Acute kidney injury (AKI) is a major complication in children with hepatic failure which leads to increased morbidity and mortality. The aim of this study was to provide paediatric data on the prevalence of dialysis-dependent AKI (dAKI), the feasibility and efficacy of dialysis methods and outcome.
BACKGROUND:Posttransplantation lymphoproliferative disorders (PTLD) present a major cause of mortality and morbidity after solid organ transplantation. The purpose of this study was to identify the factors associated with the development of early- and late-onset PTLD in pediatric solid organ transplant recipients. METHODS:We examined the medical history, laboratory parameters, and pathology of 127 children with PTLD who were registered in the German multicenter pediatric PTLD registry. Data were collected retrospectively from 1991 to 2003 and prospectively from 2004 onward. We compared early (<1 year) and late (>1 year) PTLD using survival analysis. RESULTS:The median time to PTLD was 3.00 (95% confidence interval, 2.12-3.26) years. Forty-two patients developed PTLD within the first year after transplantation (early PTLD) and 85 patients developed PTLD after 1 year (late PTLD). Early PTLD development was associated with younger age (P=0.0016), extranodal disease (P=0.019), graft organ involvement (P=0.0065), and immunosuppressive regimens including tacrolimus (P=0.001) or mycophenolate (P=0.0025). Most early PTLD patients experienced graft rejection before PTLD diagnosis (P=0.0081). Early PTLD was often of B-cell lymphoma histology (P=0.024) and tended to be Epstein-Barr virus positive (P=0.052). In contrast, Burkitt's lymphoma (P=0.0047) and Hodgkin's disease (P=0.016) were only observed in late PTLDs, which are more likely to present with nodal disease (P=0.019). Overall survival and event-free survival were not significantly different between early and late PTLD. CONCLUSION:Early and late childhood PTLD have distinct characteristics. Whereas early PTLD appears mainly as an Epstein-Barr virus-driven disease especially favored by insufficient immunosurveillance, late PTLD often resembles tumors with distinct pathogenetic alterations and nodal appearance.
We report the first detection of chloronium, H_2Cl^+, in the interstellar medium, using the HIFI instrument aboard the Herschel Space Observatory. The 2_12-1_01 lines of ortho-H_2^35Cl^+ and ortho-H_2^37Cl^+ are detected in absorption towards NGC 6334I, and the 1_11-0_00 transition of para-H_2^35Cl^+ is detected in absorption towards NGC 6334I and Sgr B2(S). The H_2Cl^+ column densities are compared to those of the chemically-related species HCl. The derived HCl/H_2Cl^+ column density ratios, ∼1–10, are within the range predicted by models of diffuse and dense Photon Dominated Regions (PDRs). However, the observed H_2Cl^+ column densities, in excess of 10^13 cm^-2, are significantly higher than the model predictions. Our observations demonstrate the outstanding spectroscopic capabilities of HIFI for detecting new interstellar molecules and providing key constraints for astrochemical models.
Purpose To identify prognostic factors of survival in pediatric post-transplantation lymphoproliferative disorder (PTLD) after solid organ transplantation. Patients and Methods A multicenter, retrospective case analysis of 55 pediatric solid organ graft recipients (kidney, liver, heart/lung) developing PTLD were reported to the German Pediatric-PTLD registry. Patient charts were analyzed for tumor characteristics (histology, immunophenotypes, cytogenetics, Epstein-Barr virus [EBV] detection), stage, treatment, and outcome. Probability of overall and event-free survival was analyzed in defined subgroups using univariate and Cox regression analyses. Results PTLD was diagnosed at a median time of 29 months after organ transplantation, with a significantly shorter lag time in liver (0.83 years) versus heart or renal graft recipients (3.33 and 3.10 years, respectively; P = .001). The 5-year overall and event-free survival was 68% and 59%, respectively, with 59% of patients surviving 10 years. Stage IV disease with bone marrow and/or CNS involvement was associated independently with poor survival (P = .0005). No differences in outcome were observed between early- and late-onset PTLD, monomorphic or polymorphic PTLD, and EBV-positive or EBV-negative PTLD, respectively. Patients with Burkitt or Burkitt-like PTLD and c-myc translocations had short survival (< 1 year). Conclusion Stage IV disease is an independent risk factor for poor survival in pediatric PTLD patients. Prospective multicenter trials are needed to delineate additional risk factors and to assess treatment approaches for pediatric PTLD.
