Sudden unexpected fatal encephalopathy in adults with OTC gene mutations-Clues for early diagnosis and timely treatment.

BACKGROUND: X-linked Ornithine Transcarbamylase deficiency (OTCD) is often unrecognized in adults, as clinical manifestations are non-specific, often episodic and unmasked by precipitants, and laboratory findings can be normal outside the acute phase. It may thus be associated with significant mortality if not promptly recognized and treated. The aim of this study was to provide clues for recognition of OTCD in adults and analyze the environmental factors that, interacting with OTC gene mutations, might have triggered acute clinical manifestations. METHODS: We carried out a clinical, biochemical and molecular study on five unrelated adult patients (one female and four males) with late onset OTCD, who presented to the Emergency Department (ED) with initial fatal encephalopathy. The molecular study consisted of OTC gene sequencing in the probands and family members and in silico characterization of the newly detected mutations. RESULTS: We identified two new, c.119G>T (p.Arg40Leu) and c.314G>A (p.Gly105Glu), and three known OTC mutations. Both new mutations were predicted to cause a structural destabilization, correlating with late onset OTCD. We also identified, among the family members, 8 heterozygous females and 2 hemizygous asymptomatic males. Patients' histories revealed potential environmental triggering factors, including steroid treatment, chemotherapy, diet changes and hormone therapy for in vitro fertilization. CONCLUSIONS: This report raises awareness of the ED medical staff in considering OTCD in the differential diagnosis of sudden neurological and behavioural disorders associated with hyperammonemia at any age and in both genders. It also widens the knowledge about combined effect of genetic and environmental factors in determining the phenotypic expression of OTCD.

Early recognition of the 2009 pandemic influenza A (H1N1) pneumonia by chest ultrasound.

INTRODUCTION: The clinical picture of the pandemic influenza A (H1N1)v ranges from a self-limiting afebrile infection to a rapidly progressive pneumonia. Prompt diagnosis and well-timed treatment are recommended. Chest radiography (CRx) often fails to detect the early interstitial stage. The aim of this study was to evaluate the role of bedside chest ultrasonography (US) in the early management of the 2009 influenza A (H1N1)v infection. METHODS: 98 patients who arrived in the Emergency Department complaining of influenza-like symptoms were enrolled in the study. Patients not displaying symptoms of acute respiratory distress were discharged without further investigations. Among patients with clinical suggestion of a community-acquired pneumonia, cases encountering other diagnoses or comorbidities were excluded from the study. Clinical history, laboratory tests, CRx, and computed tomography (CT) scan, if indicated, contributed to define the diagnosis of pneumonia in the remaining patients. Chest US was performed by an emergency physician, looking for presence of interstitial syndrome, alveolar consolidation, pleural line abnormalities, and pleural effusion, in 34 patients with a final diagnosis of pneumonia, in 16 having normal initial CRx, and in 33 without pneumonia, as controls. RESULTS: Chest US was carried out without discomfort in all subjects, requiring a relatively short time (9 minutes; range, 7 to 13 minutes). An abnormal US pattern was detected in 32 of 34 patients with pneumonia (94.1%). A prevalent US pattern of interstitial syndrome was depicted in 15 of 16 patients with normal initial CRx, of whom 10 (62.5%) had a final diagnosis of viral (H1N1) pneumonia. Patients with pneumonia and abnormal initial CRx, of whom only four had a final diagnosis of viral (H1N1) pneumonia (22.2%; P<0.05), mainly displayed an US pattern of alveolar consolidation. Finally, a positive US pattern of interstitial syndrome was found in five of 33 controls (15.1%). False negatives were found in two (5.9%) of 34 cases, and false positives, in five (15.1%) of 33 cases, with sensitivity of 94.1%, specificity of 84.8%, positive predictive value of 86.5%, and negative predictive value of 93.3%. CONCLUSIONS: Bedside chest US represents an effective tool for diagnosing pneumonia in the Emergency Department. It can accurately provide early-stage detection of patients with (H1N1)v pneumonia having an initial normal CRx. Its routine integration into their clinical management is proposed.

Efficacy and safety of vernakalant in recent-onset atrial fibrillation after the European medicines agency approval: systematic review and meta-analysis.

