Multiple frequency tympanometry: effects of ear canal volume compensation on static acoustic admittance and estimates of middle ear resonance

Three methods for compensating multiple frequency acoustic admittance measurements for ear canal volume were studied in 26 men with normal middle ear transmission systems. Peak compensated static acoustic admittance (magnitude of y) and phase angle (phi) were calculated from sweep frequency tympanograms (226-1243 Hz in 113 Hz increments). Of the procedures used to compensate for volume in rectangular form, the ear canal pressure used to estimate volume had the largest effect on the estimate of middle ear resonance. Median resonance was 800 Hz for admittance measurements compensated at 200 daPa versus 1100 Hz for measurements compensated at -350 daPa. The remaining two methods, compensation of susceptance only versus both susceptance and conductance and compensation using the minimum volume versus separate volumes at each frequency, did not affect estimates of middle ear resonance. Estimates of middle ear resonance from compensated phase angle measurements also were compared with estimates of resonance from admittance and phase difference curves. Although resonance could not be estimated from the phase difference curve, resonance estimated from the admittance difference curve agreed with the estimate from compensated phase angle.     

Admittance tympanometry in otosclerotic ears

Twenty-eight surgically confirmed otosclerotic ears were evaluated to determine whether tympanometric admittance measurements could differentiate otosclerosis from a normal population. Subjects were tympanometrically measured at test conditions B220, B660, G220 and G660 Hz. When comparing mean curve peak amplitude to normative standards, 20 ears showed significantly low admittance tympanograms. Further investigation revealed no significant differences in curve width or pressure of the curve peak. Of the remaining eight otosclerotic ears, all produced diphasic "W"-notched tympanometric configurations. Diagnostic implications and physiological hypothesis are discussed.     

Standard and multifrequency tympanometry in normal and otosclerotic ears

OBJECTIVES: The primary goal of this study was to evaluate alternative tympanometric parameters for distinguishing normal middle ears from ears with otosclerosis. A secondary goal was to provide guidelines and normative data for interpreting multifrequency tympanometry obtained using the Virtual 310 immittance system. DESIGN: Nine tympanometric measures were examined in 68 normal ears and 14 ears with surgically confirmed otosclerosis. No subjects in either group had a history of head trauma or otoscopic evidence of eardrum abnormalities. Two parameters, static admittance and tympanometric width, were derived from standard low-frequency tympanometry and two parameters, resonant frequency and frequency corresponding to admittance phase angle of 45 degrees (F45 degrees), were derived from multifrequency tympanometry. RESULTS: Differences between normal and otosclerotic ears were statistically significant only for resonant frequency and F45 degrees. Group differences in resonant frequency were larger when estimated using positive tail, rather than negative tail, compensation. Group differences in both resonant frequency and F45 degrees were larger when estimated from sweep frequency (SF), rather than sweep pressure, tympanograms. Test performance analysis and patterns of individual test performance point to two independent signs of otosclerosis in the patient group; 1) an increase in the stiffness of the middle ear, best indexed by F45 degrees derived from SF recordings, and 2) a change in the dynamic response of the tympanic membrane/middle ear system to changes in ear canal pressure, best indexed by tympanometric width. Most patients were correctly identified by only one of these two signs. Thus, optimal test performance was achieved by combining F45 degrees derived from SF recordings and tympanometric width. CONCLUSIONS: The findings confirm the advantage of multifrequency tympanometry over standard low-frequency tympanometry in differentiating otosclerotic and normal ears. Recommendations for interpreting resonant frequency and F45 degrees measures obtained using the Virtual Immittance system are also provided. In addition, the relationship among different tympanometric measures suggests a general strategy for combining tympanometric measures to improve the identification of otosclerosis.     

Interactions among tympanometric variables

To gain a better understanding of tympanometric results that have been difficult to interpret, such as asymmetrical and W-shaped tympanograms, acoustic susceptance and conductance tympanograms were measured from subjects with normal hearing and from subjects with well-defined middle ear pathology. Acoustic reactance, resistance, and impedance were computed and predicted from the measured data. Asymmetrical tympanograms derive in large part from the marked asymmetry in acoustic resistance as a function of ear canal pressure. W-shaped tympanograms result from interactions between reactance and resistance that occur when the two quantities assume similar absolute values or when reactance is mass controlled. A criterion for distinguishing between W-shaped tympanograms that are normal from those that are abnormal is discussed.     

