INTRODUÇÃO: O elevado número de fatores de risco para doença cardiovascular (DCV) é evidente em portadores de doença renal crônica (DRC). Parece que estes fatores de risco estão intrinsicamente ligados à progressão da DRC. O objetivo deste estudo foi determinar os fatores de risco para DCV independentemente associados à progressão da DRC. MÉTODOS: Através da análise prospectiva, avaliamos os fatores de risco tradicionais, não-tradicionais e os relacionados à DRC em 112 pacientes consecutivos portadores de DRC (clearance de creatinina entre 15 - 89 ml/min),. A progressão da DRC foi avaliada pela variação do clearance de creatinina (DClCr) durante o seguimento, sendo os pacientes estratificados em dois grupos: não-progressores e progressores. RESULTADOS: A frequência dos fatores de risco para DCV foi muito alta e a mediana do DClCr foi de 2,445 ml/min/ano, durante o seguimento. No início do seguimento, não havia diferença significante entre os grupos, quanto ao sexo, raça, clearance de creatinina, IMC, pressão arterial sistólica (PAS) e diastólica (PAD), índice cintura-quadril (ICQ), colesterol total, HDL-colesterol, triglicérides, marcadores inflamatórios, hemoglobina, hematócrito, paratormônio (PTHi), cálcio sérico e ácido úrico. Enquanto, a média do peso corporal, fibrinogênio sérico, LDL-colesterol, fósforo sérico, ingestão de sal e proteinúria foram significativamente maiores no grupo progressores; a média de idade e albumina sérica foi menor. Em adição, os fatores de risco para DCV, idade avançada (p= 0,0140) e história prévia de DCV (p= 0,0063) foram mais freqëntes no grupo não-progressores; ao passo que a anemia (p< 0,0001), hiperfibrinogenemia (p= 0,0112), hipoalbuminemia (p= 0,0019) e proteinúria elevada (p<0,0001) foram mais freqüentes no grupo progressores. Durante o seguimento, o grupo progressores apresentou média de PAS e PAD, LDL-colesterol e proteinúria maiores, no entanto, a albumina sérica foi menor. Os fatores de risco para DCV, durante o seguimento, anemia (p< 0,0001), hiperfosforemia (p< 0,0001), proteinúria elevada (p< 0,0001), hiperparatiroidismo (p= 0,0050) e hipoalbuminemia (p= 0,0019) foram mais freqüentes no grupo progressores. Na análise de regressão múltipla, somente o fator proteinúria, tanto no início como durante o seguimento, foi um preditor significante para a progressão da DRC. CONCLUSÃO: Os fatores de risco para DCV são muito prevalentes entre os pacientes com DRC em tratamento conservador. Embora, este estudo não possa mostrar evidências, sugerindo associação entre a maioria destes fatores de risco para DCV e a taxa de progressão da DRC, apenas a proteinúria predisse uma pior evolução da função renal / Background. The increased risk factors of cardiovascular disease (CVD) is evident in patients with chronic kidney disease (CKD). It has been hypothesized that a number of these risk factors is inextricably linked to the progression of CKD. The purpose of this study was to determine the CVD risk factors independently associated with progression of CKD. Methods. Through prospective analysis, we evaluated traditional, non-traditional, and uremia-related CVD risk factors in 112 consecutive patients with CKD (creatinine clearance between 15 89 ml/min). Progression of kidney disease was evaluated by rate of decline of creatinine clearance during follow-up period, and patients were stratified into two groups: progressor and nonprogressor. Results. The frequency of CVD risk factors was very high, and the median decline of creatinine clearance was 2,445 ml/min/yr, during follow-up period. At baseline, there were no significant differences between progressor and nonprogressor groups in terms of gender, race, creatinine clearance, body mass index, systolic and diastolic blood pressure, and waistrip ratio; cholesterol, HDL-cholesterol, triglycerides, inflammatory markers, hemoglobin, hematocrit, serum calcium, iPTH, and uric acid concentrations While, the mean body weight , serum fibrinogen, LDL-cholesterol, serum phosphate concentrations, salt ingest and proteinuria were significantly higher in the progressor group, the mean age and serum albumin concentrations were lower. In addition, CVD risk factors such as older age (p= 0,0140) and history of previous CVD (p= 0,0063) were more frequent in the nonprogressor group, whereas the hyperfibrinogenemia (p= 0.0112), anemia (p< 0.0001), proteinuria (p< 0.0001) and hypoalbuminemia (p= 0,0019) were more frequent in the progressor group. During follow-up period, the patients in the progressor group had higher systolic and diastolic blood pressure, LDL cholesterol and proteinuria, however serum albumin concentrations were lower. The CVD risk factors, during follow-up period, such as anemia (p< 0,0001), hyperphosphatemia (p< 0,0001), proteinuria (p< 0,0001) were more frequent in the progressor group. In multiple regression analysis, only the factor proteinuria at baseline and during follow-up period was a significant predictor for progression of CKD. Conclusions. CVD risk factors were very prevalent among patients with CKD not requiring dialysis. Although, this study may not show evidences suggesting association between most of these factors and the rate of progression of CKD; only proteinuria predicts an worsening of evolution of kidney function

Introdução: A cirurgia de retalho faríngeo (CRF) é um procedimento indicado para o tratamento da insuficiência velofaríngea, cujo principal sintoma é a hipernasalidade. Para complementar os achados perceptivos dos resultados de fala da CRF são utilizados métodos instrumentais, como a nasometria e a técnica fluxo-pressão. Objetivos: Verificar os resultados de fala da cirurgia de retalho faríngeo comparando-se os três tipos de fissura labiopalatina mais incidentes: fissura de lábio e palato unilateral (FLPU), fissura de lábio e palato bilateral (FLPB) e fissura isolada de palato (FP). Material e Métodos: Estudo transversal, por meio da análise retrospectiva de registros pré e pós-operatórios quanto à avaliação nasométrica e aerodinâmica de 290 pacientes (73 FLPU, 105 FLPB e 112 FP) submetidos à CRF de pedículo superior. A nasalância (correlato acústico da nasalidade) é determinada durante a leitura de amostras de fala padronizadas, utilizando-se um nasômetro (Kay Elemetrics Corp.). Valores de nasalância superiores a 27% são considerados sugestivos de hipernasalidade. Na avaliação aerodinâmica, o fechamento velofaríngeo é estimado a partir da medida da área seccional velofaríngea (sistema PERCI-SARS), durante a produção do fone [p] inserido no vocábulo rampa, permitindo estimá-lo de acordo com a seguinte classificação: valores de 0 a 4,9 mm2=fechamento adequado, 5 a 9,9 mm2=adequado para marginal, 10 a 19,9 mm2=marginal para inadequado e 20 mm2=fechamento inadequado. O teste t pareado comparou os valores de nasalância pré e pós-operatórios em cada tipo de fissura labiopalatina. e os testes ANOVA e Tukey verificaram as diferenças entre os três tipos de fissuras labiopalatinas, nas condições pré e pós-operatória. A área velofaríngea pré e pós-operatória foi analisada por meio do teste de Wilcoxon, em cada tipo de fissura labiopalatina. O teste de Kruskal-Wallis verificou a comparação intergrupos antes e após a cirurgia. Resultados: Os valores médios de nasalância obtidos foram de 40%, 39% e 44% (Pré) e 25%, 24% e 26% (Pós), respectivamente, para FLPB, FLPU e FP. As proporções de casos com fechamento velofaríngeo adequado no pré-cirúrgico e fechamento velofaríngeo adequado no pós-cirúrgico, para os três grupos (FLPB, FLPU e FP) foram de 27%, 6% e 12% e 78%, 75% e 72%, respectivamente. Em ambos os métodos não houve diferença entre os resultados obtidos nos três tipos de fissuras. Conclusão: A CRF mostrou-se igualmente efetiva na correção da insuficiência velofaríngea nos três tipos de fissuras labiopalatinas analisadas: FLPB, FLPU e FP / Introduction: Pharyngeal flap surgery (PFS) is a procedure employed in the treatment of velopharyngeal insufficiency, which main symptom is hypernasality. In order to complement the perceptual findings of speech results of the PFS, instrumental methods such as nasometry and pressure-flow technique are used. Purpose: To investigate the effect of PFS on speech outcomes comparing the three types of more incidents cleft lip and palate: unilateral cleft lip and palate (UCLP), bilateral cleft lip and palate (BCLP) and isolated cleft palate (CP). Methods: Cross-sectional study by means of retrospective analysis of pre- and postoperative findings on nasometric and aerodynamic assessments of 290 patients (73 UCLP, 105 BCLP and 112 CP) who underwent superiorly based pharyngeal flap surgery. Nasalance (acoustic correlate of nasality) is determined during the reading of standardized speech