Solid-state framing camera operating in interferometric mode.

A high speed solid-state framing camera has been developed which can operate in interferometric mode. This camera measures the change in the index of refraction of a semiconductor when x-rays are incident upon it. This instrument uses an x-ray transmission grating/mask in front of the semiconductor to induce a corresponding phase grating in the semiconductor which can then be measured by an infrared probe beam. The probe beam scatters off of this grating, enabling a measure of the x-ray signal incident on the semiconductor. In this particular instrument, the zero-order reflected probe beam is attenuated and interfered with the diffracted orders to produce an interferometric image on a charge coupled device camera of the phase change induced inside the semiconductor by the incident x-rays.

Work-specific cognitive symptoms and the role of work characteristics, fatigue, and depressive symptoms in cancer patients during 18 months post return to work.

OBJECTIVE: Cancer patients can experience work-specific cognitive symptoms post return to work. The study aims to (1) describe the course of work-specific cognitive symptoms in the first 18 months post return to work and (2) examine the associations of work characteristics, fatigue and depressive symptoms with work-specific cognitive symptoms over time. METHODS: This study used data from the 18-month longitudinal "Work Life after Cancer" cohort. The Cognitive Symptom Checklist-Work Dutch Version (CSC-W DV) was used to measure work-specific cognitive symptoms. Linear mixed models were performed to examine the course of work-specific cognitive symptoms during 18-month follow-up; linear regression analyses with generalized estimating equations were used to examine associations over time. RESULTS: Working cancer patients examined with different cancer types were included (n = 378). Work-specific cognitive symptoms were stable over 18 months. At baseline, cancer patients reported more working memory symptoms (M = 32.0; CI, 30.0-34.0) compared with executive function symptoms (M = 19.3; CI, 17.6-20.9). Cancer patients holding a job with both manual and nonmanual tasks reported less work-specific cognitive symptoms (unstandardized regression coefficient b = -4.80; CI, -7.76 to -1.83) over time, compared with cancer patients with a nonmanual job. Over time, higher depressive symptoms were related to experiencing more overall work-specific cognitive symptoms (b = 1.27; CI, 1.00-1.55) and a higher fatigue score was related to more working memory symptoms (b = 0.13; CI, 0.04-0.23). CONCLUSIONS: Job type should be considered when looking at work-specific cognitive symptoms over time in working cancer patients. To reduce work-specific cognitive symptoms, interventions targeted at fatigue and depressive symptoms might be promising.

Fatigue and depressive symptoms improve but remain negatively related to work functioning over 18 months after return to work in cancer patients.

PURPOSE: The aims of this study are to investigate the course of work functioning, health status, and work-related factors among cancer patients during 18 months after return to work (RTW) and to examine the associations between these variables and work functioning over time. METHODS: Data were used from the 18-month longitudinal "Work Life after Cancer" (WOLICA) cohort, among 384 cancer patients who resumed work. Linear mixed models were performed to examine the different courses during 18-month follow-up. Linear regression analyses with generalized estimating equations (GEE) were used to examine the associations and interactions. RESULTS: Cancer patients reported an increase of work functioning and a decrease of fatigue and depressive symptoms in the first 12 months, followed by a stable course between 12 and 18 months. Cognitive symptoms were stable during the first 18 months. Working hours increased and social support decreased during the first 6 months; both remained stable between 6 and 18 months. Fatigue, depressive, and cognitive symptoms were negatively associated with work functioning over time; working hours and supervisor social support were positively associated. CONCLUSIONS: Interventions to improve cancer patients' work functioning over time might be promising if they are aimed at reducing fatigue, depressive symptoms, cognitive symptoms, and encouraging supervisor social support. IMPLICATIONS FOR CANCER SURVIVORS: It is important to monitor cancer patients not only in the period directly after RTW but up to 18 months after RTW, allowing for timely interventions when needed.

X-ray bang-time and fusion reaction history at picosecond resolution using RadOptic detection.

