Slow Rate Of Rise Research Articles

Baseline protective behavioral strategy use predicts more moderate transdermal alcohol concentration dynamics and fewer negative consequences of drinking in young adults' natural settings.

Test whether frequent protective behavioral strategies (PBS) users report (a) fewer alcohol-related consequences and (b) less risky alcohol intoxication dynamics (measured via transdermal alcohol concentration [TAC] sensor "features") in daily life. Two hundred twenty-two frequently heavy-drinking young adults (Mage = 22.3 years) wore TAC sensors for 6 consecutive days. TAC features peak (maximum TAC), rise rate (speed of TAC increase), and area under the curve (AUC) were derived for each day. Negative alcohol-related consequences were measured in the morning after each self-reported drinking day. Past-year PBS use was measured at baseline. Young adults reporting more frequent baseline PBS use showed (a) fewer alcohol-related consequences and (b) lower intoxication dynamics on average (less AUC, lower peaks, and slower rise rates). Limiting/stopping and manner of drinking PBS showed the same pattern of findings as the total score. Serious harm reduction PBS predicted fewer negative alcohol-related consequences, but not TAC features. Multilevel path models showed that TAC features peak and rise rate partially explained associations between PBS (total, limiting/stopping, and manner of drinking) and consequences. Independent contributions of PBS subscales were small and nonsignificant, suggesting that total PBS use was a more important predictor of risk/protection than the specific types of PBS used. Young adults using more total PBS may experience fewer alcohol-related consequences during real-world drinking episodes in part through less risky intoxication dynamics (TAC features). Future research measuring PBS at the daily level is needed to formally test TAC features as day-level mechanisms of protection from acute alcohol-related consequences. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Utility of Atypical Lymphocytes and Large Immature Cells in Prediction of Dengue Severity.

Background: There is a clinical imperative to devise metrics to prognosticate dengue severity. Our objective was to determine the association between longitudinal trends in atypical lymphocytes and large immature cell count with platelet count and dengue severity. Materials and methods: Retrospective analysis of longitudinally measured clinical and hematological data from (n = 79) hospitalized dengue patients was done. Results: The cohort consisted of patients with dengue fever without warning signs (DFWOWS) (n = 40, females = 14, and age = 19.9 ± 14.6 years), dengue fever with warning signs (DFWWS) (n = 36, females = 13, and age = 16.1 ± 14.1 years) and severe dengue (n = 3, females = 2, and age = 5.3 ± 4 years). Platelet count increased at a rate of 11,524 cells/mm3/day, with a slower rate of rise as the severity increased (p = 0.001***). Concurrently hematocrit and neutrophil percentage decreased, while the lymphocyte percentage and white blood cell (WBC) count increased during the hospital stay. Every 1% increase in atypical lymphocyte count (ATY) was associated with a fall in platelet count by 16,963 cells/mm3 (p = 0.001***). A similar but weaker trend was found for large immature cells (LICs). Conclusion: The data support the usefulness of longitudinal tracking of atypical lymphocyte and large immature cell count for dengue prognosis. The time trends of the hematological parameters indicate the progression of patients from the critical to the recovery phase. How to cite this article: Peraka R, Koppula A, Muppala BS, et al. Utility of Atypical Lymphocytes and Large Immature Cells in Prediction of Dengue Severity. J Assoc Physicians India 2023;71(11):19-24.

