Impact of stem cell source on allogeneic stem cell transplantation outcome in hematological malignancies

BACKGROUND/AIM: Peripheral blood (PB) is used more frequently as a source of stem cells (SCs) for allogeneic transplantation. However, the influence of cell source on the clinical outcome of SC transplantation is not yet well established. The aim of this study was to compare the results of PBSC transplantation (PBSCT) with bone marrow transplantation (BMT) on the basis of engraftment, frequency and severity of immediate (mucositis, acute Graft versus Host Disease--aGvHD) and delayed (chronic GvHD--cGvHD) complications, as well as transplant-related mortality (TRM), transfusion needs, relapses and overall survival (OS). METHODS: We analyzed 158 patients, women/men ratio 64/94 median age 29 (range 9-57), who underwent allogeneic SC transplantation between 1989 and 2009. All included patients had diseases as follows: acute myeloid leukemia (AML)--39, acute lymphoblastic leukemia (ALL) 47, chronic myeloid leukemia (CML)--32, myelodysplastic syndrome (MDS)--10, Hodgkin's lymphoma (HL)- 2, multiple myeloma (MM) 3, granulocytic sarcoma (GrSa) 3, severe aplastic anemia (sAA)--22. The patients underwent transplantations were divided into two groups: BMT group (74 patients) and PBSCT group (84 patients). Each recipient had HLA identical sibling donor. SCs from bone marrow were collected by multiple aspirations of iliac bone and from PB by one "Large Volume Leukapheresis" (after recombinant human granulocyte colony stimulating factor, rHuG-CSF) application (5-12 microg/kgbm, 5 days). Conditioning regimens were applied according to primary disease, GvHD prophylaxis consisted of combination of a cyclosporine A and methotrexate. Results. Engraftment, according to the count of polymorphonuclear and platelets, were significantly (p < 0.001) faster in the PBSCT vs BMT group. The needs for transfusion support were significantly (P < 0.01) higher in the BMT group. Those patients had more frequently oropharingeal mucositis grade 3/4 (33.3% vs 10.0%, p < 0.05). There were no significant differences in the incidence of aGvHD and cGvHD between the two groups. The patients who underwent PBSCT had more frequently extensive cGvHD in comparison with the BMT group (29.1% vs 11.29%, p < 0.05). SC source (SCS) had no significant influence on the TRM (21.62% vs 23.8%, p = 0.64) and the incidence of relapses (21.6% vs 29.7%, p = 0.32). Finally, the patients treated by BMT hd a significantly better OS (logrank 2.33, p < 0.05). Conclusion. SCs harvesting from PB resulted in improved cell yield, faster engraftment, as well as in a decrease of immediate transplantation related complications with a reduced treatment cost. Allogeneic PBSCT were associated with more frequent extensive cGvHD, while the influence of SCS in TRM and relapses was not observed. Finally, the long-term OS was better in the patients treated by BMT. To verify impact of SC source on transplantation (PBSCT vs BMT) overall efficacy, more larger randomized clinical studies are needed.     

The elution and breakdown behavior of constituents from various light-cured composites

Objectives

Constituents of dental composites can be released from dental fillings after polymerization. The aim of this study was to examine the time-related elution and breakdown of separable constituents of polymerized composites using deuterated solvents.

Method

Elution and breakdown of constituents were investigated with deuterated solvents methanol and water by gas chromatography/mass spectrometry of following composites for 180 days: Filtek™ Supreme XT, Filtek™ Supreme XT Flow, Tetric Ceram^®, Tetric Flow^®, Grandio^®, Grandio^® Flow.

