Bovine mammary myoepithelial cells. 1. Isolation, culture, and characterization. The objective of this study was to isolate, purify, culture, and characterize myoepithelial cells from bovine mammary glands. Myoepithelial cells were separated from other mammary and blood cells after collagenase digestion and centrifugation using metrizoate-ficoll gradients. Myoepithelial cells were identified by their characteristic morphology and cloned using selective detachment. They contained many densely packed myofilaments, very few cytoplasmic organelles, elongated surface projections, and a dense, irregularly shaped nuclei. Some cells were as large as 1.2 mm in culture. Myoepithelial cells contained an extensive network of cytoskeletal proteins, including alpha-smooth muscle actin, alpha-actinin, and vimentin. When cultured, they tended to repel one another and never grew as closely associated cells. The myoepithelial nature of these cells was verified by showing that they contracted in response to oxytocin, bound oxytocin, and did not produce casein. Myoepithelial cells from fetal and lactating glands grew very well in culture. Active division of myoepithelial cells could be maintained for at least 3 mo, and cells could be serially subcultured at least seven times. The successful isolation and culture of bovine mammary myoepithelial cells make utilization of these cells possible in order to study their role in mammary growth and differentiation and milk ejection.


Bovine mammary myoepithelial cells. 2. Interactions with epithelial cells in vitro. The objective of this study was to examine interactions of bovine myoepithelial and epithelial cells in vitro. Mammary tissue was dissociated with collagenase into myoepithelial and epithelial cells. Myoepithelial and epithelial cells were separated by differential centrifugation. Both cell types were cultured on plastic in RPMI-1640 and Iscove's Modified Dulbecco's Modified Eagle Medium supplemented with 10% horse serum and 5% fetal bovine serum. Our data revealed that conditioned medium from epithelial cells caused a small but significant reduction in proliferation of myoepithelial cells from fetal mammary glands. Myoepithelial-epithelial cell interaction in culture was characterized by myoepithelial cells with extended filopodia that could grow on top of confluent monolayers of epithelial cells, imitating the in vivo situation. In confluent monolayers of epithelial and myoepithelial cells in coculture, small domelike structures consisting of mixtures of epithelial and myoepithelial cells were observed. These structures greatly resembled the in vivo organization of the bovine mammary gland. Furthermore, myoepithelial cells were capable of migration toward individual colonies of epithelial cells or single epithelial cells. Myoepithelial cells organized epithelial cells into well-defined colonies. Myoepithelial cells may play an important role in organizing the architectural framework of the mammary gland during growth and development.


Purification and properties of alkaline phosphatase in the lactating bovine mammary gland. Alkaline phosphatase has been purified 1400-fold from homogenates of lactating bovine mammary tissue. The purification procedure included subcellular fractionation, solubilization with butanol, fractionation with acetone, chromatography on concanavalin A-Sepharose, DEAE cellulose, DEAE-Sephadex, and gel filtration on Sephadex G-200. The enzyme activity was measured with the substrate p-nitrophenylphosphate in three buffers, and the maximum rate occurred at pH 10. For maximum activity, Mg2+ was required. Substrate specificity studies at three pH values indicated that the enzyme had broad specificity. It catalyzed the hydrolysis of aliphatic and aromatic phosphates and pyrophosphates, but the phosphoprotein beta-casein was a poor substrate. Potent inhibitors of the enzyme were levamisole and sulfhydryl reagents (2-mercaptoethanol, dithiothreitol, and cysteine).


Lactational response of Jersey cows to bovine somatotropin administered daily or in a sustained-release formulation. Twenty-four Jersey cows were administered either 0 or 15.5 mg of bST/d or 310 mg of bST/14 d to determine the effect on milk yield, milk composition, feed intake, and body weight. Administration of bST was from wk 14 through 42 postpartum. Cows were housed in a tie-stall barn and fed for ad libitum intake a TMR adjusted to one of two energy protein densities according to milk yield. Milk yield of cows administered bST daily or by sustained-released vehicle increased 27.6 and 24.7%, respectively, over that of control cows; FCM increased by 30.3 and 26.7%. Percentages of fat and protein in milk were unaffected by bST treatment. Dry matter intake of cows administered bST was greater than that of control cows, whether expressed as kilograms per day or as a percentage of body weight. Apparent efficiency of yield increased in cows administered bST. No significant change in body weight occurred; however, cows administered bST had lower body condition scores at 42 wk postpartum. This trial demonstrated comparable effects of bST on lactational performance when administered daily or in a 14-d sustained-release vehicle.


Effects of isolation of calves on growth, behavior, and first lactation milk yield of Holstein cows. Holstein (n = 323) calves in the herds of four experiment stations were reared individually (control) or in isolation to 70 d of age to determine whether isolation affected growth, behavior, and first lactation yield. Treatment differences were not observed for average daily gain for BW at d 28, 56 or 70. Postweaning approach distance was measured in two herds (n = 122; n = 28). Detailed pre and post-weaning behaviors were reported in one herd (n = 26). Isolation did not affect subsequent milk yield or culling percentages. In a second experiment, seven pairs of monozygous twins and a set of identical triplet calves were obtained by transferring split embryos into recipients, one member of each pair was reared in a group, and the twin was reared in isolation. Early rearing previously had been found to affect growth, feed intake, dominance rank, and learning ability of calves, and, in our study, the subsequent milk yield of calves reared in isolation tended to average more than for calves in groups. Intraclass correlations between monozygous twin pairs for milk, fat, relative value milk, and relative value fat were lower than anticipated. These data indicate that preweaning isolation did not affect first lactation milk yield traits.


Effects of a prolonged-release formulation of sometribove (n-methionyl bovine somatotropin) on Jersey cows. Milk production, feed efficiency, health, and reproduction were evaluated in 46 Jersey cows that received either 500 mg of sometribove (n-methionyl bST) in a prolonged-release formulation or an equivalent volume of excipient bi-weekly beginning at 60 +/- 3 DIM. Cows were fed a TMR for ad libitum intake and were milked twice daily. Treatment with sometribove increased 3.5% FCM production 5.3 kg/d (31.4%) over controls. Milk composition was not changed, except that milk P content averaged 51 ppm higher in bST-treated cows. Net energy intake was 4.8 Mcal/d (22.9%) higher in the bST-treated cows than in the controls. General health of all cows was good throughout the study, but the cows treated with bST had more cases of mastitis than did the control cows. The bST treatment produced localized reactions at the site of injection in some cows, but these reactions did not affect milk production. Sometribove treatment had no effect on reproductive performance; 85% of the treated and 100% of the control cows calved successfully. Treatment with bST for a full lactation did not affect performance during the initial 60 d of the subsequent lactation.


Bovine somatotropin: review of an emerging animal technology. One of the first potential biotechnology products for animal production is bST. Research in the technology of bST has involved scientists and support from federal agencies, universities, and private industry. As a consequence of this extensive cooperation, more than 1000 bST studies have been conducted, which involved over 20,000 dairy cows, and results have been confirmed by scientists throughout the world. This quantity of published research is unprecedented for a new technology and greater than most dairy technologies in use. In contrast to steroids, bST is a protein hormone. Milk yield and persistency responses to bST have been observed for all dairy breeds examined. Quality of management is the major factor affecting magnitude of milk response to bST. The mechanism of action of bST involves a series of orchestrated changes in the metabolism of body tissues so that more nutrients can be used for milk synthesis. It is these coordinated changes that allow the animal to achieve an increased milk yield while remaining normal and healthy. Bioenergetic studies demonstrated that bST-supplemented animals are not stressed. Similarly, there are no adverse health effects from bST even under poor management conditions. Composition of milk (fat, protein, lactose, cholesterol, minerals, and vitamins) is not substantially altered when bST is used and does not differ in manufacturing characteristics. Public perception is of paramount importance if bST or any new technology is to be effectively implemented. New technology must be understood and perceived as safe and beneficial both by farmers, who would utilize it, and consumers, who would purchase the dairy products. With bST use, a unit of milk is produced with less feed and protein supplement and with a reduction in animal excreta (manure, urine, and methane). Nationally, the use of bST simply reinforces, but does not fundamentally change, dairy industry trends of increased milk yield per cow, reduced number of cows, and declining dairy farm numbers. For individual farms, bST technology is size-neutral. However, poorly managed farms where animals are stressed, underfed, or sick are at an economic disadvantage because they will achieve negligible milk response to bST.


Relationship between rumen bacterial concentrations and total numbers. Based on data from 33 sheep, bacterial concentrations per gram of rumen contents were correlated highly with total bacterial numbers (r = .99). Diets ranged from all forage to 90% concentrate. Similar data were obtained from cattle fed a corn silage diet (r = .95); however, the slope of the regression lines differed between species. Weight of rumen contents was correlated poorly with total bacterial numbers.


Improved rearrangement of the integrated Michaelis-Menten equation for calculating in vivo kinetics of transport and metabolism. A multiple regression form of the integrated Michaelis-Menten equation was developed and evaluated with simulated data having controlled error. Both multiple and traditional linear regression fit errorless data perfectly, but multiple regression is much more stable with regard to accuracy and precision of estimating the Michaelis constant and maximum rate of reaction when data contain error. Bias in determining estimators of kinetic coefficients was -4 and -3% versus -56 and -35% with 10% error in the data. Multiple regression estimates for Michaelis constant and maximum rate of reaction directly as opposed to estimating 1/Km and maximum rate of reaction/Michaelis constant by linear regression. The difference in accuracy in estimating actual Michaelis constant, for example, is 4% versus 227% error with only 10% error in the data Precision of estimation is approximately the same as precision of the data for multiple regression. For the 800 data sets examined, R2 was always greater than .92 for multiple regression, but frequently was not significant for linear regression. The actual initial concentration was provided for linear regression but calculated by multiple regression with accuracy and precision equivalent to estimation of Michaelis constant and maximum rate of reaction. The multiple regression method has statistical power to determine treatment effects on Michaelis constant and maximum rate of reaction with a practical number of animals.


