Significant Pathological Lesions Research Articles

In vitro immunogenic profile of recombinant SARS-CoV2 S1-RBD peptide in murine macrophage and microglial cells.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants can infect common mice inducing significant pathological lung lesions and inflammatory responses. This substantially mimics coronavirus disease 19 (COVID-19) infection and pathogenesis in humans. To characterise the effects of recombinant SARS-CoV-2 S1 receptor-binding domain (RBD) peptide in murine macrophage and microglial cells' immune activation compared with classical PAMPs in vitro. Murine RAW 264.7 macrophages and BV2 microglial cells were exposed to increasing concentrations of the RBD peptide (0.01, 0.05, and 0.1 µg/mL), Lipopolysaccharide (LPS) and Poly(I:C) and evaluated after two and 24 h for significant markers of macrophage activation. We determined the effects of RBD peptide on cell viability, cleaved caspase 3 expressions, and nuclear morphometry analysis. In RAW cells, RBD peptide was cytotoxic, but not for BV2 cells. RAW cells presented increased arginase activity and IL-10 production; however, BV2 cells expressed iNOS and IL-6 after RBD peptide exposure. In addition, RAW cells increased cleaved-caspase-3, apoptosis, and mitotic catastrophe after RBD peptide stimulation but not BV2 cells. RBD peptide exposure has different effects depending on the cell line, exposure time, and concentration. This study brings new evidence about the immunogenic profile of RBD in macrophage and microglial cells, advancing the understanding of SARS-Cov2 immuno- and neuropathology.

Review of Chronic Ovoretention in Rattlesnakes (Crotalus and Sistrurus spp.) at a Single Zoological Institution

Chronic ovoretention, or egg binding, is a common cause of morbidity in captive female snakes. Both oviparous and viviparous species can be affected, but most literature is focused on management in oviparous species. The epidemiology and preferred treatment of chronic, unfertilized ovoretention in viviparous species, such as rattlesnakes, are not well described. This study reviewed the prevalence, morbidity, and mortality associated with ovoretention in Crotalus and Sistrurus rattlesnakes over 10 yr at a single institution. Period prevalence in mature female rattlesnakes (n = 63) was 15.9%. Ovoretention was the single most common clinical diagnosis for this cohort, comprising 32% of presentations (n = 25), and was the leading identified cause of death, with attribution in 20.8% of necropsies (n = 24). Data were abstracted from 10 cases, spanning eight crotalid species. Median age was 10 yr (range, 4–18 yr), and case fatality was 50%. Affected animals had variable parity and sperm exposure and presented with diverse clinical signs. Medical management alone was infrequently successful; most cases required procedural intervention. Salpingotomy had positive outcomes, including future reproductive success. Bacterial salpingitis, oophoritis, or both were detected in four cases. Serious comorbidities included uterine rupture, sepsis, and disseminated mycobacteriosis. Although prevalence of ovoretention in rattlesnakes likely varies across institutions, it can become a significant contributor to morbidity and mortality in rattlesnake collections. Cases may have a long subclinical period despite significant pathologic lesions, and conservative management may be unrewarding. A more proactive, evidence-based approach to ovoretention could potentially improve the survival, welfare, and fertility of female rattlesnakes in human care.

3,5-Dimethoxyphenol identification from urine by GC-MS after a lethal intoxication with Taxus baccata: A case report

Taxus baccata, also known as English or European yew, is an evergreen conifer shrub or tree that is traditionally used in ornamental landscaping, woodwork and pharmaceutical purposes. The toxic nature of the yew plant has been known for more than 2000 years. All parts of the plant, except for the red pulp of its berries, contain taxine alkaloids. Minimum lethal doses are reported in the range of 0.6-1.3 g of leaf/kg body weight, which means that for a 70-kg adult this vary between 42 and 91 g of yew leaf. Intoxication is known to be resistant to standard treatments with no effective antidote. The aim of this study was the confirmation of Taxus poisoning by 3,5-dimethoxyphenol determination. A case of an intentional fatal poisoning of a 39-year-old man is presented, hypothesized by the forensic autopsy and confirmed by application of gas chromatography-mass spectrometry. Postmortem urine sample was analysed, after liquid-liquid extraction with dichloromethane from acidic and basic environment. The autopsy has not revealed any significant traumatic injuries or specific pathological lesions. Suggestive content was found in the oral cavity, esophagus and stomach, containing partially digested food mixed with fragmented needle-shaped, green leaves. During toxicological analysis, 3,5-dimethoxyphenol (3,5-DMP), the aglycone of taxicatine metabolite, considered as a marker of Taxus poisoning, was identified in the urine using the NIST spectra library database. Taxine alkaloids are the active constituents of Taxus sp. that cause cardiotoxicity. This occurs via the dose-dependent blockade of sodium and calcium channels in cardiac myocytes, leading to atrioventricular block, evidenced by prolonged PR and QRS intervals on ECG. The clinical severity is dependent on quantity, type an route of exposure, clinical signs usually occur within 3-4 h after ingestion. Yew tree poisoning has a high mortality rate, but remains a rare occurrence, with only a few case reports in literature. Analysis of taxine alkaloids can be used to confirm the diagnosis.

