Human irritant response to different qualities and concentrations of cocoamidopropylbetaines: a possible model of paradoxical irritant response.

Cocoamidopropylbetaines are surfactants frequently used in cosmetics. We have evaluated the irritant capacity of 3 different qualities of cocoamidopropylbetaine, using the following method: patch tests have been carried out with 5 different dilutions in 67 patients and the results read at 2 days by noninvasive methods (direct visualization, transepidermal water loss (TEWL), laser Doppler flowmetry (LDF)). The results with the 3 methods were concordant. However, the results with the different concentrations were paradoxical, as irritancy did not increase at higher concentrations. We have tried to explain this by the fact that these substances contain by-products (free amidoamine and sodium monochloroacetate), the concentrations tested all being above the critical micelle concentration and therefore containing both micelles and monomer. Finally, we believe that noninvasive methods such as TEWL and LDF could be of great use in the evaluation of irritant contact dermatitis.


Occupational and non-occupational allergic contact dermatitis from beryllium.

There are various references to sensitization to beryllium in the literature. Since introducing a patch testing series for patients with suspected sensitization to metals, we have found 3 cases of sensitization to beryllium. Of these 3 cases, we regard the first 2 as having relevant sensitization. Beryllium chloride (1% pet.) was positive in 3 patients and negative in 150 controls.


A glove with exceptional protective features minimizes the risks of working with hazardous chemicals.

In continuation of our preceding studies, we disclose long-term experiments to test more extensively the protective power of the novel 4H Glove. 2 compounds encountered in modern electron microscopy technique, 1-hexadecene (1-HD) and 2-hydroxyethyl acrylate (2-HEA), which elicit allergic and/or toxic reactions in laboratory workers, were tested for their penetration through the 4H Glove material 1-HD has not to our knowledge been tested on any glove material. 2-HEA was known to have a breakthrough time exceeding 240 min; in contrast, it penetrates the common latex or vinyl gloves within minutes. When exposing the outside of a 4H Glove to 2-HEA for 200 h at 21 degrees C and then attaching the reverse unexposed side to a sensitized volunteer's forearm, 30 min of contact elicited a barely visible reddening of the skin at the contact site which disappeared within 24 h; 90 min of contact caused a somewhat stronger reddening limited to the contact area, which disappeared within 2 days. By the same criteria, 1-HD did not penetrate through the 4H Glove in 200 h. In an additional experiment, breakthrough time of 1-HD on latex gloves was less than 30 min.


Vaccination granulomas and aluminium allergy: course and prognostic factors.

21 children who had cutaneous granulomas following immunization with a vaccine containing aluminium hydroxide, and who had positive patch tests to aqueous aluminium chloride and/or to a Finn Chamber, were followed for 1 to 8 years. During the period of observation, the symptoms cleared in 5 children, improved in 11, and remained unchanged in 5. The course of the granulomas could not be correlated with sex or atopy, nor with intensity of the initial aluminium patch test. 4 children were patch tested again with aluminium.


A multicentre study of contact sensitization in children. Gruppo Italiano Ricerca Dermatiti da Contatto e Ambientali (GIRDCA).

The results of 7 months of patch testing with a standard series of 26 allergens in 323 children with eczematous conditions or itching palmoplantar psoriasis under the age of 14 years are reported. 114 (35.3%) of the children had 1 or more positive reactions to this standard series. 28 children (8.7%) were polysensitive. On the basis of personal history, additional series of allergens and/or specific allergens were also tested. 61.7% (90/146) of positive reactions were considered relevant to the current dermatitis. Metals, medicaments, preservatives or fragrances, and shoe components were the major sources of contact sensitization. It is suggested that patch testing be done more frequently in evaluating dermatitis in children.


Tinuvin P in a spandex tape as a cause of clothing dermatitis.

We report a 54-year-old female with allergic contact dermatitis from 2-(2-hydroxy-5-methylphenyl)benzotriazole (Tinuvin P) in a spandex tape sewn into underwear. Tinuvin P is used as an ultraviolet light absorber for stabilizing plastics and the other organic materials against discoloration and deterioration. It is effective in protecting synthetic and natural fibers, polyesters, chlorinated polyesters, polystyrene, polyvinyls, cellulose acetate, ethyl cellulose, acrylates, dyes, waxes, detergents, cosmetic formulations, etc. Our patient developed itchy erythema on her shoulders, chest and upper back after wearing underwear for 1 night. She showed positive reactions to spandex tape sewn into the underwear. She also reacted to 2-(2-hydroxy-5-methylphenyl)benzotriazole (Tinuvin P), which was contained in the spandex. No cross-reaction to other benzotriazoles was seen.


Allergic contact dermatitis from chironomids.

Although Type I allergy to chironomids is well-known, allergic contact dermatitis caused by these cosmopolitan insects has not previously been reported. In the case we describe in this report, patch tests disclosed a delayed-type hypersensitivity to 4 different species of chironomids (larvae of Chironomus thummi, Chironomus plumosus, and 2 different species of Glyptotendipes) as the probable cause of airborne facial contact dermatitis. An additional asymptomatic immediate-type allergy to chironomids was demonstrated by scratch tests and specific IgE. The possible sources of exposure to chironomids, their allergens and their distribution are discussed with regard to clinical implications.


Changing trends in the epidemiology of contact dermatitis in Singapore.

All patients seen in the Contact Dermatitis Clinic of the National Skin Centre, Singapore (and the former Middle Road Hospital) between January 1986 and December 1990 were analysed retrospectively. 5557 patients comprising 2634 (47.4%) males and 2923 (52.6%) females were patch tested. 3154 (56.8%) patients had 1 or more positive reactions. The majority of the patients were Chinese (78.0%), followed by Malays (11.5%), Indians (8.1%) and other minority races (2.4%). The majority of positive reactions belonged to the 21-40 age group. The incidence of positivity decreased after 60 years. The commonest allergens responsible were nickel (17.7%), fragrance (13.3%), neomycin (6.9%), colophony (6.6%) and proflavine (6.5%). Both neomycin and proflavine were commonly used as over-the-counter medicaments. Compared to an earlier report in 1988, there were differences in the incidence of contact sensitivity to some allergens. Potassium dichromate, which used to be a common allergen, was less common. Some allergens (carba-mix, naphthyl-mix, caine-mix and PCMX) have been removed from our standard series as they were uncommon causes of contact allergy. Thimerosal and Amerchol L-101 were added in their place.


Patch testing with pure palladium metal in patients with sensitivity to palladium chloride.

During a 15-month period, 536 patients being investigated for suspected contact dermatitis were patch tested with the European standard series and palladium chloride 1% pet. 13 patients (2.4%) had a positive allergic response to palladium chloride and all 13 were also allergic to nickel. 12 of these 13 patients consented to further patch testing with discs of pure palladium metal foil, and none reacted. We have shown previously that palladium chloride patch test material contains traces of nickel, and propose an explanation for these results in terms of the additive effect of allergens when tested in combination.


Air oxidation of d-limonene (the citrus solvent) creates potent allergens.

Products containing as much as 95% of d-limonene are used for, e.g., degreasing metal before industrial painting and for cleaning assemblies. Experimental studies on the sensitizing potential of limonene show diverging results. In a previous study, we found that the sensitizing potential of d-limonene increased with prolonged air exposure. The aim of this study was to make further chemical analyses, to identify compounds formed by air exposure of d-limonene and to study their allergenic potential. d-limonene was found to be a sensitizer after prolonged exposure to air according to 2 Freund's complete adjuvant test (FCAT) experiments and 1 guinea pig maximization test (GPMT) study. No significant response was obtained to d-limonene not air exposed, even if the animals were sensitized to oxidized d-limonene. 5 main oxidation products of d-limonene were identified. (R)-(-)-carvone and a mixture of cis and trans isomers of (+)-limonene oxide were found to be potent sensitizers, while no significant reactions were obtained in the animals induced with a mixture of cis and trans isomers of (-)-carveol. It can be concluded that air oxidation of d-limonene is essential for its sensitizing potential, and that potent allergens are created.


A prospective study of the development of hand eczema in an automobile manufacturing industry.

We have not been able to find any prospective study of the risk of developing occupational dermatitis in the car manufacturing industry. To try to define individual predictive risk factors for the development of hand eczema and to determine the prevalence of hand eczema within 1 year in an automobile manufacturing industry, we investigated prospectively 1564 new employees during one year of employment. Only persons with previous atopic dermatitis or hand eczema were restricted to dry and clean workplaces. The employees were personally interviewed and examined before their employment. Written questionnaires were used at 3 and 12 months to obtain information on type of work, exposure, protection and hand dermatitis. All patients developing hand eczema were examined, patch tested and followed to determine the course and consequence of their eczema. The risk turned out to be only 4% on average, but significantly higher in females (6%). Certain sections within the factory such as wet work (canteen/kitchen and cleaning) and work in the paint shop with high exposure to organic solvents carried significantly higher risks. Heavy exposure to mineral oil, a known risk factor, was effectively counteracted by the extensive use of protective gloves to yield a lower than average prevalence in the press and body shop. Individual risk factors for the development of hand eczema were previous hand eczema, atopic dermatitis, but also wool intolerance and hay fever as isolated phenomena. Most cases of hand eczema were mild, of irritant contact type and only 1 employee developed an allergic contact dermatitis due to the working environment.(ABSTRACT TRUNCATED AT 250 WORDS)


Allergic contact dermatitis from the preservative 1,2-benzisothiazolin-3-one (1,2-BIT; Proxel): a case report, its prevalence in those occupationally at risk and in the general dermatological population, and its relationship to allergy to its analogue Kathon CG.

Occupational contact allergy to 1,2-benzisothiazolin-3-one (1,2-BIT, Proxel) is analysed. This compound is widely used in industry as a preservative in water-based solutions such as pastes, paints and cutting oils. The optimal concentration for patch testing proved to be 0.4 g/l (0.04%) in water. In 4 out of 17 patients (23%) at occupational risk (painters, paper-hangers), contact allergy to 1,2-BIT was found. Of 556 consecutive dermatological patients without clear occupational risk, 10 (1.8%) showed positive patch tests to 1,2-BIT; in 3 patients 1,2-BIT contact allergy was related to domestic paper-hanging. Although the chemical structure of 1,2-BIT shows some analogy with the preservative Kathon CG, true cross-sensitivity was found to be unlikely.


Shiitake (Lentinus edodes) dermatitis.

