The von Hippel-Lindau tumour suppressor gene: uncovering the expression of the pVHL172 isoform.

BACKGROUND: The von Hippel-Lindau (VHL) gene encodes two mRNA variants. Variant 1 encodes two protein isoforms, pVHL213 and pVHL160, that have been extensively documented in the literature. Variant 2 is produced by alternative splicing of exon 2 and encodes a pVHL isoform of 172 amino acids with a theoretical molecular weight of 19 kDa (pVHL172), the expression of which has never been demonstrated so far due to the absence of suitable antibodies. METHODS: We have generated an anti-pVHL monoclonal antibody (JD-1956) using pVHL172 recombinant protein. We tested the antibody against exogenous or endogenous expressed proteins in different cell lines. We identified the pVHL172 using a silencing RNA strategy. The epitope of the antibody was mapped using a peptide array. RESULTS: We efficiently detected the three different isoforms of pVHL in cell lines and tumorigenic tissues by western blotting and immunohistochemistry and confirmed for the first time the endogenous expression of pVHL172. CONCLUSIONS: The endogenous expression of the three isoforms and particularly the pVHL172 has never been shown before due to a lack of a highly specific antibody since none of the available commercial antibodies distinguish the three isoforms of pVHL in cells or in both normal and cancerous human tissues. Evidence of pVHL172 expression emphasises the need to further study its implication in renal tumorigenesis and VHL disease.

Functional reorganization of the human auditory pathways following hemispherectomy: an fMRI demonstration.

The present study investigated the functional reorganization of ipsilateral and contralateral auditory pathways in hemispherectomized subjects. Functional reorganization was assessed using functional Magnetic Resonance Imaging (fMRI) and stimulation with complex sounds presented binaurally and monaurally. For neurologically intact control subjects, results showed that binaural stimulations evoked balanced activity in both hemispheres while monaural stimulations induced strong contralateral activity and weak ipsilateral activity. The results obtained from hemispherectomized subjects were substantially different from those obtained from control subjects. Specifically, activity in the intact hemisphere showed a significant decrease in response to contralateral stimulation but, concomitantly, an increase in response to ipsilateral stimulation. The present findings suggest that a substantial functional reorganization takes place in the auditory pathways following an early hemispherectomy. The exact nature of this functional reorganization remains to be specified.

Time-resolved laser fluorescence spectroscopy of organic ligands by europium: Fluorescence quenching and lifetime properties.

Time-resolved Laser Fluorescence Spectroscopy (TRLFS) has proved its usefulness in the fields of biophysics, life science and geochemistry to characterize the fluorescence probe molecule with its chemical environment. The purpose of this study is to demonstrate the applicability of this powerful technique combined with Steady-State (S-S) measurements. A multi-mode factor analysis, in particular CP/PARAFAC, was used to analyze the interaction between Europium (Eu) and Humic substances (HSs) extracted from Saint Lawrence Estuary in Canada. The Saint Lawrence system is a semi-enclosed water stream with connections to the Atlantic Ocean and is an excellent natural laboratory. CP/PARAFAC applied to fluorescence S-S data allows introspecting ligands-metal interactions and the one-site 1:1 modeling gives information about the stability constants. From the spectral signatures and decay lifetimes data given by TRLFS, one can deduce the fluorescence quenching which modifies the fluorescence and discuss its mechanisms. Results indicated a relatively strong binding ability between europium and humic substances samples (LogK value varies from 3.38 to 5.08 at pH 7.00). Using the Stern-Volmer plot, it has been concluded that static and dynamic quenching takes places in the case of salicylic acid and europium interaction while for HSs interaction only a static quenching is observed.

Province-wide population survey of acute appendicitis in Canada. New twists to an old disease.

