Similar success rate in proximal and distal colonic stent placement: a retrospective multi-center study.

OBJECTIVES: Stenting of malignant colon obstruction is used as a bridge to surgery or as an alternative to surgical colostomy in a palliative setting. Current guidelines recommend stent placement as the first line of treatment in colonic obstruction in both curative and palliative settings. However, it is unclear whether the location of the malignant obstruction influences the outcome of the stenting procedure. The goal of this study was to compare the outcomes of colonic stents between proximal and distal colonic strictures with regard to technical and clinical success and the risk of adverse events. METHODS: A multi-center retrospective cohort was composed of patients who underwent a colonic stent placement at two tertiary hospitals between 2013 and 2021. The technical and clinical outcome, stent type used, duration of post-procedural hospital stay and complications were noted. RESULTS: A total of 148 patients who underwent colonic stenting were identified. 41 patients underwent stent placement in the proximal colon and 107 patients underwent a distal stent placement. There was no difference in technical success (100% vs 96.3%, p = 0.209), clinical success (97.0% vs 89.6%, p = 0.199) or complications (24.4% vs 37.4%, p = 0,135). CONCLUSION: Technical success and clinical success rates are high and do not differ between stent locations. There is no significant difference in complication rates between proximal and distal colonic stents.

Pharmacokinetics of bromoform in dairy heifers.

AIMS: To determine the pharmacokinetics in dairy heifers after oral and IV administration of bromoform, a potential antimethanogenic agent found in red seaweed, Asparagopsis spp. METHODS: Twenty-four dairy heifers with a mean weight of 319 (SD 36.9) kg were used. The study was conducted in two phases, and each cohort of 12 heifers received an escalating dose of bromoform. In the first phase, 12 heifers successively received doses of 200, 400, 800, and 1600 mg of bromoform orally, separated by a 72-hour washout period. In the second phase, a different cohort of 12 dairy heifers was used. Each heifer received a total of four doses of bromoform separated by a wash-out period of 72 hours. Sequentially the treatments were (for each of the 12 heifers) an oral dose of 50 mg, followed by an IV dose of 50 mg, followed by an oral dose of 100 mg and finally an IV dose of 100 mg.Blood samples were assayed by gas chromatography-mass spectrophotometry for bromoform and dibromomethane to estimate the pharmacokinetic parameters using a non-compartmental analysis. RESULTS: Bromoform was rapidly absorbed as indicated by a short time to the maximum observed concentration of 15 minutes. For the routes of administration and dose ranges investigated, the mean terminal half-life ranged from 0.32 (SE 0.03) hours to 5.73 (SE 1.64) hours when administered orally or IV. With values for the mean area under the curve (AUC) to dose ratio ranging from 0.25 (SE 0.04) to 0.82 (SE 0.19) for oral and 1.39 (SE 0.39) to 4.02 (SE 0.37) for IV administration, bromoform appeared to exhibit non-proportional pharmacokinetic behaviour. The mean absolute bioavailability was 39.13 (SE 10.4)% and 3.36 (SE 0.83)% for 50-mg and 100-mg doses, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Bromoform is rapidly absorbed and exhibits dose dependent elimination kinetics.

A massive occult pericardial effusion in an athletic young male.

We present a case of a 27-year-old Royal Marine with a massive pericardial effusion, presenting with minimal clinical findings, suggesting that high levels of physical fitness may effectively mask the normal symptoms of this potentially life-threatening condition.

What can the Interventional Endoscopist Offer in the Management of Upper Gastrointestinal Malignancies?

The therapeutic possibilities of endoscopy have rapidly increased in the last decades and now allow organ-sparing treatment of early upper gastrointestinal malignancy as well as an increasing number of options for symptom palliation. This review contains an overview of the interventional endoscopic procedures in upper gastrointestinal malignancies. It describes endoscopic treatment of early oesophageal and gastric cancers, and the palliative options in managing dysphagia and gastric outlet obstruction. It also provides an overview of the therapeutic possibilities of biliary endoscopy, such as retrograde stenting and radiofrequency biliary ablation. Endoscopic ultrasound-guided therapeutic options are discussed, including biliary drainage, gastrojejunostomy and coeliac axis block. To aid in clinical decision making, the procedures are described in the context of their indication, efficacy, risks and limitations.