Synergistic Effects of Probiotics and Autogenous Bacterin against Salmonella enterica Serovar Typhimurium Strain U288

Salmonellosis, a disease caused by pathogenic strains of Salmonella, has been reported to have an essential degree in morbidity and mortality of humans (especially farmers) and poultry resulting in low productivity. This study was undertaken to evaluate the synergistic effects of probiotics and autogenous bacterin against Salmonella enterica serovar Tyhimurium strain U288 isolated from different poultry feed collected from Orlu-west Local Government Area of Imo State. Different types of feed samples were aseptically collected and screened for the presence of Salmonella enterica serovar Typhimurium using standard microbiological techniques. The pathogenic potentials of the organism in broiler chicks were investigated by challenging the chicks orally using 0.5ml of the inoculum (108cells/ml).The protective effects of locally prepared autogenous bacterin (B), commercially prepared probiotics (P) and autogenous bacterin plus commercially prepared probiotics (BP) were investigated using in vivo technique. The study revealed significant (p<0.05) pathological features and lesions in the liver and spleen of the infected chicks. The mean plate counts were significantly (p<0.05) recorded more in the liver than spleen. The in vivo study showed that P, B and BP showed pronounced activity against the tested isolates of which BP proved to be more effective. Therefore the combination of autogenous bacterin and probiotics exhibited synergistic activity, and was effective in preventing infection caused by S. enterica serovar Tyhimurium U288.

Rate of Incidental Pathological Lesions ın Reduction Mammoplasty Specimens and Incidence of Invasive Breast Carcinoma Following Breast Reduction Operation.

Reduction mammoplasty (RM) is one of the most frequently performed surgical procedures. The incidental determination of significant pathologic lesions (SPL), that is precursor and malignant lesions, in RM specimens is rare. The aim of this study was to determine the frequency of SPL in RM specimens, to evaluate the relationship between SPL and clinicopathological factors, and to examine the incidence of invasive breast carcinoma forming in the remaining breast tissue during the postoperative follow-up period developing in patients after RM operation. This retrospective study included 874 females who underwent RM operation between January 2012 and January 2021. Demographic, clinicopathological findings, and preoperative radiological findings were recorded. The patients were followed up after the RM operation in respect of the first occurrence of breast cancer. Invasive carcinoma was determined in 0.2% and SPL in 3.5% in RM. The probability of SPL determination was greater in patients aged ≥ 40 years and with ≥ 4 paraffin blocks (p=0.038, p=0.01, respectively). No statistically significant difference was found between patients with and without SPL in respect of radiological findings (p=0.35). The mean postoperative follow-up period was 53.6 months, and invasive carcinoma was diagnosed during follow-up in 0.2% of all patients (6.9% of the patients with SPL). Age over 40 years and an increased number of sampled blocks were found to be factors increasing the possibility of the determination of precursor and malignant lesions in RM specimens. RM could decrease the risk of the development of breast cancer. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A high infectious simian adenovirus type 23 vector based vaccine efficiently protects common marmosets against Zika virus infection

