Pyrogenic Reactions Research Articles

A Pentavalent Shigella flexneri LPS-Based Vaccine Candidate Is Safe and Immunogenic in Animal Models.

A multivalent vaccine is much needed to achieve protection against predominant Shigella serotypes. Recently, we demonstrated the clinical applicability and immunogenic potential of tri-acylated S. flexneri 2a lipopolysaccharide (Ac3-S-LPS). Using a similar approach, we designed a pentavalent LPS candidate vaccine against S. flexneri 1b, 2a, 3a, 6, and Y (PLVF). In this study, we performed molecular and antigenic characterization of the vaccine candidate and its preclinical evaluation. There were no signs of acute toxicity after subcutaneous administration of PLVF in rabbits at a proposed human dose of 125 μg. No pyrogenic reactions and adverse effects associated with chronic toxicity after repeated administration of PLVF were revealed either. The immunization of mice with PLVF led to ≥16-fold increase in S. flexneri 1b-, 2a-, 3a-, 6-, and Y-specific antibodies. In a serum bactericidal antibody (SBA) assay, we registered 54%, 66%, 35%, 60%, and 60% killing of S. flexneri 1b, 2a, 3a, 6, and Y, respectively. In the guinea pig keratoconjunctivitis model, the efficacy was 50% to 75% against challenge with all five S. flexneri serotypes. These studies demonstrate that PLVF is safe, immunogenic over a wide range of doses, and provides protection against challenge with homologous S. flexneri strains, thus confirming the validity of pentavalent design of the combined vaccine.

Problems associated with new coronavirus infection vaccination in patients with rheumatic diseases

BACKGROUND: Decreasing new coronavirus infection-associated morbidity and mortality among patients with rheumatic diseases is one of the main goals of current rheumatology. Vaccination may be one of the ways to limit the incidence of new coronavirus infection in patients with rheumatic diseases.
 AIM: To evaluate the results of vaccination in the patients with rheumatic diseases against the new coronavirus infection according to the data from real clinical practice and a review of the literature.
 MATERIALS AND METHODS: 68 out of 556 literary medical sources and data from the St. Petersburg register of patients with rheumatic diseases as of September 1, 2021 (n = 16,263) have been analyzed. The data from the register have been compared with the population data on morbidity and mortality from a new coronavirus infection (data of the Ministry of Health of the Russian Federation).
 RESULTS: Despite the matched incidence rates of new coronavirus infection associated mortality and morbidity in rheumatological patients and population (morbidity 26.2 and 34.1% mortality 3.47 and 2.8%, respectively), the patients with rheumatic diseases demonstrate three times lower frequency of vaccination against new coronavirus infection (13.2% of patients versus 31.8% in the population, respectively). Vaccination is prescribed by rheumatologists in 8.2%; 75% of patients are self-vaccinated. Data analysis from 2,134 rheumatological patients vaccinated in 2021 have shown a decrease in the incidence of the new coronavirus infection to 0.25% compared to the incidence of unvaccinated patients (25.6%) in the absence of deaths among the vaccinated. There were no serious adverse reactions to vaccination among the vaccinated rheumatological patients; in 12% of the cases, pyrogenic post-vaccination reactions, arthralgias and myalgias have been noted. A prolonged pyrogenic reaction, myalgia, arthralgia, hypercreatinophosphataemia have been revealed in 11 patients, who recovered within 6 months. Exacerbations of the underlying rheumatic disease after vaccination has been revealed in 12% of the cases, all the exacerbations have been resolved with the use of standard tactics recommended by the Association of Russian Rheumatologists.
 The question of the timing and the necessity of revaccination, as well as the long-term efficacy and safety of vaccination, has not yet been resolved. Determining the level of antibodies to coronavirus infection can be a useful option in the formation of an individual vaccination plan for rheumatological patients in the present conditions.
 CONCLUSIONS: The register data show the efficacy and safety of vaccination against COVID-19 in rheumatological patients in the short term, including in relation to exacerbation of rheumatic disease, and justify the need to comply with epidemiological safety measures after vaccination.