samples, using a nasometer (Kay Elemetrics Corp.), with a cutoff of 27%. In the aerodynamic assessment, the velopharyngeal closure is estimated from the measure of the velopharyngeal minimum cross-sectional area (PERCI-SARS system), during the production of the phone [p], inserted in the word \"rampa\", allowing to estimate it according to the following classification: values from 0 to 4,9 mm2=adequate closure, 5 to 9,9 mm2=adequate-borderline, 10 to 19,9 mm2=borderline-inadequate and 20 mm2=inadequate closure. Paired t-test compared pre and postoperative nasalance scores for each cleft typeand Anova and Tukey tests verified the differences among the three types of cleft lip and palate, in pre- and postoperative condition. Pre- and postoperative velopharyngeal area was analyzed using the Wilcoxon test for each cleft type. The Kruskal-Wallis test verified the comparison between groups before and after surgery. Results: Mean nasalance scores obtained were 40%, 39% and 44% (Pre) and 25%, 24% and 26% (Post), respectively, for BCLP, UCLP and CP. The proportions of cases with inadequate velopharyngeal closure preoperatively and adequate velopharyngeal closure postoperatively for the three groups (BCLP, UCLP and CP), were 67%, 69% and 80% and 78%, 75% and 72%. In both methods there was no difference in the outcomes between cleft type. Conclusion: PFS was shown to be equally effective in correcting velopharyngeal insufficiency in the three types of cleft lip and palate analyzed: BCLP, UCLP and CP

A doença renal crônica (DRC) é hoje um sério problema de saúde pública no Brasil e no mundo. Apesar de um número crescente de publicações abordando os mecanismos que levam à DRC e à sua progressão, são raros os estudos experimentais cujos resultados podem ser transpostos para a prática clínica. Um dos motivos para essa desproporção é o fato de que, em geral, o tratamento é iniciado em concomitância com a instalação da doença, o que aumenta artificialmente a eficácia da terapêutica, uma vez que os fatores patogênicos envolvidos podem ser mais facilmente neutralizados. Resultados bem menos animadores são obtidos se o tratamento é iniciado em fases mais tardias, quando a interação entre esses fatores, muito mais complexa, exige terapêutica mais vigorosa e a associação de dois ou mais fármacos. No presente estudo, examinamos a evolução das lesões renais em um modelo estabelecido de DRC a nefrectomia de 5/6 (Nx) - e o efeito de uma associação entre um bloqueador do receptor AT-1, o losartan (L), e a hidroclorotiazida (H) até agora, a mais eficaz manobra terapêutica para o modelo em questão. Cento e noventa e seis ratos Munich-Wistar machos e adultos foram submetidos a Nx e divididos em quatro grupos: Nx, sem tratamento; L, recebendo monoterapia com L; LH, recebendo a associação L + H; e AHHz, tratados com uma associação entre um bloqueador de canais de cálcio, a anlodipina, um relaxante da musculatura lisa, a hidralazina, e H. Este último grupo serviu para baixar a pressão arterial (PA) independentemente do sistema renina-angiotensina e assim funcionar como controle para esse parâmetro. Um grupo de ratos submetidos a nefrectomia simulada (Sham) foi também estudado. Dois protocolos de estudo foram seguidos. No primeiro (Protocolo 1), os tratamentos foram iniciados 60 dias após Nx, visando simular uma fase relativamente precoce da DRC, com comprometimento funcional e dano estrutural ainda limitado. No segundo (Protocolo 2), os mesmos tratamentos foram iniciados 120 dias após Nx, procurando mimetizar uma DRC humana em estágio mais avançado. Conforme esperado, a DRC progrediu para estágios mais avançados em ambos os protocolos. No entanto, a gravidade da DRC e a mortalidade no Protocolo 2 foram muito maiores do que no Protocolo 1. Apesar dessas diferenças, a eficácia dos tratamentos foi comparável nos dois protocolos. O tratamento com L promoveu proteção apenas parcial contra os danos observados no Grupo Nx. A associação com H propiciou proteção muito mais eficiente, logrando, em ambos os protocolos, trazer a PA, a albuminúria, a taxa de proliferação celular tubular/intersticial e os níveis plasmáticos de aldosterona a níveis inferiores aos observados antes dos tratamentos. Apesar de não reverter a progressão da glomeruloesclerose e da expansão/inflamação intersticial, a associação LH deteve completamente, em ambos os protocolos, a progressão