Effects of Child Characteristics on the Autism Diagnostic Interview-Revised: Implications for Use of Scores as a Measure of ASD Severity

The Autism Diagnostic Interview-Revised (ADI-R) is commonly used to inform diagnoses of autism spectrum disorders (ASD). Considering the time dedicated to using the ADI-R, it is of interest to expand the ways in which information obtained from this interview is used. The current study examines how algorithm totals reflecting past (ADI-Diagnostic) and current (ADI-Current) behaviors are influenced by child characteristics, such as demographics, behavioral problems and developmental level. Children with less language at the time of the interview had higher ADI-Diagnostic and ADI-Current. ADI-Diagnostic totals were also associated with age; parents of older children reported more severe past behaviors. Recommendations are provided regarding the use of the ADI-R as a measure of ASD severity, taking language and age into account.     

Cloning, sequence analysis and confirmation of derived gene sequences for three epitope-mapped monoclonal antibodies against human phagocyte flavocytochrome b

The integral membrane protein flavocytochrome b (Cyt b) is the catalytic core of the NADPH oxidase complex, a multicomponent enzyme system that initiates a cascade of reactive oxygen species that play a critical role in innate immunity and vascular physiology. Epitope-mapped, monoclonal antibodies (mAb) that recognize the large (gp91phox) and small (p22phox) subunits of Cyt b provide valuable reagents that have been used to examine structural and mechanistic aspects of oxidase function. In the present study, the heavy and light chain variable region genes of the Cyt b-specific mAbs 44.1, NS5, and NL7 have been amplified by RT-PCR, cloned and subject to DNA sequence analysis. Since the 5' degenerate primer sets used for mAb gene amplification were observed to introduce extensive heterogeneity into the heavy and light chain FR1 regions, N-terminal protein sequence analysis was also conducted to obtain the correct amino acid sequence of this region. In order to confirm the identity of the cloned genes, intact mAbs were resolved by two-dimensional electrophoresis and subject to in-gel tryptic digestion for analysis by both MALDI and nanospray LC-MS/MS. Databases searches using the derived mAb sequences predicted residues comprising CDR loops, identified candidate germline genes, and showed the respective germline genes to accurately predict the N-terminal amino acid residues for each variable region. The above studies report the amino acid sequence of Cyt b-specific mAb variable region genes with high confidence and provide essential information for future efforts at Cyt b structure analysis by resonance energy transfer and X-ray crystallography.     

Pancreaticoduodenectomy: Outcomes in a Low-Volume,Specialised Hepato Pancreato Biliary Unit

Background

This study was designed to evaluate the outcomes of pancreaticoduodenectomy (PD) at a low-volume specialised Hepato Pancreato Biliary (HPB) unit. Volume outcome analyses show significantly better results for patients undergoing PD at high-volume centres (Begg et al. JAMA 280:1747–1751, 1998; Finlayson et al. Arch Surg 138:721–725, 2003; Birkmeyer et al. N Engl J Med 346:1128–1137, 2002; Gouma et al. Ann Surg 232:786–795, 2000). Centralisation of PD seems to be the logical conclusion to be drawn from these results. In countries like Australia with a small and widely dispersed population, centralisation may not be always feasible. Alternative strategy would be to have similar systems in place to those in high-volume centres to achieve similar results at low-volume centres. Many Australian tertiary care centres perform low to medium volumes of PD (Chen et al. HPB 12:101–108, 2010; Kwok et al. ANZ J Surg 80:605–608, 2010; Barnett and Collier ANZ J Surg 76:563–568, 2006; Samra et al. Hepatobiliary Pancreat Dis Int 10:415–421, 2011). Most of these have a specialised HPB unit, accredited by the Australia and New Zealand Hepatic pancreatic and biliary association (ANZHPBA), as training units for post fellowship training in HPB surgery. It is imperative to perform outcome-based analyses in these units to ensure safety and high quality of care.

Methods

Retrospective analysis of database for periampullary carcinoma (1998 till date) was performed in an ANZHPBA accredited HPB unit based at a tertiary care teaching hospital in South Australia. Because age older than 74 years is shown to be a predictive marker of increased morbidity and mortality after a PD, we analysed the outcomes in this subset of patients separately.

Results

Fifty-three patients underwent PD in 14 years. Overall mortality was 3.8 %. The last in hospital mortality was in 1999. The morbidity rates and the oncologic outcomes were similar to those in high-volume units.

Conclusions

PD can be safely performed in a low-volume specialised unit at centres where the amenities and processes at high-volume centres can be replicated.     

Oxidative stress/reactive metabolite gene expression signature in rat liver detects idiosyncratic hepatotoxicants

Previously we reported a gene expression signature in rat liver for detecting a specific type of oxidative stress (OS) related to reactive metabolites (RM). High doses of the drugs disulfiram, ethinyl estradiol and nimesulide were used with another dozen paradigm OS/RM compounds, and three other drugs flutamide, phenacetin and sulindac were identified by this signature. In a second study, antiepileptic drugs were compared for covalent binding and their effects on OS/RM; felbamate, carbamazepine, and phenobarbital produced robust OS/RM gene expression. In the present study, liver RNA samples from drug-treated rats from more recent experiments were examined for statistical fit to the OS/RM signature. Of all 97 drugs examined, in addition to the nine drugs noted above, 19 more were identified as OS/RM-producing compounds—chlorpromazine, clozapine, cyproterone acetate, dantrolene, dipyridamole, glibenclamide, isoniazid, ketoconazole, methapyrilene, naltrexone, nifedipine, sulfamethoxazole, tamoxifen, coumarin, ritonavir, amitriptyline, valproic acid, enalapril, and chloramphenicol. Importantly, all of the OS/RM drugs listed above have been linked to idiosyncratic hepatotoxicity, excepting chloramphenicol, which does not have a package label for hepatotoxicity, but does have a black box warning for idiosyncratic bone marrow suppression. Most of these drugs are not acutely toxic in the rat. The OS/RM signature should be useful to avoid idiosyncratic hepatotoxicity of drug candidates.