Relative bioavailability of manganese from a manganese-methionine complex and inorganic sources for ruminants. Two experiments were conducted to study the relative bioavailability of Mn from a feed grade Mn-Met complex or from two feed grade MnO sources using reagent grade MnSO4.H2O as the standard. In each experiment, 42 crossbred wether lambs were fed one of seven dietary treatments for 21 d and then killed; liver, kidneys, and right metacarpus were removed for MN analysis. In Experiment 1, treatment included the basal diets (34.4 ppm of Mn, DM basis) alone or supplemented with 900, 1800, or 2700 ppm of Mn as reagent grade MnSO4.H2O or feed grade Mn-Met complex. In Experiment 2, the basal diet (31.5 ppm of Mn, DM basis) was fed alone or was supplemented with 900, 1800, or 2700 ppm of Mn as reagent grade MnSO4.H2O or 1800 ppm of Mn as feed grade Mn-Met, feed grade MnO A, or feed grade MnO B. The overall estimated relative bioavailabilities based on multiple linear regression coefficients of bone, kidney, and log-transformed liver Mn concentrations on total dietary Mn concentrations were 100, 121, 70, and 53% for MnSO4.H2O, Mn-Met complex, MnO A, and MnO B, respectively.


Effect of supplementing periparturient cows with vitamin E on distribution of alpha-tocopherol in blood. Holstein cows were fed 0 or 1000 IU/d of supplemental vitamin E during the dry period and injected with placebo or 3000 IU of vitamin E at 10 and 5 d prior to anticipated calving. Blood was collected at various times, starting at 60 d prepartum (dry off) and concluding 30 d postpartum, and separated into plasma, red blood cells, and neutrophils. Oral supplementation increased concentrations of alpha-tocopherol in plasma and red blood cells on 10 d, but not on 5 d prepartum. Injection of vitamin E increased alpha-tocopherol in plasma, red blood cells, and neutrophils at d 5 prior to and on the day of parturition. Concentrations of alpha-tocopherol and cholesterol in plasma were correlated, and both were at their nadir at parturition. Concentrations of alpha-tocopherol in plasma and red blood cells were correlated, but the correlation increased when plasma alpha-tocopherol was expressed per unit of cholesterol. alpha-Tocopherol in plasma and neutrophils had a low correlation. Injection of alpha-tocopherol increased its concentration in plasma, red blood cells, and neutrophils during the periparturient period. Concentration of alpha-tocopherol in plasma of periparturient cows may be limited by its low lipid content, and transport mechanisms for alpha-tocopherol may differ between red blood cells and neutrophils.


Amino acid limitation and flow to duodenum at four stages of lactation. 1. Sequence of lysine and methionine limitation. Four Holstein cows with ruminal and duodenal cannulas were assigned to a 4 x 4 Latin square at each of four stages of lactation (peak, wk 4; early, wk 8 to 12; mid, wk 17 to 21; and late, wk 27 to 31). Treatments were duodenal infusions of 1) Met, 2) Lys, 3) Met plus Lys, and 4) casein; periods were 7 to 10 d. Quantities of DL-Met, L-Lys, and casein infused at the four stages of lactation were 12, 30, and 400; 12, 30, and 400; 10, 25, and 333; and 8, 20, and 266 g/d, respectively. Rations were composed of corn and grass-legume silages, corn meal, wheat middlings, soybean meal, and distillers dried grains with solubles. Intake of CP (percentage of NRC) and percentage of total CP from corn sources were (peak) 87, 56; (early) 90, 71; (mid) 98, 73; and (late) 114, 77. Using content and yield of milk protein as primary response criteria, Lys appeared to be first-limiting and Met second-limiting at peak lactation, their infusion together resulted in the same production of milk (40 kg/d) and milk protein (1135 g/d) as did casein. Lysine was first-limiting in early lactation, but whether Met was second-limiting was questionable. The two AA were colimiting in midlactation. There appeared to be no AA deficiencies in late lactation. Amounts of Lys and Met (percentage of total essential AA) in duodenal digesta during peak (12.4, 3.7), early (12.6, 3.5), and midlactation (14.9, 3.9) were not adequate for optimal AA utilization.


Amino acid limitation and flow to the duodenum at four stages of lactation. 2. Extent of lysine limitation. Four multiparous Holstein cows with ruminal and duodenal cannulas were assigned to 4 x 4 Latin squares at peak (wk 4), early (wk 14 to 16), mid (wk 21 to 23), and late (wk 29 to 31) lactation to determine, in the presence of supplemental Met, the extent of Lys limitation and its required contribution to total essential AA in duodenal digesta. Treatments were duodenal infusions of 1) water alone or water with 2) 10 g/d of DL-Met plus 10 g/d of L-Lys, 3) 10 g/d of Met plus 20 g/d of Lys, and 4) 10 g/d of Met plus 30 g/d of Lys; quantities were reduced by 20% in late lactation. Rations were corn based (corn and grass-legume silages, corn meal, wheat middlings, soybean meal, and distillers dried grains with solubles) and most limiting in Lys and Met. Intakes of ruminally degraded and undegraded intake protein (percentage of NRC requirements) were (peak) 115, 97; (early) 112, 83; (mid) 113, 87; and (late) 127, 96. Contribution of Lys to passage of total essential AA to the duodenum without infusions were 13.2, 12.4, 13.8, and 14.8% at the four respective stages of lactation. Extent of Lys limitation determined from responses in content and yield of milk protein approximated 25, 20, and 10 g/d during peak, early, and midlactation.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of raw pea flour on nutrient digestibility and immune responses in the preruminant calf. Two milk substitute diets for which the protein was provided either exclusively by skim milk powder (control) or partially (34%) by dehulled raw pea flour were given for 2 and 4 wk, respectively, to five preruminant calves, each fitted with a reentrant ileocecal cannula. Ileal apparent digestibility was lower with the pea diet during wk 1 than with the control diet. Four of the cannulated calves exhibited significant intolerance to the pea diet, resulting in lower digestibility during wk 4. In contrast, fecal digestibility of the pea diet, measured in four additional calves without reentrant cannulas, did not significantly decrease between wk 1 and 4. The AA composition of ileal digesta from the first group of calves did not vary greatly, suggesting that the differences observed in their apparent digestibility of proteins were due mainly to changes in the loss of endogenous proteins. However, pea legumin survived digestion in the small intestine in amounts generally equivalent to 1 to 3% of intake. Most of that undigested fraction was smaller than the native legumin: 40 to 200 kDa instead of 360 kDa. Also, a 45-kDa fragment was detected in the urine. Increased intestinal permeability could have favored the development of the high systemic anti-pea antibody titers that were observed in all of the calves.


Predicting body weight and wither height in Holstein heifers using body measurements. Relationships between body weight, wither height, and various other body traits, including heart girth, body length, and hip width, were studied using data from six experiments with 2625 observations. Body weight and wither height were regressed on the other body traits. Regressions of body weight including the linear, quadratic, and cubic effects of a single independent variable (heart girth, wither height, hip width or body length) indicated that each measurement would be useful in predicting body weight (R2 > .95); the regression of body weight on heart girth had the highest R2, followed by hip width. Similarly, regressions of wither height on heart girth, wither height, hip width, or body length, including linear, quadratic, and cubic effects, yielded R2 > .99. Regressions considering multiple traits as independent variables showed that the addition of a second body trait added little to the already high multiple correlations found with a single variable. In management situations for which body weight or wither height cannot be measured, various other traits can be used to estimate these body measurements accurately.


Anisotropy of ultrasonic velocity and elastic properties in normal human myocardium. Measurements of ultrasonic quasilongitudinal velocity were made in the muscle fiber plane of excised human myocardium. Multiple adjacent planes across the left ventricular wall were interrogated to assess the transmural dependence of velocity. For each measurement plane, data were obtained in 2-deg increments through the full 360 deg relative to the myofibers. An approximate 1.3% magnitude of anisotropy was observed with maximum velocity along the muscle fibers and minimum velocity perpendicular to the muscle fibers. The known transmural shift in myofiber orientation was evidenced in the anisotropy of velocity as angular shifts between plots obtained from adjacent transmural planes within the same specimen. Measured values of velocity and density were used to estimate the effective C33 and C11 elastic constants of a thin layer of normal myocardium.


20-Hz pulses and other vocalizations of fin whales, Balaenoptera physalus, in the Gulf of California, Mexico. Low-frequency vocalizations were recorded from fin whales, Balaenoptera physalus, in the Gulf of California, Mexico, during three cruises. In March 1985, recorded 20-Hz pulses were in sequences of regular 9-s interpulse intervals. In August 1987, nearly all were in sequences of doublets with alternating 5- and 18-s interpulse intervals. No 20-Hz pulse sequences of any kind were detected in February 1987. The typical pulse modulated from 42 to 20 Hz and its median duration was 0.7 s (1985 data). Most other fin whale sounds were also short tonal pulses averaging 82, 56, and 68 Hz, respectively, for the three cruises; 89% were modulated in frequency, mostly downward. Compared to Atlantic and Pacific Ocean regions, Gulf of California 20-Hz pulses were unique in terms of frequency modulation, interpulse sound levels, and temporal patterns. Fin whales in the Gulf may represent a regional stock revealed by their sound characteristics, a phenomenon previously shown for humpback whales, birds, and fish. Regional differences in fin whale sounds were found in comparisons of Atlantic and Pacific locations.


Structural design of hidden Markov model speech recognizer using multivalued phonetic features: comparison with segmental speech units. A novel approach to speech recognition, on the basis of a multidimensional multivalued phonetic-feature description of speech signals, is presented and evaluated. The hidden Markov model (HMM) framework is used to provide the recognition algorithm, which assumes that the underlying Markov chain tracks the temporal evolution of the features. It is shown that this approach can naturally accommodate such coarticulatory effects as feature spreading and formant transition in the functionality of the recognizer, and can provide a high degree of acoustic data sharing that makes effective use of training data. Use of phonetic features as the basic speech units creates a framework where the Markov model's state topology in the recognizer can be designed with guidance of detailed speech knowledge. Details of such a design for a stop consonant-vowel vocabulary are described. Experimental results on the task of speaker-dependent stop consonant discrimination, evaluated from speech data from a total of ten male and five female speakers, demonstrate effectiveness of this feature-based recognizer. Over the 15 speakers, the error rates were shown to be reduced by 23%, 37%, 42%, and 38%, respectively, compared with the conventional HMM-based recognition methods using words, phonemes, allophones, and microsegments as the primary speech units.


