Добірка наукової літератури з теми "Thiosulfate d'or et de sodium"

SituationA 30 week gestation male weighing 1.66kg presented with metabolic acidosis and high lactate and subsequently developed heart failure and hypertension. He initially started enteral feeds but these were later not tolerated and TPN commenced. On day 8 calcification of the aorta was identified on echocardiogram. CT scans showed extensive arterial calcification including the thoracic and abdominal aorta, subclavian and common carotid arteries, coeliac axis, SMA, renal arteries and iliac vessels. Generalised arterial calcification of infancy (GACI) due to ENPP1 mutation was suspected.BackgroundGACI, a rare autosomal recessive condition can be caused by ENPP1 mutation leading to low levels of inorganic pyrophosphate (PPi), a negative regulator of calcification. GACI has a high mortality rate, up to 55% at 6 months. Mortality has been shown to improve in those who survive the first few months of life.1TreatmentIntravenous sodium thiosulfate, licensed for cyanide poisoning and used off-label for calciphylaxis in adults,2 was commenced to try and reduce existing calcification. Dosing that has been known to be used in three other babies from two different centres,3 was used - 12.5g/m2 over 30minutes on alternate days for 2 weeks followed by 12.5g/m2 five days a week. This is in the same scale as adult calciphylaxis dosing and up to 400mg/kg can be used in paediatric cyanide poisoning. Bisphosphonates were commenced to prevent further calcification. Etidronate, a non-nitrogen containing bisphosphonate, was preferred due to its closer structural similarity to PPi than second generation bisphosphonates. Etidronate has been discontinued in the UK so was not initially available and a dose of pamidronate was given. A Canadian import of etidronate was sourced and commenced a week later. Due to SMA and coeliac axis calcification there were concerns regarding bowel perfusion and he was TPN fed except for 20ml/kg/day EBM. Etidronate 20mg/kg/day was commenced in three divided doses to improve gastrointestinal tolerance.OutcomeInitially his heart failure stabilised and hypertension managed with carvedilol. By day 35 full enteral feeds were reached and he was breathing unassisted in air. CT after one month’s treatment showed no worsening of vascular calcification, though unfortunately calcification did not appear to have improved. At 7 weeks he became tachypnoeic due to worsening heart failure and required respiratory support. Despite ongoing medical therapies he passed away at 8 weeks of age.Challenges and lessons learntDue to the rarity of the condition information on treatment options, dosing and monitoring are limited and the need to use an imported product lead to a short delay in treatment. Etidronate is only available in tablet form but Didronel brand can be crushed and suspended in water,4 Information about the suspension’s uniformity is unavailable but due to a lack of alternatives this was the option taken. A two hour break either side of etidronate while recommended, was compromised to ninety minutes as he required three hourly feeds. Combination treatment was used to try to reduce the calcification; however the extent of calcification had already caused significant cardiac compromise which ultimately led to his demise.ReferencesFerreira C, Ziegler S, Gahl WA. Generalized Arterial Calcification of Infancy. 2014 In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews [Online]. Seattle (WA): University of Washington, Seattle; 1993–2018. Available from: https://www.ncbi.nlm.nih.gov/books/NBK253403Nigwekar SU, Brunelli SM, Meade D, et al. Sodium thiosulfate therapy for calcific uremic arteriolopathy. Clin J Am Soc Nephrol, 2013;8:1162–70.Personal communication: Medicines Information, Alder Hey Children’s NHS Foundation Trust. Email sent to: Leeds Medicines Advisory Service. 28th June 2018.White R, Bradnam V. Handbook of Drug Administration via Enteral Feeding Tubes, Third ed. Cornwall: Pharmaceutical Press; 2015. www.medicinescomplete.com (accessed August 2018).