A comprehensive review of partial replacement of cement in concrete

Cement is one of the largest used construction materials, the production of which releases large quantity of carbon di oxide. Reduction of cement in concrete will help to reduce carbon foot print and also environmental impact. With the advent of industrialization, large quantity of industrial waste is being produced all over the world. Disposal of these waste material causes environmental pollution and needs to be addressed. An extensive literature on partial replacement of cement with various industrial waste is studied and presented in this article. The partial replacement of cement by industrial waste such as Fly Ash (FA), Rice Husk Ash (RHA), Ground Granulated Blast Furnace Slag (GGBS), Silica Fume (SF), and Sugar Cane Bagasse Ash (SCBA) is reviewed. Mechanical strength, strength gain with curing time and durability in concrete with cement being partially replaced by industrial waste materials were analyzed. The maximum replacement of cement by silica fume and sugar cane bagasse ash is 10 % and 15% respectively. Maximum replacement of cement by rice husk ash is 25%. Optimum level of replacement by GGBS and FA is up to 30%. From the test results of RCPT, Carbonation and Sorptivity, durability of concrete improves to a certain extent by partially replacing cement with FA, RHA, SF, GGBS. A slower rate of rise in carbonation depth with age is reported in concrete with partial replacement of cement by SCBA. Sorptivity steadily decreases with the increasing RHA, FA, and GGBS content, maximum at 25 percent, 40 percent, and 40 percent, respectively. This article provides an overview of the mechanical characteristics, durability research, and empirical relationships of concrete with various industrial waste products, including Fly Ash (FA), Rice Husk Ash (RHA), Ground Granulated Blast Furnace Slag (GGBS), Silica Fume (SF), and Sugar Cane Bagasse Ash (SCBA). a sentence more.On the basis of past research, a statistical relation was built by accounting for concrete grade, material type, and dosage.

Characterizing Recharge in Southern Mali Using a Combination of Modeling and Stable Isotopes

Groundwater recharge in southern Mali is investigated using interpretive recharge models and stable isotopes to identify the dominant recharge mechanism and explore how local variations in geological materials influence the recharge characteristics. At a regional scale, the groundwater level hydrographs from across southern Mali (1998–2002) are relatively consistent, showing seasonal variations, suggesting diffuse recharge is the dominant mechanism. Groundwater samples plot within the range of the weighted mean monthly δ18O and δ2H concentrations for July-August-September rainfall, and below the weighted mean annual δ18O and δ2H concentrations for rainfall, suggesting a dominantly rainy season source of recharge. Recharge is simulated for four representative unsaturated zone environments, each with varying soil, laterite and sedimentary bedrock layers, and three ranges of water table depths, for a total of 12 combinations. The simulated recharge response starts in July, 1 month after the arrival of the rainy season, and recharge is greatly accelerated through August to its peak in September. On an annual basis, ~72% of annual rainfall occurs between July and September, and nearly 60% of simulated recharge occurs between August and October. The simulated regional average annual recharge is 519 mm/year (479–560 mm/year range among models). By comparison, recharge estimated from the observed storage anomaly hydrographs using the water table fluctuation method is 384 mm/year (189–619 mm/year) using a specific yield of 0.05, although the range could be as high as 83–772 mm/year given the uncertainty in specific yield values (0.02–0.07). The simulated recharge also agrees with the timing of regional observed storage anomalies for all observation wells, but somewhat less so for the regional GRACE storage anomaly (2002–2008), which has a slower rate of rise in storage and a faster rate of recession compared to the observed storage anomalies and simulated recharge response.

383: Human uterine contractility at term in relation to parity

It is well described that parous women perform better in labor than primigravid women, with less dystocic labour, shorter durations of labor and lower cesarean rates. There are no published data to our knowledge, comparing myometrial contractile parameters of nulliparous with parous women. Our study aim was to examine certain parameters in human myometrial tissue, and compare the results between the following 3 groups: Primigravid women (P0); Women with 1 previous delivery (P1); Women with more than 1 previous delivery (P>1); to determine if there was any difference between the contractile performance of each group. Myometrial biopsies were obtained at cesarean delivery (CD), at term, from n=74 women, with Institutional Ethical Review Board approval, Galway University Hospital. Each biopsy was dissected into 8 strips and suspended for in vitro tissue baths under physiological conditions, as previously described [1], giving a total of 592 samples. The following parameters of contractile performance were measured for spontaneous contractions: maximal amplitude (MAMP), mean contractile force (MCF), time to maximal amplitude, maximum rate of rise, frequency and occurrence of simple and complex (biphasic and multiphasic) contractions. Comparisons were made across the 3 groups: P0 n=14; P1 n=37; P>1 n=23. Statistical analysis was performed using T-Test Assuming Unequal Variance. The results obtained for the contractile parameters, for the 3 groups, are shown in Table 1. The MCF was greater for myometrial contractions in parous women (PO V P1 P=0.0061; P1 V P>1 P= 0.00089). Women P>1 displayed a shorter time to onset of first contraction (P=0.00046). For parous women there was a slower rate of rise and slower rate of relaxation. No difference was observed in any of the other parameters. (Table 2) These results suggest that there is an inherent biological difference between the contractile parameters of human myometrium in the third trimester, between primigravid and parous women. These findings correlate with clinical observations that parous women have more efficient and shorter labours. The increased force of contractions observed with parity, highlights the need for caution in these women undergoing augmentation of labor.

