Pyridostigmine in chronic intestinal pseudo-obstruction - a systematic review.

BACKGROUND: Chronic intestinal pseudo-obstruction (CIPO) may be a primary or secondary phenomenon and is often multifactorial. Treatment is largely directed at improving colonic motility. The use of cholinesterase inhibitors such as pyridostigmine has been hypothesized to increase acetylcholine in the bowel, improving symptoms and transit times. METHODS: A systematic review of the use of pyridostigmine in CIPO was conducted using scientific and commercial search engines identifying scientific studies enrolling adult human subjects, published from 2000 to 2022 in the English language. RESULTS: Four studies were identified including two randomized controlled trials (RCT) and two observational studies. The studies had heterogenous inclusion criteria, dosing regimens and reported outcomes. Two studies were identified as being at high risk of bias. All studies reported improved patient outcomes with use of pyridostigmine, and low rates (4.3%) of mild cholinergic side effects. No major side effects were reported. CONCLUSION: The use of pyridostigmine in management of CIPO is biologically plausible due to its ability to increase colonic motility, and early studies on its role are uniformly suggestive of benefit with low side-effect profile. Four clinical studies have been conducted to date, with small sample sizes, heterogeneity and high risk of bias. Further high-quality studies are required to enable assessment of pyridostigmine's utility as an effective management strategy in CIPO.

Massive gastric distension due to bulimia nervosa: a hotpot emergency.

Acute massive gastric distension is a rare but potentially life-threatening surgical complication of bulimia nervosa. This results from repeated binge eating and is likely compounded by increased gastric compliance and delayed gastric emptying. We describe a case of acute massive gastric distension in a 26-year-old female with undiagnosed bulimia nervosa who underwent a laparotomy and anterior gastrotomy after failed conservative measures for gastric decompression. It highlights the importance of early recognition of a potentially life-threatening condition and that a multi-disciplinary approach is necessary to prevent the recurrence and morbidity associated with it.

A rare case of transient duodenal volvulus in an elderly patient.

Duodenal volvulus is an extremely rare condition, with few cases reported in the literature. We present the case of an 83-year-old man with spontaneous duodenal volvulus diagnosed on CT imaging. Findings included volvulus of the third part of the duodenum, the chjmirocteristic whirl pattern of the superior mesenteric vessels and medialisation of the gallbladder. He was treated with nasogastric tube decompression and follow-up CT demonstrated complete resolution of the volvulus.

Assessing the risk of viral infection from gases and plumes during intra-abdominal surgery: a systematic scoping review.

BACKGROUND: The aim of this study was to identify the current evidence regarding the risk of acquiring viral infections from gases or plumes during intra-abdominal surgery. Peritoneal fluids may contain cellular material and virus particles. Electrocautery smoke and plumes from energy devices may aerosolize harmful substances and viral particles. Insufflation and desufflation during laparoscopic surgery may also aerosolize and distribute biological material. A systematic scoping review was performed to assess the evidence and inform safe surgical practice. METHODS: A systematic search of the PubMed and Medline databases was undertaken until June 2020, observing Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology, to identify articles associating viral infection of operating room staff from surgical gases and plumes. All evidence levels were included. The search strategy utilized the search terms 'surgery', 'laparoscopy', 'laparoscopic' 'virus', 'smoke', 'risk', 'infection'. RESULTS: The literature search identified 74 articles. Eight articles relevant to the subject of this review were included in the analysis, two of which specifically related to intra-abdominal surgery. Of the remaining six, four involved gynaecological surgery and two were in-vitro studies. No evidence that intra-abdominal surgery was associated with an increased risk of acquiring viral infections from exsufflated gas or smoke plumes was identified. CONCLUSION: There is currently no evidence that respiratory viruses can be found in the peritoneal fluid. Whilst there is currently no evidence that desufflated carbon dioxide or surgical smoke plumes present a significant infectious risk, there is not a wealth of literature to inform current practice. Further clinical research in this area is required.

Robotic colorectal surgery in Australia: a cohort study examining clinical outcomes and cost.

