Transmission electron microscopy helpfulness in Whipple's disease masked by immunosuppressant therapy for arthritis

A 61‐year‐old woman received a diagnosis of undifferentiated non‐erosive arthritis in 2010 and assumed methotrexate and steroids in 2014. After 1 year, she experienced watery diarrhea, vomiting, fever, weight loss, and severe hypoalbuminemia, thus being admitted into our Unit. Esophagogastroduodenoscopy showed duodenal lymphangiectasia and duodenal biopsy samples several foamy PAS‐positive macrophages and villous subtotal atrophy. Transmission electron microscope demonstrated several extracellular and intracellular rod‐shaped bacteria (Tropheryma whipplei). Therefore, we diagnosed Whipple's disease. Our patient assumed doxycycline/hydroxychloroquine with prompt remission of gastrointestinal symptoms. At 1 year of follow‐up, she was symptom‐free, histological reassessment showed almost complete mucosal healing and transmission electron microscope demonstrated bacteria breaking/disappearance. The present report demonstrates that: (i) rheumatological manifestations are common onset symptoms of Whipple's disease; (ii) immunosuppressive therapy may delay the diagnosis and worsen clinical presentation; (iii) transmission electron microscopy for specific bacteria detection/disappearance is an helpful diagnostic tool, when available.     

Novel frontiers of agents for bowel cleansing for colonoscopy

The incidence of colorectal cancer (CRC) is characterized by rapid declines in the wake of widespread screening. Colonoscopy is the gold standard for CRC screening, but its accuracy is related to high quality of bowel preparation (BP). In this review, we aimed to summarized the current strategy to increase bowel cleansing before colonoscopy. Newly bowel cleansing agents were developed with the same efficacy of previous agent but requiring less amount of liquid to improve patients’ acceptability. The role of the diet before colonoscopy was also changed, as well the contribution of educational intervention and the use of adjunctive drugs to improve patients’ tolerance and/or quality of BP. The review also described BP in special situations, as lower gastrointestinal bleeding, elderly people, patients with chronic kidney disease, patients with inflammatory bowel disease, patients with congestive heart failure, inpatient, patient with previous bowel resection, pregnant/lactating patients. The review underlined the quality of BP should be described using a validate scale in colonoscopy report and it explored the available scales. Finally, the review explored the possible contribution of bowel cleansing in post-colonoscopy syndrome that can be related by a transient alteration of gut microbiota. Moreover, the study underlined several points needed to further investigations.     

Etanercept maintains the clinical benefit achieved by infliximab in patients with rheumatoid arthritis who discontinued infliximab because of side effects

OBJECTIVE: To evaluate the efficacy of switching to etanercept treatment in patients with rheumatoid arthritis who already responded to infliximab, but presented side effects. METHODS: Charts of 553 patients with rheumatoid arthritis were retrospectively reviewed to select patients who responded to the treatment with infliximab and switched to etanercept because of occurrence of adverse effects. Clinical data were gathered during 24 weeks of etanercept treatment and for the same period of infliximab treatment before infliximab was stopped. Disease Activity Score computed on 44 joints (DAS-44), erythrocyte sedimentation rate (ESR) 1st hour, Visual Analogue Scale (VAS) of pain, Health Assessment Questionnaire (HAQ), and C reactive protein (CRP) were assessed every 8 weeks. RESULTS: 37 patients were analysed. Adverse events to infliximab were mostly infusion reactions. No statistically significant difference between infliximab, before withdrawal, and etanercept, after 24 weeks, was detected in terms of DAS-44 (2.7 and 1.9, respectively), HAQ (0.75 and 0.75, respectively), ESR (21 and 14, respectively) and CRP (0.5 and 0.3, respectively). VAS pain decreased significantly after switching to etanercept treatment (40 and 24, respectively; p<0.05). CONCLUSIONS: Our study shows that etanercept maintains the clinical benefit achieved by infliximab, and suggests that a second tumour necrosis factor (TNF) alpha inhibitor can be the favourable treatment for rheumatoid arthritis when the first TNFalpha blocker has been withdrawn because of adverse events.     

Estradiol reduces cytochrome c translocation and minimizes hippocampal damage caused by transient global ischemia in rat

It is well-established that 17beta-estradiol (17beta-E(2)) confers neuroprotection to male and female rats exposed to focal cerebral ischemia, while less is known about the effects of the hormone under conditions of transient global ischemia. Since translocation of cytochrome c from the mitochondria to the cytosol is a critical step in apoptotic cell death after cerebral ischemia, we have investigated whether 17beta-E(2) interferes with such mechanism to exert neuroprotection. Global ischemia, induced in male Wistar rats by 5-min 4 vessel occlusion (4VO), resulted in a significant increase of cytosolic cytochrome c (cyt-c) levels as detected by Western blotting at 6h after reperfusion. 17beta-E(2) (0.2mg/kg, i.p.) given 1h before ischemia minimized cytochrome c translocation and the latter effect was partially reversed by tamoxifen (0.25mg/kg, i.p.). Bilateral cell counting revealed that delayed hippocampal damage typically caused by 4VO was abolished by 17beta-E(2) and this was partially reversed by tamoxifen in the CA3 subregion, but not in CA1/CA2 or CA4. These findings provide the original observation that 17beta-E(2) reduces delayed hippocampal damage caused by 4VO in male rats and blocks cytochrome c translocation during the early stages of neuronal death, thus providing an important mechanism involved in estrogen-mediated neuroprotection.     

