Band-pass response properties of rat SI neurons

Rats typically employ 4- to 12-Hz "whisking" movements of their vibrissae during tactile exploration. The intentional sampling of signals in this frequency range suggests that neural processing of tactile information may be differentially engaged in this bandwidth. We examined action potential responses in rat primary somatosensory cortex (SI) to a range of frequencies of vibrissa motion. Single vibrissae were mechanically deflected with 5-s pulse trains at rates /=3 Hz. In contrast with this low-pass feature of the response, several other characteristics of the response revealed bandpass response properties. While average evoked response amplitudes measured 0-35 ms after stimulus onset typically decreased with increasing frequency, the later components of the response (>15 ms post stimulus) were augmented at frequencies between 3 and 10 Hz. Further, during the steady state, both rate and temporal measures of neural activity, measured as total spike rate or vector strength (a measure of temporal fidelity of spike timing across cycles), showed peak signal values at 5-10 Hz. A minimal biophysical network model of SI layer IV, consisting of an excitatory and inhibitory neuron and thalamocortical input, captured the spike rate and vector strength band-pass characteristics. Further analyses in which specific elements were selectively removed from the model suggest that slow inhibitory influences give rise to the band-pass peak in temporal precision, while thalamocortical adaptation can account for the band-pass peak in spike rate. The presence of these band-pass characteristics may be a general property of thalamocortical circuits that lead rodents to target this frequency range with their whisking behavior.     

Clinical evidence of the nonpathogenic nature of the M34T variant in the connexin 26 gene

Mutations in GJB2 are the most common cause of congenital nonsyndromic hearing loss. The controversial allele variant M34T has been hypothesized to cause autosomal dominant or recessive nonsyndromic hearing impairment and some in vitro data has been consistent with this hypothesis. In this report, we present the clinical and genotypic study of 11 families (seven familial forms of nonsyndromic sensorineural hearing loss (NSSNHL) and four sporadic cases) in which the M34T GJB2 variant has been identified. The M34T mutation did not segregate with the deafness in six of the seven familial forms of NSSNH. Eight persons with normal audiogram presented a heterozygous M34T variation and five normal hearing individuals were composite heterozygous for M34T and another GJB2 mutation. Four normal hearing individuals with a documented audiogram were M34T/35delG and one was M34T/(GJB6-D13S1830)del. Screening a French control population of 116 subjects we have found an M34T allele frequency of 1.72%. This percentage was not significatively different from the prevalence of the M34T allele in the deaf population, which was 2.12%. All these data suggest that the M34T variant is not clinically significant in human and is a frequent polymorphism in France.     

Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP)

Mutations in the PEX gene at Xp22.1 (phosphate-regulating gene with homologies to endopeptidases, on the X-chromosome), are responsible for X-linked hypophosphataemic rickets (HYP). Homology of PEX to the M13 family of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has raised important questions regarding PEX function at the molecular level. The aim of this study was to analyse 99 HYP families for PEX gene mutations, and to correlate predicted changes in the protein structure with Zn2+ metallopeptidase gene function. Primers flanking 22 characterised exons were used to amplify DNA by PCR, and SSCP was then used to screen for mutations. Deletions, insertions, nonsense mutations, stop codons and splice mutations occurred in 83% of families screened for in all 22 exons, and 51% of a separate set of families screened in 17 PEX gene exons. Missense mutations in four regions of the gene were informative regarding function, with one mutation in the Zn2+-binding site predicted to alter substrate enzyme interaction and catalysis. Computer analysis of the remaining mutations predicted changes in secondary structure, N-glycosylation, protein phosphorylation and catalytic site molecular structure. The wide range of mutations that align with regions required for protease activity in NEP suggests that PEX also functions as a protease, and may act by processing factor(s) involved in bone mineral metabolism.      

