Hematologic Diseases

to evaluate the reliability and validity of a generic job exposure matrix (JEM) applied in a small business. procedures to evaluate a JEM integrated by six sections: the number of exposed workers per area, frequency of exposure, time of exposure time, level of exposure, safety controls, and proximity to source of exposure, was evaluated. The JEM also obtains information about possible health effects from exposure to occupational/environment agents. Two observers estimated the risk of exposure to epoxy resins on 31 workers of an epoxy resin facility in Mexico City. The rater agreements between the two observers were assessed through percent agreement (PA), weighted kappa (kappa(w)) and the intraclass correlation coefficient (ICC). disagreements were greater for the number of exposed workers (PA = 61.3, kappa(w) = 0.24, ICC = 0.33), level of exposure (PA= 66.7, kappa(w) = 0.25, ICC= 0.56), and safety controls (PA = 54.8, kappa(w) = 0.23, ICC = 0.69) sections. Percent agreement and kap...

The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at Euro 23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary wa...

The aim of the study is to evaluate if occupational exposure to urban stressors could cause alterations in red blood cells (RBC), hemoglobin (HGB), hematocrit (HCT), mean cell volume (MCV), mean cell hemoglobin (MCH), mean corpuscular hemoglobin concentrations (MCHC) in traffic police compared to a control group. 694 subjects were included in the study: 347 traffic police and 347 controls matched by sex, age and length of service after excluding the subjects with the principal confounding factors. The levels of RBC, HGB, HCT were significantly higher in male (respectively p<0.001, p<0.05, p<0.01) and in female (respectively p<0.05, p<0.001, p<0.01) traffic police than in controls. The authors hypothesise that occupational exposure to urban stressors in traffic police can alter hemopoietic system.

After being successfully applied to other intraabdominal organs, the laparoscopic approach has been applied to the spleen since 1991. The experience with 17 cases of laparoscopic splenectomy performed due to immune thrombocytopenia purpura (10 instances), hereditary spherocytosis (2 cases), and Hodgkin' s disease where the staging was done according to Stanford (5 cases), have been reported. With the patient in anti-Trendelenburg position, and the surgeon between the patient's legs, four or five trocars are introduced into the upper abdominal quadrants and the spleen hilum is isolated. Hilar vessels are dissected and ligated with a surgical stapler. A plastic bag is introduced into the abdomen cavity and the spleen is slipped inside; it is then extracted through an umbilical incision after morcellation. Advantages of the open operation include a decrease in postoperative pain, a decrease in pulmonary sequelae, a reduced incidence of subphrenic abscesses, and cosmetic advantages. The decrease of postoperative sequelae reduces hospitalization and costs, which are higher for the operation itself (materials and staff's training).

Many sequencing studies are now underway to identify the genetic causes for both Mendelian and complex traits. Via exomesequencing, genes harboring variants implicated in several Mendelian traits have already been identified. The underlying methodology in these studies is a multistep algorithm based on filtering variants identified in a small number of affected individuals and depends on whether they are novel (not yet seen in public resources such as dbSNP), shared among affected individuals, and other external functional information on the variants. Although intuitive, these filter-based methods are nonoptimal and do not provide any measure of statistical uncertainty. We describe here a formal statistical approach that has several distinct advantages: (1) it provides fast computation of approximate p values for individual genes, (2) it adjusts for the background variation in each gene, (3) it allows for incorporation of functional or linkage-based information, and (4) it accommodates designs based on both affected relative pairs and unrelated affected individuals. We show via simulations that the proposed approach can be used in conjunction with the existing filter-based methods to achieve a substantially better ranking of a gene relevant for disease when compared to currently used filter-based approaches, this is especially so in the presence of disease locus heterogeneity. We revisit recent studies on three Mendelian diseases and show that the proposed approach results in the implicated gene being ranked first in all studies, and approximate p values of 10 À6 for the Miller Syndrome gene, 1.0 3 10 À4 for the Freeman-Sheldon Syndrome gene, and 3.5 3 10 À5 for the Kabuki Syndrome gene.

Many sequencing studies are now underway to identify the genetic causes for both Mendelian and complex traits. Via exomesequencing, genes harboring variants implicated in several Mendelian traits have already been identified. The underlying methodology in these studies is a multistep algorithm based on filtering variants identified in a small number of affected individuals and depends on whether they are novel (not yet seen in public resources such as dbSNP), shared among affected individuals, and other external functional information on the variants. Although intuitive, these filter-based methods are nonoptimal and do not provide any measure of statistical uncertainty. We describe here a formal statistical approach that has several distinct advantages: (1) it provides fast computation of approximate p values for individual genes, (2) it adjusts for the background variation in each gene, (3) it allows for incorporation of functional or linkage-based information, and (4) it accommodates designs based on both affected relative pairs and unrelated affected individuals. We show via simulations that the proposed approach can be used in conjunction with the existing filter-based methods to achieve a substantially better ranking of a gene relevant for disease when compared to currently used filter-based approaches, this is especially so in the presence of disease locus heterogeneity. We revisit recent studies on three Mendelian diseases and show that the proposed approach results in the implicated gene being ranked first in all studies, and approximate p values of 10 À6 for the Miller Syndrome gene, 1.0 3 10 À4 for the Freeman-Sheldon Syndrome gene, and 3.5 3 10 À5 for the Kabuki Syndrome gene.

