Endodontic Treatment Outcome of 45 Incisor Teeth in Dogs Determined by Intraoral Radiography.

A retrospective study was conducted to determine the outcome of endodontic treatment of incisor teeth in dogs. Medical and dental records from four private veterinary specialty practices over an 8-year period (2013-2021) were reviewed. Forty-five incisor teeth from 41 dogs with ages from 1 to 11-years-old were included in the study. The indications for endodontic treatment were complicated crown fracture in 23 incisors (51.1%), non-vital tooth in 15 incisors (33.3%) and complicated crown-root fracture in seven incisors (15.5%). Evaluation criteria included availability of complete medical and dental records, patient demographics, and at least one follow-up visit as recent as 6 months after the initial root canal therapy. Endodontic treatment outcome was defined as successful, no evidence of failure, or failure. Root canal therapy was successful in 42 teeth (93.3%), no evidence of failure was found in three teeth (6.6%), and none of the cases showed failure of the treatment. Duration of follow-up ranged from 6 to 64 months. Only three variables appeared to have statistical significance: presence of preoperative periapical lucency (PAL) (P = .01), postoperative PAL (P < .001) and postoperative external inflammatory root resorption (P = .014). Based on this study, following "loose criteria" (success and no evidence of failure combined), 100% of the treatments were successful, making this option an excellent therapy choice in a veterinary specialty dentistry practice.

Resilience of Neural Cellularity to the Influence of Low Educational Level.

BACKGROUND: Education is believed to contribute positively to brain structure and function, as well as to cognitive reserve. One of the brain regions most impacted by education is the medial temporal lobe (MTL), a region that houses the hippocampus, which has an important role in learning processes and in consolidation of memories, and is also known to undergo neurogenesis in adulthood. We aimed to investigate the influence of education on the absolute cell numbers of the MTL (comprised by the hippocampal formation, amygdala, and parahippocampal gyrus) of men without cognitive impairment. METHODS: The Isotropic Fractionator technique was used to allow the anisotropic brain tissue to be transformed into an isotropic suspension of nuclei, and therefore assess the absolute cell composition of the MTL. We dissected twenty-six brains from men aged 47 to 64 years, with either low or high education. RESULTS: A significant difference between groups was observed in brain mass, but not in MTL mass. No significant difference was found between groups in the number of total cells, number of neurons, and number of non-neuronal cells. Regression analysis showed that the total number of cells, number of neurons, and number of non-neuronal cells in MTL were not affected by education. CONCLUSIONS: The results indicate a resilience of the absolute cellular composition of the MTL of typical men to low schooling, suggesting that the cellularity of brain regions is not affected by formal education.

Maximizing response to intratumoral immunotherapy in mice by tuning local retention.

Direct injection of therapies into tumors has emerged as an administration route capable of achieving high local drug exposure and strong anti-tumor response. A diverse array of immune agonists ranging in size and target are under development as local immunotherapies. However, due to the relatively recent adoption of intratumoral administration, the pharmacokinetics of locally-injected biologics remains poorly defined, limiting rational design of tumor-localized immunotherapies. Here we define a pharmacokinetic framework for biologics injected intratumorally that can predict tumor exposure and effectiveness. We find empirically and computationally that extending the tumor exposure of locally-injected interleukin-2 by increasing molecular size and/or improving matrix-targeting affinity improves therapeutic efficacy in mice. By tracking the distribution of intratumorally-injected proteins using positron emission tomography, we observe size-dependent enhancement in tumor exposure occurs by slowing the rate of diffusive escape from the tumor and by increasing partitioning to an apparent viscous region of the tumor. In elucidating how molecular weight and matrix binding interplay to determine tumor exposure, our model can aid in the design of intratumoral therapies to exert maximal therapeutic effect.

Anchoring of intratumorally administered cytokines to collagen safely potentiates systemic cancer immunotherapy.