Shiitake (Lentinus edodes) is a mushroom which is eaten in Chinese and Japanese meals and is nowadays the second most commonly produced edible mushroom in the world. Shiitake dermatitis was first described by Nakamura in 1977. This disease presents with very characteristic skin manifestations. From April 1974 to April 1991, I have observed 51 patients with shiitake dermatitis. The following description reviews the clinical manifestations, laboratory investigations and sources of shiitake dermatitis.


Contact dermatitis from metallic palladium in patients reacting to palladium chloride.

1307 consecutive patients were patch tested with PdCl2 1% pet. 32 patients were positive; 29 also showed a reaction to NiSO4. 470 patients were additionally tested with a metallic palladium disc. 3 had a positive reaction, and none of them reacted to PdCl2 or NiSO4 pet. A positive patch test to PdCl2 pet. is in most cases probably due to a cross-reaction with nickel in nickel-sensitive subjects. Patients positive to PdCl2 tolerate skin contact with metallic palladium.


Propyl gallate on liposomes.

A hypothesis suggesting that the allergic potential of propyl gallate is boosted by its attachment to liposomes in cosmetics is put forward. 13 women with allergy to propyl gallate are presented.


Final diagnoses in patients referred for patch testing.

The final diagnoses made in 989 patients consecutively patch tested in 1990 have been reviewed. Among the men, their dermatitis was entirely occupational in 17.9% and partially so in 12.5%. Among the women, it was entirely occupational in 6.4% and partially so in 9.5%. In both groups, irritants exceeded allergens as the cause, whereas allergens superseded irritants in the patients with a non-occupational eczema caused or aggravated by external factors. It seems likely that domestic irritants were overlooked in patients with a non-occupational dermatitis.


Comparative study of TRUE Test and Finn Chamber patch test techniques in Singapore.

This is a report on a comparative study of the reactivity of TRUE Test and Finn Chamber patch test techniques. 413 patients attending a contact dermatitis clinic in Singapore were simultaneously patch tested with panels 1 and 2 of the TRUE Test standard series and with corresponding allergens (Hermal, Hamburg) using Finn Chambers. The left/right application of the TRUE Test and Finn Chambers was randomized. The concordance of positive patch test reactions to the 2 test techniques was studied. The number of patient with positive reactions was 38% and 42% for TRUE Test and Finn Chamber techniques, respectively (n.s.). The overall concordance of positive patch test reactions was 64% (209/328). 13% (42/328) of positive reactions appeared on TRUE Test only and 24% (77/328) on Finn Chamber only. When only relevant positive reactions were considered, the concordance rate was 67%; 11.6% of positive reactions appeared on TRUE Test only and 21% on Finn Chamber only. Positive reactions to p-phenylenediamine (PPD) and neomycin were more frequent with the Finn Chamber technique than with TRUE Test, i.e., false negative reactions to PPD and neomycin were more likely to occur with TRUE Test. It appeared that the TRUE Test and Finn Chamber techniques were comparable when used for patch testing. However false negative and false positive patch test reactions can occur when using either technique.


Further investigation of the prohapten concept: reactions to benzene derivatives in man.

p-Phenylenediamine (PPDA) is a strong contact sensitizer which is included in the standard patch test tray and which can also act as an indicator of allergy to related substances by virtue of cross-reactions. In a previous study, the pattern of cross-reactions between PPDA and related substances was investigated in the guinea pig to evaluate the prohapten concept. The results provided some support for this concept, but also indicated that a number of reactive intermediates might be behaving as haptens. This work has now been extended to an examination of the prohapten concept in man in PPDA-allergic subjects. These subjects were tested with 7 substituted benzenes, plus PPDA. Of these, the 1,4-substituted benzenes hydroquinone, Metol, PPDA and p-aminophenol are all capable theoretically of giving rise to benzoquinone by oxidation (after demethylation in the case of Metol). However, as had been the case in the guinea pig, only a limited degree of cross-reaction was observed. Only one of the subjects allergic to PPDA gave a clearly positive allergic reaction to benzoquinone. The data provided only limited support for the prohapten concept in terms of benzoquinone as the ultimate hapten for a range of 1,4-substituted benzenes. As indicated in the guinea pig, a range of reaction intermediates or indeed other oxidation products may be involved. So, for each molecule, the sensitizing activity and potential to give rise to cross-reactions may depend on the balance between routes of skin metabolism.


Possible origin of the skin sensitization potential of isoeugenol and related compounds. (I). Preliminary studies of potential reaction mechanisms.

Although many simple chemicals can give rise to the phenomenon of allergic contact dermatitis, it is rare that the mechanism of reaction between the chemical hapten and skin protein is known. A further complication is that metabolic processes may produce substantial changes to a chemical penetrating skin. Thus the skin contactant may be regarded as a prohapten which will give rise to the true hapten in vivo. In this study, the possible reaction mechanisms for a number of related simple aromatic chemicals have been investigated. The approach taken was to evaluate potential reaction mechanisms by assessing the degree to which chemicals could cross-react in sensitization tests. By careful choice of chemicals, it was then possible to confirm (or reject) options. Using this approach, a number of reaction schemes were investigated for eugenol, isoeugenol, dihydroeugenol, anethole and several related chemicals. The patterns of sensitization obtained and the cross-reactions observed indicated clearly that electrophile/nucleophile interactions were unlikely to provide a complete explanation of the sensitization processes. Eugenol and isoeugenol are not mutually cross-reactive, yet both cross-reacted with dihydroeugenol. Examination of the possible reaction mechanisms allows the speculation that eugenol reacts in part via a phenolic radical mechanism, whilst isoeugenol reacts largely via formation of an orthoquinone. Both reaction mechanisms are proposed for dihydroeugenol.


Recency, primacy, and memory: reappraising and standardising the serial position curve.

In this paper we consider the serial position curve in immediate verbal free recall. A large literature has argued that two components of the serial position curve, recency and primacy, reflect the functioning respectively of short-term and of long-term memory. However, there are a number of difficulties in interpreting the recency effect as a phenomenon uniquely associated with short-term memory. Moreover, the serial position curve has been used widely for clinical investigations in patients with memory deficits. This is despite the lack of norms for the measures derived from the curve. We present a set of standardised norms based on 321 Italian normal subjects. These norms are shown to be applicable both to an English speaking population, and to three groups of brain damaged-patients, namely Alzheimer's, amnesics, and frontals. The standardised norms offer a clinical and experimental tool which, coupled with a multiple single case approach, allows us to show dissociations and double dissociations among the performance patterns obtained from all three pathological groups. The paper concludes with a discussion of a possible interpretation of the recency effect as a emergent property of all types of memory system, including verbal short-term memory. Taking into account previous literature as well as our own data, the recency effect in immediate verbal free recall is here interpreted in terms of a two-component view of verbal short-term memory.


Foot and eye preferences in adults: relationship with handedness, sex and age.

Age, sex, and handedness effects in foot and eye preferences were studied by questionnaire in large samples of normal adult populations from five different countries (total sample, n = 5064). Foot and eye preference were significantly associated with handedness category (right or left) in all the 10 sex by country samples for foot, and in 9/10 samples for eye. The overall frequencies of crossed preferences were 5% between hand and foot and 19.5% between hand and eye. In right-handers, a gradual shift toward the "right" with increasing age was systematically observed, both for footedness and eyedness. The proportion of crossed hand-foot preference was higher in men than women (7.4% vs 2.5%), and higher in left-handers than right-handers (16.3% vs 4.1%). Sex differences in the proportion of crossed hand-eye preference were variable from one country to the other.


Darkness improves line bisection in unilateral spatial neglect.

This study was performed to determine the influence of background illumination on the performance of patients with left visual neglect. We examined six RBD patients with unilateral visual neglect, and as controls six RBD patients and six LBD patients without neglect. A luminous line consisting of LEDs was used in a line bisection task under two conditions, normal illumination and darkness. As expected, neglect patients made large rightward errors under normal illumination. Their performance improved by about 43% in darkness. Our results are discussed with reference to earlier studies of space exploration without visual guidance.


The performance of postencephalitic amnesic subjects on two behavioural tests of memory: concurrent discrimination learning and delayed matching-to-sample.

The performance of a group of three postencephalitic subjects with anterograde amnesia was examined on a series of concurrent visual discrimination problems and on a test of visual recognition, delayed matching-to-sample. These tests were chosen as they have been used to assess experimental models of anterograde amnesia in nonhuman primates. In comparison with a group of normal subjects the postencephalitic group were impaired on the more difficult concurrent discrimination problems. They also performed poorly on the matching-to-sample task when given lists of items to remember or given increased retention intervals. The pattern of performance of the postencephalitic group matched closely that of a group of Korsakoff subjects, indicating that these behavioural tests are equally sensitive to different types of anterograde amnesia.


Handedness in childhood autism shows a dissociation of skill and preference.

Hand preference and hand skill were assessed in 20 children with autism, 20 normal controls and 12 children with mental retardation. 90% of the normal controls and 92% of the children with mental retardation showed concordance for hand preference and hand skill (i.e. the preferred hand was also the more skillful), whereas only 50% of the children with autism showed concordance of preference and skill, the remaining 50% preferring to use the hand which was less skillful. Children with autism also showed a lesser degree of handedness and a lesser degree of consistency than the other groups, although this was unrelated to the discordance of skill and asymmetry. A developmental model of handedness is proposed in which the development of handedness as preference is ontogenetically prior to the development of handedness as skill asymmetry, such that in normal children the development of skill asymmetry occurs as a secondary consequence of the establishment of preference. The causal sequence is disrupted in autism, so that although preference is established, it does not subsequently result in concordant skill asymmetry.


Auditory and visual verbal short-term memory in aphasia.

Phonological short-term memory was investigated in 24 aphasic left brain-damaged patients and in 12 matched controls. Aphasic patients have a reduced auditory and visual immediate memory span and show the standard detrimental effect of phonological similarity on immediate retention only when the stimuli are auditorily presented, while in the control group the effect is present with both auditory and visual input. Most patients have phonological processing deficits, but two patients have an impaired immediate verbal memory in the absence of analysis disorders. These results, in line with most individual case studies of patients with selective deficits of verbal short-term memory, are interpreted with reference to a model distinguishing a phonological short-term store component of memory, to which auditory input has direct and automatic access, and a rehearsal component, that, after phonological recoding, conveys visually presented stimuli to the phonological store. This latter system, that appears to become fully operational later in development, is less resistive to brain damage.


