Characterization and adaptive modification of the goldfish vestibuloocular reflex by sinusoidal and velocity step vestibular stimulation.

1. The normal and adapted vestibuloocular reflex (VOR) of goldfish was characterized by means of sinusoidal, velocity step, and position step head rotations about the vertical axis. VOR adaptation was induced by short-term, 1- to 4-h, presentation of visual and vestibular stimuli that altered the ratio of eye to head velocity. 2. The VOR response measured with sinusoidal oscillations in the dark was close to ideal compensatory values over 2 decades (1/32-2 Hz). Gain approximated unity, and phase, in relation to the head, was nearly 180 degrees. The VOR was linear within the range of head velocity tested (4-64 degrees/s). 3. Head velocity steps from 1/8 to 1 Hz produced steplike eye velocity profiles that could be divided into an early acceleration-related "dynamic" component and a later constant-velocity "sustained" period frequently separated by a sag at approximately 0.1-0.15 s from the initiation of eye movement. The sustained response exhibited no decay during the constant-velocity component of the step. 4. Higher temporal resolution of the dynamic response showed the adducting eye movement to have a shorter latency, faster rise time, and larger peak gain than the abducting eye movement. The characteristics of this directional asymmetry were similar for position steps and electrical stimulation of the vestibular nerve. However, the asymmetry was not observed during sinusoidal head rotation, the sustained component of the step response, or after electrical stimulation of the VIth and IIIrd nerves. We conclude that this directional asymmetry is of central origin and may be largely due to the parallel vestibular and abducens internuclear neuron pathways onto medial rectus motoneurons. 5. The VOR adaptation process for both higher and lower eye velocity exhibited an exponential time course with time constants of 55 and 45 min, respectively. After continuous sinusoidal training for 4 h, VOR gain reached an asymptotic level 5% away from perfect suppression in the low-gain training, but 19% away from the actual performance in the high-gain paradigm. The time constant for VOR gain reversal was 5 h, and an asymptotic level 40% less than performance was reached within 10 h. 6. Adapted VOR gain was symmetrical for both directions of eye movement measured either during sinusoidal rotation or the sustained part of the velocity step. VOR adaptation also produced a comparable gain change in the nasal and temporal directions of the dynamic component, but this reflected the asymmetric characteristics observed in the preadapted condition.(ABSTRACT TRUNCATED AT 400 WORDS)


Somal membrane properties of physiologically identified sensory neurons in the rat: effects of nerve growth factor.

1. Intracellular recordings were made in situ from physiologically identified dorsal root ganglion (DRG) cells in untreated rats aged 5-8 wk and in rats treated from birth to 5 wk of age with nerve growth factor (NGF) or antisera against NGF (anti-NGF). 2. As demonstrated in cats, the shape of the somal action potential (AP) of DRG cells of normal rats is correlated with peripheral receptor type. Cells that innervate high-threshold mechanoreceptors (HTMRs) and thus respond to noxious stimulation of skin or deep tissue in the periphery have long-duration APs characterized by an inflection on the falling limb of the spike. Cells that innervate low-threshold mechanoreceptors (LTMRs) have briefer APs that lack the inflection. Somal APs of neurons supplying HTMRs tend to be larger in amplitude, have slower peak rates of rise, and on average have longer afterhyperpolarizations than those innervating LTMRs. 3. It was also found that the somal APs of HTMRs were not blocked by 200 microM tetrodotoxin (TTX) applied directly to the surface of the ganglion. In contrast, those of LTMRs were rapidly and irreversibly blocked. Despite the difference in the sensitivity of the soma, axonal conduction in both types of cells was abolished by TTX. 4. Chronic treatment with NGF resulted in an increase in duration of the falling limb of the spike compared with untreated control animals or animals treated with preimmune rabbit serum. This was true only in cells that had long duration APs to begin with, i.e., HTMRs. LTMRs were unaffected by the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)


Short-term modulation of cerebellar Purkinje cell activity after spontaneous climbing fiber input.

1. There are two opposite points of view concerning the way climbing fiber input in a Purkinje cell modifies simple spike (SS) activity transiently: depression versus enhancement of SS activity. The different groups of investigators favored one effect predominating over the other. In the decerebrate unanesthetized cat, we recorded spontaneous activity of single Purkinje cells and investigated time course of SS activity after the complex spike (CS). 2. In the peri-CS time histogram, there was a SS pause lasting, on average, 10.8 ms after onset of the CS in all of the 316 cells recorded. The pause was followed by a rapid increase in SS activity to a maximum, which was on average 175.6% of a pre-CS control level, and a gradual return to around the control level in the majority of the cells recorded (pause-facilitation type, 71.2%). The increase in SS activity was significant (P < 0.01, t test) during 20-100 ms. The SS activity during the 20-100 ms was, on average, 163.7% of the control level. In some cells (pure-pause type, 25.3%), no significant changes were found (P > 0.01) in the post-pause SS firing. In contrast, only 3.5% of the cells (pause-reduction type) showed a significant (P < 0.01) firing decrease (average 54.0% of the control level) lasting 20-60 ms after the pause period. 3. Analysis of the pre-CS time histogram revealed no significant differences (P > 0.01) in the SS activity between pre-CS periods in all of the cells recorded, suggesting that the SS activity enhancement is not due to a coactivated mossy fiber input just preceding the activation of the climbing fiber input. 4. Analysis of the raster diagram revealed variability of individual SS responses after the CS. The probability of occurrence of the increase in SS number during a post-CS period of 0-100 ms with respect to that during a pre-CS period of -100-0 ms in individual raster traces was high (on average 78.2%), medium (57.3%), and low (36.3%) in the pause-facilitation, pure-pause, and pause-reduction types of the cell, respectively. 5. Nonsequential time histograms showing frequency distribution of the pause duration after the CS in individual raster traces and that showing interspike intervals of the SS were constructed.(ABSTRACT TRUNCATED AT 400 WORDS)


Influence of temporal cues on acoustic motion-direction sensitivity of auditory neurons in the owl.

1. We studied the sensitivity of auditory neurons in the barn owl's brain stem to the direction of apparent acoustic motion. Motion stimuli were generated with an array of seven free-field speakers (Fig. 2). Motion-direction sensitivity was determined by comparing the number of spikes evoked by counterclockwise (CCW) motion with the number of spikes evoked by clockwise (CW) motion. A directionality index (DI) was defined to quantify the measurements. The statistical significance of the directional bias was determined by a chi 2 test that used the responses to stationary sounds as the null hypothesis. 2. During the search for acoustic neurons, dichotic stimuli were presented via earphones, and the sensitivity of the units for interaural time difference (ITD), interaural level difference (ILD), and frequency was measured. After a unit had been isolated, its response to moving and stationary free-field stimuli was recorded. Most of the neurons that responded to dichotic stimulation responded also to free-field stimulation. At 61 of the 211 recording sites, the response was motion-direction sensitive. 3. The spontaneous activity of all neurons was low, so that some 95% of the recorded activity was due to an excitation caused by the stimuli. 4. Neurons sensitive to the direction of motion were found in many nuclei of the auditory pathway such as the nuclei of the lateral lemniscus, the subnuclei of the inferior colliculus (IC), and the optic tectum (OT) (Figs. 3 and 5-8, Table 1). 5. In 61% of the motion-direction-sensitive neurons, the response to motion in the preferred direction was equal to the response to stationary sounds, whereas in 75% of the neurons, the response to motion in the null direction was lower than the response to stationary sounds (Table 2, Fig. 6). This observation suggested a null-direction inhibition as one important factor of generating motion-direction sensitivity. 6. Neurons having a high motion-direction sensitivity usually responded phasically, whereas tonically active neurons exhibited a low motion-direction sensitivity (Fig. 9). 7. Velocity tuning was broad (Fig. 7). A shallow peak appeared around 310 degrees/s within the range tested (125-1,200 degrees/s, 33 cells). 8. A silent gap between the bursts from successive speakers caused a decrease in motion-direction sensitivity. This decrease was linear with gap duration and depended on the apparent velocity (Figs. 10-13).(ABSTRACT TRUNCATED AT 400 WORDS)


Increased responsiveness of sensory neurons in the saphenous nerve of the streptozotocin-diabetic rat.

1. This study examined sensory neurons in the saphenous nerve of rats treated with streptozotocin to induce diabetes (STZ-D). Several physiological properties of sensory neurons were not significantly different in STZ-D compared with control (CON) rats, including percentage and rate of spontaneous activity seen in the whole nerve and mechanical and thermal thresholds of individual C-fibers. 2. The response of STZ-D and CON C-fibers to a sustained (1 min) mechanical stimulus of threshold force was similar. However, during the 5 min immediately after removal of this stimulus, there was a much greater afterdischarge in STZ-D rats (STZ-D: n = 35; 14.6 +/- 5.1 action potentials/5 min, mean +/- SE; CON: n = 34; 3.9 +/- 0.7 action potentials/5 min). The number of action potentials during a sustained (1 min) suprathreshold mechanical (445 g) stimulus was also significantly greater in the C-fibers from STZ-D rats (STZ-D: n = 44; 149.7 +/- 18.4 action potentials; CON: n = 45; 84.7 +/- 12.2 action potentials). The afterdischarge during the 5 min immediately after removal of the sustained suprathreshold stimulus was also greater in C-fibers from STZ-D rats (STZ-D: 38.7 +/- 13.1 action potentials/5 min; CON: 9.3 +/- 2.3 action potentials/5 min). 3. There was a significant difference between C-fibers from STZ-D and CON rats with respect to the distribution among certain sensory classes.(ABSTRACT TRUNCATED AT 250 WORDS)


Properties of two voltage-activated potassium currents in acutely isolated juvenile rat dentate gyrus granule cells.