Zika virus (ZIKV) has spread in many countries or territories causing severe neurologic complications with potential fatal outcomes. The small primate common marmosets are susceptible to ZIKV, mimicking key features of human infection. Here, a novel simian adenovirus type 23 vector-based vaccine expressing ZIKV pre-membrane-envelope proteins (Sad23L-prM-E) was produced in high infectious titer. Due to determination of immunogenicity in mice, a single-dose of 3×108 PFU Sad23L-prM-E vaccine was intramuscularly inoculated to marmosets. This vaccine raised antibody titers of 104.07 E-specific and 103.13 neutralizing antibody (NAb), as well as robust specific IFN-γ secreting T-cell response (1,219 SFCs/106 cells) to E peptides. The vaccinated marmosets, upon challenge with a high dose of ZIKV (105 PFU) six weeks post prime immunization, reduced viremia by more than 100 folds, and the low level of detectable viral RNA (<103 copies/ml) in blood, saliva, urine and feces was promptly eliminated when the secondary NAb (titer >103.66) and T-cell response (>726 SFCs/106 PBMCs) were acquired 1-2 weeks post exposure to ZIKV, while non-vaccinated control marmosets developed long-term high titer of ZIKV (105.73 copies/ml) (P<0.05). No significant pathological lesions were observed in marmoset tissues. Sad23L-prM-E vaccine was detectable in spleen, liver and PBMCs at least 4 months post challenge. In conclusion, a prime immunization with Sad23L-prM-E vaccine was able to protect marmosets against ZIKV infection when exposed to a high dose of ZIKV. This Sad23L-prM-E vaccine is a promising vaccine candidate for prevention of ZIKV infection in humans.

The Impact of SsPI-1 Deletion on Streptococcus suis Virulence.

(1) Background: Streptococcus suis is an important zoonotic pathogen that infects pigs and can occasionally cause life-threatening systemic infections in humans. Two large-scale outbreaks of streptococcal toxic shock-like syndrome in China suggest that the pathogenicity of S. suis has been changing in recent years. Genetic analysis revealed the presence of a chromosomal pathogenicity island (PAI) designated SsPI-1 in Chinese epidemic S. suis strains. The purpose of this study is to define the role of SsPI-1 in the virulence of S. suis. (2) Methods: A SsPI-1 deletion mutant was compared to the wild-type strain regarding the ability to attach to epithelial cells, to cause host disease and mortality, and to stimulate host immune response in experimental infection of piglets. (3) Results: Deletion of SsPI-1 significantly reduces adherence of S. suis to epithelial cells and abolishes the lethality of the wild-type strain in piglets. The SsPI-1 mutant causes no significant pathological lesions and exhibits an impaired ability to induce proinflammatory cytokine production. (4) Conclusions: Deletion of the SsPI-1 PAI attenuates the virulence of this pathogen. We conclude that SsPI-1 is a critical contributor to the evolution of virulence in epidemic S. suis.

Evaluation of antiviral activity of Bacillus licheniformis-fermented products against porcine epidemic diarrhea virus

Bacillus licheniformis (B. licheniformis) is commonly used as probiotic and its secondary metabolites are attractive anti-microbial candidate. In the present study, we aimed to evaluate the antiviral activity of crude extracts from B. licheniformis against porcine epidemic diarrhea virus (PEDV), a highly contagious enveloped porcine virus that has caused great economic loss in pigs. In vivo, PEDV-infected piglets supplemented with air-dried solid state fermentative cultivate containing B. licheniformis-fermented products (BLFP) showed milder clinical symptoms and decreased viral shedding. Importantly, no significant systemic pathological lesions and no reduction in average daily gain were noted in pigs supplemented with the BLFP, which suggests that it is safe for use in pigs. In vitro experiments revealed that while B. licheniformis crude extracts exhibited no toxicity in Vero cells, co-cultivation of B. licheniformis crude extracts with PEDV significantly reduced viral infection and replication. Summarized current results suggest that the B. licheniformis-fermented products could be a novel candidate food additive for reducing the impact of PED on the swine industry.

Sub-acute toxicological study of artemisinin-piperaquine tablets in rhesus monkeys

Artemisinin-piperaquine tablet (trade name Artequick, ATQ), is a novel combination therapy for the treatment of malaria and especially for resistant P.falciparum malaria. The aim of our study was to assess the potential sub-acute toxicity profile of ATQ by oral administration route in rhesus monkeys. Monkeys were administrated once daily with doses of ATQ (39.1, 78.2, 156.4 mg/kg) for 21 days and then followed-up a 56-day recovery period. The administration of ATQ at high dose produced significant changes in the clinical signs primarily involved in gastrointestinal and nervous systems. Body weight loss, significant decrease in food consumption and body temperature were observed in monkeys at high dose. Various hematological and biochemical parameters changes, and significant pathological lesions (adrenal gland, thymus and femur epiphyseal) were observed in the middle and high dose group at the end of the treatment period. However, the toxic effects of ATQ were reversed and delayed adverse drug reaction did not occur during the recovery period. Based on the results of this study, the no-observed-adverse-effect level for ATQ was considered to be 39.1 mg/kg in rhesus monkeys.