dessas lesões. Por outro lado, a associação AHHz, embora também tenha normalizado a PA, não impediu a progressão da nefropatia nem a da albuminúria, indicando que o efeito protetor da associação LH não se deveu a uma ação hemodinâmica sistêmica. Conclusões: 1) os presentes resultados não apoiam o conceito segundo o qual os tiazídicos deixam de funcionar em fases muito avançadas da DRC, em que a maior parte da função renal já foi perdida; 2) a associação LH é eficiente mesmo em fases avançadas da nefropatia no modelo Nx, detendo sua progressão e mantendo as lesões no nível pré-tratamento, sem, no entanto, fazê-las regredir; 3) essa renoproteção não pode ser explicada somente pelo efeito anti-hipertensivo observado, embora não se possa descartar uma ação sobre a pressão intraglomerular; 4) os mecanismos do efeito renoprotetor da associação LH ainda não estão claros, embora seja provável que envolvam uma combinação de efeitos hemodinâmicos e antiinflamatórios, além de uma notável redução da produção de aldosterona / Chronic kidney disease (CKD) is a serious public health problem in Brazil and worldwide. Despite a growing number of publications on the mechanisms that lead to CKD and its progression, few experimental studies can be translated into clinical practice. One possible reason for this is that, in general, treatment is initiated in concomitance with the onset of the disease, artificially increasing the effectiveness of therapy, since the pathogenic factors involved are more easily neutralized. Far less encouraging results are obtained if treatment is initiated at later stages, when the much more complex interaction between these factors would require more vigorous therapy and the association of two or more drugs. In the present study, we examined the evolution of renal injury in an established model of CKD - 5/6 nephrectomy (Nx) - and the effect of an association between a blocker of the AT-1 receptor, losartan (L), and hydrochlorothiazide (H) - so far, the most effective therapeutic regimen for the Nx model. One hundred ninety-six adult male Munich-Wistar rats were subjected to Nx and divided into four groups: Nx, no treatment; L, receiving L monotherapy; LH, receiving the L+H association, and AHHz, treated with a combination of the calcium channel blocker, amlodipine, the smooth muscle relaxant, hydralazine, and H. This latter group was used to lower blood pressure (BP) independently of the renin-angiotensin system, thus functioning as a control for this parameter. A group of rats subjected to sham nephrectomy (Sham) was also studied. Two study protocols were followed. In the first (Protocol 1), the treatments were initiated 60 days after Nx, aiming to simulate a relatively early stage of CKD, when functional and structural damage is still limited. In the second protocol (Protocol 2), the same treatments were started 120 days after Nx, to mimic advanced human CKD. As expected, CKD progressed to more advanced stages in both protocols. However, mortality and the severity of CKD were much higher in Protocol 2 than in Protocol 1. Despite these differences, the effectiveness of treatments in the two protocols was comparable. L treatment promoted only partial protection against the renal damage observed in Group Nx. The association with H provided much more efficient protection: in both protocols, BP, albuminuria, the rate of tubular/interstitial cell proliferation and plasma aldosterone regressed to lower levels than those observed before treatment. Although glomerulosclerosis and interstitial expansion/inflammation were not reversed, LH treatment completely detained the progression of renal injury in both protocols. On the other hand, the AHHz association, despite normalizing BP, failed to prevent the progression of albuminuria and renal injury, indicating that the protective effect of the LH association was not due to a systemic hemodynamic action. Conclusions: 1) the present results do not support the contention that thiazides have no effect in very advanced stages of CKD, in which most of the kidney function has been lost, 2) the LH association is effective even in advanced stages of nephropathy in the Nx model, arresting progression and keeping injury at pretreatment levels, although it promotes no regression of the renal lesions; 3) LH-induced renoprotection cannot be explained simply by its antihypertensive action, although an effect on intraglomerular pressure cannot be excluded, 4) the mechanisms of LH renoprotection remain unclear, although they are likely to involve a combination of anti-inflammatory and hemodynamic effects, besides a remarkable reduction in the production of aldosterone