SCIG administration: A promising and patient convenient alternative for those receiving long-term IVIG.

Background: Intravenous immunoglobulin (IVIG) therapy has been used as antibody replacement therapy in primary immunodeficiency diseases (PID) for more than 50 years. In this study, we aimed to define IVIG usage and adverse reactions and complications in PID and explain how subcutaneous immunoglobulin (SCIG) replacement therapy is an alternative that improves the patient experience. In addition, the additional nursing responsibilities associated with this service were also identified.Methods: Data and service satisfaction surveys for the last 10 years were reviewed from the Allergy and Immunology Division log registry for those on IVIG and SCIG.Results: IVIG practice: Most patients currently on IVIG in our unit have PID. Adverse reactions occur during the initial 30 to 60 minutes of the infusion and are mild and self-limited. Infusion reactions are more likely to occur in patients receiving IVIG for the first time. Infusion-related complications included pyrogenic reactions, allergic reactions, and vasomotor symptoms. Complications reported in the literature such as the transmission of blood-borne pathogens and other serious complications, including thrombotic events, renal adverse events, and aseptic meningitis were never reported. Pyrogenic reactions occurred at a rate ≥ 100 mL/hr in at least 3 patients, and a slower infusion rate of ≤ 75 mL/hr mitigated this rate-related complication.SCIG program: This program started in Qatar in 2017. Usually, the clinician assesses and evaluates several factors to help select candidates for this therapy, including the perceptions of inconvenience and/or pain of IV infusions, presence of difficult vein access, and other relevant clinical and social factors. Once training in the appropriate techniques has been accomplished (3–6 sessions), it is most often self-administered in the home setting by the patient or a parent for a child. Table 1 summarizes patients on SCIG.Additional nursing responsibilities: The nursing role in subcutaneous IgG administration is primarily that of an educator and to help the patient/family become independent. This can be achieved by the assessment of appropriate patient selection for self-administration. Determining which patients are suitable include adequate patient education with return demonstration of the necessary skill set, monitoring parameters, educating patients about their medication, and providing educational resources and support.Conclusion: SCIG administration can be a convenient alternative for patients with PID receiving long-term IVIG.

Methodology for Calculating Bacterial Endotoxin Limits

Product specification files for parenteral medicines, as well as for active ingredients used in their production, have to include the “Bacterial endotoxins” parameter that controls the content of pyrogenic impurities. The experts of the Federal State Budgetary Institution “Scientific Centre for Expert Evaluation of Medicinal Products” of the Ministry of Health of the Russian Federation proposed recommendations for calculation and selection of the bacterial endotoxin limit, which will help applicants to include correct requirements for bacterial endotoxin limits in their product specification files. The proposed algorithm for the selection of bacterial endotoxin limits will make it possible to reduce the risk of pyrogenic reactions in patients and ensure safe use of medicinal products.

Cellular and Immunological Response of THP-1 Cells in Response to Lipopolysaccharides and Lipoteichoic Acid Exposure

