Interactions between thiopental and volatile anesthetics (halothane and isoflurane) in isolated heart preparations of the rat.

Thiopental uptake into heart muscle tissue was studied in spontaneously beating rat hearts (Langendorff preparation, 0.13-0.27 mmol/l thiopental in the perfusion fluid). Up to 0.19 mmol/l the concentration of thiopental in heart muscle tissue was increased vs. control when halothane (0.8 vol%) was present. Using a constant thiopental concentration (0.13 mmol/l) and 0.8, 1.5 or 2.0 vol% halothane +12%, +29% or +43% more thiopental was taken up into heart muscle tissue compared to the control. This increased uptake was not seen in the presence of 1.2 and 2.0 vol% isoflurane. Frequency of right rat atria was decreased by increasing thiopental concentrations (0.02-0.23 mmol/l in the incubation medium). Halothane (0.8 and 1.5 vol%) and isoflurane (1.0 and 2.0 vol%) alone had no influence on frequency of right atria. Both volatile anesthetics additionally increased the negative chronotropic action of thiopental when the corresponding higher concentration was applied. Contractile force of left rat atria was decreased concentration-dependently by thiopental (0.02-0.23 mmol/l). Halothane and isoflurane alone decreased contractility. Dependent on the concentration used, both volatile anesthetics further increased the negative inotropic action of thiopental, yet preferentially at higher barbiturate concentrations.


Cardiovascular alterations in the hypothyroid rat.

We conducted the present studies in intact animals to assess alterations in integrated cardiovascular function due to hypothyroidism. Rats were surgically thyroidectomized or sham operated. Most obvious among the alterations detected under resting conditions was the bradycardia present in hypothyroid animals. Cardiac output was significantly reduced by slower heart rate; however, mean arterial blood pressure and left ventricular +dP/dt were maintained. Total peripheral resistance was increased in hypothyroid animals. Functional responsiveness to hemodynamic challenges unmasked additional characteristics. Thyroidectomized animals had normal stroke index-left ventricular end diastolic pressure relationships in response to rapid volume infusion. Peak left ventricular +dP/dt response to brief aortic occlusion was attenuated in thyroidectomized animals. Hypothyroid rats failed to augment left ventricular -dP/dt in response to isoproterenol challenge. Moreover, isoproterenol failed to reduce total peripheral resistance in the hypothyroid rat. Therefore, the hemodynamic responses observed in the intact, hypothyroid animal are consistent with the presence of (a) decreased cardiac contractile protein ATPase, (b) reduced calcium uptake by cardiac sarcoplasmic reticulum and (c) altered vascular adrenergic receptors. Many cellular and subcellular defects are compensated by integrative mechanisms operating under resting conditions, while other defects are unmasked only when examined in the intact, functional cardiovascular system undergoing hemodynamic challenge.


The effect of loop of Henle diuretics on the tubuloglomerular feedback mechanism.

Increases in the delivery of solute to the loop of Henle result in increased reabsorption, vasoconstriction of the afferent arteriole, and a reduction in the glomerular filtration. Although the details of this tubuloglomerular feedback (TGF) mechanism are not completely worked out, it appears certain that alterations in reabsorption by the loop of Henle are critical to its operation. In the following study, we assessed the effect of several different loop of Henle diuretics on the response of the TGF mechanism. The function of TGF was monitored by measuring the stop-flow pressure (SFP) in the early proximal tubule in response to alterations in perfusion rate through the loop of Henle. All drugs were given directly into the loop of Henle in a concentration of 10(-4) M. With control solutions, SFP fell in a sigmoidal fashion over a perfusion range of 5 to 45 nl/min. When furosemide was added to the perfusate at a dose of 10(-4) M, SFP did not change. Bumetanide had an effect similar to furosemide, but muzolimine failed to inhibit the reduction in SFP over the perfusion range. Three experimental compounds were tested. All three cause diuresis when administered orally to animals. MK447 had no effect on SFP, but its metabolite, MK447-SO4, had an effect similar to furosemide. Another compound with modest diuretic effects, ICI 207,828, actually increased the response in SFP. Two distal diuretics, hydrochlorothiazide and amiloride, had no effect on SFP. The response of SFP to all these compounds correlated with its measured effect on loop reabsorption of sodium. Furosemide, bumetanide and MK447-SO4 significantly reduced sodium reabsorption.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of the new hypolipidemic agent F 2833 on plasma lipoprotein levels in normal and hyperlipidemic hamsters.

The present study analyzed the effects of the new hypolipidemic agent, F 2833, in male golden Syrian hamsters fed a standard diet or a diet supplemented with 0.06% cholesterol and 20% coconut oil. F 2833 did not detectably modify the blood lipid parameters studied in hamsters receiving the standard diet. After 28 days, the hyperlipidemic diet in untreated animals significantly increased plasma cholesterol, triglycerides and phospholipids (by 91, 138 and 61%, respectively) and in the different lipoprotein classes. Treatment with F 2833 (150 and 300 mg/kg/day) caused a dose-dependent reduction of the blood lipid parameters studied. At the higher dose, this decrease was significant for cholesterol (27%), triglycerides (48%) and plasma phospholipids (27%). With regard to the different classes of lipoproteins, a significant drop in cholesterol was observed in VLDL (38%) and LDL (29%), while that in HDL (22%) was not significant. Triglycerides were significantly lowered in all lipoprotein classes with a more pronounced effect in the VLDL pool (53%). F 2833 thus decreased plasma lipids in hamsters that were fed on hyperlipidemic diet to normal values observed in animals fed a standard diet. These results confirm and extend findings previously obtained in other animal species in which F 2833 was also shown to be an effective hypolipidemic drug.


A double stopcock technique for repeated sampling of venous blood.

Repeated sampling for measurement of venous blood levels of hemoglobin, hematocrit, plasma hemoglobin, potassium and ibuprofen with a novel method of phlebotomy, the double stopcock technique (DST), was compared to heparin lock (HPL), Angiocath with obturator (AOB) and direct venipuncture (DVP) techniques. There were 12 normal subjects in this randomized, three-way crossover trial. During each portion of the crossover, simultaneous samples for hemoglobin, hematocrit, plasma hemoglobin, potassium and ibuprofen were taken from each phlebotomy site prior to and after oral dosing with 400 mg ibuprofen. The DST was the best acceptable method based on the assessment of comfort by the subjects, followed by the AOB, HPL and DVP techniques. The least amount of blood waste was with the DST. The degree of hemolysis (as shown by plasma hemoglobin and potassium) was comparable across all techniques. Across all of the techniques, measurement of hemoglobin, hematocrit and ibuprofen levels using DST, HPL and AOB yielded lower levels than DVP. These changes were small and were not clinically significant, although statistically significant in some cases. The authors conclude that when there is need for frequent, rapid and repetitive venous blood sampling with minimal blood wastage and patient discomfort, the DST should be considered.


Daily variation and effects of ambient light and circadian factors on the human light reflex.

Measures of pupillary size and the dynamic light reflex are safe and noninvasive methods to quantify and characterize the mechanism and site of drug action. The effects of variations in ambient light and time of day on pupillary measures were determined. In dark adapted volunteers (n = 13), ambient light was incrementally increased at < 0.1, 4, 40, 100 and 200 foot-candle (ftcd). Subjects adjusted to each light level for 1 min before the light reflex was elicited. Replicate measures were collected with the contralateral eye open and covered with an opaque patch. Data were collected every 3 h between 6 a.m. and 9 p.m. The prestimulus diameter of the dark adapted pupil averaged 6.4 mm at < 0.1 ftcd and 2.3 mm at 200 ftcd. Constriction amplitude decreased with increases in ambient light from 2.1 mm (< 0.1 ftcd) to 0.2 mm (200 ftcd) while constriction and dilatation velocities decreased from 7.7 to 2.8 mm/sec and 4.3 to 2.8 mm/sec, respectively. Time of day effects were small but statistically significant and the interaction of ambient light and time of recording suggests the pupil is differentially sensitive to ambient and phasic light stimuli over the course of the day. A patch over the contralateral eye increased pupil size and velocities of the light reflex. In a second study, 10 volunteers were tested twice a day at 4 and 80 ftcd for four days. While there was wide between subject variability, the within subject differences were small. Such baseline data may be useful in describing the normal variations in these increasingly popular indices of drug action.


Vowel categorization and the critical band.

Using the concept formation paradigm, two series of experiments were conducted to test the hypothesis that the critical band (CB) was a factor in learning to make absolute discriminations of vowels. The specific hypothesis being examined was that the CB is a psychoacoustic boundary in learning to make vowel categorizations, and that learning absolute discriminations of pairs of vowels that differ in one of their formants by one bark or more is significantly easier than learning absolute discriminations of vowels that differ by less than one bark. Subjects were given the task of learning to identify paired sets of synthesized vowels that differed in either F1 or F2 by 0.4, 0.6, 0.8, 1.0, or 1.2 bark. The results of these experiments suggest that the critical bandwidth is not a natural psychoacoustic boundary in the learning of vowel categories, and also that subjects seem better able to learn distinctions involving differences in F1 than distinctions involving differences in F2. The discussion raises the possibility that vowels that differ by less than one bark may not be perceptually viable because of such factors as ambient noise, articulatory constraints, and coarticulatory influences. Some evidence from Dutch and French is presented in support of this conjecture.


Perceptual restoration of filtered vowels with added noise.

Perceptual restoration is a well-known phenomenon for speech segments in context, but less is known about the effect for stimuli that occur without a linguistic context. The current study investigated restoration in the perception of isolated vowels. Vowels excised from natural speech were lowpass filtered (1000 Hz), which removed the high F2 characteristic of front vowels. This resulted in high rates of front to back vowel confusions; however, these errors were reduced when highpass filtered noise was added to the lowpass filtered vowels. Although the reduction in errors was accompanied by an increase in back to front vowel errors, addition of noise led to improved performance overall. These results suggest that listeners "restored" the high F2 of front vowels in the noise condition, despite an absence of linguistic context to influence restoration, and that addition of noise led to more effective utilization of cues below 1000 Hz.


The phonological representation of [voice] in speech perception.