Red-cell adenosine deaminase (ADA) activity in children with Diamond-Blackfan anaemia is significantly increased (1.9 1 f 0.90 U/g Hb) compared to that seen in transient erythroblastopenia of childhood (0.80 f 0.1 6 U/g Hb) or normal individuals (0.61 f. 0.13 U/g). These data thus further support that measurement of this purine metabolic enzyme is useful in diagnosing the cause of pure KBC aplasia in children. Of interest, however, elevated RBC-ADA activity also is seen in some children with acute leukaemia and other haematologic disorders. In children with acute lymphohlastic leukaemia (ALL), the increase in KBC-ADA activity is proportional to the degree of anaemia. However, the elevated RBC-ADA activity in this leukaemic population is not related to the fetal haemoglobin concentration. These data suggest increased RBC-ADA activity may be a non-specific manifestation of abnormal erythroid stem cell function, an alteration distinct from that seen with reactivation of fetal erythropoiesis. However, since almost all patients with Diamond-Blackfan anaemia manifest elevated RBC-ADA activity, this chemical alteration yet may reflect the specific erythroid differentiation lesion in this disorder.

This review describes the authors&#39; experience with 2,000 cases of benzene poisoning reported between 1983 and 1995 in Cubatão, an industrial section of São Paulo, Brazil, investigated through the integration of epidemiology and clinical research. Conflicting economic interests were reflected in disputes about medical criteria for evaluation of poisoned workers, about proper means of conducting workplace hygiene evaluations, about benzene exposure standards, and about compensation for chronic bone-marrow damage.

Bone marrow cellularity estimated by biopsy was compared to the cellularity of the aspirate particle smear and the volumetric method in two groups of children. In the first group, 101 consecutive bone marrow biopsies and aspirates were evaluated from patients with various diagnoses. In the second group, 20 patients with acute nonlympho‐blastic leukemia were studied with 80 biopsies and aspirates at diagnosis and following chemotherapy. A wide discrepancy was noted between bone marrow cellularity confirmed by biopsy vs. the particle smear or the volumetric method in both groups. Neither the volumetric nor the particle method provides a good correlation of bone marrow cellularity. We also compared the volumetric method with that of the biopsy to evaluate the efficacy of the former method in detecting bone marrow infiltration by solid tumors. The volumetric method is an accurate modality of identifying solid tumor infiltration in the bone marrow.

The purpose of this phase II trial was to investigate the use of paclitaxel and cisplatin in patients with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC), to evaluate tumor response, time to progression, survival, and toxicity of this regimen. Patients with recurrent and/or metastatic HNSCC received 175 mg/mq paclitaxel (PTX) administered as a 3-h intravenous infusion on day 1 and 75 mg/mq cisplatin (CDDP) as a 30 0 intravenous infusion on day 2; cycles were repeated every 21 days. From February 1997 to February 2000, 36 patients (18 with locoregionally recurrent disease, 8 with deemed inoperable locally advanced disease, and 8 with metastatic disease) with a median age of 60 years (range 38-73 years) were enrolled. The patients evaluable were 34 for toxic effects, length of survival, and tumor response. The overall response was 41.1%, with two (5.8%) complete responders (CR) and 12 (35.3%) partial responders (PR), 10 (29.4%) patients had stable disease and 10 (29.4%) progressed. The median time to progression (TTP) was 5 months (range 1-49 months), and the median overall survival was 11 months (range 1-53 months). The 1year-, the 2-year-, and the 3-year-survival rate were 38.2, 17.6 and 14.6, respectively. Up to date of the statistical evaluation four patients were still alive. According to the World Health Organization (WHO) criteria, transient G3 neutropenia and anaemia occurred in seven (20.5%) and four (11.7%) patients, respectively. The predominant

Oral antineoplastic agents (OAA) have reached 30-50% of all antineoplastic treatments. Although they seem safer than parenteral therapy, many severe problems can occur if the dose is not adequately adjusted in special situations. Our objective is to create a comprehensive guide with dosage adjustment recommendations for OAA in cases of renal and hepatic impairment and hematologic toxicities. We analyzed all OAA approved by EMA in July 2017. We we assessed data related to dose adjusted from the FDA&#39;s and EMA&#39;s summary of product characteristics. 53 OAA were analyzed. We identified 44 (83%) OAA requiring dosage adjustments in special situations: 20 (37.7%) in renal impairment, 37 (69.8%) in hepatic impairment and 22 (41.5%) in patients with hematologic toxicity. The dose adjustment recommendations varied in 31 (58.5%) OAA between the FDA and EMA. Detailed recommendations for each OAA were collated into comprehensive tables. Most OAA have to be adjusted in special situations. G...

Background: 5-Fluorouracil (5-FU) is administered with leucovorin (LV) to enhance clinical activity. However, simultaneous administration is not feasible due to their chemical incompatibility, so conditions for the maximum possible beneficial interaction cannot be met. To overcome this, we developed a novel all-in-one, pH neutral stable solution of 5-FU plus LV with 𝛽cyclodextrin (termed Deflexifol) and assessed its safety and tolerability in a first-inhuman phase I trial. Methods: Patients with advanced solid malignancy received Deflexifol as weekly bolus (375-575 mg/m 2) or two-weekly 46 h infusion (1200-3600 mg/m 2) for six cycles in a 3+3 dose escalation design. Adverse events, pharmacokinetics and tumor response rates were assessed by standard methods. Results: Forty patients were treated (19 bolus, 21 infusional, median age 67) with no grade 4 adverse events reported. Dose-limiting toxicities of grade 3 diarrhea and myelosuppression were reported for the bolus schedule at 575 mg/m 2 (maximum tolerated dose 525 mg/m 2), whereas none were reported for the infusional schedule. The recommended phase II infusional dose was declared as 3,000 mg/m 2 , >25% that of 5-FU used in standard-of-care regimens. Pharmacokinetic analyses showed evidence of inter-patient variability, with no evidence of saturation in clearance, and a trend to linear increase in AUC with dose. Disease control rate was 64% despite most patients having failed previous 5-FU regimens. Conclusion: Deflexifol is safer and effective in bolus and infusion schedules at higher doses than that permitted by separate infusion of 5-FU and LV. A phase II study evaluating Deflexifol is planned.