NDM-1-producing Escherichia coli isolated from pigs induces persistent infection with limited pathogenicity

NDM-1-producing Enterobacteriaceae are multidrug-resistant bacteria, also called superbacteria, that have become important global human health threats in recent years. However, data about NDM-1-producing bacteria in animals are rare. In this study, an NDM-1-producing Escherichia coli isolate (designated E120413) was obtained from pigs in Henan province, China in 2012. The susceptibility of E. coli E120413 to antimicrobial agents was determined using Kirby-Bauer disk diffusion and micro-dilution methods. Susceptibility tests indicated that E. coli E120413 was resistant to almost all common antibiotics with high MIC values obtained for most antibiotics tested. E. coli E120413 was detected in the heart, liver, spleen, lung, kidney, brain, stomach, duodenum, mesenteric lymph nodes, and fecal samples of piglets in both cohabitation and experimental groups and the bacteria persisted for more than 2 weeks. However, no obvious clinical symptoms or serious pathological lesions were observed. This is the first investigation of NDM-1-producing E. coli isolate from pigs in China. Although no significant pathological lesions were observed, NDM-1-producing E. coli was found to be highly transmissible and to cause persistent infection in pigs.

Histopathology of Surgically Resected Fallopian Tubes with Special Emphasis on Serous Tubal Intraepithelial Carcinoma

Background: The fallopian tube, though very common surgical specimen is rarely studied. It is affected by a spectrum of lesions ranging from inflammatory to rare neoplasms. Recent studies suggest a precursor lesion for high grade serous carcinoma of the ovary in the fallopian tube mucosa and is known as serous tubal intraepithelial carcinoma. In the present study, we analyzed the histopathology of fallopian tube lesions including serous tubal intraepithelial carcinoma. Methods: All the fallopian tube specimens received were grossed according to protocol and were routinely processed and stained. Atypical proliferative lesions of mucosa were subjected to immunohistochemical markers p53 and ki67. Result: Out of 350, 106 specimens showed a spectrum of lesions, of which hydrosalpinx was the commonest. Rest of the lesions were chronic and acute salpingitis, tuberculous salpingitis and tubal endometriosis. We encountered a single case of primary serous carcinoma of the fallopian tube. Immunohistochemistry on ten cases of atypical mucosal proliferations confirmed a single case each of serous tubal intraepithelial carcinoma and serous tubal intraepithelial lesion. Conclusion: Though fallopian tube is unremarkable in most cases, thorough sampling can detect significant pathological lesions including precursor lesions.

Comparison of Three Different Options for C7 Posterior Vertebral Anchor in the Indian Population-Lateral Mass, Pedicle, and Lamina: A Computed Tomography-Based Morphometric Analysis.