Introduction: Bacterial toxins are considered to be obscuring factors in multiple human diseases. Accidental contamination by bacterial lipopolysaccharides (LPS) and lipoteichoic acid (LTA) in biomedical and biotechnological products may lead to inflammation and associated pyrogenic reactions in humans. LPS are the most studied and clinically important pyrogen from gram-negative bacteria, while LTA is derived from the cell wall of gram-positive bacteria. Previous studies have identified that LPS and LTA induce a pyrogenic response in living systems. However, the detailed mechanisms of cellular toxicity have not yet been determined. The present study aimed to investigate LPS-induced and LTA-induced immune response activation and the ensuing effects on cellular integrity and organelle function in monocytes and monocyte-derived macrophages. Methods: With monocytes and macrophages being the first lines of defense against pathogenic invasion, THP-1 cells were selected as an in vitro model for the present study. THP-1 is a cancerous monocyte cell line and can differentiate into macrophages via stimulation with phorbolmyristic acid. Intracellular responses of monocytes and monocyte-derived macrophages following exposure to LPS and LTA were analyzed through several assays, including MTT, Neutral red, DCFH-DA, NO release, DilCI (5), Annexin V-PI FACS, Rhodamine phalloidine, Acridine Orange, and JC1. The expression of the inflammation-related genes NFκB, COX2, IL-1β, and TNF-α, along with activation of inflammatory signaling, was also assessed in monocytes following toxic interaction. Results & Conclusion: The results revealed that LPS and LTA can induce inflammatory signals at nanogram concentrations but are non-cytotoxic at low concentrations. LPS exposure had no significant toxic impacts on membrane integrity and organelle function. LPS induced neither apoptotic nor necrotic cell death of THP-1 cells at the selected concentration. However, LTA caused cell membrane damage and organelle dysfunction in a time and dose-dependent manner. LTA exposure led to oxidative stress and apoptotic cell death mediated by reactive oxygen species (ROS) and reactive nitrogen species (RNS). Both bacterial toxins augmented the expression of inflammatory genes and associated inflammatory signal transmission in THP-1 cells. The overall cellular effect was dependent on dose and time of exposure.

Nanocarriers to enhance solubility, bioavailability, and efficacy of artemisinins

The therapeutic potential of artemisinin (ART) and its derivatives (ARTs) is not limited to malaria but has been recently expanded to other infections with protozoans, trematodes, or viruses as well as to cancer. Due to their limited poor water and oil solubility, rapid degradation by the liver, and short half-life, they have a low bioavailability after oral administration. Consequently, there is a pressing necessity to formulate new ART preparations to raise its bioavailability and efficacy. Nanosized drug delivery systems represent important tools in modern medicine with wide clinical applications, because of their potential modulation of pharmacokinetic and biodistribution. This review focuses on polymer-based systems, lipid-based systems, and inorganic nanoparticles loaded with ARTs. The overall goal of this field of research is to enhance their solubility and stability to improve bioavailability at much lower doses and to increase long-term safety. In addition, the opportunity to reach highly specific site-targeted delivery by these nanocarriers confers a high medicinal value. Remarkably, most of the reported nanoparticulate drug delivery systems are biologically inactive or marginally immunogenic, generating no antigenic or pyrogenic reactions but only partial intrinsic toxicity. As clinical studies in human patients are available so far, there is a pressing need to translate preclinical results on ART-based nanosystems into clinical settings.

Il trattamento delle acque di dialisi: dalla storia ai giorni nostri

Nella storia della dialisi, la presenza di alcuni quadri clinici tipici, come la “sindrome dell'acqua dura”, l'encefalopatia e l'osteomalacia da alluminio o le reazioni da pirogeni, ha determinato la necessità di trattare l'acqua di rete prima di renderla disponibile per la dialisi; infatti negli anni la scelta dell'acqua per la dialisi ha subito pe-riodiche variazioni passando dall'utilizzo di quella di rete a quella ultrapura, attraverso le fasi di acqua decalcificata, demineralizzata e da osmosi. Attualmente il trattamento prevede: il pre-trattamento, il trattamento vero e proprio e il circuito idraulico. Il pre-trattamento ha il compito di rimuovere le particelle in sospensione garantendo l'integrità delle membrane poste a valle. Il trattamento vero e proprio rende l'acqua disponibile per la dialisi e comprende la biosmosi inversa, ottenuta sottoponendo l'acqua da trattare ad un doppio passaggio su membrane osmotiche. Il circuito idraulico ha il compito di distribuire l'acqua osmotizzata in sala dialisi. Gli Impianti delle Ditte Fresenius, Gambro e Farmacastelli si differenziano tra di loro per le modalità di trattamento dell'acqua, per la struttura degli impianti e i sistemi di disinfezione.