Comprehensive mutation analysis (20 families) of the choroideremia gene reveals a missense variant that prevents the binding of REP1 with Rab geranylgeranyl transferase

Choroideremia (CHM), an X-linked degeneration of the retinal pigmented epithelium (RPE), photoreceptors, and choroid, ultimately leads to blindness. It is caused by loss-of-function of the CHM gene product, the Rab escort protein 1 (REP1) that is involved, together with its homologue REP2, in prenylation of Rab GTPases, key regulators of intracellular vesicular traffic. Here, we report the molecular characterization of 20 unrelated Italian families affected by CHM. We identified 19 different mutations, nine of which are new. In most cases, we analyzed the effect of the mutations at the mRNA level. Furthermore, we demonstrated, by in vitro trancription/translation assays, that the mutated mRNAs produced truncated proteins in all cases but one. In fact, we also identified a novel REP1 missense variant (c.1520A>G; p.H507R) associated to CHM. Thus far, only two other CHM-associated missense mutations have been identified, one of which was a splicing alteration. We investigated the impact of the p.H507R amino acid change on REP1 structure and function, thus providing the first experimental demonstration that correlates a missense mutation in CHM with a functional impairment of REP1. Overall, our results indicate that the REP1-Rab geranyl-geranyl transferase interaction and consequently REP1-mediated Rab prenylation is essential for RPE and photoreceptor function.     

A microsphere-based assay for multiplexed single nucleotide polymorphism analysis using single base chain extension

A rapid, high throughput readout for single-nucleotide polymorphism (SNP) analysis was developed employing single base chain extension and cytometric analysis of an array of fluorescent microspheres. An array of fluorescent microspheres was coupled with uniquely identifying sequences, termed complementary ZipCodes (cZipCodes), which allowed for multiplexing possibilities. For a given assay, querying a polymorphic base involved extending an oligonucleotide containing both a ZipCode and a SNP-specific sequence with a DNA polymerase and a pair of fluoresceinated dideoxynucleotides. To capture the reaction products for analysis, the ZipCode portion of the oligonucleotide was hybridized with its cZipCodes on the microsphere. Flow cytometry was used for microsphere decoding and SNP typing by detecting the fluorescein label captured on the microspheres. In addition to multiplexing capability, the ZipCode system allows multiple sets of SNPs to be analyzed by a limited set of cZipCode-attached microspheres. A standard set of non-cross reactive ZipCodes was established experimentally and the accuracy of the system was validated by comparison with genotypes determined by other technologies. From a total of 58 SNPs, 55 SNPs were successfully analyzed in the first pass using this assay format and all 181 genotypes across the 55 SNPs were correct. These data demonstrate that the microsphere-based single base chain extension (SBCE) method is a sensitive and reliable assay. It can be readily adapted to an automated, high-throughput genotyping system. [Primer sequences used in this study are available as online supplementary materials at www.genome.org.]     

Shockwave intravascular lithotripsy in the treatment of under‐expanded coronary stent: Case Series

Under‐expanded coronary stent related to inadequate preparation of calcified lesion is associated with poor clinical outcomes.Off‐label use of S‐IVL to correct this clinical issue is effective and safe, probably more than other current techniques. However, this statement needs further evidence.     

Identification of human t cell leukemia/lymphoma virus type i antibodies,dna, and protein in patients with polymyositis

Objective. To investigate a possible association between human T cell leukemia/lymphoma virus type I (HTLV-I) and polymyositis (PM). Methods. Sera and muscle biopsy samples from 9 Jamaican PM patients were compared with specimens from American HTLV-I–positive PM patients and normal controls. Sera were evaluated for HTLV antibodies by enzyme-linked immunosorbent assay and Western blot. The biopsy samples were analyzed for HTLV-I/II DNA by polymerase chain reaction and were also immunohistochemically stained for HTLV gp46 envelope protein. Results. Seven of the 8 Jamaican PM patients from whom sera were available were HTLV-I seropositive. The muscle biopsies of all 9 Jamaican patients demonstrated severe lymphocytic infiltration, cellular degeneration, myofiber atrophy, and fibrosis. Each muscle biopsy specimen contained HTLV-I DNA. Two of 6 samples demonstrated intense staining for HTLV-I gp46 in many of the invading mononuclear cells and weak staining for HTLV-I gp46 in many of the invading mononuclear cells and weak staining in the adjacent myocytes. Two other specimens were weakly positive for gp46 in rare mononuclear cells. All control specimens were negative for the presence of HTLV-I DNA and protein. Conclusion. HTLV-I is associated with an inflammatory muscle disease characterized by direct invasion of the affected muscle by HTLV-I–infected mononuclear cells.