Clinical trial: a nutritional supplement Viusid, in combination with diet and exercise, in patients with nonalcoholic fatty liver disease

Background  Nonalcoholic fatty liver disease (NAFLD) is a significant health problem for which there is no universally accepted pharmacological treatment. The combination of weight loss and antioxidant drugs to ameliorate insulin resistance and improve steatosis, inflammation and fibrosis provides the rational for therapeutic trials.
Aim  To evaluate the efficacy and safety of a nutritional supplement Viusid in association with diet and exercise for NAFLD.
Methods  A randomized, controlled and parallel-group trial was conducted at a tertiary care academic centre (National Institute of Gastroenterology, Havana, Cuba). We randomly assigned 60 patients with liver biopsy-proven NAFLD to 6 months of treatment with a hypocaloric diet plus aerobic exercise daily and three Viusid sachets daily or a hypocaloric diet and exercise. Endpoints were improvement in the NAFLD activity score (NAS), fibrosis and normalization of serum aminotransferase levels.
Results  A significant improvement in steatosis, necroinflammation and fibrosis was seen in each group of treatment ( P  < 0.01 for each feature). The Viusid group, as compared with the control group, significantly reduced the mean of NAS [from 4.18 to 0.54 points in the Viusid group vs. 4.45 to 2.2 points in the control group ( P  < 0.001)]. On between-group comparison, Viusid was found to be associated with a significantly greater improvement in steatosis ( P  < 0.001), ballooning ( P  = 0.002) and lobular inflammation ( P  = 0.025), but not in fibrosis ( P  = 0.07). Viusid was well tolerated.
Conclusions  Our results indicate that treatment with diet and exercise leads to a notable improvement in the histological features of NAFLD; however, the administration of Viusid intensifies the improvements of histological findings, especially of steatosis and inflammation.     

Multiple Pilomatricomas in Association with Trisomy 9

Abstract:   Multiple appearance of pilomatricoma is a rare phenomenon that has been associated with some diseases like Gardner syndrome, myotonic dystrophy, and Rubinstein-Taybi syndrome. We present a case of association of multiple pilomatricoma and trisomy 9, which represents the third published in literature. As a result of the small prevalence of these two entities, we believe they could be related.     

Sino-Atrial Dissociation: Evidence by Intracardiac Recordings in Man and by Microelectrode Studies on Isolated Rabbit Atrium

The electrophysiologic mechanisms of sinus dysfunction have recently been determined by direct recordings of the sinus node electrogram. The association of various degrees of abnormalities in the formation of the impulse within the sinus node and of sinoatrial conduction block, represents the pathophysiological substrate of the mechanism of sinus node dysfunction. The purpose of this work is to present clinical and experimental data supporting the concept of sinus node isolation. In our clinical case, the sinus node was probably intact despite aspects of sinus node dysfunction on the surface ECG. Sinus node electrograms were recorded with a sinoatrial conduction time of 100 ms (normal values in our laboratory: 83 ms +/- 38 ms). Atrial mapping demonstrated that the area depolarized by the sinus node involved a 2 cm2 zone surrounding it. This perisinusal activity could not be recorded on the surface ECG. Both exit and entry blocks in the sinus node were demonstrated. Our experimental data showed a total desynchronization between the electrical activity of the sinus node and that of the atrium under hypoxic conditions. Both types of cases demonstrated that an atrial dysrhythmia was coexisting with regular sinus activity. From these data we concluded that a sinus node free from any pathological involvement could be associated with severe symptoms of sinus node dysfunction on the surface ECG.     

A novel homozygous mutation at the GAA gene in Mexicans with early-onset Pompe disease