Consonant recognition by some of the better cochlear-implant patients. Fifty-four of the better cochlear-implant patients from Europe and the United States were tested on two consonant recognition tests using nonsense syllables. One was produced in an accent appropriate for their own language by a male and a female talker. Recorded tokens of /ibi, idi, igi, ipi, iti, iki, ifi, ivi, ifi, isi, izi, imi, ini/ were presented. With the French syllables, six patients with the Chorimac device averaged 18% correct (6%-29%). With the German syllables, nine patients with the 3M/Vienna device averaged 34% correct (17%-44%), ten patients with the Nucleus device (tested in Hannover) averaged 31% correct (19%-42%), and ten patients with the Duren/Cologne device averaged 27% correct (10%-56%). With the English syllables, ten patients with the Nucleus device (tested in the United States) averaged 42% correct (29%-62%), and nine patients with the Symbion device averaged 46% correct (31%-69%). An information-transmission analysis and sequential information-transfer analysis of the confusions suggested that different implants provided differing amounts of feature information. The place of articulation feature was typically the most difficult to code for all implants. In the second test a male and a female talker recorded the stimuli /ibi, idi, igi, imi, ini, ifi, isi, izi/ in a single manner that was appropriate for all three languages. Six patients with the Chorimac device averaged 27% (13%-48%), ten patients with the Duren/Cologne implant averaged 29% (15%-75%), ten patients with the Nucleus device (tested in Hannover) averaged 40% (25%-58%), ten patients with the Nucleus device (tested in the United States) averaged 49% (40%-60%), nine patients with the Symbion device averaged 61% (40%-75%), and nine patients with the 3M/Vienna device averaged 41% (29%-52%) correct.


Electromagnetic midsagittal articulometer systems for transducing speech articulatory movements. This paper describes two electromagnetic midsagittal articulometer (EMMA) systems that were developed for transducing articulatory movements during speech production. Alternating magnetic fields are generated by transmitter coils that are mounted in an assembly that fits on the head of a speaker. The fields induce alternating voltages in a number of small transducer coils that are attached to articulators in the midline plane, inside and outside the vocal tract. The transducers are connected by fine lead wires to receiver electronics whose output voltages are processed to yield measures of transducer locations as a function of time. Measurement error can arise with this method, because as the articulators move and change shape, the transducers can undergo a varying amount of rotational misalignment with respect to the transmitter axes; both systems are designed to correct for transducer misalignment. For this purpose, one system uses two transmitters and biaxial transducers; the other uses three transmitters and single-axis transducers. The systems have been compared with one another in terms of their performance, human subjects compatibility, and ease of use. Both systems can produce useful midsagittal-plane data on articular movement, and each one has a specific set of advantages and limitations. (Two commercially available systems are also described briefly for comparison purposes). If appropriate experimental controls are used, the three-transmitter system is preferable for practical reasons.


Intensity discrimination under backward masking. The Weber fraction was measured for a 25-ms sinusoidal pedestal presented 100 ms before, or 100 ms after, an intense narrow-band noise. Consistent with the finding of Zeng et al. [Hear. Res. 55, 223-230 (1991)], the forward masker caused an elevation in the Weber fraction at medium pedestal levels. Surprisingly, however, a much larger midlevel elevation was observed in the backward masking conditions; in some cases, the Weber fraction was increased by over 20 dB by the backward masker. In both masking conditions, presenting a notched noise simultaneously with the pedestal reduced the magnitude of the midlevel elevation. These results indicate that it is possible to produce large masking effects on intensity discrimination in conditions where there is no possibility of the masker affecting the representation of the pedestal at the level of the auditory nerve. This suggests that there may be "central" processes underlying the original finding of Zeng et al. Despite the similarities in the results, however, it is not certain that the elevations seen in the forward and backward masking conditions were caused by the same mechanisms.


Frequency discrimination in forward and backward masking. Frequency difference limens for pure tones preceded by a forward masker or followed by a backward masker were obtained across a wide range of signal levels. Relkin and Doucet [Hear. Res. 55, 215-222 (1991)] have shown that at a masker-signal delay of 100 ms, the thresholds of high-SR (spontaneous rate) auditory-nerve fibers are recovered, while the low-SR fiber thresholds are not. Therefore, forward-masked frequency discrimination potentially offers a method to investigate the role of low-SR fibers in the coding of frequency. It has been shown that when an intense forward masker is presented 100 ms before a pure-tone signal, intensity difference limens are elevated for mid-level signals [Zeng et al., Hear. Res. 55, 223-230 (1991)]. However, Plack and Viemeister [J. Acoust. Soc. Am. 92, 3097-3101 (1992)] have shown that a similar elevation in the intensity difference limen is obtained under conditions of backward masking, where selective adaptation of the auditory neurons would not be expected to occur. A condition of backward-masked frequency discrimination was therefore included to investigate the role of interference resulting from adding additional stimuli to a discrimination task. For signals at 1000 and 6000 Hz, there was no effect of a forward masker upon frequency difference limens. For the backward-masked conditions, an elevation of the frequency difference limen was observed at all signal levels, demonstrating that the effects of forward and backward maskers upon frequency discrimination are dissimilar and suggesting that cognitive effects are present in backward-masked discrimination tasks.(ABSTRACT TRUNCATED AT 250 WORDS)


The "proportion-of-the-total-duration rule" for the discrimination of auditory patterns. A principle of auditory perception that governs the detectability of changes in components in unfamiliar sequences of tones is demonstrated in four experiments. The proportion-of-the-total-duration (PTD) rule can be stated as follows: Each individual component of an unfamiliar sequence of tones is resolved with an accuracy that is a function of its proportion of the total duration of the sequence or "pattern." An adaptive-tracking frequency-discrimination task was used in all experiments. Experiment 1 demonstrated that the PTD rule holds over a wide range of total pattern durations, numbers of components, and component durations. Experiment 2 demonstrated that the PTD rule governs discrimination performance despite variation in the relative durations of context and target tones. Experiment 3, using a variable temporal position for the target, confirmed that the PTD effect does not require that a listener be able to anticipate the temporal location of the target tone. Experiment 4, using two target tones, showed that the PTD rules applies to the proportional duration of individual components within patterns and not to the total proportional duration of nonadjacent components within the pattern. These findings are incompatible with performance limitations based on a fixed-duration short-term memory capacity and with versions of informational limitations in which the amount of information in a pattern varies either with the number of components or with the total pattern duration. The PTD rule appears to reflect the way listeners distribute their attention when presented with unfamiliar complex sounds that have no structural properties (other than proportional duration) that significantly increase the salience of individual components.


Detection of combined frequency and amplitude modulation. This article is concerned with the detection of mixed modulation (MM), i.e., simultaneously occurring amplitude modulation (AM) and frequency modulation (FM). In experiment 1, an adaptive two-alternative forced-choice task was used to determine thresholds for detecting AM alone. Then, thresholds for detecting FM were determined for stimuli which had a fixed amount of AM in the signal interval only. The amount of AM was always less than the threshold for detecting AM alone. The FM thresholds depended significantly on the magnitude of the coexisting AM. For low modulation rates (4, 16, and 64 Hz), the FM thresholds did not depend significantly on the relative phase of modulation for the FM and AM. For a high modulation rate (256 Hz) strong effects of modulator phase were observed. These phase effects are as predicted by the model proposed by Hartmann and Hnath [Acustica 50, 297-312 (1982)], which assumes that detection of modulation at modulation frequencies higher than the critical modulation frequency is based on detection of the lower sideband in the modulated signal's spectrum. In the second experiment, psychometric functions were measured for the detection of AM alone and FM alone, using modulation rates of 4 and 16 Hz. Results showed that, for each type of modulation, d' is approximately a linear function of the square of the modulation index. Application of this finding to the results of experiment 1 suggested that, at low modulation rates, FM and AM are not detected by completely independent mechanisms. In the third experiment, psychometric functions were again measured for the detection of AM alone and FM alone, using a 10-Hz modulation rate. Detectability was then measured for combined AM and FM, with modulation depths selected so that each type of modulation would be equally detectable if presented alone. Significant effects of relative modulator phase were found when detectability was relatively high. These effects were not correctly predicted by either a single-band excitation-pattern model or a multiple-band excitation-pattern model. However, the detectability of the combined AM and FM was better than would be predicted if the two types of modulation were coded completely independently.


Effect of multiple speechlike maskers on binaural speech recognition in normal and impaired hearing. Speech-reception thresholds (SRT) were measured for 17 normal-hearing and 17 hearing-impaired listeners in conditions simulating free-field situations with between one and six interfering talkers. The stimuli, speech and noise with identical long-term average spectra, were recorded with a KEMAR manikin in an anechoic room and presented to the subjects through headphones. The noise was modulated using the envelope fluctuations of the speech. Several conditions were simulated with the speaker always in front of the listener and the maskers either also in front, or positioned in a symmetrical or asymmetrical configuration around the listener. Results show that the hearing impaired have significantly poorer performance than the normal hearing in all conditions. The mean SRT differences between the groups range from 4.2-10 dB. It appears that the modulations in the masker act as an important cue for the normal-hearing listeners, who experience up to 5-dB release from masking, while being hardly beneficial for the hearing impaired listeners. The gain occurring when maskers are moved from the frontal position to positions around the listener varies from 1.5 to 8 dB for the normal hearing, and from 1 to 6.5 dB for the hearing impaired. It depends strongly on the number of maskers and their positions, but less on hearing impairment. The difference between the SRTs for binaural and best-ear listening (the "cocktail party effect") is approximately 3 dB in all conditions for both the normal-hearing and the hearing-impaired listeners.