Acoustic mechanisms: canal wall-up versus canal wall-down mastoidectomy

The contribution of the middle ear air spaces to sound transmission through the middle ear in canal wall-up and canal wall-down mastoidectomy was studied in human temporal bones by measurements of middle ear input impedance and sound pressure difference across the tympanic membrane for the frequency range 50 Hz to 5 kHz. These measurements indicate that, relative to canal wall-up procedures, canal wall-down mastoidectomy results in a 1 to 5 dB decrease in middle ear sound transmission below 1 kHz, a 0 to 10 dB increase between 1 and 3 kHz, and no change above 3 kHz. These results are consistent with those reported by Gyo et al. (Arch Otolaryngol Head Neck Surg 1986;112:1262-8), in which umbo displacement was used as a measure of sound transmission. A model analysis suggests that the reduction in sound transmission below 1 kHz can be explained by the smaller middle ear air space volume associated with the canal wall-down procedure. We conclude that as long as the middle ear air space is aerated and has a volume greater than 0.7 ml, canal wall-down mastoidectomy should generally cause less than 10 dB changes in middle ear sound transmission relative to the canal wall-up procedure.     

The effect of tonsillectomy on eustachian tube function

A two-part study was designed to investigate the effect of tonsillectomy on eustachian tube function and to identify if any change is related to postoperative pain. Middle ear pressure was measured by tympanometry and results were classified as type A (+50 daPa to -99 daPa), type B (flat) or type C (-100 daPa to -350 daPa). Thirty-one patients with type A tympanograms, undergoing tonsillectomy enrolled in study A. Patients had tympanometry the next day and filled in a questionnaire incorporating visual analogue pain scores. In study B, 30 patients underwent a similar protocol and were followed up at 1 week tympanometry and a questionnaire. A control group of 26 patients undergoing appendicectomy was recruited. Follow-up was available on 23 patients from study B. Combining A and B, on the first postoperative day 39% of patients developed type C tympanograms. No member of the control group developed any change in middle ear pressure. There was no significant relationship between pain scores for throat pain or otalgia and the development of negative middle ear pressure. By day 7 all patients had type A tympanograms. Otalgia was a delayed symptom significantly associated with increased throat pain. Transient negative middle ear pressure commonly occurs following tonsillectomy.     

Factors influencing pressurization of the femoral canal during cemented total hip arthroplasty

Successful cement pressurization with total hip arthroplasty depends on the capacity of the cement gun and its ability to pressurize the canal and the integrity of the intramedullary plug and the proximal seal used to contain the cement bolus during pressurization. In the laboratory, the authors measured the volume of cement delivered by two cement guns (from Zimmer, Warsaw, IN, and Howmedica, Rutherford, NJ) in comparison with typical values for the volume of the medullary canal following standard surgical preparation. The two cement guns studied delivered 93 and 138 mL cement, respectively. In comparison, the volume of the intramedullary canal ranged from 35 to 70 mL using a standard femoral prosthesis (Precision Hip System, Howmedica). Peak pressures developed during cement injection using the cement guns were 73.6 +/- 27.1 psi for the Zimmer system and 47.3 +/- 16.9 psi for the Howmedica system. Both devices were able to sustain a minimum pressure of at least 6.5 psi through cementing when used in conjunction with a flexible pressurizing seal. The mechanical performance of five designs of intramedullary plugs was assessed by monitoring plug displacement during cement pressurization in reamed cortical specimens. The performance of each device was judged by its ability to withstand cement pressures of 50 psi without displacement within the medullary canal. On the basis of this test, the probability that these plugs would exceed this criterion when used with the femur was estimated to range from 24 to 94%. Few of the commercially available plugs were able to withstand cement pressures routinely generated using standard cement delivery systems.     