This paper examines to what extent phonological representations affect word identification. The contrast under investigation involves the interaction between voicing and vowel length in Dutch. Dutch has underlying contrasts both in obstruent voicing and in vowel length. The voicing contrast is neutralized on the surface in syllable-final position. Also, both long and short vowels are lengthened by some 25 msec when followed by medial voiced obstruents. The present study investigated whether this vowel length cue influenced listeners when hearing stimuli with ambiguous vowel duration in an identical, neutralized consonantal context in which the underlying representation of the obstruent following the vowel differed in voicing. A vowel length continuum ([at] to [a:t]) was created and appended to initial consonants to make two pairs of real words. Each pair differed in vowel length with opposite underlying final consonant representations: /zat/-/za:d/, and /stad/-/sta:t/. Our question was whether the vowel category boundaries would be different in pairs like /zat/-/za:d/ as compared to /stad/-/sta:t/. Although the underlying consonant is either voiced or voiceless, the surface word-final consonant for both pairs of stimuli is always voiceless ([t]). If the listener uses a surface representation with a voiceless consonant to recognize the words, there should be no difference in categorization of the vowel-length continua. The results of a vowel categorization task, however, showed a significant difference in the location of the phoneme boundaries between the two continua, suggesting that listeners' perception seems to be guided by the underlying phonological representation of words.


Acoustic and aerodynamic effects of interarticulator timing in voiceless consonants.

Interarticulator timing is a mechanism for producing linguistic contrasts that is widely used in different languages. This paper explores acoustic and aerodynamic effects of variations in laryngeal-oral coordination in voiceless consonants. Measurements of voice onset time and interarticulator phasing for individual tokens of stop consonants show weak correlations, indicating that interarticulator timing is only one factor determining voice onset time. Other factors most likely involved are glottal opening, transglottal pressure and air flow, and vocal fold tension. Taken together, these observations suggest that speakers may only have limited control of voice onset time. This could explain why languages do not seem to make fine-grain use of VOT for linguistic contrasts. Measurements of peak and minimum air flow during individual source pulses, obtained by inverse-filtering oral flow, show a pattern of decrease and increase in vowels following voiceless consonants. Subtle differences in the time course of these patterns occur following different consonants, suggesting that interarticulator phasing may be partly responsible for them. Closer examination reveals consistent correlations with interarticulator phasing for one speaker but inconsistent results for another. The results are discussed in terms of speech motor control and controlled variables in speech.


Context effects in a double-weak theory of speech perception.

The present study provides an elaboration of the "double-weak" theory of speech perception proposed by Nearey (1990, 1991). In this framework, the objects of speech perception (and production) are viewed as neither primarily auditory nor primarily gestural; rather, they are abstract, symbolic elements lawfully constrained to map onto relatively simple (but not entirely transparent) patterns in both domains. Speech cannot be understood unless both articulation and acoustics are considered: Many production strategies appear to be directed at achieving acoustically-oriented goals, yet most context effects in speech perception seem to be motivated by the consequences of gestural overlap. The double-weak framework suggests that speech perception and speech production are less-than-perfect inverses of each other. Despite long-term accommodation of each for the demands of the other, real-time production and perception may operate as autonomous subsystems. A family of perceptual models is discussed that provides varying degrees of approximation to "ideal solutions" (in the sense of minimizing error rate) to classifying production data exhibiting contextual interactions. Members of this family that provide substantial, yet incomplete, compensation for the consequences of gestural overlap appear to be adequate to account for the results of many speech perception experiments. Such partial perceptual compensation allows, in principle, for the kind of imperfect "error correction" discussed by Ohala (1981, 1990) in conjunction with hypo- and hypercorrection phenomena.


Perception and production of voiceless Spanish fricatives by Chicano children and adults.

In studying language change, Ohala and Lorentz (1977) observed that when the labial-velar glide [w] occurs adjacent to fricative noise, the resulting complex of acoustic features is most often perceived and pronounced as a labial, rather than a velar consonant. However, contemporary Spanish, as spoken in Mexico and the U.S. Southwest, presents a somewhat different pattern. The current research examined two directional predictions based on Ohala and Lorentz (1977) with reference to the perception and production of Spanish fricatives by Chicano children and adults: A Differential Effect of Context hypothesis (more labial/velar fricative interchanges will occur before rounded, rather than unrounded vowels or glides), and a Labial Predominance hypothesis (before a following rounded vowel or glide, labial fricatives will be favored in labial/velar interchanges). Results of perceptual tests provided support for these acoustically-based predictions, but subjects' productions also showed strong influence from sociolinguistic factors in the opposite direction.


Phonetic features in young children's slips of the tongue.

The form in which phonological information is stored in the lexical entries of young children, and how this form changes over time, are questions which are difficult to address, given the limitations of current methodologies. However, slips of the tongue made by young children can be used to shed some light on the question. Earlier research (Stemberger, 1989; Jaeger, 1992) has shown that children as young as 1;7 (one year seven months) make slips in which single consonants or single vowels are substituted or exchanged, implying segmental organization in phonological representations. In the present paper, a corpus of 366 consonant substitutions and reversals made by young children, aged 1;7-6;0, are subjected to a multidimensional scaling analysis, and are shown to be governed by patterns of phonetic similarity, indicating that these segments have phonetic structure. A feature system based on the scaling procedure is found to be somewhat different from one generated by van den Broecke and Goldstein (1980) from adult errors, especially in manner features. While both adults and children err on the 'place of articulation' feature most often, and 'nasality' least often, children produce 'voicing' feature errors less often than adults do, indicating that voicing may be a more important organizing principle for young children than for adults. Some age-related trends in number and type of feature errors are discussed.


A performance constraint on compensatory lengthening in child phonology.

The systematic mispronunciations of young children often resemble phonological rules, and there is a temptation to treat the data as identical to adult phonological data. However, performance factors are often evident in the child's speech. Constraints in phonological theory are "hard" (all-or-nothing), but constraints in performance are often "soft" (allowing something to occur under some conditions but not under others). One child phonological process that has an obvious linguistic interpretation is compensatory lengthening, wherein a segment becomes long when a nearby segment is deleted. In data from one child, two compensatory lengthening processes led to the creation of [i:] but never [u:], even though [u:] appeared in the child's speech as the correct realization of adult /u:/. The child also showed later mastery of all back rounded vowels and glides than of the corresponding front vowels and glides. It is argued that compensatory lengthening never led to [u:] because of a soft performance constraint against back rounded segments; the hard constraints of phonological theory cannot account for such effects. Performance must be taken into account in the description of child phonology data.


A commercial large-vocabulary discrete speech recognition system: DragonDictate.

DragonDictate is currently the only commercially available general-purpose, large-vocabulary speech recognition system. It uses discrete speech and is speaker-dependent, adapting to the speaker's voice and language model with every word. Its acoustic adaptability is based in a three-level phonology and a stochastic model of production. The phonological levels are phonemes, augmented triphones (phonemes-in-context or PICs), and steady-state spectral slices that are concatenated to approximate the spectra of these PICs (phonetic elements or PELs) and thus of words. Production is treated as a hidden Markov process, which the recognizer has to identify from its output, the spoken word. Findings of practical value to speech recognition are presented from research on six European languages.


The interaction of coarticulation and prosody in sound change.

Ohala (1974, 1981a) has proposed that sound changes can originate in hearers' misinterpretations of synchronic phonetic patterns. This paper applies this idea to sound changes that are conditioned by the prosodic environment, such as the voicing of voiceless fricatives in unstressed syllables in Proto-Germanic. Browman and Goldstein's (1989, 1990) "gestural score" suggests a representation of synchronic patterns in which extreme overlap between gestures of neighboring phoneme segments in casual speech can produce the appearance of a feature change or a segment deletion. Many of the sound changes that are conditioned by prosodic environment can be viewed as a diachronic reinterpretation of just such synchronic fast-speech processes. For example, vowel reduction in unstressed syllables can be viewed as a reinterpretation of undershoot that occurs when the vowel is overlapped to a great extent by the oral gestures for neighboring consonants. Phonetic data are reviewed that support analogous accounts of stop spirantization, voiceless obstruent voicing, and even the insertion of an intrusive stop in clusters such as /ns/ in some prosodic environments.


On the role of perception in shaping phonological assimilation rules.

Assimilation of nasals to the place of articulation of following consonants is a common and natural process among the world's languages. Recent phonological theory attributes this naturalness to the postulated geometry of articulatory features and the notion of spreading (McCarthy, 1988). Others view assimilation as a result of perception (Ohala, 1990), or as perceptually tolerated articulatory simplification (Kohler, 1990). Kohler notes that certain consonant classes (such as nasals and stops) are more likely than other classes (such as fricatives) to undergo place assimilation to a following consonant. To explain this pattern, he proposes that assimilation tends not to occur when the members of a consonant class are relatively distinctive perceptually, such that their articulatory reduction would be particularly salient. This explanation, of course, presupposes that the stops and nasals which undergo place assimilation are less distinctive than fricatives, which tend not to assimilate. We report experimental results that confirm Kohler's perceptual assumption: In the context of a following word initial stop, fricatives were less confusable than nasals or unreleased stops. We conclude, in agreement with Ohala and Kohler, that perceptual factors are likely to shape phonological assimilation rules.


An acoustical basis for universal phonotactic constraints.

Spectral characteristics of some selected phoneme sequences are investigated in an attempt to explain cross-linguistic tendencies in phonotactic constraints. A hypothesis is offered that some universal sequential constraints are acoustically motivated. Two acoustic factors are posited as determinants of favored/disfavored sequences: The magnitude of acoustic modulation within a sequence and the degree of acoustic difference between sequences. The hypothesis is tested experimentally for its applicability to some of the universal constraints. Trajectories of the first three formants are obtained for selected sequences of stop + liquid + vowel, stop + glide + vowel, stop + vowel, and vowel + stop. Standard Euclidean distance in frequency is computed as a measure approximating each acoustic factor. The results show that some universally rare or unstable phoneme sequences can be explained on the basis of their lack of spectral modulation and/or their spectral similarity to other sequences, suggesting that acoustic/auditory factors play a significant role in determining the phonetic shape of language.


HLA and disease.

