse alveolar damage (9.52 percent ± 3.64 percent) and idiopathic diffuse alveolar damage (7.34 percent ± 2.11 percent) showed intermediate and lower amounts, respectively, with the difference being statistically significant between pulmonary and idiopathic diffuse alveolar damage (P < 0.05). No significant difference was found for hyaline membranes Sp-A immunostaining among pulmonary (15.36 percent ± 3.12 percent), extrapulmonary (16.12 percent ± 4.58 percent), and idiopathic (13.74 ± 4.20 percent) diffuse alveolar damage groups. Regarding factor VIII, we found that idiopathic diffuse alveolar damage presented larger amounts of immunostained hyaline membranes (14.12 percent ± 6.25 percent) than extrapulmonary diffuse alveolar damage...

OBJETIVO: Determinar a natureza da membrana hialina nas diferentes manifestações do dano alveolar difuso [pulmonar e extrapulmonar síndrome do desconforto respiratório] e idiopático [pneumonia intersticial aguda]. MATERIAIS E MÉTODOS: Espécimes pulmonares foram obtidos de 17 pacientes com SDRA e 9 pacientes com pneumonia intersticial aguda e separados em três diferentes grupos: (a) dano alveolar difuso pulmonar (DADp) (n=8) constituído por casos de pneumonia, (b) dano alveolar difuso extrapulmonar (DADexp) (n=9) constituído por casos de sepse e choque séptico e (c) dano alveolar difuso idiopático (DADi) (n=9) constituído por casos idopáticos (ou pneumonia intersticial aguda). As características das membranas hialinas do padrão histológico de dano alveolar difuso foram examinadas usando vários tipos de anticorpos. Os anticorpos usados foram surfactante apoproteina A (SP-A), anti-citokeratina 7 (CK7), citokeratina 8 (CK8), alfa actina de músculo liso (a-SMA), citokeratina AE1/AE3 (AE1/AE3) e antígeno relacionado ao fator VIII (Fator VIII). RESULTADOS: Observaram-se aumentos maiores da quantidade de membrana hialina no dano alveolar difuso pulmonar (12.65 ± 3.24 por cento), intermediários no dano alveolar difuso extrapulmonar (9.52 ± 3.64 por cento) e baixos no dano alveolar difuso idiopático (7.34 ± 2.11 por cento) respectivamente, esta diferencia foi estatística significante entre o dano alveolar difuso pulmonar e o dano alveolar difuso idiopático (p<0.05). Não se encontrou significância estatística para a quantidade de imunomarcação de Sp-A nos grupos de dano alveolar difuso pulmonar (15.36 ± 3.12 por cento), extrapulmonar (16.12 ± 4.58 por cento) e idiopático (13.74 ± 4.20 por cento). Com relação ao Fator VIII, nós encontramos maiores aumentos da imunomarcação da membrana hialina no grupo dano alveolar difuso idiopático (14.12 ± 6.25 por cento) do que no dano alveolar difuso extrapulmonar (3.93 ± 2.86 por cento), com significância estatística (p<0.001). Da mesma...

High fatality rate of Epstein-Barr virus-associated lymphoproliferative disorder occurring after bone marrow transplantation with rabbit antithymocyte globulin conditioning regimens.

Epstein-Barr virus (EBV)-associated lymphoproliferative disorder (EBV-LPD) following bone marrow transplantation can be fatal. The major risk factors for the development of EBV-LPD are ex vivo T-cell depletion or in vivo T-cell depletion with either antithymocyte globulin (ATG) or monoclonal anti-T-cell antibodies. Between March 1999 and January 2001, a total of 23 transplants with ATG of equine source (20 transplants) and ATG of rabbit source (3 transplants) used as part of the preparatory regimen were performed at the Barbara Ann Karmanos Cancer Institute in Detroit, Mich. The three patients who received rabbit ATG developed EBV-LPD between 60 and 90 days following bone marrow transplantation. However, there were no cases of EBV-LPD in the equine group. Treatment given in these cases consisted of tapering immunosuppression, antiviral therapy, unprocessed donor lymphocyte infusion, mobilized peripheral blood progenitor cell rescue infusion (one patient), and chemotherapy (one patient). All three patients died of complications from EBV-LPD. The association of rabbit ATG with the development of EBV-LPD suggests that patients receiving rabbit ATG as part of their preparatory regimens require close monitoring of the EBV viral load and possible early intervention with antiviral therapy.

