Brown-Séquard syndrome in a 11-year-old girl due to penetrating glass injury to the thoracic spine.

Injuries in children are one of the most frequent causes of high morbidity and mortality, and they present a challenge to the treating physician. Fortunately, spinal trauma in pediatric patient is relatively rare. Brown-Séquard syndrome is a rare form of incomplete spinal cord injury consisting of ipsilateral upper motor neuron paralysis (hemiplegia) and loss of proprioception with contralateral pain and temperature sensation deficits resulting from hemisection or lateral injury to the spinal cord. A 11-year-old girl was admitted to our Pediatric Trauma Emergency Department after she had suffered a penetrating back injury. Neurological examination demonstrated left lower extremity paresis and moderate spastic paralysis of the right lower extremity. The examination showed loss of temperature sensation contralateral to and below the lesion. The examination of the pain sensation was difficult because the patient was in pain shock, but it was diminished on the side opposite to the damage. Multislice spiral computed tomography (MSCT) demonstrated a triangular foreign body in spinal canal at the level of the Th11-Th12. After a Th11-L2 laminectomy and retrieval of foreign bodies, dura repair was performed. Patient was discharged from the hospital with partial recovery. Operative decompression of the neural elements in case of spinal canal compromise is the treatment of choice. Indication for surgical intervention in existing cerebrospinal fluid fistula includes closure of the dura and reducing neural elements compression and lowering the risk of infectious complications by removing bone or foreign body fragments. Patients with Brown-Séquard syndrome have good prognosis for functional recovery.

Sequential recovery of NK cell receptor repertoire after allogeneic hematopoietic SCT.

Alloreactivity of natural killer (NK) cells contributes to the GVL reaction after allogeneic hematopoietic SCT (allo-HSCT). However, various procedure-related factors may affect NK cell maturation and their ability to recognize and kill leukemic cells. In this study, we prospectively evaluated expression of NK cell inhibitory receptors in 83 adults treated with myeloablative, killer cell Ig-like receptor (KIR)-ligand-matched allo-HSCT. NK cell maturation was evaluated by comparing the phenotypic patterns after allo-HSCT with the donor ones. The frequencies of KIR3DL1 were comparable to the donor ones on day +28, while they decreased significantly starting from day +100. The expression of KIR2DL2/3 was significantly lower in patients compared with donors up to day +100. The expression of KIR2DL1, despite continues growth, remained significantly decreased for 1 year after allo-HSCT. NKG2A was over-expressed up to day +180. Within 1 year after allo-HSCT, the NK cell phenotypic pattern tended to recapitulate the donor type. The process was disturbed by the use of steroids with significant differences observed on days +56 (P=0.01) and +100 (P=0.04). Up to day +100, reconstitution of NK cell receptor repertoire correlated with the absolute numbers of circulating CD3(+), CD3(+)CD4(+) and CD3(+)CD8(+) cells. Our observations should be taken into account when trying to predict potential benefit from NK cell alloreactivity.

Immunogenic disparities of 11 minor histocompatibility antigens (mHAs) in HLA-matched unrelated allogeneic hematopoietic SCT.

We determined the alleles of 11 mHAs and investigated the association of immunogenic mHA mismatches between a donor and a recipient with a course of allogeneic hematopoietic SCT (allo-HSCT) from 10/10 alleles HLA-matched unrelated donors in 92 recipients after myeloablative conditioning between 2004 and 2006. The frequency analysis of mHA alleles, genotypes and phenotypes accompanied by appropriate restriction HLA Ags allowed for an estimation of the probability of immunogenic mismatches, which was the highest for HA-1, HA-8 and HY. GVH-directed disparity of mHAs with broad tissue distribution, especially of the sex-related HY Ag, influenced the results of allo-HSCT from HLA-matched unrelated donors by not only increasing the probability of chronic GVHD (cGVHD) but also by decreasing the relapse rate.