Marginal zone lymphomas (MZLs) are rare and indolent subtypes of non-Hodgkin lymphomas, and their clinical behaviours are heterogeneous. The aim of this study was to evaluate the clinical and prognostic characteristics of MZL. In this multicentre retrospective study, we analyzed demographical, clinical and prognostic features of 64 MZL patients. The median age was 54.0 and 78.1% of the patients had extra-nodal disease at presentation. Most of the patients were treated with chemotherapy. The 5 years and 10 years overall survival (OS) rates were 74.5% and 62.1%, respectively. The analysis of factors associated with OS showed that ECOG performance score was an important prognostic factor, with 133.0 months (95% CI 49.3-216.5) versus 18.0 months (95% CI 12.1-23.7) for ECOG 0-1 and 2-3, respectively (p = 0.011). Prognosis of MZL is favorable and ECOG performance score was found associated with OS. Further detailed studies with large patient numbers are needed to clarify the clinical features and treatment management of MZLs.

There are concerns of a reduced effect of liposomal amphotericin B (L-AmB) given sequentially after mold-active azoles due to a possible antagonism in their antifungal mechanism. To investigate this possible effect in the clinic, we retrospectively studied 182 high risk hematologic patients with invasive fungal infections (IFI) who were treated with L-AmB. Overall, 96 patients (52.7%) had possible, 52 (28.6%) probable and 34 (18.7%) proven IFI according to EORTC classification. Most had suspected or proven invasive aspergillosis. We compared patients with prior exposure to mold-active azoles (n=100) to those having not (n=82). The group with prior mold-active azoles included more patients with poor risk features for IFI as acute myeloid leukemia (p&lt;0.05) and prolonged neutropenia (p&lt;0.05). A favorable response in the IFI, defined as a complete or partial response, was achieved in 75% and 74.4% of patients in the whole cohort, and in 66% and 74.4% of patients with probable or p...

Chronic kidney disease (CKD) is associated to significant infection incidence and severity, the cause of death of, approximately, 20% of end-stage renal disease patients. Close to 80% of all infections in these patients can be related to organ or tissue other than vascular access, reflecting immune system dysfunction related to several mechanisms. Strongyloides stercoralis is an endemic nematode found especially in tropical and subtropical areas. The clinical manifestations of Strongyloides stercoralis infection vary according to the acuity of infection and the host response, from asymptomatic to the disseminated presentation, frequently lethal. Risk factors for severe presentations are related to immunosuppression states. The authors report a case of a patient with advanced CKD of unknown etiology, who developed an exuberant eczema, respiratory symptoms and severe hypereosinophilia. The etiological study revealed a disseminated form of Strongyloides stercoralis infection with myocardia involvement, diagnosed solely by serologic testing, despite microbiological tests to identify the infective agent. In this case, the patient has evolved favorably, with remission of symptoms and cardiac features, after adequate anti-helminthic treatment. The importance of parasitic colonization and its potential harm becomes clinically more relevant when patients become immunosuppressed, as in CKD progression or in the immunosuppressive therapy setting, such as solid organ transplant rejection therapy. A brief literature review related to strongyloidiasis and immunosuppression in the CKD setting is also presented.

To investigate the efficacy and the safety of gemcitabine and oxaliplatin combination in metastatic breast cancer (MBC), in patients heavily treated with anthracycline and taxane. A retrospective study including all MBC patients, treated by two different schedules of GemOx between February 2001 and December 2003 in the medical oncology department of Saint-Louis hospital. Forty-three consecutive patients were included. Median involved organs was 2. The median number of regimen of previous metastatic chemotherapy administered was 3. The median number of cycle administered was 5, with a median dose by cycle of 1,000 or 2,000 mg ⁄ m 2 of gemcitabine (D1D2 or D1D8 schedule, respectively) and 100 mg ⁄ m 2 of oxaliplatin. Of the 40 evaluable patients, three achieved a partial response giving an overall response rate of 7.5% and 11 demonstrated stable disease, giving a stabilization rate of 27.5%. Median overall survival in all treated patients was 10.6 months and median progression-free survival in all evaluated patients was 3.0 and 10.5 months for the partial responders. Hematotoxicity was prevalent, sometimes severe, with grades 3 and 4 neutropenia, thrombocytopenia, and anemia in 42%, 19%, and 14% of the patients. Grades 3 and 4 peripheral neuropathy were developed by 9% of the patients, but was not limiting. The present study reports the results of two exploratory schedules of the GemOx combination in advanced breast cancer patients. The D1D8 schedule was the most promising and deserves further clinical studies. n