The aim of this thesis work has been to develop signal analysis methods for a computerized cardiac auscultation system, the intelligent stethoscope. In particular, the work focuses on classification and interpretation of features derived from the phonocardiographic (PCG) signal by using advanced signal processing techniques. The PCG signal is traditionally analyzed and characterized by morphological properties in the time domain, by spectral properties in the frequency domain or by nonstationary properties in a joint time-frequency domain. The main contribution of this thesis has been to introduce nonlinear analysis techniques based on dynamical systems theory to extract more information from the PCG signal. Especially, Takens' delay embedding theorem has been used to reconstruct the underlying system's state space based on the measured PCG signal. This processing step provides a geometrical interpretation of the dynamics of the signal, whose structure can be utilized for both system characterization and classification as well as for signal processing tasks such as detection and prediction. In this thesis, the PCG signal's structure in state space has been exploited in several applications. Change detection based on recurrence time statistics was used in combination with nonlinear prediction to remove obscuring heart sounds from lung sound recordings in healthy test subjects. Sample entropy and mutual information were used to assess the severity of aortic stenosis (AS) as well as mitral insufficiency (MI) in dogs. A large number of, partly nonlinear, features was extracted and used for distinguishing innocent murmurs from murmurs caused by AS or MI in patients with probable valve disease. Finally, novel work related to very accurate localization of the first heart sound by means of ECG-gated ensemble averaging was conducted. In general, the presented nonlinear processing techniques have shown considerably improved results in comparison with other PCG based techniques. In modern health care, auscultation has found its main role in primary or in home health care, when deciding if special care and more extensive examinations are required. Making a decision based on auscultation is however difficult, why a simple tool able to screen and assess murmurs would be both time- and cost-saving while relieving many patients from needless anxiety. In the emerging field of telemedicine and home care, an intelligent stethoscope with decision support abilities would be of great value.

Des que es va definir la síndrome hepatorenal (SHR), als anys 60 del segle passat, s’han fet grans progressos en el coneixement d’aquesta entitat. La SHR és una insuficiència renal característica dels pacients amb cirrosi hepàtica (CH) amb molt mal pronòstic a curt plaç. El tractament curatiu és el trasplantament hepàtic perquè elimina la CH que és l’origen del problema. Però no sempre està indicat el trasplantament o no s’arriba a temps de realitzar-lo. Els estudis basats en la fisiopatologia de la SHR han estat la base per investigar sobre tractaments que puguin revertir la insuficiència renal i serveixin de pont cap al trasplantament. Fins al moment de la publicació dels treballs que formen part d’aquesta tesi, s’havien fet alguns estudis amb vasoconstrictors esplàcnics que suggerien que aquests fàrmacs eren els més efectius en la reversió de la SHR. Però no s’havien publicat estudis prospectius i aleatoritzats al respecte i aquesta és l’aportació d’un dels estudis: avaluar l’efecte de la terlipressina junt amb l’albúmina sobre la funció renal i la supervivència en pacients amb CH i SHR. Es van aleatoritzar 46 pacients, 23 en el grup de terlipressina i albúmina i 23 en el grup d’albúmina sola. La milloria de la funció renal es va donar en 10 (43,5%) dels pacients tractats amb terlipressina i albúmina i en 3 (8,7%) dels pacients tractats amb albúmina sola (p=0,017). En l’anàlisi multivariat, els factors independents predictius de milloria de la funció renal van ser el volum urinari basal, la creatinina sèrica, el recompte de leucocits i el tractament