Do "right-armed" lefthanders have different lateralization of motor control for the proximal and distal musculature?

Geschwind and Galaburda (1985) have suggested that specialization for the control of distal and proximal musculature might be located in different hemispheres in some individuals. Because inconsistent lefthanders (as defined by Ponton, 1987; Peters and Servos, 1989) tend to write with the left hand but throw with the right arm, and have a stronger right arm (Peters, 1990), it was thought that individuals in this group might provide evidence for the prediction made by Geschwind and Galaburda. This did not prove to be the case for tapping speed, where righthanders, inconsistent and consistent lefthanders all showed congruence. It appears that the question "are some left-handers right-armed?" can be answered only relative to specific activities.


Simple reaction time to lateralized visual stimuli is not related to the hemispheric side of lesion.

The effect of a single brain lesion on Reaction Times (RTs) to unpatterned visual stimuli was studied in 20 right brain-damaged (RBD) and 19 left brain-damaged (LBD) patients with single small vascular lesions confined to one hemisphere and free of visual field defects and of significant neuropsychological abnormalities (e.g. aphasia or hemineglect). The stimulus was presented in the field either ipsilateral or contralateral to the brain lesion. The stimulus location was either blocked in each hemifield or randomly alternating between fields. RTs in RBD patients were not statistically different from RTs in LBD patients. Intrahemispheric site of the lesion also was irrelevant for the lengthening in RTs. Responses to blocked presentations were faster than to random presentations. Responses to the hemifield contralateral to the brain lesion were slower than to ipsilateral hemifield, and the difference was unrelated to the absolute values of RTs. It is concluded, in contrast to other reports, but in agreement with the more recent literature, that there is no hemispheric dominance for RTs.


The septo-hippocampal pathways and their relevance to human memory: a case report.

The interaction between the septal region and the hippocampal formation appears indispensable for the maintenance of normal memory and learning mechanisms in humans. The disruption of some combination of septo-hippocampal pathways, especially the disruption of the "dorsal route", deteriorates explicit memory functions. The case of a 25-year-old male patient is presented who developed anterograde and to a certain extent retrograde amnesia following rupture and repair of an arteriovenous malformation in the atrium of the left ventricle. A left-sided lesion of the dorsal route involving the posterior cingulate bundle, the longitudinal striae (as part of the supracommissural hippocampus) and the fornix appeared responsible for his mnemonic deficits. The implications of these findings for the understanding of other clinical cases, particularly those with lesions of the septal region, the anterior and posterior singular gyrus/cingulate bundle and the fornix are discussed.


Brain correlates of hand dominance: the association between peripheral and cerebral asymmetries revisited.

Measures reflecting central processing of somatosensory stimulation were recorded in left- and in right-handed subjects in order to evaluate differences between the two handedness groups in the vertical, rather than lateral, axis of processing. Somatosensory evoked potentials were recorded in left- and right-handers following electrical stimulation of the median nerve at the wrist. The relative vertical balance of processing was probed by comparing the amplitudes of the underlying activity in early evoked potentials, presumably originating subcortically, with later, cortically originating potentials. Central conduction time (CCT) of the sensory volleys was also recorded. The data revealed higher amplitude ratios (ARs) between subcortical and cortical potentials, as well as shorter CCTs, in left-handers. These results demonstrate that transmission differences between the handedness groups may occur early in central nervous system (CNS) conductance. The results are further discussed in light of evidence suggesting that stronger reliance on a subcortical mode of processing may underlie phenomenon of left-handedness.


Subjective mood state and perception of emotion in chimeric faces.

Levy, Heller, Banich, and Burton (1983) have shown that hemispheric activational, or arousal, style, as measured by direction and consistency of choice of the "happer face" on a free-viewing Chimeric Faces Test, is highly reliable and varies across individuals who otherwise presumably have similar cortical organization (e.g., right-handed college students). The current experiment asks whether such individual differences in hemispheric arousal style are moderated by long-term, in the sense of enduring, individual differences in mood, as measured by the Profile of Mood States (POMS) questionnaire. Like Levy et al.'s subjects, most of our subjects (126 right-handed college students) made most of their choices on the Chimeric Faces Test based on the emotional cue (the smile) positioned in the half of the face to the viewer's left, or left visual hemifield (LVH), whereas a small minority were equally consistent in making their choice based on the emotional cue positioned in the half of the face to the viewer's right, or right visual hemifield (RVH). Performance on the Chimeric Faces Test, however, proved to be unrelated to scores on the POMS questionnaire. This suggests that hemispheric arousal style, as indexed by the Chimeric Faces Test, is robust enough, for a population of normal right-handers, to transcend any differences in mood as measured by the POMS questionnaire.


The effects of parental immunoreactivity on pregnancy, birth, and cognitive development: maternal immune attack on the fetus?

The effects of parental immunoreactivity were tested in two ways on questionnaire data collected from 468 children and their families. (1) It was found that the presence of learning difficulties in boys was associated with pregnancy and birth complications, as well as with maternal immunoreactivity. Paternal immunoreactivity did not appear to be related to any of the variables in question. (2) The antecedent brother effect, that children, particularly males, with older brothers have higher rates of the same set of variables, was not found. Maternal immunoreactivity emerges as a risk factor for pregnancy, birth, and cognitive development, but not exclusively by the proposed mechanism of maternal immune attack on the fetus.


Associations between hand and foot preference in 3- to 5-year-olds.

Associations between foot and hand preference behavior were examined in 3-, 4-, and 5-year-olds. Analysis of the general trichotomous (right, left, mixed) distribution of preferences indicated no sex or age group differences, while noting that 39% were mixed-footed compared to 17% not favoring one hand over the other. Frequency of paired (congruent and cross-lateral) preferences revealed that two patterns, Right-hand/Right-foot (52%) and Right-hand/Mixed-foot (23%) accounted for the vast majority (75%) of subjects. Of the total number of right-handers, most (67%) preferred the right foot, while only 19% of the left-handers were congruent. Thus, supporting findings reported on older populations that right-handers are more consistently right-footed, than left-handers are left-footed. Behavior of the mixed- and right-handed sample was similar, suggesting an overall predominance of these lateral characteristics in young children.


Multiple phantom limbs in a child.

This case report describes multiple phantom feet in a child after amputation of a leg. The subject is a 16-year-old girl who was born with a right leg 10 cm shorter than the left and who at the age of 6 was amputated below the right knee so that she could wear a prosthesis that would give her normal mobility. The girl reports that she subsequently experienced 2 phantom feet and 3 sets of phantom toes which have persisted to the present time. Each phantom has a distinct size, length and position in relation to the others and each is also the site of vivid sensations such as heat, tickle, and fatigue as well as voluntary and involuntary movement. She also describes sensations that resemble sensations experienced before the amputation: one of her phantom feet feels flat and locked into a forward position which corresponds with the actual shape and position of her congenitally deformed amputated foot. The implications of multiple phantoms are discussed with reference to recent concepts of phantom limbs.


Consistency in recalling features of former head injuries: retrospective questionnaire vs. interview retest.

The probability and features of memory concerning former head injuries with loss of consciousness was assessed in two formats: a group-test questionnaire and a retest using personal individual interview. Results are given concerning the greater likelihood of reporting short 'permanent' retrograde amnesias in the interview.


The dynamic performance model of skeletal muscle.

Applications of electrical stimulation to the nerve or muscles associated with a defunct limb joint due to stroke or spinal cord injury are a viable means of restoring a certain level of functional movement to the patient. In this article, the currently acceptable physiology of motor control is outlined and used as a criterion for electrophysiological and biomechanical performance evaluation of contemporary electrical stimulation strategies used by various systems attempting to duplicate such motor control in an effort to restore meaningful limb function. Strategies associated with surface, nerve, intramuscular, and reflex stimulation are critically reviewed with special reference to voluntary sensory motor control of a limb joint rather than an isolated muscle.


Biofluid dynamics at arterial bifurcations.

Hemodynamics has long been suspected of being involved in arterial diseases, e.g., atherosclerosis. Seemingly good correlation between the atherosclerosis localization and the flow disturbance around bends and bifurcations in large arteries has prompted many studies of blood flow around those regions. This article reviews and critiques biofluid studies at various arterial bifurcations. Both experimental and theoretical models vary greatly in the major assumptions and parameters. The issues discussed include: possible errors from two-dimensional models, the validity of steady flow studies, the existence and influence of the secondary flow, effects of non-Newtonian blood rheology, influences from arterial wall distensibility, effects of the Reynolds number, effects of the area ratio, effects of the Womersley number, effects of corner curvatures, effects of bifurcation angle, errors in the measurement and calculation of wall shear rate, and the possible existence of turbulence.


Nutritional outcome and pneumonia in critical care patients randomized to gastric versus jejunal tube feedings. The Critical Care Research Team.

To compare nutritional status, gastric colonization, and rates of nosocomial pneumonia in ICU patients randomized to gastric tube feeding vs. patients fed by an endoscopically placed jejunal tube. Randomized, prospective study. Medical and surgical ICUs at Boston City Hospital; surgical ICU at University Hospital. Of the 38 study patients, 19 were randomized to gastric tube feeding and 19 were randomized to an endoscopically placed jejunal tube. The two groups were similar in age, sex, race, underlying disease, and type of surgery. The two patient groups were similar in number of days fed, duration of ICU stay, duration of mechanical ventilation, days of antibiotic therapy, and days with fever. Compared with the gastric group, the jejunal group had more patients with circulatory shock on admission (79% vs. 68.4%), higher admission Acute Physiology Score (24.0 vs. 21.7), and fewer patients with pneumonia at randomization (26.3% vs. 31.6%). The jejunal group received a significantly higher percentage of their daily goal caloric intake (p = .05), and had greater increases in serum prealbumin concentrations (p < .05) than the patients with gastric tube feeding. Although the jejunal tube group had more days of diarrhea (3.3 +/- 6.6 vs. 1.8 +/- 2.9), this difference was not statistically significant. Nosocomial pneumonia was diagnosed clinically in two (10.5%) patients in the gastric tube group and in no patients in the jejunal tube group. Patients fed by jejunal tube received a significantly higher proportion of their daily goal caloric intake, had a significantly greater increase in serum prealbumin concentrations, and had a lower rate of pneumonia than patients fed by continuous gastric tube feeding.


Effect of acidified enteral feedings on gastric colonization in the critically ill patient.