The clinical application of cytokine therapies for cancer treatment remains limited due to severe adverse reactions and insufficient therapeutic effects. Although cytokine localization by intratumoral administration could address both issues, the rapid escape of soluble cytokines from the tumor invariably subverts this effort. We find that intratumoral administration of a cytokine fused to the collagen-binding protein lumican prolongs local retention and markedly reduces systemic exposure. Combining local administration of lumican-cytokine fusions with systemic immunotherapies (tumor-targeting antibody, checkpoint blockade, cancer vaccine, or T cell therapy) improves efficacy without exacerbating toxicity in syngeneic tumor models and the BrafV600E /Ptenfl/fl genetically engineered melanoma model. Curative abscopal effects on noncytokine-injected tumors were also observed as a result of a protective and systemic CD8+ T cell response primed by local therapy. Cytokine collagen-anchoring constitutes a facile, tumor-agnostic strategy to safely potentiate otherwise marginally effective systemic immunotherapies.

Immune and haematological parameters of Blackbelly ewes infected with gastrointestinal nematodes / Parámetros inmunológicos y hematológicos en ovejas Blackbelly infectadas con nematodos gastrointestinales / Parâmetros imunes e hematológicos de ovelhas Blackbelly infectadas por nematoides gastrintestinais

Abstract Background: It is necessary to identify phenotypic traits related to natural resistance against gastrointestinal nematodes (GIN) in order to know the host immunity status in productive ewes. Objetive: To determine haematological and immunological parameters (IgA and IgG) during pregnancy and lactation in Blackbelly ewes naturally infected with GIN Methods: The number of eggs per gram (EPG), packed cell volume (% PCV), plasmatic protein (PP), and peripheral eosinophils were determined during eight months. In addition, sera and saliva samples were collected to establish IgG and IgA kinetics by indirect enzyme-linked immunosorbent assay (ELISA). Results: The results showed 2,592 ± 2,403 EPG and 22.2 ± 4.0% PCV during lactation and 595 ± 901 EPG and 25.1 ± 2.5% PCV during pregnancy. A higher percentage of Trichostrongylus colubriformis larvae were observed in pregnancy (84 to100%) than in lactation (36 to 44%). The IgA activity in serum samples showed a marked reduction (from 80 to 10%) during lambing for both Haemonchus contortus and T. colubriformis antigens. In saliva samples, IgA activity with regard to the standard decreased from 56% at 60 days to 30% at 45 days before lambing and remained low for 45 days during lactation (23 to 32% activity). The eosinophils numbers were 2.0 x 109 cells L-1 in pregnancy and remained low at 0.7 x 109 cells L-1 in lactation. Conclusion: The studied variables reflect the breakdown of immunity against GIN in Blackbelly ewes before and after lambing.

Resumen Antecedentes: La identificación del fenotipo relacionado con la resistencia contra nematodos gastrointestinales (GIN) es necesaria para conocer la inmunidad del huésped en ovejas en producción. Objetivo: Determinar los parámetros hematológicos e inmunológicos (IgA e IgG) en gestación y lactancia en ovejas Blackbelly infectadas naturalmente con GIN. Métodos: Se determinó el número de huevos por gramo de heces (EPG), se identificaron las larvas y se registró el porcentaje del volumen celular aglomerado (% PCV), proteína plasmática (PP) y eosinófilos periféricos durante ocho meses. Además, se colectó suero y saliva para determinar la cinética de IgG e IgA por medio de un ensayo inmuno-enzimático (ELISA) indirecto. Resultados: Los resultados mostraron 2.592 ± 2.403 EPG y 22,2 ± 4,0% PCV durante la lactancia y 595 ± 901 EPG y 25,1 ± 2,5% PCV durante la gestación. Se observó un mayor porcentaje de larvas de Trichostrongylus colubriformis en gestación (84 a 100%) que en lactancia (36 a 44%). La actividad de la IgA en las muestras de suero mostró una marcada reducción después del parto para ambos antígenos de Haemonchus contortus y T. colubriformis (80 a 10%). En saliva, la actividad de la IgA disminuyó de 56 a 30% del día 60 al 45 antes del parto y se mantuvo baja en los primeros 45 días de la lactancia (actividad de 23 a 32%). El número de eosinófilos fue de 2,0 x 109 células L-1 durante la gestación, y se redujo a 0,7 x 109 células L-1 en la lactancia. Conclusión: Las variables estudiadas reflejan la ruptura de la inmunidad contra GIN en ovejas Blackbelly antes y después del parto.