Objectives: The use of laparoscopy to treat malignant hematological diseases is not completely accepted. Our aim was to analyze operative and postoperative results of laparoscopic splenectomy performed for benign versus malignant hematological disorders. Methods: Between 1994 and 2003, 76 consecutive patients underwent laparoscopic splenectomy. The first 38 cases were performed by using an anterior approach, whereas in the remaining 38 cases a semilateral position was used. Results: Baseline characteristics showed that patients with malignant diseases were significantly older (56.9 vs 32.6 years, P < 0.001). Seventy-two (94.7%) procedures were completed laparoscopically. Conversion was required in 4 cases (5.2%). Mean operative time was 138.5 minutes for benign and 151.0 minutes for malignant diseases, (P > 0.05, ns). The hand-assisted technique was used in 3 patients with massive splenomegaly. Pathologic features showed that spleen volume was higher in patients with malignant diseases (mean interpole diameter 18.1 cm vs 13.7 cm, P < 0.001). Massive splenomegaly (interpole diameter over 20 cm, weight over 1000 g) was present in 13 patients (17.1%); 9 had malignant diseases. Overall perioperative mortality was 1.3% and major postoperative complications occurred in 6 patients (7.8%). Postoperative splenoportal partial thrombosis was identified in 9.7% of patients. Conclusions: Laparoscopic splenectomy is a well-accepted, less-invasive procedure for hematological disorders. Neoplastic diseases or splenomegaly, or both, do not seem to limit the indications for a minimally invasive approach after the learning curve.

The use of laparoscopy to treat malignant hematological diseases is not completely accepted. Our aim was to analyze operative and postoperative results of laparoscopic splenectomy performed for benign versus malignant hematological disorders. Between 1994 and 2003, 76 consecutive patients underwent laparoscopic splenectomy. The first 38 cases were performed by using an anterior approach, whereas in the remaining 38 cases a semilateral position was used. Baseline characteristics showed that patients with malignant diseases were significantly older (56.9 vs 32.6 years, P &lt; 0.001). Seventy-two (94.7%) procedures were completed laparoscopically. Conversion was required in 4 cases (5.2%). Mean operative time was 138.5 minutes for benign and 151.0 minutes for malignant diseases, (P &gt; 0.05, ns). The hand-assisted technique was used in 3 patients with massive splenomegaly. Pathologic features showed that spleen volume was higher in patients with malignant diseases (mean interpole diam...

There are currently no clinic-level quality of care metrics for outpatient pediatric oncology. We sought to develop a list of quality of care metrics for a leukemia-lymphoma (LL) clinic using a consensus process that can be adapted to other clinic settings. Medline-Ovid was searched for quality indicators relevant to pediatric oncology. A provisional list of 27 metrics spanning 7 categories was generated and circulated to a Consensus Group (CG) of LL clinic medical and nursing staff. A Delphi process comprising 2 rounds of ranking generated consensus on a final list of metrics. Consensus was defined as ≥70% of CG members ranking a metric within 2 consecutive scores. In round 1, 19 of 27 (70%) metrics reached consensus. CG members&#39; comments resulted in 4 new metrics and revision of 8 original metrics. All 31 metrics were included in round 2. Twenty-four of 31 (77%) metrics reached consensus after round 2. Thirteen were chosen for the final list based on highest scores and elimina...

For many children with life-threatening hematological diseases, hematopoietic stem cell transplantation (HSCT) is the only curative option. In children lacking a matched related or unrelated donor and with the certainty that, left untreated, death will ensue alternative donors must be sought. Haplo-identical peripheral blood stem cell transplantation (PBSCT) from a healthy parent is a feasible alternative. To reduce the risk of fatal graft-versus-host disease (GvHD) as a complication of transplant across major histocompatibility antigens, intense T-cell depletion is required. Large numbers of purified, cytokine mobilized peripheral stem cells (the so-called mega-dose concept) are required to compensate for the significantly increased risk of either graft failure or early rejection. In our unit, despite this approach, graft dysfunction has, in a significant group of children, proved problematic and, despite salvage attempts at re-transplantation, usually fatal. In children with hematological malignant disease, our overall relapse-free survival is 41%. However, successful transplant outcome has been associated with considerable delays in immune reconstitution that can be implicated in subsequent viral reactivation. We are investigating new strategies to improve the outcome of haplo-identical PBSCT, which may allow us to offer this form of treatment to more children requiring urgent HSCT.

Crude spectrin was extracted from the isolated red cell ghosts with low ionic strength buffer at 37°C for 30 min. No significant alterations in crude spectrin extractability in wide range of patients with various hematologic diseases were observed. However, blood samples characterized by elevated reticulocytosis provided crude extracts with increased amount of non-heme membrane skeletal proteins. The presence of ribose in the crude spectrin extracts obtained from reticulocyte-rich blood samples indicates also the presence of nucleic acids which causes the shift of protein peak in the extract from 280 nm towards lower wavelengths. A model experiment with a normal crude spectrin extract mixed with various amounts of RNA allowed us to obtain the correction curve which served for determination of non-heme protein (crude spectrin) extractability.