Prediction of nonrelapse mortality for patients surviving 100 days after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Patients who survive 100 days after allogeneic hematopoietic stem cell transplantation (alloHSCT) are at risk for chronic graft-versus-host disease and other potentially fatal complications. As the symptoms overlap and the differential diagnosis is difficult, the goal of this study was to verify whether basic laboratory evaluation performed on day +100 may allow identification of patients who are at high risk for nonrelapse mortality (NRM), independent of the underlying complications. PATIENTS AND METHODS: We analyzed 255 patients, mean age 29 years (range, 10-56 years), who remained alive and disease-free on day +100 after myeloablative alloHSCT from an HLA-identical sibling (n=177) or a matched unrelated volunteer (n=78), performed in a single institution between 1992 and 2003. RESULTS: Upon univariate analysis, the following laboratory parameters were associated with increased incidence of NRM: peripheral blood neutrophils<1.5x10(9)/L, platelets<100x10(9)/L, hemoglobin<11 g/dL, total protein<60 g/L, elevated plasma aspartate aminotransferase, elevated alkaline phosphatase, and elevated bilirubin. Upon multivariate analysis, only decreased protein (hazard ratio [HR]=6.97 [3.3-14.7], P<.0001) and elevated bilirubin (HR=3.52 [1.91-6.48], P<.0001) independently influenced the risk for NRM. The cumulative incidence of NRM equaled 6% if none of the above factors was present; 10% for hyperbilirubinemia alone; 22% for hypoproteinemia alone; and 70% for hyperbilirubinemia and hypoproteinemia, both present. CONCLUSIONS: A simple laboratory evaluation is highly predictive of the risk for NRM in patients surviving 100 days after alloHSCT. The prognosis is particularly poor for patients with hypoproteinemia and hyperbilirubinemia. These abnormalities may reflect impaired liver and intestine functions due to various posttransplantation complications.

Beta-2-microglobulin level predicts outcome following autologous hematopoietic stem cell transplantation in patients with multiple myeloma.

Despite the widespread use of high-dose therapy combined with autologous hematopoietic stem cell transplantation (autoHSCT), the outcomes of multiple myeloma (MM) treatment remain variable. The aim of this study was to define pretransplantation factors that influence outcomes following autoHSCT in patients with MM. Eighty-one MM patients, aged 51 years (range 31-70 years), undergoing first autoHSCT were included in the analysis. Thirty patients were in complete remission and 51 were in partial remission. The conditioning regimen was based mainly on melphalan (200 mg/m(2) intravenous [iv]). The following factors were tested for their prognostic significance: beta-2-microglobulin (B2M), lactate dehydrogenase, monoclonal protein level, bone marrow plasma cell percentage (PL), hemoglobin level, age, interval from diagnosis to autoHSCT, and number of transplanted CD34-positive cells. The transplant-related mortality at day 100 was 3.7% (3/81). The incidence of progression at 9.2 years was 71% for patients with elevated B2M, and 32% for those where B2M was within normal limits (P = .02.) The probability of PFS was decreased for patients with B2M > or = versus < normal limits (29% vs 68%; P = .02) and PL > or = versus < 5% (0% vs 45%; P = 0.03). In a multivariate analysis B2M remained the only factor associated with increased risk of progression (relative risk [RR] = 3.3; P = .03) and reduced probability of PFS (RR = 3.3; P = .03). We concluded that B2M level measured at first autoHSCT was a useful predictor for progression and PFS in MM patients.

Impact of activating killer immunoglobulin-like receptor genotype on outcome of unrelated donor-hematopoietic cell transplantation.

BACKGROUND: In a previous study we demonstrated that incompatibility regarding ligands for inhibitory killer immunoglobulin-like receptors (KIRs) is associated with a survival advantage following unrelated donor-hematopoietic cell transplantation (URD-HCT). The goal of the present analysis was to evaluate whether genotype of activating KIRs of the donor may have an impact on the outcome of URD-HCT. PATIENTS AND METHODS: Twenty-five URD-HCT recipients with hematological malignancies, mean age 27 years (range, 14-43 years), were included in the analysis. The conditioning regimen was myeloablative and based on chemotherapy alone (n = 20) or total body irradiation (n = 5). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine, methotrexate, and pretransplant antithymocyte globulin. Patients were grouped according to their donors' activating KIR genotype including two loci: KIR2DS1 and KIR2DS2. RESULTS: The presence of KIR2DS1 in the donor (n = 16/25) was not demonstrated to influence outcome. In contrast, the presence of KIR2DS2 (n = 13/25 donors) was associated with decreased probability of overall survival (0% vs 92%, P = .04) and disease-free survival (0% vs 92%, P = .046). The reason for failures in the KIR2DS2-positive group was chronic GVHD (n = 4), acute GVHD (n = 2), and relapse (n = 1). The cumulative incidence of nonrelapse mortality equaled 90% for the KIR2DS2-positive group and 8% for the KIR2DS2-negative group (P = .09). CONCLUSION: The presence of KIR2DS2 gene in the donor is associated with a high risk of mortality following URD-HCT, resulting mainly from the incidence of severe GVHD. Whether this effect is associated with the activity of natural killer cells or KIR-bearing T lymphocytes requires further investigation.

