Residual Ethylene Oxide in Hollow-Fiber Dialyzers

The deaeration and extraction kinetics of ethylene oxide (ETO) in hollow-fiber dialyzers were examined. The investigations showed that both deaeration and extraction can be described by two additive first-order kinetic expressions. The ETO content of membranes decreased rapidly at first, followed by a second slower decrease. Even after prolonged storage time, residual ETO was still detectable in the milligram range. These residuals cannot be eliminated by the usual rinsing of the dialyzer prior to use.     

Mediation of Hypersensitivity Reactions During Hemodialysis by IgE Antibodies Against Ethylene Oxide

Sera from 329 hemodialysis patients, 46 of whom had experienced a hypersensitivity-type reaction during hemodialysis, were screened by an enzyme-allergosorbent test (EAST) for IgE antibodies specific for ethylene oxide (ETO). In seven of nine patients who had experienced a severe hypersensitivity reaction (type II or type III), high titers of IgE antibodies against ETO (greater than 3.0 PRU/mL) were found. However, plasma levels of IgE specific for ETO were in the normal range (less than 0.35 PRU/mL) in most (30/37) patients who had experienced a mild (type I) reaction. Selected sera from patients who had experienced severe reactions were further examined for IgE directed against isopropyl myristate (IPM), 2-chloroethanol, and extracts from unsterilized dialyzers. Importantly elevated serum levels of specific IgE against these substances could not be documented. Extracts of an ETO-sterilized, hollow-fiber dialyzer were positive, whereas extracts of an ETO-sterilized dialyzer containing a flat membrane were negative in the EAST. This difference can be explained by the different amounts of ETO present in the dialyzers. We conclude that ETO causes most severe hypersensitivity reactions by an IgE-mediated mechanism. On the other hand, the pathogenesis of mild (type I) reactions is less clearly associated with ETO allergy. Our results also suggest that other potentially allergenic substances in dialyzers (e.g., IPM, 2-chloroethanol) rarely induce specific IgE antibodies in dialysis patients.     

Generation of Nitrate During Dialysis as a Measure of Nitric Oxide Synthesis

Abstract: Nitric oxide (NO) is a recently identified mes senger, which influences the local regulation of blood flow and platelets as well as neuronal and inflammatory pathways. Disturbed NO information might be involved in the uremic syndrome and might also cause hypotension during dialysis. To clarify these issues, we analyzed plasma and dialysis fluid concentrations of nitrate, the stable NO metabolite, in 9 patients during hemodialysis. Plasma nitrate was raised at the onset of dialysis as compared with healthy subjects (83 ± 9 versus 26 ± 2 μ, mol/L). The plasma concentration decreased to 20 ± 2 μ, mol/L (p < 0.01) during the dialysis. The relative decrease was more pronounced than the relative reduction in creatinine, phosphate, and urea concentrations. A parallel decrease in nitrate was seen in effluent dialysis fluid (32 ± 4 to 14 ± 1 μ mol/L; p < 0.01). Calculations of the amount of nitrate coming to and from the dialyzer were performed in 7 of the 9 patients, and in 5 of the 7 patients, generation of nitrate within the dialyzer could be postulated. This might explain the paradoxical venodilation noted during hemodialysis.     

IgE Against Ethylene Oxide-Altered Human Serum Albumin (ETO-HSA) as an Etiologic Agent in Allergic Reactions of Hemodialysis Patients

Ethylene oxide (ETO) is used to sterilize hemodialyzers and other medical equipment. In an attempt to confirm a link between ETO and hypersensitivity reactions during hemodialysis (HD) we quantitated IgE and total antibody directed against ETO-altered human serum albumin (ETO-HSA) in the sera of 65 hemodialysis patients. In 24 patients who had experienced anaphylaxis during HD, the levels of IgE and total antibody against ETO-HSA were significantly higher than the corresponding levels in 41 patients who had not. Our data demonstrate an association between the presence of IgE and total antibody against ETO-HSA and immediate anaphylactic reactions to HD. In further studies we characterized the ETO-HSA antigen by immunoelectrophoresis, gel filtration chromatography, and cross-inhibition immunoassay. Our results suggested that ETO gas can alter HSA and induce new antigenic determinants on the molecule. Recently, we encountered a peritoneal dialysis patient with rash and eosinophilia. Suspecting ETO allergy, we measured serum IgE and total antibody to ETO-HSA and found both to be present. The data suggest that, in addition to the familiar HD reactions, ETO sensitization might cause other allergic diseases as well.     