Dim Light Melatonin Onset in Alcohol-Dependent Men and Women Compared with Healthy Controls

Sleep disturbances in alcohol-dependent (AD) individuals may persist despite abstinence from alcohol and can influence the course of the disorder. Although the mechanisms of sleep disturbances of AD are not well understood and some evidence suggests dysregulation of circadian rhythms, dim light melatonin onset (DLMO) has not previously been assessed in AD versus healthy control (HC) individuals in a sample that varied by sex and race. The authors assessed 52 AD participants (mean ± SD age: 36.0 ± 11.0 yrs of age, 10 women) who were 3–12 wks since their last drink (abstinence: 57.9 ± 19.3 d) and 19 age- and sex-matched HCs (34.4 ± 10.6 yrs, 5 women). Following a 23:00–06:00 h at-home sleep schedule for at least 5 d and screening/baseline nights in the sleep laboratory, participants underwent a 3-h extension of wakefulness (02:00 h bedtime) during which salivary melatonin samples were collected every 30 min beginning at 19:30 h. The time of DLMO was the primary measure of circadian physiology and was assessed with two commonly used methodologies. There was a slower rate of rise and lower maximal amplitude of the melatonin rhythm in the AD group. DLMO varied by the method used to derive it. Using 3 pg/mL as threshold, no significant differences were found between the AD and HC groups. Using 2 standard deviations above the mean of the first three samples, the DLMO in AD occurred significantly later, 21:02 ± 00:41 h, than in HC, 20:44 ± 00:21 h (t = −2.4, p = .02). Although melatonin in the AD group appears to have a slower rate of rise, using well-established criteria to assess the salivary DLMO did not reveal differences between AD and HC participants. Only when capturing melatonin when it is already rising was DLMO found to be significantly delayed by a mean 18 min in AD participants. Future circadian analyses on alcoholics should account for these methodological caveats. (Author correspondence: daconroy@med.umich.edu)

Sea level history of the northern Gulf of Mexico coast and sea level rise scenarios for the near future

The sea level history of the northern Gulf of Mexico during recent geologic time has closely followed global eustatic sea level change. Regional effects due to tectonics and glacio-isostasy have been minimal. Over the past several million years the northern Gulf coast, like most stable coastal regions of the globe, has experienced major swings of sea level below and above present level, accompanied by major shifts in shoreline position. During advances of the northern hemisphere ice sheets, sea level dropped by more than 100 m, extending the shoreline in places more than 100 km onto the shelf. For much of the period since the last glacial maximum (LGM), 20,000 years ago, the region has seen rates of sea level rise far in excess of those experienced during the period represented by long-term tide gauges. The regional tide gauge record reveals that sea level has been rising at about 2 mm/year for the past century, while the average rate of rise since the LGM has been 6 mm/year, with some periods of abrupt rise exceeding 40 mm/year. During times of abrupt rise, Gulf of Mexico shorelines were drowned in place and overstepped. The relative stability of modern coastal systems is due primarily to stabilization of sea level approximately 6,000 years ago, resulting in the slow rates of rise experienced during historic time. Recent model projections of sea level rise over the next century and beyond may move northern Gulf coastal environments into a new equilibrium regime, more similar to that experienced during the deglaciation than that which has existed during historic time.

