Surgical treatment of liver injuries by application of Fibrinkleber

The combination of highly concentrated fibrinogen, thrombin, clotting factor XIII, and fibrinolytic inhibitor aprotinin represents a new biological hemostatic, and adhesive system, known as Fibrinkleber. Liver injuries and injuries of parenchymatous organs, with the difficulties inherent in their surgical repair, are a suitable field of application for the new substance. In our experimental work, standardized sharp liver injuries in 29 rabbits were treated only by application of Fibrinkleber. In all cases, this procedure resulted in a complete control of bleeding as well as in a stable and lasting closure of wounds. Five of these animals died from causes unrelated to the liver trauma but rather to parasitosis. During the postoperative observation period, from 2 days to 2 months, microscopic and histological examination showed ideal repair of the glued wounds. In the control group, 5 rabbits were kept without application of Fibrinkleber. Three of the rabbits with liver injuries and all of the control group histological examinations showed separation of the wounds with minimal healing.

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Resumen Debido a su tamaño y ubicación, el hígado es un órgano muy vulnerable en casos de trauma abdominal. Las heridas hepáticas varían considerablemente y su severidad dépende del tipo y magnitud del trauma. En virtud de la vascularidad del hígado y, según la localización de la herida, el tratamiento del trauma hepático con frecuencia es difícil. La hemorragia resultante y los consiguientes complejos problemas postoperatorios significan un desafío formidable.La combinación de fibrinógeno altamente concentrado, trombina, factor XIII de coagulación y aproptinina, un inhibidor de fibrinolisis, ha venido a representar un nuevo sistema biológico hemostático y adhesivo, el cual se conoce como Fibrinkleber. Las lesiones hepáticas y en general las heridas de los órganos parenquimatosos, por las dificultades que presentan en el momento de la reparación quirúrgica, constituyen un campo propicio para la aplicación de esta nueva sustancia. En nuestro trabajo experimental se trataron heridas hepáticas estandarizadas en 29 conejos mediante la sóla aplicación de Fibrinkleber. Tal procedimiento resultó, en todos los casos, en un completo control del sangrado y en un cierre estable y duradero de las heridas por la firme adherencia de las superficies hepáticas. Cinco de los animales fallecieron por causas no relacionadas con el trauma hepático sino con parasitosis. En el curso del período de observación postoperatoria, desde el segundo día hasta dos meses, los exámenes microscópicos e histológicos mostraron una cicatrización ideal de las heridas así adheridas. En el grupo de control se incluyó a cinco conejos que no recibieron la aplicación de Fibrinkleber. Tres de estos perecieron poco tiempo después de infligida la lesión, y en todos el examen histológico demostró separación de la herida con mínima cicatrización.

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Résumé La combinaison à haute concentration de fibrinogène, de thrombine du facteur XIII et de l'aprotinine (inhibiteur de la fibrinolyse) permet de constituer un agent biologique d'hémostase et de coalescence dénommé Fibrinkleber. Les blessures du foie et plus généralement les blessures des organes parenchymateux dont la cure est difficile à assurer chirurgicalement sont susceptibles d'être traitées efficacement par cette nouvelle substance. A titre expérimental des blessures du foie identiques chez 29 lapins ont été traités uniquement par ce nouvel agent. Dans tous les cas l'hémorragie pu être arrêtée et la coalescence définitive de la plaie pu être obtenue. Cinq des 29 lapins moururent non de leur plaie hépatique mais de parasitose. Pendant la période d'observation postopératoire s'étendant du deuxième jour jusqu'à la fin du deuxième mois l'examen macroscopique et l'examen microscopique permirent de constater la cicatrisation parfaite de la plaie. Un groupe de contrôle comprenant cinq lapins qui présentaient une blessure hépatique de type identique mais traitée sans l'aide de l'agent coagulant et coalescent permit de constater que la plaie persistait et que sa cicatrisation était minime.

     

Chemotherapy of brain tumors

This is a review of chemotherapy options for patients with brain tumors, both at the time of initial diagnosis and at recurrence. Gliomas, the most common malignant brain tumors, represent the main focus of the review; chemotherapeutic options for supratentorial, brain stem, and optic track gliomas are discussed.     

“Heart failure in COVID-19 patients: Critical care experience”: A letter to the editor

Coronavirus disease 2019 (COVID-19) is associated with poor cardiovascular outcomes in patients with heart failure (HF) of all categories of ejection fraction (EF), but mainly in patients with HF with reduced EF. Moreover, cardiac transplant patients exhibit worse cardiovascular prognosis, high mortality, and more admissions to the intensive care unit. In general, COVID-19 seems to de-teriorate the clinical status of HF and favors the development of acute respiratory distress syndrome and multiorgan failure, especially in the presence of cardiovascular comorbidities such as diabetes mellitus, kidney dysfunction, and older age. COVID-19 may induce new-onset HF with complex mechanisms that involve myocardial injury. Indeed, myocardial injury comprises a large category of detrimental effects for the myocardium, such as myocardial infarction type 1 or type 2, Takotsubo cardiomyopathy, microvascular dysfunction and myocarditis, which are not easily distinguished by HF. The pathophysiologic mechanisms mainly involve direct myocardial damage by severe acute respiratory syndrome coronavirus 2, cytokine storm, hypercoagulation, inflammation, and endothelial dysfunction. The proper management of patients with COVID-19 involves careful patient evaluation and ongoing monitoring for complications such as HF.     