Imatinib therapy prior to myeloablative allogeneic stem cell transplantation.

It is unknown whether imatinib prior to myeloablative haematopoietic stem cell transplantation (HSCT) increases transplant-related toxicity. Among the side effects induced by imatinib, myelosuppression and liver injury might worsen HSCT outcomes. We retrospectively analysed engraftment, liver toxicity, acute graft-versus-host disease (aGVHD) incidence and 100-day mortality in 30 patients with BCR/ABL-positive leukaemias who received imatinib before HSCT and compared results of 48 age-matched controls who did not receive preceding imatinib. Both neutrophil and platelet engraftment occurred more rapidly among imatinib patients but the differences adjusted for Gratwohl scale were not statistically significant (P = 0.18 and 0.22, respectively). The adjusted hazards of having liver function tests (LFTs) >1.5 normal increased and the adjusted durations of elevated LFTs were not significantly different. The estimated adjusted difference in mean peak bilirubin values was also not significantly different (P = 0.48). However, the adjusted hazard of increased creatinine >1.5 normal was significantly higher in the imatinib group (HR = 4.09, P = 0.02). The adjusted odds of grades II-IV aGVHD were similar in both groups (OR = 0.86, P = 0.78), and while the adjusted odds of 100-day mortality were lower among imatinib patients, the difference was not significant (OR = 0.65, P = 0.60). These data do not provide any evidence that imatinib preceding HSCT increases acute transplant-related toxicities.

Addition of cladribine to induction/consolidation regimen does not impair peripheral blood stem cell mobilization and bone marrow harvest for autotransplantation in acute myeloid leukemia patients.

BACKGROUND: The previous study by the Polish Adult Leukemia Group has demonstrated that addition of cladribine to standard DNR+AraC induction potentiates the antileukemic activity. The goal of this study was to compare the efficacy of bone marrow or peripheral blood hematopoietic cell collection in patients who obtained remission after daunorubicine plus cytarabine induction with cladribine (DAC-7) or without addition of cladribine (DA-7) in preparation for autotransplantation. PATIENTS AND METHODS: Sixty-six patients aged 41 years (range, 17-58 years) were included in this study: 33 cases in the DAC-7 and 33 in the DA-7 arm. Hematopoietic cells were collected from the bone marrow (ABMT, n = 29) or from the peripheral blood (ABCT, n = 37) using cytopheresis after administration of AraC (2 x 2 g/m2) on days 1, 3, 5 and subsequent G-CSF (10 microg/kg) from day 7 as mobilization therapy. RESULTS: The numbers of harvested CD34+ cells were similar in the DAC-7 and DA-7 pretreated patients both after harvesting from peripheral blood (2.55 x 10(6)/kg vs 2.5 x 10(6)/kg) and from bone marrow (1.62 x 10(6)/kg vs 1.55 x 10(6)/kg), respectively. The proportion of patients with sufficient material for autologous bone marrow transplantation was higher in the DAC-7 compared with the DA-7 arm. All patients engrafted; hematopoietic recovery was similar in both subgroups. CONCLUSION: Addition of cladribine to a standard DA induction does not impair the harvesting of hematopoietic cells and their engraftment after autotransplantation.

Allogeneic transplantation of selected peripheral CD34+ cells with controlled CD3+ cells add-back in high-risk patients.

