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Scaphoid excision and capitolunate arthrodesis for radioscaphoid arthritis.

Eighteen patients with symptomatic radioscaphoid arthritis had scaphoid excision and capitolunate arthrodesis. Eight patients also had a silicone scaphoid replacement. The follow-up period averaged 3 years. Fusion was solid in 12 cases at an average of 8 weeks, and pain was significantly less at follow-up evaluation. Six patients had a pseudarthrosis and five had persistent pain. Immobilization in the pseudarthrosis group averaged 6 weeks, which was significantly less than the group that fused. Two patients underwent successful repeat fusions. Wrist extension averaged 26 degrees, flexion 34 degrees, radial deviation 11 degrees, and ulnar deviation 24 degrees. Grip strength averaged 25 kg. Presence of an implant had no significant effect on motion or strength. Pin track infection and pseudarthrosis were the main complications. Pain relief, functional motion, good strength, and patient satisfaction can be expected after scaphoid excision and solid capitolunate arthrodesis. Kirschner wires should be buried subcutaneously to avoid infection. The addition of a scaphoid implant offered no advantage over simple scaphoid excision.

Arthritis↗

Determination of methamphetamine enantiomer ratios in urine by gas chromatography-mass spectrometry.

Analysis of the enantiomers of methamphetamine and its metabolite amphetamine is an extremely important process for a number of scientific disciplines. From studies of biological activity and mechanisms through determination of precursor molecules in a criminal investigation are all served by this analytical procedure. Utilization of gas chromatography-mass spectrometry with chiral derivatizing reagents is the most common chiral procedure and produces excellent results. Of the chiral derivatizing reagents available, the most widely used is trifluoroacetyl-l-prolyl chloride (TPC). Utilization of other derivatives require either synthesis by the analyst or have not shown themselves to provide as good a separation as did the TPC reagent. Use of chiral stationary phases yield good results but the disadvantages of temperature limits of these columns and the narrow use to which the columns can be put has limited their utilization. A significant utility of the chiral stationary phase is the ability to determine the purity of a chiral derivatizing reagent. Even if not used for routine analysis of enantiomers, utilization of this procedure can determine the purity of a reagent such as TPC and allow for accurate calculation of actual amounts of each enantiomer. This can be estimated using chiral derivatives on an achiral column, but it is limited to the extent that it is not able to differentiate enantiomeric impurity in the reagent versus the drug itself. Description of chromatographic procedures primarily focusing on gas chromatographic-mass spectrometric techniques but also including liquid chromatographic techniques along with examples of extraction and derivatization procedures is the focus of this review.

Gas Chromatography-Mass Spectrometry↗

Single auditory neuron response during acute acoustic trauma.

By recording from single auditory neurons in the spiral ganglion of the guinea pig cochlea it was possible to monitor threshold changes to acoustic stimuli in the same neuron during acute exposures to continuous pure tones (100 dB SPL) delivered for periods of up to 180 min. Initial changes in the tuning curve were sensitivity losses at and above the characteristic frequency (CF). This asymmetric loss resulted in a shift in the CF to lower frequencies. Further exposure (up to 20 min) produced a complete loss of the sharply tuned portion of the tuning curve and the most sensitive area moved to lower frequencies by up to 0.75 of an actave when compared to the original CF. Sensitization of the low frequency section of the tuning curve could take place for short exposures (up to 20 min) but disappeared with further exposure, whether continuous or interrupted. Long term exposures (60--80 min) produced losses in the low frequency portion of the tuning curve until a point was reached when the unit no longer responded to stimuli at 110 dB SPL.

Acoustic Stimulation↗

Temporary threshold shift modified by binaural acoustic stimulation.

Monaural losses in hearing sensitivity induced by an intense pure tone could be reduced if an acoustic stimulus of the same frequency was simultaneously delivered to the other ear. The reduction was eliminated when the contralateral stimulus was set at a frequency other than the ipsilateral trauma frequency and also after the administration of strychnine, a known blocker of auditory efferent activity. This suggests that acoustic activation of auditory efferents is responsible for the reduced ipsilateral sensitivity loss.