Resumo Antecedentes: A identificação de traços fenotípicos relacionados à resistência natural contra nematóides gastrintestinais (GIN) é necessária para saber a imunidade do hospedeiro em ovelhas produtivas. Objetivo: Determinar parâmetros hematológicos e imunológicos (IgA e IgG) em períodos de gestação e lactação em ovelhas Blackbelly naturalmente infectados com GIN. Métodos: O número de ovos por grama (EPG), volume empacotado de células (% PCV), proteína plasmática (PP) e eosinófilos periféricos foram determinados durante oito meses. Além disso, as amostras de soro e saliva foram recolhidas para determinar a cinética de IgG e IgA por ELISA indireto. Resultados: Os resultados mostraram 2.592 ± 2.403 EPG e 22,2 ± 4,0% PCV durante a lactação e 595 ± 901 EPG e 25,1 ± 2,5% PCV durante a gravidez. A percentagem mais elevada de larvas de Trichostrongylus colubriformis foi observada na gravidez (84 a 100%) do que na lactação (36 a 44%). A atividade de IgA em amostras de soro mostrou uma redução acentuada (80 a 10%) durante o parto nos antígenos de Haemonchus contortus e T. colubriformis. Em amostras de saliva, a atividade de IgA diminuiu de 56 a 30% do dia 60 ao 45 antes do parto e permaneceu baixa por 45 dias durante a lactação (atividade de 23 a 32%). O número de eosinófilos foi de 2,0 x 109 células L-1 na gravidez e manteve-se baixo, com 0,7 x 109 células L-1 na lactação. Conclusaõ: As variáveis estudadas refletem a quebra da imunidade contra GIN em ovelhas Blackbelly antes e depois do parto.

Thrombocytosis in children.

In healthy pediatric subjects normal count platelet ranges between 250,000 µL and 450,000 µL. An elevated platelet count greater than 2 SD defines a condition of thrombocytosis. On a clinical level, thrombocytosis is classified "mild" at a platelet count between >500,000 µL and <700,000 µL; "moderate" at a platelet count between >700,000/µL and <900,000/µL; "severe" at a platelet count >900,000/µL; and "extreme" at a platelet count >1,000,000/µL. Thrombocytosis can be classified as primary or secondary. Primary thrombocytosis is divided into familial and essential. Primary thrombocytosis is an extremely rare clonal disease in childhood with incidence of one per million children, i.e., 60 times lower than in adults. It is classified as a myeloproliferative disorder with polycythemia vera, chronic myeloid leukaemia and myelofibrosis and may be associated with thrombotic or haemorrhagic events. Platelet count is generally above 1,000,000/µL. The median age at diagnosis is about 11 years. On the contrary, secondary or reactive thrombocytosis (RT) is very common in pediatric age, occurring in 3-13% of hospitalized children because of several causes. Generally, it is a reactive process caused by infection, chronic inflammation, iron deficiency, tissue damage, cancer, drugs and surgical or functional splenectomy. Thrombocytosis is mild in 72-86% of children, moderate in about 6-8%, and extreme in 0.5-3%. Consultation with a pediatric hematologist is required if elevation of platelet count persists, is unexplained or symptomatic. In the majority of cases no treatment is necessary, and the patient must be only closely monitored.

Inhibition of Toxoplasma gondii growth by pyrrolidine dithiocarbamate is cell cycle specific and leads to population synchronization.

Successful completion of the Toxoplasma cell cycle requires the coordination of a series of complex and ordered processes that results in the formation of two daughters by internal budding. Although we now understand the order and timing of intracellular events associated with the parasite cell cycle, the molecular details of the checkpoints that regulate each step in Toxoplasma gondii division is still uncertain. In other eukaryotic cells, the use of cytostatic inhibitors that are able to arrest replication at natural checkpoints have been exploited to induce synchronization of population growth. Herein, we describe a novel method to synchronize T. gondii tachyzoites based on the reversible growth inhibition by the drug and pyrrolidine dithiocarbamate. This method is an improvement over other strategies developed for this parasites as no prior genetic manipulation of the parasite was required. RH tachyzoites blocked by pyrrolidine dithiocarbamate exhibited a near uniform haploid DNA content and single centrosome indicating that this compound arrests parasites in the G1 phase of the tachyzoite cell cycle with a minor block in late cytokinesis. Thus, these studies support the existence of a natural checkpoint that regulates passage through the G1 period of the cell cycle. Populations released from pyrrolidine dithiocarbamate inhibition completed progression through G1 and entered S phase approximately 2 h post-drug release. The transit of drug-synchronized populations through S phase and mitosis followed a similar timeframe to previous studies of the tachyzoite cell cycle. Tachyzoites treated with pyrrolidine dithiocarbamate were fully viable and completed two identical division cycles post-drug release demonstrating that this is a robust method for synchronizing population growth in Toxoplasma.

