Virus discovery in dogs with non-suppurative encephalitis reveals a high incidence of tick-borne encephalitis virus infections in Switzerland.

INTRODUCTION: Viral infections are a frequent cause of disseminated non-suppurative encephalitis in dogs. However, using routine diagnostic methods, the specific virus may remain unknown due to extensive or complete viral clearance or because the virus is unexpected or new. A metatranscriptomics-based approach of combining high-throughput sequencing (HTS) and bioinformatics analysis was used to investigate the viral etiology in archival cases of dogs with non-suppurative encephalitis. In formalin-fixed paraffin embedded (FFPE) brain material from the years 1976 to 2021 a high incidence of tick-borne encephalitis virus (TBEV) was detected. Moreover, canine distemper virus (CDV) was identified without typical demyelinating lesions and canine vesivirus (CaVV) was detected as an unexpected virus associated with non-suppurative encephalitis. We demonstrated the viral presence in brain tissues at the sites of inflammation by immunohistochemistry (IHC) and in situ hybridization (ISH). These results highlight the value of emerging sequencing technologies in veterinary diagnostics and expand our knowledge on the etiologies of encephalitis in dogs.

INTRODUCTION: Les infections virales sont une cause fréquente d'encéphalite non suppurée disséminée chez le chien. Cependant, en utilisant les méthodes de diagnostic de routine, le virus spécifique peut rester inconnu en raison d'une clairance virale importante ou complète ou parce que le virus est inattendu ou nouveau. Une approche métatranscriptomique combinant le séquençage à haut débit et l'analyse bioinformatique a été utilisée pour étudier l'étiologie virale dans des cas archivés de chiens atteints d'encéphalite non suppurée. Une incidence élevée du virus de l'encéphalite à tiques (TBEV) a été détectée dans le matériel cérébral fixé au formol et inclus dans la paraffine (FFPE) des années 1976 à 2021. En outre, le virus de la maladie de Carré (CDV) a été identifié sans lésions démyélinisantes typiques et le vésivirus canin (CaVV) a été détecté comme un virus inattendu associé à une encéphalite non suppurative. Nous avons démontré la présence virale dans les tissus cérébraux au niveau des sites d'inflammation par immunohistochimie (IHC) et hybridation in situ (ISH). Ces résultats soulignent la valeur des technologies de séquençage émergentes dans le diagnostic vétérinaire et élargissent nos connaissances sur les étiologies de l'encéphalite chez les chiens.

Sacral neuromodulation for fecal incontinence in Latin America: initial results of a multicenter study.

BACKGROUND: Sacral neuromodulation (SNM) is a widely used therapeutic option for fecal incontinence (FI). Larger series are mainly from Western countries, while few reports address the results of SNM in less developed or less wealthy countries. The aim of the present study was to evaluate the efficacy of SNM in patients with FI in Latin America. METHODS: A retrospective study was conducted on patients with FI who had SNM between 2009 and 2016 at 15 specialized colorectal surgery centers in Latin America. Main outcomes measures were functional outcomes, postoperative complications, requirement of revisional surgery, and requirement of device removal. All patients had failed conservative management and had clinical assessment including recording of the validated Cleveland Clinic Florida Fecal Incontinence Score (CCF-FIS) and, when available, anal manometry and endoanal ultrasound. Patients were followed up for a median of 36.7 (1-84) months. RESULTS: One hundred and thirty-one patients [119 females, median age of 62.2 (range 19-87) years] were included. The most common etiology of FI was obstetric injury (n = 60; 45.8%). After successful test lead implantation, the stimulator was permanently placed in 129 patients (98.5%). One patient failed to respond in the test phase and one patient did not proceed to permanent implantation for insurance reasons. Nineteen patients (14.7%) had 19 complications including infection (n = 5, 3.8%), persistent implant site pain (n = 5, 3.8%), generator/lead dislodgment (n = 5, 3.8%), malfunctioning device (n = 3, 2.3%), and hematoma (n = 1, 0.7%). Reimplantation after the first and second stages was necessary in 2 (1.5%) and 3 patients (2.3%), respectively. The device removal rate was 2.2%. At a median follow-up of 36.7 (range 1-84) months, the CCF-FIS significantly improved from a preoperative baseline of 15.9 ± 2.98 to 5.2 ± 3.92 (95%CI: 15.46 vs 4.43; p < 0.0001). Overall, 90% of patients rated their improvement as "significant". CONCLUSIONS: Sacral nerve stimulation for FI is safe and efficient, even in less wealthy or less developed countries.