cGMP catabolism by phosphodiesterase 5A regulates cardiac adrenergic stimulation by NOS3-dependent mechanism

Beta-adrenergic agonists stimulate cardiac contractility and simultaneously blunt this response by coactivating NO synthase (NOS3) to enhance cGMP synthesis and activate protein kinase G (PKG-1). cGMP is also catabolically regulated by phosphodiesterase 5A (PDE5A). PDE5A inhibition by sildenafil (Viagra) increases cGMP and is used widely to treat erectile dysfunction; however, its role in the heart and its interaction with beta-adrenergic and NOS3/cGMP stimulation is largely unknown. In nontransgenic (control) murine in vivo hearts and isolated myocytes, PDE5A inhibition (sildenafil) minimally altered rest function. However, when the hearts or isolated myocytes were stimulated with isoproterenol, PDE5A inhibition was associated with a suppression of contractility that was coupled to elevated cGMP and increased PKG-1 activity. In contrast, NOS3-null hearts or controls with NOS inhibited by N(G)-nitro-L-arginine methyl ester, or soluble guanylate cyclase (sGC) inhibited by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one, showed no effect of PDE5A inhibition on beta-stimulated contractility or PKG-1 activation. This lack of response was not attributable to altered PDE5A gene or protein expression or in vitro PDE5A activity, but rather to an absence of sGC-generated cGMP specifically targeted to PDE5A catabolism and to a loss of PDE5A localization to z-bands. Re-expression of active NOS3 in NOS3-null hearts by adenoviral gene transfer restored PDE5A z-band localization and the antiadrenergic efficacy of PDE5A inhibition. These data support a novel regulatory role of PDE5A in hearts under adrenergic stimulation and highlight specific coupling of PDE5A catabolic regulation with NOS3-derived cGMP attributable to protein subcellular localization and targeted synthetic/catabolic coupling.     

Measles virus expressed Helicobacter pylori neutrophil-activating protein significantly enhances the immunogenicity of poor immunogens

Helicobacter pylori neutrophil-activating protein (NAP) is a toll-like receptor 2 (TLR2) agonist and potent immunomodulator inducing Th1-type immune response. Here we present data about characterization of the humoral immune response against NAP-tagged antigens, encoded by attenuated measles virus (MV) vector platform, in MV infection susceptible type I interferon receptor knockout and human CD46 transgenic (Ifnarko-CD46Ge) mice. Immunogenicity of MV expressing a full-length human immunoglobulin lambda light chain (MV-lambda) was compared to that of MV expressing lambda-NAP chimeric protein (MV-lambda-NAP). MV-lambda-NAP immunized Ifnarko-CD46Ge mice developed significantly higher (6–20-fold) anti-lambda ELISA titers as compared to the MV-lambda-immunized control animal group, indicating that covalently-linked NAP co-expression significantly enhanced lambda immunogenicity. In contrast, ELISA titers against MV antigens were not significantly different between the animals vaccinated with MV-lambda or MV-lambda-NAP. NAP-tagged antigen expression did not affect development of protective anti-measles immunity. Both MV-lambda and MV-lambda-NAP-immunized groups showed strong virus neutralization serum titers in plaque reduction microneutralization test. These results demonstrated that MV-encoded lambda-NAP is highly immunogenic as compared to the unmodified full-length lambda chain. Boost of immune response to poor immunogens using live vectors expressing NAP-tagged chimeric antigens is an attractive approach with potential application in immunoprophylaxis of infectious diseases and cancer immunotherapy.     

An observational study of sun and heat protection during Canada Day outdoor celebration, 2003

Attendance at summer outdoor mass gatherings may lead to heat- and sun-related illness. The purposes of this study were: (1) to estimate the proportion of people in attendance at the 2003 Canada Day celebration in the National Capital Region who used sun and heat protective items; (2) to identify factors associated with the utilization of these protective items; and (3) to provide research data to public outdoor event organizers when developing evidence-based plans for safer events. A naturalistic observational cross-sectional method was used to gather information at the 2003 Canada Day celebration in the National Capital Region on attendees' demographics, the sun and heat protective items they used and the protective resources available at the event sites. Of the 398 observed attendees, the proportion using any one of the protective items ranged from 3 percent (an open umbrella) to 51.5 percent (sunglasses). Females were more likely to use protective items more than males, and adults more likely than children. Planners of public outdoor events should consider the factors that influence the utilization of sun and heat protective behaviours and the environmental modifications that would allow participants to make safe choices.     

Incidental thyroid cancer in patients undergoing total thyroidectomy for benign disease

Aim

To determine the frequency of incidental thyroid carcinoma (ITC) in patients undergoing surgery for presumably benign thyroid diseases.

Methods

A total of 267 patients submitted to total thyroidectomy were included in the study.

Results

Histology revealed ITC in 31 (11.6%) patients. Papillary carcinoma was the commonest ITC at a percentage of 71% (22/31 patients), while follicular variant accounted for 29%. ITC was more common in patients with toxic goitre and toxic solitary nodule.

Conclusions

The result of this study show a high incidence of ITC (11.6 %). The frequency differs among patients presenting a different thyroid pathology. This is because of the small sample used in the study. Papillary carcinoma was the commonest ITC.