Vanishing bone disease (Gorham-Stout syndrome): A review of a rare entity

Vanishing bone disease (Gorham-Stout syndrome) is a rare entity of unknown etiology, characterized by destruction of osseous matrix and proliferation of vascular structures, resulting in destruction and absorption of bone. Despite the extensive investigation of the pathogenetic mechanisms of the disease, its etiology hasn’t been clarified and several theories exist. The syndrome can affect one or multiple bones of the patient, including the skull, the upper and lower extremities, the spine and pelvis. The clinical presentation of a patient suffering from vanishing bone disease includes, pain, functional impairment and swelling of the affected region, although asymptomatic cases have been reported, as well as cases in which the diagnosis was made after a pathologic fracture. In this short review we summarize the theories regarding the etiology as well as the clinical presentation, the diagnostic approach and treatment options of this rare disease.     

A Randomized Trial of Tenapanor and Phosphate Binders as a Dual-Mechanism Treatment for Hyperphosphatemia in Patients on Maintenance Dialysis (AMPLIFY)

BackgroundHyperphosphatemia is associated with cardiovascular morbidity and mortality in patients receiving maintenance dialysis. It is unknown whether combining two therapies with different mechanisms of action—tenapanor, an inhibitor of paracellular phosphate absorption, and phosphate binders—is safe and effective for the management of hyperphosphatemia in patients receiving maintenance dialysis.MethodsThis double-blind phase 3 trial enrolled 236 patients undergoing maintenance dialysis with hyperphosphatemia (defined in this trial as serum phosphorus 5.5–10 mg/dl inclusive) despite receiving phosphate binder therapy (sevelamer, nonsevelamer, sevelamer plus nonsevelamer, or multiple nonsevelamer binders). These participants were randomly assigned to receive oral tenapanor 30 mg twice daily or placebo for 4 weeks. The primary efficacy end point was the change in serum phosphorus concentration from baseline to week 4.ResultsOf the 236 randomized patients, 235 (99.6%) were included in the full analysis set; this included 116 in the tenapanor plus binder group and 119 in the placebo plus binder group. A total of 228 patients (96.6%) completed the 4-week treatment period. In the full analysis set (mean age 54.5 years, 40.9% women), patients treated with tenapanor plus binder achieved a larger mean change in serum phosphorus concentration from baseline to week 4 compared with placebo plus binder (−0.84 versus −0.19 mg/dl, P<0.001). Diarrhea was the most commonly reported adverse event, resulting in study drug discontinuation in four of 119 (3.4%) and two of 116 (1.7%) patients receiving tenapanor plus binder or placebo plus binder, respectively.ConclusionsA dual-mechanism treatment using both tenapanor and phosphate binders improved control of hyperphosphatemia in patients undergoing maintenance dialysis compared with phosphate binders alone.Clinical Trial registry name and registration number:AMPLIFY, {"type":"clinical-trial","attrs":{"text":"NCT03824587","term_id":"NCT03824587"}}NCT03824587     

A hemodialysis patient suffering from fever of unknown origin (FUO) associated with a mass in the heart

A 52-year-old man on long-term hemodialysis presented with fever of unknown origin. He had been diagnosed as having type 2 diabetes mellitus at 24 years of age. Maintenance hemodialysis had been initiated at 42 years of age because of the progression of diabetic nephropathy, and he had had an operation to implant a pacemaker at 50 years of age. In general examination on admission, there were no abnormal signs except for a mass lesion in the right ventricle of the heart. An operation was not performed owing to his rapidly deteriorating general condition. Staphylococcus aureus was detected in the blood culture. On autopsy, a mass approximately 3 cm in length was observed over the right ventricle originating from the left ventricular posterior wall. Histopathological findings of the mass revealed necrosis and abscesses with hemorrhage. Extensive inflammation was observed from the epicardium to the endocardium. Since no apparent episode that presented an opportunity for the infection had been observed, it is difficult to determine the origin of the infection. Received: January 7, 2001 / Accepted: August 2, 2002 Acknowledgments The authors are grateful to Professor Toshikazu Shirai in the Division of Pathology 2 and Professor Hiroyuki Daida in the Division of Cardiology, Department of Internal Medicine, Juntendo University School of Medicine, for their helpful support. Part of this case report was published in Jinzou in 2000 (in Japanese). Correspondence to:Y. Tomino     

Contemporary management of lower urinary tract disease with botulinum toxin A: a systematic review of botox (onabotulinumtoxinA) and dysport (abobotulinumtoxinA)

Context

The use of botulinum toxin A (BoNTA) in the treatment of lower urinary tract dysfunction has expanded in recent years and the off-licence usage list includes neurogenic detrusor overactivity (NDO), idiopathic detrusor overactivity (IDO), painful bladder syndrome (PBS), and lower urinary tract symptoms resulting from bladder outflow obstruction (BOO) or detrusor sphincter dyssynergia (DSD). There are two commonly used preparations of BoNTA: Botox (onabotulinumtoxinA) and Dysport (abobotulinumtoxinA).