We evaluated the feasibility of allogeneic transplantation of CliniMACS-selected peripheral CD34+ cells from siblings (four patients: AML-M4, M2, CLL, MDS); nonoptimal related donors (two patients: AML-M4, CML); and unrelated donors (two patients: CML, ALL, both without engraftment after preceding URDBMT). All patients had high-risk of aGVHD and/or graft failure due to multiple transplantation risk factors. Conditioning treatment was myeloablative (n=7) or nonmyeloablative (n=1). Immunosuppression consisted of CsA (n=8), Mtx (n=5), ATG (n=4). Selected CD34+ cells were transplanted (average 3.91 x 10(6)/kg, range 1.29 to 7.27 x 10(6)/kg) together with 0.01 to 0.5 x 10(7) CD3+ cells/kg to assure proper engraftment. The remaining CD34-negative fraction was cryopreserved for further CD3+ cell add-back. Average recovery and purity of CD34+ cells following CliniMACS selection were 74% and 97%. No severe complications were observed in the first 100 days. Regeneration times were satisfactory in seven of eight patients (87.5%) with ANO > 0.5 g/L and Plt > 50 g/L reached on average on days +26 and +32 (range 15 to 29 and 15 to 67), respectively. In three patients (37.5%) T-lymphocytes were added-back one to three times (due to low numbers of initially transfused CD3+ cells in two patients, in one patient with PRCA caused by ABO incompatibility). One to four additional transplantations of nonselected peripheral cells were performed on days +28 to +270 in consequence of infections (CMV-two patients; parvovirus-one patient), poor regeneration and residual disease (one patient) and prolonged transfusion dependency (one patient). Severe aGVHD grade III or IV developed in three patients (37.5%) following the nonselected cells transplantation. Finally, five patients (62.5%) are alive and in remission (median follow-up 815 days). We conclude that allogeneic transplantation of selected peripheral CD34+ cells (CliniMACS) with controlled add-back of CD3+ cells is an effective, well, tolerated procedure in high-risk patients.

[Blood gas analysis of forearm veins--at rest and after exercise of forearm muscles and laser Doppler flowmetry of skin on the back of the palm--use in evaluation of microcirculation in diabetes type 2]. / Gazometria zylna obwodu konczyny górnej--spoczynkowa i po wysilku miesni przedramienia oraz laserowa przeplywometria dopplerowska skóry grzbietu dloni--zastosowanie do oceny funkcji mikrokrazenia w cukrzycy typu 2.

The aim of the study was to compare of nondominant forearm microcirculation in adult-type diabetes and healthy subjects with use of venous blood gasometry (vbg) sampled from basilic vein before and after exercise of antebrachial muscles and with use of laser doppler fluxometry (LDF) with optode localized in dorsal palm surface. Examinations were performed in groups of 16 diabetic patients (aged 43.5 +/- 5.7) and 16 healthy subjects (aged 39.3 +/- 7.8). After exercise of antebrachial muscles in diabetic patients in vbg were: pH higher, pO2 and satO2 lower than in healthy subjects, pCO2 and -HCO3 were not different in both group. In LDF in diabetic patients impaired hypraemic reaction, impaired heating to 40 degrees C reaction and hyperaemic reaction in this temperature were found.

[Venous blood gas analysis sampled from the basilic vein before and after exercise of the antebrachial muscles--preliminary evaluation of estimated stability parameters]. / Gazometria krwi zylnej pobranej z zyly odlokciowej przed i po wysilku miesni przedramienia--wstepna ocena stalosci badanych wskazników.

UNLABELLED: The aim of the study was to compare venous blood gasometry parameters of blood sampled twice from basilic vein on different days and at different hours. In the group of 8 healthy volunteers, parameters of venous blood gasometry sampled from basilic vein before and after exercise of antebrachial muscles, twice--on different days and at different hours were estimated. CONCLUSIONS: 1. In the first and in the second sample venous blood gasometry parameters before and after exercise were different: values of pCO2, pO2, O2sat increased, pH, BE, BEexe and BB decreased and HCO3 was not changed. 2. Venous blood gasometry parameters before exercise in the first and in the second sample and after exercise in the first and in the second sample were not different.

Allogeneic and autologous bone marrow transplantation in single centre experience.

Among 290 BMT procedures: 74 AML, 78 ALL, 34 CML, 6 SAA, 3 MDS, 42 HD, 35 NHL, 11 MM, and 7 solid tumours (breast or testis cancer) Allogeneic BMT was performed in 76 patients and ABMT/APBCT in 214 patients. Survival, DFS and relapse curves were calculated using the Kaplan-Meier product limit method. Variables potentially affecting survival and DFS were assessed in a multivariate analysis by the Cox proportional hazard model in a stepwise regression. The promising results were obtained in high risk adult ALL in the first CR. DFS in CR1 patients transplanted after full dose induction and high dose consolidation was significantly longer if compared to those who received dose/time reduced or postponed treatment. For CR> or =2 patients and with CNS involvement at diagnosis ABMT offers a salvage therapy that needs further improvement. In relapsed and refractory HD better results are obtained in patients relapsing > 1 year after first CR and in patients with entirely nodal localisation of this relapse. In NHL bone marrow and spleen infiltration at diagnosis appear to be an unfavourable prognostic factor.