Neural network models of sound localization based on directional filtering by the pinna. Three-layer neural-network functions were developed to transform spectral representations of pinna-filtered stimuli at the input to a space-mapped representation of sound-source direction at the output. The inputs are modeled after transfer functions of the external ear of the cat; the output is modeled on the spatial sensitivity of superior colliculus neurons. Network solutions are obtained by backpropagation and by a method that enforces uniform task distribution in the hidden layer of the model. Solutions are characterized using bandlimited inputs to study the relative strength of potential sound localization cues in various frequency regions. This analysis suggests that the frequency region containing the first spectral notch (5-18 kHz) provides the best localization cues. Response properties of model neurons were studied using input patterns modeled after auditory nerve response profiles to pure tones at various frequencies and sound levels. The response properties of hidden layer model neurons resemble cochlear nucleus types III and IV and their composites. Neurons in both hidden and output layers show the properties of spectral notch detectors. Although neural networks have limitations as models of real neural systems, the results illustrate how they can provide insight into the computation of complex transformations in the nervous system.


Analysis of dynamic behavior of human middle ear using a finite-element method. Applying the general-purpose finite-element package program (ISAP), a three-dimensional finite-element method (FEM) model of a human right middle ear, which included ossicles, was made and the mechanical properties and boundary conditions of the middle ear were determined by a comparison between the numerical results obtained from the FEM analysis and the measurement results of the fresh cadavers, normal subjects and patients, which were obtained by our developed sweep frequency middle ear analyzer (MEA). The "Elastic" boundary condition consisting of linear and torsional springs at the eardrum attachments to the annular ligament was more appropriate for the actual condition than "fully clamped" one. Rotational axis of the ossicular chain was assumed to be a fixed straight line from the anterior process of the malleus to the short process of the incus, and a load of the ossicular chain and cochlea was simplified to be expressed by the stiffness of the cochlea. Vibration patterns of the eardrum and ossicles at the first resonance frequency, obtained under these assumptions, were in agreement with the experimental results obtained by means of time-averaged holography and by using a video measuring system, except for the relatively large displacements at the tympanic ring.


Elasticity and active force generation of cochlear outer hair cells. The cochlear outer hair cell is described by a cylindrical membrane model, characterized by area and shear moduli for a passive elastic element and an active tension element dependent on the membrane potential. In passive experiments, these moduli are determined from the pressure-strain relations. The area modulus obtained is 0.07 N m-1, similar to a lipid bilayer and the shear modulus is 0.007 N m-1. These moduli combined with previous active experiments show that the active tension is nearly isotropic and is about 1.6 x 10(-2) N m-1 V-1, resulting in a 0.5 nN/mV force per cell. This implies that the receptor potential for acoustical stimulation produces an active force comparable to the acoustic force applied to the basilar membrane per outer hair cell. This finding supports the hypothesis that the outer hair cell acts as feedback motor in the fine tuning mechanism of the mammalian ear.


Place specific influences on the wave I to V interpeak latency of the auditory brain-stem response. There is controversy over whether the wave I to V interpeak latency (I-V IPL) of the auditory brain-stem response can be manipulated by cochlear processing. In this study, a forward masking paradigm was used to test the predictions of two contrasting models of I-V IPL generation. The paradigm was designed to determine if the I-V IPL can be affected by masking selected portions of the cochlear response region. The results from ten normal hearing subjects suggest that: (1) waves I and V can be masked semi-independent of each other, and (2) the I-V IPL can be shortened or prolonged by masking the basal or apical portion of the cochlear response region respectively. These findings support the hypothesis that, at least in normal hearing subjects, wave V is biased to reflect more apical cochlear events than wave I. Additionally, they offer tentative support for anecdotal reports of shortened I-V IPLs in the presence of high-frequency hearing loss.


Academic levels in nursing.

Academic levels in nursing. With the developments of new academic courses in nursing comes the need for a debate about educational levels. This paper offers a discussion of some of the issues involved in such a debate and draws upon data collected from professors of nursing in the United Kingdom, masters students in a Dutch college and from the American literature on the topic. The need to be able to distinguish between diploma, bachelors, masters and doctoral degrees is highlighted and various suggestions about how such distinctions may be made are offered.


Outcomes evaluation: measuring critical thinking. Nursing education, along with higher education in general, is increasingly focusing on educational outcomes; critical thinking is one of these outcomes. This study examined the impact of a baccalaureate registered nurse programme on the critical thinking skills of students. Students were tested upon entry and exit of the programme and a significant (0.05) difference was found. Subtest gains were significant (0.05) on Recognition of Assumptions, and Deductions. A significant relationship (0.05) between the nursing grade point average (GPA) and the post-test total score existed, accounting for a variance of 4%. No relationship was found between the post-test total score and the general education GPA. The two GPA correlation coefficients were significantly different from one another (0.05). Since one goal of professional nursing education is to prepare nurses who engage in complex problem solving and critical thinking, both the curriculum and teaching strategies need to enhance these skills.


Evaluation of teaching: a review of the literature. Although most faculty members would agree that teaching is a vital component of their role, the evaluation of teaching continues to receive less attention than the evaluation of other academic pursuits. This paper reviews the nursing and education literature related to the evaluation of teaching. The bulk of the literature reviewed focused on the following: current issues of faculty evaluation, appraisal criteria of effective teaching, and evaluators of teaching effectiveness. The paucity of literature related to the process of faculty evaluation provides further evidence that there is a gap between what institutions say is important and what is actually practised. The implementation of faculty evaluation models may be one remedy to this current problem.


Adventurous outdoor activities: a review and a description of a new service delivery package for clients with learning difficulties who have behaviours which challenge services or society. The purpose of this paper is to describe the need for and the creation of a new service delivery package for the client with learning difficulties whose behaviour challenges services or society, or who is a 'victim of the system', and not responding to available resources. Adventure-based courses are delivered in a context of supportive therapy which effects measurable change. There is continuing research-based evaluation of this new approach which will be reported in due course.


Changing attitudes towards families of hospitalized children from 1935 to 1975: a case study. The introduction of 'open' visiting and family involvement in the care of hospitalized children created a revolution in the care of children in hospitals. This historical study utilized the situation at the Hospital for Sick Children, Toronto (HSC), as a case study illustrating change. Although psychological research provided a strong rationale for including families in the care of hospitalized children, change occurred slowly. In this regard, HSC was typical of many children's hospitals. However, there seemed to be a significant failure to learn from innovations elsewhere. Paediatric nurses, in particular, were slow to encourage family visiting and participation in care.


Patient participation: its meaning and significance in the context of caring. The ideal that patients should be participants in their own care has found wide acceptance amongst nurses. Yet within the academic discipline of nursing little has been done to clarify the nature of participation. In this paper, a phenomenology of participation is presented as it applies to the caring work of nursing. Participation requires: (a) attunement to a mutual 'stock of knowledge at hand'; (b) emotional and motivational attunement to the other's concerns; (c) taking for granted (and implicitly assuming the other takes it for granted) that one can contribute worthily; (d) feeling that one's identity is not under threat. Though it is difficult to attain, participation appears to embody many of the ideals central to current thinking in nursing. Moreover, the attempt to build participatory relationships with patients is ethically required of members of a 'caring' profession.


Health beliefs: a cultural division?

Health beliefs: a cultural division? Uptake of preventive health programmes seems to be related to people's underlying motivations, attitudes and beliefs about health and illness. Current theories used to account for variance in behaviours by social group (such as the health belief model and locus of control model) explain only some of the variance in these motivations and attitudes, and have not been adequately tested on women from different ethnic minority groups. Health beliefs have important implications for nursing given the role of the nurse in health promotion and patient teaching. This paper identifies and compares the health beliefs of women of Asian origin and white indigenous women living in an inner-London borough, through in-depth semi-structured interviews, and considers the findings in relation to health promotion practices and the role of the nurse. The Asian women rated their health as worse than the white women; this requires further study. Comments and views gathered about the causes of various diseases indicated that it may be unrealistic to fit a person's health beliefs into a distinct model. Beliefs about disease appeared to be culturally sensitive; health education, therefore, must also be culturally sensitive.


Lack of professional latitude and role problems as correlates of propensity to quit amongst nursing staff. Which job stressors are the best predictors of propensity to quit among the nursing staff in emergency wards and intensive care units are explored in this paper. Employees of 30 Quebec hospitals (i.e. 60 wards in total) participated in the study (n = 1237). Stepwise multiple regression revealed that lack of professional latitude and role problems are the best predictors of the intention to quit the organization among all nursing staff. These two job stressors are briefly addressed in the context of intervention and possible remedies aiming at improving quality of life, mental health and decreasing the rate of turnover. It is argued that such intervention would benefit the nurses, the quality of patient care, as well as the respective hospitals.


Seeking approval for research access: the gatekeeper's role in facilitating a study of the care of the relinquishing mother. While undertaking a study of midwives' care of mothers relinquishing a baby for adoption, the search for permission for access provided valuable insights into the role and functioning of the 'gatekeepers', who included a range of nursing/midwifery personnel and others. The benefits and positive aspects of this process are discussed. The variability of the response to the request for permission for research access gives insight into the gatekeepers' decision-making process. The functioning of research ethics committees is shown to be unpredictable. The gatekeepers' comments are related to the comments made by mothers in an early stage of the study. The way in which the gatekeepers utilize their own individual experience is crucial to their decisions regarding permitting research access. This experience may take the form of personal experience, occupational experience or experience of research.


Research and the practice of midwifery.

Research and the practice of midwifery. During the past decade, the professional journals have contained numerous papers authored by nurses and nurse-researchers describing the gap which persists between research and clinical practice. Problems have been highlighted and challenges explored in the quest to discover ways of encouraging practitioners to become more aware of research evidence as a knowledge base for practice. Many of the identified issues may be transposed into a midwifery setting but other factors may be recognized which are specific to the practice of midwifery. This paper considers both conceptual and pragmatic issues in an attempt to explore the complexity of the influences which may affect the integration of research into midwifery practice.


