Guillain-Barre syndrome (GBS) is the rubric encompassing highly variable phenotypic subgroups of acute, postinfectious, immune-mediated peripheral neuropathy. The hallmark of GBS phenomenology is a rapidly progressive ascending lower extremity weakness. GBS taxonomy includes a motor and sensory axonal neuropathy (AMSAN). Nitrous oxide (NO) abuse may create a pattern of neurological dysfunction almost identical to subacute combined degeneration. We report an adult with myeloneuropathy due to NO abuse that mimicked the presenting features of the GBS-subtype AMSAN. J Neuroimaging 2009;XX:1-2.

Deregulated Myc triggers a variety of intrinsic tumor suppressor programs that serve to restrain Myc's oncogenic potential. Since Myc activity is also required for normal cell proliferation, activation of intrinsic tumor suppression must be triggered only when Myc signaling is oncogenic. However, how cells discriminate between normal and oncogenic Myc is unknown. Here we show that distinct threshold levels of Myc govern its output in vivo: low levels of deregulated Myc are competent to drive ectopic proliferation of somatic cells and oncogenesis, but activation of the apoptotic and ARF/p53 intrinsic tumor surveillance pathways requires Myc overexpression. The requirement to keep activated oncogenes at a low level to avoid engaging tumor suppression is likely an important selective pressure governing the early stages of tumor microevolution.

The two fixed-dose combinations of dihydroartemisinin and piperaquine (Artekin(R) and Arterakine(R)) were found to be bioinequivalent in healthy Vietnamese subjects. However, because the Cmax and AUC of dihydroartemisinin and piperaquine were only marginally different between the two formulations similar therapeutic efficacy is expected in the treatment of malaria infections.

We compared plasma maximum concentration (Cmax) and area under the concentration-time curve (AUC) of the antimalarial drug piperaquine in 26 healthy Vietnamese subjects after treatment with either a single oral dose of 500 mg (n = 6) or 1,000 mg (n = 6) of piperaquine phosphate and a three-day course of 500 mg of piperaquine/ day in the fasting state (n = 7) or with food (approximately 17 g fat)(n = 7). The geometric mean plasma Cmax and AUC((0-28)) was 2.8-fold (200 ng/mL versus 70 ng/mL) and 1.9-fold (5,736 ng x h/mL versus 2,999 ng x h/mL), respectively, and higher in subjects receiving the 1,000-mg dose than in those receiving the 500-mg dose. The geometric mean Cmax and AUC((0-28)) was 1.7-fold (198 ng/mL versus 119 ng/mL) and 1.4-fold (11,187 ng x h/mL versus 7,954 ng x h/mL) higher in the fed state than in the fasting state. Piperaquine AUC was proportional to the two doses tested and a moderate-fat meal enhanced the bioavailability of piperaquine by 41%, which should improve the therapeutic efficacy of this drug.

Transient outward K+ currents are particularly important for the regulation of membrane excitability of neurons and repolarization of action potentials in cardiac myocytes. These currents are modulated by protein kinase C (PKC) activation, and the K+ channel subunit, Kv4.2, is a major contributor to these currents. Furthermore, the current recorded from Kv4.2 channels expressed in oocytes is reduced by PKC activation. The mechanism underlying PKC regulation of Kv4.2 currents is unknown. In this study, we determined that PKC directly phosphorylates the Kv4.2 channel protein. In vitro phosphorylation of the intracellular amino (N)- and carboxyl (C)-termini of Kv4.2 glutathione S-transferase (GST) fusion protein revealed that the Kv4.2 C-terminal was phosphorylated by PKC, while the N-terminal was not. Amino acid mapping and site-directed mutagenesis revealed that the phosphorylated residues on the Kv4.2 C-terminal were Serine (Ser) 447 and Ser537. A phospho-site specific antibody showed that phosphorylation at the Ser537 site increased in the hippocampus in response to PKC activation. Surface biotinylation experiments revealed that alanine mutation to block phosphorylation at both of the PKC sites increased surface expression compared to wildtype Kv4.2. Electrophysiological recordings of the wildtype and both the alanine and aspartate mutant Kv4.2 channels expressed with KChIP3 revealed no significant difference in the half activation or inactivation voltage of the channel. Interestingly, the Ser537 site lies within a possible extracellular regulated kinase (ERK)/mitogen activated protein kinase (MAPK) recognition (docking) domain in the Kv4.2 C-terminal sequence. We found that phosphorylation of Kv4.2 by PKC enhanced ERK phosphorylation of the channel in vitro. These findings suggest the possibility that Kv4.2 is a locus for PKC and ERK cross-talk.