Acoustic Stimulation↗

Reduced temporary and permanent hearing losses with multiple tone exposures.

Acoustic overstimulation of the guinea pig cochlea with a 16 kHz pure tone induces a loss in threshold sensitivity that can be either temporary or permanent depending on the duration of the trauma. When a second tone of lower frequency (10, 5 or 2 kHz) is presented to the same cochlea simultaneously with the first tone, then the resultant threshold loss produced by the 16 kHz tone is significantly less. This applies to both temporary and permanent threshold losses. The reduced threshold loss disappears as the intensity of the second tone decreases. This type of nonlinear cochlea behaviour is similar to other acoustically evoked nonlinearities generally grouped under the term, two-tone suppression or inhibition. The results disagree with the "equal energy hypothesis' as a method to establish damage risk criteria in noise-induced hearing loss.

Animals↗

Recovery of eighth nerve action potential thresholds after exposure to short, intense pure tones: similarities with temporary threshold shift.

Exposure of guinea pig cochleas to short (25, 250 and 1000 ms), intense (90 or 100 dB SPL) 10 kHz pure tones reduced cochlear sensitivity to 14 kHz test tones presented at intervals varying from 5 ms to 70 s after the exposure tone. The recovery of cochlear sensitivity, determined as the SPL required to evoke a 20 microV compound action potential (CAP), depended on both the intensity and the duration of the exposure tone and appeared to take place in two or more phases. After a 25 ms, 100 dB SPL exposure, CAP threshold increased by up to 13.5 dB and generally recovered very rapidly (25 ms), although some loss persisted for as long as 400 ms. A similar, but greater and longer, elevation of threshold was seen after long exposure tones. Lower exposure tone intensities (90 dB SPL) produced threshold elevations which generally lasted for only short durations (25-35 ms). The rapid recovery is consistent with the time course of recovery from rapid adaptation, while the slow recovery component is similar to that seen in the cochlea after much longer exposures and may be related to the phenomenon of temporary threshold shift. Long and/or loud exposures also frequently resulted in a third form of threshold elevation, identified in only a few animals, which recovered with a time constant in excess of 25 s. A fourth component occasionally persisted for the duration of the experiment.

Acoustic Stimulation↗

Variability of noise-induced damage in the guinea pig cochlea: electrophysiological and morphological correlates after strictly controlled exposures.

Anaesthetized guinea pigs were exposed to loud tones (1 h, 10 kHz, 112-118 dB SPL) with continuous control of the sound pressure at the tympanic membrane. N1 electrocochleograms were used to measure functional damage immediately and 21 days after the exposure. Damage to the organ of Corti was assessed by scanning electron microscopy and light and transmission electron microscopy. Principal findings were: (1) Functional impairment after 21 days showed large inter-animal variation which was not the result of changes in the effective damaging energy. (2) Structural damage to the stereocilia was also variable and did not always correlate with functional impairment, although when N1 thresholds were elevated damage to the stereocilia was always present. (3) Unknown factors within the cochlea must be responsible for variations in individual susceptibility to permanent noise-induced hearing loss.

Animals↗

The responses of inner and outer hair cells in the basal turn of the guinea-pig cochlea and in the mouse cochlea grown in vitro.

