Parental Language Input Predicts Neuroscillatory Patterns Associated with Language Development in Toddlers at Risk of Autism

Journal of Autism and Developmental Disorders - In this study we investigated the impact of parental language input on language development and associated neuroscillatory patterns in toddlers at...     

Scleroderma-like fibrosing disorders

Many conditions presenting with clinical hard skin and tissue fibrosis can be confused with systemic sclerosis (scleroderma). These disorders have very diverse etiologies and often an unclear pathogenetic mechanism. Distinct clinical characteristics, skin histology, and disease associations may allow one to distinguish these conditions from scleroderma and from each other. A prompt diagnosis is important to spare patients from ineffective treatments and inadequate management. This article highlights nephrogenic systemic fibrosis (nephrogenic fibrosing dermopathy), eosinophilic fasciitis (Shulman's syndrome), scleromyxedema, and scleredema. These often are detected in the primary care setting and referred to rheumatologists for further evaluation. Rheumatologists must be able to promptly recognize them to provide valuable prognostic information and appropriate treatment options for affected patients.     

Gastrointestinal bleeding during liver transplantation--report of two cases

A few authors have reported, especially as intraoperative complications, gastrointestinal hemorrhage related to liver transplantation. The aim of this study was to show two cases of gastrointestinal hemorrhage, which occurred during surgery. The first patient was male, 46 years old, with viral hepatic cirrhosis. He had previously presented two episodes of digestive bleeding. Upper digestive endoscopy showed esophageal gastric varices. During the hepatectomy there was bleeding inside the nasogastric tube associated with severe hemodynamics instability without other sources of bleeding. Intraoperative endoscopy evidenced bleeding gastric varices. Gastrectomy was carried out and the varices were tied. The piggyback technique was used in the liver transplantation. The surgery was concluded without problems and in the following four and a half years his condition has evolved well. In the second case, the patient was aged 17, female, with autoimmune hepatic cirrhosis. She had previously presented one episode of digestive bleeding. Intraoperative endoscopy showed median esophageal varices. During the anesthetic induction she presented an episode of hematemesis. A Sengstaken-Blakemore balloon was introduced. The transplant was performed without further problems. Her case has been followed for 14 months in the outpatients' clinic with a good postoperative course. To sum up, gastrointestinal hemorrhage can be due to portal hypertension during the liver transplantation and must be treated quickly. In these cases the surgery must be ongoing.     

Enzyme-linked immunoabsorbent assay detection of a soluble form of urokinase plasminogen activator receptor in vivo

The receptor for urokinase plasminogen activator (uPA-R, CD87) is a glycosylphosphatidylinositol (GPI)-anchored 50 to 65 kD glycoprotein that, by regulating membrane-associated plasmin activity, may facilitate the invasion of inflammatory and malignant cells. Certain other GPI-anchored glycoproteins are shed from the cell membrane and exist as soluble products in vitro and in vivo. To determine if uPA-R undergoes a similar phenomenon, we have developed a sensitive enzyme- linked immunoabsorbent assay (ELISA) (using a rabbit antiserum as both capture and detection reagents) to measure the quantity of soluble uPA- R (suPA-R) in tissue culture supernatants and biologic fluids. Using this ELISA, we have detected suPA-R in the culture supernatants of U- 937 cells and human monocytes stimulated in vitro by certain soluble inflammatory mediators (Sitrin et al, Blood 84:1268, 1994; Mizukami et al., Clin Res 42:115A, 1994). To determine if suPA-R exists in vivo, we have screened the plasma of 20 normal volunteers (mean +/- SD, 3 +/- 3 ng/mL; median, 2 ng/mL; range, 1 to 11 ng/mL [serum values slightly higher]); the plasma of 13 ICU patients with clinical sepsis syndrome (mean +/- SD, 30 +/- 11 ng/mL; median, 11 ng/mL; range, 4 to 221 ng/mL); and the extravascular fluids (pleural, pericardial, and peritoneal) of 84 individuals with presumed inflammatory or malignant conditions (mean +/- SD, 21 +/- 39 ng/mL; median, 10 ng/mL; range, 2 to 253 ng/mL). Among the latter specimens, most were inflammatory exudates (only six were malignant by positive cytology) with the highest quantities of suPA-R associated with neutrophilic exudates. The solubility of suPA-R contained within these fluids was confirmed by reanalysis after ultracentrifugation to remove particulate material. When tested in a uPA ligand capture ELISA, representative specimens of extravascular body fluids and sepsis plasma contained suPA-R capable of binding uPA ligand (generally representing a small fraction of the immunoreactive material). We conclude from these data that suPA-R is immunologically detectable in vitro and in vivo with high concentrations of receptor found under conditions of inflammatory stimulation. The possibility of suPA-R's biologic activity is suggested by its partial retention of ligand binding capacity.     