Surgical ablation for oncologic disease requiring skull base resection can result in both facial disfigurement and a complex wound defect with exposed orbital content, oral cavity, bone, and dural lining. Inadequate reconstruction can result in brain abscesses, meningitis, osteomyelitis, visual disturbances, speech impairment, and altered oral intake. This study assesses the functional outcomes of patients who undergo anterior and middle cranial fossa skull base reconstruction using microsurgical free tissue transfer techniques. Using a prospectively maintained database, a 10-year, single institution retrospective chart review was performed on patients who had surgery for anterior and middle cranial base tumor resections. The type of resection, reconstruction method, complication rate, and functional outcomes were reviewed. From 1992 to 2003, 70 patients (49 men, 21 women) with a mean age of 54 (age 6-78) underwent anterior and middle cranial skull base tumor resection and reconstruction. The patients were divided into the following groups: maxillectomy with orbital content preservation (n = 21), orbitomaxillectomy with palatal preservation (n = 26), and orbitomaxillectomy with palatal resection (n = 23). The average length of hospital stay was 12.6 days. The vertical rectus abdominis myocutaneous flap was used in the majority of cases to correct midface defects. Two flaps required emergent re-exploration; however, there were no flap failures. Early and late postoperative complications were investigated. Cerebrospinal fluid was observed infrequently (7%) and did not require additional surgical intervention. Intracranial abscesses were encountered rarely (1.4%). Patients who had maxillectomy with orbital preservation and reconstruction had minor ophthalmologic eyelid changes that occurred frequently. Patients who required palatal reconstruction had a normal or intelligible speech (93%) and unrestricted or soft diet (88%). Using a multidisciplinary surgical team approach, there is an increasing role for reconstruction of complex oncologic midface resection defects using microvascular surgical techniques. Early/late complications and functional problems after anterior cranial base resections are uncommon when free tissue transfer is used concomitantly.

BACKGROUND: Dissemination of antimicrobial resistance genes has become an important public health and biodefense threat. Plasmids are important contributors to the rapid acquisition of antibiotic resistance by pathogenic bacteria. PRINCIPAL FINDINGS: The nucleotide sequence of the Klebsiella pneumoniae multiresistance plasmid pMET1 comprises 41,723 bp and includes Tn1331.2, a transposon that carries the bla(TEM-1) gene and a perfect duplication of a 3-kbp region including the aac(6')-Ib, aadA1, and bla(OXA-9) genes. The replication region of pMET1 has been identified. Replication is independent of DNA polymerase I, and the replication region is highly related to that of the cryptic Yersinia pestis 91001 plasmid pCRY. The potential partition region has the general organization known as the parFG locus. The self-transmissible pMET1 plasmid includes a type IV secretion system consisting of proteins that make up the mating pair formation complex (Mpf) and the DNA transfer (Dtr) system. The Mpf is highly related to those in the plasmid pCRY, the mobilizable high-pathogenicity island from E. coli ECOR31 (HPI(ECOR31)), which has been proposed to be an integrative conjugative element (ICE) progenitor of high-pathogenicity islands in other Enterobacteriaceae including Yersinia species, and ICE(Kp1), an ICE found in a K. pneumoniae strain causing primary liver abscess. The Dtr MobB and MobC proteins are highly related to those of pCRY, but the endonuclease is related to that of plasmid pK245 and has no significant homology with the protein of similar function in pCRY. The region upstream of mobB includes the putative oriT and shares 90% identity with the same region in the HPI(ECOR31). CONCLUSIONS: The comparative analyses of pMET1 with pCRY, HPI(ECOR31), and ICE(Kp1 )show a very active rate of genetic exchanges between Enterobacteriaceae including Yersinia species, which represents a high public health and biodefense threat due to transfer of multiple resistance genes to pathogenic Yersinia strains.

Objectives: To determine the drug use in injured Victorian drivers involved in motor vehicle collisions and subsequently transported to a major adult trauma centre in Victoria. Methods: A blood sample was obtained from patients who had been taken to The Alfred Emergency & Trauma Centre (Prahran, Vic., Australia) following a motor vehicle collision. This was performed at the same time and under the same law as compulsory blood screening in Victoria (Section 56 of the Road Safety Act). Four hundred and thirty-six specimens were analysed. Blood stored in vacutainer tubes containing preservative were screened for drugs using enzyme-linked immunosorbent assay and gas chromatography-mass spectometry analysis. Medically administered drugs were excluded from the results. Results: Four hundred and thirty-six specimens were analysed. Metabolites of cannabis were the most commonly found drug (46.7%), the active form of cannabis (Delta9-tetrahydrocannabinol) was found in 33 specimens (7.6%). The next most prevalent drugs were benzodiazepines (15.6%), opiates (11%), amphetamines (4.1%) and methadone (3%). Cocaine was detected in 1.4% of cases. Of the motor vehicle collisions 66% involved males and females of 15-44 years old and Delta9-tetrahydrocannabinol was almost exclusively found in this age group. In motor vehicle collisions involving older drivers there was an increasing use of benzodiazepines. In women >65 years old 30% were positive for benzodiazepines. Conclusions: Drug usage found in this group of injured drivers was disturbingly high. The introduction of further initiatives to decrease the prevalence of drug use in motor vehicle drivers is required.

In a developmental center, a preemployment chest x-ray was required for all job applicants. We scrutinized the pros and cons of this practice through a review of the medical literature and our experience, and discussion with our colleagues. We concluded that such chest x-ray caused unwarranted radiation exposure, did not produce compliance with the tuberculosis laws, gave a false sense of security regarding workers' compensation risk management, was contrary to established occupational medicine practice guidelines, and was unnecessary and wasteful. We discontinued such chest x-rays. The purpose of the pre-employment examination should remain narrowly job related. Even long-established procedures require periodic utilization review.