Until recently the responses of the mechanosensitive hair cells of the cochlea have been inferred from their morphology, morphological relationships with other structures in the cochlea, and by indirect electrophysiological measurements. With the advent of techniques for making intracellular recordings from hair cells in the cochleas of anaesthetised mammals it has been possible to measure the responses of hair cells to acoustic stimulation and to assess their roles in sensory transduction in the cochlea. Intracellular recordings of the responses of inner and outer hair cells in the basal turn of the guinea-pig cochlea show that they differ considerably from each other. The receptor potentials of inner hair cells are larger, predominantly depolarizing to low frequency tones and at their best frequencies (16-20 kHz) they generate depolarizing dc receptor potentials. Outer hair cells generate predominantly hyperpolarizing potentials to low frequency tones. They do not produce significant voltage responses at high frequencies except at high intensities when they generate slowly rising depolarizing potentials which are associated with loss of cochlear sensitivity. At low frequencies the receptor potentials of the inner hair cells phase lead those of the outer hair cell. Measurements of their frequency selectivity show that inner and outer hair cells are both sharply tuned. It is proposed that the responses of inner and outer hair cells are consistent with sensory and motor roles respectively in mechanoelectric transduction and that the outer hair cells are the site of an active mechanical process responsible for the frequency selectivity and sensitivity of the cochlea. Intracellular recordings from hair cells in the mouse cochlea maintained in vivo have provided a direct measure of the mechanosensitivity of cochlear hair cells (approximately 30 mV per degree of displacement of their stereociliary bundles) and indirect evidence that the transfer characteristics of the outer hair cells in vivo may be due to their mechanoelectrical interaction with the tectorial membrane. This is because the transfer characteristics of the inner and outer hair cells are similar in vitro in the absence of a tectorial membrane. Considerable importance is attributed to the shape of the transfer characteristics of the inner and outer hair cells. Changes in these characteristics during anoxia and following exposure to intense tones are associated with depolarization of the outer hair cells and loss of cochlear sensitivity and frequency selectivity. Current-voltage studies of hair cells in vivo show the inner and outer hair cells to be electrically nonlinear.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Acoustically induced hearing loss: intracellular studies in the guinea pig cochlea.

Intracellular recordings were made from both inner and outer hair cells (IHC, OHC) in the basal coil of the guinea pig cochlea before, during and after the animal was exposed to loud, pure tones. Following multiple loud tones both types of sensory cells demonstrate a culmulative decrease in their voltage responses to a test tone. A loss in sensitivity of the compound action potential (CAP) of the eighth nerve co-incides with a decrease in both the amplitude of the IHC receptor potential and the positive summating potential (+SP) recorded at the round window. The largest decreases in sensitivity of IHCs are found at the characteristic or best frequency (CF) of each cell and this frequency selective loss of sensitivity results in a decrease in the tuning of the hair cell. During and following a loud tone the nonlinear properties of IHCs are also reduced.

Action Potentials↗

Low-frequency responses of inner hair cells: evidence for a mechanical origin of peak splitting.

Auditory nerve fibres usually respond to a preferred phase of a low frequency sinusoidal stimulus. However, at high sound pressures fibres may either change the preferred phase of response or respond to more than one phase of the stimulus. This complex firing pattern is known as peak splitting. Hypotheses for the origin of peak splitting have ranged from micromechanical models to models incorporating electrical interactions between inner and outer hair cells. In order to determine the origin of peak splitting, the potential across the IHC synaptic membrane has been measured during stimulation with low frequency tones and it is found that the IHC receptor potentials exhibit peak splitting at sound pressures that coincide with the saturation of the outer hair cell receptor potentials. Current injection experiments show that peak splitting is also recorded in the resistance change of the inner hair cell during acoustic stimulation. It is concluded from this evidence that peak splitting is present in the mechanical input to the IHC.

Acoustic Stimulation↗

Acoustic lesions in the mammalian cochlea: implications for the spatial distribution of the 'active process'.

The spatial contribution of mechanically active hair cells to tuning and sensitivity at a single point in the mammalian cochlea has been investigated in the basal turn of the guinea pig cochlea. Following the destruction of outer hair cells with acoustic overstimulation it was possible to record apparently normal tuning and sensitivity from spiral ganglion neurones innervating inner hair cells located on the apical edges of substantial lesions. The distance between the recording site, where neurones showed normal sensitivity, and areas of the cochlea showing 60-100% of the outer hair cells either damaged or missing varied between 0.2 and 1.3 mm which incorporates approximately 70 to 450 outer hair cells. In one animal neurones that demonstrated normal sensitivity were recorded within 0.2 mm of a lesion where 67% of the outer hair cells were either missing or showed severe damage to their stereocilia and within 0.5 mm of areas of the organ of Corti showing damage to 97% of the outer hair cells. This distance includes approximately 50 inner hair cells or 180 outer hair cells. The location of these neurones, whose sharp tuning presumably mirrors basilar membrane mechanics, suggests that a substantial proportion of point tuning in the cochlea may be derived over a distance of less than 0.5 mm and involve fewer than 200 active outer hair cells.