1. The properties of outward currents were investigated in acutely isolated dentate gyrus granule cells at postnatal ages of day 5-7, 10-14, 18-24 (P5-7, P10-14, P18-24) and at adulthood (2-3 mo), with the use of the whole-cell patch-clamp technique. 2. Kinetic analysis and pharmacological properties showed that an A-type K+ current (IA) and a delayed rectifier current (IK) were present in these cells. 3. IA in P10-14 cells activated and inactivated rapidly with a decay time constant of 7.5 +/- 2.1 (SD) ms with command pulses to +30 mV. The removal of inactivation was monoexponential with a time constant of 23.1 ms (holding potential, -50 mV; conditioning voltage steps of varying duration to -110 mV). V 1/2 of the Boltzmann function describing steady-state inactivation was -65.1 +/- 1.8 mV with a slope factor of -6.0. IA was sensitive to 5 mM 4-aminopyridine (4-AP) but not to 10 mM tetraethylammonium (TEA). 4. IK in P10-14 cells displayed a voltage-dependent activation time constant (4.3 +/- 0.8 ms for command pulses to +30 mV and 16.2 +/- 2.4 for command pulses to -10 mV) and a double-exponential decay (time constants 194 +/- 21 and 1,625 +/- 254 ms). The rate constant of removal of inactivation was 332.1 ms. IK showed a reduction by 61.4 +/- 5.3% with 10 mM TEA and was partially blocked by 5 mM 4-AP in a subpopulation of cells. 5. Whereas IA remained stable over time, IK showed a substantial reduction of current amplitude by 67% after 30 min of cell perfusion through the patch pipette. The time course of this reduction was monoexponential with a time constant of 6.9 min and was partly due to a shift in V1/2 of the steady-state inactivation from -79.2 to -99.6 mV. 6. IA and IK remained stable with respect to kinetic properties during ontogenesis. However, the relative contribution and pharmacological properties of the investigated K+ currents varied with age. Although IA dominated in P5-7 cells, IK was prominent in most older cells. Five millimolars 4-AP reduced IA by 40.7 +/- 26.7% in P5-7 cells and blocked IA completely in 80% of investigated P10-14 cells. Similar changes were observed for the effects of 4-AP on IK (18.7% depression in the age group P5-8, 46.1% in the age group P10-14, and 45.7% in adult animals).


Nimodipine increases excitability of rabbit CA1 pyramidal neurons in an age- and concentration-dependent manner.

1. Cellular properties were studied before and after bath application of the dihydropyridine L-type calcium channel antagonist nimodipine in aging and young rabbit hippocampal CA1 pyramidal cells in vitro. Various concentrations of nimodipine, ranging from 10 nM to 10 microM, were tested to investigate age- and concentration-dependent effects on cellular excitability. Drug studies were performed on a population of neurons at similar holding potentials to equate voltage-dependent effects. The properties studied under current-clamp conditions included steady-state current-voltage relations (I-V), the amplitude and integrated area of the postburst afterhyperpolarization (AHP), accommodation to a prolonged depolarizing current pulse (spike frequency adaptation), and single action-potential waveform characteristics following synaptic activation. 2. Numerous aging-related differences in cellular properties were noted. Aging hippocampal CA1 neurons exhibited significantly larger postburst AHPs (both the amplitude and the integrated area were enhanced). Aging CA1 neurons also exhibited more hyperpolarized resting membrane potentials with a concomitant decrease in input resistance. When cells were grouped to equate resting potentials, no differences in input resistance were noted, but the AHPs were still significantly larger in aging neurons. Aging CA1 neurons also fired fewer action potentials during a prolonged depolarizing current injection than young CA1 neurons. 3. Nimodipine decreased both the peak amplitude and the integrated area of the AHP in an age- and concentration-dependent manner. At concentrations as low as 100 nM, nimodipine significantly reduced the AHP in aging CA1 neurons. In young CA1 neurons, nimodipine decreased the AHP only at 10 microM. No effects on input resistance or action-potential characteristics were seen. 4. Nimodipine increased excitability in an age- and concentration-dependent manner by decreasing spike frequency accommodation (increasing the number of action potentials during prolonged depolarizing current injection). In aging CA1 neurons, this effect was significant at concentrations as low as 10 nM. In young CA1 neurons, nimodipine decreased accommodation only at higher concentrations (> or = 1.0 microM). 5. We conclude that aging CA1 neurons were less excitable than young neurons. In aging hippocampus, nimodipine restores excitability, as measured by size of the AHP and degree of accommodation, to levels closely resembling those of young adult CA1 neurons. These actions of nimodipine on aging CA1 hippocampal neurons may partly underlie the drug's notable ability to improve associative learning in aging rabbits and other mammals. Reversal of inhibitory postsynaptic potentials (IPSPs) by chloride ion and/or current injections into six motoneurons revealed the presence of inhibition during the period between phrenic bursts during fictive vomiting and also during the final phase of expulsion when phrenic discharge ceased by abdominal discharge continued. 3. Fictive coughing, evoked by repetitive electrical stimulation of superior laryngeal nerve afferents, was characterized by a large phrenic discharge followed immediately by a large abdominal nerve discharge. During fictive coughing, phrenic motoneurons retained their ramplike depolarizations throughout phrenic discharge; however, the amplitude of depolarization was greater than during inspiration. During the subsequent abdominal nerve discharge, the phrenic membrane potential usually underwent an initial rapid, transient hyperpolarization followed by a gradual repolarization associated with increased synaptic noise.(ABSTRACT TRUNCATED AT 400 WORDS)


Membrane potential changes of phrenic motoneurons during fictive vomiting, coughing, and swallowing in the decerebrate cat.

1. The patterns of membrane potential changes of phrenic motoneurons were compared during fictive vomiting, fictive coughing, and fictive swallowing in decerebrate, paralyzed cats. These fictive behaviors were identified by motor nerve discharge patterns similar to those recorded from the muscles of nonparalyzed animals. Phrenic motoneurons (n = 54) were identified by antidromic activation from the thoracic phrenic nerve. Intracellular recordings were obtained from 27 motoneurons during fictive vomiting, 40 during fictive coughing, and 27 during fictive swallowing. Sixteen motoneurons were recorded during both fictive coughing and fictive swallowing, eight during both fictive coughing and fictive vomiting, and two during both fictive vomiting and fictive swallowing. Seven motoneurons were studied during all three behaviors. 2. Fictive vomiting, typically evoked by electrical stimulation of abdominal vagal afferents, was characterized by a series of bursts of coactivation of phrenic and abdominal motor nerves, culminating in an expulsion phase in which abdominal discharge was prolonged both with respect to phrenic discharge and to abdominal discharge during the preceding retching phase. During fictive vomiting, phrenic motoneurons depolarized abruptly, and the amplitude of depolarization was significantly greater than during control inspirations. They then repolarized slowly throughout the phrenic burst, rapidly repolarizing at the end of each phrenic burst during retching and reaching a level similar to that observed during expiration. During the expulsion phase, the pattern was initially the same. However, after the cessation of phrenic discharge, the membrane potential repolarized slowly until the end of the abdominal burst, exhibiting greater synaptic noise than during expiration. One phrenic motoneuron, presumably innervating the periesophageal region of the diaphragm, received a strong hyperpolarization just before the onset of the emetic episode and fired for shorter periods during fictive vomiting than did other phrenic motoneurons.(ABSTRACT TRUNCATED AT 250 WORDS)


Persistent hyperexcitability in isolated hippocampal CA1 of kainate-lesioned rats.

1. Subcutaneous kainate injection in rats evoked acute seizures and led to cell loss in the hilus and areas CA1 and CA3, which resembled the pattern of hippocampal sclerosis often associated with temporal lobe epilepsy in humans. 2. Simultaneous intra- and extracellular recordings were performed in the stratum pyramidale of area CA1 while stimulating in the stratum radiatum close to the recording electrodes. Responses from control slices consisted of a brief excitatory postsynaptic potential (EPSP) with only one action potential, corresponding to a single extracellular population spike, followed by a clear biphasic inhibitory postsynaptic potential (IPSP). In slices from kainate-treated animals, however, stimulation evoked a prolonged EPSP, which often triggered multiple action potentials corresponding to multiple extracellular population spikes. 3. In slices from kainate-treated animals, the mean amplitude but not the duration of the stimulation-evoked IPSP was reduced. The extent of the kainate-induced loss of inhibition in area CA1 was highly variable. 4. Low concentrations of bicuculline in control slices led to a moderate hyperexcitability, which consisted of multiple population spikes and mirrored the responses observed in slices from kainate-treated animals in normal ACSF. Prolonged application of 10-30 microM bicuculline for > or = 30 min led to a much higher level of hyperexcitability, which was similar in slices from controls and kainate-treated rats. These findings are consistent with the hypothesis that the hyperexcitability of CA1 pyramidal neurons following kainate treatment is mainly due to decreased GABAA-receptor-mediated inhibition and that the loss of inhibition is only partial.(ABSTRACT TRUNCATED AT 250 WORDS)


Mechanisms of human vertical visual-vestibular interaction.

1. The purpose of this study was to infer the properties of the mechanisms contributing to visual-vestibular interaction (VVI) of human beings during vertical motion. Predictable trains of single-frequency sinusoids; poorly predictable sums of sinusoidal harmonics; and unpredictable random impulses of passive, whole-body rotation about a horizontal, interaural axis were produced by the use of a servo-driven chair at frequencies from 0.4 to 3.2 Hz. The vestibuloocular reflex (VOR) was studied in darkness with the use of the magnetic search coil technique to record eye movements during head rotation. Telescopic spectacles of varying magnifications and visual field areas were used as a challenging stimulus to induce substantial gain enhancement by VVI. Real and imagined targets moving with the head were used to induce gain reduction. VVI was compared with vertical smooth pursuit and small field optokinetic nystagmus (OKN) for similar stimulus motion. 2. The vertical VOR and visually enhanced VOR (VVOR) were directionally symmetrical. Viewing with telescopic spectacles of powers from x1.9-4 was associated with significantly increased gain at frequencies up to 2.0 Hz as compared with the VOR (P < 0.01). Gain enhancement was not strongly influenced by stimulus velocity for either predictable or poorly predictable head motion, and there was a trend toward greater VVOR gain at higher head velocities. Phase was compensatory at all frequencies for predictable sinusoids. For poorly predictable and unpredictable head motion, gain enhancement with telescopic spectacles was significantly less than during predictable head motion. During poorly predictable head motion, phase lags were observed that increased with frequency and telescopic spectacle power. 3. The perseverance of VVI during disappearance of the visual environment was evaluated by blanking it during various proportions of the cycle of predictable head rotation at frequencies from 0.8 to 2.4 Hz. Below 2.0 Hz, a trend toward gain enhancement was observed with x1.9 telescopic spectacles when the visual environment was present for as little as 6% of the sinusoidal cycle. This effect was statistically significant (P < 0.01) at 0.8 and 1.2 Hz when the visual environment was present for 50% of the cycle. 4. Suppression of the VOR was evaluated for visual fixation of real and imaginary head-fixed targets during predictable, poorly predictable, and unpredictable rotations. Fixation of a real target was most effective at low frequencies of predictable rotation and was significantly effective in reducing gain relative to the VOR at frequencies of < or = 2.4 Hz.(ABSTRACT TRUNCATED AT 400 WORDS)


Effects of stationary textured backgrounds on the initiation of pursuit eye movements in monkeys.