Dynamics of early locomotor network dysfunction following a focal lesion in an in vitro model of spinal injury

It is unclear how a localized spinal cord injury may acutely affect locomotor networks of segments initially spared by the lesion. To investigate the process of secondary damage following spinal injury, we used the in vitro model of the neonatal rat isolated spinal cord with transverse barriers at the low thoracic-upper lumbar region to allow focal application of kainate in hypoxic and aglycemic solution (with reactive oxygen species). The time-course and nature of changes in spinal locomotor networks downstream of the lesion site were investigated over the first 24 h, with electrophysiological recordings monitoring fictive locomotion (alternating oscillations between flexor and extensor motor pools on either side) and correlating any deficit with histological alterations. The toxic solution irreversibly suppressed synaptic transmission within barriers without blocking spinal reflexes outside. This effect was focally associated with extensive white matter damage and ventral gray neuronal loss. Although cell losses were < 10% outside barriers, microglial activation with neuronal phagocytosis was detected. Downstream motor networks still generated locomotor activity 24 h later when stimulated with N-methyl-d-aspartate (NMDA) and serotonin, but not with repeated dorsal root stimuli. In the latter case, cumulative depolarization was recorded from ventral roots at a slower rate of rise, suggesting failure to recruit network premotoneurons. Our data indicate that, within the first 24 h of injury, locomotor networks below the lesion remained morphologically intact and functional when stimulated by NMDA and serotonin. Nevertheless, microglial activation and inability to produce locomotor patterns by dorsal afferent stimuli suggest important challenges to long-term network operation.

The sea-level record of the last deglacial in the Shinano River incised-valley fill, Echigo Plain, central Japan

The Echigo Plain, on the Japan Sea coast, is in a sedimentary basin governed by subsidence controlled by the Echigo Plain Western Margin Fault Zone. The glacial incised valley in the Echigo Plain filled with the sediment discharge of the Shinano River as the sea level rose during the last deglacial. The incised-valley fill allows us to reconstruct the detailed sea-level record, because the plain is still interseismically subsiding at a rate of about 3 mm/yr and the present tidal range along the Japan Sea coast is less than 0.3 m. In this study, we reconstructed a centennial-scale sea-level record for the deglacial period (12,000–9000 cal BP) on the basis of the sedimentary facies and 54 radiocarbon dates from a sediment core obtained from the Echigo Plain near the Western Margin Fault Zone. In this core, the interval from 95 to 55 m below the present sea level consists of floodplain and salt marsh sediments deposited aggradationally during 11,600–9000 cal BP as a result of transgression. Taking into account the Holocene subsidence rate of 2.7 mm/yr at the core site, the relative sea-level rise during the period of core deposition can be divided into the periods of rapid and slow rates. Sea level rose rapidly (> 23 mm/yr) during 11,600–11,100 cal BP, followed by a slow rate of sea-level rise (2 mm/yr) during 11,200–10,300 cal BP. Another period of rapid sea-level rise (11 mm/yr) during 10,500–9400 cal BP was followed by a slow rate of rise (2 mm/yr) during 9600–9000 cal BP. This record of relative sea-level rise indicates that the rapid rate of sea-level rise during 11,600–11,100 cal BP is consistent with meltwater pulse 1B.