BackgroundCalcific tendinitis of the rotator cuff is one of the most common causes of shoulder pain. (1) Ultrasound guided percutaneous lavage (UGPL) is indicated when conservative treatments have failed. (2) Recent reports have shown the interest of topical sodium thiosulfate (STS) in the treatment of other diseases characterizes by ectopic calcifications (3, 4, 5).ObjectivesTo assess the efficacy and safety of UGPL with STS versus with saline solution (standard of care - SOC) in calcific tendinitis.MethodsDouble-blinded randomized clinical trial including adult patients with calcific tendinitis, shoulder pain for more than 3 months and at least one positive shoulder impingement test. Only dense type A calcifications (according to the Molé Classification) > 5 mm in diameter were included. Patients were randomized in two groups: STS and saline solution lavage. Informed consents were collected. Both groups were reevaluated at week 1, month 1 and month 3 after UGPL. Pain Visual Analogue Scale (VAS) at rest and during activities, shoulder range of motion and strength, impingement tests, Disabilities of the Arm, Shoulder and Hand (DASH), DASH-Work, EuroQol five-dimensional (EQ5D) and University of California at Los Angeles (UCLA) scores, ultrasound (US) and radiographic evaluations were performed on all follow up visits.SPSS was used for statistical analysis and significance level was defined as 2-sided p<0.05.ResultsTwenty-six patients were included, where 76.9% (20) were women, with a mean age of 51.2 (SD=9.0) years old. The mean duration of pain before the procedure was 12.7 months (SD=11.3) (minimum of 3 months and a maximum of 48 months).Fifteen patients (57.7%) were randomized to the control group (SOC) and performed a saline UGPL; the other 11 patients (42.3%) were randomized to the treatment group (STS). Demographic and baseline clinical characteristics are shown in Table 1. Since patient inclusion is dynamic, our sample met 23 patients at week 1 (SOC group = 13 and STS group = 10), 19 patients at month 1 (SOC group = 10 and STS group = 9) and 16 patients at month 3 (SOC group = 8 and STS group = 8).Table 1.Demographic and baseline clinical characteristics.STS lavage(n=11)Saline solution lavage (n=15)p-valueAge (years), M (SD)52.3 (10.6)50.3 (8.0)NSSex, female % (n/N)72.7% (8/11)80% (12/15)NSDominant side, right % (n/N)100% (11/11)93.3% (14/15)NSNocturnal pain, yes % (n/N)100% (11/11)100% (15/15)NSVAS at rest (0–10), M (SD)5.7 (2.0)5.9 (2.1)NSVAS during activities (0–10), M (SD)7.1 (1.8)6.0 (2.5)NSDASH Score, M (SD)60.2 (14.0)52.6 (13.8)NSDASH-Work Score, M (SD73.4 (11.0)63.4 (22.6)NSEQ5D, M (SD)0.2897 (0.3)0.4070 (0.2)NSVAS EQ5D (0–100), M (SD)54 (15.9)58 (20.0)NSUCLA score, M (SD)18.7 (4.1)14.7 (3.3)0.014Bursitis, yes % (n/N)72.7% (8/11)66.7% (10/15)NSCalcification morphology, % (n/N)Acr-shaped18.2% (2/11)40% (6/15)0.039Fragmented18.2% (2/11)26.7% (4/15)Nodular and dense, well-defined63.6% (7/11)33.3% (5/15)Calcification size, median (IQR)12.6 (5.7)10.5 (6.3)NSSD: Standard deviation; M: Mean; NS: non-significant; IQR: interquartile rangeOverall, there were no differences between control (SOC) and treatment group (STS). Both procedures were effective improving pain at rest (p=0.024), EQ5D (p=0.019), DASH-Work (p=0.032) and UCLA scores (p=0.009) and calcification size measured by US (p=0.031) at month 3.No adverse effects or complications were reported on both groups.ConclusionAlthough well tolerated with no side effects, STS UGPL has failed to show increased benefit for calcific tendinopathy local treatment. Further studies using STS will be needed to ascertain its interest in this disease. This on-going work will be reevaluated with a larger sample.References[1]Louwerens JK et al. J Shoulder Elbow Surg. 2015; 24:1588–93.[2]De Witte PB et al. Am J Sports Med. 2013; 41:1665-73.[3]Ossorio-García L et al. Actas Dermosifiliogr. 2016; 107:359-62. 21.[4]Jost J et al. J Clin Endocrinol Metab. 2016; 101:2810-5. 22.[5]Guigonis V et al. Ann Endocrinol (Paris). 2015; 76:183-4.Disclosure of InterestsNone declared

ABSTRACT Due to metabolic and morphological changes that can prevent Helicobacter pylori cells in water from growing on conventional media, an H. pylori-specific TaqMan quantitative PCR (qPCR) assay was developed that uses a 6-carboxyfluorescein-labeled probe (A. E. McDaniels, L. Wymer, C. Rankin, and R. Haugland, Water Res. 39:4808-4816, 2005). However, proper internal controls are needed to provide an accurate estimate of low numbers of H. pylori in drinking water. In this study, the 135-bp amplicon described by McDaniels et al. was modified at the probe binding region, using PCR mutagenesis. The fragment was incorporated into a single-copy plasmid to serve as a PCR-positive control and cloned into Escherichia coli to serve as a matrix spike. It was shown to have a detection limit of five copies, using a VIC dye-labeled probe. A DNA extraction kit was optimized that allowed sampling of an entire liter of water. Water samples spiked with the recombinant E. coli cells were shown to behave like H. pylori cells in the qPCR assay. The recombinant E. coli cells were optimized to be used at 10 cells/liter of water, where they were shown not to compete with 5 to 3,000 cells of H. pylori in a duplex qPCR assay. Four treated drinking water samples spiked with H. pylori (100 cells) demonstrated similar cycle threshold values if the chlorine disinfectant was first neutralized by sodium thiosulfate.