Posterior Laryngeal Clefts: Preliminary Report of a New Surgical Procedure Using Tibial Periosteum As an Interposition Graft

Objective: To present the preliminary results of a new surgical procedure for posterior laryngeal cleft repair. Design: Retrospective study in an academic tertiary care center. Method: The study included three male patients (age at surgery, 2, 13, and 14 mo). One presented with severe aspiration and cyanotic attacks, the two others with aspiration and recurrent chest infections. The types of laryngeal clefts included complete cleft of the cricoid with varying degrees of tracheal involvement but not further than the first six tracheal rings. Associated malformations included one VATER syndrome, one esophageal atresia, and one tracheoesophageal fistula. Surgery was performed under general anesthesia with nasotracheaI intubation. A vertical anterior laryngofissure was performed. The mucosal margins of the clefts were incised and then repaired in two layers with polyglactin sutures. The original feature of this procedure was the interposition of a small piece of tibial periosteum between the two layers. This fascia graft is known to be strong and resistant in cleft palate surgery. Main Outcome Measure: Clinical and endoscopic follow-up was used for evaluation of results. Results: The three patients had successful laryngeal repair at a mean follow-up of 6 months (range, 4-14 mo). Conclusion: The anterior laryngofissure provides a good surgical access to the cleft. The interposition of tibial periosteum allows durability of the cleft repair. A longer follow-up is needed to confirm these preliminary results. A computed tomography scan study and a study on the rabbit are planned in order to evaluate the outcome of these periosteal grafts.     

Chronic low-level mercury exposure, BDNF polymorphism, and associations with self-reported symptoms and mood.

Recent reports have described neurobehavioral impairments in human subjects carrying a V66M polymorphism in the gene encoding brain-derived neurotrophic factor (BDNF). Inasmuch as ventral nervous system (CNS) deficits associated with this BDNF polymorphism are similar to those observed among subjects with chronic exposure to elemental mercury (Hg degrees ), we examined the potential effect of this BDNF polymorphism on symptoms and mood in an established cohort of dental practitioners with chronic low-level Hg degrees exposure. Self-reported symptoms and mood were obtained by computerized questionnaire from 193 male dentists (DTs) and 230 female dental assistants (DAs). Spot urine samples were analyzed for mercury concentrations to evaluate recent exposure. Detailed work histories were obtained to calculate chronic indices of Hg degrees exposure. Buccal cell samples were obtained to identify the V66M polymorphism of BDNF. Scores for 11 current and 12 recent and chronic symptom groups, along with six mood factors, were evaluated with respect to recent and chronic Hg degrees exposure and BDNF polymorphism. Multiple regression analysis controlled for age, race, socioeconomic status, tobacco and alcohol use, self-reported health problems, and medications. Separate evaluations were conducted for DTs and DAs. Twenty-three associations between recent or chronic Hg degrees exposure and BDNF status and self-reported symptoms were observed with p < 0.10. All but three were in the expected direction (symptom scores increasing with Hg degrees exposure or BDNF polymorphism), and all but six were among DAs. All eight correlations between chronic exposure indices and recent and chronic symptoms among DAs were in the expected direction. All seven associations between BDNF and symptoms were in the expected direction and split between DTs and DAs. All three associations with mood factors were among DAs and in the expected direction. These results indicate that among DAs very low levels of occupational Hg degrees exposure are associated with increased symptoms. The BDNF polymorphism is also associated with increased symptom and mood scores. Notably, Hg degrees and BDNF polymorphism were additive with respect to their associations with the same symptom group.     