State-Dependent Modification of Complex Spike Waveforms in the Cerebellar Cortex

The cerebellum has been the focus of extensive research for more than a century. However, its functional role is still under debate. The comprehensive description of its anatomy and physiology seem to deepen rather than resolve the controversy about its function. Recently, it was shown that Purkinje cells' (PC) membrane potential is bistable and can be found in one of two states: periods of simple spike bursting ("up state"), followed by periods of electrical quiescence and hyperpolarized membrane potential ("down state"). This bistability, which challenges the current dogma regarding the functional organization of the cerebellum, has immediate implications on the mode by which the cerebellar cortex reads incoming input. The well-documented, all-or-none response of PCs to climbing fiber input is generated by complex interactions between the synaptic currents and intrinsic properties of PCs. Hence, it is bound to change as a function of PC membrane potential. Therefore, we compared complex spike waveforms occurring during down and up states, as recorded in both slice preparations and the intact brain of anesthetized rats. We then used the voltage derivative of the intracellular recording to compare the in-vitro intracellular recording to the in-vivo extracellular unit recordings. We found highly significant differences between CSs that occur during the up state and those occurring during the down state. CSs at the up state have a longer duration, and their wavelets have a slower rate of rise than those occurring in the down state. Corresponding changes in the extracellular unit recordings suggests that these changes are manifested in the intact brain. Hence, these state-dependent modifications have immediate, as well as long-term, effects on the output and dynamics of the cerebellar cortex.

Regulation of ryanodine receptor-dependent calcium signaling by polycystin-2

Mutations in polycystin-2 (PC2) cause autosomal dominant polycystic kidney disease. A function for PC2 in the heart has not been described. Here, we show that PC2 coimmunoprecipitates with the cardiac ryanodine receptor (RyR2) from mouse heart. Biochemical assays showed that the N terminus of PC2 binds the RyR2, whereas the C terminus only binds to RyR2 in its open state. Lipid bilayer electrophysiological experiments indicated that the C terminus of PC2 functionally inhibited RyR2 channel activity in the presence of calcium (Ca(2+)). Pkd2(-/-) cardiomyocytes had a higher frequency of spontaneous Ca(2+) oscillations, reduced Ca(2+) release from the sarcoplasmic reticulum stores, and reduced Ca(2+) content compared with Pkd2(+/+) cardiomyocytes. In the presence of caffeine, Pkd2(-/-) cardiomyocytes exhibited decreased peak fluorescence, a slower rate of rise, and a longer duration of Ca(2+) transients compared with Pkd2(+/+). These data suggest that PC2 is important for regulation of RyR2 function and that loss of this regulation of RyR2, as occurs when PC2 is mutated, results in altered Ca(2+) signaling in the heart.

The impacts of pyroclastic surges on buildings at the eruption of the Soufri�re Hills volcano, Montserrat

We investigated the impacts on buildings of three pyroclastic surges that struck three separate villages on 25 June, 21 September and 26 December, 1997, during the course of the andesitic dome building eruption of the Soufriere Hills Volcano, Montserrat, which began on 18 July, 1995. A detailed analysis of the building damage of the 26 December event was used to compare the findings on the flow and behaviour of dilute pyroclastic density currents (PDCs) with the classical reports of PDCs from historical eruptions of similar size. The main characteristics of the PDC, as inferred from the building damage, were the lateral loading and directionality of the current; the impacts corresponded to the dynamic pressure of the PDC, with a relatively slow rate of rise and without the peak overpressure or a shock front associated with explosive blast; and the entrainment of missiles and ground materials which greatly added to the destructiveness of the PDC. The high temperature of the ash, causing the rapid ignition of furniture and other combustibles, was a major cause of damage even where the dynamic pressure was low at the periphery of the current. The vulnerability of buildings lay in the openings, mainly windows, which allowed the current to enter the building envelope, and in the flammable contents, as well as the lack of resistance to the intense heat and dynamic pressure of some types of vernacular building construction, such as wooden chattel houses, rubble masonry walls and galvanised steel-sheet roofs. Marked variability in the level of damage due to dynamic pressure (in a range 1–5 kPa, or more) was evident throughout most of the impact area, except for the zone of total loss, and this was attributable to the effects of topography and sheltering, and projectiles, and probably localised variations in current velocity and density. A marked velocity gradient existed from the outer part to the central axis of the PDC, where buildings and vegetation were razed to the ground. The gradient correlated with the impacts due to lateral loading and heat transfer, as well as the size of the projectiles, whilst the temperature of the ash in the undiluted PDC was probably uniform across the impact area. The main hazard characteristics of the PDCs were very consistent with those described by other authors in the classic eruptions of Pelee (1902), Lamington (1951) and St Helens (1980), despite differences in the eruptive styles and scales. We devised for the first time a building damage scale for dynamic pressure which can be used in research and in future volcanic emergencies for modelling PDCs and making informed judgements on their potential impacts.

