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Single-channel currents from zona-free mouse eggs.

Cell-attached patch recordings were made from zona-free mouse eggs to examine currents at the single-channel level; two types were identified. A channel with a mean conductance of 130 pS showed changes in reversal potential on dilution of the patch pipette solution consistent with a cation channel; the channel current persisted when the only cation in the pipette was K+: it was concluded that this channel was permeable to K+. The binomial distribution was used to describe the proportion of time 0, 1, 2, ..., n channels were open in multichannel recordings of the K+ channel. Bursts of inward currents of about 1 pA, which showed voltage activation and could be recorded in the presence of CsCl and tetraethylammonium (TEA), were identified as Ca2+ channels.

Animals↗

Change of statistical parameters of transmitter release during various kinetic tests in unparalysed voltage-clamped rat diaphragm.

1. The statistical nature of transmitter release was studied in unparalysed cut rat diaphragm using a voltage clamp technique at room temperature (23 degrees C). 2. While the binomial distribution described observed amplitude histograms well, the Poisson distribution was clearly inadequate. Values of m ranged from 40 to 45, while values for n varied from 45 to 53 and p was between 0.82 and 0.90. 3. Estimation of the probability of release from the transient decay of e.p.c.s in short tetanic trains (11 pulses, 150 Hz) gave values of p from 0.031 to 0.054, which are more than one order of magnitude lower than statistical estimates. 4. As a result of the short tetanic stimulation (5 pulses, 20, 50 and 100 Hz) there is an initial transient facilitation which afterwards becomes masked by depression. Statistical analysis suggests that the changes in the average numbers of quanta released (m) could be attributed to the change in the immediately available store (n). 5. During long tetanic stimulation (4000 pulses, 10-100 Hz) statistical analysis suggests that the decrease in the average number of quanta released (m) could be attributed almost entirely to the decrease in the immediately available store (n). The probability of release (p) decreased only slightly. The extent of the post-tetanic potentiation indicates that it cannot be explained on the grounds of increased probability of release (p) only. There should be an increase as well in the immediately available store (n). 6. It is suggested that while depression is most likely caused by the depletion of the immediately available store due to insufficient replenishment, the facilitation is probably caused by the increase in the capacity of the immediately available store to contain transmitter.

Animals↗

The components of synaptic potentials evoked in cat spinal motoneurones by impulses in single group Ia afferents.

1. Excitatory post-synaptic potentials (e.p.s.p.s) were evoked in cat spinal motoneurones by impulses in single group Ia afferent fibres. The probability density of the fluctuations in peak amplitude of each e.p.s.p. was calculated from the recorded peak amplitude and the probability density of the recording noise. 2. Most e.p.s.p.s fluctuated between different components (i.e. individual e.p.s.p.s of a particular discrete amplitude) with peak amplitudes which were integer multiples of the increment between successive components. The average peak amplitude of this incremental e.p.s.p. was about 90 microV for e.p.s.p.s generated at or near the soma. 3. In general, the probability density of the peak amplitude could not be described using Poisson or binomial distributions. 4. For many e.p.s.p.s the complete time course of each component could be calculated. There was no variability in the amplitude of these components nor in their latency of onset. For some e.p.s.p.s there were differences in the latency and time course of the components. 5. The increments between successive components of e.p.s.p. generated proximally were no larger (at the soma) than the corresponding increments for e.p.s.p.s generated at more distal dendritic sites. 6. These results and those from subsequent papers (Jack, Redman & Wong, 1981; Hirst, Redman & Wong, 1981) reinforce earlier suggestions that each bouton behaves in an all-or-nothing manner with respect to post-synaptic effect, and the probability of failure varies at different boutons arising from the same afferent.

Animals↗

Properties of single calcium-activated potassium channels in cultured rat muscle.