We report recent progress in the development of RadOptic detectors, radiation to optical converters, that rely upon x-ray absorption induced modulation of the optical refractive index of a semiconductor sensor medium to amplitude modulate an optical probe beam. The sensor temporal response is determined by the dynamics of the electron-hole pair creation and subsequent relaxation in the sensor medium. Response times of a few ps have been demonstrated in a series of experiments conducted at the LLNL Jupiter Laser Facility (JLF). This technology will enable x-ray bang-time and fusion burn-history measurements with ∼ ps resolution.

High-resolution spectroscopy for Doppler-broadening ion temperature measurements of implosions at the National Ignition Facility.

Future implosion experiments at the national ignition facility (NIF) will endeavor to simultaneously measure electron and ion temperatures with temporal and spatial resolution in order to explore non-equilibrium temperature distributions and their relaxation toward equilibrium. In anticipation of these experiments, and with understanding of the constraints of the NIF facility environment, we have explored the use of Doppler broadening of mid-Z dopant emission lines, such as krypton He-α at 13 keV, as a diagnostic of time- and potentially space-resolved ion temperature. We have investigated a number of options analytically and with numerical raytracing, and we have identified several promising candidate spectrometer designs that meet the expected requirements of spectral and temporal resolution and data signal-to-noise ratio for gas-filled exploding pusher implosions, while providing maximum flexibility for use on a variety of experiments that potentially include burning plasma.

Impact of wind turbine sound on annoyance, self-reported sleep disturbance and psychological distress.

PURPOSE OF THE RESEARCH: The present government in the Netherlands intends to realize a substantial growth of wind energy before 2020, both onshore and offshore. Wind turbines, when positioned in the neighborhood of residents may cause visual annoyance and noise annoyance. Studies on other environmental sound sources, such as railway, road traffic, industry and aircraft noise show that (long-term) exposure to sound can have negative effects other than annoyance from noise. This study aims to elucidate the relation between exposure to the sound of wind turbines and annoyance, self-reported sleep disturbance and psychological distress of people that live in their vicinity. Data were gathered by questionnaire that was sent by mail to a representative sample of residents of the Netherlands living in the vicinity of wind turbines PRINCIPAL RESULTS: A dose-response relationship was found between immission levels of wind turbine sound and selfreported noise annoyance. Sound exposure was also related to sleep disturbance and psychological distress among those who reported that they could hear the sound, however not directly but with noise annoyance acting as a mediator. Respondents living in areas with other background sounds were less affected than respondents in quiet areas. MAJOR CONCLUSIONS: People living in the vicinity of wind turbines are at risk of being annoyed by the noise, an adverse effect in itself. Noise annoyance in turn could lead to sleep disturbance and psychological distress. No direct effects of wind turbine noise on sleep disturbance or psychological stress has been demonstrated, which means that residents, who do not hear the sound, or do not feel disturbed, are not adversely affected.

Validation of a method to measure the proprioception of the knee.

INTRODUCTION: Proprioception is an important mechanism in knee stability and function. After an injury like an anterior cruciate ligament (ACL) rupture changes appear in knee proprioception which play a major role in rehabilitation. There are several methods to measure proprioception; the threshold to detect passive motion (TTDPM) is often used to quantify proprioception. In this study the reliability and validity were tested of an apparatus, which measures the TTDPM based on the Lund technique of Fridén and Roberts (Sweden). MATERIALS AND METHODS: Sixteen healthy participants were tested on both legs, from start position 20 degrees and 40 degrees, towards extension (TE) and flexion (TF). The same measurement was repeated 12 (6-21) days later. RESULTS: An overall mean TTDPM of 0.58 degrees (95% confidence interval CI=0.53-0.62 degrees ) was found. Thresholds were different depending on direction of motion and start position. TTDPM in 20 degrees TE (0.51 degrees, CI=0.48-0.56 degrees) and in 40 degrees TF (0.54 degrees, CI=0.50-0.58 degrees ) were significantly lower than TTDPM in 40 degrees TE (0.68 degrees , CI=0.63-0.74 degrees) and in 20 degrees TF (0.58 degrees, CI=0.54-0.63 degrees). Thresholds were rising with age. Women had higher thresholds than men. CONCLUSION: The method is a reliable and valid way to measure proprioception. The next step is to use this method on patients with an ACL-rupture and compare these results with healthy subjects.