BACKGROUND: This study, sponsored and conducted by Le Collège des Médecins du Québec, audited the management of acute appendicitis in the Province of Québec (Population 7.6 million), Canada, over a period of 1 year (April 2002-March 2003). METHODS: A questionnaire was sent to the Health Records Department of all hospitals surgically treating appendicitis in the province. Data from 85 (100%) hospitals were received and reviewed. RESULTS: During the study period, 7,599 appendectomies were performed, and 5,707 (75%) were selected for study (55% men). The rate of normal and perforated appendix was 5.4% and 15.9% respectively. Median hospital stay for simple and perforated appendicitis was 2.6 and 5.8 days, respectively. At least one imaging procedure was done in 86% of cases (23% computed tomography [CT], 55% ultrasound). Antibiotics were not given in 7% of cases and in 8% of patients with a perforation. Seventeen percent of patients did not receive preoperative or intraoperative doses, and postoperatively, 69% of patients received unnecessary doses. Laparoscopy was used in 35% of cases and was associated with a reduction in postoperative stay for simple (2.6 versus 2.9 days, p < 0.001) and perforated appendicitis (4.6 versus 5.9 days, p = 0.004). A low rate of laparoscopy (<25%) was found in 53% of teaching (University and Affiliated) and 45% of nonteaching institutions. Conversion to open surgery was necessary in 9.7% of simple appendicitis and 29.3% of perforated ones (p < 0.001). CONCLUSIONS: Although results of this survey are comparable to those of similar published series, a few concerns emerge. Many have to do with patient noncompliance with recommended antibiotic usage for acute appendicitis. Further, although laparoscopy seems to be slowly making its way into the surgical armamentarium, the low rate of laparoscopic appendectomies in teaching hospitals raises the issue of appropriate resident training.

Laparoscopic colon surgery performed safely by general surgeons in a community hospital: a review of 154 consecutive cases.

BACKGROUND: The primary end point of this study was documentation of the feasibility, safety, and benefits of laparoscopic colon resection (LCR) performed by general surgeons in a community hospital. METHODS: The charts of 154 patients who underwent LCR between March 1998 and August 2003 by a group of three surgeons working in a community hospital were reviewed. Data extracted from the charts included patients' demographics, surgical indications and procedures, conversion rate, history, operative time, postoperative recovery time, and complication rates. RESULTS: Of the 154 patients, 70 were men. The mean age of the patients was 60 years. Overall, 62% of the patients had a history of prior abdominal surgery. In the majority of cases (77%), LCR was performed for benign disease. Segmental resection involving the left colon was performed for 122 patients, and right hemicolectomy was performed for 32 patients. The rates of conversion were 9.6% for open surgery and 12% for diverticulitis (n = 83). For LCR, the median operative time was 120 min, and the median hospital stay was 5 days. The complication rate was 21.6% for LCR, and the mortality rate was 2.1%. CONCLUSION: The outcomes for LCR performed by a team of general surgeons working together in a community hospital are similar to the historical results from academic health science centers.

Estimation of dissolved organic carbon (DOC) concentrations in nanoliter samples using UV spectroscopy.

A simple analytical system has been developed and tested for estimating dissolved organic carbon (DOC) concentrations in nanoliter samples of sediment porewaters. The system consists of a loop injector that introduces 200 nL of sample directly into the capillary tubing connected to a scanning UV-VIS detector equipped with a 35-nanoliter capillary flowcell. Analysis of DOC by spectroscopic and high-temperature catalytic oxidation (HTCO) methods on the same samples showed a strong linear correlation between UV absorbance at 254 nm and HTCO-DOC concentration, allowing the DOC quantification. The simplicity and the robustness of the UV system allow DOC measurements in the field at a rate of 30 samples/h. We have used the UV system successfully for determining high-resolution distributions of porewater DOC concentrations in sediments at millimeter scales.

Aerodynamic assessment of the speech of adults undergoing multichannel cochlear implantation.

This investigation was designed to evaluate the aerodynamic characteristics of the speech of adult multichannel cochlear implant (Nucleus, 21-channel) recipients. Five adults with an acquired profound sensorineural hearing loss were tested before implantation, immediately following implantation, and 3, 6, 9, and 12 months after implantation. A commercially available computerized pressure-flow instrumentation system was employed to assess the respiratory, laryngeal, velopharyngeal, and oral articulatory subsystems of speech of the implantees. The results of the investigation indicated 1) a slight increase in airflow rate values for sustained vowel /a/phonation after implantation, 2) a slight increase in duration of sustained vowel phonation from the preimplant period to the last postimplant period, 3) an increase in laryngeal airway resistance after implantation that resulted from a larger increase in estimated transglottal pressure than in transglottal airflow, 4) maintenance of normal velopharyngeal closure in oral-nasal contrastive contexts, and 5) slight increases in oral orifice area for fricative syllable utterances following implantation. Individual strategies for coordinated control of the speech mechanism appear to be potent variables to consider when assessing speech production.