Objective

To compare the reported outcomes of onabotulinumtoxinA and abobotulinumtoxinA in the treatment of NDO, IDO, PBS, DSD, and BOO for adults and children.

Evidence acquisition

We performed a systematic review of the published literature on PubMed, Scopus, and Embase in the English language reporting on outcomes of both BoNTA preparations. Review articles and series with <10 cases were excluded. The articles were graded for level of evidence and conclusions drawn separately for data with higher-level evidence.

Evidence synthesis

There is high-level evidence for the use of onabotulinumtoxinA and abobotulinumtoxinA in adults with NDO but only for abobotulinumtoxinA in children with NDO. Only onabotulinumtoxinA has level 1 evidence supporting its use in IDO, BOO, DSD, and PBS/interstitial cystitis.

Conclusions

We identified good-quality studies that evaluated onabotulinumtoxinA for all the indications described above in adults; such was not the case with abobotulinumtoxinA. Although this does not imply that onabotulinumtoxinA is more effective than abobotulinumtoxinA, it should be a consideration when counselling patients on the use of botulinum toxin in urologic applications. The two preparations should not be used interchangeably, either in terms of predicting outcome or in determining doses to be used.     

Mechanical ventilation as a surrogate for diagnosing the onset of abdominal compartment syndrome (ACS) in severely burned patients (TIRIFIC-study Part II)

Intra-abdominal compartment syndrome (ACS) is a devastating complication in burn patients with a high mortality. Apart from high-volume resuscitation as known risk factor, also mechanical ventilation seems to influence the development of ACS.The TIRIFIC trial is a retrospective, matched-pair analysis. Thirty-eight burn patients with ACS were matched for burned total body surface area (TBSA), age and mechanical ventilation (MV). In contrast to the already published part I addressing fluid resuscitation as a risk factor, the parameters analyzed in part II were maximum and average PEEP and peak pressure levels as well as serum lactate levels and prokinetic therapy. For subgroup-analysis the ACS-group was split up into an early-onset and late-onset ACS-group according to the median time between burn trauma and ACS. The groups were analyzed with a two-sided Mann–Whitney-U-test with significance set at p < 0.05.In the ACS-group all ventilation pressures (maximum and average PEEP and peak pressure levels) were significantly increased compared to control. The subgroup-analysis showed significantly increased maximum PEEP and peak pressure levels in early- and late-onset ACS-groups versus control. However, the average ventilation pressure levels were only increased in the early-onset ACS-group (average PEEP p = 0.0069; average peak pressure p = 0.05).The TIRIFIC trial showed significantly increased ventilation pressures in the ACS group in general as a surrogate parameter to support early diagnostics. Especially, maximum PEEP levels and peak pressures are significantly increased in both, early- and late-onset ACS. As an addition to the actual WSACS guidelines we suggest IAP measurement in mechanically ventilated burn patients if ventilating pressures are rising continuously without a clear pulmonary or otherwise identifiable reason.     

Selective inducible nitric oxide synthase (iNOS) inhibition attenuates remote acute lung injury in a model of ruptured abdominal aortic aneurysm