A total of 52 children, age 9 or over and at least 3 years (median ¼ 8) beyond SCT for leukaemia (n ¼ 32) or nonmalignant diseases, participated in a single-centre study of health and quality of life (QoL). QoL and self-esteem were assessed with SCHQ-CF87, a generic multidimensional self-report instrument, and with 'I think I am'. As a group, the children had good QoL, but were below norm in the bodily pain (Po0.05), general health and self-esteem dimensions (Po0.01). Lansky or Karnofsky function levels were at a median of 90. Sense of coherence (SOC-13) was normal and correlated with SCHQ-CF87. Most children were subjectively and objectively in good health according to a self-assessment symptom inventory or by a medical record-based scoring of late effects, although pain was commonly reported. A total of 25% of the patients were rated as having moderate to severe late effects, without considering cataracts or infertility. Neither age at SCT, gender, malignant vs nonmalignant disease, nor stature influenced QoL significantly. Children with moderate to severe chronic graft-versus-host disease or cognitive deficits had lower QoL in some dimensions. No correlation was, however, found between the physician-rated total late effects score and overall QoL. Contrarily, QoL was clearly related to the degree of self-rated symptoms.

proportion of patients achieving complete response or VGPR, as determined by an independent review committee by modified Owens criteria (Br J Haematol. 2013;160:171 and National Comprehensive Cancer Network Guidelines). Key secondary end points include major response rate, duration of response, progression free survival, and safety. Study recruitment is ongoing, with the first patient enrolled in January 2017 and participating sites in Europe, Asia-Pacific, and North America (NCT03053440).

Low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor (CAG regimen) for previously treated patients with relapsed or primary resistant acute myelogenous leukemia (AML) and previously untreated elderly patients with AML, secondary AML and refractory anemia with excess blasts in transformation.

Blóðflokkar byggja á mismunandi samsetningu mótefnisvaka á rauðum blóðkornum. Nú eru þekktir um 300 mismunandi blóðflokkamótefnisvakar sem tilheyra 30 blóðflokkakerfum en af þeim eru ABO-og Rhesuskerfin best þekkt og mikilvaegust varðandi blóðgjöf. 1 ABO-blóðflokkakerfið samanstendur af tveimur ríkjandi mótefnisvökum (A og B) sem tvö ósamgena sykruensím mynda, en óvirk ensím einkenna blóðflokk O. Almennt eru anti-A og/eða anti-B mótefni í sermi til staðar gegn framandi A og/eða B mótefnisvaka frá þriggja til 6 mánaða aldurs. 2 Meginhluti anti-A og anti--B eru IgM-mótefni en ABO-blóðflokkamisraemi veldur aðeins vandamálum hjá fóstri ef móðir hefur háan styrk IgG anti-A og/eða anti-B mótefna og eru það helst maeður í O-blóðflokki. Ólíkt ABO eru mótefnisvakar flestra annarra blóðflokkakerfa fjölpeptíð en ekki sykrur, til daemis Rhesus, Kell, Kidd og fleiri. Mótefni gegn fjölpeptíðamótefnisvökum eru ekki til staðar frá náttúrunnar hendi en myndast naer eingöngu eftir naemingu, til daemis við blóðgjöf eða á meðgöngu. Fóstur-og nýburablóðrof (Hemolytic disease of the fetus and newborn, FNB) stafar af eyðingu rauðkorna fósturs/nýbura vegna mótefna frá móður með tilheyrandi blóðleysi og/eða haekkun bilirúbíns hjá fóstri/ barni. Alvarlegustu afleiðingar FNB eru fósturbjúgur á Inngangur: Fóstur-og nýburablóðrof stafar af eyðingu fósturrauðkorna vegna rauðkornamótefna móður. Rofið getur leitt til blóðleysis og fósturbjúgs á fósturskeiði og gulu hjá nýburum. Prófið Direct Antiglobulin Test (DAT) greinir mótefni bundin við rauðkorn og er hluti af greiningarferli rofsins. Á Íslandi er DAT gert á naflastrengs-/blóðsýnum nýbura ef móðir er RhD-neikvaeð eða hefur rauðkornamótefni önnur en anti-A/-B. Markmið rannsóknarinnar var að rannsaka orsakir og afleiðingar jákvaeðs DAT hjá nýburum á Íslandi á 8 ára tímabili. Efniviður og aðferðir: Rannsóknarhópurinn var nýburar með jákvaett DAT á árunum 2005-2012. Úr tölvukerfi Blóðbankans voru sóttar upplýsingar um blóðflokk móður og barns, blóðgjafir og DAT. Úr maeðraskrá fengust upplýsingar um faeðingarþyngd, meðgöngulengd og ljósameðferð. Úr rafraenu sjúkraskrárkerfi Landspítala fengust upplýsingar um meðferð og afdrif nýbura. Niðurstöður: Á árunum 2005-2012 greindust 383 nýburar með jákvaett DAT á Landspítala. Í 73,6% tilvika var orsökin ABO-blóðflokkamisraemi á milli móður og barns, hjá 20,4% voru rauðkornamótefni móður önnur en anti A/-B, hjá 3,9% hvort tveggja, en hjá 2,1% var orsök óljós. Alls fengu 179 (47,6%) börn meðferð vegna jákvaeðs DAT með nýburagulu, þar af 167 (93,3%) ljósameðferð eingöngu. Átta nýburar þurftu blóðskiptameðferð, þar af 5 vegna Rhesus-mótefna en þrjú vegna ABO-blóðflokkamisraemis. Ályktun: Jákvaett DAT hjá nýburum á Íslandi árin 2005-2012 stafaði í flestum tilvikum af ABO-blóðflokkamisraemi á milli móður og barns. Taeplega helmingur barnanna þurfti meðhöndlun en oftast naegði ljósameðferð. Í alvarlegustu tilfellum ABO-blóðflokkamisraemis eða rauðkornamótefna annarra en anti-A/-B var þörf á blóðgjöf eða blóðskiptameðferð.