To evaluate the effect of acidified enteral nutritional formulas (feedings) on gastric colonization and pH in critically ill patients. Randomized, double-blind trial of three groups: a) regular feedings into the stomach; b) regular feedings into the duodenum; and c) acidified feedings into the stomach. Nasogastric aspirates for gastric pH and microbiological determinations were obtained daily for a mean of 5 days after feeding began. ICU at a tertiary care hospital. Thirty-one patients indicated to receive enteral feedings before day 4 in the ICU were randomized. Seven patients had their feedings discontinued because of intolerance, accidental extubation, or tolerance of oral supplementation. One patient received the wrong feedings and was dropped from the study. A total of 23 patients finished the study. They were mostly trauma (n = 15) or neurosurgical (n = 6) patients. The average age was 40 yrs (range 15 to 71). An enteral formula with a pH of 6.5 was used as the control feeding. Hydrochloric acid was added to the control feeding to titrate the pH to 3.5 and this acidified enteral formula was given to the experimental group. All patients received continuous enteral feedings via an 8-Fr feeding tube. Seven of eight patients receiving the acidified feedings were sterile (no microbial growth) on receiving feedings compared with five of 15 of those patients receiving regular feedings (p = .027). For those patients initially colonized, four of four patients receiving acidified feedings immediately became sterile and remained so. Only two of ten patients receiving regular feedings remained sterile (p = .021). The mean gastric pH of the acidified group was 3.2 compared with the group receiving regular feedings into the stomach (pH = 4.7) and the group receiving regular feedings into the duodenum (pH = 3.8) (p < .01). There was no evidence of gastrointestinal bleeding in any patient. Acidified enteral feedings are effective in eliminating and preventing gastric colonization in critically ill patients. Further investigation is needed to assess its effect on nosocomial infection rates.


Hypothermia in the sepsis syndrome and clinical outcome. The Methylprednisolone Severe Sepsis Study Group.

To evaluate the consequences of clinical hypothermia associated with sepsis syndrome and septic shock. Analysis of data from a multi-institutional, randomized, placebo-controlled, prospective study with predetermined end-point analysis of development of shock, recovery from shock, hospital length of stay, and death. Multi-institutional medical and surgical ICUs. Patients meeting predetermined criteria for severe sepsis syndrome. Appropriate sepsis and shock care with 50% of patients receiving methylprednisolone and 50% receiving placebo. The occurrence rate of hypothermia (< 35.5 degrees C) is 9% in this population. When compared with febrile patients, hypothermic patients had a higher frequency of central nervous system dysfunction (88% vs. 60%), increased serum bilirubin concentration (35% vs. 15%), prolonged prothrombin times (50% vs. 23%), shock (94% vs. 61%), failure to recover from shock (66% vs. 26%), and death (62% vs. 26%). The hypothermic patients were also more likely to be classified as having a rapidly or ultimately fatal disease upon study admission. This prospective study confirms that hypothermia associated with sepsis syndrome has a significant relationship to outcome manifest by increased frequency of shock and death from shock. This finding is in sharp contrast to the protective effects of induced hypothermia in septic animals and perhaps man.


Effect of hypothermia on the coagulation cascade.

The development of a multifactorial coagulopathy after massive transfusion is a well-recognized clinical problem that is almost always accompanied by hypothermia. The purpose of this study was to investigate the isolated effect of alterations of temperature on the integrity of the coagulation cascade. Prothrombin times and partial thromboplastin times were each performed 15 times on samples of pooled normal plasma at the temperatures of 37 degrees C, 34 degrees C, 31 degrees C, and 28 degrees C, as well as 39 degrees C and 41 degrees C. Mean prothrombin time results increased from 11.8 +/- 0.3 (SD) secs at 37 degrees C to 12.9 +/- 0.5, 14.2 +/- 0.5, and 16.6 +/- 0.2 secs at 34 degrees C, 31 degrees C, and 28 degrees C, respectively (p < or = .001 for each). Partial thromboplastin time determinations increased from 36.0 +/- 0.7 (SD) secs at 37 degrees C to 39.4 +/- 1.0, 46.1 +/- 1.1, and 57.2 +/- 0.6 secs at 34 degrees C, 31 degrees C, and 28 degrees C, respectively (p < or = .001 for each). Both prothrombin time and partial thromboplastin time determinations were only minimally shortened at hyperthermic temperatures. The series of enzymatic reactions of the coagulation cascade are strongly inhibited by hypothermia, as demonstrated by the dramatic prolongation of prothrombin time and partial thromboplastin time tests at hypothermic deviations from normal temperature in a situation where factor levels were all known to be normal. Clinicians who deal with critically ill massively transfused hypothermic patients all recognize the inevitable appearance of a coagulopathy that has a multifactorial origin. Unless specifically considered, the contribution of hypothermia to the hemorrhagic diathesis may be overlooked since coagulation testing is performed at 37 degrees C, rather than at the patient's actual in vivo temperature.


Respiratory syncytial virus morbidity and mortality estimates in congenital heart disease patients: a recent experience.

To determine recent morbidity and mortality rates from respiratory syncytial virus infection in a pediatric congenital heart disease population. Retrospective cohort study design. The C. S. Mott Children's Hospital, University of Michigan Medical Center. A total of 740 pediatric patients hospitalized at the University of Michigan Medical Center for symptomatic respiratory syncytial virus infection, of whom, 79 patients had clinically important congenital heart disease. None. We retrospectively examined the charts of 740 patients hospitalized at our children's hospital from July 1, 1983 to June 30, 1990 with symptomatic respiratory syncytial virus infection to assess morbidity and mortality outcomes. Seventy-nine patients had congenital heart disease and 40 of these patients had pulmonary hypertension. For the entire cohort and a subset of patients with community-acquired infection, those patients with congenital heart disease had longer durations of hospitalization and greater need for, and days of, both intensive care and mechanical ventilation than patients without congenital heart disease. Mortality risk for respiratory syncytial virus community-acquired infection was not different for congenital heart disease vs. noncongenital heart disease patients (0.0% vs. 0.2%; p = 1.00). When examining only patients with congenital heart disease, those patients with pulmonary hypertension had increased hospital days and greater intensive care and mechanical ventilation durations compared with patients without this diagnosis. The overall mortality rate was low and was equally low for congenital heart disease groups with or without pulmonary hypertension (2.5 vs. 2.6). For community-acquired illness, no mortality was found in either congenital heart disease group. When the cohort of congenital heart disease patients was divided into pre- and postribavirin administration eras, no differences in mean hospital duration, ICU days, and mechanical ventilation days were noted. Of the 79 congenital heart disease patients, only two died during their hospitalization in which respiratory syncytial virus infection occurred. Both patients had nosocomial-acquired respiratory syncytial virus and both were from the postribavirin administration cohort. One of these two patients had received antiviral therapy. Neither death was secondary to respiratory syncytial virus respiratory failure (based on pathologic examination). We conclude that respiratory syncytial virus mortality risk in pediatric patients with congenital heart disease is less than the risk reported a decade ago. Respiratory syncytial virus infection in congenital heart disease patients with pulmonary hypertension is associated with increased morbidity but not increased mortality rates. The markedly decreased respiratory syncytial virus mortality risk in patients with congenital heart disease currently experienced is likely secondary to improvements in intensive care management and advances in the surgical correction in this population rather than antiviral therapy.


Circulating interleukin-1 beta and tumor necrosis factor-alpha concentrations after burn injury in humans.

To measure plasma interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha) concentrations after burn injury and to determine if these concentrations relate to clinical status. Prospective assessment. Hospital burn unit. Thirty-one patients with second- or third-degree burns, covering 10% to 95% of body surface area. Initial concentrations of IL-1 beta were increased (mean 188 +/- 31 pg/mL), and the concentrations for each patient correlated with body temperature at the time of the blood sample (rho = 0.51, p < .015) (rho is a nonparametric statistical measure; a nonparametric analysis is mandatory for data that is categorical [Acute Physiology and Chronic Health Evaluation, APACHE, scores] and data that are not normally distributed [IL-1 beta and tumor necrosis factor, TNF, data]). Mean TNF alpha concentrations were initially 264 +/- 132 pg/mL, and these concentrations were positively related to body temperature (rho = 0.41, p < .05) and inversely related to the total WBC count (rho = -0.45, p < .025). Through the course of hospitalization, plasma cytokine levels fluctuated, but transient increases (sometimes into the nanogram/mL range) did not consistently correspond to changes in clinical signs or severity of illness, as determined by APACHE II scores. The maximum plasma cytokine levels in any patient were not related to age, but maximum IL-1 beta concentrations were inversely related to burn size (rho = -0.46, p < .015). The final IL-1 beta concentrations measured in the patients who died (n = 7) were significantly less than measurements in surviving patients matched for burn size and age taken at approximately the same time after admission. These results indicate that early after burn injury there is a correspondence of IL-1 beta and TNF alpha with certain host responses, but these correlations disappear with the progression of illness. In general, IL-1 beta and TNF alpha appear to be poor indicators of prognosis during burn injury; however, the association of mortality with low circulating IL-1 beta values supports the concept of IL-1 beta as being an essential mediator of host defenses.


Myocardial metabolism and adaptation during extreme hemodilution in humans after coronary revascularization.

This study was designed to evaluate the oxygen transport adjustments and myocardial metabolic adaptation that occurs with different levels of hemodilution during normothermia after cardiopulmonary bypass. Prospective, nonrandomized study. Operating room in a university hospital. Eight patients with ejection fractions (> 40%) undergoing elective coronary artery bypass grafting. Before the institution of cardiopulmonary bypass, blood was withdrawn from patients to a target hematocrit of 15%. After coronary artery bypass grafting, a catheter was inserted directly into the coronary sinus. After the patients were rewarmed to 37 degrees C, they were weaned from cardiopulmonary bypass. Hemodynamic indices were measured, as well as measurements of myocardial oxygen consumption (VO2) and myocardial metabolism (lactate extraction and coronary sinus hypoxanthine). Measurements were made at three different hematocrit values: 15%, 20%, and 25%. Hematocrit was increased by autologous blood transfusion. The three levels of hemodilution (hematocrit: 17.4 +/- 3.4%; 23.0 +/- 3.7%; 27.8 +/- 4.8%) were significantly different from baseline (hematocrit 37 +/- 2.6%; p < .05). Oxygen delivery, which increased with autologous transfusion, exceeded 350 mL/min/m2 at each level of dilution. The myocardial VO2 increased significantly after autologous transfusion compared with the most dilute condition (7.0 +/- 3.7 mL/min at hematocrit 17.4% vs. 11.2 +/- 4.8 mL/min at hematocrit 23.0% and 12.4 +/- 4.0 mL/min at hematocrit 27.8%). This transfusion-induced increase was also true of myocardial oxygen extraction. Lactate extraction and hypoxanthine release were normal and unchanged at each level of hemodilution. Systemic oxygen extraction ratio increased with hemodilution and decreased with autologous transfusion. Hemodilution to a hematocrit of approximately 15% is tolerated in anesthetized humans after coronary artery bypass surgery. There was no evidence of myocardial ischemia, as demonstrated by absence of S-T depression on the electrocardiogram, lactate extraction, or hypoxanthine release. In selected patients, postoperative transfusion may be based on systemic physiologic end-points, such as oxygen extraction ratio, rather than set hematocrit values.


