Tyrosinemia type 1 in pediatric nephrology: Not always straightforward

The main clinical features of tyrosinemia type 1 usually appear in the first months of life, including fever, diarrhea, vomiting, liver involvement, growth failure, and renal proximal tubulopathy with subsequent hypophosphatemic rickets. An early diagnosis is crucial in order to provide specific management and to prevent complications. Here, we report on two cases referred primarily to pediatric nephrologists for the diagnosis of “neonatal tubulopathy” and management of “X-linked hypophosphatemia (XLH),” respectively. Our aim is to emphasize that (1) even a mixed tubulopathy can reveal tyrosinemia, and (2) tyrosinemia is a classic differential diagnosis of XLH that should not be forgotten, especially in the era of the anti-FGF23 burosumab.     

LONG‐TERM FOLLOW UP OF PATIENTS WITH SMALL GASTROINTESTINAL STROMAL TUMORS IN THE STOMACH USING ENDOSCOPIC ULTRASONOGRAPHY‐GUIDED FINE‐NEEDLE ASPIRATION BIOPSY

Background: Gastrointestinal stromal tumors (GIST) are one of the most common mesenchymal tumors of the gastrointestinal tract. GIST are defined by positive immunohistochemical staining for KIT or CD34 and thus are generally diagnosed after surgery. Because small GIST are rarely diagnosed before surgery, the clinical course of these small tumors is not clear. The aim of the present study was to follow changes in size and configuration of small GIST that were pathologically confirmed using endoscopic ultrasonography‐guided fine‐needle aspiration biopsy (EUS‐FNAB). Methods: Between July 1997 and December 2003, 16 tumors in 16 patients (10 men and 6 women) with an immunohistochemical diagnosis of GIST were regularly followed in our hospital. The median patient age when EUS‐FNAB was performed was 62 years (range 26–82 years) and the median follow‐up period was 4.9 years (range 0.5–9.6 years). Results: Fourteen tumors showed no remarkable changes in size and shape during follow up compared with the initial diagnosis. Two tumors enlarged: one tumor approximately doubled its diameter in 8 years and the other tumor increased from 1.8 cm at diagnosis to up to 10 cm after only 2 years. Doubling time of the latter tumor was calculated as 3.1 months. Conclusions: We conclude that EUS‐FNAB might be a good modality for final diagnosis of GIST without surgery, and that GIST without rapid growth on follow up can be endoscopically followed.     

Role of retinol in protecting epithelial cell damage induced by Clostridium difficile toxin A

Vitamin A (retinol), a fat-soluble vitamin, is an essential nutrient for the normal functioning of the visual system, epithelial cell integrity and growth, immunity, and reproduction. Our group has investigated the effect of high doses of oral vitamin A on early childhood diarrhea in our prospective community-based studies from Northeast Brazil and found a beneficial role in reducing the mean duration but not incidence of diarrheal episodes. In this study, we explored the role of retinol supplementation in intestinal cell lines following Clostridium difficile toxin A (TxA) challenge. C. difficile is the most common anaerobic pathogen borne with antibiotic-borne diarrhea and pseudomembranous colitis. Since retinol is critical for the integrity of tight junctions and to modulate the cell cycle, we have focused on changes in transepithelial electrical resistance (TEER) in Caco-2, a more differentiated intestinal cell line, and on models of cell proliferation, migration and viability in IEC-6 cells, an undifferentiated crypt cell line, following TxA injury. In this model, retinol therapy reduced apoptosis, improved cell migration and proliferation, and prevented the reduction in TEER, following C. difficile TxA challenge in a glutamine-free medium. These results suggest the role of retinol in protecting intestinal epithelial barrier function from C. difficile TxA enterotoxic damage.     

Labially displaced ectopically erupting maxillary permanent canine: interceptive treatment and long-term results.

This case report demonstrates how extracting a maxillary deciduous canine affects the eruption path of a labially displaced ectopically erupting permanent canine. A long-term follow-up is presented, and the biologic mechanisms are discussed.     

Evolution with age of the acetylcholinesterase activity in rectal suction biopsy in Hirschsprung's disease

The acetylcholinesterase (AChE) activity in Hirschsprung's disease was analyzed for histochemical patterns according to age. Its evolutional nature was also assessed. Two hundred thirty children (0 to 16 years of age) with acute or chronic obstipation were submitted to rectal suction biopsy for AChE histochemical staining. One hundred nineteen of them showed abnormal AChE activity. Retrospective analysis of those cases permitted us to establish three histochemical patterns: Pattern I, thick nerve trunks present only in the submucosa and, characteristically, absence of AChE activity in the lamina propria. This pattern was predominant in newborn up to 3 months of age and was designated the newborn pattern. Pattern II, thin nerve fibers in the muscularis mucosae and submucosa with a clear infiltration in the lamina propria. This pattern was mainly seen in children older than 1 year of age and was called classical pattern. Pattern III, an intermediate pattern showing morphologic characteristics of the two previous patterns with predominance of one or another, according to the age. A prospective study was also made in 15 children with Hirschsprung's disease who were submitted to suction rectal biopsies at different ages. In this study, a clear evolutional character of the AChE activity was observed from the newborn pattern to the intermediate and finally to the classical pattern.     

Evaluation of the clinical, hemodynamic and neurohormonal response to levosimendan administration in decompensated heart failure patients. One-month follow-up.

INTRODUCTION: Levosimendan is an inodilatory drug with hemodynamic effects in patients with decompensated chronic heart failure. AIM: Short-term (one month) evaluation of clinical, hemodynamic and neurohormonal changes in patients with decompensated chronic heart failure undergoing levosimendan therapy. METHODS: Twenty-six (21 male) consecutive patients were studied, corresponding to 32 levosimendan administrations (bolus + 24h infusion), aged 56.7+/-13.0 years, with decompensated chronic heart failure, in NYHA functional class III-IV (78.1% in class IV), and cardiac index (CI) <2.5 l/min/m2. Clinical (NYHA class), non-invasive hemodynamic (echocardiography) and neurohormonal (Elecsys ECLIA NT-ProBNP) evaluations were performed before levosimendan administration and on days 1, 4, 10 and 30. RESULTS: 1) Until day 10, there was a progressive decrease in NT-ProBNP values and weight (p<0.001), with an increase in CI (p<0.001); 2) NYHA functional class improved progressively, with 76% of the patients in NYHA class II at day 30; 3) NT-ProBNP values at day 1 correlated inversely (r=-0.414; p=0.024) with CI at day 4; and 4) the absolute decrease in NT-ProBNP values at day 4 (relative to baseline values) correlated with weight loss at day 4 (r=0.495, p=0.005), day 10 (r=0.424, p=0.031) and day 30 (r=0.486, p=0.030). CONCLUSION: Levosimendan therapy in patients with decompensated chronic heart failure contributes to progressive NYHA class improvement. The variations seen in NYHA class and hemodynamics was reflected in changes in NT-ProBNP.