Possible Influence of Glutathione <Emphasis Type="Italic">S</Emphasis>-Transferase <Emphasis Type="Italic">GSTT1</Emphasis> Null Genotype on Age of Onset of Sporadic Colorectal Adenocarcinoma

INTRODUCTION: Glutathione S-transferase enzymes mediate exposure to cytotoxic and genotoxic agents and may be involved in cancer susceptibility. Both glutathione S-transferase mu 1 (GSTM1) and GST theta 1 (GSTT1) genes have a null variant allele in which the entire gene is absent. The association of glutathione S-transferase null genotype and risk of developing colorectal cancer is not yet fully clarified. METHODS: We tested whether the null genotypes for GSTM1 and GSTT1 genes altered the risk for sporadic colorectal adenocarcinoma in Brazilian patients. Genomic DNA from 102 sporadic colorectal adenocarcinoma patients and 300 controls was analyzed by polymerase chain reaction. RESULTS: Frequencies of GSTM1, GSTT1, and null combined genotypes were similar in patients and controls (49.9 vs. 44.6 percent, 16.6 vs. 17.3 percent, and 8.8 vs. 8 percent, respectively). We found a 1.03-fold (95 percent confidence interval, 0.96-1.10) and 1.08-fold (95 percent confidence interval, 0.99-1.18) increased risk associated with GSTM1 and GSTT1 null genotypes, respectively (P = 0.45 and P = 0.08) and a 1.18-fold (95 percent confidence interval, 0.47-2.90) increased risk associated with the combined null genotype (P = 0.74). The GSTT1 null genotype was more common in patients who were diagnosed before the age of 60 years than in those who were diagnosed at an older age (28.8 vs. 4 percent, respectively; P = 0.0008). CONCLUSIONS: The results suggest that inherited absence of this carcinogen detoxification pathway may not be associated with sporadic colorectal adenocarcinoma in the present cases. However, a higher frequency of GSTT1 null genotype in patients diagnosed before the age of 60 years suggests that this genotype could influence the age of disease onset in Brazil.     

Expanded Milan criteria on pathological examination after liver transplantation: analysis of preoperative data

BACKGROUND: We sought to evaluate the accuracy of imaging techniques related to the Milan criteria (MC) compared with the explant histology and the survival of these patients. METHODS: Between 1997 and 2006, we selected 45 cirrhotic patients with hepatocellular carcinoma distributed into two groups according to explant histology: MC and Expanded Milan Criteria (EMC). Age, gender, preoperative imaging (ultrasound [US] and/or computed tomography [CT]), maximal tumor dimension, number of tumors, explanted histology, histology degree, alpha-fetoprotein (AFP) level and vascular invasion were compared among the patients to evaluate the value of these prognostic factors for survival after liver transplantation. RESULTS: By histology 42.2% explants were identified as EMC. The mean AFP level was 204.5 ng/mL. Vascular invasion was detected in 31.5% of explants and 68.4% showed incidental tumors. The survival rates after 10 years were 47.4% whereas MC patients showed 57.77%. The mean AFP level among MC patients was 150.2 ng/mL with vascular invasion detected in 7.7% of explants, and 47.4% with incidental tumors. The overall sensitivity of the imaging techniques was 83.3% for CT and 75% for US. The specificity was 96% for CT and 80.1% for US. CONCLUSION: Scan examinations in the preoperative evaluation underestimated about 42.2% of tumors. Those patients had vascular invasion but the survival after 10 years was similar between the ECM and MC groups.     