Management and outcomes of hepatic cirrhosis: Findings from the RING study.

BACKGROUND/AIM: Hepatic cirrhosis is a frequent reason for ordinary hospital admission (OA). The RING study collected hospital discharge files (HDF) from Italian hospital gastroenterology units (IGU). This caselist provides a broad picture of the patients admitted for this pathology. MATERIAL/METHODS: More than 50,000 HDF for OA were collected between 2001 and 2004 from 26 IGU. RESULTS: Eight thousand four hundred and eighty-seven HDF (16%) had a diagnosis of hepatic cirrhosis; Child-Pugh classes were 20.2% A, 34.8% B and 45.0% C. Patients' mean age was 63.7+/-12.1 years and 62.5% were male. A 61.1% of the cirrhosis cases had ascites, 29.9% portal-systemic encephalopathy, 29.2% hepatocellular carcinoma (HCC), 10% bleeding varices, 3.0% hepatorenal syndrome (HRS). Mortality for OA for cirrhosis was 5.7% versus 2.6% for other diagnoses. The proportion varied with the severity of the cirrhosis: 0% for Child A, 1.1% B, 10.5% C. Mortality was significantly associated with: Child-Pugh at admission (odds ratio: OR 9.2), HRS (OR 11.7), bleeding varices (OR 2.2), HCC (OR 1.8). CONCLUSIONS: Hepatic cirrhosis was found in 16% of the OA to IGU and mortality was double the rate for all the other pathologies in the same wards. Child-Pugh is a useful prognostic tool, higher classes implying a greater risk of death. HRS and bleeding varices were the complications with most influence on in-hospital mortality.

Combined endoscopic treatment for cholelithiasis associated with choledocholithiasis.

BACKGROUND: The advent of endoscopic techniques changed surgery in many ways. For the management of cholelithiasis, laparoscopic cholecystectomy (LC) is the treatment of choice. This has created a dilemma in the management of choledocholithiasis. Today a number of option exist, including endoscopic sphinterotomy (ES) before LC in patients with suspected common bile duct (CBD) stones, laparoscopic bile duct exploration, open CBD exploration, and postoperative endoscopic retrograde cholangiopancreatography (ERCP). Also, the alternative technique of peroperative ES is emerging. METHODS: We report our experience of routine intraoperative cholangiography followed either by peroperative ERCP in one step or by transcystic drain and postoperative ERCP. In our technique, to facilitate Vater papilla cannulation we inserted a 450-cm transcystic guidewire that was caught by a duodenoscope. Papillotome was then inserted over the guidewire to ensure cannulation of the CBD. RESULTS: Twenty-eight patients were treated successfully in one step and 24 in two steps. The mean operative time was 181 +/- 41 min for patients treated in one step and 131 +/- 30 min for patients treated in two steps. The mean hospital stay was 4.8 +/- 3.3 days for patients treated in one step and 9.6 +/- 4.0 days for patients treated in two steps. Five patients (18%) with positive intraoperative cholangiography for stones for whom peroperative ERCP was not available showed a normal postoperative transcystic cholangiogram and therefore ERCP was canceled. Fourteen of 25 patients treated in one step and none of 17 treated in two steps had raised serum amylase, which resolved spontaneously with no symptoms. No patient developed postoperative pancreatitis. Three (10%) ERCP complications were observed, consisting of mild bleeding of the papilla. All cases were managed by endoscopic adrenaline injection. There was no mortality. CONCLUSION: We believe peroperative ERCP with the technique described should be considered as the treatment of choice for choledocholithiasis associated with cholelithiasis. When single-stage treatment is not possible, a two-step rendezvous technique should be preferred.

Gastric aspiration versus antimony and glass pH electrodes. A simultaneous comparative in vivo study.