Correlation between ear canal resonance and tympanic membrane impedance in relation to age and body mass and postmortem changes

The human temporal bone preparation is an acknowledged model for research of the physical processes affecting the outer ear canal and eardrum. Changes affecting the oscillation and resonance behavior of the tympanic membrane and ear canal between death and temporal bone preparation presently exist in only a few studies. Since the influence of age and physique, as well as the width of ear canal on the ear canal resonance may be important, we prepared two separate studies to analyze these questions. The goal of our first test series involved children and was devised to determine if changes in the outer auditory canal resonances differed according to age. In so doing, canal resonance was recorded with a real ear measurement system. Further, we recorded middle ear pressure, impedance of the tympanic membrane, ear canal volume, height, weight and surface of the body, head and ear size. We found a significant decrease in the resonance frequency of the outer ear which was age-dependent and was 2.75 kHz in the 7-year-old child. In a separate study we wanted to know if results found in the postmortem temporal bone reflected in vivo relationships. A tympanometer and real ear measurement system was used to test the resonance behavior of the auditory canal as well as the vibration of the eardrum in dependence on temperature and the time after death for 9 h. We then proved the absence of significant changes in the auditory canal and eardrum oscillation in this time period before possible postmortem changes occurred. Our findings show that the method of bone preservation after its preparation is decisive for the validity of measurements in the isolated human temporal bone.     

The effects of attenuation of frequency segments on binaural localization of sound

Perceived location of tonal stimuli d and narrow noise bands presented in two-dimensional space varies in an orderly manner with changes in stimulus frequency. Hence, frequency has a referent in space that is most apparent during monaural listening. The assumption underlying the present study is that maximum sound pressure level measured at the ear canal entrance for the various frequencies serves as a prominent spectral cue for their spatial referents. Even in binaural localization, location judgments in the vertical plane are strongly influenced by spatial referents. We measured sound pressure levels at the left ear canal entrance for 1.0-kHz-wide noise bands, centered from 4.0 kHz through 10.0 kHz, presented at locations from 60 degrees through -45 degrees in the vertical plane; the horizontal plane coordinate was fixed at -90 degrees. On the basis of these measurements, we fabricated three different bandstop stimuli in which differently centered 2.0-kHz-wide frequency segments were filtered from a broadband noise. Unfiltered broadband noise served as the remaining stimulus. Localization accuracy differed significantly among stimulus conditions (p < .01). Where in the vertical plane most errors were made depended on which frequency segment was filtered from the broadband noise.     

Sodium sensitivity in young adults with high resting end-tidal CO2

BACKGROUND: Previous research with normotensive adults aged over 40 years ('older') found that sensitivity of blood pressure of subjects with high resting end-tidal partial pressures of CO2 to high sodium intake was greater than normal. OBJECTIVE: To test the hypothesis that the lesser sensitivity of blood pressure of young normotensive adults to high sodium intake is also a function of resting end-tidal partial pressure of CO2. DESIGN: Forty-eight Caucasian men and women (age 28.5 +/- 1.4 years) had a lower than normal dietary intake of sodium chloride for 4 days, and then ingested sodium chloride capsules for 7 days (an additional 190 mmol/day sodium chloride). Resting end-tidal partial pressure of CO2 and blood pressure, and 24 h ambulatory blood pressure, were measured before and after the high-sodium diet. Overnight urine samples were collected before and after the high-sodium diet to determine dietary compliance, and to assess changes in urinary excretion of endogenous digitalis-like factors (a ouabain-like factor, and a marinobufagenin-like factor) that covary with plasma volume. RESULTS: Subjects with high end-tidal partial pressures of CO2 had lower resting heart rates and lower urinary excretion of ouabain-like factor before sodium loading. Sodium loading decreased mean partial pressure of CO2 (by 0.8 +/- 0.2 mmHg) and increased only ambulatory systolic blood pressure (by 2.1 +/- 0.8 mmHg) for the whole group. However, the changes in resting systolic (r = 0.32, P < 0.025) and diastolic (r = 0.36, P < 0.01) blood pressures and in 24 h systolic (r = 0.28, P < 0.05) blood pressure after sodium loading were all positive functions of individual resting end-tidal partial pressures of CO2. Sodium loading increased urinary excretion of marinobufagenin-like factor (by 1.78 +/- 0.88 nmol) and the magnitude of the individual increase was a function of end-tidal partial pressure of CO2. CONCLUSIONS: The results indicate that a high resting partial pressure of CO2 augments the effects of high sodium intake on plasma volume, levels of endogenous digitalis-like factors, and blood pressure in young normotensive humans.     