Detection and monitoring of human herpesvirus 7 in adult liver transplant patients: impact on clinical course and association with cytomegalovirus

We herein have described HCMV and HHV-7 detection during the follow-up of 29 adult liver recipients in our transplant unit. For basic immunosuppression, the patients received cyclosporine and symptomatic HCMV infection was treated with gancyclovir. The most prevalent etiology for liver transplantation was hepatitis C or alcohol abuse (45% of patients). The laboratory monitoring to 180 days after transplantation was performed by nested-polymerase chain reaction to HCMV or HHV-7. HCMV DNA was detected in 19/29 of patients (65.5%) and HHV-7 DNA, in 14/29 of patients (48.2%). The time-related appearance of HHV-7 and HCMV DNA differed significantly (P = .02); their detection was considered independent (P = .2). The results showed that few patients remained free of HHV-7 or HCMV after liver transplantation, indicating that most patients were actively infected with more then one virus sequentially and not concurrently. Graft dysfunction, fever, gastrointestinal system abnormalities, and interstitial pneumonitis dominated the clinical pictures. Thirteen of 29 patients (44.8%) developed symptomatic HCMV active infections. The relationship between the detection of HCMV DNA, and HCMV disease development was significant (P = .0004). In HCMV-free patients, no symptoms or significant laboratory findings were linked with HHV-7. However, HHV-7 was frequently detected sequentially after HCMV, and an interaction of HCMV and/or HHV-6 to increase their pathogenic effects could not be excluded. Further studies should be performed including HHV-6 to evaluate the relationship, among beta herpesviruses.     

Independent association of anti–β2‐glycoprotein I antibodies with macrovascular disease and mortality in scleroderma patients

Objective

Systemic sclerosis (SSc; scleroderma) is characterized by a unique widespread vascular involvement that can lead to severe digital ischemia, pulmonary arterial hypertension (PAH), or other organ dysfunction. Microthrombotic events and procoagulation factors such as anti–β2‐glycoprotein I (anti‐β₂GPI) or anticardiolipin antibodies (aCL) may be implicated in the development of these manifestations. This study was undertaken to investigate whether anti‐β₂GPI and aCL are correlated with macrovascular disease, including ischemic digital loss and PAH, in SSc patients.

Methods

Seventy‐five SSc patients with a history of ischemic digital loss and 75 matched SSc controls were evaluated. Anticentromere antibodies (ACAs), anti‐β₂GPI, and aCL were measured, and clinical associations were determined using conditional and simple logistic regression models.

Results

Positivity for anti‐β₂GPI was significantly more frequent in SSc patients with digital loss than in patients without digital loss (P = 0.017), with the IgA isotype of anti‐β₂GPI showing the strongest association (odds ratio [OR] 4.0). There was no significant difference in aCL frequency between patients with digital loss and control patients. After adjustment for demographic characteristics, disease type, smoking, and ACA, anti‐β₂GPI positivity was significantly associated with active digital ischemia (OR 9.4), echocardiographically evident PAH (OR 4.8), and mortality (OR 2.9). ACA positivity was associated with history of digital loss (OR 3.28), but not with PAH or mortality. History of digital loss was strongly associated with increased mortality (OR 12.5).

Conclusion

Anti‐β₂GPI is significantly associated with macrovascular disease in SSc and independently predicts mortality. It is unclear whether it has a pathogenetic role or simply reveals the presence of underlying endothelial injury. The use of anti‐β₂GPI as a biomarker of vascular disease in SSc should be further explored.