Nosocomial and community acquired uropathogenic isolates of Proteus mirabilis and antimicrobial susceptibility profiles at a university hospital in Sub–Saharan Africa

ObjectiveTo ascertain antimicrobial susceptibility profile of Proteus mirabilis (P. mirabilis) from clinical urine specimens at a university hospital in the spate of its recorded increasing resistance patterns.MethodsThe study was retrospective in nature. Data generated from urine cultures of patients at University of Calabar Teaching Hospital for a period of five years (2004–2009) were compiled. Relevant information obtained were age and gender of patients, organisms recovered and their antibiotic susceptibility patterns. P. mirabilis was identified using standard laboratory procedures.ResultsP. mirabilis showed the highest resistance against ampicillin, cloxacillin, amoxicillin, tetracycline, co-trimoxazole, erythromycin and chloramphenicol (100%–37.2%) while colistin, ofloxacin, ciprofloxacin, ceftriaxone, nalidixic acid and nitrofurantoin recorded the highest activity (59.1%–96.9%) with no drug recording 100% activity. The resistance of the nosocomial isolates of the organism were significantly higher than the community acquired isolates against that of the common antibiotics in use (P<0.05).ConclusionsExtreme caution should be exercised in antibiotic administration in hospital setting and the potential benefits adequately assessed while control of nosocomial infections be given a priority so as to limit the spread of resistant bacteria.     

Bacterial colonization of chronic leg ulcers: current results compared with data 5 years ago in a specialized dermatology department

Background In nearly every chronic wound different bacteria species can be detected. Nevertheless, the presence of such microorganisms is not necessarily obligatory associated with a delayed wound healing. But from this initially unproblematic colonization an infection up to a sepsis can arise in some patients. The aim of our clinical investigation was to analyse the spectrum of microbial colonization of patients with a chronic leg ulcer in our specialized dermatological outpatient wound clinic, and to compare them with the results of comparable data already collected 5 years ago. Objectives In our retrospective investigation the results of bacteriological swabs were documented in 100 patients with a total of 107 chronic leg ulcers. All patients visited the specialized wound outpatient clinic, Department of Dermatology, University of Essen in Germany. Methods A total of 60 patients were female, 40 were male. The mean age was 65 years. Altogether a total of 191 bacterial isolates and 25 different bacterial species could be identified. Results The most often detected species were Staphylococcus aureus (n = 60), Pseudomonas aeruginosa (n = 36) as well as Proteus mirabilis (n = 17). In 10 patients (10%) we identified a colonization with methicillin resistant S. aureus (MRSA). Merely in 6 patients the taken swabs were sterile. Five years ago a comparable investigation was already carried out in our wound outpatient clinic. At that time we could detect in particular more frequent MRSA (21.5% vs. 10%) and rarely P. aeruginosa (24.1% vs. 33.6%). Conclusion The results of our investigation demonstrate the current spectrum of the bacterial colonization in patients with chronic leg ulcers in a university dermatological wound centre in comparison to the last 5 years. In our institution we were able to demonstrate a shift of the detected bacterial species from gram‐positive in direction to gram‐negative germs. Beside the already known problems with MRSA, in future therapeutic strategies in patients with chronic leg ulcers the increasing amount of gram‐negative bacteria and especially of P. aeruginosa should considered.     

Response to parathyroid hormone and 1,25-dihydroxyvitamin D3 of bone-derived cells isolated from normal children and children with abnormalities in skeletal development

In order to evaluate the role of intrinsic defects in osteoblast function in the pathogenesis of diseases of skeletal development, we developed techniques which permit the evaluation of the metabolic properties of bone-derived cells in vitro. Cells from control children demonstrated a variety of properties classically attributed to osteoblasts (presence of alkaline phosphatase positive cells and synthesis of bone gla protein) and responded to PTH (cAMP production) and to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) ([3H]25-hydroxyvitamin D3 conversion into [3H]24,25-dihydroxyvitamin D3 and bone gla protein secretion). Using these techniques we evaluated the function of cultured bone cells from patients with three rare diseases of skeletal development. Cells from a patient with rickets resistant to 1,25(OH)2D3 were resistant to 1,25(OH)2D3 but responded normally to PTH. Cells from a patient with acroosteolysis with osteoporosis responded normally to PTH and 1,25(OH)2D3. Cells from a patient with hyperphosphatasia with osteoectasia responded normally to 1,25(OH)2D3 but did not respond to PTH. The results demonstrate that bone cell cultures can provide information about the role of osteoblast dysfunction in such diseases.