Objective The aim of this study was to compare robotic versus laparoscopic colorectal operations for clinical outcomes, safety and cost. Methods A retrospective cohort study was performed of 213 elective colorectal operations (59 robotic, 154 laparoscopic), matched by surgeon and operation type. Results No differences in age, body mass index, median American Society of Anesthesiologists score or presence of cancer were observed between the laparoscopic or robotic surgery groups. However, patients undergoing robotic colorectal surgery were more frequently male (P = 0.004) with earlier T stage tumours (P = 0.02) if cancer present. Procedures took longer in cases of robotic surgery (302 vs 130 min; P < 0.001), and patients in this group were more frequently admitted to intensive care units (P < 0.001). Overall length of stay was longer (7 vs 5 days; P = 0.03) and consumable cost was A$2728 higher per patient in the robotic surgery group. Conclusion Robotic colorectal surgery appears to be safe compared with current laparoscopic techniques, albeit with longer procedure times and overall length of stay, more frequent intensive care admissions and higher consumables cost. What is known about the topic? Robotic surgery is an emerging alternative to traditional laparoscopic approaches in colorectal surgery. International trials suggest the two techniques are equivalent in safety. What does this paper add? This is an original cohort study examining clinical outcomes in Australian colorectal robotic surgery. The data suggest it may be safe, but this paper demonstrates key issues in the implementation and audit of novel surgical technologies in relatively low-volume centres. What are implications for practitioners? In our study, patients undergoing robotic colorectal surgery at a single centre in Australia had equivalent measured clinical outcomes to those undergoing laparoscopic surgery. However, practitioners may counsel patients that robotic procedures are typically longer and more expensive, with a longer overall hospital admission and a higher likelihood of intensive care admission.

Hepatic cystic echinococcosis in Australia: an update on diagnosis and management.

BACKGROUND: Echinococcosis is an uncommonly encountered zoonotic disease caused by the taeniid Echinococcus. The only endemic species in Australia, Echinococcus granulosus, forms cysts in the liver in 70% of cases. The aim of this study was to review the literature to provide an evidence-based narrative update on the diagnosis and management of hepatic cystic echinococcosis in Australia. METHODS: We reviewed the literature, utilizing multiple research databases and citation tracking. Original research and review articles examining the diagnosis and management of hydatid disease in adults, published prior to 2016 and in the English language were included in our review. RESULTS: Ultrasound is the gold-standard screening test, whilst computed tomography has a role in emergency presentations and screening for multi-organ involvement. Magnetic resonance imaging is the preferred second-line imaging and better demonstrates biliary involvement. Medical therapy or PAIR (percutaneous aspiration, irrigation with scolicide and re-aspiration) may be appropriate in selected cases; however, surgery remains the definitive treatment for active, large (>5 cm), symptomatic or complicated cysts. A variety of surgical techniques have been described, including conservative, radical and minimally invasive procedures. There is currently no consensus approach; surgical modality should be tailored to patient factors, relevant anatomy, local facilities and surgeons' expertise. CONCLUSION: Diagnosis and therapy in hepatic hydatid cysts have been significantly advanced by imaging, interventional radiology and surgical approaches in recent years. Surgery remains the mainstay of treatment for large, active, complicated or symptomatic hepatic hydatid cysts.

Antiviral innate immune response of RNA interference.

RNA interference (RNAi) is an ancient, natural process conserved among species from different kingdoms. RNAi is a transcriptional and post-transcriptional gene silencing mechanism in which, double-stranded RNA or hairpin RNA is cleaved by an RNase III-type enzyme called Dicer into small interfering RNA duplex. This subsequently directs sequence-specific, homology dependent, Watson-Crick base-pairing post-transcriptional gene silencing by binding to its complementary RNA and initiating its elimination through degradation or by persuading translational inhibition. In plants, worms, and insects, RNAi is the main and strong antiviral defense mechanism. It is clear that RNAi silencing, contributes in restriction of viral infection in vertebrates. In a short period, RNAi has progressed to become a significant experimental tool for the analysis of gene function and target validation in mammalian systems. In addition, RNA silencing has then been found to be involved in translational repression, transcriptional inhibition, and DNA degradation. RNAi machinery required for robust RNAi-mediated antiviral response are conserved throughout evolution in mammals and plays a crucial role in antiviral defense of invertebrates, but despite these important functions RNAi contribution to mammalian antiviral innate immune defense has been underestimated and disputed. In this article, we review the literature concerning the roles of RNAi as components of innate immune system in mammals and how, the RNAi is currently one of the most hopeful new advances toward disease therapy. This review highlights the potential of RNAi as a therapeutic strategy for viral infection and gene regulation to modulate host immune response to viral infection.

Immune response phenotype of allergic versus clinically tolerant pigs in a neonatal swine model of allergy.