To carry out a simultaneous comparison of the 24-h in vivo performance of antimony and glass electrodes and the findings of intermittent gastric aspiration, a triple-probe system with closely adjacent tips was positioned in the gastric corpus of 10 subjects representing different clinical and pharmacologic conditions. We showed that pH values measured with the antimony and the glass units were well correlated to those assessed in gastric aspirates (rs = 0.87; b = 1.079; a = -0.33; and rs = 0.85; b = 1.121; a = -0.38, respectively). A proportional correlation (rs = 0.86; b = 0.97; a = 0.02) was also found between the two intraluminal pH measurements. With regard to the error frequency distributions obtained by comparing the three measuring systems two at a time, the pH pairs differed by no more than 1 pH unit in most cases (greater than 90%). It can be concluded that antimony and glass pH electrodes can be used interchangeably in 24-h intragastric acidity studies in man.

Is hepatic ultrasonography a valid alternative tool to liver biopsy? Report on 507 cases studied with both techniques.

In order to evaluate the diagnostic potential of liver ultrasonography (US), the charts of 23 cases with normal liver, 424 patients with chronic widespread, and 60 patients with focal hepatic diseases, who had undergone both US and liver biopsy, were reviewed. The positive predictive value of US was good in all hepatic disorders (range 86.9-96.5%), while its negative predictive value was very low (range 14.1-42.5%) in the various forms of widespread liver disease and suitable for screening purposes (74%) in focal lesions. Of the 507 cases, 39 with an ultrasonically suspected liver mass also underwent an echo-guided fine-needle aspiration, which showed a high sensitivity (85%) in the 27 biopsy-proved malignant lesions and excluded tumor cells in the remaining 12 cirrhotic cases. As regards US tissue diagnosis, hepatic tumors, fatty infiltration, and fibrosis were detected in 88%, 60%, and 49% of cases, respectively. Fat and fibrous content on biopsy were similarly and significantly correlated with both echo pattern and sound attenuation. Overall results suggest that in the group of widespread hepatic disorders the usefulness of US is greatly reduced by the fact that the patient's actual condition is not likely to be negative if US examination is normal and by the impossibility of differentiating fat from fibrosis. In focal lesions, the diagnostic value of US appears high and the method may frequently provide conclusive proof of the tumor if a positive cytodiagnosis on echo-guided aspirated material is done.

Evaluation of antisecretory activity of misoprostol in duodenal ulcer patients using long-term intragastric pH monitoring.

The effect of the new synthetic prostaglandin E1 analog, misoprostol, on intragastric acidity was evaluated by means of 24-hr intraluminal pH monitoring of 16 duodenal ulcer patients. They were randomly allocated into two groups: eight received no medication and misoprostol 400 micrograms bid and eight received ranitidine 150 mg and misoprostol 400 micrograms bid not less than one week apart. The comparison of the 24-hr areas under the curve related to the median pH values showed that no difference existed between misoprostol and untreated patients in the first group, while ranitidine was significantly more effective (P = 0.00003) than misoprostol in the second group. The analysis of arithmetic differences between the 24-hr median pH values showed that misoprostol increased pH values by at least one unit compared to the untreated subgroup for about 3.5 hr, while the antisecretory action of ranitidine was far superior to that of misoprostol throughout the whole 24-hr period. It can be concluded that the effect of twice daily doses of misoprostol 400 micrograms on 24-hr intragastric pH is small and not at all comparable to that of the well-known potent H2 blocker ranitidine.

Famotidine has no significant effect on gonadal function in man.

The effect of a single bedtime dose of famotidine 40 mg on gonadal function was studied in 8 male duodenal ulcer patients. The drug was orally administered for 4 weeks. Our results show that this new H2 blocker influences basal and stimulated serum levels of neither testosterone nor gonadotrophins (LH, FSH). Besides, no significant variations were observed before and after famotidine treatment in seminal fluid characteristics evaluated in 5 out of 8 cases. It can be concluded that famotidine appears to leave gonadal function unaffected in man.

Circadian reduction of chromium in the gastric environment.