Safety of low-dose low-molecular-weight-heparins in thrombocytopenic stem cell transplantation patients: a case series and review of the literature.

Few attempts have been made to examine the feasibility of safely administering low-molecular-weight-heparins (LMWHs) in the presence of concurrent thrombocytopenia. We retrospectively investigated the safety of low-dose LMWH in BMT patients, a population at risk of bleeding. In total, 26 patients received at least one dose of low-dose enoxaparin (ie <1 mg/kg/day) during thrombocytopenia. s.c. enoxaparin 40 mg once daily was given in 85% of the cohort. The mean number of platelet days <55 x 10(9) and <20 x 10(9)/l were 16.5 days (95% CI=8.04-24.96) and 4.14 days (95% CI=2.35-5.93), respectively. The mean number of low-dose enoxaparin administration days when platelet <55 x 10(9) and 20 x 10(9)/l were 9.89 days (95% CI=3.26-16.53) and 2.25 days (95% CI=0.57-3.93), respectively. Minor bleeding occurred in four patients (15%) whereas major episodes developed in two patients (8%). The latter two events occurred during the transition between full therapeutic (ie 1.5-2 mg/kg/day) and low-dose enoxaparin close to the onset of thrombocytopenia. The present case series, along with the discussed literature, descriptively suggests that low-dose enoxaparin may be safely administered at a platelet count in the range of 20 and 55 x 10(9)/l in BMT patients who weigh >55 kg.

Mixed hematopoietic chimerism at day 90 following allogenic myeloablative stem cell transplantation is a predictor of relapse and survival.

We retrospectively analyzed the prognostic significance of mixed chimerism and associated clinical parameters in 80 patients following unmanipulated allogenic stem cell transplantation. Chimerism studies were performed on marrow aspirates using fluorescent in situ hybridization and variable number tandem repeats techniques at day +30, day +90 and +12 months. The median overall survival (OS) was 24 months (range, 1-56 months). Mixed chimerism was found in 23, 28 and 14% of patients at day +30 (1 month), +90 (3 months), and +12 months, respectively. Day +30 chimerism studies failed to provide any prognostic information. Day +90 mixed chimeras (MC) had significantly higher relapse rates compared to day +90 complete chimeras (CC) at 6 months (P=0.03) and 18 months when compared to MC (P=0.03) following transplant. The median OS in day +90 MC and day+90 CC were, respectively (95% CI, 2-35 months), compared to 47 months (95% CI, 20-74 months) (P=0.02). In conclusion, chimerism studies on day +30 could be reserved for patients who fail to demonstrate engraftment. Day +90 MC had higher relapse rates and lower OS, and therefore may be considered for novel therapies and future studies.

[Segmental sternal dislocation in children. Apropos of a surgically treated case]. / Disjonction segmentaire du sternum chez l'enfant. A propos d'un cas opéré.

The authors report one operated case of traumatic sternal segmental dislocation in a child, and propose a mechanism for this uncommon lesion. A fourteen year old boy was admitted in emergency for anterior chest pain, occurring during an exercise in parallel bars without any fall. X ray showed traumatic dislocation of the upper sternal segment. After 12 hours, because of bad clinical tolerance (pain, dyspnea with sweats and disphagia) reduction and plate stabilization (Senegas plate) was performed with immediate pain relief. The boy returned to school after 10 days. Plate was removed two months later after healing, with good clinical and radiological results. According to rare published cases, conservative treatment can be proposed in very young children because of dislocation remodeling. By others, in case of bad tolerance, surgical treatment is suggested despite the inconvenient of device's removal. The originality of this case is the indirect lesion mechanism. Hypothesis is given by authors. Treatment by plate is easy and gives immediate pain relief with good clinical and radiological results in teen-agers.