Qualidade da água: fatos e mitos!

Objetivo: Discorrer sobre a importância da água no Centro de Material e Esterilização, as principais evidências de risco, normas, legislação relacionada e orientações para a definição de um sistema de tratamento de água para enxágue de produtos. Método: Revisão narrativa buscando fatos, mitos e descrevendo aspectos relacionados à necessidade de controle da qualidade de água utilizada no processamento de produtos para saúde. Resultados: Relatos de efeitos tóxicos locais e reações pirogênicas em pacientes demandam a padronização e controle de qualidade da água para enxágue de produtos e geração de vapor nas autoclaves. Conclusão: O tratamento e monitoramento da qualidade da água devem ser incorporados pelos serviços de saúde.

Assessing endotoxins in equine-derived snake antivenoms: Comparison of the USP pyrogen test and the Limulus Amoebocyte Lysate assay (LAL)

Snake antivenoms are parenterally administered; therefore, endotoxin content must be strictly controlled. Following international indications to calculate endotoxin limits, it was determined that antivenom doses between 20 mL and 120 mL should not exceed 17.5 Endotoxin Units per milliliter (EU/mL) and 2.9 EU/mL, respectively. The rabbit pyrogen test (RPT) has been used to evaluate endotoxin contamination in antivenoms, but some laboratories have recently implemented the LAL assay. We compared the capability of both tests to evaluate endotoxin contamination in antivenoms, and we found that both methods can detect all endotoxin concentrations in the range of the antivenom specifications. The acceptance criteria of RPT and LAL must be harmonized by calculating the endotoxin limit as the quotient of the threshold pyrogenic dose and the therapeutic dose and the dose administered to rabbits as the quotient of the threshold pyrogenic dose and the endotoxin limit. Since endotoxins from Gram-negative bacteria exert different pyrogenicity, if contamination occurred, antivenom batches that induce pyrogenic reactions may be found in spite of passing LAL specifications. Although LAL assay can be used to assess endotoxin content throughout the antivenom manufacturing process, we recommend that the release of final products be based on the results of both methods.

Bacteriological Quality of Treated Water and Dialysate in Haemodialysis Unit of A Tertiary Care Hospital.

Haemodialysis is one of the treatment modalities for patients suffering from end stage renal disease (ESRD). Dialysis patients are exposed to large volumes of water for production of dialysis fluids. Treated water and dialysate come in direct contact with the patient's bloodstream. Such patients suffer from abnormalities of the immune system, making them more susceptible to infections. Microbial contamination of the treated water and dialysate can lead to biofilm formation and release of endotoxins in Haemodialysis system. These can give rise to pyrogenic reactions in the short term and β2 amyloidosis, atherosclerosis, and increased mortality in the long term. To assess the bacteriological quality of treated water and dialysate used in the Haemodialysis unit of a tertiary care hospital. A retrospective review of records of treated water and dialysate samples sent to the Microbiology laboratory for analysis of bacteriological contamination of the water used in haemodialysis treatment from January 2013 to June 2014 was conducted. The acceptable limits for treated water and dialysate were taken as <200 CFU/ml and < 2000 CFU/ml respectively as per Government of India Guidelines for Maintenance Haemodialysis. Thirty six samples of treated water and 394 samples of dialysate were analysed for bacteriological contamination. 4 out of 36 (11.1%) samples of treated water and 44 out of 394 dialysate samples (11.2%) showed unacceptable bacteriological growth. Regular and continual monitoring of the disinfection protocol of the water distribution system in haemodialysis unit is necessary to get good microbiological quality of treated water and dialysate fluid.

Antivenoms in Snake Envenoming: Are they Safe?