1. The initial ocular pursuit of small target spots (0.25 degrees diam) that suddenly start to move at constant speed (ramps) was recorded in four rhesus monkeys with the electromagnetic search coil technique. All target motions were horizontal, and both eyes were monitored. 2. In agreement with the observations of Keller and Khan, stationary textured backgrounds substantially reduced the initial eye acceleration achieved during pursuit but did not affect its latency. Correlation techniques were used to assess the changes in the eye speed profiles and indicated that the reduction in eye acceleration due to the background was a linear function of the logarithm of target speed over the range investigated (5-40 degrees/s), averaging 60% with the fastest targets. 3. Selectively excluding the background texture from the path of the target with a horizontal strip of card (vertical width, 4 degrees) reduced the impact of the background only slightly, and, even when the vertical width of the card was increased to 60 degrees, the effect of the background was not entirely eliminated. Thus the effect involves regions of the visual field well beyond the target and is not due simply to the reduced physical salience (contrast) of the target spot. Such spatially remote interactions suggest that the neurons decoding the target's motion have very extensive visual receptive fields. 4. Textured backgrounds also caused similar reductions in the eye acceleration during initial pursuit when, before the ramps, the fixated target spots stepped forward, i.e., stepped in the direction of the subsequent ramps (step ramps). In this situation, as with no steps, initial target ramps were foveofugal. When the fixated target spots were stepped back before moving forward so that initial target ramps were foveopetal, textured backgrounds now also delayed the onset of pursuit, and the reductions in eye acceleration were not seen until some time later when tracking resulted from foveofugal target-ramp motion. Selectively excluding the texture from the path of the target with a narrow strip of card eliminated any delays in the onset of pursuit to step ramps, but the later reductions in eye acceleration were still evident. These step-ramp data indicate that the mechanisms decoding foveofugal and foveopetal target ramps differ markedly in their sensitivity to textured backgrounds. That backgrounds can influence the latency and the initial eye acceleration independently is consistent with the idea that there are independent trigger and drive mechanisms for the decoding of target motions.(ABSTRACT TRUNCATED AT 400 WORDS)


Differential responses of neocortical neurons to glucose and/or O2 deprivation in the human and rat.

1. Intracellular recordings were performed in human and rat neocortical neurons with in vitro brain slice techniques. Baseline cellular properties and the effect of O2 and glucose deprivation on these neurons were studied. 2. Intracellular labelings of electrophysiologically identified neurons showed that most neurons recorded from layers 4 and 5 of the neocortex in both rats and humans were pyramidal cells with a regular-spiking or a burst firing pattern. 3. A period of complete anoxia (4-5 min) induced little or no change in membrane potential (Vm) in rat and human neocortical neurons, contrasting with the major depolarization we have previously observed in rat brainstem neurons during a similar period of anoxia. Evident depolarization occurred only when the slices were exposed to a more prolonged period of anoxia (> 7 min in rats and > 10 min in humans). 4. Membrane input resistance (Rm) of neocortical neurons decreased in both species during anoxia. In human neocortical neurons, Rm decreased by a mean of 22% with a marked increase in rheobase and suppression in spontaneous excitatory postsynaptic potentials (EPSPs). Interestingly, the increase in rheobase in human cells occurred even at an early stage (post 2-3 min in anoxia), when Vm and Rm had not yet changed. 5. Perfusing slices with a glucose-free medium for 1-2 h produced a relatively modest change in Vm (mean congruent to 28 mV). However, combined deprivation of both glucose and O2 resulted in a major depolarization (mean congruent to 50 mV) within 5-10 min in both human and rat neocortical neurons.(ABSTRACT TRUNCATED AT 250 WORDS)


Relative contributions of burst and tonic responses to the receptive field properties of lateral geniculate neurons in the cat.

1. In an anesthetized, paralyzed in vivo preparation, we recorded extracellular responses of 61 geniculate neurons (2 W, 25 X, 33 Y, and 1 mixed) to drifting sine-wave gratings of various spatial frequency, temporal frequency, and contrast. Our goal was to study the differential contributions to these visual responses of bursting caused by voltage dependent, low-threshold (LT) Ca2+ spikes and of purely tonic responses unrelated to LT spikes. Cells responding with LT spikes are said to be in the burst firing mode and those responding in a purely tonic fashion to be in the relay or tonic firing mode. We separated the total visual response into LT burst and tonic components by use of the empirical criteria set forth in our intracellular study described in the previous paper (Lu et al. 1992). A response component was considered to be an LT burst if its action potentials displayed interspike intervals < or = 4 ms and if the first spike in the burst episode occurred after a silent period of > or = 100 ms (or > or = 50 ms when the neuron responds to visual stimuli at temporal rates > or = 8 Hz). All other activity is considered to be part of the tonic response. 2. In addition to LT bursts, we recognized another type of burst response, the high-threshold (HT) burst. These also have clusters of action potentials with interspike intervals < or = 4 ms. However, HT bursts, unlike LT bursts, lack a preburst silent period. HT bursts are part of the tonic response component and merely reflect the gradual decrease in interspike intervals that occurs as the cell becomes more depolarized and thus more responsive. Thus interspike interval is a necessary but insufficient criterion to identify LT bursts. 3. Visually evoked LT bursts were recorded among W, X, and Y cells. When evoked, LT bursts occurred in phase with drifting sine-wave grating stimuli at a rate never exceeding one per stimulus cycle. In response to individual cycles of the visual stimulus, LT bursts could comprise the total response, a tonic component could comprise the total response, or an LT burst and tonic component could be mixed. When a stimulus evoked a mixture of LT bursts and tonic response components, LT bursts were always the first response. 4. Of the 61 cells tested with grating stimuli, 47 exhibited LT bursts and 14 did not. Those that did exhibited varying amounts of burstiness.(ABSTRACT TRUNCATED AT 400 WORDS)


Velocity- and acceleration-sensitive units in the trunk lateral line of the trout.

1. The two main types of lateral line organs of lower vertebrates are the superficial neuromasts (SN), with a cupula that protrudes in the surrounding water, and the canal neuromasts (CN), located in the lateral line canal. The scales of the trunk lateral line canal of fish contain SNs as well as CNs. In this study, we examine whether there exist two functional classes of afferent fibers in the trunk lateral line nerve of the rainbow trout that can be attributed to the SNs and CNs. 2. The response properties of the afferent fibers in the trunk lateral line nerve have been determined during stimulation with sinusoidally varying water motion generated by a small vibrating sphere. Linear frequency response analysis revealed the presence of two distinct populations of afferent fibers in the lateral line nerve. The fibers belonging to the two populations showed significant differences in the frequency at which the sensitivity was maximal, the low-frequency response slope and the low-frequency asymptotic phase angle. 3. One population of fibers has a maximum sensitivity at 36 +/- 13 (SD) Hz (n = 22) and responds up to this frequency to water velocity. The low-frequency slope of the frequency response of these fibers was 20 +/- 3 (SD) dB/decade and the low-frequency phase lead was 121 +/- 11 degrees (mean +/- SD), both with respect to sphere displacement. The fibers of the other population have a maximum sensitivity at 93 +/- 14 (SD) Hz (n = 12) and respond up to this frequency to water acceleration. The low-frequency slope of these fibers was 35 +/- 5 (SD) dB/decade, and the low-frequency phase lead was 188 +/- 13 degrees (mean +/- SD). 4. Analysis of the stochastic properties of the spontaneous activity of both types of fibers revealed that the mean firing rate of the fibers responding to water velocity (26 +/- 12 spikes/s, mean +/- SD; n = 22) was significantly higher than that of the fibers responding to acceleration (36 +/- 11 spikes/s, mean +/- SD; n = 12). The other statistical properties of the spontaneous activity were found to be indistinguishable. 5. From comparison of the results with the available quantitative data on frequency responses of lateral line organs in other species, it has been concluded that the fibers responding (< or = 40 Hz) to water velocity innervate SNs and that the fibers responding (< or = 90 Hz) to water acceleration innervate CNs.(ABSTRACT TRUNCATED AT 400 WORDS)


Purkinje cell complex and simple spike changes during a voluntary arm movement learning task in the monkey.

1. To evaluate the role of the cerebellum during improvement of voluntary motor performance over time, the discharge of 88 Purkinje cells in the intermediate and lateral cerebellum of two primates (Macaca mulatta) was investigated during a motor learning task involving visually guided arm movements. The animals were trained to move a draftsman's style manipulandum over a horizontally placed video screen. The animals were required to move a cursor from the start box to one of four target boxes by movement of the manipulandum. Errors were introduced into the movement by altering the visual feedback loop, changing the gain between the cursor movement and the hand movement. When a novel gain was presented over 100-200 movement trials, the animals adapted the movements to the new gain. The animals used a strategy of scaling the amplitude and velocity of the initial phase of the movement while keeping the time to peak velocity constant. 2. The learning paradigm consisted of an initial control phase with 35-100 trials at the gain of 1.0. The next 100-200 trials, the learning phase, were presented at one of four gains (0.6, 0.75, 1.5, 2.0). Lastly, a testing phase involved 80% of 100 trials at the learned gain and 20% of the trials randomly interspersed at the control gain of 1.0. An additional "distance control" was used in most experiments to control for the movement scaling associated with learning. In this series of movements using a gain of 1.0, the target box was placed at the distance and direction the hand would have to move in the adapted state. Two aspects of the kinematics were the same for the distance control and the movement at the learned gain: movement amplitude and time to peak velocity. There were, however, slight differences in the peak velocity attained. For gains < 1.0, the peak velocity of the learned task was 14-20% lower than the distance controls, and for gains > 1.0, it was 10-18% higher. 3. After implantation of chronic unit recording hardware, Purkinje cell simple and complex spike discharge was recorded extracellularly during the learning task. The cells were located primarily in the ipsilateral intermediate zone or nearby hemisphere of lobules V and VI. Simple and complex spike histograms, as well as averages of the hand displacement and velocity profiles, were calculated for each phase of the paradigm. To determine the time course of any changes, the learning trials were subdivided into three equal phases.(ABSTRACT TRUNCATED AT 400 WORDS)


Role of calcium influx and buffering in the kinetics of Ca(2+)-activated K+ current in rat vagal motoneurons.

