Uso de treprostinil sistémico en una paciente con hipertensión pulmonar grave, sin respuesta a la máxima terapia disponible / Use of treprostinil in a patient with a severe pulmonary arterial hypertension no responding to the maximal therapy available

En los pacientes con Hipertensión Arterial Pulmonar (HAP) de alto riesgo, en clase funcional (CF)IV, la terapia específica debe ser combinada y debe incluir una prostaciclina (PGI2) de uso sistémico en espera de trasplante bipulmonar (TBP). En el sistema público la única PGI2 disponible para asociar a Sildenafil y algún inhibidor de endotelina (Ambrisentan o Bosentan) es Iloprost nebulizado, que si bien es efectiva, no logra estabilizar los casos graves con severa disfunción del ventrículo derecho (VD). Se presenta el primer caso en el Instituto del Tórax, centro de referencia nacional de HAP, del uso de treprostinil en una paciente de 24 años con HAP grave e indicación de TBP. Treprostinil es un análogo sintético de PGI2 de uso subcutáneo en dosis desde 1 a 40 ng/kg/min. La paciente presentaba una situación de extrema gravedad: CF IV, distancia recorrida en el test de caminata de 6 min (DRTC 6 min) < 300 m,derrame pericárdico y severa disfunción del VD con TAPSE (índice de disfunción del VD) de 13 cm/s asociado a ProBNP >2.500 pg/ml. Luego de 6 meses de hospitalización en intermedio, terapia triple (Sildenafil, Ambrisentan e Iloprost nebulizado) asociado a O2,diuréticos y milrinona, logró ser dada de alta a las 3 semanas del inicio de treprostinil, regresando al trabajo a los 2 meses y estabilizando su condición en CF III, con DRTC 6 min > 440 m, mejoría de la función del VD(TAPSE 19). El ProBNP persistió elevado, 1.491 pg/ml, indicando que su enfermedad es grave y progresiva; sin embargo, ha logrado un nivel de estabilidad clínica que le permite una adecuada vida de relación familiar y laboral.

In high risk Pulmonary Arterial Hypertension (PAH) patients with functional class (FC) IV, specific therapy must be combined and must include systemic prostacyclin (PGI2), meanwhile they are enlisted for double lung transplant (DLT). In Chilean Public Health System, nebulized Iloprost is the only PGI2 available to combine with Sildenafil and either Ambrisentan or Bosentan as endothelin receptor antagonist. This association is not enough for severe cases with right ventricular (RV) dysfunction. The first case from the National Institute of Thorax as a referral center is presented now in a 24 years-old lady treated with treprostinil. She has severe PAH with DLT indication. Treprostinil is a PGI2 analog, for subcutaneous use in a dose from 1 to 40 ng/kg/min. She was extremely sick, with FC IV, she walked < 300 m at 6 min walking test (6 MWT), presented pericardial effusion and severe RV dysfunction, with TAPSE (echocardiography index for RV dysfunction)=13 cm/s, ProBNP > 2,500 pg/ml. Six months after being at intensive care unit with triple therapy (Sildenafil, ambrisentan and nebulized Iloprost) plus oxygen, diuretics and milrinone, she was finally discharged after receiving a 3 weeks treprostinil course. She came back to work two months later and her condition was more stable: FC III, she walked > 440 m at 6MWT, with a significant improvement in RV function with TAPSE = 19. Although ProBNP decreased to 1,491pg/ml, it was still high, pointing out the progressive nature of her disease. However, she met a better clinical condition which allows her to reach a much better quality of life from a personal, familial and social point of view.

Phenylpropanoids in radioregulation: double edged sword

Radiotherapy, frequently used for treatment of solid tumors, carries two main obstacles including acquired radioresistance in cancer cells during radiotherapy and normal tissue injury. Phenylpropanoids, which are naturally occurring phytochemicals found in plants, have been identified as potential radiotherapeutic agents due to their anti-cancer activity and relatively safe levels of cytotoxicity. Various studies have proposed that these compounds could not only sensitize cancer cells to radiation resulting in inhibition of growth and cell death but also protect normal cells against radiation-induced damage. This review is intended to provide an overview of recent investigations on the usage of phenylpropanoids in combination with radiotherapy in cancer treatment.

Pulmonary arterial hypertension in children: a medical update.