Vernakalant is an emergent antiarrhythmic drug that, in preclinical studies, has demonstrated high efficacy in restoring sinus rhythm and safety in patients with rapid recent-onset atrial fibrillation. The aim of this work was to evaluate the efficacy and safety of vernakalant for cardioversion of recent-onset atrial fibrillation. PubMed, EMBASE, Clinical Trials Registry, and European Medicines Agency public reports were searched for randomized clinical trials, until May 2011, of vernakalant compared with controls (placebo/other antiarrhythmic drug) in enrolled patients with high ventricular rate atrial fibrillation. Five randomized trials that met inclusion criteria enrolled a total of 1099 patients. Among these, 810 had recent-onset atrial fibrillation. When compared with controls (placebo/other oral antiarrhythmic drugs), vernakalant was associated with a significant increase in cardioversion within 90 minutes from drug infusion (relative risk, 8.4; 95% confidence interval, 4.4-16.3; P < .00001). Compared with controls, vernakalant was not associated with a significant difference in serious adverse events (relative risk, 0.9; 95% confidence interval, 0.6-1.4; P = .64). The authors conclude that compared with controls, vernakalant is effective and safe for rapidly converting recent-onset atrial fibrillation. Questions remain surrounding safety because 1 unpublished trial was discontinued for this reason. Further cost-effective analysis and comparison with other antiarrhythmic agents, such as class I antiarrhythmic agents, should be investigated, especially in the emergency department.

Ultrasound M-mode assessment of diaphragmatic kinetics by anterior transverse scanning in healthy subjects.

The purpose of this study was to set an effective standardized method to assess diaphragmatic kinetics by ultrasound. Forty healthy volunteers were submitted to a B- and M-mode ultrasound study using a convex transducer positioned in the subcostal anterior area for transverse scanning. Ultrasound examination was completed in 38/40 cases (95%), spending on average <10 min for examination. The resting and forced diaphragmatic excursions were 18.4 ± 7.6 and 78.8 ± 13.3 mm, respectively, unrelated to demographic or anthropometric parameters: intraobserver variability on three successive measurements resulted in 6.0% and in 3.9%, respectively. An inexperienced sonographer completed the ultrasound examination in 37/40 cases, spending on average >15 min, with significant, although marginal, interobserver variability (31.9% and 14.7% for resting and forced diaphragmatic excursion, respectively). Bedside ultrasonography by an anterior subcostal transverse scanning on semi-recumbent patient proves to be a safe, feasible, reliable, fast, relatively easy and reproducible way to assess diaphragm movement.

The role of emergency ultrasound in the diagnosis of acute non-traumatic epigastric pain.

The epigastrium is the site where pain coming from both abdominal and extra-abdominal organs is frequently referred. Although acute or chronic diseases of the stomach, duodenum, liver, pancreas and biliary tree are the most common causes of acute epigastric pain, several other entities, potentially more severe, should also be suspected and investigated. Clinical bedside ultrasonography (US) is actually the first-line imaging in acute epigastric pain patients presenting to the hospital Emergency Department (ED) because it is rapid, noninvasive, relatively inexpensive and focused, repeatable and reliable. Moreover, the systematic use of emergency US as a complement to routine management might save economic resources by avoiding further costs for complications and substantially reducing the time for making an accurate diagnosis. The purpose of this paper is to review the US spectrum of the most common diseases responsible for acute epigastric pain onset. We also propose a focused, well codified US protocol, that we call the "$ approach", based on our clinical experience and the current literature for acute non-traumatic epigastric pain evaluation in an emergency setting. Its systematic application by the emergency physician may reduce the wait for diagnosis and the over-usage of second-line radiological techniques, including computed tomography, as well as to increase the diagnostic accuracy with potential benefits for patient (safety), physician (efficacy) and the institution (efficiency).

CagA antigen of Helicobacter pylori and coronary instability: insight from a clinico-pathological study and a meta-analysis of 4241 cases.

BACKGROUND: Cytotoxin-associated gene-A (CagA) antigen is expressed by some virulent strains of Helicobacter pylori (H. pylori). The role of CagA antigen in coronary instability is unknown. We performed a clinico-pathological study and a meta-analysis in the attempt to shed new light on this complex issue. METHODS: In the clinico-pathological study, 38 patients with unstable angina (UA), 25 patients with stable angina (SA), 21 patients with normal coronary arteries (NCA) and 50 age and sex matched healthy volunteers were enrolled. Serology for CagA was assessed in all patients. Specimens of atherosclerotic plaques were obtained from all patients by directional coronary atherectomy, and prepared for immunohistochemistry using anti-CagA monoclonal antibodies. The meta-analysis includes 9 studies assessing the association between seropositivity to CagA strains and acute coronary events. RESULTS: The titre of anti-CagA antibodies was significantly higher in patients with unstable angina (161+/-90 RU/ml) compared to those with stable angina (83+/-59 RU/ml p<0.02), NCA (47.3+/-29 RU/ml p<0.01) and healthy controls (73+/-69 p<0.02). Anti-CagA antibodies recognized antigens localized inside coronary atherosclerotic plaques in all specimens from both stable and unstable patients. In the meta-analysis, seropositivity to CagA was significantly associated with the occurrence of acute coronary events with an odds ratio (OR) of 1.34 (95% CI, 1.15-1.58, p=0.0003). CONCLUSIONS: Taken together these findings suggest that in a subset of patients with unstable angina, an intense immune response against CagA-positive H. pylori strains might be critical to precipitate coronary instability mediated by antigen mimicry between CagA antigen and a protein contained in coronary atherosclerotic plaques.