1. Intracellular recordings were obtained from neurons of the dorsal motor nucleus of the vagus (DMV) in transverse slices of the rat medulla maintained in vitro. These neurons had a resting potential of -59.8 +/- 8.7 (SD) mV. Single action potentials elicited by brief depolarizing current pulses were followed by a prolonged afterhyperpolarization (AHP). Under voltage clamp, the current underlying the AHP was found to be a calcium-activated potassium current. 2. The outward current (GkCa,1) was voltage insensitive and was not blocked by tetraethylammonium (TEA) (10 mM). Unlike the slower time course calcium-activated potassium current recorded in some other neurons, GkCa,1 was blocked by apamin (25-100 nM), indicating that SK type calcium-activated potassium channels underlie this current. 3. GkCa,1 was maximal within 10 ms of the action potential and its decay was well described by a single exponential. After a single action potential the time constant of decay of GkCa,1 was 155 +/- 66 (+/- SD) ms. 4. Calcium influx was increased by adding TEA to the extracellular solution or by firing more than one action potential. As the calcium load was increased, both the peak amplitude and the time constant of decay of GkCa,1 increased. In cells impaled with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA)-filled electrodes, the time constant of decay of GkCa,1 after a single action current was 71 +/- 19 ms. 5. A simple diffusion-based model that incorporates two intrinsic calcium buffers is developed that accounts for many of the properties of GkCa,1. It is concluded that the decay of GkCa,1 reflects the time course of removal of calcium that has entered the cell during the action potential.


A long closed state of the synaptosomal bursting potassium channel confers a statistical memory.

1. The statistical properties of the bursting potassium channel from fused Torpedo synaptosomes were studied by using patch-clamp recording and time series analysis. 2. Voltage steps produce channel openings; the number of channels opening fluctuates from trial to trial. The maximal current observed in each trial is strongly dependent on the previous history of the membrane patch. Trials with no activity are frequently clumped together and so are trials with intense activity. 3. Autocorrelation analysis reveals a strong interdependence of successive responses, which is voltage dependent. 4. We propose that the strong statistical interdependence of responses to successive depolarizing pulses (the statistical "memory") is a manifestation of a long lived closed state. We speculate that this statistical memory may be of significance in frequency modulation of transmitter release.


[Enophthalmos following radical operation of the maxillary sinus and ethmoidal sinus].

Enophthalmos is usually a consequence of orbital trauma resulting in a blowout fracture of the orbital floor. We report here the case of a 35-year-old male who had a radical operation of the maxillary sinus and the ethmoidal sinus, and 2 months after the operation, developed spontaneous enophthalmos and ocular pain. The left orbit was enophthalmic by 5mm according to Hertel enophthalmometry. Surgical correction was performed under general anesthesia. The left orbit was explored through a transcutaneous incision of the left lower lid which revealed marked periosteal adhesions and absence of the bony floor of the orbit. A rib cartilage graft was used to reconstruct the floor of the orbit, and the globe was brought forward by means of retrobulbar placement. Enophthalmos and ocular pain disappeared postoperatively.


[A case of Bezold's abscess associated with cholesteatoma].

Since the advent of antibiotics, otogenic complications have decreased considerably. However, incomplete antibiotic therapy has altered the clinical course of middle ear disease so as to be more insidious. This paper reports a case of Bezold's abscess associated with cholesteatoma. A 48-year-old man visited our hospital presenting with a 4-day history of right otorrhea and a tender swelling in the right neck. Physical examination showed a febrile patient (38.8 degrees C) with right facial paresis and trismus. A hyperemic, hard and tender swelling was observed in his right neck from the lateral cervical to the mental region. The tympanic membrane was invisible because of granulation and swelling of the posterior wall of the external auditory canal. Intravenous clindamycin and ceftazidime therapy was started immediately. A CT-scan revealed a diffuse shadow with bony destruction in the right mastoid cortex. Extensive abscess formation was also found in the right sternocleidomastoid muscle, in the anterior neck and in the posterior neck. He was diagnosed as having Bezold's abscess associated with cholesteatoma. Radical mastoidectomy and drainage of the neck abscess was performed on the third day under general anesthesia. The mastoid cavity was found to be filled with pus and cholesteatoma debris. A small area of defective bone was found at the mastoid tip, through which there were communications between the mastoid cavity and the abscesses in the neck. Bony destruction was also found in the horizontal and vertical portion of the facial canal. Bacteroides and three kinds of gram-negative rods were cultured from the mastoid cavity.(ABSTRACT TRUNCATED AT 250 WORDS)


[Development of endolymphatic hydrops following immune response in the endolymphatic sac of guinea pigs--long-term observation].

We report findings for endolymphatic hydrops in specimens obtained 5 to 28 weeks after a direct challenge with secondary KLH antigen to the endolymphatic sac (ES) of guinea pigs. Following gradual disappearance of endolymphatic hydrops (EH) in the period between the 5th and 8th weeks, the inferior labyrinth EH gradually developed again from the 3rd month onward in the saccule and from the 4th month onward in the cochlea. Many lymphocytes and plasma cells infiltrated into the perisaccular space for up to 7 months. These results suggest that an immune response in the ES may ultimately induce chronic dysfunction of the ES and thereby lead to progressive EH.


[Gd-DTPA-enhanced MR imaging of cholesteatoma].

It is sometimes difficult to differentiate a cholesteatoma from an accompanying cholesterol granuloma, mucosa, fluid and, especially, granulation tissue. This study was designed to assess the reliability with which cholesteatoma can be differentiated from such accompanying lesions by Gd-DTPA-enhanced MR imaging. Twenty-one patients with cholesteatoma were studied with magnetic resonance (MR) imaging. The cholesteatoma had intermediate to high signal intensities similar to those of granulation tissue, on both T1- and T2-weighted images. On Gd-enhanced images, however, there was marked enhancement of all granulation tissues while the cholesteatoma showed no such enhancement. Gd-DTPA-enhanced images distinguished cholesteatoma from granulation tissues and permitted determination of the exact extent of the cholesteatoma. Cholesterol granulomas showed high signal intensities on both T1- and T2-weighted images. Cholesterol granuloma can, therefore, be distinguished from cholesteatoma and granulation tissues on both T1- and T2-weighted images. Gd-DTPA-enhanced MR imaging is a valuable tool in the evaluation and management of cholesteatoma.


[Maxillary prosthesis for better QOL--early setting and faster construction of maxillary prosthesis].

The maxillofacial prosthesis (MFP) is well accepted as one of the modalities to ameliolate the postsurgical crippling in the patients with maxillary malignancy. In this report, we analyzed 55 primary cases of MFP out of 100, from July, 1981 to July, 1987 in terms of the time of start after operation, and the duration and procedure of the MFP-making. MFP-making set about within 4 weeks in 35% of patients, 8 weeks in 25%, 12 weeks in 22%, and more than 12 weeks in 18%. The completion of MFP-making averaged 10 days. As a result of simplifying of MFP-making, we shortened a period requiring MFP-making within 3 days in recent 10 cases. There were no adverse effects of early wear of MFP after operation. We believe that early wear of MFP after operation improve the quality of life of patients with maxillary malignancy and considered that wear of MFP is not the completion of treatment, but is one of the procedures of treatment for the patients undergone maxillectomy.


[Laryngeal closure--a simple method and a reversible method for phonation preservation].

Patients with dysphagia due to a disorder in swallowing phase II are candidates for laryngeal closure operation. The operation prevents bolus drainage into the larynx and therefore permits oral feeding. Operative methods in general should be simple and reliable, and furthermore, with regards to this laryngeal closure procedure, they should preferably be reversible to maintain phonatory function, in the event that patients improve swallowing function later on. A laryngeal closure operation which satisfies both conditions has not been previously reported. We present two laryngeal closure operations. One is relatively simple and reliable but irreversible in terms of phonatory function. The other procedure requires more effort but is reversible and therefore allows for preservation of phonatory function. We performed one of these operations on two cases each and obtained good results. 1. Laryngeal closure at the vocal cords. (simple method) The frontal neck skin is incised vertically. The thyroid cartilage perichondrium is incised in the midline and retracted widely on both sides. Then the anterior thyroid lamina is removed at the crico-arytenoid joint. A control hole is opened into the laryngeal lumen by an incision made from the cricoarytenoid membrane to the anterior commissure. The larynx is cut horizontally from the anterior to posterior commissure between the upper and lower lips of the vocal cords. Finally the vocal cords are sutured at the top and bottom of the cut stump. 2. Closure at the false vocal cords. (reversible method for phonation preservation) After the vertical incision has been made, the laryngeal lumen is opened by laryngofissure.(ABSTRACT TRUNCATED AT 250 WORDS)


[Genotypic analysis of lethal midline granuloma].

So-called lethal midline granuloma is of great clinical and theoretical interest. The etiology of lethal midline granuloma is unknown and the pathogenesis is variable, with debate as to precise classification and natural history. In this study, we reported genotypic and immunopathological features in 3 cases of lethal midline granuloma. The histopathological diagnosis of their biopsy specimens was initially polymorphic reticulosis/midline malignant reticulosis. Immunohistologic study of the specimens revealed that immature or atypical cells had phenotypes of T-cells, CD2, CD3, CD4 (Case 1), CD4 (Case 2), and CD2, CD3 (Case 3). Those cells were also found to be positive for HLA-DR, which indicated that they were activated T-cells. Immunohistology in T-cells, however, was not able to give a similar clue to clonarity as it was possible within B-cell neoplasms by immunophenotyping the light chains. With the establishment of cDNA probes for the T-cell receptor genes it was possible to analyze neoplasms of lymphocyte origin for lineage and clonality. The Southern blot analysis of 3 cases showed rearrangement of TCR gene, TCR beta and TCR gamma chain (Cases 1 and 2) and TCR beta and TCR delta chain (Case 3), whereas none of them showed rearrangement of immunoglobulin heavy chain. These findings represented conclusive evidence for a monoclonal T-cell proliferation within lethal midline granuloma. On the ground of immunohistological and genotypic studies, lethal midline granuloma histologically diagnosed as polymorphic reticulosis/midline malignant reticulosis are proven to be a T-cell lymphoproliferative disorder.


[Solute movement across the round window membrane in comparison with that across the blood-labyrinth barrier].

The permeability of the normal round window membrane of the guinea pig to trimethylphenylammonium (TMPA) was assessed using ion-selective electrodes and compared with the rate of TMPA entry from the systemic blood circulation into the scala tympani (ST) of the cochlea across the so-called blood-labyrinth barrier. While the round window niche was irrigated with artificial perilymph containing 1 mM TMPA, the TMPA concentration in ST of the basal turn rose rapidly so as to reach 20-50% of the irrigating medium concentration in one hour. Following this procedure, the concentration declined significantly faster when the niche was subsequently irrigated with TMPA-free artificial perilymph than when the niche was left free of any fluid. This result shows that the membrane is fairly permeable to TMPA in both directions. Furthermore, TMPA entry from blood to STs of the basal and third turns was observed while the plasma TMPA concentration was maintained at about 0.5 mM by continuous intravenous infusion of isotonic 50 mM TMPA medium (1 part 150 mM TMPA + 2 parts lactated Ringer solution). TMPA appeared to distribute evenly from the blood to both turns at a much slower rate than across the round window membrane. In another experiment, the round window niche was irrigated with TMPA-free artificial perilymph during the intravenous infusion of 50 mM TMPA medium. The TMPA concentration increase in ST of the basal turn was greatly suppressed, whereas that of the third turn was not affected for at least an hour.(ABSTRACT TRUNCATED AT 250 WORDS)


[Comparison of vulnerability between avian and mammalian inner ears--electrophysiological and morphological studies].