Infectious and mechanical complications of central venous catheters placed by percutaneous venipuncture and over guidewires.

To compare the frequency of infectious and mechanical complications of central venous and pulmonary artery catheters placed by initial venipuncture vs. over a guidewire at existing sites. Exchange of central venous catheters and pulmonary artery catheters over a guidewire as opposed to fresh venipuncture reduces mechanical complications without increasing risk of infection. Chart audit. Medical, surgical, and coronary ICU patients requiring invasive monitoring or central venous access. Patients requiring prolonged catheterization underwent periodic exchange of catheters over a guidewire. Rates of catheter-related infections and mechanical complications were determined for central venous catheters placed by initial venipuncture and those catheters placed by guidewire exchange. Over a 12-month period, 939 catheters were inserted in 454 patients. Of these 939 catheters, 534 were placed by guidewire exchange. Use of a guidewire was associated with a decreased frequency of pneumothorax and hemothorax compared with initial venipuncture (0/405 [0%] vs. 7/534 [1.3%], respectively; p < .05) but not with increased risk of infection (9/405 [2.2%] vs. 14/534 [2.6%], respectively; NS). Guidewire-facilitated replacement of multiple consecutive catheters at the same site did not increase the risk of catheter-related infection. Catheters placed via internal jugular veins were more likely to become infected than catheters placed via subclavian veins (17/477 [3.6%] vs. 3/430 [0.7%], respectively; p < .01). When prolonged central venous or pulmonary artery catheterization is necessary, periodic catheter replacement over a guidewire is associated with fewer mechanical complications than initial venipuncture. Periodic catheter replacement over a guidewire is also associated with no increase in risk of infection.


Increased antioxidant activity in bronchoalveolar lavage fluid after acute lung injury in anesthetized sheep.

To determine if bronchoalveolar lavage fluid is a more potent antioxidant after acute lung injury in a sheep model compared with the baseline condition. Nonrandomized, controlled study, with repeated measures. University research laboratory. Seven healthy adult sheep (25 to 50 kg) were studied with five experimental sheep and two control sheep. Sheep with lung-lymph fistulas were used to study the antioxidant activity of serum, lymph, and bronchoalveolar lavage fluid, both at baseline and after the iv infusion of endotoxin and subsequent induction of acute lung injury. Antioxidant activity was measured, and it reflects the ability of serum, lymph, and bronchoalveolar lavage fluid to inhibit lipid peroxidation. When compared at several volumes, bronchoalveolar lavage fluid after acute lung injury was a more potent inhibitor of lipid peroxidation than bronchoalveolar lavage fluid at baseline. In contrast, antioxidant activity in both serum (69.6 +/- 4.5% vs. 47.2 +/- 4.6%; p = .001) and lymph (45.0 +/- 2.3% vs. 31.9 +/- 1.2%; p = .001) decreased with acute lung injury. These findings suggest that the alveolar fluid after acute lung injury possesses enhanced antioxidant activity that is likely due to the influx of serum proteins. Thus, the high permeability pulmonary edema of acute lung injury, while detrimental to gas exchange, may be beneficial in preventing further oxidant-mediated lung injury.


Fibrinolytic activity in bronchoalveolar lavage of baboons with diffuse alveolar damage: trends in two forms of lung injury.

Alveolar fibrin deposition is prominent in diffuse alveolar damage, the morphologic hallmark of the adult respiratory distress syndrome. To determine if a persistent abnormality of fibrin clearance occurs in the alveolar compartment during evolving diffuse alveolar damage, we characterized abnormalities of fibrin turnover in serial bronchoalveolar lavage specimens from two baboon models: a) diffuse alveolar damage induced by 80% oxygen and bronchoscopic seeding of Pseudomonas aeruginosa; and b) a more fulminant form of diffuse alveolar damage induced by bronchoscopic seeding of Pseudomonas and the infusion of oleic acid. Lavage procoagulant activity, due mainly to tissue factor associated with Factor VII, was increased and exceeded regulation by extrinsic pathway inhibitor in both models. Fibrinolytic activity was transiently diminished in baboons with evolving diffuse alveolar damage induced by oleic acid/Pseudomonas, but was preserved after 80% oxygen/Pseudomonas. Concentrations of plasminogen activator inhibitor-2 did not increase in lavage specimens obtained during evolving diffuse alveolar damage. Concentrations of alpha 2 antiplasmin and plasminogen activator inhibitor-1 tended to be higher in the lavage of oleic acid/Pseudomonas baboons with low fibrinolytic activity. Immunohistochemical analyses showed that tissue factor was distributed along the alveolar surface of controls and baboons with diffuse alveolar damage. Alveolar fibrin deposition was increased, by morphometric analyses, in both models. These data indicate that while increased procoagulant activity is characteristic of evolving diffuse alveolar damage and favors alveolar fibrin deposition, fibrinolytic activity may be transiently diminished or remain intact during evolving diffuse alveolar damage in baboons.


Pluronic F 127 liquid sensitizes mice to low doses of Escherichia coli lipopolysaccharide.

In murine models of endotoxemia, large amounts of lipopolysaccharide have to be administered to induce mortality. If mice are pretreated with D-galactosamine, the amount of lipopolysaccharide required to induce mortality is significantly lowered. Pluronic F 127 liquid is a relatively non-toxic copolymer that exhibits reverse gelation properties. Thus, it is a liquid at cold temperature and a gel at body temperature. The present studies were performed to ascertain whether the reverse gelation properties of Pluronic F 127 liquid could be used in devising a model of septic shock where a sustained delivery of lipopolysaccharide occurred. In evaluating this model, dose-response studies were conducted with lipopolysaccharide when a) it was administered intraperitoneally in saline or in Pluronic F 127 liquid, and b) it was administered intravenously to mice that had been pretreated with saline or Pluronic F 127 liquid. Mortality was followed for up to 72 hrs. Various doses of Escherichia coli lipopolysaccharide dissolved in saline or in Pluronic F 127 liquid were administered intraperitoneally to mice. The lethal dose of lipopolysaccharide required to kill 50% of the mice (LD50) administered in Pluronic F 127 liquid was approximately ten- to 15-fold less than the values obtained for lipopolysaccharide administered in saline. This decrease in the LD50 of lipopolysaccharide was also observed if the mice were treated intraperitoneally with Pluronic F 127 liquid and challenged 6 hrs later with iv lipopolysaccharide. The concentrations of tumor necrosis factor and interleukin-6 in the plasma were significantly higher when a low dose of lipopolysaccharide was administered to mice that had been pretreated with Pluronic F 127 liquid. While there was no effect on the liver enzymes, Pluronic F 127 liquid caused an increase in the plasma triglycerides. The data reported in this paper indicate that the LD50 of lipopolysaccharide is significantly decreased if it is administered in Pluronic F 127 liquid or administered to mice that have been pretreated with the Pluronic F 127 liquid. Thus, Pluronic F 127 liquid appears to sensitize mice to low levels of lipopolysaccharide. Unlike the D-galactosamine model, lipopolysaccharide can be administered as late as 6 hrs after treatment with Pluronic F 127 liquid. While the mechanisms by which Pluronic F 127 liquid sensitizes mice is not known, plasma triglycerides were increased in mice treated with this agent, suggesting that tissues responsible for the synthesis and/or degradation of triglycerides play a role in this sensitization process.


Effect of extracorporeal membrane oxygenation on tobramycin pharmacokinetics in sheep.

Critically ill infants undergoing extracorporeal membrane oxygenation (ECMO) therapy often receive multiple pharmacologic agents. Although the disposition of many drugs has been assessed in patients undergoing cardiopulmonary bypass and in patients receiving mechanical ventilation, only limited data exist for selected medications in patients undergoing ECMO. To evaluate the potential influence of ECMO on aminoglycoside pharmacokinetics, we studied the disposition of tobramycin in ten sheep before and during ECMO therapy. Each sheep received a single iv dose of tobramycin during a control period before ECMO and on a study day during ECMO. Identically timed serial blood samples over 4 hrs were obtained after each tobramycin dose. Paired serum tobramycin concentrations were obtained pre- and postmembrane oxygenator during ECMO in six sheep. Alterations in specific pharmacokinetic variables for tobramycin were observed as a result of ECMO. Estimates of elimination half-life and volume of distribution for tobramycin were significantly increased during ECMO as compared with control (pre-ECMO) values (1.8 +/- 0.3 vs. 2.7 +/- 0.8 [SD] hrs [p < .01] and 0.3 +/- 0.1 vs. 0.5 +/- 0.2 L/kg [p < .005], respectively). Tobramycin body clearance was unaffected by the procedure (1.8 +/- 0.8 vs. 1.7 +/- 0.4 mL/min/kg). Paired serum tobramycin concentrations obtained pre- and postmembrane oxygenator demonstrated no drug removal. These data suggest that ECMO circuitry does not sequester tobramycin and that the prolonged elimination half-life observed during ECMO therapy is not due to a change in drug clearance but is due to an ECMO-induced increase in tobramycin volume of distribution. To achieve and maintain preselected target tobramycin serum concentrations during ECMO, the usual dosage interval should remain unchanged, but the dose should be increased to compensate for the alteration in the drug's volume of distribution. The clinical applicability of these findings needs to be confirmed in carefully controlled clinical studies involving infants receiving ECMO therapy.


Mean airway pressure: physiologic determinants and clinical importance--Part 1: Physiologic determinants and measurements.