Study Design Radiological cohort study.PurposeThe options of posteriorly stabilizing C7 vertebra include using lateral mass, pedicle or lamina, as bony anchors. The current study is a computed tomography (CT)-based morphometric analysis of C7 vertebra of 100 Indian patients and discusses the feasibility of these different techniques.Overview of LiteratureC7 is a peculiar vertebra with unique anatomy, which poses challenges for each of these fixation modalities. There are no reports available in the literature, which discuss and compare the feasibility of diverse posterior C7 fixation techniques in Indian population.MethodsWe included 100 consecutive cervical spine CT scans of Indian patients performed between July 2016 and September 2016. We excluded CT scans with any significant congenital anomaly or other pathological lesions of C7 and patients with non-Indian ethnicity. Regarding screw placement, we assessed and studied various dimensions of the C7 lateral mass, pedicles, and laminae in relevant sections.ResultsThe mean age of our patients was 49.5±16.1 years. We included 56 male and 44 female patients. The mean anteroposterior and mediolateral dimensions of the lateral mass were 11.38±1.76 and 12.91±1.82 mm, respectively. The mean length of the lateral mass screw (Magerl technique) was 12.17±1.9 mm; 92% of patients could accommodate a lateral mass screw at least 10-mm long (unicortical), whereas 48% could accommodate a screw (unicortical) longer than 12 mm. Foramen transversarium was found in 30.5% of lateral masses. The mean outer and inner cortical widths of the pedicles were 6.5±0.71 mm and 3.72±0.61 mm, respectively. Approximately 58% of pedicles could accommodate 3.5-mm screws (based on the inner cortical pedicle width). The outer cortical and inner cortical widths of the laminae were 6.21±1.2 mm and 3.23±0.9 mm, respectively. Subsequently, 37% of the laminae could accommodate 3.5-mm screws. The mean angle of intralaminar screw trajectory was 50.7°±5.1°, and the mean length of the intralaminar screw was 32.6±3.05 mm. In addition, 96.4% and 60.7% of male patients could accommodate lateral mass screws longer than 10 mm and 12 mm, respectively. However, only 86.4% and 31.8% of female patients could accommodate 10- and 12-mm long lateral mass screws, respectively. Furthermore, 75% of male patients and 36% of female patients had pedicles that could accommodate 3.5-mm diameter screws, and 48.2% of male patients had laminae that could accommodate 3.5-mm screws; however, only 22.7% of female patients could accommodate 3.5-mm laminar screws.Conclusions Based on our CT-guided morphometric analysis, 92% and 48% of Indian patients could accommodate at least 10- and 12-mm long lateral mass screws, and 58% of pedicles and 37% of laminae could accommodate 3.5-mm screws. Thus, lateral mass screws (between 10- and 12-mm long) seem to be the safest feasible option for C7 fixation. In case of the need for an alternative mode of stabilization (pedicle or intralaminar screw), particularly in female patients, careful preoperative planning with a CT scan is of utmost importance.

Pathological and molecular studies of the renal trematode Paratanaisia bragai in Indian peafowls (Pavo cristatus).

Endoparasitic diseases are commonly encountered in free-ranging birds. Although not all endoparasites cause disease, persistent infection with large numbers of parasites almost always affects normal physiological functions, leading to deleterious effects on the host. This paper describes the anatomopathological alterations caused by the renal trematode Paratanaisia bragai in Indian peafowl (n = 3) and examines the phylogeny of these and related parasites. Peafowl from forests in and around the Bareilly region, Uttar Pradesh, India, were necropsied, and microscopic and molecular investigations were performed. The peafowl were confirmed to be infected with P. bragai. Significant gross pathological lesions suggested nephrosis, and microscopic findings indicated a mild-to-moderate degree of nephrosis caused by the parasites in the tissue. The parasites were identified as P. bragai by histomorphological analysis of adult and eggs in the ureters, and the identification was confirmed by PCR and phylogenetic analysis. Nucleotide sequencing of the PCR products from the renal trematodes recovered from Indian peafowl revealed a close association with P. bragai from Columbiformes in the United Kingdom and Spain. The pathology and molecular epidemiology of parasitic diseases affecting peafowl is not well understood in India. This is the first report from India and the second report worldwide to document P. bragai infection in peafowl.

Clinicopathological significance of atypical glandular cells on cervicovaginal Pap smears

To evaluate the histologic correlation and clinical significance of atypical glandular cells (AGC) detected on Pap tests. Pap tests interpreted as AGC were retrieved from an institutional cytopathology database. The AGC subcategories according to the Bethesda system 2001 include atypical glandular cells, not otherwise specified (AGC-NOS), atypical endometrial cells (AEM), and atypical endocervical cells (AEC). Clinicopathologic variables were collected from medical records retrospectively, and histologic follow-up diagnoses were correlated with AGC subcategories. From January 2009 to December 2014, 741 (0.17%) of 435778 cervical smears were interpreted as AGC. Of 713 cases included in the study analysis, the distribution of AGC subcategories was as follows: AGC 15.3%, AEM 59.6%, and AEC 25.1%. Of 508 cases with histologic follow-up results, 33.9% of cases were diagnosed to have clinically significant lesions, which include cervical squamous or glandular neoplasia (1.4% and 10.0%), endometrial neoplasia (21.5%), and other metastatic carcinoma (1.0%). Endometrial neoplasia was the most common significant pathology in women aged ≥40 years (28.4%), whereas cervical glandular neoplasia was the most commonly diagnosed lesion in women aged <40 years (14.5%, P < 0.001). When considering past histories which could affect the Pap results, IUD use (10.3%) and pregnancy (7.3%) were most frequently documented. Although IUD users showed low prevalence of significant pathology (2.6%), AGC cases related with pregnancy preceded significant pathologic lesions in 14.3%. The relatively high incidence of significant neoplasia linked to AGC emphasizes the importance of adherence to the AGC management guidelines which recommend early and intensive investigation using multiple testing modalities.