Probiotic therapy in couples with infertility: A systematic review.

The reproductive microbiome is becoming increasingly recognised for its influence on fertility. While there has been much work to investigate the treatment of bacterial vaginosis and disordered microbiomes in optimizing outcomes in Assisted Reproductive Technology (ART), the role of routinely prescribed probiotics is yet to be established. The therapeutic potential of probiotic therapy remains an exciting opportunity in ART and this review endeavours to summarise its evidence to date. A systematic review of MEDLINE (Pubmed), Allied Health Literature (CINAHL), EMBASE, Web of Science and the Cochrane database was performed on 7th May 2019, and repeated on 26th August 2019. The search was built using the terms 'subfertility;' 'probiotic therapy;' 'clinical pregnancy rate' and 'assisted reproductive outcomes.' The primary outcome was change in clinical pregnancy rate. Secondary outcomes included improvements in male and female fertility parameters and microbial assessment. The initial search found 882 articles, of which 26 full manuscripts were reviewed. Four articles were eligible for inclusion. Of the two studies that reported the primary outcome, only one study found probiotics increased the clinical pregnancy rate non-significantly (48.0%-58.8%, p = 0.47). It also found higher miscarriage rate (30 % vs 16.6 %, p = 0.47) in the group treated with probiotics. Both studies on males with oral probiotic found significantly improved sperm motility. While benefit in sperm motility has been observed with male probiotic therapy, there is conflicting evidence on the efficacy of probiotic therapy for women undergoing assisted reproduction. High quality randomized studies are needed to definitively examine probiotic therapy and establish its benefit for couples undergoing assisted reproduction.

The number of single nucleotide polymorphisms and on-farm data required for whole-herd parentage testing in dairy cattle herds.

New platforms utilizing single nucleotide polymorphisms (SNP) offer operational advantages over the conventional microsatellite-based ones, making them a promising alternative for parentage exclusion. Through simulation and empirical data, a 40-SNP panel (where the minor allele frequency was 0.35 on average) was shown to be a comparable or better diagnostic tool than the current 14-microsatellite panel that is used to parentage test New Zealand dairy animals. The 40 SNP alone did not have sufficient power of exclusion to match more than 75% of the progeny to the correct sire and dam. Utilizing mating records and grouping progeny and dams by birth and calving dates, respectively, decreased the number of sire-dam combinations that each progeny was tested against and dramatically increased the utility of the SNP. These results highlight the importance of combining genotypes with on-farm data to maximize the ability to assign parentage in the New Zealand dairy herd.

DNA fingerprints of rice (Oryza sativa) obtained from hypervariable chloroplast simple sequence repeats.

The aim of this research was to develop a convenient polymerase chain reaction-based assay that would allow intraspecific chloroplast variability to be detected. Our approach is based on the detection of length polymorphism within chloroplast mononucleotide microsatellite loci. Information from the fully sequenced rice chloroplast genome was used to identify 12 regions with a minimum of ten uninterrupted mononucleotide repeats. Primers flanking these repeats were used in conjunction with polymerase chain reaction to examine levels of polymorphism in six wild and 14 cultivated rice accessions. A total of six of the primer pairs revealed length polymorphism with between two and five size variants being detected. Diversity indices varied between 0.07 and 0.72. The length variation detected at multiple, physically linked sites was used to identify 15 unique haplotypes with an overall diversity index of 0.90. This level of polymorphism is sufficiently high to allow chloroplast variability to be studied at the intraspecific level. An additional 47 Oryza sativa accessions were also assayed with 31 unique chloroplast haplotypes being detected. The distribution of these haplotypes is described in relation to isozyme groupings and subspecies differentiation. The relevance and implications of these results for plant population genetics and the management of germplasm collections is discussed.

Depression of the cat cortical visual evoked potential by soman.