The prevalence of childhood food allergy and the duration of these allergies, particularly those considered to be transient, like egg and milk allergy, are increasing. The identification of allergic individuals using minimally invasive, non-anaphylaxis-threatening methods is therefore of increasing importance. In this experiment, correlates were sought of an allergic immune response (IR) phenotype in pigs. Using pigs pre-treated with heat-killed bacteria or bacterial components before allergic sensitization with the egg white protein ovomucoid (Ovm), differences were determined in IR phenotype of pigs in the categories treated-allergic, treated-tolerant, control-allergic (CA) and control-tolerant. Phenotype was established by measuring immunoglobulin (Ig)-associated antibody activity (AbA), cytokine profiles and the proportion of blood T-regulatory cells (T-regs) and observing late-phase allergen-specific skin tests (ST). Although 100% of pigs became sensitized to Ovm, only 33% of pigs had clinical signs of allergy after oral challenge with egg white. Pigs without clinical signs were classified as clinically tolerant. Sixty-seven percent of allergic pigs had a positive, late-phase ST classified as very strong or strong, while 84% of clinically tolerant pigs did not have late-phase ST. Treated-allergic pigs and CA pigs had greater total antibody IgG (H+L), IgE and IgG1 AbA than clinically tolerant pigs. Cytokine profiles of allergic pigs and the proportion of circulating T-regs, did not differ significantly between allergic and clinically tolerant pigs. Therefore, measurement of allergen-specific IgG, IgG1 and/or IgE activity and evaluation of late-phase ID ST may be useful in identifying allergic IR phenotypes in swine models of food allergy, which may be extended toward human use.

Effect of heat-killed Escherichia coli, lipopolysaccharide, and muramyl dipeptide treatments on the immune response phenotype and allergy in neonatal pigs sensitized to the egg white protein ovomucoid.

Predisposition to food allergies may reflect a type 2 immune response (IR) bias in neonates due to the intrauterine environment required to maintain pregnancy. The hygiene hypothesis states that lack of early environmental stimulus leading to inappropriate development and bias in IR may also contribute. Here, the ability of heat-killed Escherichia coli, lipopolysaccharide (LPS), or muramyl dipeptide (MDP) to alter IR bias and subsequent allergic response in neonatal pigs was investigated. Three groups of three litters of pigs (12 pigs/litter) were given intramuscular injections of E. coli, LPS, MDP, or phosphate-buffered saline (PBS) (control) and subsequently sensitized to the egg white allergen ovomucoid using an established protocol. To evaluate change in IR bias, immunoglobulin isotype-associated antibody activity (AbA), concentrations of type 1 and 2 and proinflammatory cytokines released from mitogen-stimulated blood mononuclear cells, and the percentage of T-regulatory cells (T-regs) in blood were measured. Clinical signs of allergy were assessed after oral challenge with egg white. The greatest effect on IR bias was observed in MDP-treated pigs, which had a type 2-biased phenotype by isotype-specific AbA, cytokine production, and a low proportion of T-regs. LPS-treated pigs had decreased type 1- and type 2-associated AbA. E. coli-treated pigs displayed increased response to Ovm as AbA and had more balanced cytokine profiles, as well as the highest proportion of T-regs. Accordingly, pigs treated with MDP were more susceptible to allergy than PBS controls, while pigs treated with LPS were less susceptible. Treatment with E. coli did not significantly alter the frequency of clinical signs.

Practical immunoregulation: neonatal immune response variation and prophylaxis of experimental food allergy in pigs.

The importance of environment in immune response is identified and the increase in prevalence of allergic, autoimmune and chronic inflammatory diseases reviewed. In particular, altered opportunity to acquire evolutionarily anticipated commensal microbiota is associated through the "hygiene hypothesis" with defective developmental and response signals to the innate and adaptive immune systems. Evidence of the detrimental effects of such environments is reviewed as is evidence for remediation using controlled exposure to bacteria or their active components such as LPS or peptidoglycan ligands for TLR and NOD-like receptors. Occurrence of major environmentally associated changes in porcine immune response phenotype are described. The prophylactic effects of heat-killed Escherichia coli given intramuscularly or of oral Lactococcus lactis on experimental ovomucoid-induced allergy in piglets are described in the context of altered immune response bias favouring reduced type-2 phenotypes. The high frequency of clinical tolerance to developing allergic signs even in the face of classical sensitization indicates possible function in this pig model of regulatory effectors such as Treg cells.

Immunoglobulin isotypes of lactating Holstein cows classified as high, average, and low type-1 or -2 immune responders.