1. Properties of the Ca-activated K channel were studied in excised patches of surface membrane from cultured rat muscle cells using single channel recording techniques.2. Increasing the concentration of calcium at the intracellular membrane surface [Ca](i), increased both the frequency and effective duration of channel openings. Ca at the extracellular membrane surface was not sufficient to activate the channels.3. An approximate third power relationship (slope = 2.7) was observed between [Ca](i) and the percentage of time the channels spent in the open state.4. Both the frequency and effective duration of channel openings increased as the intracellular membrane surface was made more positive; the percentage of time spent in the open state increased e-fold for a 15 mV depolarization for low levels of activity.5. The percentage of time spent with 1, 2,...n channels open in membrane patches with n channels was described by the binomial distribution, suggesting that the channels opened and shut independently of one another.6. Single channel conductance (144 mM-K on both sides of the membrane) was essentially independent of membrane potential (-50 to +50 mV) and [Ca](i) (0.1 muM -1 mM), but did increase with temperature, from 100 pS at 1 degrees C to 300 pS at 37 degrees C.7. Channel activity occurred in apparent bursts, with the duration of the apparent bursts increasing with increasing [Ca](i).8. Two exponentials were required to describe the distribution of observed channel open times, suggesting two different open channel states of apparently normal conductance. The observed mean channel open time of these states at +30 mV was 0.34 and 2.2 msec with 0.1 muM-Ca(i) and was 0.47 and 6.9 msec with 0.5 muM-Ca(i).9. The channel occasionally entered an apparent third open channel state with a single channel current amplitude about 40% the amplitude of the normally observed single channel currents. The reduced conductance state was immediately preceded and followed by a normal conducting state.10. While the kinetics of the Ca-activated K channel appear complex, its large conductance and high Ca and voltage sensitivity suggest that it is uniquely suited to resist depolarizations of the cell membrane potential that are accompanied by increases in intracellular Ca.

Animals↗

Evidence for multiple molecular forms of yeast beta-glucosidase in a hybrid yeast.

A mixture of beta-glucosidases from Saccharomyces fragilis (Y-18) and S. dobzhanskii (Y-19) eluted from diethylaminoethyl cellulose in two peaks, whereas the enzyme from a hybrid, S. fragilis x S. dobzhanskii (Y-42), eluted in a single broad peak. The highest Y-42 activity fractions eluted at a sodium chloride molarity which was intermediate to the molarities at which most of the Y-18 and Y-19 activity was eluted. In cellulose polyacetate strips, Y-42 enzyme migrated as a diffuse band which spanned the distances migrated by the enzymes from the parent yeast strains. Antisera against either Y-18 or Y-19 enzyme precipitated 80 to 90% of Y-42 enzyme activity. When Y-42 enzyme was dissociated by heat or urea and reacted with parental antiserum, a concomitant increase in the opposite parental activity was demonstrable in both precipitation and complement-fixation (CF) tests. Urea-dissociated beta-glucosidases were resolvable by sucrose-gradient centrifugation into multiple bands displaying specific CF activity. When the enzymes were exposed to 4 m urea for 12 min, particles of approximately 110,000 molecular weight were obtained. By extending the exposure time to 40 min, and incorporating 0.5 m urea in the gradients, smaller particles were detected with molecular weights ranging from 18,000 to 23,000. Attempts to regenerate enzyme activity after dissociation with urea were only moderately successful. Results suggested that a slightly acidic environment favored reassociation, as did the presence of 2-mercaptoethanol. Residual urea also seemed important. It is proposed that the structural genes for both Y-18 and Y-19 enzyme are present in Y-42 cells with either independent or closely interacting regulatory mechanisms. Since synthesis of the two parental-type polypeptides may be unequal, the availability of enzyme subunits for subsequent polymerization in the cell cytoplasm might be equalized at the polysome level. Random association of subunits would produce a binomial distribution of true hybrid enzyme molecules.

Centrifugation, Density Gradient↗

Incidence of primary Sjogren's syndrome in Slovenia.