Effectiveness of an intensive speech perception training program for adult cochlear implant recipients.

A staggered multiple baseline single-subject experimental design was used to assess the effectiveness of a postimplant intensive aural rehabilitation program. Four adults with an acquired profound hearing loss were provided with a Nucleus 22-channel cochlear implant. The subjects completed a speech perception test protocol once before their cochlear implant operation and at 3-month intervals for a period of 12 months postimplantation. Each subject participated in a 12-week postimplant intensive aural rehabilitation program. A comparison of the prerehabilitation and postrehabilitation results failed to reveal any systematic improvements in performance on the speech perception tests that could be attributed unequivocally to the aural rehabilitation program.

Alteration and release of aliphatic compounds by the polychaete Nereis virens (Sars) experimentally fed with hydrocarbons.

In the laboratory, marine worms were fed with a mixture of algae and several aliphatic hydrocarbons for 15 days. After ingestion by the worms, 34.9% of hydrocarbons are found in the faeces and only 3.1% accumulated in the gut. The comparison between the initial mixture and the faeces shows that the worm's digestive process lead to changes in the distribution of the n-alkane mixture. These changes are different from those only due to physical processes in the experimental conditions. In our experiment, no variation in the distribution of hydrocarbons in faeces with time and no microbial hydrocarbon biodegradation were evidenced. Our results suggest that marine worm feeding can substantially affect the fate of hydrocarbons in the sedimentary marine ecosystem by predominantly stimulating dissolution processes.

Auditory sequential organization among children with and without a hearing loss.

The present investigation examined the ability of children with and without a hearing loss to correctly reproduce sequences of acoustic stimuli that varied in number, temporal spacing, and type. Forty-eight children took part in the investigation. They were divided into four groups: two groups of 6- and 7-year-old children, 12 with normal hearing and 12 with a sensorineural hearing loss; and two groups of 9- and 10-year-old children, 12 with normal hearing and 12 with a sensorineural hearing loss. All of the children completed auditory temporal sequencing tasks with verbal (/ba/ and /da/) and nonverbal (a 1-kHz pure tone and a wide band noise) acoustic stimuli. For the 6- and 7-year-old children, the results revealed a significant difference between the children with a hearing loss and their peers with normal hearing for immediate recall of verbal sequences. There were no significant differences in performance between the children with a hearing loss and their peers with normal hearing on the nonverbal sequencing tasks or on the nonverbal and verbal memory span tasks. For the 9- and 10-year-old children, the results did not show any significant differences in performance between the two groups of children for the reproduction of sequences containing more than two verbal or nonverbal elements nor for the auditory memory span task when the sequences consisted of verbal stimuli. For the recall of two verbal stimuli with a variable interstimulus interval (ISI) duration, the results showed that the children with a hearing loss experienced more difficulty than the children with normal hearing. Overall, the results indicated that on the auditory sequential organization tasks, the poorer performance of the children with a hearing loss is likely attributable to auditory perceptual processing deficits rather than to poorer short-term memory capabilities. Also, an analysis of the data revealed that the older children obtained significantly better results than the younger children on auditory sequential organization tasks.

Some limitations of evaluative investigations based solely on normed outcome measures.

The present article argues that evaluative research in audiologic rehabilitation should be consistent with contemporary conceptual frameworks of rehabilitation. Moreover, comprehensive evaluative research investigations should include an evaluation of (1) the process of intervention and (2) the impacts and consequences of the intervention program. An approach to rehabilitation based on the principle that intervention should be viewed as a solution-centered problem-solving process is outlined. Then, three illustrative cases are described and compared from the perspective of traditional evaluative research paradigms and from the perspective that audiologic rehabilitation is a solution-centered problem-solving process. Some shortcomings of traditional approaches to evaluative research are discussed. Finally, some guidelines that could lead to the development of comprehensive evaluative research in rehabilitation are outlined.