Infectious diseases are detrimental to the health and economy of the livestock industry. Observations of cattle resistant to natural infections have implied the feasibility of breeding livestock for disease resistance. Studies of pigs selected for antibody (AMIR)- and cell (CMIR)-mediated immune responses have demonstrated increased immune responsiveness suggesting enhanced protection by both type 2 and type 1 responses, respectively. Additionally, natural or artificial infections of cattle suggest that the production of particular immunoglobulin (Ig) M, IgG1 and IgG2 isotypes are important for protecting against pathogens. In fact, IgG1/IgG2 ratios are often used to establish whether type 1 (CMIR) or type 2 (AMIR) responses predominate following immunization or infection. The objectives of this study were therefore; (1) to evaluate the Ig isotype bias responses to Candida albicans and hen-egg white lysozyme (HEWL) in cows classified as high responders (HR), average responders (AR) or low responders (LR) based on AMIR or CMIR; (2) to determine if ranking based on IFN-γ (a type 1 cytokine) and DTH responses were analogous in terms of ranking; and (3) to estimate IFN-γ, Ig isotypes, and DTH correlations. Antibody responses to HEWL and DTH to C. albicans were detected such that cows were phenotypically classified as HR, AR and LR for AMIR or CMIR with significant differences (p ≤ 0.05) among classified groups. C. albicans-induced IFN-γ allowed classification of cows, some of which had the same ranking as that of DTH response. The lowest IgG1/IgG2 ratio was to the C. albicans purified antigen (candin), but no differences were observed in anti-HEWL or anti-candin IgG1/IgG2 ratios between classified groups. Anti-HEWL IgG1 and IgG2 responses at day 21 post-immunization were negatively and significantly correlated with DTH to candin at 24h. There were no significant correlations between anti-HEWL or anti-candin IgG1 or IgG2 responses with IFN-γ. Based on Ig isotype bias, IFN-γ and DTH responses, it was concluded that immunization with C. albicans can be used to classify CMIR responder cows based on DTH read-out.

Antibody and cell-mediated immune responses to Staphylococcus aureus small colony variants and their parental strains associated with bovine mastitis.

Persistence of bovine Staphylococcus aureus mastitis may be associated with the small colony variant (SCV) form that is adapted to intracellular life and resists elimination by the immune system. This study evaluated antibody-mediated (AMIR) and cell-mediated immune responses (CMIR) to two bovine SCV forms and their parent strains isolated from cows with mastitis. Four groups of healthy cows, five cows/treatment group, were challenged by the intramammary route with naturally occurring bovine SCV Heba3231, its parent strain 3231, a hemB mutant displaying the SCV phenotype or its parent strain, Newbould 305. Blood and milk samples were collected at day 0 before challenge and at days 1, 14, 21 and 36 post-challenge to determine antigen-specific immunoglobulin (Ig) IgG(1) and IgG(2) antibody responses as indicators of type 2 and type 1 responses, respectively. At day 24 post-challenge cows in each group were inoculated with the UV-killed homologous strain intradermally in the neck to induce delayed-type hypersensitivity (DTH) as an indicator of CMIR. The SCV Heba3231 and 3231 strains induced significant IgG(1) and IgG(2) antibody responses in sera and in sera and milk whey, respectively. The hemB SCV mutant and Newbould 305 strains induced significant IgG(1) antibody in milk whey, and in sera and milk whey, respectively. The SCV Heba3231 and 3231 strains induced DTH, the hemB mutant induced intermediate hypersensitivity, and Newbould 305 failed to induce DTH. These results indicate marked differences in immune responses induced by parent and SCV forms of the same strain of S. aureus and by the two wild-type strains. This is the first study to evaluate both AMIR and CMIR in the context of persistent bovine mastitis to different and genetically characterized strains of S. aureus including two SCVs. The findings expand our understanding of immune responses to persistent S. aureus mastitis.

Endogenous antiviral mechanisms of RNA interference: a comparative biology perspective.

RNA interference (RNAi) is a natural process that occurs in many organisms ranging from plants to mammals. In this process, double-stranded RNA or hairpin RNA is cleaved by a RNaseIII-type enzyme called Dicer into small interfering RNA duplex. This then directs sequence-specific, homology-dependent, posttranscriptional gene silencing by binding to its complementary RNA and triggering its elimination through degradation or by inducing translational inhibition. In plants, worms, and insects, RNAi is a strong antiviral defense mechanism. Although, at present, it is unclear whether RNA silencing naturally restricts viral infection in vertebrates, there are signs that this is certainly the case. In a relatively short period, RNAi has progressed to become an important experimental tool both in vitro and in vivo for the analysis of gene function and target validation in mammalian systems. In addition, RNA silencing has subsequently been found to be involved in translational repression, transcriptional inhibition, and DNA degradation. In this article we review the literature in this field, which may open doors to the many uses to which this important technology is being put, including the potential of RNAi as a therapeutic strategy for gene regulation to modulate host-pathogen interactions.

Porcine allergy and IgE.