OBJECTIVE: To determine the annual incidence of primary Sjögren's syndrome (pSS) in Slovenia. METHODS: All patients admitted to our department of rheumatology or referred to our outpatient clinic between 1 January 2000 and 31 December 2002 owing to sicca symptoms or because of a suspicion of SS were examined. Our rheumatological department is the only tertiary referral centre for the Ljubljana region, which has a population of 599 895 Caucasian people. All patients were evaluated by the validated European criteria for SS. The exact 95% confidence interval (CI) based on binomial distribution was created for the incidence estimate. RESULTS: 248 patients were examined; 71 of them (28.6%; 65 women, 6 men) were diagnosed as having pSS. Their mean (SD) age was 51.3 (14.5) years (range 19-78). The average annual incidence for pSS in our study population was calculated as 3.9 cases per 100 000 inhabitants (95% CI 1.1 to 10.2). CONCLUSION: The estimated annual incidence of pSS in Slovenia is 3.9/100 000.

Adult↗

Disabling injuries of the cervical spine in Argentine rugby over the last 20 years.

OBJECTIVE: To investigate the incidence and risk factors of disabling injuries to the cervical spine in rugby in Argentina. METHODS: A retrospective review of all cases reported to the Medical Committee of the Argentine Rugby Union (UAR) and Rugby Amistad Foundation was carried out including a follow up by phone. Cumulative binomial distribution, chi 2 test, Fisher test, and comparison of proportions were used to analyse relative incidence and risk of injury by position and by phase of play (Epi Info 6, Version 6.04a). RESULTS: Eighteen cases of disabling injury to the cervical spine were recorded from 1977 to 1997 (0.9 cases per year). The forwards (14 cases) were more prone to disabling injury of the cervical spine than the backs (four cases) (p = 0.03). Hookers (9/18) were at highest risk of injury (p < 0.01). The most frequent cervical injuries occurred at the 4th, 5th, and 6th vertebrae. Seventeen of the injuries occurred during match play. Set scrums were responsible for most of the injuries (11/18) but this was not statistically significant (p = 0.44). The mean age of the injured players was 22. Tetraplegia was initially found in all cases. Physical rehabilitation has been limited to the proximal muscles of the upper limbs, except for two cases of complete recovery. One death, on the seventh day after injury, was reported. CONCLUSIONS: The forwards suffered a higher number of injuries than the backs and this difference was statistically significant. The chance of injury for hookers was statistically higher than for the rest of the players and it was particularly linked to scrummaging. However, the number of injuries incurred in scrums was not statistically different from the number incurred in other phases of play.

Adolescent↗

The reliability and validity of the physical activity questions in the WHO health behaviour in schoolchildren (HBSC) survey: a population study.

OBJECTIVE: To assess the test-retest reliability and validity of the physical activity questions in the World Health Organisation health behaviour in schoolchildren (WHO HBSC) survey. METHODS: In the validity study, the Multistage Fitness Test was administered to a random sample of year 8 (mean age 13.1 years; n = 1072) and year 10 (mean age 15.1 years; n = 954) high school students from New South Wales (Australia) during February/March 1997. The students completed the self report instruments on the same day. An independent sample of year 8 (n = 121) and year 10 (n = 105) students was used in the reliability study. The questionnaire was administered to the same students on two occasions, two weeks apart, and test-retest reliability was assessed. Students were classified as either active or inadequately active on their combined responses to the questionnaire items. Kappa and percentage agreement were assessed for the questionnaire items and for a two category summary measure. RESULTS: All groups of students (boys and girls in year 8 and year 10) classified as active (regardless of the measure) had significantly higher aerobic fitness than students classified as inadequately active. As a result of highly skewed binomial distributions, values of kappa were much lower than percentage agreement for test-retest reliability of the summary measure. For year 8 boys and girls, percentage agreement was 67% and 70% respectively, and for year 10 boys and girls percentage agreement was 85% and 70% respectively. CONCLUSIONS: These brief self report questions on participation in vigorous intensity physical activity appear to have acceptable reliability and validity. These instruments need to be tested in other cultures to ensure that the findings are not specific to Australian students. Further refinement of the measures should be considered.