Alanine aminotransferase course, serum hepatitis B virus DNA, and liver stiffness measurement for therapeutic decisions in hepatitis B e antigen-negative chronic hepatitis B.

To evaluate the utility of the combination of alanine aminotransferase (ALT) course, hepatitis B virus (HBV) DNA level, and liver stiffness measurement (LSM) for determining significant liver disease in hepatitis B e antigen (HBeAg)-negative patients. Three hundred and ninety nine consecutive HBeAg-negative patients with HBV DNA >2000IU/mL and documented serial measurements of ALT were enrolled to undergo LSM followed by liver biopsy. Using ALT <40IU/L as a normal value, 142 patients had persistently normal ALT (PNALT), whereas 257 had persistently or intermittently elevated ALT (PIEALT) in the prior year. Among patients with HBV DNA of 2000-19999, 20000-199999, and ≥200000IU/mL, significant pathological lesions defined as the presence of moderate to severe necroinflammation and/or significant fibrosis by METAVIR scoring was present in 40%, 45%, and 71% of the PIEALT group, and 15%, 31%, and 36% of the PNALT group, respectively. In PNALT patients with HBV DNA <20000IU/mL, liver biopsy could be avoided in 88% when LSM <7 kPa is used as an indicator of non-significant liver histology but 12% of those who indeed had significant pathological lesions would be missed. In PIEALT patients with HBV DNA ≥20000IU/mL, the need for liver biopsy could be reduced by 53% with a false positive rate of 14% when LSM ≥7 kPa is used as a predictor of significant pathological lesions. The combination of serial ALT, viral load, and LSM appears to be a promising non-invasive tool. A management algorithm for HBeAg-negative patients comprising these non-invasive measures is proposed with liver biopsy being pursued in selected cases.

Gastrointestinal cryptosporidiosis in captive psittacine birds in the United States: a case review.

Histopathologic analysis performed on tissue samples from 34 captive psittacine birds over a 14-year period demonstrated gastrointestinal cryptosporidiosis. Although 8 birds had died unexpectedly, at least 10 showed gastrointestinal signs before death. Most birds had other significant pathologic lesions, unrelated to cryptosporidiosis, in which case Cryptosporidium was likely a secondary pathogen. However, in 11 birds the only significant histopathologic finding was gastrointestinal cryptosporidiosis. In 2 lovebird (Agapornis species) cases, direct sequencing of proventricular samples confirmed the presence of Cryptosporidium avian genotype III. A description and analysis of the pathologic findings in these 34 birds, as well as a review of avian gastrointestinal cryptosporidiosis, is provided.

Development of a tailored vaccine against challenge with very virulent infectious bursal disease virus of chickens using reverse genetics

Due to the problems associated with traditional methods for infectious bursal disease virus (IBDV) vaccine development and the pressure of evolution and variation of very virulent strains, it is urgent to develop IBDV vaccine rapidly with novel approaches. Using reverse genetics, the aim of this study was to generate a tailored vaccine strain (rGtHLJVP2) with its VP2 gene similar to very virulent IBDV (vvIBDV) to prevent the prevalence of IBDV. Characteristics of rGtHLJVP2 were evaluated in both cell culture and SPF chickens. rGtHLJVP2 replicated well as its parental strain Gt in vitro and in vivo. Immunization of SPF chickens with rGtHLJVP2 resulted in comparable antibody titers against IBDV as that of the medium virulent live vaccine B87, which was significant higher than that of attenuated vaccine Gt. Challenge studies with 104ELD50 of prevalent homogeneous or heterogenous vvIBDV revealed complete (100%) protection in the groups immunized with rGtHLJVP2. No significant clinical and pathological lesions were observed in chickens immunized with rGtHLJVP2. Our data demonstrated that rGtHLJVP2 could be used as a novel vaccine candidate for prevention against vvIBDV.