To discuss the theoretical relationship of mean alveolar pressure to its most easily measured analog, the mean airway pressure, and to describe the key determinants, measurement considerations, and clinical implications of this index. Relevant articles from the medical and physiologic literature, as well as mathematical arguments developed in this article from first principles. Theoretical, experimental, and clinical information that elucidates the physiologic importance, measurement, or adverse consequences of mean airway pressure. Mathematical models were used in conjunction with data from the published literature to develop a unified description of the physiological and clinical relevance of mean airway pressure. Geometrical and mathematical analyses demonstrate that shared elements comprise mean airway pressure and mean alveolar pressure, two variables that are related by the formula: mean alveolar pressure = mean airway pressure + (VE/60) x (RE-RI), where VE, RE, and RI are minute ventilation and expiratory and inspiratory resistances, respectively. Clear guidelines can be developed for selecting the site of mean airway pressure determination, for specifying technical requirements for mean airway pressure measurement, and for delineating clinical options to adjust the level of mean airway pressure. Problems in viewing mean airway pressure as a reflection of mean alveolar pressure can be interpreted against the theoretical basis of their interrelationship. In certain settings, mean airway pressure closely relates to levels of ventilation, arterial oxygenation, cardiovascular function, and barotrauma. Because mean airway pressure is associated with both beneficial and adverse effects, a thorough understanding of its theoretical and practical basis is integral to formulating an effective pressure-targeted strategy of ventilatory support. Mean airway pressure closely reflects mean alveolar pressure, except when flow-resistive pressure losses differ greatly for the inspiratory and expiratory phases of the ventilatory cycle. Under conditions of passive inflation, mean airway pressure correlates with alveolar ventilation, arterial oxygenation, hemodynamic performance, and barotrauma. We encourage wider use of this index, appropriately measured and interpreted, as well as its incorporation into rational strategies for the ventilatory management of critical illness.


Care of the dying: an ethical and historical perspective.

To provide a historical perspective, from ancient Greece to the middle of the 20th century, on ethical issues and principles commonly associated with medical care for the dying in Western civilization. Writings of noted philosophers, historians, ethicists, and physicians, as well as published legal and ethical guidelines. INFORMATION EXTRACTION: The sources used highlight the origins of various ethical principles associated with care of the dying. They also identify the opinions of prominent individuals throughout the history of medical ethics. Devotion to medical beneficence, concern for the quality of life, and respect for the sanctity of life are all expressed in the earliest medical and philosophical writings of ancient Greece. With regard to care of the dying, these considerations led to a wide acceptance of avoiding or terminating treatment in hopeless cases. They also led to active debate regarding medicine's role in hastening the dying process. The rise of Christianity during the Middle Ages markedly suppressed such debate by strongly reinforcing the principle of sanctity of life. Later, the optimism of the enlightenment added the hope of prolonging life. Finally, modern advances in medical science have made that hope a reality of complex ethical dimensions. Ethical debates regarding appropriate care for the dying are as old as medicine itself. Although beneficent concerns have characterized the medical community in almost every period of history, tensions have repeatedly arisen as diverse religious and philosophical ideologies have produced varying standards to define such beneficence. In the Christian world, the sanctity of life was often extolled as the paramount standard. For the ancient Greeks and Romans, and again in many post-Renaissance philosophies, quality of life considerations assumed equal or greater importance. Modern life-prolonging technologies heighten the debate by allowing these two standards to dramatically conflict, particularly in the critical care setting.


Effects of dimethyl sulfoxide on cultured rat hepatocytes in sandwich configuration.

A recently developed sandwich culture system, in which hepatocytes are sandwiched between two layers of collagen, has been shown to be capable of maintaining long-term expression of hepatocellular function (J. C. Y. Dunn et al., Biotechnol. Prog. 7, 237-245, 1991). The development of an adequate technique for the cryopreservation of hepatocytes in such a stable culture configuration would ensure a ready supply of hepatocytes for use in bioreactors or bioartificial liver support devices. This report describes the effects of exposing hepatocytes in sandwich culture to different concentrations of the cryoprotectant dimethyl sulfoxide (Me2SO) at 22 degrees C on Day 7 of culture. Cell function, morphology, and cytoskeletal organization were followed for 14 days after exposure. Hepatocellular morphology and albumin secretion remained normal when cultures were exposed for up to 120 min to predicted final Me2SO concentrations up to 1.33 M. Exposure for less than 60 min to equilibrium concentrations of up to 3.33 M Me2SO did not adversely affect cell morphology or albumin secretion rate, but at the highest concentration (3.33 M), increase of the exposure time to 60 or 120 min resulted in dramatic, irreversible cell damage and loss of function. Actin filament organization was shown to be undisturbed when the cells were exposed to 1.33 M Me2SO for 60 min, but was irreversibly disrupted by exposure to 3.33 M for 120 min. Based on these results, a simple and safe procedure is suggested for the addition of Me2SO to hepatocytes in a sandwich culture configuration and its subsequent removal, which will be valuable for studies on hepatocyte cryopreservation.


Thawed human hepatocytes in primary culture.

In drug metabolism studies, isolated and cultured human hepatocytes provide a useful model for overcoming the difficulty of extrapolating from animal data. In vitro studies with human hepatocytes are scarce because of the lack of livers and suitable methods of storage. After developing a new method for cryopreservation of human hepatocytes, we evaluated the effects of deep freezing storage on their viability, morphology, and functional and toxicological capabilities in classical culture conditions. Freshly isolated human hepatocytes were cryopreserved in medium containing 10% Me2SO and 20% fetal calf serum, using a Nicool ST20 programmable freezer (-1.9 degrees C/min for 18 min and -30 degrees C/min for 4 min). Cells were stored in liquid nitrogen. Viability of thawed human hepatocytes was 50-65% as assessed by erythrosin exclusion test prior to purification on a Percoll density gradient. Morphological criteria showed that thawed human hepatocytes require an adaptation period to the medium after seeding. Functional assessments showed that human hepatocytes which survive freezing and thawing preserve their protein synthesis capabilities and are able to secrete a specific protein, anionic peptidic fraction, which is involved in the hepatic uptake of bile-destined cholesterol. We then studied Midazolam biotransformation to test metabolic functions, and erythromycin toxicity by Neutral Red test (cell viability) and 3-(4,5-dimethylthiazol-2-yl)-diphenyl tetrazolium bromide test (cell metabolism). All of these experiments indicated that thawed human hepatocytes should be used 38 h after seeding for optimum recovery of their functions: membrane integrity, protein synthesis, and stabilization of drug metabolism enzymes.


Freezing preservation of the mammalian cardiac explant. V. Cryoprotection by ethanol.

We studied the colligative cryoprotective effect of ethanol (EtOH) in preserving the isolated rat heart frozen at -3.4 degrees C or unfrozen at -1.4 degrees C. Addition of 4.7% (v/v) EtOH to a cardioplegic solution, CP-14, raised the osmolality from 280 to 1100 mOsm/kg H2O and lowered the melting point from -0.52 to -2.1 degrees C. Freezing of the cardiac explant at -3.4 degrees C for 6 h resulted in 34.3 +/- 1.9% of the tissue water as ice; recovery of cardiac output (CO) was 50%. Polyethylene glycol, which at 5% (w/v) has been shown to cryoprotect the hearts during freezing at -1.4 degrees C, did not improve the protective effect of 4.7% EtOH. CP-14 + 4.7% EtOH did not freeze at -1.4 degrees C. After 6 h storage, CO in hearts flushed with CP-14 + 4.7% EtOH oxygenated with 95% O2/5%CO2 returned to almost control level and was much higher than that in hearts flushed with 100% O2 saturated-CP-14 + 4.7% EtOH. Storage of 8 and 12 h reduced CO to 87 +/- 9 and 60 +/- 5% of control. By employing EtOH as a colligative cryoprotectant, we preserved the adult mammalian heart frozen at -3.4 degrees C or unfrozen at -1.4 degrees C, suggesting that this small molecular weight, penetrating substance may be a suitable cryoprotectant for long-term storage of the cardiac explant at high subzero temperatures.


Freezing preservation of the mammalian cardiac explant. VI. Effect of thawing rate on functional recovery.

This study investigated the effect of thawing rate on the preservation of frozen isolated rat hearts. The hearts were flushed with a hyperosmotic cardioplegic solution, CP-14/EtOH (1.15 Osm/kg), frozen at a rate of 0.18 degree C/hr for 6 h to -3.2 degrees C. Thereafter, the hearts were thawed at rates ranging from 0.08 to 1.1 degrees C/min for 1 to 14 min until the heart temperature reached -2.1 degrees C, the melting point (MP) of the flush solution; then they were held at -1 degree C for 11 to 24 min so that the total thaw time was 25 min. Post-thaw function was assessed by working reperfusion and expressed as percentage of unstored control function. Cardiac output (CO) and other hemodynamic performance showed biphasic responses to the thaw rate. At 0.08 degree C/min rate, CO recovered to 29.1 +/- 4.1 ml/min (40.8 +/- 5.8% of control). Thawing at 0.13 degree C/min enhanced the recovery of CO to 60.5 +/- 4.9%. Between 0.13 and 0.34 degree C/min, recovery was statistically insignificant. Faster thawing at 0.59 and 1.1 degrees C/min caused progressively less recovery. Overall, 0.13 degree C/min offered the highest recovery. In conclusion, function in slowly frozen heart is intimately affected by the thawing rate; there was an optimal intermediate thawing rate and both too slow and too fast thawing were detrimental.


In vitro fertilization and development of frozen-thawed bovine oocytes.

Bovine oocytes were vitrified (V-oocytes) or frozen slowly (S-oocytes) at the germinal vesicle (GV) stage or after maturation in vitro (IVM) and their survival assessed morphologically and also by in vitro fertilization (IVF) and culture. The morphological survival of S-oocytes was 30.7% after freezing at the GV stage and 53.3% after IVM. The corresponding survival rates of V-oocytes were significantly lower, viz. 14.6 and 14.0%, respectively. The fertilization rate of S-oocytes frozen after IVM (51.0%) was lower than that of unfrozen controls (75.8%), but higher than after other treatments. Development continued in 16.0% of the fertilized S-oocytes, compared to 39.4% of control IVF zygotes and 1.6% developed into morulae or blastocysts (4.5% in controls). Only 0.8% of frozen-thawed GV stage oocytes and 4.6% of post-IVM V-oocytes cleaved after IVF and none formed morulae or blastocysts. Transfer of four embryos (two morulae and two blastocysts) derived from post-IVM S-oocytes into a recipient heifer resulted in pregnancy and the birth of twin calves.