The effects of intravenous administration of the anticholinesterase agent soman (pinacolyl methylphosphonofluoridate, 3-15 micrograms/kg) on the visual evoked potential (VEP) were examined in cats using phase-reversed sine wave grating stimuli of different spatial frequencies and contrasts. Doses of 5-7 micrograms/kg caused a depression of the VEP across all spatial frequencies in an abrupt, non-graded fashion. Studies in which contrast was varied showed that VEP depression resulted primarily from a decrease in the system gain rather than a change in the contrast sensitivity, and that response depression increased with increasing contrast. The dominant changes in gain revealed by these studies are consistent with a modulation of potassium conductance in the cell membrane which previous studies have shown to be dependent on a cholinergic mechanism.

Pretreatment with physostigmine, mecamylamine and atropine reduces the impact of soman on the cortical visual evoked potential of the cat.

A pretreatment regimen of physostigmine, mecamylamine and atropine was evaluated for its ability to alleviate the impact of soman on visual system function as measured by changes in the cortical visual evoked potential (VEP) of the cat. Data from unprotected animals showed a threshold (30% depression in the VEP) of 6.4 micrograms/kg, while in pretreated animals, the threshold dose was 32.7 micrograms/kg, yielding a protection ratio of 5:1. Extending the time between pretreatment and exposure reduced the degree of protection. Pretreatment also reduced the degree of VEP depression at suprathreshold doses, indicating a therapeutic effect even in cases of severe exposure.

Systemic uptake of chromium in human volunteers following dermal contact with hexavalent chromium (22 mg/L).

This study examined the systemic uptake of chromium in four human volunteers following three hours of contact with water containing hexavalent chromium [Cr(VI)] at a concentration of 22 mg/L. Volunteers were immersed below the shoulders in water at 91 +/- 2.5 degrees F. On the day prior to the experiment and for five days afterwards, samples of urine, plasma, and red blood cells (RBCs) were collected and analyzed for total chromium. Red blood cell chromium concentrations were used as a specific biomarker for systemic uptake of Cr(VI). Although total chromium concentrations in RBCs and plasma increased relative to historical background concentrations on the day of exposure, no sustained elevation of chromium concentrations was observed in RBCs or plasma of the volunteers tested. Since absorption of chromium in the hexavalent state would result in the irreversible binding of Cr(VI) to hemoglobin within the RBC (manifested as a sustained elevation of total chromium concentrations in the RBC), the pattern of blood uptake and urinary excretion observed was consistent with uptake and distribution of chromium in the trivalent state. Small increases were observed in the concentration of total chromium in urine within 48 h of exposure, indicating that some trivalent chromium [Cr(III)] may have penetrated the skin at a rate of about 3.3 x 10(-5) to 4.1 x 10(-4) micrograms/ cm2-h. In short, the data indicated that a 3-h contact with Cr(VI) at concentrations in water plausible for environmental exposure (e.g., swimming) was not expected to result in systemic uptake of measurable amounts of Cr(VI), although a small quantity of Cr(VI) may have penetrated the skin where it was subsequently reduced to Cr(III) prior to systemic uptake.

A cross-cultural study of colour grouping: evidence for weak linguistic relativity.

We report a cross-cultural study of colour grouping carried out as a test of the Sapir-Whorf hypothesis (linguistic relativity theory). Speakers of English, Russian and Setswana-languages that differ in their number of basic colour terms, and in how the blue-green region is categorized--were compared on a colour sorting task. Informants sorted a representative set of 65 colours into groups so that members of the groups looked similar to each other, with no restriction on the number of groups formed. If linguistic relativity theory is true, then there should be reliable differences between the three samples in the composition of the groups they formed associated with the differing positions of colour category boundaries in the languages. The most striking feature of the results, inconsistent with linguistic relativity theory, was the similarity amongst the patterns of choice of the three samples. However, there were also significant differences amongst the samples. Setswana speakers (who have a single basic term for BLUE or GREEN) were more likely to group BLUE colours with GREEN colours than either English or Russian speakers. But Russian speakers (who have two basic colour terms for BLUE) were no more likely than English speakers to group light and dark BLUE separately. In addition there were general structural differences in grouping among the samples: they differed in the level of consensus in grouping, the number of groups formed and in the distribution of the number of colours placed in a group. These structural differences may reflect differences in the availability and salience of the colour categories across the languages. Our data support perceptual universalism modulated by weaker linguistic effects.