Glycogen-storage disease type II, also named Pompe disease, is caused by the deficiency of the enzyme acid alpha-glucosidase, which originates lysosomal glycogen accumulation leading to progressive neuromuscular damage. Early-onset Pompe disease shows a debilitating and frequently fulminating course. To date, more than 300 mutations have been described; the majority of them are unique to each affected individual. Most early-onset phenotypes are associated with frameshift mutations leading to a truncated alpha-glucosidase protein with loss of function. Founder effects are responsible from many cases from few highprevalence world regions. Herein we described two apparently unrelated cases affected with classical early-onset Pompe disease, both pertaining to a small region from Central Mexico (the State of San Luis Potosí), the same novel homozygous frameshift mutation at gene GAA (c.1987delC) was demonstrated in both cases. This GAA gene deletion implies a change of glutamine to serine at codon 663, and a new reading frame that ends after 33 base pairs, which leads to the translation of a truncated protein. This report contributes to widen the knowledge on the effect of pathogenic mutations in Pompe disease. Here we postulate the existence of a founder effect.Key words: Early-onset Pompe disease, Acid maltase deficiency, Founder effectGlycogen storage disease type II (Online Mendelian Inheritance in Man, OMIM, accession number 232300), also called Pompe disease, was described by Johannes C. Pompe in 1932. The disorder is caused by a deficiency of the enzyme acid alpha-glucosidase (acid maltase, EC 3.2.1.20, Swiss) which originates lysosomal glycogen accumulation leading to lysosomal swelling, cellular damage and dysfunction (1-3). Affected individuals develop progressive neuromuscular damage, showing a debilitating and frequently fulminating course on the classical, early-onset type of the disease. Other main findings are hypertrophic cardiomyopathy, hypotonia, hepatomegaly, macroglossia, feeding problems and breath difficulty. Currently it is recognized that the late form of Pompe disease has a very variable phenotype that can be confused with a wide range of neuromuscular, pulmonary and cardiovascular diseases with mild, moderate or severe symptoms that present either alone or combined (4-6).Pompe disease has an autosomal recessive inheritance and it is caused by more than 300 mutations that occur all over the gene coding for acid alpha-glucosidase (GAA) located at locus 17q25.2q25.3. The molecular phenomenon responsible of the different types of clinical expression occur by the presence of two either homozygous or compound heterozygous pathogenic mutations in early-onset Pompe cases, whereas late-onset Pompe have one variant and one pathogenic mutation (7). The majority of disease-causing mutations are unique; nonetheless, relatively frequent mutations have been described in certain populations with a possible founder effect traced from the original mutated carrier to the newly occurring cases. Affected cases have been described worldwide with a few high-prevalence regions like South-Africa, Taiwan and Holland (1, 8-10).Herein, we described two unrelated cases affected with classical early-onset Pompe disease, both pertaining to the same small Mexican region, with the same novel homozygous frameshift mutation at gene GAA (c.1987delC), identified by complete gene sequencing.     

Cyclooxygenase-1 and Cyclooxygenase-2 in the Human Optic Nerve Head

To investigate the hypothesis that eicosanoids act as cellular mediators in the optic nerve head of normals and of patients with glaucoma, we have determined the presence of the two cyclooxygenase (COX) isoforms in human tissue. Histological sections of optic nerve heads were studied by immunohistochemistry. Age matched normal donors were compared with eyes from glaucoma patients with moderate to severe nerve damage. Polyclonal antibodies to human COX-1 and COX-2 were localized with immunoperoxidase staining. Specific antibodies for vascular endothelia and microglia were also co-localized. In normal and glaucomatous eyes, COX-1 was localized exclusively to the prelaminar and lamina cribrosa regions of the optic nerve head. No staining for COX-1 was observed in the nerve fiber layer or the myelinated optic nerve. COX-1 was associated with the astrocytes of the glial columns and the cribriform plates, but not with the endothelia lining the capillaries. In glaucoma, more astrocytes appeared to be stained with antibody to COX-1 than in normals and staining was intensely perinuclear. There was no staining for COX-2 in normal tissue. A few COX-2 positive cells were found in the prelaminar, lamina cribrosa and postlaminar regions of the glaucomatous optic nerves. Positive staining for COX-2 was not associated with microglia. COX-1 is constitutively present in astrocytes that are localized exclusively to the prelaminar and lamina cribrosa regions of the human optic nerve head. Eicosanoids, synthesized by COX-1 in this tissue, may have a homeostatic and a neuroprotective role related to the axons of the retinal ganglion cells. The sparse presence of COX-2 in glaucomatous tissue probably reflects the lack of inflammation associated with glaucomatous optic neuropathy.     

Beyond pain: predictors of postoperative maladaptive behavior change in children

Objectives & Aim: Using well‐validated measures and controlling for potential confounding variables such as pain and surgical and anesthetic technique, the goal of this project was to identify the incidence of and risk factors for the development of behavior change in children after surgery. Background: Although researchers have described maladaptive behavior change following surgery, many previous studies are limited by potential confounding variables, including postoperative pain, type of surgery, and surgical and anesthetic procedure. Methods: Participants included 260 children undergoing tonsillectomy and adenoidectomy. Baseline and demographic data were collected prior to surgery and pain and behavioral recovery were recorded for 2 weeks following surgery. A standardized approach to anesthesia and surgical procedure was implemented and well‐validated assessment measures were used. Results: On the first day at home following surgery, 80.4% of children exhibited negative behavior change. Nearly one‐third of children continued to exhibit behavior changes 2 weeks after surgery. Logistic regression analyses that controlled for pain severity identified several predictors of behavior change: preexisting somatic and anxious/depressed problems predicted new onset postoperative general anxiety, χ² (8) = 20.10, P = 0.010; younger age predicted separation anxiety, χ² (4) = 20.41, P < 0.01; and inhibited temperament predicted postoperative sleep disturbance, χ² (2) = 9.19, P = 0.010. Conclusions: Individual child factors above and beyond pain predict maladaptive postoperative behavior change; identification of these predictors may be helpful in both preventing and ameliorating difficulties with behavioral recovery following surgery.