Tympanometric detection of middle ear effusion in infants and young children

Tympanometry, a test of middle ear status new to clinical pediatrics, was carried out on 280 subjects, 10 days through 5 years of age. The tympanograms obtained were compared with otoscopic findings and, in 107 of the subjects, with findings at myringotomy. Seven distinct tympanometric curve types were identified and defined, based on their degree of correlation with the presence or absence of middle ear effusion. In subjects 7 months of age and older, curves suggesting normal (high) tympanic membrane compliance in combination with atmospheric or near-atmospheric middle ear air pressure were rarely associated with effusion. Conversely, curves suggesting low tympanic membrane compliance were highly correlated with the presence of effusion. Curves suggesting intermediate compliance or reduced middle ear air pressure were also correlated with effusion, but the degree of correlation was dependent on the shape of the curve. In infants less than 7 months of age, many of the ears with effusion had "normal" tympanograms, presumably because external auditory canal walls in such infants tend to be highly distensible. Tympanometry is a simple, rapid, atraumatic, valid, and objective test, easily administered by paraprofessional personnel. Its use can result in improved detection of middle ear effusion and other middle ear abnormalities, and also appears to promote improvement in diagnostic acumen.     

Rat utricular macula: blood flow and stereological assessment of capillary morphology

Vascular compromise has long been proposed as a cause of inner ear disorders. However, the examination of blood flow and its control mechanisms in the vestibular system has been very limited. Combining stereological techniques with the microsphere injection technique, capillary morphology and regional blood flow were determined for the rat utricular macula. Results are as follows: total utricular blood flow 0.158 +/- 0.078 microL/min; blood flow to the neuroepithelium (excluding nerve) 0.0995 +/- 0.046 microL/min; blood flow per unit volume 7.71 +/- 4.31 microL/min per cubic millimeter, neuroepithelial volume 0.01344 +/- 0.0018 mm3; absolute capillary surface area 0.159 +/- 0.039 mm2; mean capillary diameter 5.84 +/- 0.56 microns; absolute capillary length 8.45 +/- 1.6 mm; and capillary lumen volume fraction 0.0175 +/- 0.004. Comparisons to previous data for the posterior canal ampulla indicate that the capillary diameter in the rat utricular macula is smaller; the capillary length is greater; and the end organs are similar with respect to neuroepithelial volume, capillary surface area, and blood flow. The size of the microsphere used in the present study (9.21 microns), in comparison to the mean capillary diameter (5.84 microns) of the utricular neuroepithelium, would indicate that the blood flow data likely represent a minimum value. These findings indirectly indicate that the utricular macula metabolic rate is greater than that of the posterior canal crista, and that there is variation from end organ to end organ in mean capillary diameter.     

Mean systemic pressure and mean pulmonary pressure: their effects on the total artificial heart

Mean systemic pressure (MSP) and mean pulmonary pressure (MPF), which are mean driving pressures for venous return in the natural heart, were studied in 11 calves in which the natural heart had been replaced with a total artificial heart (TAH). They were measured simply by stopping the artificial heart pumping. Although blood translocation from the arterial to the venous side was not performed, the eventual right and left atrial pressures reached six to eight seconds after stopping the TAH would represent MSP and MPP with reasonable accuracy. The MSP varied from nine to 3k mmHg (20+/-6 mmHg), whereas the MPP varied from nine to 39 mmHg (22+/-7 mmHg). The MSP varied in close relation to the right atrial pressure prior to cessation of the TAH (r=0.9124). Increases in RAP and MSP were mainly attributed to an increase in circulating blood volume. In the performance of the TAH, MSP (or MPP), proper diastolic duration and vacuum application during diastole was of prime importance in determining the end-diastolic ventricular volume.     