OBJECTIVE: Abdominal aortic aneurysm rupture is associated with a systemic inflammatory response syndrome and acute lung injury. Using a selective inducible nitric oxide synthase (iNOS) inhibitor, N(6)-(iminoethyl)-lysine (L-NIL), we explored the role of iNOS in the early pro-inflammatory signaling and acute lung injury in experimental abdominal aortic aneurysm rupture. MATERIALS AND METHODS: Anesthetized rats were randomized to sham control or shock and clamp (s + c) groups, which underwent one hour of hemorrhagic shock, followed by 45 minutes of supramesenteric aortic clamping, and then two hours resuscitated reperfusion. Animals in s + c were randomized to receive intravenous L-NIL at 50 microg/kg/h or saline at the start of reperfusion. Pulmonary permeability to (125)I-labeled albumin, myeloperoxidase (MPO) activity, cytokine levels, and semi-quantitative RT-PCR for mRNA were indicators of microvascular permeability, leuco-sequestration, and pro-inflammatory signaling, respectively. RESULTS: Lung permeability index were significantly increased in s + c compared to sham (4.43 +/- 0.96 versus 1.30 +/- 0.17, P < 0.01), and attenuated by L-NIL treatment (2.14 +/- 0.70, P < 0.05). Lung tissue MPO activity was significantly increased in s + c compared to sham (2.80 +/- 0.32 versus 1.03 +/- 0.29, P < 0.002), and attenuated by L-NIL treatment (1.50 +/- 0.20, P < 0.007). Lung tissue iNOS activity was significantly increased in s + c compared to sham animals (P < 0.05), and attenuated by L-NIL treatment (P < 0.05). Lung tissue iNOS mRNA was upregulated 8-fold in s + c compared to sham (P < 0.05). Data represents mean +/- standard error mean, comparisons with ANOVA. CONCLUSIONS: These data suggest that in our model of ruptured abdominal aortic aneurysm iNOS plays a crucial role in reperfusion lung injury. Selective inhibition of iNOS during early reperfusion prevents neutrophil mediated acute lung injury.     

A Rare Autosomal Dominant Variant in Regulator of Calcineurin Type 1 (RCAN1) Gene Confers Enhanced Calcineurin Activity and May Cause FSGS

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Potassium sensitivity test (PST) as a measurement of treatment efficacy of painful bladder syndrome/interstitial cystitis: a prospective study with cyclosporine A and pentosan polysulfate sodium

AIMS: Potassium sensitivity test (PST) has been used as an optional tool in diagnosing painful bladder syndrome/interstitial cystitis (PBS/IC). The role of PST in the follow-up of patients with PBS/IC is elusive. We performed PST before and after treatment of PBS/IC with cyclosporine A (CyA) or pentosan polysulfate sodium (PPS), to test whether the result of repeated PST correlates with alleviation of PBS/IC-related symptoms. MATERIALS AND METHODS: Sixty-four patients who participated in a randomized clinical study comparing CyA and PPS in the treatment of PBS/IC were recruited to the present study. Patients underwent 0.4 M PST before and after 6 months of treatment. The primary end point was a change from positive PST to negative among patients who responded to both treatments determined by global response assessment (GRA). RESULTS: Potassium sensitivity test (PST) was more likely to change from positive to negative among patients who responded to their treatment according to GRA (P < 0.001). The PST change follows the clinical course (ICSI score, voiding frequency, VAS score), which was more beneficial in the CyA-treated patients. CONCLUSIONS: Potassium sensitivity test (PST) reflects symptom severity of PBS/IC patients. Change of pre-treatment positive PST to negative correlates well with clinical alleviation of PBS/IC-related symptoms. In patients with persistent symptoms it may be painful and does not offer additional information. Thus, we do not recommend PST to be used as a routine clinical test in monitoring of PBS/IC treatment efficacy.     

A case of acetaminophen (paracetamol) causing renal failure without liver damage in a child and review of literature

Acetaminophen (paracetamol) is a widely used drug and known as a safety antipyretic and analgesic drug in childhood. Acetaminophen-associated liver damage is more recognized than kidney damage. Nephrotoxicity and hepatotoxicity can be seen together after acetaminophen overdose, but renal damage without liver damage is a rarely seen entity in all age groups being reported more rarely in childhood. We present here a 16-year-old girl with renal failure without liver damage because of acetaminophen toxicity and a review of literature for pathophysiological mechanisms, clinical course, treatment, and outcome.     

Use of the Central Sensitization Inventory (CSI) as a treatment outcome measure for patients with chronic spinal pain disorder in a functional restoration program

Background Context

The Central Sensitization Inventory (CSI) is a valid and reliable patient-reported instrument designed to identify patients whose presenting symptoms may be related to central sensitization (CS). Part A of the CSI measures a full array of 25 somatic and emotional symptoms associated with CS, and Part B asks if patients have previously been diagnosed with one or more specific central sensitivity syndromes (CSSs) and related disorders. The CSI has previously been validated in a group of patients with chronic pain who were screened by a trained psychiatrist for specific CSS diagnoses. It is currently unknown if the CSI can be a useful treatment-outcome assessment tool for patients with chronic spinal pain disorder (CSPD) who are not screened for comorbid CSSs. It is known, however, that previous studies have identified CS-related symptoms, and comorbid CSSs, in subsets of patients with CSPDs. Studies have also shown that CS-related symptoms can be influenced by cognitive and psychosocial factors, including abuse history in both childhood and adulthood, sleep disturbance, catastrophic and fear-avoidant cognitions, and symptoms of depression and anxiety.