Introduction: Fungal pneumonia is a major cause of morbidity and mortality in immunocompromised patients with hematological diseases. This study is aimed to evaluate the feasibility and outcome of computed tomography (CT) guided lung biopsy or fine needle aspiration cytology (FNAC) in the diagnosis of fungal pneumonia in patients with hematological diseases. Methodology: Seven hundred and seventy six consecutive patients with febrile neutropenia were evaluated prospectively over the period of three years. Patients with suspected fungal pneumonia, based on typical CT scan findings, were considered for lung biopsy. Results: Of the 776 patients evaluated for fever, 235 (30.3%) showed CT scan findings consistent with fungal pneumonia. Of the 235 patients, CT-guided lung biopsy/FNAC was recommended for 178 patients but could be performed in only 34 (19.1%) patients. Fungal pneumonia was proven in 15 (44%) out of 34 patients (aspergillus in 12;  mucormycosis in 3 patients). Lung biopsies ...

Langerhans cell histiocytosis (LCH) is a disease with unknown etiology. It presents as single-system (affecting a single organ or tissue) or as multisystem (with or without risk organ involvement). The oral cavity may be involved or be the site of the first manifestation. Aim: To describe, group, and determine the frequency of oral lesions in pediatric patients with LCH, and to relate these lesions to age and the different disease subtypes. Materials and Method: Clinical and radiographic examinations were used to evaluate 95 patients diagnosed with LCH, aged 0 to 16 years, who were referred to the

The transplantation of bone marrow cells or isolated hematopoietic stem cells from the bone marrow or peripheral blood is a widely utilized form of therapy for patients with incurable diseases of the hematopoietic and immune systems. Successful engraftment of the transplanted stem cells in an adequately prepared recipient normally leads to bone marrow reconstitution over a period of several weeks, accompanied by more gradual reconstitution of the immune system. Since the recipient is profoundly ill during the initial treatment period, laboratory data is critical for monitoring engraftment, detecting residual/recurrent disease, and identifying problems that may delay bone marrow reconstitution or lead to other medical complications. Accurate blood cell counts are imperative, and most bone marrow transplantation patients undergo periodic monitoring with bone marrow aspirates and biopsies with cytogenetic, molecular, and multiparametric flow cytometric studies. The potential complications of bone marrow transplantation include engraftment failure and delayed engraftment, infection, residual bone marrow disease, acute and chronic graft versus host disease, myelofibrosis, therapy-related acute leukemia, post-transplant lymphoproliferative disorders, and toxic myelopathy.

Objective -To present the latest information on inherited platelet disorders in domestic animals. Data Sources -Research articles and reviews spanning 40 years available on PubMed. Human Data Synthesis -Information regarding inherited platelet disorders in people is plentiful and often descriptions of human conditions have led to the identification of similar disorders in veterinary species. There are exceptions, however, in which specific inherited platelet disorders were first described in animals with subsequent identification in people. Veterinary Data Synthesis -Many inherited platelet disorders have been documented in animals at the functional and molecular level and that information is presented in this review. Conclusions -Much progress has been made in the past 20 years in the characterization of inherited platelet disorders in animals at the functional, biochemical, and molecular level. The study of inherited platelet disorders has greatly enhanced the understanding of platelet physiology and has led in some instances to the development of platelet inhibitory medications. Characterization of inherited disorders at the molecular level greatly facilitates diagnosis and identification of affected and heterozygous animals thus avoiding propagation of the defect by breeders. When used with available functional and biochemical diagnostic tests, it significantly enhances the quality of care and case management.

El término escorbuto procede de una palabra del antiguo escandinavo, scorbruck, que significa "hinchazones ulceradas". Es una entidad infrecuente en pediatría, causada por deficiencia nutricional exógena de ácido ascórbico. Los seres humanos, a diferencia de otros seres vivos, no pueden sintetizar la vitamina C y, en consecuencia, dependen estrictamente de su aporte exógeno. El escorbuto puede simular varios desórdenes reumatológicos. Aunque es poco común, puede presentarse como pseudovasculitis o artritis crónica. Para el diagnóstico en pacientes que presentan síntomas músculo esqueléticos se requiere un alto índice de sospecha. Se reporta el caso de un paciente masculino de 9 años que desarrolló la enfermedad por un hábito alimentario selectivo de larga evolución, sin ingesta de frutas ni verduras. El objetivo del presente reporte es alertar al pediatra acerca del desarrollo de escorbuto como potencial consecuencia de las dietas restrictivas, y la importancia de realizar una anamnesis alimentaria completa ante la sospecha diagnóstica. Escorbuto, vitamina C, Ac ascórbico, dietas restrictivas.

El término escorbuto procede de una palabra del antiguo escandinavo, scorbruck, que significa "hinchazones ulceradas". Es una entidad infrecuente en pediatría, causada por deficiencia nutricional exógena de ácido ascórbico. Los seres humanos, a diferencia de otros seres vivos, no pueden sintetizar la vitamina C y, en consecuencia, dependen estrictamente de su aporte exógeno. El escorbuto puede simular varios desórdenes reumatológicos. Aunque es poco común, puede presentarse como pseudovasculitis o artritis crónica. Para el diagnóstico en pacientes que presentan síntomas músculo esqueléticos se requiere un alto índice de sospecha. Se reporta el caso de un paciente masculino de 9 años que desarrolló la enfermedad por un hábito alimentario selectivo de larga evolución, sin ingesta de frutas ni verduras. El objetivo del presente reporte es alertar al pediatra acerca del desarrollo de escorbuto como potencial consecuencia de las dietas restrictivas, y la importancia de realizar una anamnesis alimentaria completa ante la sospecha diagnóstica. Escorbuto, vitamina C, Ac ascórbico, dietas restrictivas.