In the Lusatia area a pilot plant for the treatment of acidic mine waters by microbial iron oxidation and a concomitant iron hydroxysulfate precipitation is operated. Molecular based studies of acidic waters from this iron hydroxysulfate producing pilot plant revealed the presence of 16S rRNA gene sequences from undescribed iron-oxidizing bacteria. Most of these were related to autotrophic Betaproteobacteria (see Heinzel et al. IBS 2007, poster number 98). For cultivating different iron-oxidizing bacteria water samples from this pilot plant were directly plated on various solid media. Double-layer plates were used, with a heterotrophic Acidiphiliumstrain in the underlayer, because of the high sensitivity of autotrophic bacteria towards organic substances. The media contained different iron-substrates with and without organic carbon sources. Colonies appeared at the latest after three weeks and they were encrusted with ferric iron. The phylogeny of the isolated strains was determined and the physiological requirements, like temperature, pH optima, preferred carbon source and iron concentrations, were analyzed. Many isolates which were related to Acidithiobacillus ferrooxidans strains could be cultivated, as well as an isolate related to the genus Thiomonas and one isolate related to a Ferribacter polymyxa species. The Thiomonas-like isolate showed best growth in media containing tryptone soya broth, sodium thiosulfate and ferrous sulfate at pH 2.5 and 30°C. The other Betaproteobacterium grew on ferrous sulfate medium at pH 2.5 between 16 and 37°C. In liquid culture experiments the cells of both isolates were attached to the iron minerals built in the medium. These physiological characteristics of the isolates helped to vary parameters in the pilot plant to optimize the process of iron oxidation and improved waste water remediation.

Abstract Background: Calciphylaxis (calcific uremic arteriolopathy) is a rare complication seen in, although not limited to, patients with end-stage renal disease (ESRD). The abnormal regulation of calcium (Ca) and phosphorus (P) homeostasis in this patient group results in intravascular Ca deposition. These patients often develop secondary/tertiary hyperparathyroidism, presenting unique treatment challenges. When patients do not respond to medical therapy, parathyroidectomy is an option that may be complicated by hungry bone syndrome (HBS). We present a case of a patient with calciphylaxis with HBS post-parathyroidectomy. Case Report: The patient is a 41 y.o. male with ESRD on hemodialysis who presented with lower extremity ulcers complicated by calciphylaxis. On admission, the PTH was elevated at 2200 U with a normal corrected Ca 8.7 and P 8.5. He was found to have a non-displaced pathologic fracture of the right femoral neck. CT scan of the neck revealed nodular parathyroid hyperplasia affecting all four glands. His hyperparathyroidism was managed medically with cinacalcet, phosphate binder, and sodium thiosulfate to optimize his condition before surgery. He underwent a subtotal parathyroidectomy, with post-op course complicated by HBS. Repeat labs showed PTH 444, P 6.1, corrected Ca 7.4, and ionized Ca &lt;4. Despite frequent repletion with IV Ca and addition of calcitriol, he remained persistently hypocalcemic with symptoms (paresthesia, perioral numbness) and prolonged QTc (560 ms) on 12-lead EKG. After weighing the more imminent risk of unstable arrhythmia versus exacerbation of HBS by targeting too high of a Ca level post-op, ICU admission was decided where Ca levels could be more closely monitored and titrated. The patient eventually demonstrated an improvement in his Ca level and symptoms. Discussion: This patient with ESRD complicated by hyperparathyroidism presented with ulcers and calciphylaxis refractory to medical therapy, requiring parathyroidectomy. HBS was a concern in this particular patient given his risk factors. Hypocalcemia is an expected electrolyte imbalance that usually resolves within 2–4 days after parathyroidectomy. Severe and persistent hypocalcemia on day 4 after the procedure should raise concern for HBS. It has been shown that the risk is higher in patients who have secondary hyperparathyroidism, prolonged duration of elevated PTH, age &gt;60, and radiologic evidence of bone disease. ConclusionCalciphylaxis is an uncommon but potentially fatal illness seen in ESRD patients associated with Ca and P abnormalities. Whether this may increase the risk of HBS status-post parathyroidectomy is unknown; however, HBS requiring ICU management to treat refractory hypocalcemia has been reported in this group1. It is arguable that calciphylaxis may serve to identify such patients. (1) Hassanein M, et al. BMJ Case Rep 2018;11:e226696. doi:10.1136/bcr-2018–226696