Utility of the stroke-thrombolytic predictive instrument.

OBJECTIVE: The goal of this study was to evaluate the utility of the stroke thrombolytic predictive instrument (s-TPI) in predicting clinical outcome in patients with acute ischaemic stroke treated with intravenous tissue plasminogen activator (t-PA). METHODS: The study assessed the external validity of the s-TPI in 301 consecutive stroke patients treated with intravenous t-PA. Clinical outcome was measured with the modified Rankin scale (mRs) at 3 months. The study used the s-TPI to calculate probabilities of a good outcome (mRs 0-1) and a poor outcome (mRs 5-6). We compared these probabilities with the observed outcome using receiver-operator characteristics (ROC) curves and calibration curves. Subgroup analyses for different onset-to-treatment time windows were performed. RESULTS: According to the s-TPI, the mean predicted probability of a good and a poor outcome in the validation cohort were 0.45 and 0.17. The area under the ROC curves were 0.80 (4.5-hour time window), 0.82 (3-hour time window) and 0.77 (3-4.5 hours time window) for predicting good outcome, and 0.78 (4.5 hours), 0.80 (3 hours) and 0.74 (3-4.5 hours) for predicting poor outcome. Calibration curves revealed a slight overestimation of probabilities of a good outcome and underestimation of probabilities of a poor outcome. CONCLUSIONS: The s-TPI appears to be reasonably valid for predicting outcome after t-PA treatment in daily practice, although a slight overestimation of a good and underestimation of a poor outcome was observed.

Measuring disability in stroke: relationship between the modified Rankin scale and the Barthel index.

BACKGROUND AND PURPOSE: The effectiveness of therapeutic interventions in acute stroke trials is traditionally measured with the modified Rankin scale (mRs) and the Barthel index (BI). The mRs is a global disability scale divided into six steps from total independence to total dependence. The BI assesses ten basal activities of daily living, of which eight assess level of dependence (bathing, grooming, using stairs, dressing, feeding, toilet use, transfers and walking). The aim of this study was to investigate the relationship between the mRs and the total scores and item-scores of the BI. METHODS: During a period of 3 months mRs and BI scores were collected from two multicentre randomised, placebo-controlled trials with lubeluzole (515 and 519 patients). In each patient we compared the mRs grades with the total BI score and the scores on the ten subitems. RESULTS: For both trials there was extensive overlap of BI scores between mRs grades and a wide range in BI scores among patients with mRs grades 3 and 4. We also found discrepancies between the BI item-scores and mRs grades. About 40% of patients with mRs grades 1 (able to carry out all usual activities) and 2 (able to look after own affairs without assistance) were not independent on at least one activity of the BI. In both studies, about 30% of the patients needed help or supervision for walking, although they were classified as mRs 3 (requiring some help but able to walk without assistance). CONCLUSIONS: Investigators in stroke trials use the mRs as a subjective global disability scale, and they do not strictly take into account limitations in performing specific basal activities of daily living, as assessed by the BI, to assign mRs grades.

Two mouse retinal degenerations caused by missense mutations in the beta-subunit of rod cGMP phosphodiesterase gene.