Acoustic Stimulation↗

Hearing loss in Paget's disease of bone: the relationship between pure-tone thresholds and mineral density of the cochlear capsule.

We have developed a unique method of quantitative computed tomography (QCT) that enables measurement of the density of the cochlear capsule in vivo. We performed pure-tone audiometry and QCT on 67 ears from 35 subjects with radiographically confirmed Paget's disease of the skull and on 40 ears from twenty volunteer subjects. The Pearson product-moment correlation coefficients (age- and sex-adjusted) in the group affected by Paget's disease were -0.63 for left ears and -0.73 for right ears for high-frequency air conduction pure-tone thresholds (mean of 1, 2, and 4 kHz) versus cochlear capsule density. Correlation coefficients (age- and sex-adjusted) between cochlear capsule density and air-bone gap (mean at 0.5 and 1 kHz) for the affected group were -0.67 for left ears and -0.63 for right ears. All correlations between hearing thresholds and cochlear capsule density in pagetic subjects were significant at p < 0.001. The regressions were consistent throughout the ranges of hearing level. There were no significant correlations between cochlear capsule mean density and hearing level in the volunteer subjects. These findings demonstrate the feasibility of precise and accurate density measurements in the temporal bone in vivo and support the use of the mean cochlear capsule density as a marker of disease effect. Alteration of cochlear capsule bone density may be related to the mechanisms of hearing loss in Paget's disease of bone.

Adult↗

Enantiomeric composition of amphetamine and methamphetamine derived from the precursor compound famprofazone.

Fourteen different metabolic precursors of amphetamine or methamphetamine have previously been identified. Many of these drugs are available only by prescription and several are only available in some parts of the world and not in others. One of these drugs, famprofazone, is available over-the-counter which complicates the interpretation of methamphetamine urine drug testing results. To assist in the interpretation of typical laboratory results, a study was conducted to determine the enantiomeric composition of the methamphetamine and amphetamine produced from the metabolism of famprofazone. Fifty mg of famprofazone was administered to a volunteer followed by collection of urine for the next 6 days. The resulting quantity, enantiomeric composition and percent conversion from famprofazone to the product amphetamine and methamphetamine was determined. The results showed the amphetamine and methamphetamine to include both the d- and l-enantiomers. Percent conversion and peak concentrations were similar to those reported in previous studies.

Amphetamines↗

Predictors of total mortality and sudden death in mild to moderate heart failure. Captopril-Digoxin Study Group.

The relation between baseline clinical variables and subsequent mortality was examined in 295 patients with mild to moderate heart failure who participated in a multicenter trial comparing the effect on treadmill exercise tolerance of captopril, digoxin and placebo given in addition to a diuretic drug. At baseline study, all patients had a left ventricular ejection fraction less than or equal to 40%; 81% were in New York Heart Association functional class II. The etiology of heart failure was ischemic in 62% and nonischemic in 38%. During an average follow-up period of 16 months, 47 patients (16%) died and 24 deaths were classified as sudden. By univariate analysis, left ventricular ejection fraction, ventricular premature beat frequency, couplet frequency, ventricular tachycardia frequency, functional class, treadmill exercise time and nonischemic heart disease were statistically associated with mortality. With multiple logistic regression analysis, left ventricular ejection fraction was identified as the variable most closely associated with total mortality (p = 0.006). Twenty-seven percent of patients with an ejection fraction less than or equal to 20% died compared with 7% with an ejection fraction greater than or equal to 30%. Ventricular tachycardia frequency on Holter monitoring was independently associated with both total mortality (p = 0.008) and sudden death (p = 0.003). Patients with a ventricular tachycardia frequency of greater than 0.088 events/h had a mortality rate of 34% compared with 12% in those without ventricular tachycardia. In the multivariate model, functional class (p = 0.02) and etiology of nonischemic heart disease (p = 0.04) remained as independent predictors of mortality, whereas treadmill exercise duration did not.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Output, Low↗

Plasma atrial natriuretic factor in essential hypertension: relation to cardiac size, function and systemic hemodynamics.