Calculation of the acoustic nonlinearity parameter B/A for four linear alkanes by Lee–Kesler equation of state

The acoustic nonlinearity parameter B/A has been calculated for four linear alkanes over the temperature range from 273.15 to 473.15 K and the pressure range from 1 atm to 1000 atm by using the Lee–Kesler equation of state. The calculated results are in agreement with the experimental data in the literature. It is found that under low pressure (1 atm and 20 atm), B/A increases linearly with temperature. Under high pressure, the value of B/A increases with temperature first, however, at a slower rate of rise. After a broad maximum, the ratio B/A decreases slowly as the temperature increases. At the fixed temperature, the B/A value decreases with the number of carbon chain of alkanes. It is shown that the B/A decreases monotonically with pressure over the whole temperature and pressure ranges.

Intra-axonal recording from large sensory myelinated axons: demonstration of impaired membrane conductances in early experimental diabetes.

Diabetic neuropathy is accompanied by a range of positive (paresthaesia, dysesthaesia, pain) and negative (hypesthaesia, anesthaesia) neurological symptoms suggesting widespread alterations in axonal excitability. The nature and the mechanisms underlying these alterations in axonal excitability are not well understood. The aim of this study was to examine the extent of changes in membrane properties of an identified neuronal structure-the large myelinated sensory axons in early experimental diabetes in rats. Intra-axonal microelectrode recordings from large sensory myelinated axons from the isolated sural nerve in short-term streptozotocin-induced diabetic rats were used to study membrane properties using standard current-clamp technique. In addition to decreased conduction velocity we found several differences in physiological properties of sensory axons from diabetic rats: decreased resting membrane potential, decreased single action potential amplitude associated with slower rate of rise and decrease in inward rectification associated with slight alteration in outwardly rectifying conductances indicating impaired potassium conductances. These results extend previous indirect evidence that potassium and sodium ionic conductances, most notably the inward rectifier (IR, I(h)), are altered in large sensory axons of diabetic rats. The depression of IR could underly clinical neurological findings in diabetic patients.

Bradykinin increases intracellular calcium levels in rat testis peritubular cells via the B2 receptor subtype.

1. RT-PCR and Western blots were used to detect bradykinin B(2) receptors in testis and isolated peritubular cells of pre-pubertal rats. RT-PCR demonstrated expression of a single transcript, whereas Western blots showed up to three specific bands that were in accordance with the described native, glycosylated and dimeric form of B(2) receptor proteins, respectively. 2. Fura-2-loaded peritubular cells responded with an instantaneous, linear and transient rise in [Ca(2+)](i) after adding bradykinin. Stimulation of cells with bradykinin concentrations between 1 micro M and 1 pM showed a dose dependent increase of [Ca(2+)](i). The calcium response to bradykinin was diminished after stimulation of peritubular cells in calcium-free buffer. After blocking the SERCA-pumps by thapsigargin and subsequent stimulation with bradykinin, no rise of [Ca(2+)](i) was appreciated. 3. Multiple stimulation of a single peritubular cell by local perfusion with a brief addition of BK (10 nM) resulted in a fast and immediate response. However, the second and third stimuli had slower rise rates and diminished [Ca(2+)](i) peaks, showing desensitization of the kinin receptor. 4. Addition of the bradykinin B(1) receptor agonist [des-Arg(9)]-bradykinin (100 nM) to Fura-2-loaded peritubular cells did not change the [Ca(2+)](i). However, the B(2) receptor antagonist HOE 140 (100 nM) strongly inhibited the bradykinin-induced calcium response. 5. We conclude that the bradykinin-induced increase in [Ca(2+)](i), in testicular peritubular cells is mediated by the stimulation of kinin receptors of the B(2) subtype.