We report the chromosomal localization, mutant gene identification, ophthalmic appearance, histology, and functional analysis of two new hereditary mouse models of retinal degeneration not having the Pde6brd1("r", "rd", or "rodless") mutation. One strain harbors an autosomal recessive mutation that maps to mouse chromosome 5. Sequence analysis showed that the retinal degeneration is caused by a missense point mutation in exon 13 of the beta-subunit of the rod cGMP phosphodiesterase (beta-PDE) gene (Pde6b). The gene symbol for this strain was set as Pde6brd10, abbreviated rd10 hereafter. Mice homozygous for the rd10 mutation showed histological changes at postnatal day 16 (P16) of age and sclerotic retinal vessels at four weeks of age, consistent with retinal degeneration. Retinal sections were highly positive for TUNEL and activated caspase-3 immunoreactivity, specifically in the outer nuclear layer (ONL). ERGs were never normal, but rod and cone ERG a- and b-waves were easily measured at P18 and steadily declined over 90% by two months of age. Protein extracts from rd10 retinas were positive for beta-PDE immunoreactivity starting at about the same time as wild-type (P10), though signal averaged less than 40% of wild-type. Interestingly, rearing rd10 mice in total darkness delayed degeneration for at least a week, after which morphological and functional loss progressed irregularly. With the second strain, a complementation test with rd1 mice revealed that the retinal degeneration phenotype observed represents a possible new allele of Pde6b. Sequencing demonstrated a missense point mutation in exon 16 of the beta-subunit of rod phosphodiesterase gene, different from the point mutations in rd1 and rd10. The gene symbol for this strain was set as Pde6bnmf137, abbreviated nmf137 hereafter. Mice homozygous for this mutation showed retinal degeneration with a mottled retina and white retinal vessels at three weeks of age. The exon 13 missense mutation (rd10) is the first known occurrence of a second mutant allele spontaneously arising in the Pde6b gene in mice and may provide a model for studying the pathogenesis of autosomal recessive retinitis pigmentosa (arRP) in humans. It may also provide a better model for experimental pharmaceutical-based therapy for RP because of its later onset and milder retinal degeneration than rd1 and nmf137.

Safety of routine IV thrombolysis between 3 and 4.5 h after ischemic stroke.

BACKGROUND: The administration of tissue plasminogen activator (t-PA) has been proven effective for ischemic stroke within 3 h after onset. A pooled-analysis of six trials showed that intravenous t-PA still improves outcome when given between 3 to 4.5 h after stroke onset. On the basis of this pooled analysis, t-PA was also routinely offered to our patients between 3-4.5 h. We report the safety and clinical features of this group together with the features of the group given t-PA within 3 h. METHODS: Prospectively patient characteristics, stroke severity, stroke subtype, incidence of symptomatic intracerebral hemorrhage (SICH), in-hospital mortality, and 3-months modified Rankin Scale scores (mRS) were registered. Data was analyzed separately for patients treated within 3 h (early group) and those treated between 3-4.5 h (late group). RESULTS: Among 176 patients who underwent intravenous thrombolysis, 101 were treated in the early group and 75 in the late group. Six (5.9%; 95% CI 2.8%-12.3%) patients in the early group and 4 (5.3%; 95% CI 2.2%-12.9%) in the late group developed SICH (p=1.0). In the early group 13 (12.9%; 95% CI 7.7%-20.8%) patients died within 7 days after admission, compared to 5 (6.7%; 95% CI 3.0%-14.7%) in the late group (p=0.179). In the early group 44 (43.6%; 95% CI 43.3%-53.3%) were independent (mRS< or =2) at three months, compared to 36 (48.0%; 95% CI 37.0%-59.1%) in the late group (p=0.559). CONCLUSION: Our data show no trend of decreased safety of thrombolysis beyond 3 h. Due to a small sample size a harmful effect cannot be excluded but seems unlikely.

Measuring somatic symptoms with the CES-D to assess depression in cancer patients after treatment: comparison among patients with oral/oropharyngeal, gynecological, colorectal, and breast cancer.

There is a high prevalence of depression after cancer treatment. In the literature, several authors have raised questions about assessing somatic symptoms to explore depression after cancer treatment. These somatic sequelae are a consequence of cancer treatment and should cause higher depression rates in cancer patients. In this study, the Somatic domain on a depression questionnaire, the Center for Epidemiologic Studies-Depression scale (CES-D) was analyzed in different cancer patients after treatment, as compared with a control group. Data from 566 cancer patients (oral/oropharyngeal, gynecological, colorectal, and breast cancer) and 255 randomly chosen comparison patients were analyzed. The total score on the CES-D domain of Somatic Retarded Activity significantly differed between the cancer and comparison groups; but the cancer groups showed both less somatic morbidity (colorectal cancer) and more somatic morbidity (oral/oropharyngeal, breast) than the comparison group. In the analyses of the CES-D with and without the Somatic domain, the prevalence of depression symptoms with the Somatic domain is lower for the cancer groups. Authors conclude that cancer patients are not a homogenous group as regards somatic sequelae. Evidence for removing Somatic items from the CES-D for patients after cancer treatment was not confirmed.