Adolescent↗

Chemical modification and hybrid enzyme formation as probes of the active site and subunit interactions in Escherichia coli succinyl-CoA synthetase.

Succinyl-CoA synthetase from Escherichia coli has an alpha 2 beta 2 subunit structure and is known to display half-of-the-sites reactivity with respect to its phosphorylation by ATP. The studies reported herein are a component of our attempts to rationalize the heterologous tetrameric structure in terms of catalytic function. The isolated refolded beta subunit interacts specifically with an affinity column of agarose-hexane-CoA, consistent with the idea that the CoA-binding subsite of the active center is located on the beta subunit. The enzyme is inactivated by phenylglyoxal according to biphasic kinetics; saturating levels of the substrates CoA and ATP, alone or in combination, give only partial protection against such inactivation. Treatment of the enzyme with the sulfhydryl reagent 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) resulted in rapid inactivation, accompanied by the reaction of three to four-SH groups per molecule; prolonged incubation with NBD-Cl eventually results in reaction of 16 of the 24 sulfhydryl groups of the tetramer. Hybrid enzyme preparations have been constructed by refolding mixtures containing beta and various ratios of native and NBD-Cl-modified alpha subunits. The loss of activity associated with the incorporation of chemically modified alpha is not that predicted by a simple model based on binomial distribution, but is complex and consistent with the kind of intersubunit communication that may be expected for catalytic cooperativity between the two active sites of the enzyme molecule.

4-Chloro-7-nitrobenzofurazan↗

(99m)Tc sestamibi breast imaging for the examination of patients with dense and fatty breasts: multicenter study.

PURPOSE: To evaluate the accuracy of scintimammography as an adjunct to physical examination and mammography in the detection of breast cancer in women with dense and fatty breasts. MATERIALS AND METHODS: A total of 558 women were prospectively enrolled from 42 centers in North America. Images were interpreted by readers blinded to the subjects' clinical history, mammographic findings, and other test results. The Breast Imaging Reporting and Data System classification was used to describe breast density. Parenchymal patterns of "heterogeneously dense" and "extremely dense" were used to classify breasts as dense, whereas "almost entirely fat" and "numerous vague densities" defined fatty breasts. Between-group differences were evaluated with the 2 test for categorical variables and Student t test for continuous variables. Accuracy of scintimammography was assessed against the core laboratory histopathologic evaluation, the standard. The 95% CIs around point estimates of sensitivity, specificity, and positive and negative predictive values were calculated with the normal approximation to the binomial distribution. RESULTS: The analyses were based on 580 breasts with an abnormality; 276 (48%) breasts were dense and 228 had a malignant lesion. Diagnostic properties for scintimammography of fatty versus dense breasts were, respectively, sensitivity, 72% versus 70%; specificity, 80% versus 78%; positive predictive value, 72% versus 67%; negative predictive value, 81% versus 81%; and accuracy, 77% versus 75% (all not significant). Scintimammography led to similar and significant changes in the posttest likelihood of cancer for both dense and fatty breasts. CONCLUSION: The diagnostic accuracy of scintimammography is not affected by breast density.

Adipose Tissue↗

Mammographic screening of TRAM flap breast reconstructions for detection of nonpalpable recurrent cancer.