Reviving post-mortem diagnostics as a tool to increase porcine herd health and strengthen early detection of pig diseases - the PathoPig project 2014-2016.

INTRODUCTION: Post-mortem diagnostics are an important tool for disease diagnosis and therefore early detection of (re-)emerging animal diseases and zoonoses as well as nationwide disease surveillance programs. To counteract the decline of porcine necropsies in Switzerland over the last ten years, the Federal Food Safety and Veterinary Office (FSVO) launched a national project in 2014 called PathoPig. Post-mortem examinations of pigs from herds with health problems were financially supported by the FSVO. During the first 3 years of the project, the number of pig necropsies increased by 195% (mean). An underlying cause of disease was identified in 74% of the cases. These findings resulted in specific recommendations by the attending veterinarians or by the Swiss Porcine Health Service. A follow-up survey revealed that herd health had improved in 90% of the farms implementing the recommendations.

INTRODUCTION: Les diagnostics post-mortem constituent un outil important pour le diagnostic des maladies et, partant, la détection précoce des maladies animales et des zoonoses (ré)-émergentes ainsi que pour les programmes nationaux de surveillance des maladies. Pour contrer le déclin des nécropsies porcines en Suisse au cours des dix dernières années, l'Office fédéral de la sécurité alimentaire et vétérinaire (OSAV) a lancé en 2014 un projet national baptisé PathoPig. Les examens post-mortem des porcs provenant d'exploitations avec des problèmes de santé ont été soutenus financièrement par l'OSAV. Au cours des trois premières années du projet, le nombre de nécropsies porcines a augmenté de 195% (moyenne). Une cause sous-jacente de maladie a été identifiée dans 74% des cas. Ces constatations ont abouti à des recommandations spécifiques des vétérinaires participants ou du Service sanitaire porcin suisse. Une enquête de suivi a révélé que la santé des troupeaux s'était améliorée dans 90% des exploitations appliquant les recommandations.

An unusual cause of obstructed defecation.

Obstructed defecation is one subtype of constipation, and may be due to functional or mechanical causes. Here, we report an unusual cause, never described before, of obstructed defecation due to a large uterine myoma that reverted to normal bowel habits after surgery. The importance of an accurate evaluation of the causes of constipation is highlighted, to recognize potential curable factors.

Stop-flow technique for loco-regional delivery of high dose chemotherapy in the treatment of advanced pelvic cancers.

AIM: To verify the rationale of a pelvic stop-flow technique for the perfusion of high-doses of mitomycin C and anthacyclines in patients with inoperable, recurrent pelvic cancer. METHODS: The stop-flow technique was realized by using percutaneous double-balloon arterial-venous catheters that selectively isolate the pelvic vascular section and a perfusion provided by an extracorporeal pump for 20 min. Ten patients (pts) with unresectable pelvic recurrence from colon-rectal cancer were treated with a combination of Mitomycin C (MMC, 20 mg/sqm) plus doxorubicin (DOXO, 75 mg/sqm; 8pts) or epirubicin (EPI, 75 mg/sqm; 2pts) infused into the isolated pelvic compartment. Blood samples were collected from the extracorporeal vascular flow and from peripheral plasma, and analysed for drug quantitation. RESULTS: During the procedure, there were no technical or hemodynamic complications, and no deaths occurred during surgery or in the postoperative period. MMC and DOXO peak levels measured in the extracorporeal system which irrotates the tumor area, were on average 21.6 (range: 4.3-44.3, MMC) and 17.2 (range: 1.8-48.4, DOXO) times higher than those observed in the peripheral blood. Similarly; the area under concentration (AUC) versus time curves measured in the pelvic compartment during stop-flow perfusion were 19.9 (range: 3.8-45.0, MMC) and 13.4 (range: 1.2-26.6, DOXO) times higher than the corresponding value in peripheral circulation. The drug percentage eliminated in the ultra filtrate was only 7.7% (MMC) and 0.9% (DOXO), and the plasmatic AUC(0-24) were similar to those observed with iv bolus of equivalent drug doses. Minimal systemic and local toxicities were observed. One complete pathological and 2 partial responses were observed; pain remission in 8/10 patients. median survival was 12 months (8-31). CONCLUSION: The endo-arterial administration into the local vasculature produces high pelvic-systemic concentration gradients during the stop-flow perfusion with limited local and systemic toxicity. The encouraging clinical results suggest further evaluation.

