Effects of galacto-oligosaccharides and a Bifidobacteria lactis-based probiotic strain on the growth performance and fecal microflora of broiler chickens.

A galacto-oligosaccharide (GOS) prebiotic was prepared by reacting a high concentration of lactose (40% wt/vol) with a beta-galactosidase enzyme for 24 h at 37 degrees C. The enzyme was produced from recombinant Pichia pastoris X-33 cells. The study aimed at evaluating the effects of the prebiotic, a Bifidobacterium lactis-based probiotic, and the combination of these dietary additives on BW, feed intake, feed conversion ratio, and fecal counts of total anaerobic bacteria, lactobacilli, and bifidobacteria in broiler chickens. No significant differences in BW, feed intake and feed conversion ratio were found among the various groups. The study showed that GOS selectively stimulated the fecal microflora of broiler chickens. Total anaerobic bacteria and lactobacilli were increased by 3.4- and 3.56-fold, respectively, in chickens fed the diet containing GOS (3 kg per 25 kg) and B. lactis for 40 d compared with those fed the control diet. The bifidobacteria population in chickens fed the diet containing GOS (3 kg per 25 kg) and B. lactis significantly increased 21-fold in comparison to the control-fed birds. In particular, increasing the dietary concentration of GOS was accompanied by significant increases (P < 0.05) in bifidobacteria counts. The detectable population of bifidobacteria was also greater (P < 0.05) in chickens fed the diet containing GOS and bifidobacteria when compared with chickens fed a bifidobacteria-containing ration only. These results suggest that using GOS in combination with a B. lactis-based probiotic favored intestinal growth of bifidobacteria in broiler chickens.

Effects of Lactobacilli and an acidophilic fungus on the production performance and immune responses in broiler chickens.

Accumulated lines of evidence indicate that inactivated probiotics could have beneficial effects similar to those of live probiotics. Two strains of disrupted, cobalt-enriched, lactic acid bacteria (Lactobacillus acidophilus and Lactobacillus casei) and a disrupted fungal mycelium (Scytalidium acidophilum) were spray-mixed onto a mash basal feed, in 2 concentrations, prior to pelleting. The effects of these probiotics on production performance and immune response in broiler chickens were investigated. The production parameters, including BW, feed intake (FI), BW gain (BWG), and feed conversion ratio (FCR), were monitored weekly during a 6-wk trial. The immune response was evaluated by immunizing the birds with the antigen keyhole limpet hemocyanin (KLH) followed by a serological assay to measure blood IgA and IgG titers. Some of the production parameters were significantly improved by low L. casei (LCL; for BW and BWG), high L. acidophilus (LAH; for BW and BWG), and high fungal (FH; for BW, BWG, and FI) in comparison with the nonadditive control (NC-). However, these 3 treatments (LCL, LAH, and FH) did not enhance the measured immune responses. Instead, the titers of serum KLH-specific IgA in high L. casei (LCH) and low L. acidophilus (LAL) were significantly higher than those of NC-, 10 d after immunization. None of the probiotic treatments increased the titer of KLH-specific IgG in blood. Our results indicate that disrupted and cobalt-enriched L. acidophilus or L. casei was able to enhance production performance of broiler chickens. The fungal mycelium, S. acidophilum, when used at a high concentration, also demonstrated its potential for the first time to be used as a probiotic. In addition, the optimal concentration for administering probiotics is strain dependent. A higher dose does not always result in a better performance.

Some effects of duration on vowel recognition.

This study was designed to examine the role of duration in vowel perception by testing listeners on the identification of CVC syllables generated at different durations. Test signals consisted of synthesized versions of 300 utterances selected from a large, multitalker database of /hVd/ syllables [Hillenbrand et al., J. Acoust. Soc. Am. 97, 3099-3111 (1995)]. Four versions of each utterance were synthesized: (1) an original duration set (vowel duration matched to the original utterance), (2) a neutral duration set (duration fixed at 272 ms, the grand mean across all vowels), (3) a short duration set (duration fixed at 144 ms, two standard deviations below the mean), and (4) a long duration set (duration fixed at 400 ms, two standard deviations above the mean). Experiment 1 used a formant synthesizer, while a second experiment was an exact replication using a sinusoidal synthesis method that represented the original vowel spectrum more precisely than the formant synthesizer. Findings included (1) duration had a small overall effect on vowel identity since the great majority of signals were identified correctly at their original durations and at all three altered durations; (2) despite the relatively small average effect of duration, some vowels, especially [see text] and [see text], were significantly affected by duration; (3) some vowel contrasts that differ systematically in duration, such as [see text], and [see text], were minimally affected by duration; (4) a simple pattern recognition model appears to be capable of accounting for several features of the listening test results, especially the greater influence of duration on some vowels than others; and (5) because a formant synthesizer does an imperfect job of representing the fine details of the original vowel spectrum, results using the formant-synthesized signals led to a slight overestimate of the role of duration in vowel recognition, especially for the shortened vowels.