Optimising delivery of care in coeliac disease - comparison of the benefits of repeat biopsy and serological follow-up.

BACKGROUND: The majority of deleterious health consequences of coeliac disease (CD) are most likely to be secondary to intestinal inflammation; hence, mucosal recovery is a desirable goal of therapy. Follow-up in CD is controversial and serological response is often used as a surrogate for histological recovery. AIMS: To inform the clinical management of CD using comparative serological and histological data from a biopsy-driven pathway of care. METHODS: A retrospective analysis of the Cambridge Coeliac Clinic database of 595 patients routinely followed up by biopsy and serology. RESULTS: Paired biopsy results were available for 391 patients (15% seronegative). Persisting villous atrophy (VA) occurred in 182 patients (47%). The sensitivity of anti-tissue transglutaminase (TTG) antibody for ongoing VA was only 43.6%. Information on dietetic management and further biopsy to assess response was available for 94 initially unresponsive patients, in whom targeted dietetic intervention by removal of identified gluten sources or avoidance of trace amounts of gluten led to resolution of persistent VA in 50%. The effects of institution of a formal care pathway are analysed in 298 patients. Discharge to primary care and clinical management was facilitated by the information derived from repeat biopsy. CONCLUSIONS: Serology appears to be a poor surrogate marker for mucosal recovery on a gluten-free diet; dietary assessment fails to identify a potential gluten source in many patients with ongoing villous atrophy. The benefits of re-biopsy on diet include stratification of patients with coeliac disease suitable for early discharge from secondary care or those requiring more intensive clinical management.

Endoscopy and implantable electronic devices.

The increasing use of implantable electronic devices such as cardiac pacemakers and neurostimulators means that they are being increasingly encountered in endoscopy departments. The electromagnetic fields generated during electrosurgery and with magnetic imaging systems have the potential to interfere with such devices. The authors present a case that highlights some of the steps necessary for minimising risk, review the evidence and summarise the currently available guidance.

Sodium valproate in combination with ganciclovir induces lysis of EBV-infected lymphoma cells without impairing EBV-specific T-cell immunity.

Histone deacytelase inhibitiors (HDACi) represent a new class of anti-lymphoma therapeutics. Data in the clinical setting regarding on- and off-target effects of these agents are limited. Epstein-Barr virus (EBV)-positive lymphomas represent a highly defined system in which to make these observations. We present a case of a patient with multiple relapsed EBV-positive Diffuse Large B-cell Lymphoma that was chemo-refractory to anthracylcines, alkylating agents and rituximab. Treatment was commenced with the HDACi sodium valproate (VPA) in combination with the anti-viral nucleoside analogue ganciclovir (GCV). Therapy resulted in detectable cell-free unencapsulated circulating EBV-DNA providing supportive evidence for the first-time that lysis of virus infected lymphoma cells is induced using this therapeutic combination. EBV-specific CD8+ effector T-cell immunity was not impaired by VPA/GCV. Although GCV/VPA was insufficient to induce clinical remission, our data furthers the rationale that more potent HDAC inhibitors such as butyrate or gemcitabine together with GCV, perhaps in combination with chemotherapy, should be further investigated as therapy in relapsed/refractory EBV-positive lymphomas.

Pyoderma gangrenosum and myelodysplasia.

Pyoderma gangrenosum has been recognized occurring in association with acute and chronic leukaemia. More recently it has been described in patients with myelodysplasia (Jacobs, Palmer & Gordon-Smith 1985). We report a case of pyoderma gangrenosum in a patient with a preceding history of myelodysplasia, illustrating the problem of controlling the skin disease in this condition and the eventual transformation of the myelodysplasia into acute leukaemia. Treatment of the leukaemia resulted in improvement of the skin lesions.