Hydrogen sulfide is produced endogenously by a variety of enzymes involved in cysteine metabolism.Clinical data indicate that endogenous levels of hydrogen sulfide are diminished in various forms of cardiovascular diseases.The aim of the current study was to investigate the effects of hydrogen sulfide supplementation on cardiac function during reperfusion in a clinically relevant experimental model of cardiopulmonary bypass.Twelve anesthetized dogs underwent hypothermic cardiopulmonary bypass.After 60 minutes of hypothermic cardiac arrest, reperfusion was started after application of either saline vehicle (control, n = 6), or the sodium sulfide infusion (1 mg/kg/hour, n = 6).Biventricular hemodynamic variables were measured by combined pressure-volume-conductance catheters.Coronary and pulmonary blood flow, vasodilator responses to acetylcholine and sodiumnitroprusside and pulmonary function were also determined.Administration of sodium sulfide led to a significantly better recovery of left and right ventricular systolic function (P < 0.05) after 60 minutes of reperfusion.Coronary blood flow was also significantly higher in the sodium sulfide-treated group (P < 0.05).Sodium sulfide treatment improved coronary blood flow, and preserved the acetylcholine-induced increases in coronary and pulmonary blood (P < 0.05).Myocardial ATP levels were markedly improved in the sulfide-treated group.Thus, supplementation of sulfide improves the recovery of myocardial and endothelial function and energetic status after hypothermic cardiac arrest during cardiopulmonary bypass.These beneficial effects occurred without any detectable adverse hemodynamic or cardiovascular effects of sulfide at the dose used in the current study.
Posttransplant lymphoproliferative disorders (PTLD) have been recognized as severe side effects of immunosuppressive therapy after organ transplantation. However, no standard diagnostic and therapeutic approaches have been defined. Furthermore, few interdisciplinary perspectives comparing patients with heart/liver/kidney transplants are available. Here, we present results of a multicenter, retrospective analysis of pediatric patients treated for PTLD in Germany and Switzerland from 1990 to 2003. Patients were recruited by surveys through the working groups of pediatric renal, liver, and heart/lung transplantation as well as from the registry of pediatric Non-Hodgkin's lymphomas (NHL-BFM). Inclusion criteria consisted of a history of solid organ transplantation, biopsy-proven diagnosis of PTLD, and age at onset of PTLD 18 years of less. Patient charts were analyzed for clinical course from transplant to onset of PTLD, virus serology, treatment regimen, and outcome. A total of 53 patients from 19 centers could be included, among them 25 renal graft recipients, 14 heart-, 11 liver-, and 1 lung transplant recipients as well as 2 patients after combined heart/lung transplantation. PTLD was diagnosed at a median time of 34 months [range 2 – 119 months] post organ transplantation. Histological evaluation based on the WHO classification showed 2 early lesion PTLD, 8 polymorphic PTLD, 26 high-grade B-cell lymphomas, 12 Burkitt-like lymphomas, 3 cases of Hodgkin's disease and 2 T-cell lymphomas. Cytogenetic analysis revealed translocations involving chromosome 8 in five patients with Burkitt-like lymphomas. EBV gene products were detected in 31 tumors by in situ hybridization or immunohistochemistry, while 13 tumors were EBV negative (no data available on 9 tumors). EBV serology was negative in 55% of patients at the time of organ transplantation. However, in 29 patients EBV primary infection/reactivation was documented after organ transplantation (median time to infection/reactivation 5.9 months). In all patients immunosuppressive therapy was reduced. Treatment and follow up data were available in 51 patients: six patients remained in complete remission without additional treatment, in one patient autologous EBV-specific T-cells were infused. 41 patients received monoclonal antibodies (anti-CD20; n=7), chemotherapy (n=28), or a combination thereof (n=5). Fifteen of 51 patients died of progressing PTLD (n=7; among them 3 patients in which treatment was refused), treatment-related mortality (n=7), or fatal graft failure (n=2). Mortality was higher in patients with Burkitt-like lymphomas (7 of 12 patients) compared to all other entities (8 of 39 patients; p=0.026). Patients with stage IV disease had an inferior outcome compared to patients with stage I-III disease (mortality 6 of 7 vs. 9 of 44 patients, p=0.002). Thus, pediatric PTLD is a heterogeneous disease often associated with fatal outcome. The PED-PTLD study group has initiated a prospective multicenter trial of standardized diagnosis and treatment of PTLD after solid organ transplantation in children.