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by a progressive pulmonary vasculopathy with ensuing right heart failure if left untreated. In the 1980's, prior to the current treatment era, idiopathic pulmonary arterial hypertension (IPAH) carried a poor prognosis with a 10 month median survival for children after diagnosis. However, in 1995 continuous intravenous epoprostenol was approved for the treatment of severe PAH, improving hemodynamics, quality of life, exercise capacity, functional class and survival. In the past decade there have been further advances in the treatment of PAH; however, there is still no cure. While much of the groundbreaking clinical research has been performed in adults, children have also seen the benefits of PAH novel therapies. The target population among pediatric patients is expanding with the recent recognition of pulmonary hypertension as a risk factor for sickle cell disease patients. With rapid advances, navigating the literature becomes challenging. A comprehensive review of the most recent literature over the past year on available and emerging novel therapies as well as an approach to target pediatric populations provides insights into the management of pediatric PAH patients.

Short-term effect of COX-2 selective inhibitor as an adjunct for the treatment of periodontal disease: a clinical double-blind study in humans

Adjunctive therapeutic strategies that modulate the inflammatory mediators can play a significant role in periodontal therapy. In this double-blind, placebo-controlled study, 60 subjects diagnosed as periodontitis patients were evaluated for 28 days after periodontal treatment combined with selective cyclooxygenase-2 (COX-2) inhibitor. The experimental group received scaling and root planning (SRP) combined with the Loxoprofen antiinflammatory drug (SRP+Loxoprofen). The control group received SRP combined with placebo (SRP+placebo). Plaque index (PI), probing pocket depth (PD) and bleeding on probing (BOP) were monitored with an electronic probe at baseline and after 14 and 28 days. Both groups displayed clinical improvement in PD, PI and BOP. They also showed statistically similar values (p>0.05) of PD reduction on day 14 (0.4 mm) and on day 28 (0.6 mm). At the baseline, few deeper sites (>7 mm) from SRP+Loxoprofen group were responsible and most PD reduction was observed after 14 days (p<0.05). The percentage of remaining deep pockets (>7 mm) after 14 days in the SRP+Loxoprofen group was significantly lower (p<0.05) than in the SRP+placebo group. Loxoprofen presents potential effect as an adjunct of periodontal disease treatment, but long-term clinical trials are necessary to confirm its efficacy.

Estratégias terapêuticas adjuvantes que modulam os mediadores inflamatórios podem ter função significante na terapia periodontal. Neste estudo duplo-cego controlado com placebo, 60 indivíduos diagnosticados com periodontite foram avaliados por 28 dias após tratamento periodontal combinado com inibidor seletivo de COX-2. O grupo experimental foi tratado com raspagem e alisamento radicular combinado com medicação anti-inflamatória Loxoprofeno (RAR+Loxoprofen). O grupo controle foi tratado com raspagem e alisamento radicular combinado com medicação placebo (Raspagem e alisamento radicular - RAR+placebo). Presença de placa (PI), profundidade de sondagem (PS) e sangramento à sondagem (SS) foram monitoradas com auxílio de uma sonda computadorizada no início do estudo e após 14 e 28 dias. Os dois grupos demonstraram melhora clínica em relação a PS, PI e SS. Também foi observado valores semelhantes (p>0,05) de redução da PS nos períodos de 14 dias (0,4 mm) e 28 dias (0,6 mm). No início do estudo, alguns sítios profundos (>7 mm) do grupo RAR+Loxoprofen foram os responsáveis pela maior redução da PS depois de 14 dias (p<0,05). A porcentagem de bolsas periodontais profundas >7 mm após 14 dias no grupo RAR+Loxoprofen foi significativamente inferior do que o grupo RAR+placebo (p<0.05). A medicação Loxoprofen apresenta potencial efeito adjuvante à terapia periodontal, mas estudos de longo prazo são necessários para confirmar sua eficácia.

Analgesia con pirprofén en el posoperatorio de cirugía general / Postoperative analgesia with pirprofen in the postoperative period of general surgery

Se valoró, por medio de método doble ciego, el efecto analgésico de la administración en dosis única de pirprofén, diflunisal y zomepirac en el posoperatorio de cirugía general de 90 pacientes distribuidos en tres grupos. Las valoraciones se realizaron mediante una escala visual análoga al momento de tomar el medicamento, a los 15 y 30 minutos, y a la una, dos, tres y cuatro horas después. El efecto analgésico inmediato de pirprofén fue satisfactorio y estadísticamente superior a diflunisal y zomepirac (p=<0.01). Al final del estudio los tres medicamentos tuvieron resultados semejantes entre sí. En cuanto a la tolerancia, fue satisfactoria para los tres medicamentos

Pirprofén en cirugía bucal / Pirprofen in oral surgery

Se valoró, mediante estudio doble ciego, el efecto analgésico de pirprofén, diflunisal y zomepirac, comparando los efectos de la administración en dosis única en 60 pacientes adultos sometidos a cirugía bucal. Los resultados demuestran que pirprofén tuvo acción más rápida que diflunisal, con efecto similar casi al final del estudio, y que tanto pirprofén como diflunisal resultaron más eficaces que zomepirac