Criteria for evaluating the clinical and practical utility of models used by nurses. Arguably, nursing, like all health care disciplines, is an applied science. Essentially, this refers to the application of theory in order to understand and respond to the health problems of clients. These theories may be drawn (borrowed) from any applied science, or generated inductively from clinical nursing practice. Alternatively, nurses may attempt to apply deductive theory (global theoretical frameworks) known as nursing models. In this paper, all theoretical approaches, irrespective of origin, are referred to as models used by nurses. Thirteen criteria by which clinicians, and others, can evaluate the clinical and practical utility of models used by nurses which are expressed in the form of questions are identified and discussed. The criteria are an extension, both in detail and in number, of those developed by Reynolds and Cormack and subsequently applied by those writers to the Johnson Behavioural System Model of Nursing. The value, or otherwise, of individual models, or of models in general, will not be discussed in this paper. However, the authors propose that if the evaluation criteria described here are applied to existing models, serious deficits will be identified in relation to their clinical and practical utility.


The use and limitations of Phaneuf's Nursing Audit. The use of Phaneuf's Nursing Audit in an action research project that is investigating quality assessment and peer review is discussed. A brief description of the project is given followed by an analysis of the audit tool. This analysis suggests that the tool has more disadvantages than advantages. The paper concludes with a discussion about why the tool may be of use despite the disadvantages identified.


Evaluating the quality of patient care in district nursing. This paper examines the process of evaluating the quality of care provision in district nursing at a local level. The definitions of audit and quality assurance are considered, and the current situation in community nursing is briefly compared with that in hospital settings. Finally, the use of evaluative tools in practice is examined, together with ways in which district nursing evaluation can be improved.


An examination of the implications of adopting a process approach to curriculum planning, implementation and evaluation. A process may be seen as that which has purpose, organization and structure, facilitating an act of moving forward. Thus, a process reflects Bruner's view of education as facilitating cognitive growth and as a way in which individuals explore and gain mastery over a complex world. A process approach is not without its problems, namely in that some nursing skills require a precise, predetermined outcome best achieved by the use of behavioural objectives. A curriculum promoting growth and continued learning calls for increased funding, which may cause problems in today's financial climate. Exploration of concepts calls for careful planning of practical experience and may be difficult where supernumerary status is not fully implemented. However, a process approach may reduce the theory practice gap and lead to a reflective and proactive practitioner. On-going education of clinical staff is required and increased communication between educational and clinical staff. This approach may lead to a more holistic view of nursing education and achievement measured in not only quantitative but also qualitative terms. Solving the problems that a process approach may present may cause nursing education to be enhanced.


A simplified method for determination of peptide-protein molar ratios using amino acid analysis. In this report, we have described methods to improve the efficiency of coupling synthetic peptides to keyhole limpet hemocyanin (KLH) and for the analysis of the composition of the resulting peptide-protein conjugates. KLH was first dissolved in buffers containing 3 M guanidine hydrochloride to maintain solubility and derivatized with either of two water soluble, heterobifunctional crosslinkers, m-maleimido-benzoyl-N-hydroxy-sulfosuccinimide ester (SMBS), or sulfosuccinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SSMCC) (300:1 molar excess over KLH). Synthetic peptides containing an amino terminal cysteine were then crosslinked to the modified KLH via sulfhydryl reaction with the crosslinker maleimide groups. Following dialysis to remove free peptide, the amino acid composition of the conjugate was determined. The molar ratio of peptide to protein within the conjugate was obtained by comparing the conjugate composition with that of both the KLH and peptide analyzed separately, and by a multiple regression, least squares analysis of the data. This method is generally applicable to the analysis of the molar ratios of protein-protein conjugates of unknown sequence or composition, and requires only the prior determination of the experimental amino acid composition of each component of the conjugate separately.


A simultaneous three-color T cell subsets analysis with single laser flow cytometers using T cell gating protocol. Comparison with conventional two-color immunophenotyping method. We describe a method for simultaneous analysis of CD3, CD4, and CD8 positive cells from whole blood utilizing single laser flow cytometers. All three T cell values are attained from a single test tube. CD4 and CD8 positive cells are identified only if they are CD3 positive. Thus the values obtained by this method for T helper/inducer and T cytotoxic/suppressor cells can be reported directly as a percentage of T lymphocytes. Analysis for CD4 and CD8 positive cells is accomplished, by first gating on CD3 positive T lymphocytes, hence the approach is referred to as a T gating method. As the third dye, conjugated to anti-CD3 monoclonal antibodies (MAbs), we utilized peridinin chlorophyll protein (PerCP), a new red fluorochrome. The proposed method may prove to be practical for monitoring disease progression in AIDS, where longitudinal T helper/inducer and T cytotoxic/suppressor cell enumeration must be performed unambiguously by a simple, reproducible, and fast method.


Development of a monoclonal antibody to the conserved region of p34cdc2 protein kinase. Mice and rabbits were injected with various forms of a 16 amino acid synthetic peptide representing PSTAIR, the evolutionarily conserved region of the protein kinase p34cdc2, for polyclonal antisera and hybridoma-monoclonal antibody production. Antisera from mice injected with an unconjugated monomeric form of the peptide showed no reaction to the peptide. Of four animals injected with the monomeric form of the peptide conjugated to keyhole limpet hemocyanin via m-maleimidobenzoyl-N-hydroxysulfosuccinimide (MBS), antisera from only one mouse had a very low titer to the peptide, and all four animals produced antibody to the MBS bridge. Both mice injected with an octameric multiple antigen peptide (MAP) of PSTAIR produced antisera reactive to the octameric MAP form of the peptide in ELISA and also to the cdc2 protein expressed in bacteria in an immunoblotting assay. Splenocytes from one mouse injected with the octameric MAP form of the peptide were successfully used for hybridoma-monoclonal antibody production. A monoclonal antibody was produced that reacted with octamer, monomer and cdc2-expressed protein and specifically with the carboxyl terminus of the 16 amino acid peptide.


Assessment of complement activation in clinical samples. Comparison of immunochemical and functional measurements of complement components with quantitation of activation fragments. We have compared functional and immunochemical measurements of complement components with assays measuring the generation of activation fragments, for the assessment of classical pathway activation in vitro and in vivo. The generation of the C3a, C3b/C3bi cleavage fragments of C3, and of the C4d cleavage fragment of C4 measured by ELISA and RIA, was correlated with the decrease in total complement hemolytic activity (CH50) and in functional activity of C3 and C4 in normal human serum in which the classical pathway had been activated with aggregated IgG. The decrease in CH50 in in vitro activated serum was also correlated with the generation of C5a and soluble SC5b-9 complexes. In contrast, no or little increase in the concentration of C3a, C3b/C3bi and C4d was observed in plasma samples from patients with low CH50 and with low levels of immunochemical C3 and C4, indicating that fragment quantitation assays provide no information on the presence and extent of complement activation in vivo. Analysis of samples from patients expressing the four C4 genes and patients having one or two C4 null alleles indicated that a ratio of hemolytic C4 to C2 > or = 1 was indicative of complement activation without C4 deficiency, whereas a ratio below 1 was indicative of C4 deficiency with or without classical pathway consumption. Classical pathway activation and C4 deficiency in clinical samples are best predicted by the concomitant assessment of immunochemical levels of C3 and C4 and hemolytic levels of C4, C2 and C3.


A new method for measuring clustering in suspension between accessory cells and T lymphocytes. Specifying the molecular basis and clinical significance of cluster formation between antigen-presenting cells and T lymphocytes will be important in many areas of immunology. In this paper we describe a novel and reproducible technique for measuring cluster formation in suspension between purified human blood monocytes and purified autologous T lymphocytes, and its application to determining the effects of recall antigens and mitogen. Blood monocytes and T lymphocytes from eight normal subjects were separately prelabelled with two different carbocyanine dyes prior to co-culture in suspension with or without antigen (PPD, SKSD) or mitogen (PHA). At 24 h the co-cultures were examined for cluster formation by ultraviolet microscopy and flow cytometry. Control experiments showed that the carbocyanine dyes were non-toxic in vitro, that cell labelling was stable for culture periods up to 120 h, and that the two dyes did not leak from cell to cell. By this technique we measured the proportion of monocytes clustering one or more T lymphocytes in the presence and absence of recall antigen or PHA. There was a close correlation between visual and flow cytometric measurement of monocyte: T lymphocyte clustering (p < 0.001) as well as a close relationship between the ability of the two recall antigens to increase the extent of clustering above baseline (p < 0.001). Antigen-increased cluster formation did not correlate with baseline clustering, unlike PHA-increased clustering, which was related to baseline levels (p = 0.02), suggesting the operation of distinct mechanisms. The method is applicable to measuring cell-cell associations in suspension during extended periods of culture, as well as for the study of agents which might modify intercellular adhesion processes.


A simplification of the enzyme-linked immunospot technique. Increased sensitivity for cells secreting IgG antibodies to Haemophilus influenzae type b capsular polysaccharide. A simplified enzyme-linked immunospot (ELISPOT) technique is described for the detection of cells secreting antibodies to tetanus toxoid (TT), diphtheria toxoid (DT) or Haemophilus influenzae type b capsular polysaccharide (PRP). By combining the cell suspension with the enzyme-linked secondary antibodies in one incubation, the second incubation and washing procedure could be omitted from the original technique. The simplified assay had the same sensitivity for anti-TT and anti-DT spot-forming cells as the ordinary ELISPOT assay. The IgG anti-PRP spots were, however, improved both in quality and in quantity (median: 40% more spots), while the detection of IgM and IgA anti-PRP spot-forming cells was the same in the two techniques. This simplified technique can probably also be used to save time in other antigen systems and should be considered when designing ELISPOT assays for the detection of polysaccharide-specific antibody-secreting cells.