In order to assess the vulnerability of the inner ear, auditory function and morphology of the inner ear were compared between adult budgerigars and adult guinea pigs. Budgerigars have been considered to have an excellent auditory-vocal system. Two experimental conditions were produced in each species; one by acoustic hyperstimulation (1500 Hz, 120 dBSPL) for 96 hours, the other by administration of kanamycin (200 mg/kg) for 7 weeks. Measurement of auditory evoked potentials (AEP) and observation of hair cells by electron microscopy were performed both immediately and 14 days after exposure. In the acoustic hyperstimulation experiment, AEPs of budgerigars showed less damage and better recovery than those of guinea pigs, probably because of morphological differences between the two species in hair and supporting cells. Electron microscopic observation on the budgerigars showed that a small part of the hair cell area was damaged and that regeneration of hair cells had occurred in this area 14 days after exposure. Such observations in guinea pigs revealed that outer hair cells had been damaged and replaced by supporting cells 14 days after exposure. In the kanamycin administration experiment, AEPs showed the same degree of damage and recovery in both species. This suggests that blood supply and drug transport to the inner ear are almost the same although the structure of the inner ear differs markedly between the two species. Electron microscopic observation did not show an apparent regeneration of hair cells 14 days after administration in the budgerigars. Guinea pigs had a tendency to show progressive damage of both auditory function and inner ear morphology even after the cessation of administration. Regeneration of hair cells in the budgerigar differed under both experimental conditions, suggesting that there is a difference in the mode of auditory disturbance between acoustic hyperstimulation and administration of kanamycin. In conclusion, resistance to acoustic hyperstimulation is higher in the avian inner ear than in the mammalian inner ear, while resistance to administration of kanamycin does not differ significantly between the two species.


The setting for the crack era: macro forces, micro consequences (1960-1992).

This article provides an overview of the social history leading up to the crack era, especially 1960 to the present. The central theme holds that several major macro social forces (e.g., economic decline, job loss, ghettoization, housing abandonment, homelessness) have disproportionately impacted on the inner-city economy. These forces have created micro consequences that have impacted directly on many inner-city residents and have increased levels of distress experienced by households, families, and individuals. Economic marginality has generated high levels of alcohol and other drug abuse as well as criminality, which are exemplified in this article by one inner-city household having an extensive family history exhibiting the chronic impacts of these macro forces and their micro consequences.


From bag brides to skeezers: a historical perspective on sex-for-drugs behavior.

There are many ways that women support their use of crack cocaine, including sex-for-crack bartering and other forms of prostitution. Empirical studies conducted in the mid-1970s and in the mid-1980s in New York City, and in Chicago in the late 1980s to early 1990s are compared, analyzing similarities and differences between the contemporary crack-prostitution scene and previous prostitution scenes. Findings suggest that the arrival of crack cocaine has directly and indirectly affected the drugs-prostitution nexus by lowering the price of sex for street prostitutes, altering the social status of cocaine, and increasing the level of social disorganization in illicit street activities, including prostitution. Barterers are shown to be the heaviest drug users, using the greatest variety of drugs, using larger amounts of drugs, and using more frequently.


High-risk sex behavior among young street-recruited crack cocaine smokers in three American cities: an interim report. The Multicenter Crack Cocaine and HIV Infection Study Team.

Since crack cocaine appeared in urban areas in the United States in the mid-1980s, reports have suggested that crack smokers may be at increased risk of sexually transmitted diseases (STDs), including infection with HIV, because they have multiple sex partners, trade sex for money or drugs, and rarely use condoms. A cross-sectional survey is being conducted in urban neighborhoods in Miami, New York and San Francisco--where crack use is common--to explore these issues. Indigenous street outreach workers are recruiting men and women who are either current regular crack smokers or who have never smoked crack; each group is further stratified according to whether participants had ever injected drugs. Participants were interviewed about their sexual and drug-use practices. Overall, crack smokers, whether injectors or not, engaged in higher-risk sexual behaviors than nonsmokers, reported greater numbers of sex partners than nonsmokers, and were more likely than nonsmokers to have exchanged sex for money or drugs or to have had an STD. Differences between crack smokers and nonsmokers were generally greater among non-injectors than among injectors, and generally greater among women than among men. Condom use, although somewhat more common with paying than nonpaying partners, was infrequent overall. Most of the subjects had not been in substance abuse treatment in the preceding 12 months, and a majority had never been in substance abuse treatment. Education and prevention programs specifically targeted at crack smokers not currently in substance abuse treatment are needed to reach these high-risk persons.


Studying crack abusers: strategies for recruiting the right tail of an ill-defined population.

This study attempts to better understand a limited segment of the drug-abusing population, especially individuals who repeatedly use crack and other drugs. This article addresses the methodological strategies and underlying paradigms informing the recruitment of hard-to-reach and ill-defined subpopulations of crack abusers and noncrack drug abusers. Subjects were recruited from diverse social contexts: streets or communities where most drug users do their business, arrested persons who were released, jail inmates, probationers and parolees, prison inmates, and treatment settings. A systematic comparison of subject attributes across recruitment locales and with other, similar target groups is presented. The utility and external comparability of the recruitment techniques are supported by the findings.


The developmental cycle of a drug epidemic: the cocaine smoking epidemic of 1981-1991.

Although Americans have experienced many drug epidemics, the majority of which have ended within ten years of onset, they nevertheless believed that the use of smokable cocaine, which took the popular form of crack cocaine in 1984, would grow exponentially throughout the 1990s unless it was vigorously combated. However, in 1991 it appears that crack use is in decline even in the inner-city neighborhoods where it had been most entrenched, and that the decline is due more to natural controls than to the War on Drugs. The cyclical nature of drug epidemics, as well as their progression through regular stages, was again affirmed. The cocaine-smoking epidemic of 1981-1991 (which included crack) afforded the opportunity to research it in its entirety. In this article, the advantages of recognizing the developmental cycles of drug epidemics are outlined, the most important of which concerns the future. In the terminal stage of the developmental cycle of a drug epidemic, remaining abusers play a pivotal role. If humanely treated, they may serve as deterrents to future drug use: frustrated in current drug use, however, yet insensitively treated by the wider society, they may author the next epidemic.


Crack cocaine use and sexual activity in Miami, Florida.

Data are analyzed from the Multicenter Study of Crack Cocaine and HIV Infection in Miami, Florida, examining interrelationships among use of crack cocaine, use of other drugs, sexual activity, and exchange of sex for money and drugs. This study was designed to recruit two groups of approximately equal size: persons who reported current use of crack cocaine three or more times per week, and those who had never used crack. Participants (N = 641) were recruited in Miami. Participants' median age for first use of crack cocaine was higher than for use of alcohol, marijuana or powdered cocaine. It was also higher than participants' ages at first sexual activity, and somewhat higher than the median age for reporting initiation of trading sex for money or drugs. The median age of first crack use was lower among younger participants, suggesting that crack use in older participants followed quickly upon availability of the drug. Crack users reported reduced desire for sex and diminished ability to have sex after smoking crack. However, crack use was associated with increased sexual activity, trading sex for money or drugs, and sex with multiple partners. Participants who traded sex for money or drugs (traders) reported higher rates of condom use than nontraders; however, neither traders nor nontraders reported rates of condom use sufficient to substantially reduce the transmission of sexually transmitted diseases and HIV infection.


Five confirmed human cases of gnathostomiasis nipponica recently found in northern Japan.

Five confirmed human cases of gnathostomiasis nipponica exhibiting creeping eruption and itching were found sporadically from the autumn of 1991 to the winter of 1992 in the northern region of the mainland of Japan. In all cases, a causative gnathostome with 3 transverse rows of hooklets on the head bulb was detected in biopsied skin. The morphological characteristics agreed with the advanced third-stage larvae of Gnathostoma nipponicum. Within a few weeks before development of symptoms, all patients had histories of eating raw freshwater fishes, kokanee (Salmo nerka nerka), carp (Cyprinus carpio), crucian carp (Carassius gibelio langsdorfi), or common ice-fish (Salangichthys microdon). However, they had never eaten raw loach, which is known as a source of human infections with G. nipponicum.


Women who use cocaine too much: smoking crack vs. snorting cocaine.

Monique (an African-American 19-year-old) and Becky (a white 21-year-old) were interviewed as part of a NIDA-funded study of women and cocaine. Although they were not necessarily typical, they do illustrate some of the differences among women who use cocaine. Despite the fact that they were close in age and both used cocaine, their scenarios and outcomes were very different, as one was a white middle-class woman and the other was an underclass woman of Color. The argument presented in this article is that it is not simply substance use that frames the experiences of women who use cocaine too much, but the social class mediated by gender and race. Through these life histories, the lives of these women are examined prior to cocaine use. Then the differential processes of initiation into and continuation of cocaine are described and analyzed, followed by a discussion of their lives after cocaine use.


Characterization of Eimeria tenella unsporulated oocyst-specific cDNA clones.

A cDNA library was constructed with poly(A)+ RNA from unsporulated oocysts of Eimeria tenella in pUC18. After screening, 4 cDNA clones that hybridized to RNA of unsporulated and sporulating oocysts but not to RNA of either sporulated oocysts or second generation merozoites were isolated and characterized. Each of the cDNA clones is unique. The loci for 2 of the clones are on E. tenella chromosome 7, the site of the third is located on chromosome 6 and the last clone hybridizes, for the most part, to chromosome 5 but also to other E. tenella chromosomes. The cognate RNAs for each of the cDNA clones show differential patterns of hybridization during oocyst sporulation with the levels of RNA being low at the start of sporulation (0 hr), increasing to peak levels between 6.5 and 23 hr after the onset of sporulation and, in each case, decreasing to low hybridization levels at 48 hr after initiation of sporulation. These results establish that specific mRNA levels are differentially regulated during sporulation.


Cultivation of excysted metacercariae of Echinostoma caproni to ovigerous adults in the allantois of the chick embryo.