Many human diseases are associated with HLA class I, class II and class III antigens. It appears that the class III antigen disease associations can be explained by a direct defect operating at the level of either the class III gene or its gene product. The mechanism underlying class I and class II antigen disease associations is at present unknown. In this review we have considered thirty diseases which have been ranked according to their relative risk as defined by the frequency of a given HLA antigen in patient and control populations. The chronic inflammatory disorder, ankylosing spondylitis and its association with HLA B27 has been used as a model to study the HLA linked diseases. We have suggested that the disease may be caused by the Gram-negative microorganism Klebsiella which has antigenic similarity to HLA B27. It is proposed that some antibodies made against Klebsiella bind to HLA B27, thereby acting as autoantibodies leading to the pathological sequelae of chronic inflammatory arthritis. This is the crosstolerance hypothesis or molecular mimicry model and it has been compared to the receptor model. It is further suggested that the crosstolerance hypothesis can be utilised as a general theory to explain the association of other diseases with the class I and class II antigens, and offer a possible explanation for the polymorphism of HLA.


Fundamental frequency as an acoustic cue to accent perception.

It is generally recognized that the most significant cue to accent location is fundamental frequency (F0) in both Japanese and English. Furthermore, it is widely believed that a syllable is perceived as accented if the syllable contains an F0 peak. However, Sugito (1972) found that, in Japanese, if an F0 peak is followed by a steep F0 fall, the syllable preceding the F0 peak may be perceived as accented. In this article we present two experiments which investigate the relationship between F0 peak and F0 fall rate in accent perception for Japanese and English. The first experiment confirms that, for Japanese, both F0 peak location and F0 fall rate affect listeners' judgements of accent location. Specifically, the later the F0 peak occurs in a given syllable, relative to the syllable boundary, the greater the F0 fall rate necessary for listeners to perceive the preceding syllable as accented. The second experiment shows that this phenomenon is not unique to Japanese: Perception of accent location in English is also influenced by both F0 peak location and post-peak F0 fall rate.


The phonetics and phonology of perceptually motivated articulatory covariation.

This paper presents evidence that the acoustic effects of demonstrably independent articulations are integrated in the perception of vowel height and [voice] contrasts. This evidence supports two hypotheses: That, in at least some instances, articulatory covariation is perceptually motivated, and that the objects of speech perception are auditory rather than articulatory. Furthermore, it appears that perceptual integration can either increase or decrease the distinctiveness of contrasting speech sounds, so it may not only create favored patterns of articulatory covariation but also disfavored patterns. This suggests that integration is a product of general auditory mechanisms, not of mechanisms specific to speech perception.


Reversal of drug resistance in Mycobacterium leprae by ampicillin/sulbactam.

The multiplication of Mycobacterium leprae in foot pads of experimentally-infected mice was suppressed by intramuscular administration of ampicillin combined with sulbactam or YTR-830H, two potent inhibitors of beta-lactamase in the bacteria. The antibiotic or the inhibitors by themselves were inactive. Ampicillin/sulbactam also inhibited the growth of drug-resistant M. leprae which grew in the presence of rifampin or dapsone. The finding provides a new approach to treat leprosy and to overcome drug resistance of the mycobacteria.


Changes with time in the oral microflora and dental caries induction in hyposalivated rats fed on sucrose diet.

The effects of hyposalivation on the induction of dental caries and the change in oral microflora were examined at weekly intervals in Sprague-Dawley rats fed on diet 2000 containing 56% sucrose. In hyposalivated rats, significant dental caries was induced within one week and its severity increased with the experimental period. Bacteriological examinations demonstrated that the number of total cultivable microorganisms, lactobacilli and Staphylococcus aureus increased significantly shortly after surgical induction of hyposalivation, while the number of streptococci and yeasts did not increase significantly until the 7th week, beyond which time remarkable gross caries developed. A positive correlation was found between the caries score and the recovery of lactobacilli from mandibles of hyposalivated rats, while there was no statistically significant correlation between the caries score and the recoveries of S. aureus. On the other hand, dental caries was not induced in control rats fed on sucrose diet with no surgically-induced hyposalivation. It was also found that the number of lactobacilli increased significantly shortly after diet 2000 was given to control rats, but S. aureus was rarely recovered from the mandibles of control rats throughout the experiments. The roles of lactobacilli and S. aureus in the induction of dental caries under the hyposalivated condition were discussed and it was suggested that lactobacilli may play some significant role in the induction of dental caries in hyposalivated rats.


An improved method for the serotyping of free coagulase from Staphylococcus aureus.

The serotyping of free coagulase, one of the most reliable ways to identify strains of Staphylococcus aureus, and widely employed in Japan, has been improved by adding magnetite sand to the reaction mixture. Culture medium supernatant and a type-specific antibody are mixed in a well of a microtiter plate, and plasma-enriched bovine fibrinogen is treated with magnetite sand. The use of tranexamic acid and gum arabic in the reaction mixture also increases the sensitivity of the reaction. Finally, the plate is placed on a magnetic stirrer. If the type of the coagulase corresponds to that of the antibody, no clot formation will occur, and this is easily confirmed by the movement of the sand. Although the amount of reaction mixture required is much less than that for the conventional tube method, our new method is able to detect slight increases in viscosity of the reaction mixture due to fibrin formation even before complete clotting occurs, thus providing very high sensitivity. Clot formation can also be judged by observing a turbid mass of fibrin in the well (Hwang's method), but this approach is a little slower than our method involving immobilization of magnetite sand.


Suppression of cell-mediated immunity by street rabies virus infection.

An attempt to define a severe suppression of cell-mediated immunity by street rabies virus infection was undertaken by using the mice lethally and peripherally infected with a street rabies virus (1088 strain). The cell-mediated cytotoxic (CMC) activity of the spleen cells from those mice once slightly increased until day 4 after infection but declined rapidly thereafter until their death on days 10 to 12 after infection. In parallel with a decrease of CMC response of the spleen cells from 1088-infected mice, proliferative response to Con A, IL-2 activity in the culture supernatants of Con A-induced proliferation, responsiveness to exogenously added IL-2 and to Con A to express IL-2R, of those cells became suppressed, and the marked decrease of the total number of spleen cells was observed. Selective depletion of CD4+ and CD8+ cells in the spleens, abnormalities of IL-1 and E-type prostaglandins (PGE2) production or production of inhibitory component able to block IL-2 activity by spleen cells were not observed and these factors did not appear to be associated with the suppression of proliferative response to Con A. However, an apparent association of CD8+ cells in the suppression of differentiation of pre-cytotoxic lymphocytes (CTL) into CTL was demonstrated in the co-culture experiments of the spleen cells from 1088-infected mice with spleen cells of mice infected with an attenuated rabies virus (ERA strain) which can induce higher levels of CMC response. There was no evidence of the productive replication of rabies virus in thymus and spleen of 1088-infected mice. The relationship of these observations to current theories on virus-induced immunosuppression was discussed.


Establishment of stable cell lines producing anti-Pseudomonas aeruginosa monoclonal antibodies and their protective effects for the infection in mice.

Human-human hybridomas producing monoclonal antibodies (MoAbs) specific for five major serotypes of Pseudomonas aeruginosa were developed by fusing P. aeruginosa primed and Epstein-Barr virus-transformed cells with human myeloma P109 cells using polyethyleneglycol. The MoAbs which were produced by the hybridomas were protective against lethal intraperitoneal (i.p.) challenge of P. aeruginosa (10 LD50) in mice. The 50% effective dose (ED50) values of MoAbs ranged from 0.5 to 10.2 micrograms/mouse and were 26 to 240 times more protective than a commercial human IgG preparation. MoAb administration to mice promoted bacterial clearance in peritoneal cavity, and prevented bacterial invasion into blood in the way of increasing both the number of bacteria trapped by a macrophage and the ratio of macrophages that trapped bacteria. MoAbs also showed protective effects against lethal infection of P. aeruginosa in the mice which were decreased in polymorphonuclear cells (PMN) by cyclophosphamide (CY). All MoAbs showed serotype-specific binding to the clinical isolates of P. aeruginosa as well as to the immunized strains. The hybridoma cell lines maintained their capacity to produce MoAb continuously for more than 12 months and produced 10 to 60 micrograms MoAbs per 10(6) cells in 24 hr. It is practicable to use these cell lines for large-scale production of anti-P. aeruginosa MoAbs and such MoAbs must be useful for the therapeutics of patients with P. aeruginosa infection.


[Role of phenylalanine in the biosynthesis of fluorescent pigment in Pseudomonas putida bacteria].

The contemporary data of the participation of phenylalanine in the biosynthesis of fluorescent pigment pyoverdine PM of Pseudomonas putida strain M are presented. Using aro1phu1 mutant of this strain, it has been shown that one of the precursors of the dihydroxyquinoline moiety of the pyoverdine PM is phenylalanine in the D- or L-form. These results were confirmed in experiments with 14C-phenylalanine incorporation. Pyoverdine PM that was synthesized by aro1phu1 mutant from exogenous phenylalanine is identical with the pigment from wild type cells.


[Regulation of the expression of plasmid determination responsible for caprolactam degradation by bacteria of the genus Pseudomonas].

On the basis of the study of some Tn5 induced mutants in Pseudomonas putida strain BS836 containing the plasmid pBS268 coding caprolactam degradation, growth on caprolactam and its intermediates, and the data on the induction of oxidative activities in plasmid containing P. putida strain BS831 it was shown that plasmid and chromosome genes regulated the expression of CAP-determinants. The regulation has some elements of the negative control mechanism. Caprolactam is the inducer of the synthesis of key enzymes cleaving it and its intermediates (aminocaproic and adipic acids). At the same time each of its intermediates induced the synthesis of enzymes responsible for its cleavage.


Self-aggregation of squid cranial cartilage proteoglycans.

Squid cranial cartilage has been found to contain three different proteoglycan populations, two of which form aggregates (Vynios, D.H. and Tsiganos, C. P., Biochim. Biophys. Acta 1033: 139-147, 1990). The aggregation involves interaction of their protein cores as assessed by electron microscopy and biochemical data. Aggregating oligopeptides were isolated after mild trypsin digestion which inhibited self-aggregation of proteoglycans. The aggregation does not involve interaction of the side chains of polar amino acids and evidence is provided that it is mediated through hydrophobic interaction. It is enhanced upon concentration or incubation of the samples at 37 degrees C.


[Extracellular amino acids of aerobic spore-forming bacteria].