Differential reactivity of Agaricus bisporus lectin with human IgA subclasses in gel precipitation. The interaction between purified Agaricus bisporus lectin and several human proteins was studied using the Ouchterlony double diffusion and immunoelectrophoresis techniques. Only one precipitation line was observed with normal human serum, normal human colostrum, IgA1 myeloma serum, both serum monoclonal and secretory IgA1 and monoclonal IgD. No reaction was observed with monoclonal and secretory IgA2, IgG, IgM, alpha 2 macroglobulin or pregnancy-associated alpha 2 glycoprotein. These results were confirmed by hemagglutination inhibition assays when IgA1, IgA2 and IgD were tested. On the basis of this reactivity, ABL could be a useful tool for distinguishing and isolating human IgA subclasses.


Kinetics of antibody binding at solid-liquid interfaces in flow. We have developed the theoretical framework for a displacement immunoassay conducted in flow under nonequilibrium conditions. Using a repetitive displacement technique, we determined the displacement rate and apparent dissociation rate constant at different flow rates. Our data suggest that the kinetics are best described by a first-order function. The displacement efficiency, the displacement rate, and therefore the apparent dissociation rate constant were calculated and demonstrated to be flow rate dependent. The theoretical framework developed in this study was successful in predicting the behavior of antigen displacement in flow.


Measurement of antigen-dependent interleukin-4 production by human peripheral blood mononuclear cells. Introduction of an amplification step using ionomycin and phorbol myristate acetate. The study of T cell responses in parasitic disease and allergy in humans has been limited by difficulties in the measurement of interleukin-4 (IL-4) in supernatants from antigen-stimulated peripheral blood mononuclear cells (PBMC). To obtain measurable amounts of IL-4 in vitro, we have added an amplification step to the antigen-specific response. Human PBMC were stimulated by tetanus toxoid (TT) or tuberculin (PPD) for 6 days and then pulsed with ionomycin and phorbol myristate acetate (PMA) for 24 h. TT-stimulated cells from nine revaccinated donors but not from seven unvaccinated donors and four that had only received childhood vaccinations against tetanus produced high levels of IL-4 (median (range) 1500 (300-3800), 316 (0-1600), and 270 (100-410) pg/ml, respectively, as measured by an enzyme linked immunosorbent assay, P = 0.005). PPD did not increase IL-4 production above the background level, although the majority of PPD-stimulated PBMC proliferated and produced interferon-gamma (IFN-gamma) in cultures without ionomycin and PMA. TT-induced IL-4 production correlated positively with proliferation. Culture supernatants did not interfere with IL-4 immunoreactivity and failed to affect ionomycin and PMA induced IL-4 production. The findings suggest that proliferating antigen-specific T cells were the source of IL-4 in these experiments. The method should prove useful for comparing the IL-4 producing ability of antigen-specific T cells from different individuals.


Application and limitations of the multiple antigen peptide (MAP) system in the production and evaluation of anti-peptide and anti-protein antibodies. The multiple antigen peptide (MAP) system has been proposed as a novel and valuable approach for eliciting antibodies to peptides and developing synthetic vaccines. The MAP system consists of a small immunogenically inert core matrix of lysine residues with alpha- and epsilon-amino groups for anchoring multiple copies of the same or different synthetic peptides. Several MAP systems, each containing eight copies of 6-15 residue-long peptides derived from the terminal and central regions of various proteins were analyzed in this study. The immunogenicity of MAPs was compared to that of the same peptides linked to carrier protein by means of conventional conjugation procedures. The various peptide antisera were tested in ELISA with homologous peptides conjugated to a carrier protein via their C terminal (as in the MAP system) or their N terminal end, or with their parent proteins. The antigenic properties of MAPs were studied with anti-peptide sera obtained by classical methods and with anti-protein sera. The results showed that the MAP system was an efficient antigen in ELISA except when the peptide corresponded to a C terminal epitope. However, the value of MAPs for raising anti-peptide antibodies cross-reactive with the cognate protein appeared much more limited. In the case of one N terminal peptide, the MAP construction was not immunogenic while the conventionally conjugated peptide induced antibodies that reacted strongly with the corresponding protein. In the case of the two C terminal peptides tested, the antibodies raised against MAP constructs reacted well with homologous MAPs but did not cross-react with the whole protein. Only in the case of a peptide from an internal domain of histone H2A did immunization with a MAP generate antibodies that cross-reacted with the protein.


Use of passive immunization for the production of monoclonal antibodies against Actinobacillus pleuropneumoniae serotype 1,6 and 12. Hyperimmune sera from BALB/c mice immunized intraperitoneally (IP) with Actinobacillus pleuropneumoniae serotype 2 were used for passive intraperitoneal (i.p.) immunization of BALB/c mice. The immunized mice were subsequently immunized i.p. with a mixture of A. pleuropneumoniae serotypes 1, 6 and 12. Numerous monoclonal antibodies specific for serotypes 1, 6 and 12 were obtained. Using this immunization scheme antibodies can be obtained against specific antigens from closely related bacteria.


A 7-day course of ciprofloxacin for enteric fever. A prospective, open and non-randomised clinical trial using a 7-day short course of oral ciprofloxacin 500 mg twice daily was conducted on 25 adult patients with bacteraemic enteric fever. Twenty-four patients (96%) were cured and there was one treatment failure. Two patients with typhoid fever relapsed 6 weeks after finishing treatment. Defervescence of fever was rapid (median: 4 days) and the duration of hospitalisation was short (median: 8 days). Both factors resulted in patient satisfaction. A short-course regime of ciprofloxacin for the treatment of enteric fever, is therefore, highly promising.


Serological diagnosis of infection by Shigella dysenteriae-1 in patients with bacillary dysentery. A total of 192 samples of serum from 113 Sri Lankan patients with clinical dysentery was examined for antibodies of the IgM class to the lipopolysaccharides (LPSs) of Shigella dysenteriae-1 and Escherichia coli O157:H7. By means of ELISA and immunoblotting, 59 patients were found to have serum antibodies to the LPS of S. dysenteriae-1 only. Four samples from one patient were found to contain serum antibodies to the LPSs of both S. dysenteriae-1 and E. coli O157:H7. Antibodies to the LPS of S. dysenteriae-1 were also detected in 16 samples from 25 children, from Sri Lanka, with no previous history of dysentery; one of these children also had antibodies to the LPS of E. coli O157:H7. Analysis of 16 samples from apparently healthy children in the U.K. showed that only one serum contained antibodies to the LPS of S. dysenteriae-1. This patient had a history of recent travel to Pakistan. The isolation of S. dysenteriae-1 remains the preferred test for the diagnosis of bacillary dysentery. The use of serology as a means of providing evidence of infection with S. dysenteriae-1, however may prove to be a useful adjunct to cultural techniques but needs to be validated in an area where this organism is endemic.


Assessment of assays for the serodiagnosis of Venezuelan equine encephalitis. An enzyme-linked immunosorbent assay (ELISA), an immunofluorescence assay (IFA), a plaque-reduction neutralization (PRN) assay and an immunoblot assay, all by means of an antigen prepared from the attenuated Venezuelan equine encephalitis (VEE) vaccine strain of virus, were compared with the conventional haemagglutination-inhibition (HAI) assay for the serodiagnosis of VEE. The HAI assay, which includes the use of wild type virus antigen, was less sensitive than the other assays when known-positive samples of serum from an epidemic of VEE were tested. The superior sensitivity of the IgG ELISA was confirmed by assaying both VEE epidemic samples and a bank of samples from VEE vaccinees. Samples with antibody specific for other Alphaviruses, however, cross reacted weakly in this assay. The PRN, immunoblot and HAI assays, although less sensitive than the ELISA, proved more specific. Experimental infection of guinea-pigs demonstrated the value of the IgM ELISA in the early detection of VEE virus infection. Immunoglobulin M was first found at 4 days post-inoculation (p.i.) during the viraemic phase of infection. Immunoglobulin G was detected by ELISA, PRN assay and IFA at 6 days p.i. Immunoblot and HAI assays, however, did not give positive results until 10 days p.i. The results support the diagnostic use of ELISA for detecting VEE virus-specific IgM and IgG, and the use of the specific PRN assay for confirming the diagnosis.


Bacillus cereus meningitis in two neurosurgical patients: an investigation into the source of the organism. Two patients developed Bacillus cereus meningitis following neurosurgery. During the subsequent investigation into the source of the organism, linen was discovered to be heavily contaminated with B. cereus. No other prolific source of the organism was found. It seems probable that lint from contaminated fabric was the vehicle of transmission of the organism during extended surgery. Linen should be considered as a possible source of B. cereus infection.


Streptococcal necrotising fasciitis.

Streptococcal necrotising fasciitis. Three cases of streptococcal necrotising fasciitis are described. Its relative rarity and the lack of superficial inflammation leading to diagnostic difficulty is emphasised. The diagnosis is readily confirmed microbiologically but the clinician should bear in mind that antibiotics may not be curative and that surgery is often required.


Primary abdominal actinomycosis in a diabetic woman--an intractable disease. Primary abdominal actinomycosis is very unusual. Only five previous cases have been reported in the English literature. We describe the case of a 57-year-old diabetic woman with primary abdominal actinomycosis, refractory to several antimicrobial regimens and surgical procedures. We conclude that primary abdominal actinomycosis in such a diabetic woman is an intractable disease.


Diphtheria: another risk of travel.

Diphtheria: another risk of travel. A 19-year-old woman presented with cellulitis of her foot 10 days after returning from Bali. Swabs of a central necrotic area grew toxigenic Corynebacterium diphtheriae biotype gravis. The patient was treated with parenteral penicillin and made a complete recovery. Diphtheria immunisation should be regularly updated for travellers to the tropics. Clinical and laboratory recognition of this infection is essential for appropriate public health measures to be undertaken.


Influenza B virus infection associated with non-bacterial septic shock-like illness. We report the details of four children aged between 6 months and 5.5 years who had underlying chronic disease and who developed life-threatening illness in association with influenza virus B infection. Influenza has received relatively little attention, yet its morbidity and mortality in children can be considerable. This report emphasises the need to vaccinate the population groups at high risk, such as children with cardiovascular disorders, chronic bronchopulmonary, metabolic and renal disease and chronic neurological disorders.


