A mediastinal mass causing Budd-Chiari-like syndrome in a cat.

Background: Budd-Chiari syndrome (BCS) is considered a rare condition in cats that is characterized by the obstruction of the hepatic venous outflow tract from the level of the small hepatic veins to the level of the termination of the inferior vena cava into the right atrium in the absence of cardiac or pericardial disease, or sinusoidal obstruction syndrome. Case description: This report presents a 13-year-old cat with a two-week history of progressive lethargy, inappetence, weight loss, and abdominal distension. Findings/treatment and outcome: The radiological study was consistent with pleural effusion, as well as alveolar and interstitial pulmonary patterns. Ultrasonography confirmed hepatic venin congestion and ascites. Abdominocentesis revealed a modified transudate. A computed tomography (CT) angiography showed a mass at the level of the caudal mediastinum that compressed the caudal vena cava (CVC). Mediastinal lymphoma was considered the most likely differential diagnosis. These findings were interpreted as Budd-Chiari-like syndrome (BCLS) secondary to a mediastinal mass although, unfortunately, no further diagnostic or treatment procedures were accepted by the owners. BCLS is a rare condition in cats, where most of the reported cases occurred as a result of obstruction of the caudal vena cava. In this report, BCLS was caused by a mass located in the caudal mediastinum oppressing the caudal vena cava. Conclusion: This is the first report of BCLS in cats diagnosed by CT angiography, and it shows the value of this technique to define the origin and extent of the mass and to evaluate the presence or absence of metastatic lesions.

[COVID-19 Pandemic: Impact and rapid reaction of Urology]. / Pandemia COVID-19: impacto y reacción rápida de la Urología.

The COVID-19 pandemic caused by the SARS-CoV-2 virus has caused tens of thousands of deaths in Spain and has managed to breakdown the healthcare system hospitals in the Community of Madrid, largely due to its tendency to cause severe pneumonia, requiring ventilatory support. This fact has caused our center to collapse, with 130% of its beds occupied by COVID-19 patients, thus causing the absolute cessation of activity of the urology service, the practical disappearance of resident training programs, and the incorporation of a good part of the urology staff into the group of medical personnel attending these patients. In order to recover from this extraordinary level of suspended activity, we will be obliged to prioritize pathologies based on purely clinical criteria, for which tables including the relevance of each pathology within each area of urology are being proposed. Technology tools such as online training courses or surgical simulators may be convenient for the necessary reestablishment of resident education.

[COVID-19 Pandemic: Impact and rapid reaction of Urology]. / Pandemia COVID-19: impacto y reacción rápida de la Urología.

The COVID-19 pandemic caused by the SARS-CoV-2 virus has caused tens of thousands of deaths in Spain and has managed to breakdown the healthcare system hospitals in the Community of Madrid, largely due to its tendency to cause severe pneumonia, requiring ventilatory support. This fact has caused our center to collapse, with 130% of its beds occupied by COVID-19 patients, thus causing the absolute cessation of activity of the urology service, the practical disappearance of resident training programs, and the incorporation of a good part of the urology staff into the group of medical personnel attending these patients. In order to recover from this extraordinary level of suspended activity, we will be obliged to prioritize pathologies based on purely clinical criteria, for which tables including the relevance of each pathology within each area of urology are being proposed. Technology tools such as online training courses or surgical simulators may be convenient for the necessary reestablishment of resident education.

Molecular characterization of congenital myasthenic syndromes in Spain.

Congenital myasthenic syndromes (CMS) are a heterogeneous group of genetic disorders, all of which impair neuromuscular transmission. Epidemiological data and frequencies of gene mutations are scarce in the literature. Here we describe the molecular genetic and clinical findings of sixty-four genetically confirmed CMS patients from Spain. Thirty-six mutations in the CHRNE, RAPSN, COLQ, GFPT1, DOK7, CHRNG, GMPPB, CHAT, CHRNA1, and CHRNB1 genes were identified in our patients, with five of them not reported so far. These data provide an overview on the relative frequencies of the different CMS subtypes in a large Spanish population. CHRNE mutations are the most common cause of CMS in Spain, accounting for 27% of the total. The second most common are RAPSN mutations. We found a higher rate of GFPT1 mutations in comparison with other populations. Remarkably, several founder mutations made a large contribution to CMS in Spain: RAPSN c.264C > A (p.Asn88Lys), CHRNE c.130insG (Glu44Glyfs*3), CHRNE c.1353insG (p.Asn542Gluf*4), DOK7 c.1124_1127dup (p.Ala378Serfs*30), and particularly frequent in Spain in comparison with other populations, COLQ c.1289A > C (p.Tyr430Ser). Furthermore, we describe phenotypes and distinguishing clinical signs associated with the various CMS genes which might help to identify specific CMS subtypes to guide diagnosis and management.