An ability to synthesize and accumulate in the growth medium for extracellular amino acids of 108 strains of 13 aerobic sporeforming bacteria species at deep cultivation on the simple synthetic glucose-mineral liquid nutrient medium optimized for the representatives of this genus. Has been studied the bacillus strains studied in the present conditions synthesize 19 amino acids and 2 amino carbons in different quantities and combinations. Amino acids being synthesized the most and least by these microorganisms have been determined in quantitative expression. Extracellular amino acid accumulation was proved to be a strain property not of genus. In general, the genus studied was evaluated as active one in amino acid production. The most active strains may present an interest as initials for further selective obtaining of producers of separate amino acids. The outlook for aerobic bacilli strains having marked amino-synthesizing properties and complex of other biological activities is being discussed for construction of medicinal and prophylactic of live microbial culture preparations.


Synthesis of low buoyant density proteoglycans by human chondrocytes in culture.

Human chondrocyte strains were derived from explant outgrowth of nonarthritic or osteoarthritic human cartilage. Chondrocytes radiolabeled with [35SO4] or [35S]-methionine were used to measure the biosynthesis of proteoglycans recovered from the most buoyant fraction (A4) of a CsCl density gradient centrifugation performed under associative conditions. The proteoglycans isolated from the A4 fraction (rho < 1.47 g/ml) were hydrodynamically small and contained both large and small glycosaminoglycan chains. When assessed by SDS/PAGE using 3-16% gradient gels, two subpopulations of small proteoglycans (smPG) were identified. The larger of the two species (smPG-I) migrated slower than the 200 kDa marker protein; when reassessed on 3-5% acrylamide gels, its apparent molecular mass was larger than the 480 kDa and 440 kDa alpha and beta heavy chains of dynein. We estimated the apparent molecular size of this smPG to be approximately 520 kDa. The smaller smPG (smPG-II) had an apparent average molecular mass of 180 kDa (range 170-210 kDa) after 3-16% SDS/PAGE. Three monoclonal antibodies, 1C6, 5D4, and S103L, reactive with the hyaluronic acid binding region of the aggregating proteoglycan core protein, keratan sulfate, and a core protein domain in the chondroitin sulfate attachment region, respectively, reacted with a single protein (apparent molecular mass, 180 kDa) that was similar in size to smPG-II.


[Study of asynchronous and synchronous yeast cultures using flow cytofluorometry].

Distribution of Saccharomyces cerevisiae, Candida boidinii and Candida tropicalis cells according to DNA content was investigated using laser flow cytofluorometry. Cells distribution curves according to DNA content possessed two maxima in case the sample belonged to the exponential phase of the asynchronous batch culture, or one maximum in case the sample was from the stationary phase of growth. In synchronous cultures variations of cells distribution curves according to DNA content (age structure of the population) were demonstrated and the curves with one maximum and plateau were observed.


Verapamil decreases cyclic load-induced calcium incorporation in ROS 17/2.8 osteosarcoma cell cultures.

Bone is a tissue that responds to mechanical load by changing its internal architecture. However, the mode of transmission of mechanical stimuli into biological signals and the effect of load at the cellular level are still not clear. An in vitro system, a Flexercell Strain Unit, was used to apply cyclic load to osteoblast-like cells in culture. In the first series of experiments, ROS 17/2.8 rat osteosarcoma cells, cultured on Flex I, flexible bottomed culture plates, were subjected to a 0.05 Hz, 0.24 STRAIN cyclic load regime for 3 and 7 days, in vitro. One group subjected to load received verapamil, a calcium channel blocker, throughout the experimental period. A second group was exposed to load but received no verapamil. A third group had no drug or load and a fourth group had no load but received verapamil. Cultures were incubated for 24 hours prior to collection with 10 microCi of 45CaCl in the medium, then well bottoms were divided to yield outer (maximum) and inner (minimum) load zones for assay of radioactivity. The effect of verapamil during a 7-day loading period was studied by adding the drug to individual cultures at daily intervals. Results indicated that mechanical loading stimulates calcium incorporation in ROS 17/2.8 cell cultures by day 7 but not by day 3. Only early verapamil addition decreased load-induced calcium incorporation when drug was added prior to day 4. If verapamil was added after 4 days, the channel blocker did not diminish load-induced calcium incorporation.


Demonstration of type III collagen in the dentin of mice.

It has been reported that, although type III collagen is present in human dentin where there is dentinogenesis imperfecta and in reparative dentin, it is absent in normal dentin. In a preliminary study, however, we observed evidence showing that small amounts of fibers showing positive labeling for type III collagen are present in the molars of normal mice. In the present study, in order to localize type III in normal dentin, immunofluorescent and immunoelectron microscopic examinations of the molars of normal mice were carried out using affinity-purified antibodies to mouse type III and type I collagen. The fibers positive for type III collagen were much more frequently observed in the root than in the crown. These fibers ran in peritubular dentin or near that in parallel to them. The incidence of the existence of dentinal tubules associated with type III collagen-positive fibrils either in or near peritubular dentin was low. These fibrils positive for type III collagen showed a clear cross-banding. In dentinal tubules, unusual collagen aggregations, segment long-spacing-like and fibrous long-spacing-like structures which were intensively stained for type I collagen but weakly so for type III collagen were seldom observed. Type III collagen-positive fibers often extended towards the pulp beyond the odontoblast layer, suggesting that these fibers were produced, at least partly, by the pulp cells.


The serine proteinase inhibitory proteins of the human intervertebral disc: their isolation, characterization and variation with ageing and degeneration.

Serine proteinase inhibitory proteins (SPIs) were extracted from human disc tissues using 2 M GuHCl and subjected to CsCl density gradient ultracentrifugation. The SPIs recovered in the low buoyant density fractions (rho < or = 1.35 g/ml) were purified by a combination of gel-permeation, ion-exchange, trypsin affinity, and reverse-phase high performance chromatographies. Characterisation of the major disc SPI by polyacrylamide gel electrophoresis, isoelectric focussing, enzyme inhibition and pH stability studies indicated that this small molecular weight (12-14 kDa), highly basic (pI > 9.5), acid-stable but alkaline-labile protein possessed potent inhibitory activity against bovine pancreatic trypsin and chymotrypsin, and human leukocyte elastase and cathepsin G. Two-major and two-minor low molecular weight cationic SPI species were identified by reverse-phase HPLC. The predominant species was identical to a human articular cartilage SPI sharing amino terminal sequence homology with the mucus proteinase inhibitors (MPIs). It also cross-reacted with an antiserum to the MPIs and behaved identically to secretory leucocyte proteinase inhibitor (SLPI) when examined by reverse phase HPLC, and SDS PAGE. A higher molecular weight (54 kDa), anionic (pI approximately 4.6) SPI was also purified and identified as alpha 1-proteinase inhibitor (alpha 1-PI). Quantification of alpha 1-PI and the small molecular weight cationic disc inhibitors indicated that the latter were depleted in morphologically degenerate disc tissues while levels of alpha 1-PI were somewhat higher although a large proportion of the alpha 1-PI was inactive. A depletion of total SPI levels was evident overall in degenerate discs suggesting a functional role for these inhibitory proteins in the maintenance of IVD matrix homeostasis.


Interleukin-6 does not regulate interstitial collagenase, stromelysin and tissue inhibitor of metalloproteinases synthesis by cultured human fibroblasts.

We have examined the effect of interleukin-6 (IL-6) on the synthesis of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMP) by human skin fibroblasts, both at protein and messenger RNA levels. IL-6 did not modulate the production of MMPs and TIMP. Furthermore IL-6 did not modify the stimulatory effect exerted by interleukin-1 (IL-1) on the expression of MMPs and TIMP. These results strongly suggest that IL-6 is not involved in the extracellular matrix breakdown, either directly by acting on cell production of MMPs or TIMP, or indirectly by modulating the effect of IL-1 on the synthesis of MMPs and TIMP.


Monoclonal antibodies against human fibroblast collagenase and the design of an enzyme-linked immunosorbent assay to measure total collagenase.

Monoclonal antibodies have been raised against purified human fibroblast collagenase and characterised. One of these antibodies has been used in combination with a polyclonal anticollagenase antibody in a double antibody sandwich ELISA to measure collagenase. The assay range was 2-50 ng/ml collagenase. The assay measures total collagenase, i.e. pro- and active enzyme as well as collagenase in complex with TIMP. The level of collagenase has been measured in sera samples from patients with rheumatoid arthritis and compared with age- and sex-matched controls. The levels measured were: rheumatoid arthritis, 69 +/- 29 ng/ml; normal, 49 +/- 14 ng/ml.


Dissociation of collagenase-tissue inhibitor of metalloproteinases-1 (TIMP-1) complex--its application for the independent measurements of TIMP-1 and collagenase activity in crude culture media and body fluids.

Collagenase-tissue inhibitor of metalloproteinases-1 (TIMP-1) complex was prepared from activated collagenase and TIMP-1 purified from culture media of human skin fibroblasts. After having been confirmed to be a complex by zinc chelate chromatography, the complex was demonstrated to dissociate by passage through an anti-TIMP-1 monoclonal antibody-affinity column. On the basis of above evidence, a simple strategy was set up for the independent measurements of TIMP-1 concentration, and both active and total collagenase activities in crude culture media and body fluids.


In vivo neutralization of tumor necrosis factor-alpha and interferon-gamma abrogates resistance to Yersinia enterocolitica infection in mice.

Cytokines are important mediators of the inflammatory host response against infectious agents. In this study, the role of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in the elimination of a primary infection with highly virulent Yersinia enterocolitica serotype 0:8 strain WA-P has been investigated in C57BL/6 mice. The injection of anti-TNF-alpha or anti-IFN-gamma antibodies ("serotherapy") prior to the intravenous challenge of a sublethal dose of Y. enterocolitica caused an increased bacterial net-growth in the spleens, although this effect was more pronounced for anti-TNF-alpha treatment. The later treatment with anti-TNF-alpha or anti-IFN-gamma antibodies on day 3 post infection likewise abrogated resistance to Y. enterocolitica and, subsequently, led to death from progressive infection. Our data demonstrate for the first time that the endogenous production of both the cytokines TNF-alpha and IFN-gamma is required for the restriction of a primary Y. enterocolitica infection in mice.


Determination of IgG subclass antibodies to Pseudomonas aeruginosa outer membrane proteins in cystic fibrosis lung infection using immunoblotting and enzyme-linked immunosorbent assay.