Destructive membranous periodontal disease is a rare, destructive and poorly defined entity, which is the part of a systemic disease due to plasminogen deficiency and fibrin deposition. The disease is characterised by gingival enlargement and periodontal tissue destruction that leads to rapid tooth loss despite treatment attempts. Biopsy is essential to rule out other periodontal disease in the differential diagnosis.

Background: This phase-II study was conducted to investigate the potential benefit from the addition of mitomycin to a conventional anthracycline-cisplatin-and 5-fluorouracil-based chemotherapy for recurrent and metastatic undifferentiated carcinoma of nasopharyngeal type (UCNT). Patients and methods: Between July 1989 and December 1991, 44 consecutive patients (M/F 36/8; median age: 45, range 20-72; performance status (PS) 0: 20 patients, PS 1: 14 patients, PS 2: 10 patients) with recurrent or metastatic UCNT were entered in this study after complete clinical, biological, and radiological pre-therapeutic work-ups. Chemotherapy (FMEP regimen) consisted of 800 mg/m 2 /day 5-fluorouracil in continuous infusion from day 1 to day 4 combined with 70 mg/m 2 epirubicin, 10 mg/m 2 mitomycin, and 100 mg/m 2 cisplatin on day 1, every four weeks for six cycles. Mitomycin was delivered in cycles 1, 3, and 5 only. Eleven patients had isolated loco-regional recurrences, 12 patients had local recurrences associated with distant metastasis, and 21 patients had metastasis only. Toxicity and response were evaluated according to WHO criteria. Toxicity: Grade 3-4 neutropenia was observed in 122 of 212 evaluable cycles (57%) and 39 of 44 patients (89%); febrile neutropenia occurred in 16 patients (36%) and 24 cycles (11.3%). Grade 3-4 thrombocytopenia was observed in 27 patients (61%) and 45 cycles (21%), including 27 of 45 cycles (60%) with mitomycin. Grade 3 anemia was noted in 18 patients (40%) and 23 cycles (11%), including 18 of 23 cycles (78%) with mitomycin. Grade 3-4 mucositis occurred in 25 cycles (11%) and 14 patients (32%), mainly in those previously treated with radiation therapy in the head and neck area. There were four treatment-related deaths (9%); three of them neutropenia-related, and one of cardiac toxicity. Response: Forty-four patients were evaluable for response: There were 23 of 44 objective responses (52%), including six complete responses (13%), and 17 partial responses (38%). Additional radiotherapy was given to 13 patients after documentation of response: Nasopharyngeal tumor + cervical nodes (eight patients) and /or on bone metastasis sites (five patients); mediastinal lymph nodes (one patient). At a median follow-up of 87 months (range 71-100), five patients are alive and in continuous complete remission. The median survival time was 14 months and the median time to progression nine months. The regimen under study is active in recurrent/ metastatic UCNT, but associated with excessive toxicity.

Purpose: We performed a Phase I and pharmacokinetic study to determine the maximum tolerated dose of irofulven (6-hydroxymethylacylfulvene; MGI-114, MGI PHARMA, Inc.), administered in intermittent weekly schedules in patients with advanced solid tumors.Experimental Design: Three schedules were tested: A, days 1, 8, and 15 every 4 weeks; B, days 1 and 8 every 3 weeks; C, days 1 and 15 every 4 weeks. Drugs were administered as 5- and 30-min (schedules B and C) infusions. Dose levels of 10, 12, and 14 mg/m2/week were explored.Results: Ninety-nine patients received 256 cycles. Fifteen of 74 patients evaluable for maximum tolerated dose experienced 16 dose-limiting toxicities (5 of 17 patients on schedule A, 2 of 25 on schedule B, and 8 of 32 on schedule C), principally treatment delay for thrombocytopenia. Schedule A was considered unsuitable because of frequent thrombocytopenia and treatment discontinuations. Twenty-three percent of the overall population (22 patients with grade 1–2, a...

in Riyadh between January 01 and March 31, 2014. The study included 140 patients with SCD attending the hematology out-patient clinics. Sixty of these patients fulfilled the criteria of the study as they were having regular follow up and they were on hydroxyurea treatment. These patients were interviewed and they were requested to answer specific questions included in a questionnaire. Their medical records and their laboratory data were reviewed. In order to obtain all the necessary details, the patients and their families were contacted by phone.

We compared flow cytometric immunophenotyping results obtained by using the lysed whole blood method of sample preparation with those obtained by using Ficoll-Hypaque-separated cells on 44 consecutive specimens from patients with various hematologic malignancies. When the samples were analyzed as a group, seven antigens (CD2, CD3, CD5, CD11c, CD20, CD22, and CD34) demonstrated significantly different percentages of positively staining cells. When the samples were grouped by disease, results for patients with acute lymphocytic leukemia were discordant for CD22 and HLA-DR and results for patients with hairy cell leukemia were discordant for CD34. Most of the differences, however, were not with antigens critical to the evaluation of the malignancy. Additionally, the most frequent reason for differences in the percentage of positive cells was due to isotype control-based placement of the quadrant markers and not an actual discrepancy in staining. However, analysis of the CD34 antigen yi...