The following report will discuss in detail all lethal invasive fungal infections (IFI) that occurred in a group of 2021 children with acute lymphoblasic leukaemia (ALL). The German ALL-Berlin-Frankfurt-Muenster (BFM) study group is one of the largest cooperation for the treatment of childhood ALL. Between 1995 and 2000, 2021 children with ALL received chemotherapy according to the German BFM 95 protocols (ALL-BFM 95). This population was retrospectively screened, whether a lethal fungal infection occurred: totally, in this group, 43 of 2021 (2.1%) children died because of infections. Nine of 43 (21%) patients died in the context of an IFI: six fatal Aspergillus infections and three fatal yeast infections were reported. The following report will focus on the nine children with ALL who died from IFI. The underlying risk factors (RF) included neutropenia (seven of nine patients) and steroid medication (nine of nine patients). Seven of nine children had additional medical complications (e.g. liver failure, haemolytic uraemic syndrome and acute renal failure). In six of nine children the fungal infection was progressive despite intravenous antimycotic therapy, three patients received no antifungal therapy, as IFI was not considered. The progression of IFI despite antimycotic therapy illustrates the inherent problems of diagnosis and the need for innovative therapeutic modalities. The high percentage (21%) of death from IFI among lethal infections in paediatric ALL patients illustrates the relevance of fungi in this group of patients. On the contrary, the total number of IFI in paediatric ALL patients remains to be determined, as only lethal infections were included in this report.
EDITOR: We present the cases of two children suffering from complex regional pain syndrome, Type 1, who were treated successfully with intravenous (i.v.) regional blocks of guanethidine and prilocaine, in combination with physiotherapy, once per week for 6 weeks. The treatment produced pain relief and normalization of the peripheral sensory dysfunction in both children. Complex regional pain syndrome, Types 1 and 2, is a pathological condition still misdiagnosed and poorly treated. It usually develops after an initiating traumatic event and is characterized by a triad of autonomic, motor and sensory symptoms. The prominent features are constant burning pain, hyperalgesia, hyperaesthesia and allodynia, not confined to the distribution of a single peripheral nerve. Oedema, trophic changes of the skin, an abnormal regulation of blood flow and sudomotor activity in the affected region may be present at different times [1]. The lack of response of the condition to conventional analgesics and the clinical manifestations of the signs and symptoms related to sympathetic activity led to the use of i.v. regional guanethidine blocks [2]. The treatment gives a functional sympathetic block by first releasing norepinephrine and then preventing its reuptake at the norepinephric postsynaptic axon terminals. It has been suggested that repetitive guanethidine blocks produce a permanent lesion of the peripheral sympathetic neurons, possibly due to an autoimmune-mediated mechanism [3]. Although initial clinical reports supported the usefulness of i.v. regional guanethidine blocks [4,5], controlled trials failed to confirm the results [6]. However, in the majority of these trials, only one block was performed, while serial blocks may be required to achieve effective results. Physiotherapy is difficult to perform in patients affected by complex regional pain syndrome owing to their unwillingness to have the limb touched, since this intensifies the severity of the pain. However, during i.v. regional blocks, physical treatment become feasible. The first patient was a 10-yr-old female (weight 43 kg) who had fractured her left coracoid bone falling off a bicycle. A few weeks after the fracture had healed, she started to complain of constant non-dermatomal pain in the entire left arm. Neurological examination of the upper limbs was normal, except for patchy areas of hyperalgesia, and static and dynamic allodynia in the left arm. Additionally, she was very limited in any passive or active movements. The severity of pain was rated by the patient as 8 on a visual analogue scale (VAS; 0-10 cm). A course of i.v. regional blocks of guanethidine and prilocaine, combined with physiotherapy at the time of each block, was planned. The patient was admitted to the Day Case Unit and premedicated with an oral solution of midazolam 20 mg, 30 min before the start of the procedure. After reducing the amount of venous blood in the symptomatic arm, by arm elevation and external compression with an Esmarch bandage, a tourniquet was placed on the left forearm and inflated to 250 mmHg. A solution of prilocaine hydrochloride 0.5% 10 mL, sodium chloride 0.9% 10 mL and guanethidine monosulphate 10 mg was slowly injected into a superficial vein of the hand. The block lasted 20 min, during which time physiotherapy of the left arm was performed, including active assisted movement and neural mobilization for the ulnar, radial and median nerves. Blood pressure, heart rate and arterial oxygen saturation were constantly monitored during the procedure and for a further 30 min in the recovery room