Acute delta hepatitis without hepatitis B surface antigen detectable in the blood. The case is described of a 42-year-old man suffering from acute delta hepatitis without hepatitis B surface antigen (HBsAg) being detectable in his blood. Tests on the patient's blood were negative for anti-HBcIgM and HBeAg but positive for anti-HBs, anti-HBe, HDAg and anti-DIgM. It is well known that the delta antigen-antibody system is detectable only in HBsAg carriers except rarely in persons recently recovered from acute hepatitis B virus (HBV) and delta infection. We report one of the rare cases in which the circulating HBsAg as well as anti-HBcIgM and HBeAg were not found in the patient's serum, thus indicating the absence of recent infection with HBV.


Meningococcal disease in Wales: clinical features, outcome and public health management. In Wales, in 1988, 119 patients with meningococcal disease were identified, so giving a crude annual incidence of 4.2 patients per 100,000 population. The combined classical clinical features of fever, vomiting, neck stiffness, headache and purpuric rash were identified in only 9% of patients. Fever and vomiting were the commonest symptoms, both being present in 60% of patients. A rash was noted in 77% of patients but neck stiffness in only 39%. Rash was more common in children, headache and photophobia in adults. A total of 13 patients died, the fatality rare increasing with age from 3% in infants to 20% in older teenagers and adults. Only 15% of 75 patients admitted to hospital by general practitioners were known to have received intravenous or intramuscular penicillin before admission as recommended by the Chief Medical Officers of the Health Departments in the U.K. Only 24% of patients received rifampicin to clear nasopharyngeal carriage before or at discharge from hospital. Altogether, 375 household contacts of patients were identified. At least 84% of them received chemoprophylaxis.


Protective effect of intradermal BCG against leprosy; a case-control study in central Brazil. A case-control study was undertaken to evaluate the protective efficacy of intradermal BCG against leprosy in a high-endemic area of leprosy in central Brazil. Sixty-two cases and 186 controls were included in the study. Cases were all newly diagnosed leprosy patients under 16 years of age attending an outpatient health service, and all of them were schoolchildren. Three controls under 16 years old, frequency matched by sex and age group, were selected from schools geographically located in the area from which the cases came. The presence of BCG was negatively associated with leprosy, indicating a 5.3 risk of leprosy for those nonvaccinated and protective efficacy of 81%. Paucibacillary patients were more likely to have a BCG scar than multibacillary patients.


Sensitization potential and reactogenicity of BCG with and without various doses of killed Mycobacterium leprae. A study was conducted in 997 individuals in two villages in south India to find the acceptability and sensitizing effect of the antileprosy combination vaccine of BCG plus killed Mycobacterium leprae (KML). Three preparations of the combination, BCG 0.1 mg + 6 x 10(8) KML (I), BCG 0.1 mg + 5 x 10(7) KML (II), and BCG 0.1 mg + 5 x 10(6) KML (III), along with BCG 0.1 mg (IV), and normal saline (V), were used in the study. Each individual received one of the above five preparations by random allocation. They were also tested with Rees' M. leprae soluble skin-test antigen (MLSA) and lepromin-A, both at intake and 12 weeks after vaccination. Reactions to Rees' MLSA were measured after 48 hr; those to lepromin-A after 48 hr and 3 weeks. The character and size of the local response at the vaccination site were recorded at 3, 8, 12, 15, and 27 weeks after vaccination. The mean sizes of postvaccination sensitization to both Rees' MLSA and lepromin-A in the vaccine groups were significantly larger than those in the normal saline group, clearly demonstrating the ability of the vaccines to induce sensitization as measured by responses to the two skin tests. The sensitizing effect was the highest following vaccination with vaccine I. It was not significantly different for vaccines II, III, and IV, although, generally, a dose-response effect was observed. The sensitizing effect attributable to the vaccine was more clearly seen in children than in adults. The above conclusions were the same irrespective of which results were considered, reactions to Rees' MLSA or Fernandez or Mitsuda reactions to lepromin-A. A significant finding of the study was that at intake the Mitsuda reactions provided a measure of sensitizing effect due to vaccine. The healing of vaccination lesions was uneventful. In more than 90% of vaccinated individuals, the lesions had healed by the 12th week in vaccine groups II, III, and IV, and by the 15th week in vaccine group I. The results showed that vaccination with BCG or combination vaccines was equally safe in individuals with or without previous BCG scars. Thirteen persons, aged 10 years or older, developed suppurative lymphadenitis around the 8th week (7 in vaccine group I, 3 each in vaccine groups II and III). However, healing was prompt after drainage in these individuals.


Serological response to purified mycobacterial phosphatidylinositol mannoside in healthy controls and in patients with tuberculosis and leprosy. The serological response to a monoclonal antibody-defined phosphatidylinositol mannoside (L4-PIM) present in all mycobacteria was examined in patients with various mycobacterial diseases and healthy subjects from different populations. IgG but not IgM antibodies were detected in most patients with untreated lepromatous (84%) or borderline lepromatous (65%) leprosy, but in only a minority of those with disease at the tuberculoid end of the leprosy spectrum (< 17% positive). The response to L4-PIM was correlated with the IgM response to disaccharide octyl-bovine serum albumin (dBSA), and decreased with successful treatment. On the other hand, the test proved to be of little value in the diagnosis of untreated tuberculosis (4/15 positive) or atypical mycobacterial infection in patients with AIDS (0/11 positive). IgG antibodies to L4-PIM were also found in a significant proportion of healthy individuals, irrespective of their Mantoux status. These antibodies were shown to be specific for L4-PIM on immunoblotting, and their incidence increased with age in random donors from both urban Australia and rural Papua New Guinea. Despite the limited value of the assay in diagnosis of any particular mycobacterial disease, the presence of antibodies to L4-PIM appears to be a sensitive indicator of subclinical infection with environmental mycobacteria in subjects with an intact immune system.


Maxillary antrum involvement in multibacillary leprosy: a radiologic, sinuscopic, and histologic assessment. Thirty patients having lepromatous leprosy (22 males, 8 females) and showing radiological involvement of the maxillary antrum were subjected to sinuscopy, biopsy, and histopathological examination. Radiological observations showed diffuse opacity in 33.3% of the sinuses, localized mucosal thickening in 28.6%, and generalized thickened mucosa in 38.1%. Sinuscopy revealed inflamed mucosa as the most common finding (40%), followed by ulcerative (26.7%) and granulomatous (10%) lesions of the mucosal lining. The mucosal thickening (localized or generalized) evident on radiology was always associated with granuloma formation and acid-fast bacilli in the histology. The presence of an external nasal deformity indicated a statistically significant chance of encountering mucosal involvement on sinuscopy and histopathology (p < 0.05). There was more chance of finding positive sinuscopic lesions in those patients with a bacterial index above 3+.


Delayed clearance of circulating immune complexes in mice following administration of antileprosy drugs. In this report we describe an animal experiment which showed delayed clearance of preformed 125I-HSA-anti-HSA immune complexes (with five times excess HSA) from the circulation of mice treated with antileprosy drugs (dapsone, clofazimine, and rifampin--multidrug therapy for 7 days) in comparison with normal (untreated) mice. The results also showed delayed retention of the preformed immune complexes in the spleen and kidneys of the antileprosy-drug-treated animals. The exact mechanism of the delayed handling of preformed immune complexes in mice fed antileprosy drugs could not be ascertained. However, in light of the anticomplementary effects of clofazimine and dapsone, as reported earlier, and in light of the large accumulation of clofazimine and rifampin in macrophages, it has been postulated that in the drug-fed animals either the immune complexes could not be phagocytosed by macrophages, through the avenue of their C3b receptors, or the immune complexes could not be downgraded easily within the macrophages overloaded with clofazimine and rifampin. These results might have clinical significance and might throw some light on the prolonged persistence of circulating immune complexes in the vascular bed of lepromatous patients even after clinical remission of erythema nodosum leprosum.


An experimental study to evaluate the bactericidal activity of ofloxacin against an established Mycobacterium leprae infection. The bactericidal effect of a new quinolone, ofloxacin (OFLO), was determined on an established Mycobacterium leprae infection in nude mice. Various drug regimens, including combinations of drugs, were examined for different treatment periods. OFLO and rifampin (RMP) individually failed to produce significant killing after treatment with a single large dose. However, when single large doses of OFLO and RMP were given in combination, a 100-fold reduction in viability was achieved. For a longer period of treatment both of these drugs, at lower doses, produced a moderate reduction in viability. The addition of dapsone to the lower dose of OFLO resulted in a significant reduction in viability, while lower doses of RMP and OFLO together produced a moderate reduction in viability.


Chemoprophylaxis of leprosy with a single dose of 25 mg per kg rifampin in the southern Marquesas; results after four years. In January-February 1988, a program of chemoprophylaxis for leprosy, using a single 25 mg/kg dose of rifampin, was conducted among 2786 (98.7%) inhabitants of the Southern Marquesas and 3144 South Marquesan "emigrants" and their families. Among the treated population, during the 4 years which followed the implementation of the program, two leprosy patients were detected, one of whom can be considered as a failure of chemoprophylaxis because she was not known by the leprosy control unit. During the same period (1988-1991), a decrease in detection rates for leprosy in the entire French Polynesian population has been observed, an event which makes the interpretation of these findings very difficult. Nevertheless, according to presently available data, the effectiveness of chemoprophylaxis with a single dose of 25 mg/kg rifampin is estimated to be about 40% to 50%. When considering not only the results of the present study but also the financial and logistic constraints raised by such a program, one is led to the conclusion that chemoprophylaxis, even with a single dose of rifampin, is not likely to become an effective component of leprosy control programs.