[The influence of corticosteroid therapy on selected parameters of bone metabolism in children with nephrotic syndrome]. / Wplyw kortykosteroidów na wybrane parametry metabolizmu kostnego u dzieci z zespolem nerczycowym.

The aim of the study was to evaluate the influence of prednisone therapy on selected parameters of bone metabolism [carboxyterminal propeptide of type I procollagen (PICP), carboxyterminal pyridinoline crosslinked telopeptide of type I collagen (ICTP), alkaline phosphatase (AP), parathormone (PTH), and calciuria (Cau) in children with nephrotic syndrome. Twenty patients (aged 4-15 years, mean: 9.2 years) were treated with prednisone. Blood and urine samples were taken: T0--before prednisone treatment; T1--after two weeks of treatment with prednisone 1-2 mg/kg/24 h; T2--after two weeks of treatment with prednisone 1-2 mg/kg/48 h; T3--after 3 months of treatment with prednisone; T6--in 6th month of treatment with prednisone, at dose 0.2-0.4 mg/kg/48 h. Mean values of PICP, ICTP, AP concentration, and PICP/ICTP ratio found in the T1 period were significantly lower, and mean Cau value was higher in comparison to means of these parameters observed before steroid treatment. After two weeks of prednisone administered every 48 hours mean values of PICP, ICTP concentrations and PICP/ICTP ratio were significantly higher than in the T1 period of treatment. There were no significant differences in mean concentrations of PTH before and during everyday doses of prednisone therapy. Mean value of PTH concentration decreased significantly during T2 in comparison with T1 period of prednisone treatment. Our data demonstrate that short-term treatment with high daily doses of prednisone in children with nephrotic syndrome is associated with increase of calciuria and suppression of serum markers of type I collagen's turnover. Changes of PICP, ICTP, and PICP/ICTP ratio depend on a method of steroid administration. Decreased PICP/ICTP ratio during daily steroid treatment may indicate stronger inhibition of bone formation than bone resorption, but significance of PICP/ICTP ratio in later phases of treatment needs further studies. Present study suggests that prednisone influences bone metabolism directly rather than by stimulating the parathyroids.

Regulation of rat AMP deaminase 3 (isoform C) by development and skeletal muscle fibre type.

AMP deaminase (AMPD) is characterized by a multigene family in rodents and man. Highly conserved rat and human AMPD1 and AMPD2 genes produce protein products that exhibit cross-species immunoreactivities (AMPD1, rat isoform A and human isoform M; AMPD2, rat isoform B and human isoform L). A third gene, AMPD3, has been described in humans, but antisera raised against its purified protein product (isoform E) reportedly does not cross-react with a third activity purified from rat tissues (isoform C). This study was designed to address this latter issue by cloning, sequencing and expressing rat AMPD3 cDNA species. Similarly to the human AMPD3 gene, the rat AMPD3 gene produces multiple transcripts that differ at or near their 5' ends. The boundary at which these alternative sequences diverge is precisely conserved in both species. Across the region that is common to all rat and human AMPD3 cDNA species, nucleotide and predicted amino acid sequences are 89% and 93% identical respectively, although the rat open reading frame is lacking two separate in-frame codons in the 5' end. Extreme 5' regions between the two species are entirely divergent, and one alternative rat sequence is predicted to confer at least 36 additional N-terminal residues to its encoded AMPD3 polypeptide. A comparison of 3' untranslated regions indicates that the rat sequence is 250 bp longer and contains multiple consensus polyadenylation signals. Examination of relative rat AMPD3 gene expression shows (1) variable patterns of alternative mRNA abundance across adult tissues, (2) developmental regulation in skeletal muscle and liver, and (3) greater mRNA abundance in adult red (soleus) than in mixed (plantaris) and white (outer gastrocnemius) skeletal muscle. Finally, baculoviral expression of rat and human AMPD3 proteins produces enzymes that are chromatographically and kinetically similar. Moreover, both recombinant activities immunoreact with anti-C and anti-E serum. These combined results demonstrate that rat isoform C and human isoform E are homologous cross-species AMPD3 proteins.