Sildenafil in pediatric pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a life-threatening disease of varied etiologies. Although PAH has no curative treatment, a greater understanding of pathophysiology, technological advances resulting in early diagnosis, and the availability of several newer drugs have improved the outlook for patients with PAH. Sildenafil is one of the therapeutic agents used extensively in the treatment of PAH in children, as an off-label drug. In 2012, the United States Food and Drug Administration (USFDA) issued a warning regarding the of use high-dose sildenafil in children with PAH. This has led to a peculiar situation where there is a paucity of approved therapies for the management of PAH in children and the use of the most extensively used drug being discouraged by the regulator. This article provides a review of the use of sildenafil in the treatment of PAH in children.KEY WORDS: Child, phosphodiesterase (PDE)-5 inhibitor, Pulmonary hypertension therapy     

Interstitial flow as a guide for lymphangiogenesis

The lymphatic system is important in tissue fluid balance regulation, immune cell trafficking, edema, and cancer metastasis, yet very little is known about the sequence of events that initiate and coordinate lymphangiogenesis. Here, we characterize the process of lymphatic regeneration by uniquely correlating interstitial fluid flow and lymphatic endothelial cell migration with lymphatic function. A new model of skin regeneration using a collagen implant in a mouse tail has been developed, and it shows that (1) interstitial fluid channels form before lymphatic endothelial cell organization and (2) lymphatic cell migration, vascular endothelial growth factor-C expression, and lymphatic capillary network organization are initiated primarily in the direction of lymph flow. These data suggest that interstitial fluid channeling precedes and may even direct lymphangiogenesis (in contrast to blood angiogenesis, in which fluid flow proceeds only after the vessel develops); thus, a novel and robust model is introduced for correlating molecular events with functionality in lymphangiogenesis.     

Neoadjuvant Treatment of Duodenal Adenocarcinoma: A Rescue Strategy

Aim  

To evaluate the role of neoadjuvant chemoradiation therapy and rescue surgery in the management of unresectable or recurrent duodenal adenocarcinoma.     

Identifying facilitators and barriers for home injury prevention interventions for pre-school children: a systematic review of the quantitative literature

Injuries are the leading cause of childhood death internationally; steep social gradients exist in mortality and morbidity. The majority of pre-school injuries occur in the home, but implementing research into practice for injury prevention has received little attention. This systematic review describes key facilitators and barriers when implementing injury prevention interventions. The review used articles included in a Cochrane systematic review of the effectiveness of home safety education, with or without the provision of safety equipment. Each paper was screened to ensure that children under 5 years, intervention details and process measures and/or barriers and facilitators were included. Two authors independently reviewed each paper and extracted data. Themes were identified and framework analysis used in an iterative process. Ninety-nine papers were identified, 42 excluded and 57 included in the analysis. Seven facilitators and six barriers were identified. Facilitators related to the approach used, focused messages, minimal changes, deliverer characteristics, equipment accessibility, behaviour change and including incentives. The barriers included complex interventions, cultural, socio-economic, physical and behavioural barriers and deliverer constraints. Barriers and facilitators should be addressed when implementing injury prevention interventions and studies should explicitly explore factors that help or hinder the process.     

Endoscopic ultrasound-guided trucut biopsy of the cyst wall for diagnosing cystic pancreatic tumors.

BACKGROUND & AIMS: Nonoperative methods for diagnosis of pancreas cysts often lack sufficient accuracy. Accurate diagnosis is needed to determine prognosis and guide clinical management. The aim of this study was to determine whether the tissue obtained by endoscopic ultrasound-guided trucut biopsy (EUS TCB) is sufficient for histologic diagnosis of cystic pancreatic tumors (CPTs). METHODS: EUS TCB was performed in patients with a suspected CPT. A dedicated gastrointestinal pathologist reviewed the core biopsies. The final diagnosis was based on clinical, laboratory, imaging, and biopsy findings, and resected specimens when available. RESULTS: EUS TCB was performed in 10 patients with a suspected CPT. Final diagnoses included serous cystadenoma (SCA, n=5), islet cell tumor (n=2), mixed seromucinous lesion (n=1), polycystic disease of the pancreas (n=1), and pseudocyst (n=1). EUS TCB was nondiagnostic in 3 of 10 patients. Among the other 7 patients, TCB diagnosed 4 SCAs, obviating the need for planned surgery in 3 patients. In the fourth patient with an SCA, the TCB result ruled out metastatic disease from locally recurrent lung cancer, allowing a narrowed radiation field. EUS TCB confirmed the need for surgery in 2 patients with an islet cell tumor. In 1 patient, EUS TCB findings were "partially" diagnostic, leading to previously unplanned surgery. CONCLUSIONS: This report establishes the capability and safety of EUS TCB to collect sufficient tissue for diagnosing CPTs. The results might help guide clinical management.     

Serological studies on Mycoplasma hominis: serotypic distribution of recent clinical isolates.

Serotyping of strains of Mycoplasma hominis, freshly isolated from various sources, was conducted using the complement-independent growth agglutination (GA) test, using the 7 reference antisera prepared in our laboratory. Multiple isolates from a common source indicated that only a single serotype tends to be found, making it possible to serotype clinical isolates without further cloning. However, cultures collected at different times from the same individual may contain different serotypes. A total of 213 recent cultures were serotyping and a majority of these were assigned to the closely related serogroups 1, 2, and 3. Strains isolated during pregnancy, that were associated with various disorders of pregnancy, were serotypically diverse and no one strain seemed to be particularly likely to be associated with disorders of pregnancy.     

Protection of ovarian function by oral contraceptives in women receiving chemotherapy for Hodgkin's disease

It has been reported by us and by others that after chemotherapy for Hodgkin's disease the ovary contains fewer than 5 primordial and primary follicles per 5 x 5 mm biopsy section. In young women this is associated with premature menopause. We report here that before treatment the tissue contains 18--55 such follicles per biopsy section. When women took combination oral contraceptives throughout the course of MVPP therapy, the posttreatment ovarian biopsy tissue had more than 20 follicles per histologic section. Normal menses were established in the five women who discontinued oral contraceptives at the end of MVPP therapy, and one of them is now pregnant.     

Russia's imperial blood: Was Rasputin not the healer of legend?

The only son of Russia's last Tsar, a great-grandson of Queen Victoria, continues to be used as the favorite example of the X-linked inheritance of hemophilia, in spite of the fact that this popular historical diathesis has never been confirmed by any form of modern medical laboratory testing. Certain to be controversial, a new study of the symptoms that were witnessed by those who were closest to the teenaged Russian heir now raises the possibility that his blood disorder might well have been something other than hemophilia. The key to discovering Tsarevich Alexei's true diagnosis is found in those now legendary allegations that the infamous "Mad Monk", Grigory Rasputin, had possessed a power of healing that was somehow responsible for the young boy's mysterious history of spontaneous recoveries. If we are to accept the popular diagnosis of history and call it a clotting factor deficiency, then the boy's now famous sudden recoveries will remain a complete mystery. The so-called "Mad Monk" Rasputin, as a direct result of the revolutionary propaganda of the time, is then overblown into a larger-than-life legend. If, however, we are to change the diagnosis and call it a platelet disorder, then the air is let out of the legend, and Rasputin is revealed to have been nothing more than a very ordinary middle-aged Siberian hippie who did not possess any healing powers at all.