Chemically excysted metacercariae of Echinostoma caproni inoculated into the allantois of domestic chick embryos became ovigerous in that site within 9 days postinoculation. The egg preparation technique of Saville and Irwin was markedly better than that of a modified Zwilling procedure for obtaining large numbers of postinoculation embryos with worm infections. Adults of E. caproni from the allantois were larger and became ovigerous sooner than worms grown on the chorioallantois. Only worms from the allantois produced eggs with fully developed miracidia. Miracidia were released from these eggs, but an insufficient number was available to attempt infections in Biomphalaria glabrata snails.


A gender comparison of health status among users of crack cocaine.

This study examines a population of inner-city crack cocaine users in Miami, Florida. Many study participants were also injection drug users; others were the sexual partners of injection drug users. In general, the self-reported health status of the study population was good, but men perceived their health in a more positive light than did women. HIV-seronegative men were most likely to report excellent or good health, and seropositive women reported the greatest incidence of poor health, regardless of the amount of crack use. Serostatus was statistically significant for women but not for men. Pneumonia was reported more frequently by women, while hepatitis and tuberculosis were reported more frequently by men. There was a significant gender difference in reported endocarditis among light users of crack, with more women that men reporting a history of endocarditis. Among sexually transmitted diseases, men reported more gonorrhea and women reported more syphilis. These gender differences were statistically significant only for heavy users of crack. A gender difference was evident in the HIV seropositivity rates, with 25.7% of men and 32.2% of women testing positive for antibodies to HIV. While this difference held true when frequency of crack use was controlled, the difference was not statistically significant. Women were significantly more likely than men to trade sex for drugs and/or money. Women who were heavy crack users traded most often and would be expected to be at correspondingly increased risk for HIV infection or transmission.


Cultivation of Eimeria tenella in Japanese quail embryos (Coturnix coturnix japonica).

Complete development of Eimeria tenella in Japanese quail embryos was observed. Sporozoites were inoculated into the allantoic cavity of 7-day-old Japanese quail embryos (Coturnix coturnix japonica), after which the infected embryos were incubated at 41 C. In the chorioallantoic membrane mature first generation schizonts, mature second generation schizonts, and gametes were detected at 48 hr postinoculation of sporozoites (PI), 84 hr PI, and 126 hr PI, respectively. Mature gametes and zygotes were found at 132 hr PI, and oocysts were detected at 138 hr PI. Mortality of embryos increased with increment of inoculum size of sporozoites. LD50 was 1.7 x 10(2) sporozoites. Oocyst production was also dependent on inoculum size. Oocysts harvested from embryos sporulated. The oocysts were inoculated into 13-day-old chickens, and oocysts, capable of sporulating normally, were recovered from ceca 7 days after inoculation.


Cocaine use patterns and overdose.

The question of how cocaine overdoses are related to preferred routes of cocaine administration and other aspects of cocaine use patterns is sufficiently complex that very little information is available on it. Even the most extensive information on cocaine overdoses, that of the Drug Abuse Warning Network, is severely limited for purposes of examining this topic. Findings are presented from a 1988-1990 study of a purposive but demographically diverse sample of 699 crack and other cocaine users in Miami, 349 of them interviewed in residential treatment and 350 interviewed on the street. Among these respondents: a history of cocaine overdose is extremely common; overdose episodes do not commonly motivate treatment entry and in some populations are relatively unlikely to result in an emergency room visit; cocaine overdose is less associated with crack smoking than with snorting or intravenous (IV) use, whereas IV use is especially likely to result in overdose; and the street and treatment samples are strikingly different in regard to drug use patterns, overdose history, changes some users made to use patterns as a result of overdose experiences, and reasons given by other users for not making such changes.


Resumption of feeding in vitro by hookworm third-stage larvae: a comparative study.

Third-stage infective larvae of the canine hookworm Ancylostoma caninum resume feeding in vitro in response to several stimuli. Experiments were conducted to characterize the in vitro feeding behavior of several hookworm species. Reduced glutathione and, to a lesser extent, canine and human serum stimulated third-stage larvae of Ancylostoma duodenale to resume feeding. Glutathione-induced feeding reached a maximum by 16 hr and was concentration-dependent between 0- and 15-mM glutathione. Oxidized glutathione and the reducing agents dithiothreitol and L-cysteine failed to induce feeding, suggesting that reducing conditions alone were not stimulatory. Serum incubated with glutathione was the most efficient stimulus for Ancylostoma ceylanicum, Ancylostoma braziliense, and Ancylostoma tubaeforme larvae, whereas Uncinaria stenocephala larvae responded best to canine serum alone. Necator americanus larvae did not resume feeding in response to glutathione, serum, glutathione plus serum, or linoleic acid (0.1-10 mM). These differences in feeding behavior suggest that generalizations concerning hookworm biology must be interpreted cautiously.


Endogenous development of Eimeria intestinalis in rabbits (Oryctolagus cuniculus).

The endogenous life cycle of a pure strain of Eimeria intestinalis was studied by light and electron microscopy in coccidia-free rabbits. Four schizont generations could be observed: the first one, not previously described, was seen between 36 and 144 hr postinoculation (PI), the second one between 64 and 168 hr PI, the third one between 96 and 192 hr PI, and the fourth one between 168 and 240 hr PI. Gamogony apparently started as early as 144 hr PI. Thus, it was possible for oocysts to develop from third generation merozoites, later oocysts developing after the fourth schizont generation. Electron microscopic observation suggested that oocysts were derived mainly from merozoites of the fourth schizont generation. During the first stage of the life cycle, sporozoites were seen in intraepithelial lymphocytes. All asexual generations, except the fourth, were characterized by 2 schizont types: the first, regarded as female, contained mononuclear merozoites and the second, regarded as male, contained polynuclear merozoites.


Crack use and correlates of use in a national population of street heroin users. The National AIDS Research Consortium.

Traditionally, researchers and clinicians have viewed street heroin users as representing an end point in a drug-using career. It is toward this population that major national treatment efforts have been directed. Concomitant with the historical national concern about heroin use has been concern about the increase in crack cocaine use. There has been speculation that crack use may have become a substitute for the higher risk of heroin injection. This article examines the impact of crack use in a national population of heroin users. It was consistently found that there was a correlation between the frequency of crack use and the frequency of speedballing as well as the use of other forms of cocaine, amphetamines, and marijuana. There was also a positive relationship between frequency of crack use and such HIV risk behaviors as renting needles and having a large number of sex partners. The data suggest that in this population of heroin users, crack is not a substitute for heroin but rather is a part of a drug-use pattern that includes an increased use of other drugs and increased high-risk behaviors for contracting HIV.


Infectivity of plerocercoids of Schistocephalus solidus (Cestoda: Ligulidae) and fecundity of the adults in an experimental definitive host, Gallus gallus.

Aspects of the infectivity of the plerocercoid stage and the fecundity of the adult stage of Schistocephalus solidus were examined using the chicken, Gallus gallus, as an experimental host. To investigate size-related infectivity of the plerocercoid stage to a definitive host, a range of plerocercoids (166) were weighed, and each was fed to an individual male chicken. Only a very small percentage of plerocercoids weighing less than 50 mg established compared with in excess of 50% in all other weight classes. To examine the factors affecting the quantity of eggs produced by the adult stage, 15 similar-sized plerocercoids (160-218 mg) were fed to chickens. The majority of plerocercoids administered established as adults and survived until the experiment was terminated on day 7 postinfection (PI). Fecal egg counts indicated that all established worms commenced egg production on day 2 PI with peak output on day 2 or 3 PI. By day 7 PI, egg production in the surviving worms had declined, but it was still evident. The final weight of the adult and the average egg output per worm were unrelated to the initial weight of the infecting plerocercoid. However, the average egg output was predicted by the final adult dry weight and to a lesser extent by the proportion of weight lost in the transition from plerocercoid to adult, but not by the absolute weight loss.


Induction of anti-secretory factor in mice by the nonintestinal parasite Schistosoma mansoni.

Anti-secretory factor (ASF) was determined by the rat intestinal loop model in the pituitary gland and in the blood at various intervals after experimental infection of mice with Schistosoma mansoni. ASF could be detected in the pituitary gland by 6 hr after percutaneous infection with cercariae and in the blood at 24 hr after infection. A peak level was reached 3 days after infection and, after a decline, 2 more peaks were noted between 4 and 8 wk after infection. Characterization of ASF induced by S. mansoni by means of isoelectric focusing revealed 2 distinct peaks at approximately pH 4 and pH 5, respectively. Upon affinity chromatography on agarose, the activity dissociated in a gradient of methyl-alpha-D-glucoside at 1.0 M but not at 0.1 or 0.3 M concentrations.


Differential cardiac histopathology in inbred mouse strains chronically infected with Trypanosoma cruzi.

Seven inbred mouse strains were examined for the presence of chronic Chagas' cardiomyopathy in postacute Trypanosoma cruzi infection. DBA/1, DBA/2, BALB/c, B10.T (6R), B10.Q, B10.D2, and B6 mice were infected for 100 days with the Brazil strain of T. cruzi. Standard histologic examination of cardiac tissue from these mice revealed the following relationship among the different strains based on the severity of observed inflammation (myocarditis): BALB/c, DBA/1, and DBA/2 were the most inflamed; B10.T (6R) and B10.Q were intermediate; and B6 and B10.D2 showed the least inflammation. Examination of these tissues for characteristics of myocardiopathy such as cell swelling, edema, vacuolization, necrosis, myocytolysis, connective tissue infiltration, and thinning of the right ventricular wall indicated a relative relationship among the different strains relative to the severity of cardiomyopathy as follows: BALB/c, DBA/2, and DBA/1 showed the most cardiopathy (pathopermissive); B10.T (6R) and B10.Q showed intermediate pathology; and B6 and B10.D2 showed the least involvement (pathoresistant). Anti-heart antibody present in the sera of all these mice showed specific reactivity in western blots to a 43-kDa glycoprotein from normal heart tissue. Also, anti-heart antibody enzyme-linked immunosorbent assay titers for all mouse strains were similar and showed no correlation with the severity of tissue damage. The fact that different inbred strains show various degrees of myocarditis and cardiomyopathy may be useful in the study of pathogenesis of chronic Chagas' disease. Results from this limited list of inbred strains suggest that background genes, rather than the major histocompatibility complex, play the major role in the expression of cardiac pathogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)


Characterization in vitro and in vivo of resistance to ionophores in a strain of Eimeria tenella.