The measurement of the lateralization of narrow bands of noise using an acoustic pointing paradigm: the effect of sound-pressure level

The effects of varying interaural time delay (ITD) and interaural intensity difference (IID) were measured in normal-hearing subjects as a function of eleven frequencies and at sound-pressure levels (SPL) from 60 to 90 dB SPL and at 25-dB sensation level. Using an "acoustic" pointing paradigm, the IID of a 500-Hz narrow-band (100 Hz) noise (the "pointer") was varied by the subject to coincide with that of a "target" ITD stimulus. ITDs of 0, +/- 200, and +/- 400 microseconds were obtained through total waveform delays of narrow-band noise (NBN), including envelope and fine structure. The results of this experiment confirm the traditional view of binaural hearing for like stimuli: There is little perceived displacement away from 0 IID at frequencies of 1250 Hz and above. In the low frequencies, subjects required IIDs greater than the expected 10 dB to perceive a fully lateralized image, and they varied in the maximum value of IID that they required, regardless of frequency. Our subjects did not always perceive the intracranial locations of ITD targets symmetrically: When the signal was delayed to one ear, the resultant matching IID was often different in magnitude than for the same ITD target delayed to the opposite ear for the identical frequency. The results of two subjects suggested that people with asymmetric normal hearing have adapted to their asymmetry for lateralization tasks: The subjects were found to lateralize toward the ear with the greater SPL stimulus, regardless of the ear to which the signal was delayed, when signals of equal SL were presented, and toward the leading ear when signals of equal SPL were presented (unequal SL). Increasing the presentation levels above 60 dB SPL had an effect on the perception of high-frequency ITD targets: As the intensity level increased, the slopes of the IID versus ITD functions increased indicating better discrimination of ITD. This study is in agreement with other studies in providing strong evidence of individual differences in lateralization experiments. These individual differences might be attributable to differential sensitivity to ambiguous time stimulus cues, differential task sensitivity, age effects, threshold asymmetries, or criterion variability.     

Studies on supratentorial subdural bleeding using a porcine model

A porcine model for an acute lethal arterial subdural bleeding in man is presented. Blood from the abdominal aorta was led via an electronic drop recorder into a collapsed intracranial subdural rubber balloon. Systemic arterial pressure (SAP), two intracranial pressures and 6 other vital parameters were monitored continuously in spontaneously breathing (n = 4) and mechanically ventilated (n = 4) pigs. In both animal groups bleeding caused an immediate rise in intracranial pressures (ICP) with transtentorial pressure gradients developing. As a result the cerebral perfusion pressures (CPP) decreased progressively, leading to an isoelectric EEG. In spontaneously breathing animals, the pressure changes resulted in apnoea within 2-4 minutes, irregularities in heart rhythm and in a marked rise in SAP (the Cushing reaction). A final collapse of all pressures occurred after 222 +/- 68 sec at a mean bleeding volume of 10.3 +/- 1.9 ml. In contrast, in mechanically ventilated animals, the course of bleeding was less dramatic. No change in cardiac rhythm or rise in SAP appeared despite a larger mean bleeding volume (12.0 +/- 1.6 ml). Instead, SAP slowly fell, reaching a level of approximately 40 mm Hg within 1 hour, while CPP concomitantly decreased from 120 mm Hg to 15 mm Hg. The findings in this and in a parallel study are explained in terms of the intracranial volume tolerance concept (Zwetnow et al. 1986). The beneficial effect of assisted ventilation on the course of subdural bleeding is multifactorial, involving both metabolic and mechanical mechanisms.     