Role of F0 and amplitude in the perception of intervocalic glottal stops.

Glottal stops that occur in vowel-consonant-vowel context are often not realized as stops at all, but rather show voicing that is continuous throughout the glottal constriction gesture. Glottal articulations that are realized in this way are apparently marked by reductions in amplitude and fundamental frequency. In the present study measurements from naturally produced utterances containing the sequence /o?o/ (i.e., a glottal stop separating two identical vowels) were used to create a set of synthetic stimuli that varied in their F0 and amplitude contours. The utterances were resynthesized in six ways: (a) original pitch/original amplitude, (b) original pitch/flat amplitude, (c) flat pitch/original amplitude, (d) flat pitch/flat amplitude, (e) flat pitch/inverted amplitude, and (f) inverted pitch/flat amplitude. Results indicated that: (a) a dip in the pitch contour is nearly always sufficient to cue the presence of a glottal stop in the absence of any drop in amplitude, (b) a dip in the amplitude contour is usually sufficient to cue the presence of a glottal stop, and (c) signals with inverted contours were not heard as glottal stops, indicating that it is not merely an abrupt change that is needed to signal a glottal stop.

Acoustic correlates of breathy vocal quality: dysphonic voices and continuous speech.

In an earlier study, we evaluated the effectiveness of several acoustic measures in predicting breathiness ratings for sustained vowels spoken by nonpathological talkers who were asked to produce nonbreathy, moderately breathy, and very breathy phonation (Hillenbrand, Cleveland, & Erickson, 1994). The purpose of the present study was to extend these results to speakers with laryngeal pathologies and to conduct tests using connected speech in addition to sustained vowels. Breathiness ratings were obtained from a sustained vowel and a 12-word sentence spoken by 20 pathological and 5 nonpathological talkers. Acoustic measures were made of (a) signal periodicity, (b) first harmonic amplitude, and (c) spectral tilt. For the sustained vowels, a frequency domain measure of periodicity provided the most accurate predictions of perceived breathiness, accounting for 92% of the variance in breathiness ratings. The relative amplitude of the first harmonic and two measures of spectral tilt correlated moderately with breathiness ratings. For the sentences, both signal periodicity and spectral tilt provided accurate predictions of breathiness ratings, accounting for 70%-85% of the variance.

Creating filters with arbitrary response characteristics for use in hearing and speech research.

Digital filters with conventional lowpass, highpass, bandpass, and band reject frequency response curves are perfectly adequate for many research applications in speech and hearing. However, there are some specialized applications for which these conventional response characteristics are less than ideal. In this paper we describe a simple method for generating digital filters with virtually any amplitude and phase response. The process involves (a) calculating the impulse response of a finite impulse response filter from a text file that specifies the desired magnitude and phase response of the filter, and (b) convolving the impulse response with the input signal. Sample applications of this method are described.

Opioid responsiveness of cancer pain syndromes caused by neuropathic or nociceptive mechanisms: a combined analysis of controlled, single-dose studies.

We performed a combined analysis of the results from four controlled single-dose relative-potency studies to assess the impact of inferred pain mechanism on the response to an opioid drug. A total of 168 patients received 474 administrations of either morphine or heroin, and we assessed the analgesic response during a 6-hour period with visual analog scales. We summarized this as a total pain relief (TOTPAR) score. Two experienced pain clinicians reviewed information about pain characteristics and designated each case according to the inferred pain mechanism (neuropathic, nociceptive, or mixed) and the degree of confidence in the inferred mechanism (definite versus probable/possible). They grouped the cases as follows: nociceptive pain only (n = 205), neuropathic pain only (n = 49), and mixed (n = 220). We compared pain relief achieved by patients with different mechanisms, with TOTPAR adjusted for significant covariates (duration of prior opioid administration, doses of opioid administered in the previous 48 hours, pain intensity at the start of the study, BUN:creatinine ratio, and dose of administered opioid). The adjusted mean TOTPAR score of the group with any neuropathic pain was significantly lower than that of the group with nociceptive pain only (26.1 versus 20.4, p = 0.02). The score of the group with definite nociceptive pain alone (adjusted mean TOTPAR = 28.0) was significantly higher than scores of the groups with possible/probable nociceptive pain (TOTPAR = 19.9), mixed mechanisms (TOTPAR = 20.2), definite neuropathic pain alone (TOTPAR = 20.6), and possible/probable neuropathic pain alone (TOTPAR = 22.9).(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of opioid-induced constipation with oral naloxone: a pilot study.