Digital correction of magnification in pelvic x rays for preoperative planning of hip joint replacements: theoretical development and clinical results of a new protocol.

The introduction of digital radiological facilities leads to the necessity of digital preoperative planning, which is an essential part of joint replacement surgery. To avoid errors in the preparation and execution of hip surgery, reliable correction of the magnification of the projected hip is a prerequisite. So far, no validated method exists to accomplish this. We present validated geometrical models of the x-ray projection of spheres, relevant for the calibration procedure to correct for the radiographic magnification. With help of these models a new calibration protocol was developed. The validity and precision of this procedure was determined in clinical practice. Magnification factors could be predicted with a maximal margin of error of 1.5%. The new calibration protocol is valid and reliable. The clinical tests revealed that correction of magnification has a 95% margin of error of -3% to +3%. Future research might clarify if a strict calibration protocol, as presented in this study, results in more accurate preoperative planning of hip joint replacements.

Concentrations of mercury in tissues of beluga whales (Delphinapterus leucas) from several communities in the Canadian Arctic from 1981 to 2002.

Beluga whales have been hunted for food by Native People in the Canadian Arctic since prehistoric time. Here we report the results of analyses of total mercury in samples of liver, kidney, muscle and muktuk from collections over the period 1981-2002. We compare these results with human consumption guidelines and examine temporal and geographic variation. Liver has been analyzed more frequently than other organs and it has been used as the indicator organ. Mercury accumulates in the liver of the whales over time so that the whale ages are usually linked statistically to their levels of mercury in liver. Virtually all the samples of 566 animals analyzed contained mercury in liver at concentrations higher than the Canadian consumption guideline of 0.5 microg g-1 (wet weight) for fish. (There is no regulatory guideline for concentrations in marine mammals in Canada.) Samples from locations in the Mackenzie Delta in the western Canadian Arctic and from Pangnirtung in the eastern Canadian Arctic were obtained more often than from other location and these offered the best chances to determine whether levels have changed over time. Statistical outlier points were removed and the regressions of (ln) mercury in liver on age were used to calculate the level of mercury in whales of age 13.1 years in order to compare age-adjusted levels at different locations. These age-adjusted levels and also the slopes of regressions suggested that levels have increased in the Mackenzie Delta over the sampling period although not in a simple linear fashion. Other locations had fewer collections, generally spread over fewer years. Some of them indicated differences between sampling times but we could not establish whether these differences were simply temporal variation or whether they were segments of a consistent trend. For example, the levels in whales from Arviat were considerably higher in 1999 than in 1984 but we have only two samples. Similarly, samples from Iqaluit in 1994 exceeded considerably those in 1993 and the interval seems too short to reflect any regional temporal trend and more likely represent an extreme case of year-to-year variation. Previous analyses of data from geographically distinct groups had suggested that whales in the western Canadian Arctic had higher levels of mercury than those from the eastern Canadian Arctic. The present analysis suggests that such regional differences have diminished and are no longer statistically significant. No site has indicated significant decreases in more recent samples. The levels of total mercury in the most analyzed organs fell in the order of liver (highest levels), kidney, muscle and muktuk (lowest level). While muktuk had the lowest level of the organs most frequently analyzed, it is the preferred food item from these whales and it still exceeded the consumption guideline in most instances.

Comparing self-report, clinical examination and functional testing in the assessment of work-related limitations in patients with chronic low back pain.