Presynaptic Ca(2+) influx at the inhibitor of the crayfish neuromuscular junction: a photometric study at a high time resolution.

Presynaptic calcium influx at the inhibitor of the crayfish neuromuscular junction was investigated by measuring fluorescence transients generated by calcium-sensitive dyes. This approach allowed us to correlate presynaptic calcium influx with transmitter release at a high time resolution. Systematic testing of the calcium indicators showed that only low-affinity dyes, with affinities in the range of micromolar, should be used to avoid saturation of dye binding and interference with transmitter release. Presynaptic calcium influx was regulated by slowly increasing the duration of the action potential through progressive block of potassium channels. The amplitude of the calcium transient, measured from a cluster of varicosities, was linearly related to the duration of the action potential with a slope of 1.2. Gradual changes in potassium channel block allowed us to estimate the calcium cooperativity of transmitter release over a 10-fold range in presynaptic calcium influx. Calcium cooperativity measured here exhibited one component with an average value of 3.1. Inspection of simultaneously recorded presynaptic calcium transients and inhibitory postsynaptic currents (IPSCs) showed that prolonged action potentials were associated with a slow rising phase of presynaptic calcium transients, which were matched by a slow rate of rise of IPSCs. The close correlation suggests that fluorescence transients provide information on the rate of calcium influx. Because there is an anatomic mismatch between the presynaptic calcium transient, measured from a cluster of varicosities, and IPSC, measured with two-electrode voltage clamp, macropatch recording was used to monitor inhibitory postsynaptic responses from the same cluster of varicosities from which the calcium transient was measured. Inhibitory postsynaptic responses recorded with the macropatch method exhibited a faster rising phase than that recorded with two-electrode voltage clamp. This difference could be attributed to slight asynchrony of transmitter release due to action potential conduction along fine branches. In conclusion, this report shows that fluorescence transients generated by calcium-sensitive dyes can provide insights to the properties of presynaptic calcium influx, and its correlation with transmitter release, at a high time resolution.

Identification of rhythmically active cells in guinea-pig stomach.

1. When intracellular recordings were made from the antral region of guinea-pig stomach, cells with different patterns of electrical activity were detected. 2. One group of cells, slow-wave cells, generated slow waves which consisted of initial and secondary components. When filled with either Lucifer Yellow or neurobiotin, the cells identified as smooth muscle cells lying in the circular muscle layer. 3. A second group of cells, driving cells, generated large, rapidly rising, potential changes, driving potentials. They had small cell bodies with several processes. With neurobiotin, a network of cells was visualized that resembled c-kit positive interstitial cells of the myenteric region. 4. A third group of cells generated sequences of potential changes which resembled driving potentials but had smaller amplitudes and slow rates of rise. These cells resembled smooth muscle cells lying in the longitudinal muscle layer. 5. When simultaneous recordings were made from the driving and slow-wave cells, driving potentials and slow waves occurred synchronously. Current injections indicated that both cell types were part of a common electrical syncytium. 6. The initial component of slow waves persisted in low concentrations of caffeine, but the secondary component was abolished; higher concentrations shortened the duration of the residual initial component. Driving potentials continued in the presence of low concentrations of caffeine; moderate concentrations of caffeine shortened their duration. 7. Hence three different types of cells were distinguished on the basis of their electrical activity, their responses to caffeine and their structure. These were smooth muscle cells, lying in the longitudinal and circular layers, and interstitial cells in the myenteric region. The observations suggest that interstitial cells initiate slow waves.

Spectral characteristics of sleep EEG in chronic insomnia.