after the tourniquet had been deflated. The patient was discharged 3 h later. The combined treatment was repeated weekly for the following 6 weeks. Quantitative sensory tests were performed on the affected and contralateral hand before and after the 6 weeks of treatment. Sensory tests were carried out with a Senselab Thermotest® (Somedic AB, Sweden). Skin temperature on both arms was also measured. Room temperature was kept stable to between 20 and 22°C. After the first block and physiotherapy, the child gained partial movement of the arm and the pain at rest improved (VAS = 6). During treatment, the patient gained further ranges of movement; the pain at rest and on movement gradually reduced in severity (Fig. 1). One month after the combined treatment, the child could use the left arm and play basketball in the physiotherapy gymnasium. Before initiation of the combined treatment, the sensory tests showed a high asymmetry between the painful and the contralateral site in the feeling of warmth threshold. This difference disappeared after 6 weeks treatment (Fig. 2). Similarly, the discrepancy in skin temperature between the painful and contralateral arm (33.6 and 31.1°C respectively) disappeared at the end of the treatment (painful arm 31.6°C, contralateral arm 31.1°C).Figure 1: Pain score before, during and after the course of i.v. regional blocks with guanethidine and prilocaine combined with physiotherapy in the two children measured with a VAS (0-10 cm). □: first patient; ▪: Second patient.Figure 2: Warm and cold mean thresholds before and after the course of i.v. regional blocks with guanethidine and prilocaine combined with physiotherapy. The sensory tests were carried out with a Senselab Thermotest®. ▪: Affected limb; □: contralateral limb.The second patient was a 13-yr-old female (weight 48 kg) who had strained her right forearm while playing volleyball. Soon afterwards, she started to complain of constant pain in the arm, being more severe in the hand, with patchy distribution. A sensory examination of the limb showed areas of static and dynamic allodynia. Additionally, she showed very limited active movement in the right arm. A course of i.v. regional blocks of guanethidine and prilocaine, combined with physiotherapy at the time of each block, was planned. The severity of pain was rated as VAS = 7 by the patient. The child was admitted to the Day Case Unit and received midazolam orally (20 mg), followed 30 min later by the i.v. regional block of guanethidine and prilocaine (at the same doses as in the first patient), combined with physiotherapy. The treatment was repeated once weekly for 6 weeks. Quantitative sensory tests were performed on the affected and contralateral hand before and after the 6 weeks of treatment. Both pain at rest and on movement decreased gradually (Fig. 1) and the patient gained movement, being able to open the right hand completely. The sensory tests showed a normalization in the feeling of cold threshold between the painful and contralateral site after the 6 weeks of combined treatment (Fig. 3).Figure 3: Warm and cold mean thresholds before and after the course of i.v. regional blocks with guanethidine and prilocaine combined with physiotherapy. The sensory tests were carried out with a Senselab Thermotest®. ▪: Affected limb; □: contralateral limb.Complex regional pain syndrome, Type 1, is a pathological disorder characterized by pain, sensory abnormalities, possible abnormal blood flow, sweating and trophic changes. Its pathophysiology remains unclear, but the initial event (usually trauma) apparently sensitizes the small diameter-C fibres, generating an abnormal reaction to mechanical, thermal and chemical stimulation. Although used in the management of complex regional pain syndrome, the effectiveness of i.v. regional guanethidine blocks is not supported by the outcome of randomized-controlled studies [6]. However, as previously mentioned, most of these studies did not compare the effects of repetitive blocks. We have shown that a course of i.v. regional blocks of guanethidine and prilocaine, combined with physiotherapy, was a successful treatment for complex regional pain syndrome, Type 1, in two children. However, we could not establish to what extent the positive outcome was due to the combination of physiotherapy with the regional block. This fact will require a prospective controlled study with patients assigned to different groups (prilocaine alone versus guanethidine + prilocaine versus guanethidine + prilocaine + physiotherapy). Acknowledgement Sensory testing was performed at the sensory physiology laboratory at Guy's Hospital, London. The authors thank Derek Light for his kind technical support. P. P. di Vadi S. Brill T. Jack Department of Anaesthetics and Pain Management; University Hospital Lewisham; London, UK C. Brown T. Edwards Department of Physiotherapy; University Hospital Lewisham; London, UK
This paper describes the synthesis and pharmacology of a novel series of benzofurans which are antagonists of angiotensin II. One of these, the bromobenzofuran 11b, is a potent (apparent pK(B) = 9.8) and specific antagonist angiotensin II which, after oral administration (10mg/Kg), causes marked and long-lasting (> 24h) falls in blood pressure in renal hypertensive rats.