PURPOSE: To compare the work-related limitations assessed using self-report, clinical examination and functional testing in patients with chronic low back pain (CLBP). METHODS: Work-related limitations of 92 patients were assessed using self-report, clinical examination and functional testing. To obtain the assessed limitations the patient (self-report), the physician (clinical examination) and a trained evaluator (functional testing) completed a scorings form about the work-related limitations of the patient. The Isernhagen Work Systems Functional Capacity Evaluation (IWS FCE) was used to obtain the functional testing results. A kappa value of more than 0.60, absolute agreement of more than 80% and ICC of more than 0.75 were considered as acceptable. RESULTS: Little agreement and correlation among self-report, clinical examination and functional testing were found for the assessment of work-related limitations. Self-reported limitations were considerably higher than from those derived from clinical examination or functional testing. Additionally, the limitations derived from the clinical examination were higher than those derived from the IWS FCE. CONCLUSION: Comparing self-report, clinical examination and functional testing for assessing work-related limitations in CLBP patients showed large considerable differences in limitations. Professional health care workers should be aware of these differences when using them in daily practice.

[Reduction in the consumption of benzodiazepines due to a letter to chronic users from their own general practitioner]. / Vermindering van gebruik van benzodiazepinen door een brief van de eigen huisarts aan chronische gebruikers.

OBJECTIVE: To investigate the effectiveness of a minimal intervention in reducing the volume of prescription of benzodiazepines at the regional level. DESIGN: Prospective. METHOD: Patients on compulsory health insurance who had received 180 or more daily doses of benzodiazepines in the course of one year received a letter from their general practitioner (GP) with information about the risks of chronic use, the advice to reduce or stop use, and an invitation to make an appointment to discuss the problem. This intervention took place in 19 GP practices in East Groningen. A reminder was sent six months later to the patients who had not responded in 9 randomly selected GP-practices. Thirty-seven practices in East Groningen and 91 practices in Northwest Groningen served as controls. Outcome measures were: (a) the percentage of patients who stopped, and (b) the change in average benzodiazepine consumption. RESULTS: During the period 6-12 months after the first letter in the intervention group (n = 1343), 11.3% of the patients (95% CI: 9.6-13.1) received no prescription whatsoever for benzodiazepines compared to 5.4% (4.6-6.3) and 4.9% (4.2-5.5) in East Groningen (n = 2932) and in Northwest Groningen (n = 4562), respectively. The average decrease in prescription volume was 13% (-9.9 to -15.1) in the intervention group compared to 3% (-0.1 to -4.1) and 3% (-1.5 to -4) in the control groups. The reminder sent half a year later had no additional effect. CONCLUSION: The informative letter from the GP to chronic users of benzodiazepines with the advice to stop or reduce this use was effective.

Medical students' experiences of diseases in internal medicine in university and community hospitals.

Because medical students in The Netherlands should achieve common national objectives, it is important to know whether clinical experiences in different hospitals are comparable. The research questions were: (1) Do students achieve learning experiences of the required diseases during the internship in Internal Medicine and to what extent do they achieve these experiences? (2) Are there differences between the diseases experienced at a university hospital and at community hospitals? Completed logbooks of students were analysed; the percentage of students that achieved the required diseases and the mean number of experiences of diseases were calculated. A t-test was done to test for differences. Medical students in the university and in community hospitals get broad experience (76-131%) of the required diseases. In both hospitals there are many students who are not achieving the requirements, but the mean number of experiences of students at the community hospitals is higher than those at the university hospital. To eliminate the differences between students from the university hospital and the community hospitals, the educational programmes within both hospitals should be adjusted.

The reliability of logbook data of medical students: an estimation of interobserver agreement, sensitivity and specificity.

