Clinical findings, treatment and outcome of trapped neutrophil syndrome in Border Collies: 12 cases (2011-2022).

OBJECTIVES: This study aimed to evaluate clinical signs, diagnostic findings, treatment administered and short- (survival to 28 days) and long-term prognosis (survival >6 months) in dogs diagnosed with trapped neutrophil syndrome. MATERIALS AND METHODS: Medical records of 12 dogs (10 Border Collies and two Border Collie Crossbreeds) homozygous for VPS13B gene mutation causing trapped neutrophil syndrome from seven veterinary institutions between January 2011 and June 2022 were evaluated retrospectively. RESULTS: The most common clinical signs at the time of diagnosis were pyrexia, abnormal gait and gastrointestinal signs. Concurrent metaphyseal osteopathy and immune-mediated polyarthritis were common. Seven dogs had a segmented neutrophil count below, four dogs within and one dog above the analyser reference interval at presentation. Two dogs had a septic source identified and both were additionally identified to be homozygous mutant positive on DNA testing by polymerase chain reaction (PCR) for canine cyclic neutropenia. All dogs received at least one antimicrobial agent and 10 dogs received treatment with prednisone or prednisolone (median starting dose 1 mg/kg/day; range 0.5 to 2.5 mg/kg/day). Nine dogs were alive at 28 days and six dogs were alive at 6 months post-diagnosis. CLINICAL SIGNIFICANCE: Trapped neutrophil syndrome should be suspected in young Border Collies with pyrexia, lameness and gastrointestinal signs. Neutropenia may not always be present and long-term survival is possible. A septic focus was not commonly identified in our population; however, our results suggest that if identified, testing for concurrent canine cyclic neutropenia should be considered.

Association between PNPLA3[G]/I148M variant, steatosis and fibrosis stage in hepatitis C virus - genetic matters.

There is an established correlation between the PNPLA3 rs738409 C > G single nucleotide polymorphism (SNP) and hepatic steatosis and fibrosis in hepatitis C virus (HCV) infected patients. However not all data is convergent regarding the exact impact of this SNP on the pattern of disease progression in different clinical settings. In this study, we aimed to further bridge the knowledge gap on this topic by investigating the role of the G allele in promoting steatosis, fibrosis and disease progression in relation to other metabolic and anthropometric host factors. Two hundred and fifty consecutive patients, previously diagnosed with chronic hepatitis C (CHC) underwent liver biopsy. Histology was assessed using the Metavir scoring system. Transient elastography was used for follow-up. Ninety-eight patients were genotyped for PNPLA3 rs738409 and followed up for fibrosis progression. PNPLA3 rs738409[G] allele was significantly correlated with severe steatosis (P = 0.04), severe fibrosis at the time of enrollment (P = 0.0005) and fibrosis progression with an OR of 10.31 (95% CI 1.06 - 99.59, P = 0.04), after a mean follow-up time of 62.85 (95%CI: 52.21 - 76.15) months. Severe steatosis at the time of enrollment had an OR of 11.02 (95% CI 1.48 - 82.09, P = 0.01) for the association with fibrosis progression. The HOMA-IR index was also positively correlated with severe fibrosis (P = 0.03) and fibrosis progression on univariate analysis (P = 0.02). PNPLA3 rs738409[G] allele is a reliable predictor for steatosis and fibrosis in CHC. The presence of G allele, along with severe steatosis and insulin resistance are significant predictors for fibrosis progression.

The utility of the predictive scores in polytrauma with abdomino-pelvic injuries: a series of 38 patients.

UNLABELLED: Trauma is the principal cause of mortality among the population under 40 years. The aim of our study was to compare predictive trauma scores and demonstrate their utility in the evaluation of the quality of care in polytrauma. MATERIAL AND METHODS: A retrospective study was performed between 2000-2011 including polytrauma patients with abdominal lesions and pelvic fracture who under went emergency laparotomy. We calculated ISS, GCS, RTS,TRISS, ASCOT trauma scores and W score for evaluation of treatment quality. RESULTS: We obtained the necessary data to calculate the predictive scores in 38 cases. Comparing the scores of the survivals and non-survivals we noted the following regarding mortality predictive scores: GCS 13.74 vs. 6.13 (p 0.0001),ISS 28.52 vs. 35 (p=0.0169), RTS 6.96 vs. 3.07 (p 0.0001),TRISS 84.67% vs. 28.7% (p 0.0001), ASCOT 10.34% vs.64.32% (p 0.0001). The W score in TRISS and ASCOT methodology was -2.05 (p=0.7997) and -7.81 (p=0.336),respectively. There was no statistically significant difference between actual and predicted mortality, the former being 39.47%. CONCLUSION: We did not observe differences between the two methodologies TRISS and ASCOT in mortality prediction (p=0.5401). Both of them can be used to predict polytrauma patient evolution. The W score is useful in treatment quality assessment.