Physiology of primary saccular afferents of goldfish: implications for Mauthner cell response

Mauthner cells receive neurally coded information from the otolith organs in fishes, and it is most likely that initiation and directional characteristics of the C-start response depend on this input. In the goldfish, saccular afferents are sensitive to sound pressure (< -30 dB re: 1 dyne cm-2) in the most sensitive frequency range (200 to 800 Hz). This input arises from volume fluctuations of the swimbladder in response to the sound pressure waveform and is thus nondirectional. Primary afferents of the saccule, lagena, and utricle of the goldfish also respond with great sensitivity to acoustic particle motion (< 1 nanometer between 100 and 200 Hz). This input arises from the acceleration of the fish in a sound field and is inherently directional. Saccular afferents can be divided into two groups based on their tuning: one group is tuned at about 250 Hz, and the other tuned between 400 Hz and 1 kHz. All otolithic primary afferents phaselock to sinusoids throughout the frequency range of hearing (up to about 2 kHz). Based on physiological and behavioral studies on Mauthner cells, it appears that highly correlated binaural input to the M-cell, from the sacculi responding to sound pressure, may be required for a decision to respond but that the direction of the response is extracted from small deviations from a perfect interaural correlation arising from the directional response of otolith organs to acoustic particle motion.     

Immunologic aspects in the pathogenesis and treatment of immune thrombocytopenic purpura in children

1. The nature of the muscarinic receptor involved in mediating cardiovascular changes caused by unilateral microinjection of carbachol (5 nmol) into, and electrical stimulation (200-300 microA) of, the amygdaloid complex was investigated in conscious, unrestrained female Sprague-Dawley rats. 2. Unilateral microinjection of carbachol (5 nmol; n = 6) and electrical stimulation (200-300 microA, 80 Hz, 30 s; n = 4) caused a significant rise in blood pressure of 21 +/- 4 mmHg and 25 +/- 5 mmHg, respectively. These changes were associated with no overall effect on heart rate. The effects of electrical stimulation were found to be repeatable. 3. Pretreatment i.c.v. with pirenzepine (5-20 mmol; n = 6-7 for each dose), dose-dependently inhibited the rise in blood pressure induced by carbachol, whereas AF-DX 116 (100 nmol; n = 6) failed to have any effect on the carbachol-induced pressure response. Neither antagonist alone had any effect on resting baseline variables. 4. Unilateral microinjections of atropine sulphate (1-100 nmol; n = 4-6 for each dose), pirenzepine (0.03-10 nmol; n = 4 for each dose) or AF-DX 116 (10-60 nmol; n = 4-5 for each dose), into the amygdala, dose-dependently inhibited the rise in blood pressure caused by electrical stimulation (200-300 microA). The ID50 values were 1.05, 0.23 and 39.5 nmol, respectively. Although pirenzepine seemed to be more potent than atropine, this difference was not significant. 5. It is concluded that the rise in blood pressure elicited by unilateral microinjection of carbachol into, or electrical stimulation of, the amygdaloid complex is mediated by M1-muscarinic receptors.     

Cecum of guinea pig is a reservoir and sigmoid is a high-resistance conduit

We compared the filling responses of the cecum and the sigmoid of the guinea pig using volumes up to 60 ml and 2.5 ml, respectively. In the isolated cecum, each 1-cm increment of hydrostatic pressure above zero led to accommodation of 10 ml volume; in the sigmoid, the yield pressure (at which accommodation first occurred) was 6 cm H2O, and pressure increments up to 20 cm H2O produced volume increments of less than 0.5 ml. Resting pressure at half-maximal filling was 5.0 +/- 0.7 cm H2O for the sigmoid and 1.7 +/- 0.6 cm H2O for the cecum. K+ depolarization led to a significant upward shift in the pressure curves of both segments. Ca2+ withdrawal decreased sigmoid and cecal pressures at some volumes. Distension of the cecum triggered intermittent contractions, which began with the shortening of the teniae and were associated with low-amplitude pressures and expulsion of a 5- to 10-ml volume. Distension of the sigmoid produced propagating contractions that were associated with high-amplitude pressures and lengthening; compartmentalization in the sigmoid prevented efflux from it, and volume inflow was not affected by pressure waves. Our observations indicate that its large capacity and great distensibility make the cecum suitable for reservoir functions, whereas its narrowness and lack of distensibility make the sigmoid a high-resistance conduit.     