Abstract Ko Kuei Chen (陈克恢, 1898–1988) (Fig. 1) was a pharmacologist who ceaselessly strove for medical research all his life. He was a pioneer of modern pharmacological research in Chinese medicine (Qian, 2014). He systematically studied the pharmacological action of ephedrine and published the first paper on this topic in the world. He discovered that injecting sodium nitrite and sodium thiosulfate intravenously could effectively treat acute cyanide poisoning (Chen et al., 1952). He isolated cinobufagin and cinobufotoxin from Ch’an Su, the dried venom of the Chinese toad. His research in pharmacology enriched the treasure trove of medicine. Ko Kuei Chen was a pioneer of pharmacology in Chinese medicine, and his research had epoch-making significance in the field. His pharmacological research on ephedrine set a milestone in the world medicine history.

L’objectif global de cette thèse était d’étudier, à partir de la cohorte des patients du centre de référence PXE du CHU d’Angers, différente aspects du phénotype cardiovasculaire (CV) du PXE. Ainsi, dans un premier travail, nous avons pu montrer dans l’étude GOCAPXE, que les calcifications ectopiques seraient un processus actif pouvant être détecté par une imagerie moléculaire utilisant un traceur spécifique de l’activité ostéoblastique, le 18-Fluorure de Sodium (18F-NaF); que ce processus était détectable avant même que ces calcifications ne soient visibles par les techniques d’imageries classiques; que ce processus était localisé aux zones habituellement lésées dans le PXE : les plis de flexion et le cou pour la peau et l’artère fémorale superficielle pour le vaisseau. Cette technique mériterait d’être validée dans une étude longitudinale et son rôle en tant biomarqueur diagnostique et de suivi serait ainsi envisageable. Le deuxième travail de cette thèse a été d’étudier les conséquences morphologiques et fonctionnelles d’une augmentation chronique de la pression artérielle chez les patients PXE. Cette question était pertinente car dans la littérature, la question d’une hypertension artérielle (HTA) chez les PXE reste controversée. Nous avons ainsi montré pour la première fois que dans un modèle d’HTA induite par le Deoxycorticostérone (DOCA)-Salt chez la souris Abcc6-/- cette augmentation de la pression artérielle induisait un remodelage CV avec à la fois de la fibrose et des calcifications dystrophiques. Les résultats de cette étude suggèrent la nécessité d’un contrôle optimal de la pression artérielle chez les patients PXE. Le troisième travail de cette thèse a été de caractériser une lésion de la carotide interne détectée avec une fréquence élevée dans la cohorte angevine. Nous avons pu montrer que cette anomalie était une hypoplasie de la carotide interne d’origine probablement congénitale. Chez les patients de la cohorte angevine, cette lésion était associée à des anévrismes intracrâniens mais nous n’avons pas retrouvé d’association avec la survenue d’accident vasculaire cérébral. Ainsi, les résultats de cette étude invitent les praticiens prenant en charge des patients PXE à la rechercher systématiquement dans le bilan vasculaire d’un patient PXE. Si une telle lésion est retrouvée, une imagerie vasculaire intracrânienne devrait être proposée à la recherche d’anévrismes et leur prise en charge discuté en concertation multidisciplinaire. Enfin, le dernier travail a permis de montrer qu’un traitement systémique par le Thiosulfate de Sodium (STS), utilisé dans la calciphylaxie rénale, était efficace sur la régression des calcifications artérielles et cutanées chez une jeune garçon ayant un phénotype CV gravissime résultant de la combinaison délétères de plusieurs gènes pathogènes du spectre PXE Ce traitement mériterait d’être validé dans un essai thérapeutique chez l’humain mais aussi la démonstration de ses mécanismes d’action dans le modèle murin Abcc6-/-. Nous suggérons d’utiliser ce traitement en