To determine whether the spectral characteristics of the sleep electroencephalogram (EEG) of insomniacs differ from that of healthy subjects, we compared in each of the first four non-rapid eye movement (NREM) and rapid eye movement (REM) episodes: (a) the time courses of absolute power, averaged over the subjects in each group, for the delta, theta, alpha, sigma and beta frequency bands; (b) the relationship between these time courses; and (c) the overnight trend of integrated power in each frequency band. The results show that NREM power, for all frequencies below the beta range, has slower rise rates and reaches lower levels in the insomniac group, whereas beta power is significantly increased. In REM, insomniacs show lower levels in the delta and theta bands, whereas power in the faster frequency bands is significantly increased. Thus, the pathophysiology of insomnia is characterized not only by the generally acknowledged slow wave deficiency, but also by an excessive hyperarousal of the central nervous system throughout the night, affecting both REM and NREM sleep. This hyperarousal is interpreted in terms of the neuronal group theory of sleep which provides a possible explanation for the discrepancies observed between subjective impressions and objective measures of sleep. Also, it is suggested that the progressive hyperpolarization of the thalamocortical neurons as sleep deepens is slower in the patient population and that this may explain the observed slow wave deficiency. The homeostatic control of slow wave activity, on the other hand, would appear to be intact in the patient population.

Does This Patient Have an Abnormal Systolic Murmur?

Our objective was to review the available evidence of the precision and accuracy of the clinical examination for abnormal systolic murmurs. We conducted a MEDLINE search, manually reviewed all reference lists, and contacted authors of published studies. Each study was independently reviewed by 2 observers and graded for methodologic quality. We found that most studies were conducted using cardiologist examiners. In the clinical setting, the reliability of detecting systolic murmurs was fair (kappa, 0.30-0.48). The most useful findings for ruling in aortic stenosis are a slow rate of rise of the carotid pulse (positive likelihood ratio, 2.8-130), mid to late peak intensity of the murmur (positive likelihood ratio, 8.0-101), and decreased intensity of the second heart sound (positive likelihood ratio, 3.1-50). The most useful finding for ruling out aortic stenosis is the absence of murmur radiation to the right carotid artery (negative likelihood ratio, 0.05-0.10). Smaller, lower-quality studies indicate that cardiologists can accurately rule in and rule out mitral regurgitation, tricuspid regurgitation, hypertrophic cardiomyopathy, and echocardiographic mitral valve prolapse. We conclude that the clinical examination by cardiologists is accurate for detecting various causes of abnormal systolic murmurs. Studies of the clinical examination by noncardiologists are needed.

Effect of membrane potential on the initiation of acetylcholine-induced Ca2+ transients in isolated guinea pig coronary myocytes.

The muscarinic stimulation of single voltage-clamped coronary arterial smooth muscle cells of the guinea pig was used to evaluate the effect of membrane potential on the inositol 1,4,5-tris-phosphate (IP3)-mediated changes of ionized [Ca2+] in the cytoplasm (Ca2+ transient) measured with indo 1. When applied at the membrane potential of -50 mV, 10 micromol/L acetylcholine (ACh) induced a [Ca2+]i increase after the mean latency of 2.6+/-0.9 s. The latency was reduced to 1.1 +/- 0.3 s when the same dose was applied at a holding potential of +50 mV. In paired experiments in the same cells, the latency of response at +50 mV was reduced by a factor of 2.2 +/- 0.3 compared with the response at -50 mV. Supramaximal [ACh] (100 micromol/L) induced Ca2+ transients with a 0.4 +/- 0.1-s latency, which was independent of membrane potential. When applied repetitively at -50 mV, ACh induced Ca2+ transients with a progressively reduced amplitude and slower rate of rise. Depolarization to +50 mV accelerated the rate of rise of the Ca2+ transient by a factor of 3.4 +/- 0.4 without affecting the amplitude. The modulation of the initiation of Ca2+ transient by a 100-mV depolarization can be explained by an approximately threefold increase in the rate of IP3 accumulation.