Unsedated transnasal esophagogastroduodenoscopy for the evaluation of dysphagia following treatment for previous primary head neck cancer

Dysphagia is not uncommon after curative treatment for primary head and neck cancer. Local recurrences or second primary cancers in the upper digestive tract need to be excluded firstly before treatment for dysphagia. However, many patients have trismus or pharyngeal stenosis following treatment, both of which prevent rigid/flexible transoral laryngoscopy/esophagoscopy evaluating the entire upper digestive tract. The purpose of this study was to prospectively investigate the diagnostic value of unsedated transnasal esophagogastroduodenoscopy (EGD) in 36 primary head and neck cancer patients with post-treatment dysphagia. Except three patients with very narrow space or the presence of the tumor in the neopharynx, transnasal EGD could completely evaluate the upper digestive tract in 33 patients and found one patient with local recurrent hypopharyngeal cancer, seven patients with newly diagnosed hypopharyngeal cancer, four patients with esophageal cancer, and one patient with simultaneous hypopharyngeal and esophageal cancers, which were all successfully biopsied and proven microscopically. Five patients previously receiving total laryngectomy had various degrees of stenosis of the neopharynx without local recurrence or esophageal cancer. Thirteen patients had no significant organic or pathological lesions. One patient had a benign tumor on the epiglottis and the other NPC patient had extensive soft tissue necrosis in the pyriform sinus as a cause of dysphagia. The mean duration of the entire procedure was 16min. All patients tolerated the procedure well. No significant complications were noted during and after examination. The present study indicates that unsedated transnasal EGD is feasible to confidently distinguish between functionally/anatomically-related dysphagia and newly growing tumors in the upper digestive tract, and to obtain biopsy specimens for pathological diagnosis from the tumors in a single session.

Clinicopathological study of experimentally induced canine monocytic ehrlichiosis

The aims of this study are to investigate the hematology, blood chemistry, pathological study, including macroscopic and microscopic lesions, of experimentally induced canine monocytic erhlichiosis in Thailand and to demonstrate the distribution of Ehrlichia canis in target organs by nested polymerase chain reaction (PCR). Five experimental healthy dogs were inoculated with 5 ml of whole blood (estimated number of E. canis morulae 15 × 10–5% per monocytes) from the splenectomized dog via the saphenous vein. Two healthy dogs served as a negative control. Hematology revealed nonregenerative normocytic normochromic anemia, thrombocytopenia and mild leukopenia. Blood chemistry revealed an increase in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (AP), hypoproteinemia, hypoalbuminemia, and hyperglobulinemia by day 66 post-inoculation. Pathology revealed anemia, ascites, jaundice, interstitial pneumonia, splenomegaly, generalized lymphadenopathy, and severe fatty liver. The detection of E. canis was performed using tissue embedded in paraffin wax by nested PCR showing positive in all target organs. This study concluded that acute induced experimental canine monocytic ehrlichiosis can cause significant clinical and pathological lesions.

Early Sirolimus Use With Cyclosporine Elimination Does Not Induce Progressive Proteinuria

Proteinuria has been reported in several papers after conversion from calcineurin inhibitors to Sirolimus (SRL), but this complication has not been analyzed in randomized clinical trials using de novo SRL. It is not known whether de novo use of SRL is a risk factor for proteinuria. We analyzed a series of patients included in a big multicenter randomized trial (RMR trial) corresponding to all patients in Spain and Portugal with respect to this issue. We retrospectively evaluated 24-hour proteinuria in all the patients during the study period (5 years postransplant) for comparison between treatment arms group A, continuous cyclosporine (CyA) + SRL and group B SRL with CyA elimination at 3 months postransplant. The elimination of CyA after the third month was not followed by significant changes in proteinuria. Nevertheless, during the last year of follow-up (between 48 and 60 months postransplant) an impressive increase in proteinuria was observed in group A. This surprising finding seemed to be a consequence of a protocol amendment that recommended CyA elimination in patients of group A, due to poorer results in the intermediate analysis of the trial. This fact suggests that the hemodynamic changes induced by elimination of the vasoconstrictor CyA might be responsible for the proteinuria but only in the long term probably when significant pathological lesions are already present. This finding argues for earlier conversion.