amb terlipressina i albúmina. La supervivència a 3 mesos no va ser significativament diferent entre els dos grups de tractament (terlipressina i albúmina 27% vs albúmina sola 19%, p=0,7). En l’anàlisi multivariat, els factors independents predictius de supervivència als 3 mesos van ser el MELD basal i la resposta al tractament. A falta d’altres opcions, la terlipressina junt amb albúmina és l’opció terapèutica més efectiva per revertir la SHR i és el tractament que s’ha d’utilitzar, sobretot en els pacients en lista per a trasplantament hepàtic, com a pont fins a l’arribada de l’organ necessari. D’altra banda, malgrat els progressos realitzats en la SHR, els pacients amb CH poden presentar altres tipus d’insuficiència renal i aquest és un camp poc estudiat. En el segon estudi que forma part d’aquesta tesi, basant-nos en un gran número de pacients hospitalitzats, es van avaluar els diferents tipus d’insuficiència renal que poden presentar els pacients amb CH des del punt de vista de la repercusió en el pronòstic. Es van incloure de forma prospectiva, 562 pacients amb CH i insuficiència renal a l’ingrés o que la van desenvolupar durant el mateix. La causa de la insuficiència renal es va classificar en 4 grups: associada a infeccions, a deplecció de volumen, SHR i nefropatia parenquimatosa. La insuficiència renal associada a infeccions va ser la més freqüent (46%), seguida de l’associada a hipovolèmia (32%), SHR (13%) i nefropatia parenquimatosa (9%). Un 17.6% dels casos presentava combinació de causes. La probabilitat de supervivència als 3 mesos va ser del 73% en la nefropatia parenquimatosa, 46% en la insuficiència renal associada a hipovolèmia, 31% en la insuficiència renal associada a infecciones i 15% en la SHR (p<0.0005). En l’anàlisi multivariat ajustat per factors potencialment confusius, la causa de la insuficiència renal estava independentement associada al pronòstic, junto amb el MELD, el sodi sèric i l’encefalopatia hepàtica en el moment del diagnòstic de la insuficiència renal. Aquesta informació és molt important de cara a avaluar els pacients per a trasplantament hepàtic. / Hepatorenal syndrome (HRS) is a type of renal failure common and specific in patients with advanced cirrhosis. The prognosis of HRS is poor and there are no randomized studies with effective treatment for HRS. In one study of this thesis, 46 patients with cirrhosis and HRS were randomly assigned to receive either terlipressin and albumin (n=23) or albumin alone (n=23) for a maximum of 15 days. Primary outcomes were improvement of renal function and survival at 3 months. Improvement of renal function ocurred in 10 patients (43.5%) treated with terlipressin and albumin compared with 2 patients (8.7%) treated with albumin (P=.017). Independent predictive factors of improvement of renal function were baseline urine volume, serum creatinine, leukocyte count, and treatment with terlipressin and albumin. Survival at 3 months was not significantly different between the 2 groups (terlipressin and albumin 27% vs albumin 19%, P=.7). Independent predictive factors of 3-month survival were baseline MELD score and improvement in renal function. In conclusion, the administration of terlipressin and albumin should be considered for the management of patients with cirrhosis and HRS, particularly in patients who are candidates to liver transplantation. The prognostic value of the different causes of renal failure (RF) in cirrhosis is not well stablished. In the other study of this thesis, 562 consecutive patients with cirrhosis and RF (serum creatinine >1.5mg/dl) were prospectively included. The cause of RF was classified into 4 groups: RF associated with bacterial infections, RF associated with volume deplection, HRS and parenchymal nephropathy. The primary end point was survival at 3 months. The frequency of RF was: RF associated with infections: 213 cases ( 46%),hypovolemia-associated RF: 149 (32%), HRS: 60 (13%), and parenchymal nephropathy: 41 (9%). Three-month probability of survival was73% for parenchymal nephropathy, 46% for hypovolemia-associated RF, 31% for RF associated with infections, and 15% for HRS (P<.0005). In the multivariate analysis, cause of RF was independently associated with prognosis, together with MELD score, serum sodium and hepatic encephalopathy. This information may help in decision making in liver transplantation.