A rare case of multiple leiomyomas on rudimentary uterus in a woman with Mayer Rokitansky Kuster Hauser (MRKH) syndrome: A challenging diagnosis and laparoscopic approach

Mayer Rokitansky Kuster Hauser (MRKH) syndrome is a congenital disorder involving reproductive, genitourinary, bone, and cardiac malformation. The incidence is 1 in 4000–5000 females livebirths. The phenotype is female 46 XX karyotype, normal secondary sexual characteristics, and normal functional ovaries. The occurrence of leiomyoma in uterine remnant in MRKH syndrome is a very rare case, even though several cases have been reported. The diagnosis and management approach, in this case, is quite challenging. Here, we report a 38 years old female who represents multiple leiomyomas on the rudimentary uterus, then we did laparoscopic removal of the fibroids and adjacent rudimentary uterus.     

A case of symptomatic Morgagni’s hernia and a review of Morgagni’s hernia in Japan (263 reported cases)

An 81-year-old female patient was admitted to the emergency room of our hospital with complaints of respiratory distress, abdominal ache, nausea, and intermittent vomiting. A plain X-ray of the abdomen and chest revealed air-fluid levels on the abdomen and the right side of the chest. Laboratory tests showed severe acidemia with a blood base excess level of −24.9 mmol/L. Since the patient was considered to have acute intestinal obstruction due to transverse colon herniation into the thorax through a foramen of Morgagni, emergency surgery was performed. Operative findings revealed that the retrosternal diaphragm had a defect of 5 cm in diameter and 20 cm in length with the transverse colon herniated into the thorax. The diaphragm defect was sutured first, and partial resection of the transverse colon was performed. After the operation, the patient had no symptoms and no recurrence has been observed during the 1-year follow-up. There have been 263 reported cases of Morgagani hernia in Japan. The case of the Morgagni hernia is reported here with some bibliographical comments.     

Acute lung injury in a rat model of intestinal ischemia-reperfusion: the potential time depended role of phospholipases A(2)

BACKGROUND: A pivotal role of phospholipase A(2) (PLA(2)) and platelet-activating factor-acetylhydrolase (PAF-AcH) as enzymes involved in lung inflammation has recently been suggested. The objective of this study was to elucidate the role and the time dependence of PLA(2) and PAF-AcH fluctuations in the lung relative to the evolution of intestinal ischemia-reperfusion (IIR). MATERIALS AND METHODS: Rats were randomly allocated to five groups of IIR induced by occlusion of the superior mesenteric artery for 45 min followed by 1 min, 2, 4, and 8 h of reperfusion (expGroups) and five corresponding sham groups (sGroups). Bronchoalveolar lavage fluid was obtained from the right lung and its biochemical (protein, PLA(2), PAF-AcH) and cytological characteristics were determined. Plasma malonyldialdehyde was measured as a marker of lipid peroxidation. The 4 and 8 h reperfusion expGroups had significantly (P < 0.05) elevated alveolar-arterial O(2) gradient values compared with the corresponding controls. Total protein, PLA(2) and PAF-AcH levels significantly (P < 0.05) increased in expGroups compared with the corresponding shams after 4 h of reperfusion. Total bronchoalveolar lavage fluid cells and plasma malonyldialdehyde were significantly (P < 0.05) elevated in expGroups compared with the sGroups after 2 h of reperfusion. CONCLUSIONS: PLA(2) could act synergistically or parallel with the reactive oxygen species produced during IIR, resulting in the induction or even in the exacerbation of the inflammatory reaction in acute respiratory distress syndrome. PAF-AcH could play an anti-inflammatory role by reducing the concentration of PAF.     

A systematic review of outcomes assessed in randomized controlled trials of surgical interventions for carpal tunnel syndrome using the International Classification of Functioning, Disability and Health (ICF) as a reference tool

Background  

A wide range of outcomes have been assessed in trials of interventions for carpal tunnel syndrome (CTS), however there appears to be little consensus on what constitutes the most relevant outcomes. The purpose of this systematic review was to identify the outcomes assessed in randomized clinical trials of surgical interventions for CTS and to compare these to the concepts contained in the International Classification of Functioning, Disability and Health (ICF).