Relapses among leprosy patients treated with multidrug therapy: experience in the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT) in Ethiopia; practical difficulties with diagnosing relapses; operational procedures and criteria for diagnosing relapses. Multidrug therapy (MDT), according to the recommendations of a WHO Study Group of 1982, was introduced in the leprosy control program of the All African Leprosy and Rehabilitation Training Center (ALERT), Ethiopia, in January 1983. Paucibacillary (PB) patients are treated with 6 months of MDT. Multibacillary (MB) patients are treated with at least 2 years of MDT and until skin-smear negativity. An analysis was made of the relapses which had been diagnosed among self-reporting patients in four rural districts and Addis Ababa. Among 3065 PB patients, 34 relapses (1.1%) were diagnosed during an average period of 6.1 years after stopping MDT (range 2 1/2 to 7 1/2 years). Among 2379 MB patients, 24 relapses (1.0%) were diagnosed during an average period of 4.7 years after stopping MDT (range 2 1/2 to 6 years). The estimated relapse rate per 1000 patient-years after release from MDT was 2.1 for PB patients and 2.4 for MB patients. From the analysis of the clinical, bacteriological, and histopathological findings, it was concluded that there was strong positive evidence for the diagnosis for 16 of the 34 relapses in the PB patients and for 0 of the 24 relapses in the MB patients. The main cause for overdiagnosis of MB relapses was that too much reliance had been put on skin-smear results, without a careful comparison of the results with those from before, during, and at completion of MDT; the diagnosis was based on the finding of positive smears in one set of smears only; insufficient attention was given to finding solid-staining bacilli; and findings in biopsies, if these were examined, did not confirm the diagnosis. The main cause of overdiagnosis of PB relapses was that too much reliance was put on histological findings, while these are often inconclusive for differentiating between a relapse and late reversal reaction. Recommendations are made on how to limit overdiagnosis of relapses. Operational procedures and criteria for making the diagnosis under conditions where facilities for back-up histological and mouse foot pad investigations are not available are proposed.


Duration of multidrug therapy in paucibacillary leprosy patients; experience in the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT) in Ethiopia. Multidrug therapy (MDT), according to the recommendations of a WHO Study Group of 1982, was introduced in the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT), Ethiopia, in January 1983. Of 6042 paucibacillary patients who were put on MDT during a period of 7 years, 5485 patients (90.8%) completed the course of MDT; 437 patients (7.2%) did not fulfill the requirement for clinic attendance and either discontinued MDT themselves or the treatment was discontinued by the service. The remaining 120 patients (2.0%) either died, were transferred, left the control area or continued MDT after 9 months. The urine spot test for the presence of dapsone showed a significantly higher proportion of positive results for patients on MDT than for patients on dapsone. The analysis of the compliance with the prescribed doses of MDT showed that of 963 patients, 81.9% received six doses of MDT and 18.1%, more than six doses; 82.6% of these 963 patients attended with 100% regularity, 12.7%, 3.6%, and 1.1% missed one, two, or three clinic appointments, respectively, while fulfilling the requirement for overall clinic attendance. Of the 429 patients who had not been treated with dapsone before MDT, the skin lesions were clinically active at the time of stopping MDT in 130 patients (30.3%). In all, except one of the 114 patients (0.9%) who attended for follow-up examinations, the skin lesions had become clinically inactive within 2 years after stopping MDT. The recommended duration of MDT is discussed based on findings in the ALERT leprosy control programs and observations by others.


Nonhuman sources of leprosy.

Nonhuman sources of leprosy. Our findings establish that there are known extrahuman reservoirs of M. leprae in three animal species. There is considerable evidence that the armadillo plays a role in the epidemiology of leprosy in humans in Texas and Louisiana. The elimination of leprosy as a public health problem (defined by the World Health Organization as one active patient per 10,000 population) may be attainable by the wide application of current control measures; however, the ultimate eradication of leprosy must take into account extrahuman reservoirs of M. leprae. The impact that attempts to control or to eliminate leprosy in such reservoirs (e.g., the armadillo in Louisiana and Texas) would have on environmental and wild-life considerations would be profound. Whether or not similar situations prevail in other leprosy-endemic geographic areas is not known. Based on the armadillo experience, there seems to be ample justification for undertaking, forthwith, carefully designed surveys for enzootic leprosy in some of the major endemic areas of leprosy. At the current state of our knowledge of the subject, such surveys should be initiated in the natural habitats of the mangabey monkey and chimpanzees--in West Africa.


Carcinoma of the lip.

Carcinoma of the lip. Carcinoma of the lip represents the most common malignancy of the oral cavity with an incidence in the United States of approximately 1.8/100,000. Lip cancers represent 15% to 20% of all malignancies of the oral cavity. With increasing public awareness of the harmful effects of solar radiation, physicians need to be aware of the etiological factors as well as appropriate treatment plans to ensure that patients obtain the most favorable outcome possible.


Assessment of cognition, mood, and function: vital clinical data in geriatric psychiatry. Systematic assessment of cognition, mood, and function in geriatric psychiatry using simple psychological tests provides vital data for diagnosis, management, and treatment outcome. Use of such tests can assist in differentiating depressive pseudodementia and delerium from true dementia. This article presents a computer database program using serial administration of basic psychological tests which are readily obtainable and easily administered. Case histories describe how this testing format provides graphic data documenting treatment course and outcome. Research applications are suggested.


Behavioral aspects of trichotillomania.

Behavioral aspects of trichotillomania. Trichotillomania is characterized by an inability to resist urges to pull out hair. It is estimated to occur in at least 1 out of 200 persons by college age. The disorder usually begins in childhood or adolescence with a chronic course more likely in patients with a later onset. Some investigators hypothesize a relationship between trichotillomania and obsessive compulsive disorder, but this proposal has not yet been substantiated. Little rigorous treatment research has been done, but the current treatments of choice are clomipramine and behavior therapy (habit reversal training).


Adolescent suicide: prevention and treatment of psychiatric causes. There has been a dramatic increase in suicide among adolescent males in the last 20 years. White males are at the highest risk. For this group, suicide is the second most common cause of death. Because of the gravity of the problem, much interest has developed in the causes and means of preventing suicide. Precipitating causes include getting in trouble and disturbances in the peer and family relationship. These are common occurrences for all adolescents. Investigations following death show that the majority of those that complete suicide had psychiatric diagnoses. The most common diagnoses are depression, substance abuse, and conduct disorder. The assessment and treatment of these disorders is discussed.


Psychopharmacology in the elderly.

Psychopharmacology in the elderly. By the year 2030, it is estimated that 17% of the population (52 million people) will be over age 65. Most of these individuals will be taking several medications, and one or more of these medications may be a psychotropic, that is, an antidepressant, anxiolytic, antipsychotic, or lithium. This article summarizes the pharmacokinetic changes that accompany aging and highlight how these changes impact the elderly.


A review of the medical and social consequences of generalized anxiety disorder and panic disorder. Over the past two decades, anxiety disorders have become the focus of much research after years of relative obscurity. The accumulating data has suggested that anxiety disorders may have many consequences including decreased quality of life, economic dependence, multiple somatic complaints, maladaptive personality traits, and increased mortality due to suicide, cardiovascular, and cerebrovascular causes. Aggressive management of these disorders may greatly lessen the impact.


Survival of persons with AIDS in Kentucky. Of all reported Kentucky adult/adolescent cases of AIDS (124) with diagnosis dates from July 1, 1990, through June 30, 1991, 33% died within three months of diagnosis. To discern possible reasons for these very short survival times, information was analyzed from the CDC AIDS Confidential Case Report of the 124 patients and from the hospital charts of the 29 patients who were reported as having died within the month of or the month following diagnosis. Data suggested that survival for three months appears to be less likely for blacks, for males, and for those 30 through 34 years old. In the cohort the first diagnosis of AIDS was made at 40 different hospitals and the patients presented to 77 different physicians. Of chart-reviewed patients, 16 of the 29 (55.1%) were previously known to be HIV-positive. The most commonly identified likely reason for short survival time from AIDS diagnosis to death was that the diagnosis had been previously missed (10 of the 29 patients--34%). The study showed that many known to be HIV-positive for some time had apparently received little or no care for their infection from testing until diagnosis with AIDS. Medical review of patient charts suggested that scatter of caregivers may have resulted in some errors in diagnosis and treatment decisions. Also, considerable numbers of persons with HIV infection are either not utilizing the existing HIV counseling, testing, and follow-up systems or are not receiving medical care for their infection once it is identified.


Solitary fibrous tumor of the pleura with hypoglycemia: the Doege-Potter syndrome. The occurrence of hypoglycemia with an intrathoracic tumor was reported in 1930 independently by Doege and Potter. Since then, the presence of a nonpancreatic tumor associated with low blood sugars has often been referred to as the Doege-Potter syndrome. We report a patient with a recurrent solitary fibrous tumor of the pleura who experienced symptomatic hypoglycemia attributable to his tumor.


An unusual prevalence of complications of chronic suppurative otitis media in young adults. The complications of chronic suppurative otitis media as seen in 117 patients are presented. Fifty per cent of the patients had cholesteatoma, and 28 per cent revealed complications. Two-thirds of these complications, especially the serious intracranial ones, were encountered in young females. This female predominance was attributed to late presentation because of social reasons, or to undue susceptibility to the destructive effect of cholesteatoma. Radical and modified radical operations were recommended to render the ears safe, as most of the patients came from distant rural areas and were judged to have poor compliance to report for regular checks.


Computer simulation of human tympanic membrane. Because of the difficulties in studying the mechanical properties of the human tympanic membrane in situ, structural data from the cadaveric tympanic membrane samples is used for simulation of the surface structure of the tympanic membrane with the help of a computer. The hitherto poorly understood contour of the tympanic membrane is available for the development of a tympanic membrane and middle ear model.


Treatment of tympanic membrane retraction pockets by excision. A prospective study. The treatment of tympanic membrane retraction pockets by simple excision is described in 66 ears in 50 patients. After one operation 65 per cent of the retraction pockets were successfully treated (mean follow up 14.1 months). Persisting perforations occurred in five patients after one excision. Retrotympanic cholesteatoma was found in one patient, after two retraction pocket excision operations. The number of myringotomies with grommet insertion and the presence of bilateral disease does not predict the outcome of the procedure. Simple excision should be considered in the first instance, rather than reinforcement tympanoplasty using temporalis fascia or cartilage graft, in the treatment of tympanic membrane retraction pockets.