OBJECTIVE: Logbooks are widely used in medical schools as an evaluation tool to assess students' progress towards objectives. To estimate whether students fill in their logbooks reliably, we measured interobserver agreement by comparing doctors' data and students' data. METHOD: Completed logbooks were collected at two subdivisions of the department of Internal Medicine at the University Hospital of Groningen. The logbook contains 231 preprinted diseases. Doctors and students recorded the diseases they had encountered. Interobserver agreement, expressed by the Jaccard coefficient (J), was calculated for the complete set of diseases and for a subset of core diseases. To assess the kinds of errors which students made, sensitivity and specificity were determined. RESULTS: Logbook data of doctors and students are not fully consistent (mean J for the complete set of diseases was.23 and for the core diseases.36). The quality of the logbook data is high in the sense that students do not record many false identifications (mean specificity for the complete set of diseases and for the core diseases were.96 and.93, respectively); the quality is poor in the sense that students do not record all the diseases which could be seen at the department (mean sensitivity for the complete set of diseases is.36 and for the core diseases it is.51). CONCLUSION: This study shows inconsistencies in recording diseases in a logbook by students compared with doctors. In particular the diseases which are present at a department are under-reported by students. Supervision and feedback are important mechanisms to optimize the students' use of (1) all diseases which could be encountered and (2) the logbook.

Serologic survey of Brucella spp. antibodies in some marine mammals of North America.

A serologic survey of anti-Brucella spp. antibodies was undertaken on 2,470 samples of 14 North American marine mammal species collected between 1984-97. Serum or blood from eight species of cetaceans and six species of pinnipeds was sampled from Pacific, Atlantic, and Arctic oceans. Two competitive enzyme-linked immunosorbent assays (C-ELISA's), using specific monoclonal antibodies to Brucella abortus cell wall components, were used to detect anti-Brucella spp. antibodies in the samples. Sera from 33 cetaceans and 61 pinnipeds gave inhibition values, in one or both of the tests, which exceeded the threshold that indicates Brucella spp. exposure in cattle. Seropositive animals were identified from Pacific, Atlantic, and Arctic oceans. While Brucella spp. was not isolated, differences in the response of seropositive cetacean and pinniped sera in the two assays suggest that two antigenically distinct species or biovars of Brucella spp. are present. No pathology consistent with clinical brucellosis was noted in any of the animals tested although detailed examination was not conducted on all carcasses.

Development of rat chorda tympani sodium responses: evidence for age-dependent changes in global amiloride-sensitive Na(+) channel kinetics.

In rat, chorda tympani nerve taste responses to Na(+) salts increase between roughly 10 and 45 days of age to reach stable, mature magnitudes. Previous evidence from in vitro preparations and from taste nerve responses using Na(+) channel blockers suggests that the physiological basis for this developmental increase in gustatory Na(+) sensitivity is the progressive addition of functional, Na(+) transduction elements (i.e., amiloride-sensitive Na(+) channels) to the apical membranes of fungiform papilla taste receptor cells. To avoid potential confounding effects of pharmacological interventions and to permit quantification of aggregate Na(+) channel behavior using a kinetic model, we obtained chorda tympani nerve responses to NaCl and sodium gluconate (NaGlu) during receptive field voltage clamp in rats aged from 12-14 to 60 days and older (60+ days). Significant, age-dependent increases in chorda tympani responses to these stimuli occurred as expected. Importantly, apical Na(+) channel density, estimated from an apical Na(+) channel kinetic model, increased monotonically with age. The maximum rate of Na(+) response increase occurred between postnatal days 12-14 and 29-31. In addition, estimated Na(+) channel affinity increased between 12-14 and 19-23 days of age, i.e., on a time course distinct from that of the maximum rate of Na(+) response increase. Finally, estimates of the fraction of clamp voltage dropped across taste receptor apical membranes decreased between 19-23 and 29-31 days of age for NaCl but remained stable for NaGlu. The stimulus dependence of this change is consistent with a developmental increase in taste bud tight junctional Cl(-) ion permeability that lags behind the developmental increase in apical Na(+) channel density. A significant, indirect anion influence on apical Na(+) channel properties was present at all ages tested. This influence was evident in the higher apparent apical Na(+) channel affinities obtained for NaCl relative to NaGlu. This stimulus-dependent modulation of apical Na(+) channel apparent affinity relies on differences in the transepithelial potentials between NaCl and NaGlu. These originate from differences in paracellular anion permeability but act also on the driving force for Na(+) through apical Na(+) channels. Detection of such an influence on taste depends fundamentally on the preservation of taste bud polarity and on a direct measure of sensory function, such as the response of primary afferents.