IgG subclass antibodies to Pseudomonas aeruginosa outer membrane proteins (OMP) were investigated in serum from cystic fibrosis (CF) patients by immunoblotting and enzyme-linked immunosorbent assay (ELISA). Fifteen patients (eight in good and seven in poor clinical condition) have been followed for an average of 13 years with multiple serum samples covering the preinfection, and early and late stages of chronic infection. Laser-scanning densitometry of photographs taken from immunoblots was used to quantify antibody level and compare with ELISA titres. The earliest anti-OMP antibodies to appear were of the IgG1 subclass. There was no significant difference in IgG subclass antibody levels to OMPs between patients in relatively good and poor clinical condition. Data presented indicate a high positive correlation among measurements of IgG subclass antibodies to P. aeruginosa OMPs using ELISA and immunoblotting.


Lack of activity of transferrins towards Streptococcus spp.

Clinically relevant Streptococcus spp. were tested for their susceptibility towards human serum transferrin (TR) and lactoferrin (LF). Neither clinical isolates or type strains were inhibited by transferrins (5 mg/ml). All species tested were shown to be able to grow under iron-limiting conditions (< 0.1 microM) and this might account for the lack of TR or LF activity towards streptococci. Even if not sensitive to LF and TR, some species were shown to bind LF in the apo-form.


[Results and experiences of transvenous endocardial defibrillator therapy].

We studied the follow-up of 72 patients who underwent implantation of a transvenous defibrillation lead system (ELS) (Endotak, CPI). All patients had ventricular tachycardia (VT) or fibrillation (VF) refractory to antiarrhythmic drug therapy. There were 51 patients with coronary disease and 21 patients had non-ischemic VT/VF. ELS was combined with a subcutaneous patch in 52 patients and implanted alone ("single lead only") in 20 patients. 40 patients received the ELS combined with antitachycardia pacing devices (Ventak PRx, CPI; Cadence, Ventritex) and 32 patients with the Ventak P 1600 or P2, CPI. Implantation of the ELS was attempted in 80 patients and performed in 72 patients (90%): Intraoperatively, the mean defibrillation threshold (DTF) was > 25 Joule (J) in five patients and no reliable ELS position was possible to achieve in three patients. These eight patients underwent thoracotomy with epicardial patch implantation. The mean DFT was < or = 20 J in all 72 patients with a mean DFT of 14 +/- 8 J in VT patients and 17 +/- 10 J in VF patients. Two of 80 patients (3%) died: one patient died intraoperatively and one during the mean follow-up of 6 +/- 2 (< 1 to 18) months. Complications occurred in three patients (4%): Dislocation of the Endotak electrode was observed in two patients (3%) and one patient developed pneumothorax postoperatively. Our data show that the ELS is most suitable in the majority of patients with VT/VF and is the approach of first choice for cardioverter defibrillator implantation at the present time. However, despite a relatively low intra- and perioperative complication rate, this approach should not be performed in institutions without cardiac surgery.


[The role of human atrial natriuretic peptide on pathogenesis of nephropathy in patients with type I diabetes mellitus].

Divergent findings in recent clinical and experimental studies have caused considerable controversy as to whether or how elevated plasma levels of human atrial natriuretic peptide (hANP) may contribute to the pathogenesis of diabetic nephropathy in type I diabetic patients. Therefore, we decided to examine potential changes of urinary albumin excretion (UAE), urinary excretion of alpha-1-microglobulin (A-1-M), mean arterial blood pressure (MAP), hANP levels, creatinine clearance and HbA1 in the course of a prospective one-year study in 19 patients (13 females, six males, age 29 +/- 2 years). All patients had intensified insulin treatment. Seven patients at increased risk for eventually developing nephropathy (group 1) were identified by repeatedly showing elevated UAE ( > 30 mg/24 h). The other patients served as controls (group 2). Patients in group 1 differed from those in group 2 in increased A-1-M (maximal difference, 10.1 +/- 1.5 vs. 5.5 +/- 1.0 mg/l, p < 0.01). In the second half of the study, 43% of the MAP measurements in group 1 exceeded 100 mmHg in comparison to 19% in group 2 (p < 0.01). Simultaneously, 38% of the hANP levels in plasma in group 1 were higher than 25 pg/ml (upper limit of normal range) in comparison to 15% in group 2 (p < 0.05). There were no differences in creatinine clearance between both groups. 58% of the HbA1 concentrations measured in group 1 in the course of the study exceeded 8.5% in comparison to 47% in group 2 (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


[Upper intestinal endoscopy in 188 bronchial cancer patients and 118 breast cancer patients with abdominal symptoms. The GI Metastases Study Group].

With the aim of analysing the pathological findings of upper gastrointestinal endoscopy in patients with bronchial or breast cancer and gastrointestinal symptoms a multicenter study was carried out over one year (1990) by 26 medical departments. One duodenal metastasis was verified among 188 patients with lung cancer. Seven of 118 patients with breast cancer developed symptomatic stenosis of the esophagus. A total of 42.9% of the patients with lung cancer and 38.6% of the patients with breast cancer had pathological findings detected by upper gastrointestinal endoscopy. Most frequent findings were duodenal and gastritic ulcers (lung cancer 15.0%, breast cancer 15.8%), esophagitis (lung cancer 16.3%, breast cancer 8.9%) and symptomatic stenosis of the esophagus (lung cancer 9.5%, breast cancer 7.0%). The authors conclude that there is a high frequency of relevant pathological upper gastrointestinal tract findings in symptomatic patients with breast or lung cancer, but that true metastatic disease is a rare phenomenon with the exception of metastatic involvement of the esophagus.


[Traveler's diarrhea in Turkey. Prospective randomized therapeutic comparison of charcoal versus tannin albuminate/ethacridine lactate].

In most cases traveler's diarrhea is a self-limiting disease not requiring professional assistance. As data on self-treatment are very limited, a prospective randomized trial was performed in 620 German tourists spending a two week-holiday in Turkey. 31.6% of these travelers developed diarrhea and 186 were assigned to two treatment groups, receiving either medical coal or a combination of tannalbuminate and ethacridinlactate (TA/EL). In the TA/EL group stool frequencies significantly earlier returned to normal and complaints of moderate to severe abdominal pain were recorded less frequently (50 vs. 82.2%) than in patients receiving charcoal preparations. Both medications were well tolerated and TA/EL appeared more efficient for self medication of uncomplicated traveler's diarrhea.


[Herpes simplex virus infection in pregnancy: epidemiologic, diagnostic and therapeutic data. An unusual case of HSV-1 in monozygotic twins].

The Authors report a case of two pre-term monocorial twins affected by HSV-1 infection (Herpes Simplex Virus type 1), with generalized sepsis and involvement of the central nervous system (CNS), born by mother with primary infection who presented a typical vesicular eruption a week before delivery. As the HSV-1 was a disseminated type and the CNS was involved in both the twins, the diagnosis was based on clinical and laboratory findings (specific IgM and IgG) and on the use of Delpech-Lichtblau antibody liquoral index, a significant results both in the first and the second twin. Intensive care and early specific treatment with Acyclovir allowed a slow but progressive improvement of the twins' clinical picture. The antibody liquoral index may therapy of the viral sepsis cases involving the CNS, more than the cultural or antigen isolation of the treated virus.


[Evaluation of a pediatric emergency room: ten years later].

Utilization of the pediatric Emergency Room has been evaluated during the year 1991, by a questionnaire study on 694 children. By comparison with a previous research in 1981 it was possible to identify a further decrease of urgent and appropriate visits with increase of those inappropriate. Visits were more frequently urgent of appropriate in case of acute health problems, inappropriate if related to recurrent problems. Without considering true emergencies, three main causes for ER consultation have been identified: family custom, inappropriate relationships with the practitioner, dependence on the hospital. In the first group of children most of the visits proved inappropriate. The study points out a further increase of inappropriate utilization of ER, due mainly to inappropriate relationships between the family and the practitioner. This has to be corrected to reduce costs and improve child care.


[Ambulatory and day hospital: pediatrics without any time spent in hospital].

The Authors show their six years' experience (1985-1990) in ambulatory activity and day hospital replacing the children's ward in a Lombard Hospital in order to prove the real efficaciousness of the formula "pediatrics without any time spent in hospital". They purpose a nosological framing of the services done in ambulatory and in hospital; they point out the indications for a really favourable use of the day hospital, they report the pathology treated in ambulatory (13,615 examinations) and in day hospital (1,632 admissions to hospital). After six years' experience, the Authors say that "Pediatrics without any time spent in hospital" can really meet most of the sanitary demands of the pediatric population and it is an instrument really improving and not reducing the treatment of the child.


[Ureteric peristalsis in congenital vesico-ureteral pathology. Integrated sonographic and scintigraphic studies].

Ureteric peristalsis is a key point for urinary progression. Its preoperative evaluation is important to assess indications for surgery. The study of the distal ureter is possible by means of ultrasound. Renal scintigraphy allows for a complete study of urinary progression along the ureter. A combined ultrasound and 99mTc-MAG3 preoperative work-up, has been performed in 32 urinary tracts (16 children ranging in age between 45 days and 11 years). Urinary progression occurs whenever peristaltic contraction makes the ureter lumen unpatent.


[Niemann-Pick disease type C in monozygotic twins].

The Authors describe two monochorionic twins affected by Niemann-Pick disease type C with a clinical picture beginning in the neonatal age and with a progressive mental deterioration, loss of speech and spasticity started at 30 months. The importance of cultured skin fibroblasts is emphasized. The evidence of a defective intracellular cholesterol esterification is established as an intrinsic feature of Niemann-Pick disease type C.


[Psychomotor management in the rehabilitation of patients with myopathy in infancy. Case studies].