A field isolate of Eimeria tenella (FS139) was propagated several times in chickens medicated with 200 ppm of dietary monensin. In a laboratory test with 2-wk-old-chickens, the strain was resistant to monensin, salinomycin, and lasalocid given at double use level and was resistant to narasin and maduramicin at the normal use level. In comparison, a laboratory strain (WIS) was controlled by the normal use level of each product. When free WIS sporozoites were treated in vitro with 1.0 microgram/ml of monensin for 0.5 or 4.0 hr at 41 C and inoculated into primary cultures of chicken kidney cells the invasion was reduced by 35.6% or 96.3%, but invasion of FS139 sporozoites was increased by 18.5% by 0.5 hr treatment and was about the same as controls after 2 hr of treatment. Few sporozoites from the WIS strain developed into schizonts, but numerous sporozoites from the FS139 strain developed into normal first and second generation schizonts. The structure of free WIS sporozoites was distorted after 3 hr of treatment with 2.5 micrograms/ml of monensin at 41 C, as observed by light and scanning electron microscopy, whereas there was no change in structure of most treated FS139 sporozoites.


Resistance of Trypanosoma cruzi to blood clearance induced by acute-phase immune mouse serum.

To investigate functional changes in Trypanosoma cruzi parasites induced during their interaction with the vertebrate host, we compared the blood clearance profiles of blood forms isolated from infected normal mice (Reg-Tc) or from infected mice immunodepressed after treatment with cyclophosphamide (Cy-Tc). Parasite blood numbers were measured at various time intervals in animals injected intravenously (i.v.) with 1-2 x 10(6) T. cruzi of either isolate. In the absence of added immune sera (spontaneous clearance), Reg-Tc and Cy-Tc were cleared from blood at similar rates. However, when acute immune mouse serum (Ac-IMS) was injected i.v. 2 min after inoculation of parasites, a significant proportion of Cy-Tc only was cleared from the blood an hour later, whereas Reg-Tc were not, their clearance profile being identical to that observed in mice injected with normal mouse serum. Cy-Tc susceptibility to Ac-IMS was not the result of a toxic effect of cyclophosphamide over T. cruzi as parasites recovered from animals immunodepressed by irradiation before infection were cleared similarly by acute serum. Contrary to Ac-IMS, chronic immune mouse serum induced similar rates of disappearance of Reg-Tc and Cy-Tc from blood. Our results suggest the occurrence of T. cruzi selection or modification during the acute phase, which leads to an increased parasite resistance to the clearance properties of acute-phase antibodies.


Population structure of Lankatrematoides gardneri (Digenea: Opisthotrematidae) in the pancreas of the dugong (Dugong dugon) (Mammalia: Sirenia).

The distribution among size and reproductive classes of the digenean Lankatrematoides gardneri was recorded from the pancreatic ducts of 41 dugongs from the Gulf of Papua, Papua New Guinea. Infrapopulation sizes ranged from 5 to 921 worms and showed no correlation with host age, sex, or month of capture. Immature worms tended to be concentrated in intermediate size classes, the largest immatures being no more numerous than matures. The mean proportion of mature worms in the 29 infrapopulations containing them was small (9.8%). Mature worms were significantly greater in mass than the largest immatures. There is evidence of an interaction between the presence or absence of mature worms and the distribution of immatures among classes.


Parasites of cottontail rabbits of southern Illinois.

Fifteen species of parasites including Haemaphysalis leporispalustris, Ixodes dentatus, Amblyomma americanum, Cediopsylla simplex, Odontopsyllus multispinosus, Cuterebra sp., Obeliscoides cuniculi, Trichostrongylus calcaratus, Trichostrongylus affinis, Longistriata noviberiae, Dermatoxys veligera, Trichuris sp., Mosgovoyia sp., Taenia pisiformis, and Hasstilesia tricolor as well as coccidia oocysts were collected from 96 cottontail rabbits (Sylvilagus floridanus) confined to a pen in southern Illinois in 1983 and 1984. The diversity of parasites and the intensities of infections were similar to published reports on free-ranging populations. Most variations in parasite abundances were attributable to season. Few lesions were seen in association with parasitism.


Allozymic and biological characters of Trichinella pseudospiralis isolates from free-ranging animals.

To evaluate biological and biochemical variability in nonencapsulated Trichinella isolates, biological and allozymic studies were conducted on isolates of Trichinella collected from a raptoral bird (Aquila rapax) and a fox (Vulpes corsac) in Kazakhstan and from a dasyurid marsupial (Dasyurus maculatus) on the island of Tasmania, Australia. Allozyme profiles of bird and marsupial isolates showed close similarity with the type isolate of Trichinella pseudospiralis. The avian and fox isolates successfully interbred with the type T. pseudospiralis isolate, but they failed to interbreed with 3 encapsulating species, Trichinella spiralis, Trichinella nativa, and Trichinella britovi. The reproductive index assessed in 4 inbred and 1 outbred strains of mice was lower for the avian isolate than for the marsupial and the type T. pseudospiralis isolates (P < 0.001).


Collection of eggs and hatching and culturing second-stage larvae of Toxocara vitulorum in vitro.

Eggs of Toxocara vitulorum were harvested from the feces of infected buffalo calves and embryonated in vitro. Optimum conditions for hatch and culture of the second-stage larvae were determined. Maximum hatch of larvae occurred from eggs that were decoated by treatment with saturated Ca(OCl)2 for 16-24 min followed by treatment with CO2 and incubation at 37 C. Larvae could be cultured in RPMI-1640 medium for up to 3 mo but survived for only 3 wk in Eagle's minimum essential medium.


Further evidence that the genes controlling susceptibility of Aedes aegypti to filarial parasites function independently.

Comparisons were made of in vivo labeled polypeptides from Aedes aegypti strains refractory to either Brugia malayi or Dirofilaria immitis. There does not seem to be a generalized "anti-parasite" polypeptide response that mosquitoes refractory to filarial worm infection produce following bloodfeeding. Instead, it seems that any response produced by these mosquitoes is localized to the tissue in which the filarial parasite develops.


A bioassay for mefloquine.

A bioassay method that allows for the estimation of serum concentrations of mefloquine is presented. Concentrations obtained by bioassay and high performance liquid chromatography showed a good correlation. This bioassay should be helpful in assessing prophylactic/treatment failures to mefloquine under field conditions.


Differentiation of Rhipicephalus ticks (Acari: Ixodidae) by gas chromatography of cuticular hydrocarbons.

Gas chromatography of the cuticular hydrocarbons of 4 species of ticks belonging to the genus Rhipicephalus (R. sanguineus, R. turanicus, R. pusillus, and R. bursa) showed a unique pattern for each taxon. The hydrocarbon fractions were composed of a mixture of straight-chain, terminally methylated, and internally branched alkanes; however, only a small quantity of alkenes was detected. Freshly collected, dried, and alcohol-stored specimens of R. sanguineus were analyzed and their patterns found to be nearly identical. Collection of specimens from separate localities demonstrated a species-specific pattern for Spanish material.


On-site diagnosis of Plasmodium falciparum, P. vivax, and P. malariae by using the Quantitative Buffy Coat system.

The Quantitative Buffy Coat (QBC) system was used for the detection and identification of malaria parasites in blood specimens from 570 residents of Oksibil, an isolated highland valley in the eastern Jayawijaya Mountains of Irian Jaya (Indonesian New Guinea). The availability of a battery-powered centrifuge and a fiberoptic Paralens enabled us to complete and interpret the assay in this remote environment. Of 322 QBC tubes examined for 2-4 min each, results of 295 (92%) concurred with findings on the matched Giemsa-stained thick smear (GTS). The 27 discrepant results included 13 QBC+/GTS- that, upon reexamination, were found to be GTS+. When using the corrected GTS results as the standard, the sensitivity and specificity of the QBC were 94% and 96%, respectively. Because electricity was available only 3 hr per day, it was decided to decrease the examination for an additional 248 QBC to a maximum of 90 sec per tube. This shortened inspection time resulted in a reduction of sensitivity to 53% but specificity was preserved at 89%. Forty-two of 45 conflicting results, QBC-/GTS+ from cases of light Plasmodium falciparum infections with < 1 trophozoite or gametocyte per field, were resolved by reexamination of the QBC in the laboratory. Tubes held at 4 C could be reexamined, without noticeable loss of fluorescence, for at least 6 wk after collection. Despite some difficulty in the identification of Plasmodium species, it was concluded that the QBC is an easy, sensitive method for the rapid diagnosis of malaria in the field and that it provides the inexperienced microscopist with an additional means for on-site identification of individuals needing treatment.


Schistosome antigen gp50 is responsible for serological cross-reactivity with Trichinella spiralis.

The 50-kDa component (gp50) present in Schistosoma mansoni eggs and secretions of the various life stages of the parasite was recognized by experimentally infected mice and by humans with S. mansoni, Schistosoma haematobium, and Schistosoma japonicum infection. All sera reacting with crude S. mansoni-soluble egg antigens (SEA) also reacted strongly with gp50 in enzyme-linked immunosorbent assay. No reactivity against gp50 was seen with sera from individuals without schistosomiasis, with the exception of sera from patients with Trichinella spiralis infection. All of 10 sera from patients with trichinellosis also reacted with schistosomes by immunofluorescence essentially recognizing testes, ovaries, ootype epithelium and ducts of the reproductive system. Cross-reacting antigens were seen in T. spiralis hypodermis, stichocytes and possibly germinal primordia using anti-gp50 monoclonal antibodies and anti-gp50-positive schistosomiasis patient sera. The results suggest that the anti-gp50 antibody response constitutes a significant part of the anti-SEA antibody response in infected individuals and is a major reason for the previously recognized serological cross-reactivity between T. spiralis and schistosome species.


Cystic fibrosis: a new perspective in genetic counseling.

Recent developments in DNA technology mean that all individuals can be tested to identify whether they carry one of the known mutations for cystic fibrosis. This testing will allow people to know whether they are at risk to have a child with cystic fibrosis. However, this knowledge has the potential to create harm if the testing programs are not managed carefully. Implications of this new technology for nurses and the general public are discussed.


Breast-feeding problems and telephone consultation.

Parents and health care providers may have difficulty obtaining accurate and current information for the management of breast-feeding concerns. This study documents the types of problems that lead family members and health care professionals to seek telephone consultation from a breast-feeding service managed as an activity of a school of nursing faculty practice. During the 6-month study period, calls from 387 individuals (64% mothers and 31% health care providers) were received, for a mean of 64 calls per month. These calls required approximately 9.5 hours monthly to manage. Thirty-one percent of the calls were requests for general information (including stooling and urination or frequency and duration of breast-feeding); an additional 24% requested consultation from or referral to the service. Twenty-five percent of the calls resulted in a consultation with either the clinicians (9.9% inpatient; 9.6% outpatient) or referral to another health care professional (6%). Suggestions for pediatric nurse practitioner practice with breast-feeding mothers and babies were developed from the results of this clinical study.