Theoretical investigation of an artificial joint with micro-pocket-covered component and biphasic cartilage on the opposite articulating surface.

This paper presents a theoretical investigation of a geometrically idealized artificial joint with micro-pocket-covered component and biphasic cartilage on the opposite articulating surface. The fluid that exudes from the biphasic cartilage fills and pressurizes the micro-pockets. In this way, a poro-elasto-hydrodynamic regime of lubrication is developed. Assuming that lower friction would result in lower adhesive wear, and neglecting the fatigue as well as the abrasive wear, the proposed bearing system hypothetically could reduce the amount of wear debris. Equations of the linear biphasic theory are applied for the confined and unconfined compression of the cartilage. The fluid pressure and the elastic deformation of the biphasic cartilage are explicitly presented. The effective and equilibrium friction coefficients are obtained for the particular configuration of this bearing system. The micro-pockets geometrical parameters (depth, radius, surface distribution and edge radius) must be established to reduce the local contact stresses, to assure low friction forces and to minimize the biphasic cartilage damage. The influence of the applied pressure, porosity of the micro-pocket-covered component, filling time, cartilage elasticity, permeability and porosity upon the micro-pockets depth is illustrated. Our results are based upon the previously published data for a biphasic cartilage.

Endothelin-1 and endothelin-converting enzyme-1 gene regulation by shear stress and flow-induced pressure.

Hemodynamic forces have been shown to modulate the expression of endothelin (ET-1) and endothelin-converting enzyme (ECE-1) in endothelial cells. We have subjected E.A. hy 926 cells in culture to steady fluid shear stress with and without flow-induced pressure. The effect of combining these two mechanical forces on the expression of genes in the ET system was studied and the changes were compared to the mRNA levels in static culture. Analysis of total RNA by Northern blot analysis and RNAse protection showed that steady shear stress induced ET-1 gene expression three- to fourfold in this system. The same condition had little to no effect on altering expression of ECE-1 isoforms. A range of flow-induced pressure (80-160 mm Hg) was not able to further augment ET-1 or ECE-1 gene expression. Overall, with the mechanical environment studied, we have been able to detect a predominant contribution of shear stress to altering the ET-1 gene in our system. Furthermore, this induction was independent of an alteration of ECE-1 gene levels, suggesting that these two genes have a different pattern of regulation by the same stimuli in this cell type.

Model for the alignment of actin filaments in endothelial cells subjected to fluid shear stress.

Cultured vascular endothelial cells undergo significant morphological changes when subjected to sustained fluid shear stress. The cells elongate and align in the direction of applied flow. Accompanying this shape change is a reorganization at the intracellular level. The cytoskeletal actin filaments reorient in the direction of the cells' long axis. How this external stimulus is transmitted to the endothelial cytoskeleton still remains unclear. In this article, we present a theoretical model accounting for the cytoskeletal reorganization under the influence of fluid shear stress. We develop a system of integro-partial-differential equations describing the dynamics of actin filaments, the actin-binding proteins, and the drift of transmembrane proteins due to the fluid shear forces applied on the plasma membrane. Numerical simulations of the equations show that under certain conditions, initially randomly oriented cytoskeletal actin filaments reorient in structures parallel to the externally applied fluid shear forces. Thus, the model suggests a mechanism by which shear forces acting on the cell membrane can be transmitted to the entire cytoskeleton via molecular interactions alone.

Synergistic effects of fluid shear stress and cyclic circumferential stretch on vascular endothelial cell morphology and cytoskeleton.