The salient features are described of the psychomotor treatment given to two sisters: SA aged 11 yrs 5 months and MGA aged 9 yrs 9 months both affected with aspecific congenital myopathy and under medical treatment since they were 3 months old. These two cases were selected as examples for the following reasons: (1) they may offer the opportunity to highlight what should be the focal objective of all treatment of myopathic children whatever the syndrome involved, namely to ensure that the children retain capacities required for normal social life as long as possible and to help them retain the essential physical capabilities required for everyday life; (2) because the slower course of this type of myopathy permits the gradual implementation of a diversified treatment protocol in the various social contexts (family, school, play groups) in which these patients are able to lead a life whose limitations are scarcely visible for a long time. Experience in the treatment of these two cases confirms that the role of Psychomotor Education in the treatment of myopathy cases is essentially that of teaching the child to be aware of and responsible for its own movements as the disease progresses, while showing it how touse all its available sensomotorial instruments to counteract its muscular inadequacies which progressively damage the child's body image. Psychomotor education also provides the child with the self-assurance it needs in order to retain its autonomy within the framework of a knowledgeable and motivated family.


[Macleod's syndrome as a cause of recurrent pneumonia in a child].

Macleod's syndrome is a rare cause of recurrent pneumonia in children. A case report is described and the diagnostic utility of chest roentgenogram and CAT is emphasized.


[Effects of moderate maternal drinking on some neonatal parameters].

A cross-sectional study was conducted on 2415 mother/newborn pairs, in order to evaluate the relationship between maternal alcohol consumption and birth weight. The results of this study are consistent with previous reports, that pointed out the casual relationship between maternal drinking during pregnancy, and reduction in birth weight. This reduction was evident only on the subset of smokers. A further stratification by the sex of newborn, showed a heavier effect on male newborns, who experienced a significant reduction of 6.2 grams in birth weight for each g of absolute alcohol consumed daily during pregnancy by mother. The findings of this study support the evidence of neonatal functional damages due to alcohol, even at very low doses. A strong increase of early jaundice were found among the outcome of exposed women (OD = 3.30; 95% CI 1.03-10.54).


Nurse Education Tomorrow Conference 1991. An examination of selected current student nurse issues.

Clinical teaching has become increasingly complex and difficult for nursing instructors. Pressures for public accountability in nursing education and patient care, economic stresses, marked changes in the nursing curricula, and the growth of collective bargaining units have all complicated the task of educating student nurses. Traditional issues focusing on teaching strategies, academic and clinical evaluation concerns have been extensively researched. What are the current issues facing nurse educators? Our project aimed to identify some current student nurse issues in selected nursing programmes. Using a convenience sample, data were collected from the chairmen of nursing education in selected agencies. Analysis following the Fox and Diamond framework (1965) revealed recurring issues relating to mature students, stress and the clinical environment, and the mentor needs are a few of the issues discussed in this paper.


Simulation: current status in nurse education.

This paper suggests that in the light of recent developments in nurse education a review of available teaching and evaluation strategies is required. It is further suggested that the use of simulation for both teaching and evaluation purposes has much potential which has as yet to be fully exploited in nurse education.


Portfolios: an 'affective' assessment strategy?

The curriculum research and development work undertaken to facilitate the implementation of a portfolio assessment strategy, as an integral component of a Project 2000 course, is described. Many excellent assessment schemes have floundered at the point of being put in to use, thus the question of consultation, reflection and preparation needs to figure from the early stages in the scheme is to be successful. This should include in-service education for nurse and midwifery educators and preparation of students. The principle questions explored in the paper are: What educational values do portfolios have? Against what criteria should students make decisions in relation to content? Against what criteria are educators to assess portfolios? The issue of evaluation of portfolio schemes is likely to determine whether portfolios maintain the important place they have captured in the nursing and midwifery education imagination. Finally, it is argued that innovations, such as portfolios, should be seen as catalysts, as points of departure, rather than as things to be implemented.


Self-evaluation in nursing students in Finland.

The article explores the self-evaluation in nursing students in clinical evaluation: the structure and topics in evaluation sessions and the student-teacher relationships. The data were collected by means of non-participant observation: evaluation sessions of 81 (= n) students were observed in hospitals and health centres. The results indicated the rather passive role of nursing students in self-evaluation; teacher-dominated relationships were the most frequent in sessions. In future there is a need for a deeper analysis of the clinical evaluation.


The use of learning contracts in the clinical area.

This paper examines the implementation and evaluation of learning contracts in the clinical area with a small group of RGN students who were 18 months into their programme. An action research approach was used with the researcher acting as participant observer. Data collection methods included questionnaire, students self-evaluation, nominal group evaluation and researchers notes. The results indicated that through using learning contracts the tutor can effectively facilitate learning in the clinical area. Data collected indicated that the students did benefit from the experience. An important aspect that was identified is the need for adequate preparation of all those involved. The paper concludes that, although there are limitations, contract learning is a useful and valuable strategy to use in the clinical area providing the tutor with an alternative model for clinical contact.


Cooperation project in basic nursing education--the introduction of a new nursing education program in Tianjin, China.

Over the last few decades, traditional basic nursing education has taken place in nursing schools in China. In 1988, a new cooperation project for basic nursing education was tried between a Tianjin nursing school and several hospitals (Tianjin is one of the industrial cities in China). In this paper, an experiment in nursing education in Tianjin is described. In order to help readers to understand the Cooperation Project, the preparation courses are also described. Several advantages and disadvantages are discussed; some new proposals are also put forward at the end of the paper.


Communication for nurses: implications for nurse education.

To prepare the student of nursing to meet the demands of caring for the individual or a community within a dynamic and multi-cultural society, it is important that the nurse and the client see the healing process as being a co-operative venture. This co-operation relies on the growth of trust and confidence between interlocutors. Underpinning this is not only a sound clinical knowledge base but a sophisticated communication process at which individuals must be competent. The author argues that this competence is not automatic; it must be worked at and developed if the nurse is to be truly committed to the healing process. It is the responsibility of nurse educators to facilitate the growth and development of this competence in the students of today, if they are to be the nurses of tomorrow meeting new challenges. This paper examines some of the issues involved.


Institutional restraints upon education reforms: the case of mental health nursing.

The purpose of this paper is to temper over-optimistic expectations about the degree to which Project 2000 training will improve the quality of psychiatric nursing care. The paper commences by citing evidence that, to date, psychiatric nurses have tended not to adopt therapeutic approaches towards their patients. Curricular innovations aimed at encouraging them to do so have had little effect. It is argued that the effects of the latest education reforms may be similarly compromised. The reasons for mental health nurses not engaging in therapeutic care are as much to do with the institutions they work in as with the training that they receive. As long as nurses feel that it is part of their role to maintain institutional order, their therapeutic role will be compromised; while the latter requires social proximity, the former demands social distance. Moreover, because it is informal, rather than formal, therapeutic interactions that patients value in their dealings with nurses, it is not clear that the sort of knowledge that Project 2000 curricula are designed to impart will be therapeutically effective.


CD-ROM: towards a strategy for teaching and learning.

Compact Disc Read Only Memory (CD-ROM) represents an exciting innovation in nurse education yet paradoxically has a potential to induce disillusionment and frustration. Purchasers of systems may well find that their investment does not bring the benefits they had been lead to expect. CD-ROM systems have the capacity to generate huge quantities of data on an equally large number of nursing topics. Arguably this very capability ensures certain 'built-in' problems. The purpose of this articles is to provide nurse teachers with information about CD-ROM, to highlight the resource implications of CD-ROM use and to consider the relative merits of various teaching and learning methods. To be worthwhile, strategies developed must be part of an information retrieval skills programme.


Interactive video: an analysis of its value to nurse education.

This paper attempts to explain the emerging technology of interactive video and examine its possible place in nursing education. A brief description of the media is given with an exploration of the educational theory and justification underlying its use. A range of approaches to the evaluation of the technology itself and software available are given, which examine advantages and disadvantages for individual learners and for an organisation considering investment in this area. The possible role of interactive video in nurse education is discussed and a recommendation given that nurse educators need to keep up-to-date with developments in this type of educational technology and develop software suitable for the needs of nurses, rather than having to use packages developed for other purposes which have limited application for nursing.


[Vascular proliferation in the stroma of gastric cancer and its significance].

To elucidate vascular characteristics in the stroma of gastric cancer, the morphological and immunohistochemical changes of vascular components were examined in 27 gastric cancers and 7 noncancer gastric tissues including 2 peptic ulcers. In differentiated adenocarcinoma, a large number of blood vessels were observed in vicinity of the cancer glands and type IV collagen (C-IV) was localized around the blood vessels and cancer glands, and ultrastructurally, cytoplasmic organelle and weibel-Palade bodies were encountered in the endothelium. In poorly differentiated adenocarcinoma, a small number of blood vessels were distributed sporadically in the stroma and there were vascular endothelia in which von Willebrand factor (VWF) was localized, and there were much more endothelia in which VWF was not localized compared with differentiated adenocarcinoma. C-IV was localized only around the blood vessels and OKM5 was localized in the endothelia which were distributed in the center of cancer nest in poorly differentiated adenocarcinoma. Ultrastructurally, there were not so many Weibel-Palade bodies in the endothelia without complete basement membrane. The morphological and functional changes of blood vessels were correlated with cancer differentiation and metastasis. These changes may provide biological feature of cancer and may be induced by cancer cells, vascular endothelia and mesenchymal cells.


[Experimental study on platelet activating factor and systemic circulatory failure caused by ischemic liver].

Ischemic hepatic failure is often accompanied by systemic circulatory failure. In hepatic graft failure, this circulatory derangement is reported to be cured by retransplantation. This suggests that ischemic liver might release some substance which causes circulatory depression. In the present study, the role of platelet activating factor (PAF) in systemic circulatory failure after liver ischemia was investigated. Partial hepatic ischemia was induced in ten dogs by clamping the afferent vessels to almost 70% of the liver for 60 minutes, and non-ischemic lobes were resected after declamping. Five were pretreated with 3 mg/kg of PAF antagonist (CV6209) i.v. (PAF antagonist group), and the others were pretreated with saline (control group). The mean arterial pressure markedly decreased after declamping in control group (89 +/- 25mmHg 25 min after declamping), but it did not fall in PAF antagonist group (155 +/- 221mmHg). Three died from either shock or hepatic failure within a week in control group, but none died in PAF antagonist group. In conclusion, ischemic liver was suggested to release PAF and depress systemic circulation. And a PAF antagonist was expected to be an effective drug for the circulatory derangement caused by ischemic liver.


[Experimental study on the effect of ursodeoxycholic acid in liver transplantation].