The genogram: a strategy for assessment.

One of the strongest components of the role of the pediatric nurse practitioner (PNP) is that of assessing pediatric clients and their families. Many tools have been developed to assist the PNP in assessing family relationships and dynamics to formulate plans of care that promote physical and mental health. This article explores the use of the genogram as a tool for successful family assessment. A case study is presented to guide the PNP to incorporate the technique into the practice setting.


Utility of Fourier transform-Raman and Fourier transform-infrared diffuse reflectance spectroscopy for differentiation of polymorphic spironolactone samples.

Thirteen bulk pharmaceutical preparations of spironolactone were examined by Fourier transform (FT)-Raman spectroscopy and by diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) for residual solvents (including the hydrolysis product, thioacetic acid), the presence of enolic tautomeric forms, and evidence for different polymorphic forms. One sample (L) only was found to contain solvent residue (benzene). No evidence for the possible existence of enolic tautomers in the solid state was found. From these specimens, four different representative polymorphic samples (A, B, C, and D) were selected on the basis of their DRIFTS patterns in the 3600-3200-cm-1 region. Samples K and L were considered to represent mixtures of two or more of the above representative types. Similar differentiation of the samples was made on the basis of their Raman spectra over the frequency range 1800-400 cm-1. The various fundamental stretching frequencies for the C = O and C = C bonds have been assigned, and these assignments, in turn, were used to account for all the bands in the 3600-3200-cm-1 region as overtone and combination frequencies of the fundamentals. The Raman lines at 637 and 655 cm-1 were assigned to the two C-S stretching modes of the thioacetyl moiety.


The fear of healthy eating: understanding the paranoia.

Scientific research continues to point to the health benefits of including more fruits and vegetables in the diet. At the same time, some groups claim that pesticides used in their production pose significant health risks. This article reviews some of the position statements, describes the principles of risk and hazard assessment, and identifies regulatory processes to assure the safe use of pesticides.


Evaluation of cytotoxicity of some Mannich bases of various aryl and arylidene ketones and their corresponding arylhydrazones.

Mannich bases were synthesized and converted to the corresponding arylhydrazones. X-ray analysis of a ketone (1a) and a hydrazone (4d) revealed structural features of interest. All of the compounds showed cytotoxicity toward murine lymphocytic leukemia L1210 cells in the 4.9-25.0-microM range. The correlation coefficients generated by plotting the IC50 values (the concentrations of compounds that inhibit the growth of tumors by 50%) of some hydrazones against certain electronic, hydrophobic, and steric constants of the aryl substituents indicated only weak correlations. A few ketones and hydrazones displayed significant cytotoxicity to the WiDr human colon cancer cells, and these derivatives, especially the ketones, may serve as prototypes for future drug development. The KB tumor (a human epidermoid carcinoma of the nasopharynx) was somewhat refractory to selected compounds. In an in vitro assay conducted by the National Cancer Institute and involving approximately 53 tumor cell lines originating from eight neoplastic diseases, 65% of the compounds showed some selectivity toward one or more groups of cancers, principally leukemia, melanoma, and colon cancer. The bioevaluation of the ketones and hydrazones against the L1210, WiDr, and KB tumors, as well as evidence from proton nuclear magnetic resonance studies did not support the suggestion that hydrazones may be prodrugs of the corresponding ketones.


Cardiovascular risk stability: from grade school to high school.

School-based, cardiovascular risk reduction programs have increased dramatically over the past decade. Though a wide range of evaluation plans have been implemented, limited longitudinal data are available to estimate the effectiveness of these risk reduction programs. The purposes of this study were to describe the stability of risk factors, the changes in cardiovascular risk from grade school to high school, and the differences in risk between gender. The sample (N = 195) of high school students was developed from three cohorts of elementary school students who participated in a risk reduction program in the sixth grade. Three to six years had elapsed since the students participated in the risk reduction program, thus providing a longitudinal view of participants' risk. Subject risk for obesity and high cholesterol level was stable although significant changes were noted for heart rate recovery and blood pressure. The only gender difference in risk was for elevated cholesterol level among female students. Nursing implications are presented.


In vitro release of nitroglycerin from topical products by use of artificial membranes.

An in vitro testing method for measuring the release of nitroglycerin from topical drug products was evaluated. The method involved measuring the amount of nitroglycerin that diffused from ointments and patches through various synthetic membranes into receptor fluid contained in a modified Franz diffusion cell. Plots of the amount of nitroglycerin released against the square root of time for all 10 synthetic membranes were linear. Five membranes (group I) were found to release nitroglycerin at similar rates (difference not significant; p > 0.05). Use of the other five membranes (group II) in diffusion cells resulted in release rates significantly slower than those of group I membranes (p < 0.05). Rapid permeation of nitroglycerin from a solution through a polysulfone membrane demonstrated a lack of significant diffusion barrier properties of this membrane. Rates of release of nitroglycerin from commercially available ointments were found to be similar. A comparison of three commercial nitroglycerin patches revealed that these products released nitroglycerin at different rates in vitro.


Molecular modeling of beta-cyclodextrin complexes with nootropic drugs.

The geometry and structural features of the inclusion complexes of beta-cyclodextrin (beta-CD) with the chiral antiamnesic drugs (+/-)-1-benzyl-4-hydroxymethylpyrrolidin-2-one (WEB-1868). (+/-)-1-benzenesulfonyl-5-ethoxypyrrolidin-2-one (RU-35929), and (+/-)-1-(3-pyridinlysulfonyl)-5-ethoxypyrrolidin-2-one (RU-47010) were studied by the molecular modeling method (MacroModel interactive computer program). Docking procedures yielded the most stable complexes, which showed the aromatic ring of the guests inside the cavity and the pyrrolidinone ring out from the side of the beta-CD secondary hydroxyl groups. The binding energies were essentially due to hydrogen-bonded structures involving the C=O group of the guests. Selective interactions allowed chiral discrimination, and accordingly, separate beta-CD complexes of the R and S enantiomers of each guest compound were studied. The almost round beta-CD structure, in all the cases, assumed an elliptic shape on passing from the isolated molecule to the docked complex. The optimized structures and conformations of beta-CD and its inclusion compounds showed acceptable general agreement with information from proton nuclear magnetic resonance studies.


Proton nuclear magnetic resonance spectroscopy studies of the inclusion complex of piroxicam with beta-cyclodextrin.

Proton nuclear magnetic resonance spectroscopy showed that piroxicam sodium salt forms an inclusion complex with beta-cyclodextrin in aqueous solution. The 1:1 stoichiometry of the complex was determined by the continuous variation method. Significant nuclear Overhauser effects were observed between the inner protons of beta-cyclodextrin and protons of both the aromatic rings of piroxicam sodium salt, a result indicating that two isomeric 1:1 complexes must be present in solution within the range of concentrations investigated. The overall association constant was 113 M at 298 K. At concentrations less than 1.0 x 10(-3) M, the complex is completely dissociated.


Oral bioavailability of griseofulvin from aged griseofulvin:lipid coprecipitates: in vivo studies in rats.

The bioavailabilities of aged coprecipitates of griseofulvin (Gris), dimyristoylphosphatidylcholine (DMPC), or egg phosphatidylcholine (EPC) and cholesterol (CHOL) in rats and correlations with their in vitro dissolution behaviors were determined. In vivo absorption studies of Gris:DMPC (4:1, w/w) or Gris:DMPC:CHOL [4:1(1:0.33 mole ratio)] coprecipitates yielded evidence of a 40% increase in the peak concentration in plasma (Cmax) and a 2.5- to 3-fold decrease in the time to reach Cmax (tmax), compared with those obtained with micronized Gris but a statistically unchanged area under the concentration in plasma--time curve (AUC) when 1-day-aged samples at equivalent doses were used. On the other hand, a 10% decrease in the AUC, a 20% increase in the Cmax, and a three- to fourfold decrease in the tmax were observed for the same formulations aged for 90 days. In comparison, the Cmax produced by the 1-day-aged Gris:EPC:CHOL [4:1(1:0.33 mole ratio)] coprecipitate was the same as that produced by micronized Gris, but the tmax and the AUC were significantly lower; the Cmax produced by the 90-day-aged coprecipitate was 30% higher than that produced by micronized Gris, but the tmax and the AUC remained unchanged. The Gris concentrations after 5 and 30 min (dissolution parameters) and the percent dissolution efficiency also showed excellent correlations with the concentration in plasma after 1 h, the Cmax, and the AUC (in vivo parameters) for all formulations, but the individual in vitro parameters showed poor correlations with the AUC results.(ABSTRACT TRUNCATED AT 250 WORDS)


Gastric emptying of tablets and granules in humans, dogs, pigs, and stomach-emptying-controlled rabbits.

Rates of gastric emptying of nondigestible tablets and granules in humans were compared with those in three animal models: dogs, minipigs, and stomach-emptying-controlled rabbits. The rates of gastric emptying of both dosage forms in dogs tended to be faster than or similar to those in humans, whereas the rates in pigs were slower. In stomach-emptying-controlled rabbits, no tablets were emptied from the stomach because of their large size. The rate of gastric emptying of granules in rabbits was slow and variable. Food delayed gastric emptying in dogs, especially for tablets. In rabbits, the rate of gastric emptying of granules was faster when the granules were given before feeding, in comparison with that after feeding or under fasting conditions. We concluded that the dog is a better animal model for bioavailability studies under fasting conditions than the pig and the rabbit.


Simultaneous determination of otilonium bromide and diazepam by first-derivative spectroscopy.

A rapid, simple assay procedure was developed for simultaneous analysis of otilonium bromide, a smooth-muscle relaxant, and diazepam in tablets containing 20 mg of otilonium bromide and 2 mg of diazepam (20:2 tablets) or 40 mg of otilonium bromide and 2 mg of diazepam (40:2 tablets) by "zero-crossing" first-derivative spectroscopy. The tablets were dissolved in 0.01 N HCl, mixtures were centrifuged at 3500 rpm (2472 x g) for 5 min, and first-derivative spectra were recorded. The absolute values of the derivative were measured at 264 nm for determination of otilonium bromide and between 406 and 408 nm (380 nm for analysis of 40:2 tablets) for determination of diazepam. The method is linear, quantitative, and reproducible and can also be used for the tablet dissolution test. Ten tablets of the same batch were analyzed by the described method and by a high-performance liquid chromatographic method, and the results were in good agreement.