cas de PXE sévère et rapidement progressif notamment sur le plan vasculaire. Au terme de ce travail de thèse, nous avons montré que le gène ABCC6 était impliqué dans le remodelage vasculaire à la fois au niveau développemental (Hypoplasie Carotidienne) mais aussi acquis (Fibrose, Calcification Cardiaque Dystrophique). Nous avons montré aussi que les calcifications dans le PXE étaient tissus et localisations spécifiques, que ces calcifications étaient actives. Enfin nous avons ouvert la porte à un traitement des formes graves du PXE avec le Thiosulfate de Sodium. Une approche thérapeutique multimodale ciblant plusieurs mécanismes concourant aux calcifications seraient judicieux à évaluer dans les futurs essais cliniques
Since the discovery of the ABCC6 gene in 2000, mutations are at the origin of PseudoxanthomeElastic (PXE), knowledge of genetics, pathophysiology, phenotypic characterizations have has mademajor advances, notably with the Discovery in 2013 of the fundamental role of Pyrophosphateinorganic (PPi) as a deficient anti‐calcifying factor in patients. The overall goal of this thesis was tostudy, from the cohort of patients at the center of PXE reference of the CHU d'Angers, differentaspects of cardiovascular phenotype (CV) of PXE. Thus, in a first work, we were able to show in thestudy GOCAPXE, that ectopic calcifications would be a active process that can be detected by imagingUsing a specific activity tracer Osteoblastic, 18‐sodium fluoride (18F‐NaF); that this process wasdetectable even before these calcifications are not visible by conventional imaging techniques; thatthis process was localized to areas usually injured in the PXE: flexion folds and neck for skin and thesuperficial femoral artery for the vessel. This technique should be validated in a study longitudinaland its role as a diagnostic biomarker In this way, monitoring and monitoring could be considered.The second work of this thesis was to study the morphological consequences and functional of achronic increase in blood pressure in PXE patients. This question was relevant because in theliterature, the question of a high blood pressure (hypertension) in PXE remains controversial. Wehave thus shown for the first time that in a model of HTA induced by the Deoxycorticosterone(DOCA)‐Salt in Abcc6‐/‐ this increase in blood pressure led to a CV remodeling with both fibrosis andcalcifications dystrophic. The results of this study suggest need for optimal control of blood pressurein patients. The third work of this thesis was to characterize a lesion of the internal carotid detectedwith high frequency in the Angevine cohort. We have could show that this abnormality washypoplasia of the Probably congenital internal carotid. In the patients of the angevine cohort, thislesion was associated with intracranial aneurysms but we have not found in association with theoccurrence of vascular accident brain. Thus, the results of this study invite practitioners supportingPXE patients to search for it systematically in the vascular balance of a PXE patient. If such a lesion isfound, vascular imaging Intracranial should be proposed to research Aneurysms and theirmanagement discussed in consultation multidisciplinary. Finally, the latest work has made it possibleto show that systemic treatment with Thiosulphate Sodium (STS), used in renal calciphylaxia, waseffective on the regression of arterial calcifications and skin in a young boy with a phenotype CVGravel resulting from the deleterious combination of several pathogenic genes of the PXE spectrumThis treatment would deserve be validated in a human therapeutic trial but also the demonstrationof its mechanisms of action in the Abcc6‐/‐murin model. We suggest using this treatment for severeand rapidly progressive PXE especially on the vascular plane.At the end of this thesis work, we showed that the ABCC6 gene was involved in vascular remodelingat both at the developmental level (Carotid Hypoplasia) but also acquired (Fibrosis, CardiacCalcification Dystrophic). We also showed that calcifications in PXE were tissues and locationsspecific, that these calcifications were active. Finally we have opened the door to a treatment ofsevere forms of PXE with Sodium Thiosulphate. An approach multimodal therapy targeting multiplemechanisms this would be useful to evaluate in future clinical trials