Effect of trimetazidine on 99Tcm-tetrofosmin uptake in patients with coronary artery disease.

Myocardial uptake of 99Tcm-tetrofosmin in vivo is determined by a combination of flow and metabolic status of myocytes. The accumulation of tetrofosmin in the mitochondria is related to their ability to transduce metabolic energy into electronegative membrane potential. Trimetazidine (TMZ), an anti-ischaemic drug, appears to have a metabolic cytoprotective effect related to mitochondrial function, since it does not induce systemic or coronary haemodynamic changes. In this study, we evaluated the effects of TMZ on tetrofosmin uptake in hypoperfused myocardial regions in patients with coronary artery disease (CAD). Twenty-two patients, 14 with previous myocardial infarction (group A) and eight with a history of angina (group B), with angiographically documented CAD were studied. All patients underwent two tetrofosmin SPET studies at rest, before (baseline) and 1 week after TMZ administration (post-TMZ). On quantitative analysis, 131 segments showed less tetrofosmin uptake at baseline. In these segments, tetrofosmin uptake was 51 +/- 13% at baseline and 55 +/- 15% post-TMZ (P < 0.001 vs control). In the 86 hypoperfused segments of group A, tetrofosmin uptake was 48 +/- 14% at baseline and 52 +/- 17% post-TMZ (P < 0.001 vs control). In the 45 hypoperfused segments of group B, tetrofosmin uptake was 56 +/- 9% at baseline and 60 +/- 10% post-TMZ (P < 0.001 vs control). In the remaining 309 segments, no significant difference in tetrofosmin uptake before and after TMZ was observed. In conclusion, our results suggest that TMZ administration may increase myocardial uptake of tetrofosmin in hypoperfused regions at rest in patients with CAD, based on its metabolic effect.

Relation of insulin resistance to left ventricular hypertrophy and diastolic dysfunction in obesity.

OBJECTIVE: To assess relations of left ventricular (LV) geometry and function to insulin resistance in obesity-a condition associated with volume overload and abnormal LV relaxation. DESIGN: Cross-sectional relational study. SUBJECTS: 27 healthy overweight-obese subjects (18 women, body mass index (BMI) = 35.0+/-4.0 kg/m2) and 31 age-matched normal-weight controls (21 women, BMI = 22.6+/-2.4 kg/m2). MEASUREMENTS: Subjects were studied by Doppler-echocardiography the same day and hour (08.00 h) as measurements of fasting insulin and blood glucose were made. Insulin resistance was determined by the 'Homeostasis Assessment Model'. RESULTS: Twelve obese subjects with insulin resistance (IR) had higher body size than 15 patients without IR and higher blood pressure than normal-weight controls (all P < 0.01). Relative IR was related to isovolumic relaxation time. This relation was not maintained after controlling for age, blood pressure, weight and height. Isovolumic relaxation time was, however, positively related to diastolic blood pressure, a measure of load, in normal controls (r=0.44) and obese without IR (r=0.62) but not in insulin resistant subjects (r=0.14). CONCLUSION: IR does not independently influence myocardial relaxation in uncomplicated obesity, but modulates the effect of load on active diastole.

Left ventricular filling in arterial hypertension. Influence of obesity and hemodynamic and structural confounders.