[Aicardi-Goutieres syndrome due to mutation of the IFIH1 gene with pontine involvement. A case report]. / Sindrome de Aicardi-Goutieres por mutacion en el gen IFIH1 con afectacion pontina. A proposito de un caso.

INTRODUCTION: Aicardi-Goutieres syndrome is a rare progressive subacute encephalopathy of early onset - generally in the first year of life - characterised by psychomotor retardation, microcephaly, alterations in the white matter of the brain, intracranial calcifications, pleocytosis and elevated levels of interferon alpha in the cerebrospinal fluid. It is associated to an increase in the expression of genes stimulated by interferon in peripheral blood, a fact known as the interferon signature. The levels of genes stimulated by interferon has been postulated as a good biomarker, as they remain high in peripheral blood over time and are more sensitive, in comparison to determinations of interferon alpha and neopterins in cerebrospinal fluid, which descend as of one year of life. To date, mutations have been reported in seven genes that overstimulate the interferon alpha pathway, and the last to be discovered is IFIH1 (interferon induced with helicase C domain 1), with a pattern of dominant autosomal inheritance. CASE REPORT: We present the first case reported in the Hispanic literature caused by a de novo mutation in the IFIH1 gene. The clinical features, studies conducted and review of the clinical, neuroradiological and genetic aspects are described. CONCLUSIONS: The inheritance of the mutations reported for Aicardi-Goutieres syndrome was classically considered as being recessive autosomal, but these findings show that dominant autosomal mutations in the IFIH1 gene can cause the disease. As a previously unreported neuroimaging finding, it presents a lesion consisting in cystic encephalomalacia in the pons.

TITLE: Sindrome de Aicardi-Goutieres por mutacion en el gen IFIH1 con afectacion pontina. A proposito de un caso.Introduccion. El sindrome de Aicardi-Goutieres es una rara encefalopatia subaguda progresiva de inicio precoz ­generalmente en el primer año de vida­ caracterizada por retraso psicomotor, microcefalia, alteraciones en la sustancia blanca cerebral, calcificaciones intracraneales, pleocitosis y niveles elevados de interferon alfa en el liquido cefalorraquideo. Asocia un incremento en la expresion de los genes estimulados por interferon en la sangre periferica, hecho conocido como interferon signature. Los niveles de genes estimulados por interferon se han postulado como un buen biomarcador, pues se mantienen elevados en la sangre periferica en el tiempo y son mas sensibles, en comparacion con las determinaciones de interferon alfa y neopterinas en el liquido cefalorraquideo, las cuales descienden a partir del año de vida. Hasta la fecha se han descrito mutaciones en siete genes que sobreestimulan la via del interferon alfa, y el ultimo en descubrirse ha sido el IFIH1 (interferon induced with helicase C domain 1), con un patron de herencia autosomico dominante. Caso clinico. Se presenta el primer caso descrito en la bibliografia hispana debido a mutacion de novo en el gen IFIH1. Se expone el cuadro clinico, los estudios realizados y la revision de los aspectos clinicos, neurorradiologicos y geneticos. Conclusiones. La herencia de las mutaciones descritas para el sindrome de Aicardi-Goutieres era clasicamente autosomica recesiva, pero estos hallazgos muestran que mutaciones autosomicas dominantes en el gen IFIH1 pueden causar la enfermedad. Como hallazgo de neuroimagen no descrito previamente, presenta una lesion de encefalomalacia quistica en la protuberancia.

Characterization of two Bunodosoma granulifera toxins active on cardiac sodium channels.

1. Two sodium channel toxins, BgII and BgIII, have been isolated and purified from the sea anemone Bunodosoma granulifera. Combining different techniques, we have investigated the electrophysiological properties of these toxins. 2. We examined the effect of BgII and BgIII on rat ventricular strips. These toxins prolong action potentials with EC50 values of 60 and 660 nM and modify the resting potentials. 3. The effect on Na+ currents in rat cardiomyocytes was studied using the patch-clamp technique. BgII and BgIII slow the rapid inactivation process and increase the current density with EC50 values of 58 and 78 nM, respectively. 4. On the cloned hH1 cardiac Na+ channel expressed in Xenopus laevis oocytes, BgII and BgIII slow the inactivation process of Na+ currents (respective EC50 values of 0.38 and 7.8 microM), shift the steady-state activation and inactivation parameters to more positive potentials and the reversal potential to more negative potentials. 5. The amino acid sequences of these toxins are almost identical except for an asparagine at position 16 in BgII which is replaced by an aspartic acid in BgIII. In all experiments, BgII was more potent than BgIII suggesting that this conservative residue is important for the toxicity of sea anemone toxins. 6. We conclude that BgII and BgIII, generally known as neurotoxins, are also cardiotoxic and combine the classical effects of sea anemone Na+ channels toxins (slowing of inactivation kinetics, shift of steady-state activation and inactivation parameters) with a striking decrease on the ionic selectivity of Na+ channels.