Snake antivenoms are the only definitive management of snake envenoming. Parenteral administration of antivenom mitigates the toxic effects due to snake venom components. However, these benefits come with additional risk of antivenom reactions. The morbidity and mortality of antivenom reactions largely go unnoticed due to lack of awareness and many times these are wrongly attributed to effects of snake venoms. Depending upon the duration between antivenom administration and onset of clinical manifestations, World Health Organization (WHO) has classified these reactions into three types; namely i) early anaphylactic reactions: occur within 10-180 minutes after antivenom infusion, ii) pyrogenic (endotoxic) reactions: develop within 1-2 hours after initiation of treatment, and iii) late reactions: usually develop 1-12 (mean 7) days after treatment. The conjunctival or skin hypersensitivity tests are not only unreliable but can also be sensitizing to antivenom reactions, and hence, not recommended by WHO. The majority of early anaphylactic reactions are non-IgE mediated owing to anticomplementary activity of antivenom and few reactions are attributed to IgE mediated release of anaphylotoxins namely histamines, leukotriens etc. Contamination of antivenom with endotoxins during manufacturing process leads to development of pyrogenic reactions. Late antivenom reactions are the result of production of IgM or IgG antibodies in patients towards antivenom proteins, which ultimately cause formation of immune complexes. The deposition of these immune complexes throughout body leads to manifestations of late reactions. There should be a vigilant approach towards prediction and prevention of antivenom reactions for a better quality of health care.

Biological safety of fish (tilapia) collagen.

Marine collagen derived from fish scales, skin, and bone has been widely investigated for application as a scaffold and carrier due to its bioactive properties, including excellent biocompatibility, low antigenicity, and high biodegradability and cell growth potential. Fish type I collagen is an effective material as a biodegradable scaffold or spacer replicating the natural extracellular matrix, which serves to spatially organize cells, providing them with environmental signals and directing site-specific cellular regulation. This study was conducted to confirm the safety of fish (tilapia) atelocollagen for use in clinical application. We performed in vitro and in vivo biological studies of medical materials to investigate the safety of fish collagen. The extract of fish collagen gel was examined to clarify its sterility. All present sterility tests concerning bacteria and viruses (including endotoxin) yielded negative results, and all evaluations of cell toxicity, sensitization, chromosomal aberrations, intracutaneous reactions, acute systemic toxicity, pyrogenic reactions, and hemolysis were negative according to the criteria of the ISO and the Ministry of Health, Labour and Welfare of Japan. The present study demonstrated that atelocollagen prepared from tilapia is a promising biomaterial for use as a scaffold in regenerative medicine.

Immune Response to Snake Envenoming and Treatment with Antivenom; Complement Activation, Cytokine Production and Mast Cell Degranulation

BackgroundSnake bite is one of the most neglected public health issues in poor rural communities worldwide. In addition to the clinical effects of envenoming, treatment with antivenom frequently causes serious adverse reactions, including hypersensitivity reactions (including anaphylaxis) and pyrogenic reactions. We aimed to investigate the immune responses to Sri Lankan snake envenoming (predominantly by Russell's viper) and antivenom treatment.Methodology/Principal FindingsPlasma concentrations of Interleukin (IL)-6, IL-10, tumor necrosis factor α (TNFα), soluble TNF receptor I (sTNFRI), anaphylatoxins (C3a, C4a, C5a; markers of complement activation), mast cell tryptase (MCT), and histamine were measured in 120 Sri Lankan snakebite victims, both before and after treatment with antivenom. Immune mediator concentrations were correlated with envenoming features and the severity of antivenom-induced reactions including anaphylaxis. Envenoming was associated with complement activation and increased cytokine concentrations prior to antivenom administration, which correlated with non-specific systemic symptoms of envenoming but not with coagulopathy or neurotoxicity. Typical hypersensitivity reactions to antivenom occurred in 77/120 patients (64%), satisfying criteria for a diagnosis of anaphylaxis in 57/120 (48%). Pyrogenic reactions were observed in 32/120 patients (27%). All patients had further elevations in cytokine concentrations, but not complement activation, after the administration of antivenom, whether a reaction was noted to occur or not. Patients with anaphylaxis had significantly elevated concentrations of MCT and histamine.Conclusions/SignificanceWe have demonstrated that Sri Lankan snake envenoming is characterized by significant complement activation and release of inflammatory mediators. Antivenom treatment further enhances the release of inflammatory mediators in all patients, with anaphylactic reactions characterised by high levels of mast cell degranulation but not further complement activation. Anaphylaxis is probably triggered by non allergen-specific activation of mast cells and may be related to the quality of available antivenom preparations, as well as a priming effect from the immune response to the venom itself.