We assessed the relations of left ventricular filling to load and geometry by Doppler echocardiography in 80 normotensive subjects (40 normal-weight [36 +/- 12 years, 24 women] and 40 obese [35 +/- 13 years, 24 women]) and 61 hypertensive subjects without silent coronary heart disease (29 normal-weight [43 +/- 13 years, 15 women] and 32 obese [42 +/- 13 years, 19 women]) and comparable left ventricular midwall performance. Left ventricular mass divided by height to the 2.7 power was higher in all groups than in normotensive normal-weight subjects (all P < .0001) and in hypertensive than normotensive obese subjects (P < .001). After controlling for age, sex, blood pressure, and heart rate, isovolumic relaxation time was prolonged in hypertensive subjects and normotensive obese subjects compared with normotensive normal-weight subjects (all P < .0001). Body mass index, left ventricular dimension and mass, and circumferential end-systolic stress did not influence these differences. In pooled groups, prolonged isovolumic relaxation time was predicted by high mean blood pressure (beta = 0.52, P < .001), low end-systolic stress (beta = -0.33, P < .001), increased left ventricular mass (beta = 0.24, P < .004), and high body mass index (beta = 0.14, P < .05, multiple R = .72, SEE = 16.5 milliseconds, P < .0001). Between-group differences in peak early transmitral flow velocity, the deceleration time of early filling velocity, and the ratio of early to late left ventricular filling disappeared after controlling for left ventricular mass. Thus, (1) isovolumic relaxation time is prolonged in both arterial hypertension and obesity; (2) the presence of obesity does not significantly increase isovolumic relaxation time in hypertension; and (3) abnormalities of left ventricular filling in arterial hypertension are offset after controlling for left ventricular mass.

Left ventricular filling pattern in uncomplicated obesity.

To determine if uncomplicated obesity is associated with systolic dysfunction or impairment of left ventricular (LV) filling, 40 normotensive, white, asymptomatic, obese subjects (16 men and 24 women, mean +/- SD age 35 +/- 13 years; body mass index 36 +/- 6 kg/m2) and 40 normotensive, normal-weight, white volunteers matched for age and sex distribution, were studied by Doppler echocardiography. Endocardial and midwall shortening did not show differences between groups (obese = 33 +/- 4% and 17 +/- 2%; normal weight = 33 +/- 3% and 18 +/- 2%, respectively). LV mass index was higher in obese than in normal-weight subjects (p <0.0001). Obese persons had prolonged isovolumic relaxation time (p <0.0001), lower transmitral peak early diastolic filling wave (E) velocity (p <0.02), higher E velocity deceleration time (p <0.002) and lower E/atrial diastolic filling wave (A) flow velocity ratio (p <0.01) than did normal-weight subjects, even after controlling for age and blood pressure. Between-group differences in E and E velocity deceleration time disappeared when controlling for LV mass index, whereas prolonged isovolumic relaxation time in obesity was independent of LV mass, chamber dimension, and end-systolic stress. LV filling variables were not statistically related to endocardial or midwall shortening, both as absolute value or as a percentage of that predicted from wall stress. We conclude that uncomplicated obesity is associated with primary impairment of LV isovolumic relaxation; abnormalities of early passive filling flow in obesity are associated with increased LV mass.

Subacute cardiac rupture complicating myocardial infarction. A case report.

The authors have focused this study on the emergence of subacute ventricular free wall rupture in a seventy-six-year-old patient admitted to hospital for inferior acute myocardial infarction. After six days he showed clinical signs of bradycardia and hypotension evolving to electromechanical dissociation. Given an adequate pharmacologic therapy, the patient was submitted to echocardiography, which was believed to be consistent with myocardial rupture, showing a moderate to large pericardial effusion. Pericardiocentesis of 150 mL of bloody fluid resulted in a further improvement in his hemodynamics. The patient underwent cardiac surgery with repair of the myocardial rupture through a large diaphragmatic infarction by a Dacron polyester fiber graft and pacemaker placement. In conclusion the authors confirm the relevant role of clinical data such as persistent chest pain and hemodynamic instability and the value of echocardiography in identifying subacute myocardial free wall rupture after an episode of acute myocardial infarction.

Heterocyclic modulators of the NMDA receptor.

The design of new heterocyclic derivatives as modulatory agents at EAA receptors is described. In particular, the potent and selective activity at the NMDA receptor of trans-4-hydroxypipecolic acid-4-sulfate, as well as the neuroprotective properties of substituted thiokynurenates, a new class of competitive antagonists at the glycine site of the NMDA receptor complex, are reported.

How reliable are currently available methods of measuring the anorectal angle?