Over seven million Americans suffer from Chronic Venous Insufficiency (CVI), a painful and debilitating disease that affects the superficial and deep veins of the legs. Problems associated with CVI include varicose veins, bleeding, ulcerations, severe swelling, deep vein thrombosis, and pulmonary embolism, which may lead to death. The presence of CVI results from damaged (incompetent) one-way vein valves in leg veins. These valves normally allow forward flow of blood to the heart, and prevent blood from pooling at the feet. However, incompetent valves allow reflux of blood, causing clinical problems. There are few effective clinical therapies for treating CVI. Vein valve transplantation is a surgical option for treatment. However, it is often difficult to find suitable donor valves. Very few prosthetic valves developed in the past have demonstrated sufficient clinical or mechanical functionality. Persistent problems include thrombus formation, leaking valves, and valves that do not open at physiologic pressure gradient. The primary objective of this research was to develop a clinically relevant functional prosthetic vein valve. The novel prosthetic valve is flexible, biocompatible, has low thrombogenecity, and is easy to manufacture. It was designed to address well-defined consumer needs and functional design requirements. The valve was required to 1) withstand 300 mmHg of backpressure with leakage less than 1.0 mL/min, 2) open with a pressure gradient less than 5 mmHg, and 3) meet criteria 1 and 2 after 500,000 cycles of operation. The valve met these design requirements in bench testing. The valve can open with a pressure gradient of 2.6 0.7 mmHg, and can withstand 300 mmHg with leakage less than 0.5 mL/min. The valve remained functional after opening and closing over 500,000 times. The valve presented in this research is operationally functional, and is a potential solution for treating venous incompetence in CVI patients.

Sepsis claims over 215,000 lives in the US annually. Inducible glucocorticoids (iGC) is produced during sepsis. However, the precise effects of iGC in sepsis remain unclear due to a lack of appropriate animal models. Glucocorticoid (GC) insufficiency is associated with a marked increase in mortality and occurs in 60% of severe septic patients. Yet the conclusion of GC therapy on septic patients is still controversial. Scavenger receptor class B type I (SR-BI) in the adrenal mediates the selective uptake of cholesteryl ester from lipoproteins for GC synthesis. SR-BI-/- mice completely lack iGC during sepsis and are highly susceptible to septic death, which presents SR-BI-/- mice as a GC insufficient model. However, SR-BI-/- mice display multiple defects contributing to septic death, making it difficult to study iGC by using these mice. Therefore, we utilized adrenal-specific SR-BI-/- mice (ADR-T SR-BI-/-) generated by adrenal transplantation. As expected, the ADR-T SR-BI-/- mice failed to generate iGC under cecal ligation and puncture (CLP)-induced sepsis and showed a significantly higher mortality than the control mice, demonstrating that iGC is essential for preventing septic death. High blood urea nitrogen (BUN) was observed in the ADR-T SR-BI-/- mice but not in the control mice in CLP, indicating that iGC protects kidney injury in sepsis. Plasma IL-6 was remarkably higher in the ADR-T SR-BI-/- mice than the control mice, demonstrating an anti-inflammatory effect of iGC in sepsis. The ADR-T SR-BI-/- mice also displayed significantly lower phagocytic activity of monocytes and neutrophils in the blood and lower activation of T cells in the spleen compared to the control mice in CLP, suggesting that iGC is immunomodulatory in sepsis. Low-dose GC supplementation significantly improved the survival of SR-BI-/- mice in CLP, but did not increase the survival rate of SR-BI+/+ mice in CLP, indicating that GC supplementation improves the survival specifically in mice with adrenal insufficiency. Overall, we revealed that iGC is essential for sepsis survival. iGC prevents kidney damage, modulates inflammatory responses and exerts immunomodulatory functions in sepsis. GC supplementation specifically improves survival of individuals with adrenal insufficiency in sepsis.