To evaluate determinants of elevated plasma atrial natriuretic factor levels in patients with hypertension, immunoreactive plasma atrial natriuretic factor in 54 normal subjects and 40 untreated hypertensive patients was compared with echocardiographic measurements of cardiac size, function and systemic hemodynamics. In normal subjects, plasma atrial natriuretic factor was related to age, systolic blood pressure and left atrial and ventricular chamber sizes, but only age and ventricular size were independent predictors. In untreated hypertensive patients, atrial natriuretic factor was directly related to age, atrial size, systolic pressure, peripheral resistance and ventricular systolic performance; age, atrial size and peripheral resistance were independent predictors. Eight patients with elevated atrial natriuretic factor values (greater than 25 fmol/ml) were significantly (p less than 0.01) older and had greater atrial and ventricular size and higher systolic pressure and function than normal subjects or patients with normal natriuretic factor levels. Plasma atrial natriuretic factor was inversely related to peak diastolic filling rate in normal subjects (r = -0.59; p less than 0.001), whereas it was positively related to the proportional contribution of atrial systole to left ventricular filling in hypertensive patients (r = 0.77; p less than 0.001). These findings suggest that in normal subjects, impairment of ventricular relaxation with age may contribute to atrial natriuretic factor secretion by increasing left atrial afterload; the correlation with left ventricular size may reflect physiologic fluctuations in plasma volume. In patients with uncomplicated hypertension, left atrial enlargement and consequent stronger atrial contraction contributed to increased atrial natriuretic factor release, whereas no independent relation existed with left ventricular hypertrophy or systolic function. Because ventricular relaxation was normal and ventricular size and systolic performance were increased in hypertensive patients with high atrial natriuretic factor levels, the observed increase in left atrial size and atrial contribution to ventricular filling might reflect a primary increase in venous return in this subset of hypertensive patients.

Adult↗

Parasympathetic withdrawal is an integral component of autonomic imbalance in congestive heart failure: demonstration in human subjects and verification in a paced canine model of ventricular failure.

Although enhanced sympathetic tone is a well recognized component of the autonomic profile characteristic of congestive heart failure, the contribution of parasympathetic withdrawal to this autonomic imbalance is less well described. The technique of spectral analysis of heart rate variability provides a dynamic map of sympathetic and parasympathetic tone and was thus used to define the nature of sympathetic-parasympathetic interactions in humans with idiopathic dilated cardiomyopathy and in a paced canine model of congestive heart failure. Humans with cardiomyopathy were found to have an augmentation of the sympathetically mediated low frequency area of the power density spectrum. Parasympathetic withdrawal was demonstrated by significant reductions in the parasympathetically mediated high frequency area (p less than 0.05) and the ratio of high to low frequency areas (p less than 0.01). Administration of atropine to normal subjects resulted in a significant reduction in the high frequency area (p less than 0.05) and the high/low frequency area ratio, both of which decreased within the range noted in patients with congestive heart failure. Administration of isoproterenol in normal subjects led to an augmentation of the low frequency area but to only a small decrease in the high/low frequency area ratio. Induction of congestive heart failure in a paced canine model resulted in alterations in the autonomic profile that resembled those seen in humans with ventricular failure. The prominent high frequency region of the spectrum at baseline, indicating a predominance of parasympathetic tone, was absent after the evolution of congestive heart failure, and there was a marked augmentation of the low frequency region of the spectrum.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