Anaphylaxis was reported in 1963 in pigs experimentally sensitized with ovalbumin and was subsequently associated indirectly with IgE-related antibodies by functional assays to confirm heat-labile passive cutaneous anaphylaxis (PCA), reverse passive anaphylaxis (RPA) and Prausnitz-Küstner (PK) reactions to this and other allergens. The immunoglobulin mediating immediate hypersensitivity could be cross-adsorbed with anti-human IgE. Porcine IgE epsilon chain has been cloned and sequenced. Rabbit anti-pig IgE has been described by two groups, as has cross reactivity with pig IgE of various heterologous polyclonal and monoclonal anti-IgEs. Pigs develop transient post-weaning food allergy to soy allergens which can be prevented by pre-weaning feeding of soy proteins in sufficient quantity. Natural hypersensitivity also occurs to nematodes. Recently, experimental allergy has been induced in outbred pigs to peanut and to egg allergens which manifest as respiratory, cutaneous and enteric signs similar to those of human food allergy. These models are platforms for comparative allergy research as realistic alternatives to use of inbred mice or humans for investigation of pathogenesis, prophylaxis and therapy.

Attenuation of allergy to ovomucoid in pigs by neonatal treatment with heat-killed Escherichia coli or E. coli producing porcine IFN-gamma.

Food allergy is epidemic and prompts investigation to reduce allergic predisposition. It was hypothesized that heat-killed Escherichia coli injected intramuscularly (im) with or without interferon gamma (IFN-gamma), reduces neonatal susceptibility to experimental egg allergy. Two litters of Yorkshire pigs were assigned to three intramuscular treatment groups (four/group): control (PBS), heat-killed E. coli with or without IFN-gamma-expressing plasmid. Pigs were sensitized to ovomucoid (Ovm) by intraperitoneal injection with cholera toxin. To assess induction of allergy, pigs were fed egg white in yoghurt and assigned scores for allergic signs. Significantly fewer pigs developed allergy and passive cutaneous anaphylaxis in E. coli and E. coli+IFN-gamma vs control groups. E. coli-treated pigs also had significantly lower frequency of mean clinical scores. E. coli and E. coli+IFN-gamma groups did not differ. Serum antibody associated with IgG (H & L), IgG(1), IgG(2) or IgE all correlated but did not differ by treatment groups. Thus, treatment of neonatal pigs with heat-killed E. coli by im injection reduced susceptibility to allergic sensitization with Ovm. Inclusion of the type-1 cytokine, IFN-gamma, had no additional effect. Results indicate a method for prophylaxis of allergy and suggest support for the "hygiene hypothesis".

Steering orally induced deviation of xenogeneic immunity with exogenous cytokines in rats fed porcine proteins.

Immune response to xenoantigens is a barrier to xenotransplantation. The objective of this study was to determine if rat cell-mediated immunity (CMI) and antibody (Ab) to discordant porcine xenoantigens could be suppressed by oral administration of porcine protein with adjunct systemic cytokine therapy. Based on principles of oral tolerance, it was hypothesized that: a. Feeding proteins from porcine blood mononuclear cells (PBMC) would induce a type 2 response, inhibiting CMI and type 1 Ab (associated with xenograft rejection) but increasing the amount of type 2 Ab. b. IL-4, a type 2 cytokine would exaggerate type 2 bias, enhancing immune deviation. c. IFN-gamma, a type 1 cytokine was expected to down-regulate overall Ab production, but increase CMI and type 1 Ab. DA rats fed porcine proteins with or without subcutaneous and intraperitoneal injections of IFN-gamma or IL-4 received PBMC by subcutaneous injection. Dermal delayed-type hypersensitivity to PBMC was the indicator of CMI. The IgG Ab to porcine proteins was quantified and type 2 (IgG(1)+IgG(2a)) to type 1 (IgG(2b)) Ab ratios indicated IR bias. Unfed, PBMC-challenged controls had a type 1 response bias but feeding PBMC induced a type 2 bias that suppressed CMI and type 1 Ab and increased type 2 Ab but not total IgG Ab. Contrary to the T(H)1/T(H)2 paradigm, IL-4 decreased oral-induced type 2 IR deviation and did not provide significant benefits relative to feeding alone. Treatment with IFN-gamma prevented a switch to type 2 IR but feeding-induced suppression of CMI was not significantly compromised. The IFN-gamma potently suppressed Ab, including, surprisingly, type 1 IgG isotypes. Contrary to the hypothesis tested, feeding Ag in combination with systemic delivery of recombinant IFN-gamma apparently created an immunoregulatory environment most favorable to xenograft survival.