Cardiac cellular actions of hydrochlorothiazide.

In long term treatment, thiazide diuretics such as hydrochlorothiazide (HCTZ) lower blood pressure by decreasing peripheral resistance rather than by their diuretic effect. This action has been attributed to the opening of Ca2+-activated K+ channels in vascular smooth muscle cells. However, little is known about their cardiac cellular actions. Here we investigated the possible actions of HCTZ on action potential and contraction of rat ventricular muscle strips and on the ionic currents of isolated rat ventricular cardiomyocytes. HCTZ depressed ventricular contraction with an IC30 of 1.85 microM (60% decrease at 100 microM). Action potential duration at -60 mV and maximal rate of depolarization were, however, only slightly decreased by 12% and 22%, respectively, at 100 microM. At the single cell level, HCTZ (100 microM) depressed the fast Na+ current (INa) and the L-type Ca2+ current (ICaL) by 30% and 20%, respectively. The effects on ICaL were not voltage-or frequency-dependent. In cells intracellularly perfused with 50 microM cyclic adenosine, monophosphate HCTZ reduced ICaL by 33%. The transient (Ito), the delayed rectifier and the inward rectifier potassium currents were decreased by 20% at 100 microM HCTZ. The effects on Ito were voltage-dependent. In conclusion, HCTZ at high concentrations possesses a negative inotropic action that could be in part due to its blocking action on INa and ICaL. The actions of HCTZ on multiple cardiac ionic currents could explain its weak effect on action potential duration.

Modulation of voltage-dependent facilitation of the T-type calcium current by sodium ion in isolated frog atrial cells.

Sodium ions have been reported to alter the permeation properties of L- and N-type Ca2+ channels. Here in frog atrial cardiomyocytes under whole-cell patch-clamp conditions, we have examined the effects of lowering the external Na+ concentration on the amplitude of T-type Ca2+ current, ICaT, and on the relief of its steady-state inactivation by large depolarizing prepulses, ICaT facilitation. A partial reduction in Na+ ion concentration did not significantly alter ICaT amplitude elicited at -50 mV. However, after a large depolarization, low- Na+ solutions enhanced the relief of inactivation and induced ICaT facilitation. This facilitation occurred independently of the divalent charge carrier, high intracellular Ca2+ buffering or the intracellular Na+ content. Its effects were additional to the beta-adrenergic effects mediated by a decrease of Gi/o-protein inhibitory tone. In Ca2+-free solution the very large T-type current, then carried by Na+ ions, showed only a weak relief of inactivation. In conclusion, ICaT facilitation--which, as previously reported, is modulated by the transient voltage-dependent relief of Gi-protein inhibitory tone--is further enhanced in a low-Na+ solution. In Ca2+-free solution, relief of inactivation due to re-openings dependent on the divalent charge carrier is improbable. It thus appears that for a short while after a large depolarization, external Na+ compete with Ca2+ ions on permeation-controlling sites, so as to modulate channel re-openings and thus the amplitude of voltage-facilitated ICaT independently of the control exerted by the inhibitory G-protein.

Frequency-dependent increase in cardiac Ca2+ current is due to reduced Ca2+ release by the sarcoplasmic reticulum.

"Ca(2+)-current facilitation" describes several features of increase in current amplitude often associated with a reduction in inactivation rate. The aim of this study was to investigate the mechanism of frequency-dependent increase in L-type Ca2+ current, I(Ca) taking advantage of recent knowledge on the control of Ca2+ current inactivation in cardiac cells. The frequency-dependent increase in I(Ca) was studied in adult rat ventricular myocytes using the whole-cell patch-clamp technique. I(Ca) was elicited by a train of 200-ms depolarizing pulses to +20 mV applied at various frequencies (0.2 up to 1.3 Hz). The increase in frequency induced a rate-dependent enhancement of I(Ca), or facilitation phenomena. In most cells, that showed two inactivation phases of I(Ca), facilitation was mainly related to slowing of the fast I(Ca) inactivation phase that occurred besides increase in peak I(Ca) amplitude. Both the decrease and slowing of the fast component of inactivation phase were attenuated on beta -adrenergic-stimulated current. Frequency-dependent I(Ca) facilitation paralleled a reduction in Ca2+ transient measured with fluo-3. After blocking sarcoplasmic reticulum-Ca2+ release by thapsigargin, the fast I(Ca) inactivation phase was reduced and facilitation was eliminated. Facilitation could not then be restored by 1 microM isoprenaline. Thus in rat ventricular myocytes, frequency-dependent facilitation of I(Ca)reflects a reduced Ca(2+)-dependent inactivation consecutive, in most part, to reduced Ca2+ load and Ca2+ release by the sarcoplasmic reticulum rather than being an intrinsic characteristic of the L-type Ca2+ channel.