Subtype-specific involvement of metabotropic glutamate receptors in two forms of long-term potentiation in the dentate gyrus of freely moving rats

In this study, the role of metabotropic glutamate receptors in N-methyl-D-aspartate receptor-dependent and voltage-gated calcium channel-dependent long-term potentiation in the dentate gyrus of freely moving rats was investigated. Antagonists for group 1 metabotropic glutamate receptors ((S)-4-carboxyphenylglycine), group 1/2 metabotropic glutamate receptors ((RS)-alpha-methyl-4-carboxyphenylglycine) and group 2 metabotropic glutamate receptors ((RS)-alpha-methylserine O-phosphate monophenylester) were used. The N-methyl-D-aspartate receptor antagonist, D(-)-2-amino-5-phosphonopentanoic acid, and the L-type voltage-gated calcium channel antagonist, methoxyverapamil were used to investigate the N-methyl-D-aspartate receptor and voltage-gated calcium channel contribution to the long-term potentiation recorded. Field excitatory postsynaptic potential slope and population spike amplitude were measured. Drugs were applied, prior to tetanus, via a cannula implanted into the lateral cerebral ventricle. 200 Hz tetanization produces a long-term potentiation which is inhibited by application of D(-)-2-amino-5-phosphonopentanoic acid and (RS)-alpha-methyl-4-carboxyphenylglycine. In this study, a dose-dependent inhibition of 200 Hz long-term potentiation expression was obtained with (S)-4-carboxyphenylglycine. Long-term potentiation induced by 400 Hz tetanization was not inhibited by D(-)-2-amino-5-phosphonopentanoic acid, although the amplitude of short-term potentiation was reduced. (RS)-alpha-methyl-4-carboxyphenylglycine and (S)-4-carboxyphenylglycine, both in the presence and absence of D(-)-2-amino-5-phosphonopentanoic acid, inhibited the development of 400 Hz long-term potentiation. (RS)-alpha-methylserine O-phosphate monophenylester had no significant effect on long-term potentiation induced by either 200 or 400 Hz tetanization. Application of methoxyverapamil significantly inhibited 400 Hz long-term potentiation, but had no effect on 200 Hz long-term potentiation. These data suggest that 400 Hz long-term potentiation, induced in the presence of D(-)-2-amino-5-phosphonopentanoic acid, requires activation of L-type calcium channels. Furthermore, these results strongly support a critical role for group 1 metabotropic glutamate receptors in both N-methyl-D-aspartate receptor- and voltage-gated calcium channel-dependent long-term potentiation.     

Examination of the compaction properties of a 1:1 acetaminophen:microcrystalline cellulose mixture using precompression and main compression

The compaction properties of a 1:1 acetaminophen and microcrystalline cellulose (MCC) mixture have been studied using a compaction simulator to make tablets by single compression and by a combination of precompression and main compression. The tensile strengths of the tablets and the energies involved in the compressions were determined. The tensile strengths of the tablets increased with increases in single compression pressure from 80 to 400 MPa and as the total applied pressure increased from 80 MPa up to around 400 MPa when combinations of precompression and main compression pressures were used. The tablet porosity decreased with increase in main compression pressure while the tablet tensile strengths increased. At minimum tablet porosity, further increase in main compression pressure could no longer result in increase in tablet strengths. Tablets compressed with combinations of precompression and main compression were stronger (2.15 +/- 0.02 to 3.99 +/- 0.1 MPa) than those produced with single compression (0.73 +/- 0.01 to 3.09 +/- 0.05 MPa). The total gross energies of compression increased with an increase in pressure of both the precompression and main compression. The elastic energies during main compression increased with an increase in precompression pressure as the tablet exhibited greater elastic deformation and reduced plasticity on second compression. The increase in elastic energies during main compression may also be because elastic energy is recoverable and is independent of precompression. As the precompression pressure increased, the minimum tablet porosity was attained; hence, the plastic energy during main compression became smaller while the elastic energy increased. Thus, a combination of low precompression and main compression pressures of 160/80 MPa or 80/160 MPa are more advantageous in the tableting of the 1:1 acetaminophen:MCC than a high single compression pressure of 320 or 400 MPa.