Opioids cause constipation by binding to specific opioid receptors in the enteric and central nervous systems. First-pass glucuronidation limits systemic bioavailability of oral naloxone. This study was designed to determine if oral naloxone could reverse opioid-induced constipation without precipitating abstinence or recrudescence of pain in opioid-dependent individuals. Concentrations of unmetabolized and total naloxone, including naloxone glucuronide, were measured by radioimmunoassay. A dose-related increase in symptoms of laxation resulted in all three opioid-dependent patients studied that paralleled the increase in active and total naloxone plasma levels. Withdrawal symptoms occurred with plasma naloxone area under the plasma concentration-time curves above 550 ng.min/ml and with dosing intervals less than 3 hours. Peak plasma levels did not predict withdrawal. Oral naloxone ameliorates opioid-induced constipation in opioid-dependent persons. Titration of dose to a maximum of 12 mg at least 6 hours apart may be needed to avoid adverse reactions.

Cancer pain management with a controlled-release oral morphine preparation.

An open-label pilot study was conducted to assess the efficacy and acceptability of a controlled-release oral morphine formulation, MS Contin tablets, when administered "by the clock" two to three times daily as a substitute for opioids given on request to patients with pain caused by advanced cancer. Initially, four-hourly does of standard "immediate-release" oral morphine sulfate tablets were substituted for the patients' prior analgesic medication and titrated to individual needs. Forty of the 47 patients enrolled in the study were subsequently switched to an eight-hourly MS Contin regimen (three patients became too ill to continue the study, and four left the study during the immediate-release titration phase because of adverse reactions that may have been drug related). Small "rescue" doses of standard oral morphine were available to the patients, but they were taken infrequently. Twenty-one of the 37 patients maintained on the eight-hourly schedule consented to be treated with, and were subsequently stabilized on, MS Contin administered every 12 hr, with a reduction of over 20% in their average daily morphine dose. Most of the patients rated the controlled-release medication superior to the standard oral morphine tablets in terms of both convenience and adequacy of relief.

Guidelines for use of controlled-release oral morphine in cancer pain management. Correlation with clinical experience.

An open study of 47 patients with cancer pain treated with repeated doses of a controlled-release oral morphine tablet was conducted to assess the acceptability of this drug and develop guidelines for its use. Each patient kept a detailed record of pain, analgesic intake, side effects, and other medications. A nurse observer/clinician followed these patients on a daily basis and kept similar records. Of 47 patients who began the study, 37 were successfully stabilized with standard morphine sulfate tablets and then switched to controlled-release morphine (CRM). Twenty-one patients who completed the study took CRM every 12 h, and 16 patients received a dose every 8 h. Doses of the CRM ranged from 30 mg every 12 h to 360 mg every 8 h. Less frequent doses and uninterrupted sleep were reported advantages. All of the patients completing the study chose to continue this method of pain management and extended care data were obtained from each patient poststudy through continued monitoring.

Sublingual absorption of selected opioid analgesics.

Ongoing interest in the improvement of pain management with opioid analgesics had led to the investigation of sublingual opioid absorption. The present report determined the percent absorption of selected opioid analgesics from the oral cavity of normal subjects under conditions of controlled pH and swallowing when a 1.0 ml aliquot of the test drug was placed under the tongue for a 10-minute period. Compared with morphine sulfate at pH 6.5 (18% absorption), buprenorphine (55%), fentanyl (51%), and methadone (34%) were absorbed to a significantly greater extent (p less than 0.05), whereas levorphanol, hydromorphone, oxycodone, heroin, and the opioid antagonist naloxone were not. Overall, lipophilic drugs were better absorbed than were hydrophilic drugs. Plasma morphine concentration-time profiles indicate that the apparent sublingual bioavailability of morphine is only 9.0% +/- 11.9% (SD) of that after intramuscular administration. In the same subjects the estimated sublingual absorption was 22.4% +/- 9.2% (SD), indicating that the sublingual absorption method may overestimate apparent bioavailability. When the oral cavity was buffered to pH 8.5, methadone absorption was increased to 75%. Thus, an alkaline pH microenvironment that favors the unionized fraction of opioids increased sublingual drug absorption. Although absorption was found to be independent of drug concentration, it was contact time dependent for methadone and fentanyl but not for buprenorphine. These results indicate that although the sublingual absorption and apparent sublingual bioavailability of morphine are poor, the sublingual absorption of methadone, fentanyl, and buprenorphine under controlled conditions is relatively high.