Results

Within 180 days no compounds were formed as the products of breakdown. 19 compounds were identified as elution products: Bis-EMA, TEGDMA, DDDMA, EGDMA, MAA, BPA, CQ, HQME, DMABEE, CSA, BL, TEG, BHT, TINP, TPP, TPSB, DEDHTP, DCHP, ß-PHEA.The highest concentration of Bis-EMA was measured for Tetric Flow^® in deuterated methanol on day 90 at 36.993 mmol/l and in deuterated water also on day 90 at 0.031 mmol/l.The highest TEGDMA concentrations were measured for Grandio^® Flow in deuterated methanol on day 60 at 1.322 mmol/l and for Filtek™ Supreme XT Flow in deuterated water on day 3 at 0.689 mmol/l. The highest BPA concentration was measured for Tetric Flow^® in deuterated methanol on day 90 at 1.469 mmol/l. The highest BPA concentration was measured for Grandio^® in deuterated water on day 180 at 0.007 mmol/l.Significance Examination of time-related elution indicates that various elution products (e.g. Bis-EMA, BPA) were only released in small quantities during the first 90 days, but in high quantities between day 90 and day 180.     

Isolation,biochemical characterization and anti-bacterial activity of BPIFA2 protein

Objective

Human BPIFA2 (parotid secretory protein) is a ubiquitous soluble salivary protein, which belongs to the PLUNC family of proteins. Having sequence similarity to bactericidal/permeability-increasing protein and lipopolysaccharide-binding protein, PLUNC proteins are probably involved in local antibacterial response at mucosal sites, such as oral cavity. The aim of the study was to isolate and characterize human BPIFA2.

Design

In this paper, we report one-step affinity chromatography method for BPIFA2 purification from whole human saliva. The isolated BPIFA2 was identified by trypsin mass fingerprinting and characterized by electrophoretic methods. Antibacterial activity of BPIFA2 against model microorganism Pseudomonas aeruginosa was shown in minimum inhibitory concentration and time kill study assays.

Results

The protein showed microheterogeneity, both in molecular weight and pI value. BPIFA2 inhibited the growth of P. aeruginosa in microgram concentration range determined by minimum inhibitory concentration assay. In the time kill study, 32 μg/mL BPIFA2 showed clear bactericidal activity and did not cause any aggregation of bacteria.

Conclusion

Affinity chromatography is well suited for isolation of functional BPIFA2 with a potent bactericidal activity against P. aeruginosa.     

The role of calcification for staging cystic echinococcosis (CE)

The prevalence of calcified cysts and the significance of calcification as a sign of cyst inactivity in cystic echinococcosis (CE) was evaluated. Seventy-eight patients (36 females, 42 males, mean age 40.8 +/- 16.9 years) with CE, having a total of 137 abdominal cysts (116 hepatic, three splenic, one renal and 17 peritoneal cysts), were diagnosed and followed-up by ultrasound during and after albendazole treatment or as part of the watch-and-wait approach recording changes in the cyst wall and content. In 48 patients with 94 cysts, computed tomography (CT) imaging was additionally available and was correlated with ultrasound findings. Cyst wall calcification was classified into (1) "sprinkled", (2) "eggshell-like", and (3) "circular". Calcification of the cyst wall and/or cyst content was detected in 67 echinococcal cysts (48.9% of all cysts) in 39 patients (15 females, 24 males, mean age 40.8 +/- 14.8 years). Of the total of 67 calcified cysts, only 23 were compatible with WHO type CE5, 18 with WHO type CE4. Judged by cyst content, the remaining 26 were of WHO type CE1, CE2 and CE3 (n = 1, n = 8, and n = 17, respectively). During a mean period of 34.3 months (+/- 21.3 months) the majority of cysts (n = 32) did not exhibit any change in cyst content and wall properties. Fourteen cysts showed signs of progressive involution, five cysts (all of WHO type CE3) of renewed activity defined by recurring fluid collection. In 16 cysts, no follow-up was available due to surgery or drop out. Calcification of the cyst is not restricted to the inactive WHO cyst types CE4 and CE5, but occurs in all stages and in up to 50% of cysts. The completeness and, most importantly, the stability of consolidation of cyst content over time predicts cyst inactivity more reliably.     