The development of atherosclerosis is thought to be initiated by a dysfunctional state of the vascular endothelium. The proposal that mechanical forces play a role in the localization of this disease has led researchers to develop in vitro models to assess their effects on cultured endothelial cells. The arterial endothelium is exposed simultaneously to circumferential hoop stretch and wall shear stress, yet previous investigations have focused on the isolated effects of either cyclic stretch or shear stress. The influence of physiological levels of combined shear stress and hoop stretch on the morphology and F-actin organization of bovine aortic endothelial cells was investigated. Cells subjected for 24 hours to shear stresses higher than 2 dyne/cm2 or to hoop stretch greater than 2% elongated significantly compared with unstressed controls and oriented along the direction of flow and perpendicular to the direction of stretch. Exposure to more than 4% stretch significantly enhanced the responses to shear stress. Both shear stress and hoop stretch induced formation of stress fibers that were aligned with the cells' long axes. Simultaneous exposure to both stimuli appeared to enhance stress fiber size and alignment. These results indicate that shear stress and hoop stretch synergistically induce morphological changes in endothelial cells, which suggests that circumferential strain might modulate sensitivity of endothelial cells towards shear stress.

A device for subjecting vascular endothelial cells to both fluid shear stress and circumferential cyclic stretch.

The proposal of the role of mechanical forces as a localizing factor of atherosclerosis has led many researchers to investigate their effects on vascular endothelial cells. Most previous efforts have concentrated on either the fluid shear stress, which results from the flow of blood, or the circumferential "hoop" stretch, which results from the expansion of the artery during the cardiac cycle. In fact, arterial endothelial cells are subjected to both fluid shear stress and cyclic hoop stretch in vivo. Therefore, a more complete investigation of mechanical phenomena on endothelial cell behavior should include both kinds of mechanical stimuli. This study was undertaken to design an experimental apparatus that could subject cultured vascular endothelial cells to simultaneous physiologic levels of both shear stress and cyclic hoop stretch. The experimental apparatus consists of four cylindrical elastic tubes so that the following conditions may be studied: (a) static conditions: (b) shear stress only; (c) hoop stretch only; and (d) shear stress and hoop stretch. In order to establish the functional capabilities of the apparatus, bovine pulmonary artery endothelial cells were cultured in the tubes, and their morphology and f-actin structure were observed with confocal microscopy. The cells remained healthy and attached to the walls throughout the 24 hr experiment. Preliminary results indicated that the alignment of endothelial cells subjected to shear stress was significantly enhanced by the addition of hoop strain.

Study of serum ceruloplasmin and of the copper/zinc ratio in cardiovascular diseases.

The serum copper and zinc concentration, the Cu/Zn ratio and ceruloplasmin activity have been studied in 400 subjects divided into 4 groups of study: 50 normal subjects (controls), 100 patients with ischemic heart disease, 100 subjects with myocardial infarction in the past history and 150 patients with acute myocardial infarction. It was observed that in normal subjects the Cu/Zn ratio is about 1, in acute myocardial infarction it reaches 2.5 but it returns to normal during convalescence. In the patients with ischemic heart disease the ratio decreases to 0.8 and in the subjects with infarction in the past history it is about 1.6 (almost normal). The variation of these ratio is due to the serum zinc concentration which in ischemic heart disease presents values over the upper normal limit and in acute myocardial infarction below the lower normal limit. In the subjects with acute infarction ceruloplasmin (copper depending enzyme) the activity was observed to be inversely proportional to the Cu/Zn ratio in the first 4 days after the onset of the disease. The quick normalization of one or of both parameters is a sign of positive evolution of the disease.

Seasonal variations of serum cholesterol detected in the Bucharest Multifactorial Prevention Trial of Coronary Heart Disease. Ten years follow-up (1971-1982).

A group of 4800 men, aged fourty to sixty at entry, subjected to a multifactorial prevention trial of coronary heart disease for a ten-year period, showed spontaneous seasonal variations of serum cholesterol, characterized by increases in winter and decreases in summer. The authors discuss the relationship between the food changes and the seasonal variation of serum cholesterol values.

Biochemical changes induced by Campylobacter pylori in the gastric juice.

The biochemical changes induced in the gastric juice by the presence of Campylobacter pylori (CP) were followed up in 151 patients with various gastric and duodenal diseases. The diagnosis of CP infection was made by the urease test. In the presence of CP urea decreased in the gastric juice and ammonia increased. The sialic acid, fucose and hexoses, glucide components of the mucus glycoproteins dissolved in the gastric juice, underwent no change in the presence of CP. The hexosamines in the gastric mucus increased significantly in CP patients. Urease activity is present in the gastric juice even in the absence of CP, probably due to other microorganisms present in the human stomach. This does not exclude the use of the urease test for the diagnosis of CP infection. However the test can only be used in the bioptically removed gastric mucosa samples, not in the gastric juice.

Helicobacter-like organisms in gastroduodenal diseases.