We investigated the effects of combination of cyclosporine A (CsA) and ursodeoxycholic acid (UDCA) in order to reduce hepatopathy caused by host-versus-graft-reaction (HVG reaction). DA/S1c rats were used as donors, and LEW/Sea rats were used as recipients in orthotopic liver transplantation. The liver transplanted rats were divided to four groups as follows; group A was control that was not given CsA nor UDCA, group B was given CsA alone, group C was given UDCA alone and group D was given combination of CsA and UDCA. These groups were compared and evaluated in case of same dose of CsA that was administered with or without UDCA. The survival periods of group D were significantly longer than those of group B. Blood biochemical levels in group D were significantly lower than those of group B. Histological study of the liver graft of group D showed that destruction of hepatic structure was mild in comparison to that of group B. It was demonstrated that the combination of low dose of CsA and UDCA could prevent hepatopathy due to HVG reaction. These results suggested that addition of UDCA to CsA would be able to reduce the dose of CsA in clinical liver transplantation.


[Cystic disease of right popliteal artery with spontaneous resolution].

The case was 50-year-old man. He was admitted to our hospital suffering from intermittent claudication. DSA and CT showed stenosis of the right popliteal artery due to compression by the tumor like lesion. The adventitial cystic disease was suggested. Three weeks later he had no symptom. DSA and CT revealed no reappearance of the adventitial cystic disease. The popliteal adventitial cyst spontaneously decreased in size. It is a very rare case.


Nucleotide sequence of bup, an upstream gene in the bmi-1 proviral insertion locus.

The ability of Moloney murine leukemia virus to accelerate lymphomagenesis in E mu-myc transgenic mice is frequently associated with proviral integration within a locus denoted bmi-1. This locus contains not only the bmi-1 gene implicated as a collaborator with myc in lymphomagenesis but also just upstream an unknown gene denoted bup. The nucleotide sequence reported here for bup cDNA and flanking genomic sequences reveals that this widely expressed gene comprises at least 7 exons and potentially encodes a polypeptide of 195 amino acid residues. Computer searches with this polypeptide sequence revealed no close homolog in the databases, nor any conserved motifs, and it is unrelated to the product of the mel-13 gene, which lies just upstream from the bmi-1 homolog mel-18.


Characterization of the genes encoding U4 small nuclear RNAs in Arabidopsis thaliana.

Three genes encoding U4 small nuclear RNA (U4 snRNA) in the higher plant Arabidopsis thaliana have been isolated and characterized. Two of the genes, AtU4.1 and AtU4.2, contain all the transcriptional signals known to be essential for U-snRNA gene activity in dicot plants: the Upstream Sequence Element (USE), the -30 TATA box and the downstream 3' end formation sequence. The USE and TATA elements are centered approximately four helical DNA turns apart, a feature characteristic of RNA polymerase II-transcribed U-snRNA genes of plants. The genes AtU4.1 and AtU4.2 are actively transcribed in transfected plant protoplasts and in Arabidopsis plants. Expression of the third gene, AtU4.3, could not be demonstrated. Since this gene is missing the downstream signal important for RNA 3' end formation, it probably represents a pseudogene. The genes AtU4.1 and AtU4.2 encode 152-153 nt long RNAs which show 85-89% sequence similarity with broad bean and pea U4 RNAs and 60-65% similarity with mammalian U4 RNAs. Arabidopsis U4 and U6 snRNAs can be folded into the base-paired Y-shaped model supporting the importance of the U4/U6 interaction during pre-mRNA splicing in plants as well as animals.


Estrogen-induced synthesis of uterine proteins declines during aging.

The synthesis of total cellular as well as acid-soluble nuclear proteins and estrogen receptor is high in the uteri of young (22 weeks) and decreases to half in old (104 weeks) rats. Administration of estrogen induces the synthesis of these proteins significantly in young but shows no remarkable effect in old rats. Interestingly, a specific cytosolic protein of 45 kDa is stimulated about two-fold after estrogen injection in young but not in old rats. These findings further establish the reduced responsiveness of uterus to estrogen in old age.


Detection of antibodies to DNA: a technical assessment.

Antibodies to DNA can be found in the circulation of the majority of patients with Systemic Lupus Erythematosus (SLE). They are quite specific for this disease, which makes their detection an important diagnostic aid to the clinician. Fluctuations in the level of anti-dsDNA in an individual patient generally parallel the clinical state of that patient. Furthermore, the presence of anti-dsDNA may precede the diagnosis of SLE by more than a year. Four methods relevant for the measurement of anti-dsDNA antibodies are discussed in this paper: the ELISA, the indirect immunofluorescence test on Crithidia luciliae, the PEG assay, and the Farr assay. Each of these methods detects a part of the spectrum of anti-dsDNA antibodies present in the circulation of an individual patient. The ELISA is the most sensitive method, whereas the Farr assay is the most specific for SLE. However, with the latter method only antibodies of a relative high avidity for DNA are detected. Mild forms of SLE, where patients only have anti-dsDNA of a low avidity in their circulation, may easily be missed by this technique. Clinically, high avidity anti-dsDNA is related with the more frequent occurrence of nephritis, whereas low avidity anti-dsDNA antibodies are more often found in patients with central nervous system involvement.


Susceptibility of yeast isolates from defined German patient groups to 5-fluorocytosine.

Susceptibility and development of resistance to 5-fluorocytosine (5-FC) in Candida strains isolated from defined German groups of probands was investigated. 5-FC susceptibility was determined in a microdilution assay in yeast nitrogen base after 24 h of incubation at 37 degrees C. The range of 5-FC concentration investigated was between 0.015 and 16 micrograms ml-1. Isolates with a minimum inhibitory concentration (MIC) of > 16 micrograms ml-1 were regarded as 5-FC resistant. In total 335 Candida isolates were investigated, and 20 of them (6.0%) were found to be resistant. The Candida isolates were rather different with respect to their origin: out of 57 vaginal isolates from non-risk patients from Southern Germany 3.5% were 5-FC-resistant strains. One hundred and fifty-nine isolates from the urine of long-term intensive care patients from the whole of Germany showed 5-FC resistance (6.3%). Out of 74 isolates of different localization from intensive care patients of the University Clinics of Freiburg, 10.8% showed 5-FC resistance. Among 45 isolates from the oral cavity of HIV-positive patients from the Frankfurt region, no 5-FC-resistant strain was found. The epidemiology of 5-FC resistance is based mainly on the percentage of non-albicans isolates of the proband groups (C. tropicalis, C. krusei and others), and is less based on the frequency of Candida albicans serotype B isolates. In sequential observations with individual intensive care patients, no increase of 5-FC resistance in their Candida isolates could be observed with longer periods of hospitalization.


Quantitative assessment of the efficacy of oral ketoconazole for oral candidosis in HIV-infected patients.

Fifteen male patients with manifest oral candidosis due to Candida albicans, suffering from AIDS-related complex (ARC) or full-blown AIDS, were investigated both clinically and microbiologically before and about 1 and 4 weeks after 7 to 10 days of treatment with 200 mg ketoconazole p.o. per day. Candida albicans was quantitated in mouthwash fluid. The antimicrobial susceptibility of the Candida albicans isolates was assessed using the IC30 test. In the short term, clinical cure was obtained in 87%, mycological cure in 53%. In the long term, the corresponding figures were 56 and 9%, respectively. Eradication of Candida albicans was not possible if IC30 values exceeded 256 micrograms ml-1. While pretreatment counts of Candida albicans in those patients also taking zidovudine did not differ from those in the rest of the study population, both the clinical and the mycological efficacy of ketoconazole seem to be higher both in the short and the long term when administered together with zidovudine. In consideration of the high relapse rate after about 4 weeks, an interval treatment protocol with oral ketoconazole is proposed.


Vaginal yeast colonization and promiscuity. A study of 197 prostitutes.

In order to study the role of promiscuity in yeast colonization of the vagina we examined vaginal smears of 197 prostitutes. Forty-two (21%) showed yeast infection on culture, and Candida albicans was isolated in 93% of these cases. This rate is comparable to the rates in reports of large series of non-promiscuous women in the literature and does not suggest that promiscuity alone is a predisposing factor for vaginal yeast carriage. The rate of Candida infections was approximately the same in prostitutes taking oral contraceptives as in those not taking the pill (22 and 21%, respectively; P > 0.05). The prevalence of vaginal yeast colonization, however, was significantly higher in prostitutes under the age of 31 (30%) as compared with those over 30 (10%; P < 0.002), thus suggesting that women in the third decade of life are more prone to vaginal Candida infections than older age groups.


Long-time survival and morphological stability of preserved Sporothrix schenckii strains.

The survival and stability of morphological traits of 33 Sporothrix schenckii strains were evaluated. Strain subcultures were maintained under mineral oil for different periods of time lasting as long as 41 years, or in sterile distilled water for as long as 23 years. Of the 33 strains preserved under mineral oil, 28 (85%) maintained viability and unchanged macro- and microscopic characteristics. All of the 4 strains maintained in distilled water also remained viable, with no morphological changes. The results confirm the efficiency of the methods used to preserve strains of the pathogenous and anamorphous fungus Sp. schenckii, especially in laboratories of limited resources.


Candidosis, aspergillosis and zygomycosis in an oncology department.

The incidence, aetiology and treatment of fungal infections in a 60-bed department of clinical oncology over 2 years is reported. During the second year, after the moving of the department from an old to a new building with an improved epidemiologic regimen, the incidence decreased rapidly, although the mortality due to systemic disseminated mycosis did not change.


Onychomycoses due to Microascus cirrosus (syn. M. desmosporus).

Microascus cirrosus is very rarely the aetiological agent of onychomycosis. We report two additional cases of toenail infections caused by this fungus.


Dermatophyte infection in ichthyosis vulgaris.

A 31-year-old male who had been suffering from ichthyosis vulgaris developed hyperkeratosic lesions on the palms and soles and ungual alterations of both hands and feet. These lesions were resistant to topical corticosteroid and emollient cream treatments and were found to be caused by Trichophyton rubrum. Association of ichthyosis vulgaris and dermatophytosis--both very common disorders--is to our knowledge a very rare event.


Biochemical and morphological changes in rat lenses after long-term UV B irradiation.