Interaction between Helicobacter pylori infection and untreated coeliac disease on gastric histological pattern.

OBJECTIVE: Helicobacter pylori infection is the major agent of gastric damage. Coeliac disease may affect the morphology and function of the entire gastrointestinal tract from the stomach to the colon. The aim of this study was to assess the gastric histological pattern in patients with H. pylori and untreated coeliac disease. MATERIAL AND METHODS: We retrospectively enrolled 183 H. pylori-positive patients with (85, group A) and without (98, group B) untreated coeliac disease. The groups were similar for age, gender and smoking habit, and all the patients came from the same geographical area. Histological evaluation of gastric pattern was performed on 4 biopsies (2 in the antrum, 2 in the corpus). Gastric damage was classified according to the modified Sydney System. Diagnosis of H. pylori infection was based on positivity to histology. The chi-square test was used to assess differences between groups. A p-value <0.05 was considered significant. RESULTS: Group A showed a significantly higher prevalence of follicular gastritis than group B (23.5% versus 12.2%, p=0.045). A significantly lower prevalence of atrophic gastritis was observed in group A compared with that in group B (6% versus 22.5%, p=0.002). The prevalence of chronic superficial gastritis, activity degree and intestinal metaplasia was similar between the two groups. CONCLUSIONS: In patients with H. pylori infection, untreated coeliac disease could represent a risk factor for follicular gastritis and is associated with a lower prevalence of atrophic gastritis. The complex interaction between H. pylori and untreated coeliac disease on Th-1/Th-2 balance in the gastric mucosa could explain these results.

[A case of cardiogenic syncope in a drug-addict patient]. / Un caso di sincope di origine cardiogena in paziente farmaco-dipendente.

Torsade de pointes is a polymorphic ventricular tachycardia, associated with prolonged QT interval and characterized by twisting of the mean electrical axis of the QRS complexes around an isoelectric line. The long QT syndrome can be divided into two categories, congenital and acquired. The congenital long QT syndrome may be caused by some gene mutation, whereas the acquired form is usually associated with drugs and electrolyte imbalance. It usually remains asymptomatic or causes presyncope, although it may degenerate into ventricular fibrillation and may cause sudden death. The different presentation depends on the polymorphism that characterizes genotypic and phenotypic expression of proteic channel subunits, and on drug toxicity that provoke subunit dysfunction. The case report presented here is an example of prolonged QT interval syndrome in a patient with cocaine abuse and electrolyte disturbances.

A "progressive" visual loss.

An unusual cause of acute-onset and progressively worsening visual loss is presented. A 60-year-old woman was referred for left homonymous hemianopsia to our Emergency Medicine Department because of a suspected vascular accident. Ten years earlier she had been diagnosed as having chronic lymphocytic leukemia. Brain computed tomography and magnetic resonance imaging revealed "bilateral foci of white matter abnormalities in the occipital regions, compatible with a diagnosis of progressive multifocal leukoencephalopathy". Her cerebrospinal fluid was positive for papovavirus JC. Progressive multifocal leukoencephalopathy due to papovavirus JC, a typical complication in AIDS patients, is a rare complication in patients with other immunosuppressive conditions, such as chronic lymphocytic leukemia.

Potential therapeutic effect of antioxidants in experimental diabetic retina: a comparison between chronic taurine and vitamin E plus selenium supplementations.