Interventions for postoperative pain in children: An overview of systematic reviews

The aim of this study was to conduct an overview of systematic reviews that summarizes the results about efficacy and safety from randomized controlled trials involving the various strategies used for postoperative pain management in children. We searched the Cochrane Database of Systematic Reviews, CINAHL, Database of Reviews of Effect, Embase, MEDLINE, and PsycINFO from the earliest date to January 24, 2016. This overview included 45 systematic reviews that evaluated interventions for postoperative pain in children. Out of 45 systematic reviews that investigated various interventions for postoperative pain in children, 19 systematic reviews (42%) presented conclusive evidence of efficacy. Positive conclusive evidence was reported in 18 systematic reviews (40%) for the efficacy of diclofenac, ketamine, caudal analgesia, dexmedetomidine, music therapy, corticosteroid, epidural analgesia, paracetamol, and/or nonsteroidal anti‐inflammatory drugs and transversus abdominis plane block. Only one systematic review reported conclusive evidence of equal efficacy that involved a comparison of dexmedetomidine vs morphine and fentanyl. Safety of interventions was reported as conclusive in 14 systematic reviews (31%), with positive conclusive evidence for dexmedetomidine, corticosteroid, epidural analgesia, transversus abdominis plane block, and clonidine. Seven systematic reviews reported equal conclusive safety for epidural infusion, diclofenac intravenous vs ketamine added to opioid analgesia, bupivacaine, ketamine, paracetamol, and dexmedetomidine vs intravenous infusions of various opioid analgesics, oral suspension and suppository of diclofenac, only opioid, normal saline, no treatment, placebo, and midazolam. Negative conclusive statement for safety was reported in one systematic review for caudal analgesia vs noncaudal regional analgesia. More than half of systematic reviews included in this overview were rated as having medium methodological quality. Of 45 included systematic reviews, 10 were Cochrane reviews and they had higher methodological quality than non‐Cochrane reviews. As evidence concerning efficacy and safety is inconclusive for most of the analyzed interventions, our review points out the need for more rigorous trials concerning pain management in children.     

Technetium-99m-dimercaptosuccinic acid renal scintigraphy in children with urinary tract infections

The aim of this study was to determine the incidence of abnormal dimercaptosuccinic acid-Tc-99m ((99m)Tc-DMSA) renal scintigraphy findings in children with culture proved urinary tract infection (UTI) with or without vesicoureteral reflux (VUR). (99m)Tc-DMSA renal scintigraphy was performed in 343 children with culture documented UTI (247 girls and 96 boys) aged from three months to 14 years (middle age of 4.82 years). The children studied were all those submitted for renal scintiscan to the Institute of Nuclear Medicine, Military Medical Academy, Belgrade during a five-year period (2000-2004). Micturating cystoureterography (MCU) performed in all patients before (99m)Tc-DMSA scan, revealed VUR in 213 children, while in 130 children VUR was not detected by MCU. In 15 of the 213 children the grade of VUR was I, in 88 was II, in 57 was III, in 33 was IV and 20 children had grade V of VUR. Findings of (99m)Tc-DMSA renal scintigraphy were classified as: normal, equivocal and abnormal. Statistical analysis was performed using c(2)test. In all patients abnormal findings were detected in 38% (131/343), normal in 51% (174/343) and equivocal findings in 11% (38/343). In children with UTI and VUR the incidence of abnormal findings was 53% (112/213), of normal 37% (80/213) and of equivocal findings 10% (21/213). In children with UTI without VUR the incidence of abnormal findings was 15% (19/130), of normal findings 72% (94/130), and of equivocal findings 13% (17/130). The incidence of abnormal findings was significantly higher in children with UTI and VUR than in those with UTI without VUR (P<0.001). In children with VUR grades I, II, III, IV and V abnormal findings were 33%, 32%, 60%, 79% and 95% respectively. The incidence of abnormal findings was higher in children with VUR grades IV and V, than in grade I and II (P<0.001). Our results suggest that (99m)Tc-DMSA renal scintigraphy in children can discriminate between grade I-II and IV-V of VUR and also that in children with UTI and VUR abnormal findings in the scintiscan were more than three times higher than in children with UTI alone.     