Auditory processing in a patient with a unilateral lesion of the inferior colliculus.

The role of the inferior colliculus (IC) in human auditory processing is still poorly understood. We report here the results obtained with a 12-year-old boy (FX) who suffered a very circumscribed lesion of the right IC without additional neurological damage. The child underwent an extensive battery of psychophysical hearing tests. Results revealed normal peripheral auditory functioning, bilaterally. Furthermore, masking-level differences and frequency-pattern recognition were normal for each ear. When the right ear was stimulated, behavioural tests assessing central auditory processing yielded normal results. However, when the left ear was stimulated, speech recognition in the presence of a competing ipsilateral signal and duration-pattern recognition were impaired. Similarly, performance on two dichotic speech recognition tests was poor when the target stimulus was presented in the left and the competing signal in the right ear. Finally, sound-source localization in space was deficient for speakers located on the side contralateral to the lesion. The pattern of results suggests that auditory functions such as recognition of low-redundancy speech presented monaurally, recognition of tone duration patterns, binaural separation and integration, as well as sound-source localization in space, depend on the integrity of the bilateral auditory pathways at the IC level.

Blind subjects process auditory spectral cues more efficiently than sighted individuals.

The goal of the present study was to investigate how monaural sound localization on the horizontal plane in blind humans is affected by manipulating spectral cues. As reported in a previous study (Lessard et al. 1998), blind subjects are able to calibrate their auditory space despite their congenital lack of vision. Moreover, the performance level of half of the blind subjects was superior to that of sighted subjects under monaural listening conditions. Here, we first tested ten blind subjects and five controls in free-field (1) binaural and (2) monaural sound localization tasks. Results showed that, contrary to controls and half the blind subjects, five of the blind listeners were able to localize the sounds with one ear blocked. The blind subjects who showed good monaural localization performances were then re-tested in three additional monaural tasks, but we manipulated their ability to use spectral cues to carry out their discrimination. These subjects thus localized these same sounds: (3) with acoustical paste on the pinna, (4) with high-pass sounds and unobstructed pinna and (5) with low-pass sounds and unobstructed pinna. A significant increase in localization errors was observed when their ability to use spectral cues was altered. We conclude that one of the reasons why some blind subjects show supra-normal performances might be that they more effectively utilize auditory spectral cues.

Excess masking among listeners with a sensorineural hearing loss.

Three experiments were conducted to determine whether listeners with a sensorineural hearing loss exhibited greater than normal amounts of masking at frequencies above the frequency of the masker. Excess masking was defined as the difference (in dB) between the masked thresholds actually obtained from a hearing-impaired listener and the expected thresholds calculated for the same individual. The expected thresholds were the power sum of the listener's thresholds in quiet and the average masked thresholds obtained from a group of normal-hearing subjects at the test frequency. Hearing-impaired listeners, with thresholds in quiet ranging from approximately 35-70 dB SPL (at test frequencies between 500-3000 Hz), displayed approximately 12-15 dB of maximum excess masking. The maximum amount of excess masking occurred in the region where the threshold in quiet of the hearing-impaired listener and the average normal masked threshold were equal. These findings indicate that listeners with a sensorineural hearing loss display one form of reduced frequency selectivity (i.e., abnormal upward spread of masking) even when their thresholds in quiet are taken into account.

Reflections on evaluative research in audiological rehabilitation.

Changes in service delivery triggered by current conceptualizations of rehabilitation require an accompanying paradigm shift in the approaches used to evaluate the effectiveness of intervention programs in audiological rehabilitation. The present article outlines three fundamental principles of contemporary rehabilitative audiology that have implications concerning the way that audiological rehabilitation services should be conceived and dispensed, as well as the way in which comprehensive evaluative research investigations should be designed and conducted. Traditional treatment efficacy paradigms used to assess the effectiveness of intervention programs in rehabilitative audiology are critiqued. Finally, factors that should guide the development of comprehensive evaluative research paradigms which are consistent with current models of intervention in audiological rehabilitation are outlined.