A prospective study was undertaken to compare two different methods of measuring the anorectal angle (ARA), balloon proctography (BP) and cinedefecography (CD), as well as to evaluate the reproducibility of this measurement using each technique. One hundred four consecutive patients (75 women and 29 men) with constipation (63 patients), fecal incontinence (25 patients), or rectal pain (16 patients) underwent both BP and CD. The ARA was measured by taking lateral radiographs of the pelvis during rest (R), squeeze (S), and push (P). The same interpretation process was performed 2 to 12 months later by the same observer, blinded as to diagnosis and initial measurements. There were highly significant differences in each measurement category, R (P less than 0.0001), S (P less than 0.0001), and P (P less than 0.0004) between BP and CD. However, the correlation between the first and second measurements was excellent (P less than 0.0001). BP was consistently more difficult to interpret because of balloon configuration. Although BP and CD have poor correlation with each other, each examination can be reliably interpreted. CD appears to be a superior examination because of the added ability to delineate rectoceles, intussusceptions, and other structural defects.

HLA and prognostic factors in primary breast cancer.

A group of 157 women with primary breast cancer (BC) were typed for HLA antigens, and gene frequencies were compared to those of 327 control healthy individuals. Diagnosis of BC was made for all patients on surgical mastectomy specimens; histologic grading, estrogen (ER) and progesterone (PgR) receptors were determined on all primary tumors. Typed antigens included the majority of the specificities controlled by the HLA-A, -B and -C loci, according to the 8th International Histocompatibility Testing Workshop recommendations. No significant discrepancy in their frequencies was found in the undivided sample as compared to controls. The analysis of HLA gene frequency was extended to subsets of patients identified by the following prognostic features: (a) age at tumor diagnosis (pre-menopause vs. post-menopause); (b) receptor status (presence vs. absence of ER and PgR); (c) mammary gland dysplasia (presence vs. absence); (d) histologic grade (grade 3 vs. grades 1 and 2 combined); (e) time to relapse before or after 24 months following mastectomy). A moderate deviation from normal of some genes was found in several subsets, often affecting only one of the antithetical subgroups (feature present vs. feature absent). In the instance of B5, the increase in frequency of the gene in one of the subset pair (ER + subjects) was balanced by a decrease of the same gene in the counterpart (ER-subjects). Increased frequencies were found for the B7 gene in the following prognostic groups: (a) lack of ER (0.08); (b) lack of PgR (0.09); (c) absence of mammary dysplasia (0.075); (d) histologic grade 3 (0.10); and (e) premenopause (0.12), the last two showing significant divergence from normal. When features (d) and (e) on the one hand and (a), (b), (d) and (e) on the other were combined, B7 reached frequencies of 0.18 (p less than 5 X 10(-4] and of 0.29 (p less than 5 X 10(-6], respectively.

Decreased antithrombin III activity in diabetes may be due to non-enzymatic glycosylation--a preliminary report.

Antithrombin III activity was moderately but significantly decreased in insulin dependent diabetics (p less than 0.005), while no difference has been found between the diabetic (n = 25) and control groups (n = 22) in antithrombin III plasma concentration. Moreover, antithrombin III activity was inversely correlated with glycosylated plasma proteins (r = 0.57; p less than 0.01). These data show that in diabetes there is a depressed biological activity of antithrombin III and suggest that this reflects nonenzymatic glycosylation of antithrombin III protein.

Lesiones esofagogastricas por ingestion de causticos. / Esophagogastric injuries caused by caustic ingestion

La ingestion accidental o intencional de sustancias causticas de uso quimico o industrial, crea una expectativa de gravedad por el pronostico imprevisible de estos pacientes. Los causticos mas comunmente utilizados son los acidos muriatico, sulfurico y nitrico. Entre los anos 1961 y 1968 y desde 1969 hasta 1979, se trataron 20 casos (11 mujeres y 9 varones), propiciando la intervencion quirurgica precoz de los pacientes, adecuando la tecnica a los hallazgos intraoperatorios, con una mortalidad en ambas series del 40%

Lesiones esofagogastricas por ingestion de causticos. / Esophagogastric injuries caused by caustic ingestion

La ingestion accidental o intencional de sustancias causticas de uso quimico o industrial, crea una expectativa de gravedad por el pronostico imprevisible de estos pacientes. Los causticos mas comunmente utilizados son los acidos muriatico, sulfurico y nitrico. Entre los anos 1961 y 1968 y desde 1969 hasta 1979, se trataron 20 casos (11 mujeres y 9 varones), propiciando la intervencion quirurgica precoz de los pacientes, adecuando la tecnica a los hallazgos intraoperatorios, con una mortalidad en ambas series del 40%