Patients with Acute Lacunar Infarction Have Benefit from Intravenous Thrombolysis

Introduction: Usefulness of intravenous thrombolysis in patients with acute lacunar cerebral infarction is questionable. The aim of this study was to evaluate the efficacy and safety of intravenous thrombolysis in patients with lacunar infarction in comparison with patients with nonlacunar infarction as well as with patients with lacunar infarction who were not treated with intravenous thrombolysis. Materials and methods: In the first part of the study, among patients with acute ischemic stroke treated with intravenous thrombolysis, characteristics and outcomes of 46 patients with lacunar and 221 patients with nonlacunar infarction were compared. In the second part, 46 patients with lacunar infarction treated with intravenous thrombolysis were compared with 45 lacunar infarction patients who were not treated with intravenous thrombolysis. Results: Patients with lacunar infarction had a lower National Institutes of Health Stroke Scale score (9.2 versus 13.9, P < .001), a greater Alberta Stroke Program Early computed tomography (CT) score (9.7 versus 9.2, P?=?.002), a lower prevalence of atrial fibrillation (6.5% versus 41.2%, P < .001), and significantly more frequently an excellent outcome after 3 months (76.1% versus 36.2%, P < .001) compared with patients with nonlacunar infarction. Among patients with lacunar infarction, an excellent outcome at discharge was significantly more frequent in the intravenous thrombolysis group (41.3% versus 15.6%, P?=?.01), and the length of hospitalization was significantly shorter (9.5 days versus 14.3 days, P?=?.002). There was no hemorrhagic transformation among patients with lacunar infarction treated with intravenous thrombolysis. Conclusion: Intravenous thrombolysis has proven to be effective and safe in patients with lacunar infarction and should always be applied if there are no absolute contraindications.     

Influence of manufacturing procedure on stability of Unguentum contra perniones preparations

BACKGROUND: Application of various technological procedures for the manufacture of officinal preparation ointment against chilblains (Unguentum contra perniones) produce essential variations in the quality and stability of the final product. Changing the sequence of admixing active substances into the ointment base indicated the presence of incompatibility between the active substances, as well as between the active substances and the ointment base components. The aim was to examine the influence of various technological manufacturing procedures on quality and stability of the preparation. METHODS: Changes in the samples of ointments and aqueous solutions of active substances were analysed microscopically. RESULTS: Microscopic analysis of hydrosoluble active substance solutions demonstrated destruction of ichthammol, induced by an acidic medium due to the dissolution of tannin and resorcinol, which is well known from the literature. It also demonstrated the destruction of tannin and resorcinol in aqueous solution, which had not been described in the literature. Application of the prescribed procedure for the manufacturing of ointment against chilblains, conceals the incompatibility reactions due to a slow dissolution of the tannin suspended in the officinal ointment base Unguentum cera lanae. Admixture of an ready-made aqueous solution of tannin caused an instant contact between ichthammol and the acidic medium, which caused the destruction or the complete absence of the formation of emulsion droplets. The problem of incompatibility reactions between lanolin alcohols in the ointment base and ichthammol and resorcinol, as well as the reaction between Peruvian balsam and sulfur from the ichthammol sulfate ion was observed. Numerous incompatibility reactions of ointment against chilblains, components indicated that it was necessary to introduce alterations in both the qualitative and quantitative composition of the preparation. CONCLUSION: Excipient preparation procedure, as well as the technological procedure for incorporation of active ingredients can cause the incompatibilities and therefore the formulation stability problems.     

Regulation of membrane histamine H1-Receptor binding sites by guanine nucleotides,mono- and divalent cations

Agonist interaction with histamine H₁-receptor in [³H] mepyramine bovine aortic membranes labeled with [³H] mepyramine is selectively regulated by cations and guanine nucleotides. GTP and his nonhydrolisable analog Gpp(NH)p' markedly decrease histamine affinity for [³H] mepyramine binding sites. The effect of GTP is reversed in the presence of divalent cation, magnesium. Calcium and sodium ions have little effect on histamine binding whereas magnesium ions decrease the affinity of histamine for the radioantagonist binding sites about tenfold.GTP has little effect on [³H] mepyramine binding and the interaction of H₁-antagonist triprolidine with histamine H₁-receptors. The above results indicate that the effect of guanine nucleotides, mono and divalent cations involves the effect on membrane signal transducing mechanism probably GTP-binding protein(s) cation regulatory site(s) rather than receptor binding site directly.