The aim of the present study was to investigate biochemical and morphological changes in rat lenses following long-term UV B irradiation. After an irradiation period of 156 days with follow-up documentation by means of Scheimpflug photography, section-related biochemical analyses of the lenses as well as histological investigations were performed. The video-based Scheimpflug photography (Zeiss SLC) again proved to be an excellent method for the documentation of the UV cataract induced in rats. The biochemical analyses provided indications to potential damaging mechanisms; the section-related technique used allows more precise analyses than the processing of whole lenses in a cataract type restricted to a certain layer, as is the case with UV B damage. The most prominent biochemical findings were a significant decrease in glyceraldehyde-3-phosphate dehydrogenase in the equatorial region in the group with the highest irradiation dosage and a decrease in lactate dehydrogenase in the nuclear region. The histological results reflect the local extent of the UV damage as well as its progression after a prolonged irradiation period.


Diagnostic tests for dry eye disease in normals and dry eye patients with and without Sjögren's syndrome.

In order to compare the diagnostic tests for dry eye disease and the results of conjunctival impression cytology, we examined three groups of eyes: 146 eyes of normal controls, 108 eyes of keratoconjunctivitis sicca (KCS) patients without Sjögren's syndrome (SS) and 102 eyes of patients with SS. The clinical tests (break-up time, Schirmer test, Rose Bengal staining) and conjunctival impression cytology specimens from the superior part of the bulbar conjunctiva were evaluated from all the eyes. Our results showed that the patients with KCS without SS have abnormal lacrimal tests (p < 0.001) without changes in impression cytology [nucleo/cytoplasmic ratio (N/C), p > 0.1]. The patients with KCS and SS have also abnormal lacrimal tests (p < 0.01), and their epithelial cells presented squamous metaplasia (N/C, p < 0.001). The goblet cell number remained unchanged in the three groups (p > 0.1).


Susceptibility of +/+, +/nu and nu/nu BALB/c mice to ocular herpes simplex virus infection.

Athymic (nude) mice have played an important role in defining the function of the immune system and its role in infectious diseases. In the majority of these studies, heterozygous +/nu mice have been used as normal controls for the nu/nu mice, and it has been assumed that +/nu mice have essentially normal immune systems. We have compared the response of +/+, +/nu and nu/nu BALB/c mice following ocular infection with HSV-1 and have found that +/nu mice develop significantly more severe blepharitis, vascularization of the cornea, stromal keratitis and extraocular disease (herpetiform spread) than +/+ BALB/c mice. The extraocular disease was particularly severe in the +/nu mice, suggesting that factors regulating herpetiform spread of the virus are deficient in these mice. Susceptibility to lethal encephalitis did not differ between +/+ and +/nu mice. These results suggest that significant differences exist in the response to ocular HSV infection between +/+ and +/nu mice.


Ocular pulsation correlates with ocular tension: the choroid as piston for an aqueous pump?

In 26 random out-patients, including 13 treated glaucoma patients and ocular hypertensives, the higher the ocular tension, the greater the pulse amplitude, by Alcon pneumotonometry, at a statistically significant level. In a single untreated hypertensive, when 2-hourly pneumotonometry was done for 24 h, the correlation was similar and significant. The higher the diastolic blood pressure, the higher the ocular pulsation, also significantly. Pulsation is suggested to be a pump, the choroid being the piston, contributing (1) to an increase in the outflow of aqueous humour and (2) to a homeostatic mechanism contributing to normalization of the intra-ocular pressure, wherein pulsation increases or decreases, as the intraocular pressure increases or decreases, respectively.


Localization of elastic fibers and elastin mRNA in the uvea of chick embryo.

The distribution of elastic fibers and elastin mRNA was studied in the uvea of 19-day-old chick embryos by light and electron microscopy and in situ hybridization techniques using a 35S-labeled RNA probe. Light and electron microscopic examination revealed that elastic fibers were present in the uveal portion of the ciliary body, but not in the posterior choroid. Electron microscopically, elastic fibers were also found in Bruch's membrane. Abundant amounts of elastin mRNA were strictly localized in the fibroblasts in the uveal portion of the ciliary body, and no elastin mRNA was found in any of the cells in the posterior choroid by in situ hybridization. Cultured uveal tissue obtained from the ciliary body was found to produce large amounts of tropoelastin as compared with cultured posterior choroid. Using V8 protease peptide mapping and Northern blot analysis, the tropoelastin and its mRNA produced by the ciliary body were identical to those produced by the smooth muscle cells in the aorta. The results suggest that elastin is synthesized in the ciliary body, acting as a supporting substance in this area.


Corneal concentration and systemic absorption of cyclosporin-A following its topical application in the rabbit eye.

To ascertain the corneal storage and the possible systemic absorption of 2% cyclosporin-A (CsA) eyedrops, the authors studied, by RIA with monoclonal specific antibodies, the corneal and blood levels of the drug following its topical administration on healthy albino rabbit eyes. When topical CsA was administered following a low-dose application schedule [such as a single dose of 100 microliters every 12 h for 5 days (group 1)], CsA corneal levels of 260.8 +/- 59.8 ng/ml and blood levels of 55.67 +/- 24.4 ng/ml (expressed as means +/- SD) were achieved. These levels significantly increased to 1,111.27 +/- 449.4 ng/ml (p > 0.0001) and 88.66 +/- 59.7 ng/ml (p > 0.05), respectively, when a higher dosage was used [100 microliters every 6 h for 10 days (group 2)]. It is shown that a dose-dependent corneal concentration of CsA, due to a cumulative effect, is achieved in the intact rabbit cornea following topical application of the drug. Systemic absorption of CsA, although irregular, does exist. Therefore, when using topical 2% CsA as in this study, a systemic effect of the drug (especially in low weight animals) should be considered when analyzing the results of topical application.


Comparison of effects of oxygen and antioxidative enzymes on cell growth between retinal pigment epithelial cells and vascular endothelial cells in vitro.

We assayed the proliferation of porcine retinal pigment epithelial (RPE) cells, bovine melanotic and amelanotic RPE cells, and bovine aortic endothelial cells exposed to 20, 10 and 5% oxygen and compared their responses to oxygen and antioxidative enzymes (superoxide dismutase and catalase). Irrespective of the cell type, the cell growth was optimal in 10% oxygen that is most closely approximating to the oxygen concentration prevailing in the cellular environment of the choroid and the retina in vivo. However, the effects of oxygen concentrations were cell specific because bovine endothelial cells were influenced by lowering of oxygen concentrations more significantly than bovine and porcine RPE cells. Moreover, addition of antioxidative enzymes caused significant improvement in growth of porcine RPE cells, but had no significant effects on bovine RPE cells. On the contrary, the bovine vascular endothelial cells represented the only one cell type significantly inhibited by antioxidative enzymes, i.e., a decrease in reactive intermediates of oxygen was seen in the media. Our results show that responses of vascular endothelial cells to reactive species of oxygen were distinctly different from those of RPE cells and more easily influenced by the environment related to hypoxia than RPE cells.


Connective tissue of the orbital cavity in retinal detachment: an ultrastructural study.

The connective tissue from Tenon's capsule of 7 patients who underwent surgery for retinal detachment was studied ultrastructurally. Five patients were 58-70 years old, and 2 were young adults. The Tenon capsules of 6 children and of 2 aged patients without retinal problems were used as controls. In young controls the Tenon capsule was composed mainly of round, smooth collagen fibrils and a few elastic fibers. The collagen fibrils varied in size from 70 to 110 nm. In the aged patients with retinal detachment, the collagen fibrils showed marked variation of size and also abnormalities of shape in 4 out of 5 cases. The diameter of collagen fibrils varied from 32 to 160 nm, and the elastic fibers were fewer as compared with controls. The possibility arises that age-related structural changes of the orbital connective tissue could predispose to retinal detachment.


Rabbit diurnal ocular tension variations.

Ocular tension recorded by pneumatonography was estimated at 4-hour intervals during six consecutive 24-hour periods in 8 New Zealand rabbits. The animals had been acclimatized for more than 8 weeks to artificial light from 08.00 to 20.00 h and dark for the other 12 h. Inter- and intrarabbit consistency was enough to allow the generalization that the lowest pressure occurred at noon (mean -0.8 mm Hg from baseline average), while the highest pressures (mean + 1.2 mm Hg above baseline average) occurred at 16.00 and 20.00 h. Only three other studies have measured rabbit ocular tensions throughout 24 h, but for shorter periods: one observed a light-induced rise as in the present study, but the other two studies found a rise during darkness.


Reasonable expectations: from the Institute of Medicine. Interview by Paul M. Schyve.

When the Omnibus Budget Reconciliation Act of 1989 created a new agency in the U.S. Public Health Service to foster the development of practice guidelines and outcomes and effectiveness research, the Institute of Medicine was engaged to develop the criteria for guideline development and medical review. The new agency--the Agency for Health Care Policy and Research (AHCPR)--has used those criteria to develop and disseminate its first three commissioned guidelines, released this spring. Those criteria are elaborated in the IOM's 1990 book. In a second book, released this summer, the IOM Committee on Clinical Practice Guidelines reviews the constructive expectations for guidelines and the conditions needed to ensure rigor in their development, application, evaluation, and revision to help realize these expectations. Key recommendations for action are development of an instrument to assess guidelines and establishment of an organization to carry out the assessment of guidelines. In an appendix, the report offers "A Provisional Instrument for Assessing Clinical Practice Guidelines." While asking that organizations undertake more field testing and revision of the instrument, the Committee on Clinical Practice Guidelines believes that the provisional instrument will be useful as an educational tool for those beginning to develop guidelines, a self-assessment tool that developers of guidelines can use to check their work, and a tool for external groups to use in judging whether a set of guidelines should or should not be recommended or adopted.


Implementing clinical practice guidelines: social influence strategies and practitioner behavior change.

Clinical practice guidelines offer potentially valuable tools for rationalizing health care delivery and improving patient outcomes. Currently, major efforts are under way to develop, test, and refine guidelines for a wide variety of medical conditions and procedures. Although methods for producing guidelines are fairly well understood and continue to improve, experience suggests that guidelines rarely translate directly into changes in practice. For various reasons, including physician resistance or incomplete understanding of the need for guidelines, they have proven difficult to implement. This article describes a broad range of strategies for implementing clinical practice guidelines based on the social influences that affect health practitioner behavior. The article also examines issues surrounding the selection and use of individual strategies or combinations of strategies in specific efforts to improve the quality of health care.