PURPOSE: To evaluate findings from routine mammographic screenings in patients with transverse rectus abdominis musculocutaneous (TRAM) flap reconstructions. MATERIALS AND METHODS: During a 25-month study period, 214 consecutive screening mammograms in 113 asymptomatic women (mean age, 51 years) with TRAM flap reconstructions were obtained. Mastectomies were performed for cancer in 106 (94%) of the 113 women and for prophylaxis in seven (6%). Prospectively, a Breast Imaging Reporting and Data System (BI-RADS) assessment category 1-5 was assigned to each mammogram. Surgical, medical, pathologic, and radiographic records were retrospectively reviewed. CIs were determined by the normal approximation to the binomial distribution. RESULTS: Seven (3%) of 214 examinations were BI-RADS category 4 or 5. Six (86%) of seven patients underwent biopsy. Two (33%) of these six biopsies demonstrated invasive ductal carcinoma. Cancer detection rate for mammography was 1.9% (two of 106) (95% CI: 0.33%, 7.32%) for women with reconstruction for breast cancer during the 2-year period. One (6%) of 16 BI-RADS category 3 examinations later proved to be invasive ductal carcinoma at follow-up. No interval cancer was discovered in 171 cases of BI-RADS category 1 or 2 examinations with 1-year follow-up. No cancers occurred in women who underwent prophylactic mastectomy. A biopsy positive predictive value of 33% (95% CI: 6%, 76%) was observed. CONCLUSION: Screening mammography of TRAM flap-reconstructed breasts enables detection of nonpalpable cancer before clinical examination.

Adult↗

Incidental colonic fluorodeoxyglucose uptake: correlation with colonoscopic and histopathologic findings.

PURPOSE: To evaluate the pattern and degree of incidental colonic fluorodeoxyglucose (FDG) uptake in patients without colorectal carcinoma who underwent whole-body FDG positron emission tomography (PET) for other purposes and compare them with colonoscopic and/or histopathologic findings. MATERIALS AND METHODS: Cases of 27 patients without known history of colorectal carcinoma who were referred for evaluation with whole-body FDG PET and displayed incidental colonic uptake were reviewed retrospectively. Colonoscopy was performed in 10 patients; histopathologic analysis, in two; and both, in 15. The colonic FDG uptake patterns were nodular-focal, nodular-multifocal, segmental, and diffuse. The FDG uptake level was scored with a four-point scale in relation to hepatic uptake. Binomial distribution was used to calculate 95% CIs for the probability of finding an abnormality at histologic examination, as predicted by findings at FDG PET. RESULTS: Colonoscopic findings in eight patients with a diffuse uptake pattern were normal. Thirteen patients with nodular high FDG uptake had pathologic findings. Six (22%) of the 27 patients were not suspected of having a malignancy, and seven had benign neoplasms. With a 95% CI, nodular high FDG uptake implies at least a 79% chance that histopathologic findings may be abnormal. Colitis was seen in five of six patients with a segmental pattern of high FDG uptake. CONCLUSION: Colonoscopy is a reasonable next step for further diagnostic examination of patients who display nodular high FDG uptake in the colon. Diffuse FDG uptake often is associated with normal findings at colonoscopy, while segmental high uptake may imply inflammation.

Adult↗

Ion channel classes in purified olfactory cilia membranes: planar lipid bilayer studies.

Ciliary membrane fragment fusion to planar lipid bilayers resulted in the insertion of four ion channel types. cAMP-activated, cation-selective channels could be detected only in the absence of Ca2+ and had a conductance of 23 pS. They exhibited an apparent dissociation constant (Kd) for the cyclic nucleotide of approximately 30 microM and an estimated permeability ratio (PNa/PK) of 2.4. The cAMP cation-selective channel coinserted with a K(+)-selective channel refractory to cAMP, Ca2+, and D-myo-inositol 1,4,5-trisphosphate. This K+ channel was voltage independent and exhibited open-conductance substates of 60 and 112 pS. cAMP was also found to modulate a novel K+ channel with a Kd = 140 microM. It displayed three nearly equally spaced open substates with conductances of 34, 80, and 130 pS. In the absence and in the presence of cAMP the probability of occurrence of the open substates was binomially distributed. A fourth channel type was a Ca(2+)-activated K+ channel with a conductance of 240 pS. It was blocked by charybdotoxin at nanomolar concentrations (Kd = 3 nM). These results add support to the idea that, besides cAMP-activated cation-selective channels, vertebrate chemosensory olfactory membranes possess an arrangement of ion channels.

Animals↗

A model of graded calcium release and L-type Ca2+ channel inactivation in cardiac muscle.