Samples of gastric juice from variously treated subjects efficiently reduced hexavalent chromium and decreased its mutagenicity. Chromium reduction was due to thermostable components of gastric secretions and was favoured by the acidity of the intragastric environment. The circadian monitoring of pH and of chromium reduction, as assessed by colorimetric analysis at hourly intervals, showed a basal activity (less than 10 micrograms/ml gastric juice) during the night and interdigestive periods, and peaks (tens of micrograms/ml) during the 3-4-h periods after each meal. Assays in the Ames reversion test confirmed that the decrease in mutagenicity of sodium dichromate produced by gastric juice was significantly enhanced after meals. This physiological mechanism is expected to provide an important protective barrier against the oral toxicity of this metal, and may explain its lack of oral carcinogenicity.

Single bedtime dose of famotidine: assessment of its antisecretory action by 24-hour intragastric pH monitoring.

The antisecretory efficacy of a single bedtime dose of famotidine, a new potent H2-receptor antagonist, was evaluated by means of continuous 24-hour intragastric pH monitoring. Of 20 patients with duodenal ulcers, ten randomly received famotidine 40 mg at 10 PM and ten were monitored without medication for control. Famotidine regimen led to a remarkable reduction of gastric acidity in patients who were treated for duodenal ulcer and the drug-induced pH levels were significantly different (P less than .0001) from those of untreated controls. The antisecretory action lasted for 12 hours, which comprised the nocturnal period, whereas no important difference was found between the two groups for the most part of the daytime. The drug was able to keep intragastric pH above 4 units during almost 50% of the whole 24-hour period. These results confirm that famotidine is a powerful and long-acting H2 blocker that relieves gastric acidity during the night and morning hours when administered as a single bedtime dose of 40 mg.

24-H comparison between pH values of continuous intraluminal recording and simultaneous gastric aspiration.

This study was undertaken to show whether the correlation between pH values indicated by an intraluminal pH electrode and those simultaneously recorded for gastric aspirates is not only linear but also proportional, so that the two measurement techniques can be considered alternative. A 24-h intragastric pH-monitoring with an antimony electrode, to which a nasogastric tube for hourly aspiration of gastric juice was closely attached, was performed on 20 duodenal ulcer patients. Our data show that the slope of the straight line related to 335 pH pairs is virtually equal to 1, whereas the elevation is almost equal to zero, and this result strongly suggests that a proportional relationship exists between intragastric and aspirate pH levels throughout the whole 24-h period. Besides, in the majority of cases (81%) the pH pairs differ by no more than 1 pH unit. It can be concluded that these two pH monitoring methods may be alternative.

Continuous 24-hour intragastric pH monitoring in the evaluation of the effect of a nightly dose of famotidine, ranitidine and placebo on gastric acidity of patients with duodenal ulcer.

In 11 duodenal ulcer patients, the antisecretory effects of bedtime famotidine 40 mg were compared to those obtained with ranitidine 300 mg and placebo by means of continuous 24-hour intragastric pH monitoring. The 24-hour areas under the curve of pH profiles of the two H2 blockers were significantly different from those related to placebo (p approximately 0 for ranitidine and p = 0.00001 for famotidine), but not from each other (p = 0.51). Onset and duration of the famotidine action, however, were respectively earlier and longer lasting (12 vs. about 9 h) than those of ranitidine. Famotidine was also significantly superior (p approximately 0) to ranitidine in keeping intragastric pH at high values (especially those comprised between 6 and 8 pH units), although theoretically equipotent doses of the two H2 antagonists were used.

Continuous 24 hour intragastric pH monitoring: focus on reproducibility in duodenal ulcer patients. A preliminary report.

Continuous 24 h intragastric pH monitoring is increasingly recommended for deciding which is the most appropriate regimen and dosage of new gastric antisecretory drugs. In order to assess its reproducibility, we have repeated the test twice on consecutive days in six patients with endoscopically proven duodenal ulcers because this type of patient seems to be the most suitable for studies on the efficacy of the above mentioned therapy. No patient received medication during the two examination days. Our data showed there was no significant difference (t = 0.31, p = 0.76) between the 24 h areas under the curve of pH profiles of the first day compared with those of the second (mean +/- SD : 3.152 +/- 681 vs 3.073 +/- 1,122). The lack of significant difference (p = 0.20) between the mean times elapsed at the various pH levels during the first and second days was further proof of the reproducibility of the method. As wells these results suggest that day-to-day reproducibility of the technique is good in duodenal ulcer patients. Therefore, its repeated use on the same patient to investigate the effects of various drugs and their different dosages on gastric acidity appears to be reliable.