The Memorial Pain Assessment Card. A valid instrument for the evaluation of cancer pain.

Effective evaluation and treatment of cancer pain require valid and independent measurement of pain intensity, pain relief, and psychological distress. The Memorial Pain Assessment Card (MPAC) is a simple instrument designed to provide rapid evaluation of these subjective experiences. On the 8.5 by 11 inch card are printed the eight pain intensity descriptors, and three visual analog scales which measure pain intensity, pain relief, and mood. Experienced patients can complete it in less than 20 seconds. The authors administered the MPAC to 50 hospitalized cancer patients within 48 hours of referral to the Pain Service for inadequate pain control, together with standard measures: The McGill Pain Questionnaire, Profile of Mood States, Hamilton Depression Scale, and Zung Anxiety Scale. Correlational and multiple regression analyses revealed that the MPAC can distinguish pain intensity from pain relief and from general psychological distress, and it can provide multidimensional assessment that is practically equivalent to the full assessment battery. We conclude that the MPAC is valid and effective for clinical use, and recommend it for the assessment of individual patients, and as an outcome measure in clinical trials.

Pharmacokinetics and pharmacodynamics of methadone in patients with chronic pain.

Concentrations of methadone in plasma, estimates of pain relief, and pupillary size were determined after a single intravenous dose (10 to 30 mg) of methadone hydrochloride to eight patients with chronic pain, five of whom had cancer. The pharmacokinetic parameter estimates reveal rapid and extensive distribution (Varea) and a slow apparent elimination half-life (t1/2) (mean Varea = 3.59 L/kg and harmonic mean t1/2 = 23 hours). The harmonic mean blood clearance is 106 ml/min, the harmonic mean renal clearance is 3.9 ml/min, the mean hepatic extraction ratio is 0.089, and plasma protein binding is 86% to 89%. These results suggest that only the free (unbound) fraction of methadone present in blood is extracted by the liver and that methadone can be classified as a low (hepatic)-extraction drug. The data were fit to a pharmacokinetic-pharmacodynamic model to obtain estimates of the steady-state plasma methadone concentration required to produce 50% of the maximum pain relief. This value varied from 0.04 to 1.13 micrograms/ml (mean = 0.29 micrograms/ml). These results indicate substantial interindividual variation in the relationship between changes in plasma methadone concentration and analgesia in patients with chronic pain receiving opioids. A pharmacokinetic-pharmacodynamic model may be useful for the individualization of analgesic dosage and therefore the optimization of pain management in patients with chronic pain.

Crossover trials in clinical analgesic assays: studies of buprenorphine and morphine.

Analgesic studies of buprenorphine, a thebaine derivative and potent partial narcotic agonist, were carried out in patients with cancer who had postoperative or chronic pain. Intramuscular buprenorphine was compared with intramuscular morphine in a series of sequentially related, twin crossover assays and was found to be about 25 times as potent as morphine. Side effects were essentially morphine-like. In a second assay, the acceptability and analgesic activity of sublingual buprenorphine was studied in a 6-dose, balanced, incomplete block assay, a modification of the twin crossover design employed in the all-intramuscular trial. Sublingual buprenorphine was found to be about 15 times as potent as intramuscular morphine and was well accepted by our patients. The 4-dose twin crossover trial in which doses are adjusted sequentially is more flexible in that a wide range of doses may be studied, but it lacks the ability of the 6-dose design to provide estimates of the curvature of the dose-response slopes of the study drugs. When first-dose-only data were analyzed as parallel group assays, the main difference in results compared with the crossover studies was a decrease in efficiency and sensitivity.

Benzydamine HCl, a new agent for the treatment of radiation mucositis of the oropharynx.

Benzydamine HCl is a new nonsteroidal analgesic and anti-inflammatory compound which is not chemically related to local anesthetics such as procaine and xylocaine. A double-blind, randomized clinical investigation was carried out to determine the analgesic and anti-inflammatory effectiveness of benzydamine HCl in patients with radiation-induced mucositis of the oropharynx. Of the 67 patients in the study, 37 were on benzydamine and 30 on placebo. Patients developed radiation mucositis, hyperemia, and throat pain when the total radiation dose reached above 2,000 rad over 2 weeks (200 rad per fraction, five treatments per week). Analysis of the data showed that benzydamine HCl used as a rinse/gargle provided a statistically significant and clinically meaningful alleviation of the symptoms of oropharyngeal mucositis. There was also significant improvement in terms of reduction in hyperemia and mucositis in benzydamine group. No systemic side effects associated with benzydamine medication were noted. In view of the relative ineffectiveness of systemic analgesics and topical anesthetics for these conditions, benzydamine HCl promises to be a useful addition to the therapeutic armamentarium.