We have developed a model of Ca(2+) handling in ferret ventricular myocytes. This model includes a novel L-type Ca(2+) channel, detailed intracellular Ca(2+) movements, and graded Ca(2+)-induced Ca(2+) release (CICR). The model successfully reproduces data from voltage-clamp experiments, including voltage- and time-dependent changes in intracellular Ca(2+) concentration ([Ca(2+)](i)), L-type Ca(2+) channel current (I(CaL)) inactivation and recovery kinetics, and Ca(2+) sparks. The development of graded CICR is critically dependent on spatial heterogeneity and the physical arrangement of calcium channels in opposition to ryanodine-sensitive release channels. The model contains spatially distinct subsystems representing the subsarcolemmal regions where the junctional sarcoplasmic reticulum (SR) abuts the T-tubular membrane and where the L-type Ca(2+) channels and SR ryanodine receptors (RyRs) are localized. There are eight different types of subsystems in our model, with between one and eight L-type Ca(2+) channels distributed binomially. This model exhibits graded CICR and provides a quantitative description of Ca(2+) dynamics not requiring Monte-Carlo simulations. Activation of RyRs and release of Ca(2+) from the SR depend critically on Ca(2+) entry through L-type Ca(2+) channels. In turn, Ca(2+) channel inactivation is critically dependent on the release of stored intracellular Ca(2+). Inactivation of I(CaL) depends on both transmembrane voltage and local [Ca(2+)](i) near the channel, which results in distinctive inactivation properties. The molecular mechanisms underlying many I(CaL) gating properties are unclear, but [Ca(2+)](i) dynamics clearly play a fundamental role.

Animals↗

Capillary recruitment in exercise: rate, extent, uniformity, and relation to blood flow.

Erythrocyte-containing capillaries were counted in dog gracilis muscles freeze-clamped at rest and after twitch contraction at 4/s. In each of 21 muscles, 6--8 blocks were examined at -70 degrees C without fixation or staining; 15 fields were counted per block. Frequency analysis of capillaries per field based on the negative binomial distribution indicated that capillary density at rest was controlled by arterioles. Active vasomotion of these arterioles was "switched off" within 5 s after onset of exercise. Capillary density was then determined passively by stochastic rheologic factors acting at the individual capillaries. Thus exercise changes the site and the mechanism of capillary control. Recruitment occurred first where capillary density was lowest, and was complete in 15 s; this greatly decreased the heterogeneity of capillary spacing. Mean capillary density increased 1.5- to 3-fold, whereas flow increased almost 7-fold. Calculated mean velocity and mean transit time of erythrocytes in capillaries were 1.1 mm/s and 920 ms at rest and 4.2 mm/s and 215 ms after 3 min of exercise.

Animals↗

Temporal firing patterns of Purkinje cells in the cerebellar ventral paraflocculus during ocular following responses in monkeys II. Complex spikes.

Many theories of cerebellar motor learning propose that complex spikes (CS) provide essential error signals for learning and modulate parallel fiber inputs that generate simple spikes (SS). These theories, however, do not satisfactorily specify what modality is represented by CS or how information is conveyed by the ultra-low CS firing rate (1 Hz). To further examine the function of CS and the relationship between CS and SS in the cerebellum, CS and SS were recorded in the ventral paraflocculus (VPFL) of awake monkeys during ocular following responses (OFR). In addition, a new statistical method using a generalized linear model of firing probability based on a binomial distribution of the spike count was developed for analysis of the ultra-low CS firing rate. The results of the present study showed that the spatial coordinates of CS were aligned with those of SS and the speed-tuning properties of CS and SS were more linear for eye movement than retinal slip velocity, indicating that CS contain a motor component in addition to the sensory component identified in previous studies. The generalized linear model to reproduce firing probability confirmed these results, demonstrating that CS conveyed high-frequency information with its ultra-low firing frequency and conveyed both sensory and motor information. Although the temporal patterns of the CS were similar to those of the SS when the sign was reversed and magnitude was amplified approximately 50 times, the velocity/acceleration coefficient ratio of the eye movement model, an aspect of the CS temporal firing profile, was less than that of the SS, suggesting that CS were more sensory in nature than SS. A cross-correlation analysis of SS that are triggered by CS revealed that short-term modulation, that is, the brief pause in SS caused by CS, does not account for the reciprocal modulation of SS and CS. The results also showed that three major aspects of the CS and SS individual cell firing characteristics were negatively correlated on a cell-to-cell basis: the preferred direction of stimulus motion, the mean percent change in firing rate induced by upward stimulus motion, and patterns of temporal firing probability. These results suggest that CS may contribute to long-term interactions between parallel and climbing fiber inputs, such as long-term depression and/or potentiation.

