Myocarditis in admitted patients with dengue fever.

PURPOSE: Cardiac involvement in dengue fever is underdiagnosed due to low index of clinical suspicion and its contribution to hemodynamic instability in severe dengue is not well known. METHODS: A prospective observational study was conducted among admitted patients ≥ 14 years of age having confirmed dengue fever. Patients on medications affecting heart rhythm/rate, pre-existing heart disease and electrolyte abnormalities were excluded. A baseline electrocardiography (ECG), Trop-I and NT-proBNP were done for all patients. The biomarkers were measured using enzyme-linked fluorescent assay and recommended cut-off were used. Patients with elevated biomarkers underwent 2-dimensional echocardiography. Diagnosis of myocarditis was as per European Society of Cardiology (ESC) 2013 criteria. RESULTS: A total of 182 patients were recruited with mean age of 30 ± 12.6 years and 31% were females. Dengue with warning signs was present in 85 (47%) and severe dengue in 60 (33%) patients. ECG abnormalities were observed in 44 (24%) patients, biomarkers were elevated in 27 (15%) patients and 11 (6%) patients had echocardiographic abnormalities. According to ESC 2013 criteria, dengue fever with myocarditis was diagnosed in 13 [7.1% (95% CI 3.4-10.9)] patients. The patients with myocarditis were more likely to have shortness of breath, bleeding manifestations and higher respiratory rate at baseline. Clinical features of fluid overload were more common (69% vs. 1.7%, p < 0.01) and the duration of hospital stay longer in myocarditis group (7 ± 4.3 vs. 4.8 ± 1.9 days, p < 0.01). CONCLUSION: Myocarditis among admitted dengue patients is not uncommon and may lead to increased morbidity.

A second source of precursor cells for the developing enteric nervous system and interstitial cells of Cajal.

The enteric nervous system is believed to be derived solely from the neural crest cells. This is partly based on the belief that the neural crest cells are the sole neural tube-derived cells colonizing the gastrointestinal tract. However, recent studies have shown that after the emigration of neural crest cells an additional population of cells emigrate from the cranial neural tube. These cells originate in the ventral part of the hindbrain, emigrate through the site of attachment of the cranial nerves, and colonize a variety of developing structures including the gastrointestinal tract. This cell population has been named the ventrally emigrating neural tube (VENT) cells. We followed the fate of these cells in the gastrointestinal tract. Ventral hindbrain neural tube cells of chick embryos were tagged with replication-deficient retroviral vectors containing the LacZ gene, after the emigration of neural crest from this region. In control embryos, the viral concentrate was dropped on the dorsal part of the neural tube. Embryos were sacrificed from embryonic days 3-12 and processed for the detection of LacZ positive ventrally emigrating neural tube cells. These cells colonized only the foregut, specifically the duodenum and stomach. Immunostaining with the neural crest cell marker HNK-1 showed that they were HNK-1 negative, indicating that they were not derived from neural crest. Cells were detected in three locations: (1). the myenteric and submucosal plexus of the enteric nervous system; (2). circular smooth muscle cell layer; and (3). mucosal lining of the lumen. A variety of specific markers were used to identify their fate. Some ventrally emigrating neural tube cells differentiated into neurons and glial cells, indicating that the enteric nervous system in the foregut develops from an additional source of precursor cells. It was also found that some of these cells differentiated into interstitial cells of Cajal, which mediate impulses between the enteric nervous system and smooth muscle cells, whereas others differentiated into epithelium. Altogether, these results indicate that the ventrally emigrating neural tube cells are multipotential. More importantly, they reveal a novel source of precursor cells for the neurons and glial cells of the enteric nervous system. The developmental and functional significance of the heterogeneous origin of the cell types remains to be established.

Ventrally emigrating neural tube cells contribute to the normal development of heart and great vessels.

We investigated the contributions of a recently described population of neural tube cells, which participates in the development of a variety of tissues, to the development of the heart and great vessels. These cells, termed as the ventrally emigrating neural tube (VENT) cells, originate in the ventral part of the hindbrain neural tube, emigrate at the site of attachment of the cranial nerves, and populate their respective target tissues. VENT cells of the caudal hindbrain neural tube at the level of the vagus nerve, which were previously reported to migrate into the heart, were tagged with replication-deficient retroviruses containing the LacZ gene in chick embryos, after the emigration of neural crest from this region. In older embryos, VENT cells were detected in a variety of locations including the ventricles, atria, their septa, aorticopulmonary septum, and great vessels of the heart. Immunostaining with a specific marker revealed that VENT cells differentiated into smooth muscle cells of great vessels. Differentiation of VENT cells into cardiac muscle cells was reported previously. Extirpation of the VENT cells prior to their departure from the neural tube resulted in some common cardiovascular malformations: thin-walled ventricles and atria, ventricular and atrial septal defects, persistent truncus arteriosus, and stenosis of the great vessels. These results suggest that a novel population of neural tube cells also contributes to the normal development of the heart and great vessels. Thus, the heart and great vessels develop from three sources of cells: mesoderm, neural crest, and VENT cells.