Intramuscular meptazinol and morphine in postoperative pain.

Meptazinol is an agonist-antagonist opioid analgesic believed to be unique in its selectivity for mu1 (high affinity) receptors and its cholinergic activity. Our objectives were to determine the relative analgesic potency of intramuscular meptazinol and morphine and to compare mood and side effects in 102 patients with cancer who have postoperative pain. Meptazinol (50, 100, and 200 mg) and morphine (4, 8, and 16 mg) were given for moderate to severe pain in a double-blind, randomized but balanced, incomplete block design. Serial multiple assessments of pain, relief, mood, and side effects were made. The most precise estimates of relative analgesic potency indicate that meptazinol is equivalent to 10 mg morphine at 120 mg (95% confidence interval 80 to 170 mg) for peak effect and at 175 mg (95% confidence interval 125 to 270 mg) for total effect. Mean (+/- SE) times to peak effect and to remedication were 0.9 +/- 0.1 and 3.6 +/- 0.2 hours for meptazinol and 1.4 +/- 0.1 and 4.8 +/- 0.4 hours for morphine at equianalgesic peak effects. The percentages of subjects with one or more side effects were 18, 49, and 73 for graded meptazinol doses and 32, 49, and 65 for graded morphine doses. Mean numbers of side effects per subject were 0.3, 1.5, and 3.5 for meptazinol and 0.5, 0.7, and 1.7 for morphine. Profiles of side effects differed. Mood improvement and overall satisfaction were dose related and greater for morphine than for meptazinol. Side effects may limit the use of meptazinol in doses that relieve severe postoperative pain.

A clinical study of benzydamine for the treatment of radiotherapy-induced mucositis of the oropharynx.

A double-blind, randomized clinical study was undertaken to determine the analgesic and antiinflammatory effectiveness of benzydamine in patients with radiation-induced mucositis of the oropharynx. Of the 67 patients in the study, 37 patients were on benzydamine and 30 patients on a placebo. The results of the study showed that benzydamine possessed a significant analgesic activity as evidenced by relief of mouth and throat pain induced by radiation therapy. It is also noted that the patients on benzydamine exhibited a cumulative relief of oral pharyngeal pain and discomfort over the time of treatment, as compared to those on the placebo. These effects of benzydamine in the present study might be a result of the antiinflammatory property of the drug. The cumulative and prolonged effectiveness of benzydamine makes it of distinct value compared with the commonly available local anaesthetics such as lidocaine. Benzydamine appears to provide a useful addition to the therapeutic armamentarium for alleviating the symptoms of oral pharyngeal mucositis.

Parenteral meptazinol: a US clinical trial.

The effectiveness and safety of i.m. meptazinol (50, 100, 200mg), a unique mu 1-selective opioid analgesic, was compared with i.m. morphine (4, 8 and 16 mg) in 128 cancer patients with moderate to severe postoperative pain; 102 patients completed the crossover study. The study design was a modification of the sequential, twin-crossover assay. Meptazinol was found to be one-fifteenth to one-twentieth as potent as morphine on a mg basis, and to provide a more rapid time to peak effect (about 40 min vs 1 h) than morphine. Morphine improved selected aspects of mood while meptazinol did not. Sleepiness was the most common side effect on morphine (n = 43), and nausea was most common on meptazinol (n = 35). The incidence of side effects appeared to be dose-related for both drugs.

Prediction of contextual speech intelligibility from isolated word intelligibility measures.

The purpose of this study was to evaluate the efficacy of two nonlinear formulae posited by Boothroyd (1978) for prediction of contextual intelligibility from measures of isolated word intelligibility with four different sets of speech intelligibility data. Both of Boothroyd's formulae, Pc = 1 - (1 - Pi)2 and Pc = 1 - (1 - Pi)1.5 (1 + Pi), provided excellent fit of measured contextual intelligibility with predicted contextual intelligibility for all sets of data. Attempts to improve correlation coefficients between measured and predicted contextual intelligibility by iterating Boothroyd's suggested exponents did not significantly improve the predictive ability of the original formulae.