BACKGROUND: The impact of ABO incompatibility on hematopoietic stem cell transplantation (HSCT) outcome is controversial. As ABH substances are expressed on tissues and secreted in body fluids, they could drive an immune response in minor ABOincompatible HSCT. The aim of the study was to investigate the prognostic role of the recipients' ABH secretor status. STUDY DESIGN AND METHODS: Patients who underwent minor ABO-incompatible HSCT were included. Secretor status was determined either serologically or by molecular genetics. RESULTS: Between March 1996 and June 2012, a total of 176 patients received minor ABO-incompatible HSCT and 150 (85%) were secretors. Incidence and severity of acute graft-versus-host disease (GVHD) and chronic GVHD did not differ between secretors and nonsecretors (cumulative incidences ± standard errors: acute GVHD on Day 100, 41 ± 11 and 46 ± 5%, p = 0.59; chronic GVHD at 2 years, 52 ± 13 and 56 ± 5%, p = 0.62, for secretors and nonsecretors, respectively). Additionally, nonrelapse mortality (NRM) and overall survival (OS) were similar in the two groups (2-year NRM, 27 ± 9 and 23 ± 3%, p = 0.45; 4-year OS, 64 ± 10 and 55 ± 4%, p = 0.28, for secretors and nonsecretors, respectively). CONCLUSION: The recipients' ABH secretor status in minor ABO-incompatible HSCT has no prognostic impact on major transplant outcomes.

Oral chronic GVHD (cGVHD) is a common, late complication of alloSCT that is associated with significant patient morbidity. The NIH Oral Mucosal Score (NIH OMS) was developed to assess oral cGVHD therapeutic response, but has not been fully validated. This study's purpose was to conduct a rigorous construct validity and internal consistency analysis of this score and its components (erythema, lichenoid, ulcers, mucoceles) using established measures of oral pain, oral function, oral-related quality-of-life, nutrition and laboratory parameters in 198 patients with cGVHD. The construct validity of the NIH OMS was supported: a moderate correlation was observed between NIH OMS and mouth pain (rho ¼ 0.43), while a weaker correlation was observed with low albumin (rho ¼ À 0.26). Total NIH OMS, erythema and lichenoid components were associated with malnutrition, oral pain and impaired oral QOL, while ulcers were only associated with oral pain. No associations were found between mucoceles and any indicator evaluated, including salivary function or xerostomia. Kappa determined between scale components was low overall (all p0.35), supporting a conclusion that each component measures a distinct manifestation of oral cGVHD. This study supports the use of the NIH OMS and its components (erythema, lichenoid and ulcerations) to measure clinician-reported severity of oral cGVHD.

A 12 year old, 38 kg, mix-breed, intact male dog presented with a 20 day history of clinical signs consistent with hyperviscosity syndrome secondary to multiple myeloma. The dog received three double filtration plasmapheresis treatments on day 0, 7 and 22 after presentation. A significant (p&lt;0.05) reduction in serum total protein, alpha-2 and gamma globulins was found following each treatment. These reductions were accompanied by a complete resolution, although temporary, of the clinical signs of hyperviscosity syndrome. The present study reported for the first time the use of double filtration plasmapheresis to reduce clinical signs of hyperviscosity syndrome in a dog with multiple myeloma.

ALS betegség tünetei, kezelési lehetőségei Az amiotrófiás laterálszklerózis (ALS) a központi idegrendszert érintő gyógyíthatatlan megbetegedés, mely során izomgyengeség/izomsorvadás lép fel az izmok mozgatásáért felelős idegsejtek károsodása miatt. Bár a betegség túlélése néhány évre tehető, az életminőség romlását lehet lassítani a megfelelő terápiával. A modern orvostudomány egyre többet tud az idegrendszeri betegségek hátterében álló folyamatokról. A legújabb kutatások rávilágítanak, hogy számos idegrendszeri betegség kialakulásában kulcsszerepet játszanak a gyulladásos folyamatok [1,2]. Jelenleg az amiotrófiás laterálszklerózis (ALS) kezelése tüneti kezelést jelent, a betegségre nincs még ismert gyógymód. A cél tehát a tünetek enyhítése, és az érintett személy életminőségének javítása.

Few data are available on compliance and safety of adjuvant chemotherapy when indicated in elderly breast cancer patients; CMF (cyclophosphamide, methotrexate, fluorouracil) can be reasonably considered the most widely accepted standard of treatment. We retrospectively reviewed compliance and safety of adjuvant CMF in patients older than 60. The treatment was indicated if patients had no severe comorbidity, a high-risk of recurrence, and were younger than 75. Toxicity was coded by NCI-CTC. Toxicity and compliance were compared between two age subgroups (&lt; 65, &gt; or = 65) by Fisher exact test and exact Wilcoxon rank-sum test. From March 1991 to March 2002, 180 patients were identified, 100 older than 60 and younger than 65, and 80 aged 65 or older. Febrile neutropenia was more frequent among older patients (p = 0.05). Leukopenia, neutropenia, nausea, cardiac toxicity and thrombophlebitis tended to be more frequent or severe among elderlies, while mucositis tended to be more evid...

We describe here the isolation and the full-length sequence of the coding region of the HLA new variant at the HLA-A locus officially named A*68020102. This variant shows an 11 base pairs deletion within the 5= UTR region. The exon sequence is identical to that of A*6802 and the commercially available anti-A68 typing sera react with the antigen coded by the allele A*68020102. This variant was originally identified in two unrelated Caucasoid families because of discrepant HLA typing results between serology, Sequence Specific Oligonucleo-tide Probe (SSOP), and SBT. In fact, the A68 assigned by serology was undetectable with the molecular techniques. This has occurred because the deletion present in A*68020102 prevents specific amplification of HLA-A locus by some commercially available typing kits.