Viability of nuclei of two-cell mouse embryos stored at 4 degrees C and fused with blastomeres of fresh two-cell embryos.

This study compares the resistance of the nuclei and the cytoplasm of two-cell mouse embryos to short-term storage at low temperature above 0 degrees C. Two-cell embryos were stored at 4 degrees C for 24-96 h in PB1 containing 0.25, 0.5, 0.75, and 1.0 M sucrose. The development to blastocysts in culture was highest in the presence of 0.5 M sucrose. However, only 3% of the embryos developed into blastocysts after 96 h of storage. On the other hand, the viability of the nuclei of two-cell embryos stored at 4 degrees C was significantly prolonged when they were transplanted into a blastomere of enucleated fresh F1 (C57BL/6JXCBA) two-cell embryos. The proportions of chimeric embryos that developed to blastocysts were 88, 67, 76, 71, 64, 45, 32, and 20% following storage for 0, 48, 72, 96, 120, 144, 168, and 192 h, respectively. In addition, there was no difference in the coat color of the young derived from nuclei stored at 4 degrees C or fresh nuclei, although the proportions of chimeric embryos that developed into live young after transfer tended to decrease with increased storage time. Moreover, the viability of nuclei stored at 4 degrees C for 192 h was confirmed in the germ cell population of chimeric mice mated with albino mice. These results demonstrated that the nuclei in the two-cell mouse embryos were more resistant to storage at low temperature than the cytoplasm.


Cryoinjury in human granulocytes and cytoplasts.

Although most isolated cells can be successfully cryopreserved, human granulocytes have little functional recovery after cryopreservation, even under optimized conditions. Cytoplasts, which are vesicles created from human granulocytes by depletion of organelles including granules and the nucleus, can carry out some of the complex functions of the parent granulocyte such as phagocytosis of bacteria, even after cryopreservation. Human granulocytes and cytoplasts were used in this comparative study of low-temperature responses to assess the relative importance of the plasma membrane and the granules in cryoinjury to human granulocytes. Boyle-van't Hoff plots of cell volume as a function of the reciprocal of osmolality showed that granulocytes and cytoplasts have similar osmometric behavior and equivalent osmotically inactive fractions. The hydraulic conductivities were also similar, indicating that the osmotic properties of the plasma membrane and cytoplasm were retained during preparation of the cytoplasts. Assessment of membrane integrity using fluorescein diacetate after graded freezing stresses showed that the low-temperature responses of cytoplasts were similar to those of human lymphocytes and hamster fibroblasts, with recoveries much higher than those of human granulocytes, particularly after post-thaw incubation at 37 degrees C. The results indicate that the plasma membrane is not the primary site of injury to granulocytes during freezing and thawing, and suggest that activation of cytoplasmic elements, such as granules, may constitute the early events in cryoinjury to human granulocytes. These studies have significance in approaches to the cryopreservation of granulocytes and other types of cells, such as platelets, with increased sensitivity to the conditions encountered during freezing and thawing.


Cryoprotection of purified rat kidney transamidinase by polyethylene glycol.

Polyethylene glycol is a water-soluble polymer which is widely used in the pharmaceutical, cosmetic, and chemical industries. In this study, it is shown that polyethylene glycol is an effective cryoprotectant of rat kidney transamidinase purified from both the mitochondria and cytosol. Much of the activity is lost when the purified enzyme is frozen and thawed in sodium-potassium phosphate buffer in the absence of cryoprotectants. Polyethylene glycols with molecular weights of 4000 to 10,000 were effective cryoprotectants. However, polyethylene glycols with a molecular weight of 1000 or lower inhibited the purified enzyme. A concentration of only 0.01% polyethylene glycol 4000, 8000, or 10,000 was required for complete cryoprotection. In addition to polyethylene glycol, 0.5 mM ethylenediaminetetraacetic acid was required in the phosphate buffer for complete cryoprotection. The stabilization of purified transamidinase by polyethylene glycol will facilitate characterization experiments designed to compare the properties of the mitochondrial and cytosolic isozymes.


The role of freezing in trypsin activity oscillations.

The importance of the frozen phase in the formation of cryooscillations of trypsin activity has been shown in experiments conducted at -10 degrees C under frozen and supercooled conditions, respectively. A solution containing trypsin obtained by trypsinogen activation and 0.1 M MnCl2 was distributed in test tubes with or without previous freezing and kept at -10 degrees C and pH 8.4. At given time intervals the frozen and supercooled samples were tested simultaneously for tryptic activity. Although a temporal motion of trypsin activity was produced by the frozen samples, the activity of the supercooled samples began to oscillate only after spontaneous freezing of the solutions. This phenomenon suggests the importance of compartmentalization of the frozen heterogeneous system, which results in an increase in concentration vs a decrease in diffusion rate of the components.


Viscosity of water in hibernating and nonhibernating mammals estimated by proton NMR relaxation times.

Longitudinal (T1) and transverse (T2) nuclear magnetic resonance relaxation times were measured in vitro at 37, 30, 25, 15, and 5 degrees C on serum, brain, liver, kidney, and heart samples from a hibernator, the European hamster, active in summer (SA), active in winter, or in the hibernating state in winter; from a less efficient hibernator, the golden hamster; and from a homeotherm, the rat. T1 and T2 relaxation times varied between species and in the European hamster between the active and hibernating subjects. Despite the major relaxation time differences between the organs, NMR relaxation time measurements showed a general trend to an increase in the viscosity of water for the European hamster in the active state. Although these modifications were not directly related to the process of hibernation itself, the relaxation times observed in the hibernating animals were closer to those seen in the rat. This evidenced that changes of physical properties of water reflect a better adaptation to low temperatures of the hamster, as compared to the nonhibernator, given that the low water viscosity of SA hamster allows the decrease of the viscosity with temperature during the hibernating state. These in vitro studies permit the study the viscosity which is an important physicochemical parameter involved in NMR longitudinal relaxation time of water proton. More detailed studies of other physiological parameters must be undertaken by further in vivo measurements.


Protective action of aromatic compounds against cold-shock injuries in boar spermatozoa.

Butylated hydroxytoluene has been known to protect spermatozoa from cold shock injury. To determine whether such protective action is a common property of aromatic compounds, the effect of 14 hydrophobic and 2 hydrophilic aromatic compounds on the protection of boar spermatozoa from cold shock was investigated. The majority of the hydrophobic compounds tested provided protection; the hydrophilic compounds were ineffective. Of the aromatic compounds tested, naphthalene was most effective in reducing the effect of cold shock on motility and acrosomal integrity of boar spermatozoa.


No aging in India: the uses of gerontology.

This paper develops a critique of international gerontology through an ethnography and analysis of gerontological practice in India. The central theme of Indian gerontology - that of an imminent demographic and social explosion of an aging population who will tax the country's slender resources - misrepresents available data and fails to signify the experience of most Indian old people. Narrative and deconstructive techniques are deployed to examine the language of crisis and the complex sources of this misrepresentation. Three sources are explored: local disjunctions of class and gender in India, neocolonial biases in the structure of knowledge on aging central to international discourse, and subaltern strategies within India for subverting Western and elite Indian imperatives of what it means to be old. A variety of textual, ethnographic, and historical materials are examined: Indian and American literature pertaining to the 1982 World Assembly on Aging, a series of sociological texts each entitled "Aging in India," and four contemporary Indian institutions designed to meet the needs of old people: a social service agency, a geriatric clinic, a retirement community, and an old age home.


Pharmaceuticals as folk medicine: transformations in the social relations of health care in Uganda.

The deterioration of government health services in Uganda since 1971 has been accompanied by a process of privatization which has made pharmaceuticals readily available outside of biomedical institutions. On the basis of material from eastern Uganda, the article analyses this development in terms of the 'sector model' of health care systems, with special attention to the relations between the professional and folk sectors. Folk practitioners of pharmaceutical medicine include a broad range of specialists, from government trained paramedicals in private practice to vendors bringing medicine to local markets. Like other folk specialists, they respect the customer's opinion, provide treatment by proxy and adjust their services to the customer's ability to pay. Although there are negative aspects of this development, from the local point of view there are also positive ones, which deserve the consideration of health planners.


Si dios quiere: Hispanic families' experiences of caring for a seriously mentally ill family member.

Among Hispanics, the family is viewed as the primary care giver for seriously mentally ill family members. This paper reports on a study of minority families' conceptions of serious mental illness, of their interaction with mental health resources, and on the burdens experienced by families in caring for a seriously mentally ill family member. The focus of this paper is on Hispanic families in New Jersey, with some comparative data from other ethnic group families. Families' conceptions of serious mental illness are explored and analyzed to demonstrate the importance of concepts of nervios and fallo mental in shaping families' responses to their ill family member. Social support systems for families are also explored with particular attention to the role of religious institutions and religious healing as a major source of solace.


"Chronicity," "nervios" and community care: a case study of Puerto Rican psychiatric patients in New York City.

The role of ethnicity, community structure, and folk concepts of mental illness in facilitating the adaptation of long term psychiatric patients to community living has received little attention. This article examines the cultural concepts of mental illness and the community involvement of 30 Puerto Rican psychiatric patients participating in a New York City treatment program. It is shown that many of the attributes usually associated with chronic mental illness do not apply to this population. It is argued that the folk concept of nervios helps to foster the integration of these patients in a wide range of community networks. The impact of gentrification on these patients' community integration is also discussed.


Controlling domestic life and mental illness: spiritual and aftercare resources used by Dominican New Yorkers.

This research addresses the differential use of spiritual and mental health resources by 15 Dominican migrant women with major psychiatric disorders in Northern Manhattan. Methods included interviews and participant observation with patients, kin, and mental health staff. Structured instruments were used to examine patients' networks and functioning. Folk and popular healing traditions, adopted by some patients and kin through private observances or through a connection with a healer, yielded symbolic supports, companionship for patients, and ways of communicating and coping with distress. Episodes of health-seeking revealed multiple participants competing for control of the patients' lives and illness careers. Consultations with healers offered family members potential mastery over illness and domestic life, with no surrender of centrality, dignity or control in the quest for care.


Charisma, crowd psychology and altered states of consciousness.