Background: Pulmonary artery sarcoma is a rare tumor with a poor prognosis. Case Report: We report the case of a 64-year-old man with an intimal pulmonary artery sarcoma presenting with severe high oxygen flow-demanding dyspnea and weight loss of 12 kg in the last 6 months. On echocardiography, right heart insufficiency, markedly elevated right ventricular pressure, a pressure gradient along the right outflow tract, and a tumor mass adherent to the wall of the truncus pulmonalis were detected. The tentative diagnosis by echocardiographic findings was pulmonary artery sarcoma. Computed tomography of the thorax and 18-fluorodeoxyglucose positron emission tomography showed an advanced local tumor manifestation. Surgical resection of the tumor to improve hemodynamics confirmed the diagnosis. Conclusions: Pulmonary artery sarcoma should be considered as a rare differential diagnosis in patients with dyspnea due to right heart failure, particular in the case of additional weight loss, and echocardiographic examination is a useful first diagnostic approach in establishing the diagnosis. / Hintergrund: Das Pulmonalarteriensarkom ist eine seltene Erkrankung mit einer schlechten Prognose. Fallbericht: Wir berichten über einen 64-jährigen Mann mit einem intimalen Pulmonalarteriensarkom, der sich mit starker Luftnot trotz hoher Sauerstoffsubstitution und einem Gewichtsverlust von 12 kg in den letzten 6 Monaten vorstellte. Echokardiographisch fielen eine Rechtsherzinsuffizienz, ein deutlich erhöhter rechtsventrikulärer Druck, ein Druckgradient über dem rechten Ausflusstrakt und eine Tumormasse im Bereich des Trunkus pulmonalis mit Kontakt zur Gefäßwand auf. Die mittels Echokardiographie erhobene Verdachtsdiagnose lautete Pulmonalarteriensarkom. Die Computertomographie des Thorax und die 18-Flur-Desoxyglukose-Positron-Emissionstomographie erbrachten den Befund eines lokal fortgeschrittenen Tumors. Die chirurgische Resektion des Tumors, die zur Verbesserung der Hämodynamik durchgeführt wurde, bestätigte die Diagnose. Schlussfolgerungen: Das Pulmonalarteriensarkom sollte differenzialdiagnostisch als eine seltene Ursache der Luftnot im Rahmen einer Rechtsherzinsuffizienz, insbesondere bei zusätzlichem Gewichtsverlust, in Erwägung gezogen werden. Die Echokardiographie stellt eine wertvolle initiale Untersuchungsmethode bei der Diagnosestellung dar. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Statement of the problem. Hypernasality resulting from velopharyngeal insufficiency or incompetency is a resonance disorder that has negative consequences for speech production and intelligibility of afflicted individuals. Purpose. The purpose of this prospective study is to ascertain if a palatal lift prosthesis with a generic silicon velar lamina, termed the Toronto Palatal Lift Prosthesis (TPLP), can assist velopharyngeal valve function to reduce hypernasality in patients. Methods. A prospective study of six patients treated with the TPLP was compared by the outcome measures of nasalance scores, perceptual evaluations, and patient satisfaction to those obtained using a contemporary acrylic palatal lift prosthesis. Results. The six patients had varying degrees of reduction in hypernasality and acceptance of the TPLP. Conclusion. On the basis of this preliminary study on the TPLP it is possible to fabricate a palatal lift prosthesis with a generic silicon velar lamina that reduces hypernasality in select patients.

Statement of the problem. Hypernasality resulting from velopharyngeal insufficiency or incompetency is a resonance disorder that has negative consequences for speech production and intelligibility of afflicted individuals. Purpose. The purpose of this prospective study is to ascertain if a palatal lift prosthesis with a generic silicon velar lamina, termed the Toronto Palatal Lift Prosthesis (TPLP), can assist velopharyngeal valve function to reduce hypernasality in patients. Methods. A prospective study of six patients treated with the TPLP was compared by the outcome measures of nasalance scores, perceptual evaluations, and patient satisfaction to those obtained using a contemporary acrylic palatal lift prosthesis. Results. The six patients had varying degrees of reduction in hypernasality and acceptance of the TPLP. Conclusion. On the basis of this preliminary study on the TPLP it is possible to fabricate a palatal lift prosthesis with a generic silicon velar lamina that reduces hypernasality in select patients.