Although good glycaemic control can delay the development and progression of diabetic retinopathy, new therapies are needed to obtain a better control of this diabetic complication. Oxidative stress seems to be a contributing factor in diabetic retinal alterations, therefore, it has been suggested that antioxidants may be beneficial in reducing diabetic retinal changes. However, many questions are still open. In fact, it remains to be ascertained which antioxidants are the most active when they are chronically administered in vivo and their effective dosages. Therefore, we compared the effect of chronic taurine supplementations versus a mixture of vitamin E + selenium on biochemical retinal changes induced by diabetes at different stages of the disease. Briefly, streptozotocin (STZ) diabetic rats were administered for 4 months following the dietary supplements: (a) 2% (w/w) taurine; (b) 5% (w/w) taurine; (c) 200 IU vitamin E + 8 mg selenium/kg diet (d) 500 IU vitamin E + 8 mg selenium/kg diet. In STZ diabetic rat in poor metabolic control (i.e. serum glucose >16.5 mmol/l), at 2, 4, 8, 16 weeks following the onset of diabetes, retinal conjugated dienes (CD) and lipid hydroperoxides (LP) were significantly and progressively increased, while sodium pump activity was gradually and significantly reduced. In taurine and vitamin E + selenium supplemented diabetic rats, glycaemia and body weight were not significantly different from those of non-supplemented diabetic animals. In diabetic rats, 2 and 5% taurine significantly decreased CD. This reduction is long lasting. Regarding CD, both vitamin E + selenium supplementations reduced CD only during the first 4 weeks of diabetes. Two percent taurine supplementation significantly lowered LP for the first 8 weeks of the disease while 5% taurine-induced-reduction lasted for the whole experimental time. A 200 IU vitamin E + 8 mg selenium supplementation did not significantly modify LP, while 500 IU vitamin E + 8 mg selenium significantly lowered them for the whole studied period. Finally, taurine preserved ATPase activity being more effective at 5% than 2%. Two hundred IU vitamin E + 8 mg selenium did not generally modify pump activity, while 500 IU vitamin E + 8 mg selenium partially prevented the decrease in pump activity. We conclude that taurine and vitamin E + selenium supplementations ameliorate biochemical retinal abnormalities caused by diabetes. These effects are dose- and time-dependent Moreover, the effect of taurine on CD is longer lasting than that of vitamin E + selenium. In addition, taurine seems to better preserve ATPase activity in comparison with vitamin E + selenium. Finally, in diabetic animals a negative correlation is found between CD and LP on one side and Na+K+ATPase activity on the other; thus, lipid peroxidation and pump activity seem to be associated. The same inverse correlations are present in vitamin E + selenium supplemented diabetic rats, but are lost in taurine supplemented animals. Therefore, taurine effects may not be simply mediated by its antioxidant activity. Thus, chronical (4 months) taurine and vitamin E + selenium supplementations reduce biochemical retinal alterations in diabetic rat in poor metabolic control.

Thrombopoietin serum levels in patients with inflammatory bowel disease with and without previous thromboembolic events.

BACKGROUND/AIMS: Patients affected by inflammatory bowel disease frequently suffer from thromboembolic complications and mesenteric microvascular occlusion could be involved in the pathogenesis of inflammatory bowel disease. Increased platelet counts and abnormal platelet function seem to play a crucial role in determining the hypercoagulable state observed in inflammatory bowel disease. Thrombopoietin is considered the primary regulator of thrombopoiesis and recent studies have investigated the role of thrombopoietin in inflammatory bowel disease. However, the available data are not conclusive. The aim of this study was to assess thrombopoietin serum levels in inflammatory bowel disease patients according to platelet counts, disease activity and previous thrombotic events. METHODOLOGY: Seventy-one patients with inflammatory bowel disease [41 with ulcerative colitis and 30 with Crohn's disease] and 30 healthy controls were investigated. Eight (11%) inflammatory bowel disease patients had suffered previous thromboembolic complications, none had active thrombosis. Thrombopoietin serum levels were measured by ELISA. RESULTS: Mean thrombopoietin levels were significantly increased in inflammatory bowel disease patients with active disease compared to both healthy controls and patients with inactive disease. Platelet counts were significantly higher only in patients with active disease with respect to healthy subjects. No correlation was found between thrombopoietin levels and platelet counts in either controls or inflammatory bowel disease patients. No differences were found either in thrombopoietin levels or in platelet counts comparing inflammatory bowel disease patients with and without thromboembolic complications. CONCLUSIONS: Our data show elevated thrombopoietin levels in active inflammatory bowel disease. However, no correlation was found between platelet counts and thrombopoietin levels, supporting the hypothesis that other circulating factors than thrombopoietin interact in determining reactive thrombocytosis. Furthermore, thrombopoietin levels did not differ in inflammatory bowel disease patients with or without previous thromboembolic events. This finding could be probably explained by the lack of patients with active thrombosis at the moment of inclusion in the study.