This paper argues that an interpretive meaning-centered analysis is not adequate for understanding collective behavior that is outside the range of calculating rationality. Alternative approaches to collective irrational action are drawn from the work of Weber and Durkheim, as well as from the crowd psychologists Le Bon and Tarde. These approaches are then illustrated in a short analysis of the trajectories and recruitment techniques of two contemporary American religious annunications: est and Scientology, and the findings applied to the general social formation.


Grief and rage: collective emotions in the politics of peace and the politics of gender in Israel.

Collective emotions of rage and grief dominate Israeli political discourses regarding the Middle East conflict. The weekly peace vigils of the Women in Black who protest the state's occupation of the West Bank and Gaza and the opposition which the vigils encounter, publicly display politicized collective emotions. In these weekly confrontations, grief and rage articulate intense contestations regarding the politics of peace as well as the politics of gender in Israel. Rage and grief unravel two drastically different visions of transcending national vulnerabilities and two disparate constructions of gender identity.


Reflections on Tamazai, a Tuareg idiom of suffering.

In this essay, I explore ways in which the theatrical and the medical are inextricably mixed and affect each other, in the Nigerien Tuareg idiom of tamazai. Tamazai is locally-described as "an illness of the heart and soul, not curable by Koranic verses," but by exorcism of spirits. A case study and analysis of healing rituals demonstrate how this idiom communicates women's relationships and empowers dramatic framing.


Ataques de nervios: proposed diagnostic criteria for a culture specific syndrome.

The authors propose a set of diagnostic criteria and report two cases of ataque de nervios, a syndrome of brief duration seen primarily in Spanish-speaking people of the Caribbean. Following a psychosocial stressor, the afflicted person demonstrates impulsivity, dissociation and communication and perceptual disturbances. The symptoms often begin in the presence of the family, allow a temporary relinquishing of social roles, and result in the mobilization of the social network in support of the person. Further research is needed to improve our understanding of this culture specific syndrome and its relationship to psychiatric disorder.


Transcultural aspects of eating disorders: a critical literature review.

A review of studies addressing anorexia nervosa and bulimia nervosa among Native Americans, African-Americans, Hispanics, Asians, Africans, and Middle Easterners yielded only 35 studies, of which 22 were qualitative case reports, three were clinical quantitative studies, and ten were non-clinical quantitative studies. The case studies reported symptoms similar to those of Caucasian patients, and eating disorders were reported in all SES classes. The clinical studies, all reported from Asian countries, described a number of cases for eating disorders quite different from one another. The non-clinical quantitative studies reported a number of cases consistent with the ranges previously reported for controlled samples of non-clinical Caucasian populations. We found few or no quantitative studies on eating disorders from Hispanic, Middle Eastern, African, or Asian countries other than Japan.


The aftermath of youth suicide--providing postvention services for the school and community.

Suicide is one of the leading causes of death in adolescence. Due to the risk of contagion and maladaptive coping responses in the aftermath of suicide, clinicians have responded by developing postvention services. Based on a considerable amount of experience in this field, target groups of individuals have been identified to receive such assistance. These groups include school administrators, staff, students, families, and community members at large. In addition, it has become clear that the local media response to suicide is of critical importance, and that school administrators and local mental health officials should work effectively with reporters so that news stories do not contribute to suicide contagion.


Somatic cell hybrid mapping of human chromosome band 5q31: a region important to hematopoiesis.

As a means of characterizing the distal long arm of chromosome 5, in particular, the region spanning 5q23-->q31, we analyzed somatic cell hybrids prepared from cells with overlapping chromosomal rearrangements. In one hybrid, the derivative chromosome 5 from a patient with acute myeloid leukemia (AML) de novo, whose bone marrow cells had a balanced translocation, t(5;7)(q31;q22), involving chromosome band 5q31, was isolated in a somatic cell hybrid (B294). In addition, we prepared somatic cell hybrids from a lymphoblastoid cell line (CC) derived from a patient who has a constitutional interstitial deletion of chromosome 5 spanning 5q23.1-->q31.1. By a combination of Southern hybridization analysis and fluorescent in situ hybridization, we constructed a map dividing 5q23-->q31 into four regions. We can assign genes to these regions and relate them to anonymous RFLP markers that have been genetically mapped.


Isolation of new probes from Xq12-->q13: an example of the screening of reference libraries with Alu-PCR products from radiation hybrids.

In order to isolate new probes from the juxtacentromeric region of the long arm of the human X chromosome, we used Alu-mediated polymerase chain reaction (Alu-PCR) products as probes to directly screen a chromosome X-specific gridded cosmid library. These Alu-PCR products were synthesized from radiation hybrids containing the loci DXS159, PGK1, and PGK1P1. This approach allowed us to select 18 cosmids capable of hybridizing with at least two Alu-PCR products. Four cosmids hybridized to more than three Alu-PCR products. Three of these four cosmids were contiguous, and the fourth was independent. Two cosmids that hybridized with two Alu-PCR products were further characterized. Physical mapping indicated that all of these clones are located in the expected region on Xq, confirming the validity of our approach.


Localisation of the gene for human aromatic L-amino acid decarboxylase (DDC) to chromosome 7p13-->p11 by in situ hybridisation.

The human gene for aromatic L-amino acid decarboxylase (DDC) was previously assigned to chromosome 7 by analysis of a panel of somatic cell hybrids. We report here refinement of this localisation, by in situ hybridisation, to 7p13-->p11.


Regional localization of the selenocysteine tRNA gene (TRSP) on human chromosome 19.

The human selenocysteine tRNA gene (TRSP) has been localized on chromosome 19q13.2-->q13.3 by in situ hybridization and ordered with respect to other genes and anonymous DNA markers in this region by linkage analysis in the forty CEPH pedigrees. These loci span only 10 cM in males and about 30 cM in females. The order of the loci is cen ... D19S7-D19S9-D19S47-CYP2A-CYP2F1-APOC2++ +-(TRSP, CKM). CYP2B flanks the CYP2A and CYP2F1 loci, but it cannot be determined whether it is proximal or distal to the other two cytochrome P450 loci with respect to the centromere.


Localization of the human urate oxidase gene (UOX) to 1p22.

The human urate oxidase (E.C.1.7.3.3) gene, UOX, is assigned to chromosome 1 by Southern analysis of human x hamster cell hybrids. Using fluorescent in situ hybridization, we have mapped this gene to 1p22.


Chromosomal localization of the rat Harvey-ras-1 gene (HRAS) by in situ hybridization.

The rat Harvey-ras-1 protooncogene (HRAS) has previously been assigned to rat chromosome 1. In this study we further refine its localization to region 1q41-->q42 through the use of fluorescent in situ hybridization.


Chromosomal assignments of genes for rat glutathione S-transferase Ya (GSTA1) and Yc subunits (GSTA2).

Chromosomal assignments of genes for rat glutathione S-transferase Ya (GSTA1) and Yc subunits (GSTA2) were performed by Southern blot analyses of somatic cell hybrid DNAs.GSTA1 and GSTA2 were assigned to rat chromosomes 8 and 9, respectively.


A chromosome 1-specific DNA library from the domestic pig (Sus scrofa domestica).

Chromosomes were prepared from lymphocytes of a male domestic pig and flow-sorted on a dual-laser FACS. Twenty spots were observed, corresponding to the known pig karyotype of 18 pairs of autosomes plus the X and Y. DNA was isolated from 10,000 copies of the presumed chromosome 1 spot, restricted with Sau3A, ligated into the vector pGEM4z, and PCR amplified using universal primers; the products were then re-ligated into pUC18. After transformation into Escherichia coli, 210,000 independent colonies were obtained, 5% of which contained only vector DNA. The average insert size of the library was 405 bp. Southern blotting revealed that 36% of the clones contained single-copy DNA and that the remainder contained moderately or highly repetitive DNA. Screening with a (CA)n probe revealed that roughly 1% of the clones contained microsatellite sequences. A bulk insert of the library was biotinylated by PCR and used as a probe for chromosomal in situ suppression hybridization to pig chromosomes, which confirmed that the library is specific for chromosome 1. However, sequences from the centromeric and telomeric regions seem to be underrepresented in the library.


New gene assignments to rabbit chromosomes; implications for chromosome evolution.

The genes for SOD1 and SOD2 (superoxide dismutases 1 and 2), RB1 (retinoblastoma), TYMS (thymidylate synthase), and TK1 (thymidine kinase) were mapped by in situ hybridization using biotinylated probes to rabbit chromosomes 6, 12, 8, 9, and 19, respectively. This confirms their proposed homoeologies with human chromosomes 21, 6, 13, 18, and 17, respectively, and provides additional information on the modification of these chromosomes during evolution.


Tandem and centric fusions in the chromosomal evolution of the South American phyllotines of the genus Auliscomys (Rodentia, cricetidae).

The karyotypes of three of the four extant species of the genus Auliscomys (A. micropus, living in central [2n = 32, NF = 34] and southern [2n = 34, NF = 36, 37] Chile; A. sublimis [2n = 28, NF = 32] and A. boliviensis [2n = 22, NF = 32], which inhabit the Andean Altiplano) were analyzed. Comparisons of G-, C-, and AgNOR-banded karyotypes showed that extensive conservation of entire chromosomes and chromosomal regions had occurred during the evolution of this genus, with centromeretelomere tandem fusions and centric fusions probably being the most frequent chromosome changes. A chromosomal phylogeny, based on the chromosome homoeologies detected and parsimonious analysis of the nature and distribution of the inferred chromosomal changes, is proposed. This hypothetical phylogeny assumes that the ancestral telocentric karyotype would have undergone three consecutive tandem fusions, first originating the 2n = 32 (NF = 34) karyomorph exhibited by present-day specimens of A. micropus captured in central Chile and then the 2n = 28 (NF = 32) karyotype of A. sublimis. Subsequent centric fusions involving the tandem-fusion products would presumably have generated the 2n = 22 (NF = 32) A. boliviensis karyotype. Assuming some conditions related to early geographic distribution, this chromosomal phylogeny is in agreement with a paleogeographic model, which explains the present distribution of living Auliscomys species mainly on the basis of geologic and climatic events.(ABSTRACT TRUNCATED AT 250 WORDS)


Localisation of the beta crystallin Cryb gene to mouse Chromosome 2B-->C1 by in situ hybridisation.

The beta crystallin gene Cryb (betaA3/A1) has been assigned to mouse Chromosome 2 region B-->Cl by in situ hybridisation to metaphase chromosomes from mouse foetal liver and bone marrow preparations of Rb(2.17)4H mice using a murine cDNA (pMbeta23Crl) probe.