Dialysis Water Treatment Systems: From past to Present

In the past dialysis was associated with typical syndromes, such as “hard water syndrome”, aluminium-linked encephalopathy and osteomalacia, and pyrogenic reactions. With time it was recognized that water required treatment before being used for haemodialysis. With experience, the type of water for haemodialysis changed from tap to decalcified, then to demineralised, next to osmosis and finally ultra-pure water, the current gold standard. At present, water treatment systems involve pre-treatment, real treatment and a hydraulic circuit. The pre-treatment process removes suspended particles which would damage the osmotic membranes. Real treatment prepares water for haemodialysis by using reverse osmosis. The hydraulic circuit distributes osmotic water to the dialysis room and into each machine. The water treatment systems considered were supplied by Fresenius, Gambro and Farmacastelli. They differ from one another in treatment protocols, construction and disinfection systems.

Bacteriological and Toxicological Qualities of Dialysis Water and Associated Pyrogenic Reactions Involved in Haemodialysis Patients

Bacteriological and Toxicological Qualities of Dialysis Water and Associated Pyrogenic Reactions Involved in Haemodialysis Patients

Implementing On-Line Hemodiafiltration as a Renal Replacement Therapy for ICU Acute Renal Failure: A Single-Center Report of Feasibility, Safety and Hemodynamic Tolerance over a Seven-Year Period

Background/Aims: On-line hemodiafiltration (HDF) is not yet routinely used in ICUs given the potential risk of microbial contamination of dialysis fluids. We evaluated the safety and the tolerance of its use in our ICU. Methods: A weekly measurement of bacterial growth (CFU/ml) and endotoxin level (endotoxin units/ml) was performed in dialysis fluids over a 7-year period. Intradialytic hypotensive events and pyrogenic reactions were collected during 466 on-line HDF sessions. Results: A bacterial count <0.1 CFU/ml was achieved in 977/978, 288/290, and 278/280, and an endotoxin level <0.03 endotoxin units/ml in 564/576, 330/337 and 318/323 ultrapure water, dialysate, and infusate samples, respectively. Seventy-six intradialytic hypotensive events but no pyrogenic reaction occurred. Conclusion: The great majority of dialysis fluid samples were considered suitable with a 99% compliance rate. Use of on-line HDF, at a large scale of dialysate and infusate flows, is well tolerated and may be safely performed in critically ill.

Further evaluation of a novel nano‐scale gene vector for in vivo transfection of siRNA

In this research, a lipid-cationic polymer (LCP) containing the side-chain branching of brassidic acid was synthesized using chemical methods. As a gene vector for small interfering ribonucleic acid (siRNA) transfection, the efficiency and biosafety of LCP were preliminarily evaluated to investigate its possible application on tumor gene therapy. The toxicity, side-effects, and biosafety of LCP were investigated in animals based on the results of in vitro experiments. The siRNA against cyclooxygenase-2 (COX-2) was transfected by LCP to interfere with the COX-2 expression in nude-transplanted tumors. Hematoxylin and eosin stains, immunohistochemistry, reverse transcription-polymerase chain reaction, and Western blot were performed to evaluate the efficiency of LCP for siRNA transfection. The animal toxicity experiment showed that a high concentration of LCP had a low toxic effect on animals and did not induce allergic or pyrogenic reactions. The results from the in vivo transfection indicated that LCP could efficiently transfect siRNA and silence the target gene expression. The LCP gene vector for siRNA transfection is highly efficient during in vivo transfection and had low toxicity. From all aspects of tumor gene therapy and basic research, LCP is valuable for scientific research and medical applications.