The incidence of the Helicobacter-like organisms (HLO) was investigated on biopsy specimens of antral gastric mucosa, stained by the Wayson technique, in 509 patients with various gastric and duodenal diseases. The incidence of HLO was: 72.8 percent in gastric ulcer, 69.6 percent in duodenal ulcer, 69.2 percent in bulbitis, 61.0. percent in chronic gastritis, 37.5 percent in the postoperative stomach, 50 percent in gastric cancer, and 34.3 percent on healthy controls. The HLO were present over the whole year, with a peak in March. Sex and age had little influence on the HLO incidence. The Wayson staining technique proved to be a good technique of detection of HLO on gastric mucosa smears.

Possible correlation between the zinc and copper concentrations involved in the pathogenesis of various forms of anemia.

The concentrations of three trace elements (iron, copper and zinc) involved in hematopoiesis were studied in 200 patients with iron-deficit anemia, hemolytic anemia and Biermer's anemia, in comparison with a group of normal subjects. The method used was atomic absorption spectrophotometry. The results obtained showed that in iron-deficit anemia resistant to iron therapy the copper and ceruloplasmin serum concentrations are at the lowest limit of normal. This copper deficit has a negative effect on the disease by preventing hemoglobin synthesis. In iron-deficit anemias responding to iron therapy the relatively low (about 90 gamma %) zinc values have a negative effect by blocking the iron in the iron reserve. In hemolytic anemia the very high zinc serum concentrations (over 200 gamma %) may lead to a shortening of the erythrocytes life span due to its "entatic state". In Biermer's anemia zinc by its high concentration has a positive role owing to carbonic anhydrase which eliminates more rapidly carbon dioxide from the organism.

Variations of zinc, calcium and magnesium in normal subjects and in patients with neoplasias.

The serum zinc, calcium and magnesium concentration as well as the possible relationship between these elements was determined by means of atomic absorption spectrophotometry in 150 patients with prostatic, lung, liver and breast neoplasms as well as with chronic leukemia, and in 80 normal subjects. These determinations showed that zinc concentration is increased in almost all the forms of cancer except prostatic and lung cancer in which the zinc values were below the lowest normal limits. From this study it also resulted that high zinc values favour the development of cancer. The antagonic relationship between zinc and calcium or magnesium in neoplasias proves the protective role played by the latter elements in the forms of cancer in such cases.

Contributions to the study of gastric carcinogenesis.

Investigations were carried out on duodeno- and jejunogastric reflux, gastric juice acidity, microbial population and the concentration of nitrites in 199 subjects. In gastric cancer patients or those with gastric ulcer, chronic atrophic gastritis, stomach resection or more seldom with removal of the gallbladder, a significant increase over normal values of the pH, duodenogastric reflux, microbial flora contamination (especially intestinal) and nitrite concentration was found. In smokers the salivary nitrite concentration was greater than in non-smokers and in direct relationship to gastric concentrations. The parallelism of these alterations suggests a causative relation between them and their presence in diseases or conditions of notorious increased incidence in gastric cancer highlights the direction to be followed in the primary prophylaxis of this disease.

Study of the relationship between the granulocyte LDH, alkaline phosphatase and Zn at the level of the leukocyte in patients with chronic myeloid leukemia.

Mixed leukocyte suspensions were prepared from heparinized blood collected from healthy subjects and from patients with chronic myeloid leukemia (CML). In all the suspensions determinations were made for: zinc, by atomic absorption; granulocyte alkaline phosphatase (GAP), using the method with p-nitrophenylphosphatase; granulocyte LDH, by means of the enzymatic autoanalyser LKD 8,600. In the patients with CML, the values of zinc and of granulocyte alkaline phosphatase activity were very low while the granulocyte LDH values were higher than normal. The chromatogram of the granulocyte LDH isoenzymes on DEAE-Sephadex A50 minicolumn (0.5 X 12 cm) showed an "alpha type abnormality" revealed by the increased activity of the isoenzymes with high electrophoretic mobility LDH2 and LDH1 specific for tissues with intense oxidative phosphorylation. In the normal subjects the chromatogram of the leukocyte LDH isoenzymes showed a type M (skeletal muscle) prevalence denoting intense anaerobic glycolysis. Therefore the low zinc concentrations (0.55 micrograms mg N2 as compared with the normal 1.24 micrograms mg N2) in these patients cause the decrease of GAP activity by the lack of zinc in the active center of the enzyme and the decrease of cellular permeability thus allowing the extracellular release of granulocyte LDH.