Action Potentials↗

Statistical model relating CA3 burst probability to recovery from burst-induced depression at recurrent collateral synapses.

When neuronal excitability is increased in area CA3 of the hippocampus in vitro, the pyramidal cells generate periodic bursts of action potentials that are synchronized across the network. We have previously provided evidence that synaptic depression at the excitatory recurrent collateral synapses in the CA3 network terminates each population burst so that the next burst cannot begin until these synapses have recovered. These findings raise the possibility that burst timing can be described in terms of the probability of recovery of this population of synapses. Here we demonstrate that when neuronal excitability is changed in the CA3 network, the mean and variance of the interburst interval change in a manner that is consistent with a timing mechanism comprised of a pool of exponentially relaxing pacemakers. The relaxation time constant of these pacemakers is the same as the time constant describing the recovery from activity-dependent depression of recurrent collateral synapses. Recovery was estimated from the rate of spontaneous transmitter release versus time elapsed since the last CA3 burst. Pharmacological and long-term alterations of synaptic strength and network excitability affected CA3 burst timing as predicted by the cumulative binomial distribution if the burst pace-maker consists of a pool of recovering recurrent synapses. These findings indicate that the recovery of a pool of synapses from burst-induced depression is a sufficient explanation for burst timing in the in vitro CA3 neuronal network. These findings also demonstrate how information regarding the nature of a pacemaker can be derived from the temporal pattern of synchronous network activity. This information could also be extracted from less accessible networks such as those generating interictal epileptiform discharges in vivo.

Algorithms↗

Indications for liver transplantation in British Columbia's Aboriginal population: a 10-year retrospective analysis.

OBJECTIVES: To study the indications for liver transplantation among British Columbia's First Nation population. MATERIALS AND METHODS: A retrospective analysis of the British Columbia Transplant Society's database of Aboriginal and non-Aboriginal liver transplant recipients from 1989 to 1998 was undertaken. For primary biliary cirrhosis (PBC), the transplant assessment database (patients with and without transplants) was analyzed using a binomial distribution and compared with published census data regarding British Columbia's proportion of Aboriginal people. RESULTS: Between 1989 and 1998, 203 transplantations were performed in 189 recipients. Fifteen recipients were Aboriginal (n=15; 7.9%). Among all recipients, the four most frequent indications for liver transplantation were hepatitis C virus (HCV) infection (n=57; 30.2%), PBC (n=34; 18.0%), alcohol (n=22; 11.6%) and autoimmune hepatitis (n=14; 7.4%). Indications for liver transplantation among Aboriginal people were PBC (n=8; 53.3%; P<0.001 compared with non-Aboriginal people), autoimmune hepatitis (n=4; 26.67%; P=0.017), acute failure (n=2; 13.3%) and HCV (n=1). Among all patients referred for liver transplantation with PBC (n=43), 29 (67.44%) were white and 11 (25.6%) were Aboriginal. A significant difference was found between the proportion of Aboriginal people referred for liver transplantation and the proportion of Aboriginal people in British Columbia (139,655 of 3,698,755 [3.8%]; 1996 Census, Statistics Canada) (P<0.001). CONCLUSIONS: Aboriginal people in British Columbia are more likely to be referred for liver transplantation with a diagnosis of PBC but are less likely to receive a liver transplant because of HCV or alcohol than are non-Aboriginal people.

British Columbia↗