Snake antivenoms: adverse reactions and production technology

Antivenoms have been widely used for more than a century for treating snakebites and other accidents with poisonous animals. Despite their efficacy, the use of heterologous antivenoms involves the possibility of adverse reactions due to activation of the immune system. In this paper, alternatives for antivenom production already in use were evaluated in light of their ability to minimize the occurrence of adverse reactions. These effects were classified according to their molecular mechanism as: anaphylactic reactions mediated by IgE, anaphylactoid reactions caused by complement system activation, and pyrogenic reactions produced mainly by the presence of endotoxins in the final product. In the future, antivenoms may be replaced by humanized antibodies, specific neutralizing compounds or vaccination. Meanwhile, improvements in antivenom quality will be focused on the obtainment of a more purified and specific product in compliance with good manufacturing practices and at an affordable cost.

Anti-snake venom: use and adverse reaction in a snake bite study clinic in Bangladesh

Snakebites can present local or systemic envenomation, while neurotoxicity and respiratory paralysis are the main cause of death. The mainstay of management is anti-snake venom (ASV), which is highly effective, but liable to cause severe adverse reactions including anaphylaxis. The types of adverse reaction to polyvalent anti-snake venom have not been previously studied in Bangladesh. In this prospective observational study carried out between 1999 and 2001, in the Snake Bite Study Clinic of Chittagong Medical College Hospital, 35 neurotoxic-snake-bite patients who had received polyvalent anti-snake venom were included while the ones sensitized to different antitoxins and suffering from atopy were excluded. The common neurotoxic features were ptosis (100%), external ophthalmoplegia (94.2%), dysphagia (77.1%), dysphonia (68.5%) and broken neck sign (80%). The percentage of anti-snake venom reaction cases was 88.57%; pyrogenic reaction was 80.64%; and anaphylaxis was 64.51%. The common features of anaphylaxis were urticaria (80%); vomiting and wheezing (40%); and angioedema (10%). The anti-snake venom reaction was treated mainly with adrenaline for anaphylaxis and paracetamol suppository in pyrogenic reactions. The average recovery time was 4.5 hours. Due to the danger of reactions the anti-snake venom should not be withheld from a snakebite victim when indicated and appropriate guidelines should be followed for its administration.

Ultrapure Dialysate for Home Hemodialysis?

Use of ultrapure dialysate (bacteria < 0.1 CFU/mL and endotoxin < 0.03 EU/mL) is associated with a reduction in inflammation and morbidity in patients treated with conventional thrice-weekly dialysis. The improved outcomes obtained with more frequent dialysis schedules have reawakened interest in home hemodialysis. More frequent dialysis also appears to reduce inflammation, and whether combining more frequent dialysis with use of ultrapure dialysate will have an additive effect on inflammation and its consequences remains unclear. Routinely producing ultrapure dialysate in a home environment with a conventional hemodialysis machine poses technical challenges related to the design of the equipment and the intermittent nature of hemodialysis. Solutions to these problems include use of a system in which the water-treatment equipment is fully integrated with the dialysis machine, use of dry-powder cartridges or sterile prepackaged liquids for bicarbonate concentrate, and use of a bacteria-retentive and endotoxin-retentive filter for final purification of the dialysate immediately before it enters the dialyzer. Alternatively, ultrapure dialysate may be achieved with newer machines designed specifically for home hemodialysis that use a new batch of dialysate for each treatment. The volume of dialysate available with these machines, however, currently limits their use to short-daily dialysis.