A study was undertaken to establish conditions and relationships for the production of lipases during hydrocarbon fermentation. A culture of Candida lipolytica was isolated by a kerosene enrichment technique from oil-soaked soil and this microbe was used to study the production of lipase on a kerosene-mineral salts medium. The optimum pH, medium, and temperature for lipase synthesis were established and the properties of the isolated enzyme in terms of its activity and lipid specificity were studied.
1H and 13C NMR spectroscopy and molecular weight studies of a series of hepta-2,6-dienylpalladium(II) carboxylate complexes have demonstrated the existence in solution of an equilibrium between trihapto-dimeric complexes with bridging carboxylates and pentahapto-monomeric complexes with terminal carboxylate ligands. At constant temperature, the position of equilibrium is a function of carboxylate ligand, substituents at position 6 on the heptadienyl ligand, and the solvent. The dimer monomer rearrangement is fast on the 1H NMR time scale. These observations together with previously reported data concerning the reactivity of allyl and carboxylate ligands coordinated to palladium(II) are considered as model systems for the π-allylnickel carboxylate catalysed cis-1,4-polymerization of 1,3-butadiene. A mechanism is proposed that provides a rationalization for the majority of the factors affecting the initial rate of the nickel complex catalysed polymerization of 1,3-butadiene as reported by Dawans.
The structure of µ-diphenylacetylene-bis-(π-pentaphenylcyclopentadienyl)dipalladium(I), which is readily and quantitatively synthesised by the reaction of diphenylacetylene with palladium acetate in methanol, has been determined by X-ray crystallography.
Light optical techniques, including high and low spatial frequency filtering and superposition of images, have been applied to dark field electron micrographs of uranium, platinum, iodine, and palladium atoms in small model molecules, and osmium atoms bound to DNA. Contrast in the images is increased and the signal to noise ratio enhanced. The improvement for a series of images of one small molecule is so great that substructures of the molecule are revealed, substructures consisting of groups of atoms as light as arsenic and carbon that are completely masked by noise in the untreated images. These results corroborate that images of single atoms are seen in the original micrographs.
Solution isomers of dimeric allylic palladium 1,3-diphenyltriazene and 1-methyl-3-phenyltriazene complexes are identified by low temperature NMR spectroscopy. The data obtained indicate that the bridging triazenido ligands in these complexes are nonlabile and relatively inert to ligand substitution.
Chemischer Informationsdienst. Organische ChemieVolume 2, Issue 19 Preparative Organic Chemistry ChemInform Abstract: KONFORMATIONS-STUDIEN AN PI-ALLYL-PALLADIUM-KOMPLEXEN DES 1,3-DIPHENYLTRIAZENS UND 1-METHYL-3-PHENYLTRIAZENS T. JACK, T. JACKSearch for more papers by this authorJ. POWELL, J. POWELLSearch for more papers by this author T. JACK, T. JACKSearch for more papers by this authorJ. POWELL, J. POWELLSearch for more papers by this author First published: May 11, 1971 https://doi.org/10.1002/chin.197119136Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume2, Issue19May 11, 1971 RelatedInformation