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Insomnia is a common sleep complaint even in young adults and has important daytime consequences. Several subjective and objective tools are recommended to assess the magnitude of the problem and to try to find a cause. Chronic insomnia is often caused by precipitating factors, such as acute stress, work conditions, illness, and travel, and perpetuating factors, such as poor sleep hygiene, anxiety, and medications. Insomnia may have implications in athletic performance resulting from physical and cognitive effects. Several pharmacologic and nonpharmacologic approaches are employed in the management of insomnia that have proven effective for short-term treatment. The pharmacologic approaches include the use of zolpidem and specific GABA agonists, benzodiazepines for specific indications, antidepressants, and melatonin. The nonpharmacologic approaches include stimulus control, sleep restriction, relaxation strategies, and cognitive behavioral therapy.

To determine whether insomnia impact the professional life of patients and have an economical weight, this review article focused on the socioeconomic impacts of sleep related problems in working populations. The goal is to summarise the work that has been accomplished in that field. Several occupational factors have an impact on insomnia: the work schedules (shift work and night work), the physical environment at work and the occupational stressors. Insomnia is also a common problem in daytime workers. The daytime functioning of insomniacs is a key point to understand the impact of insomnia on workers. Absenteeism is one major target in the evaluation of severe insomnia at the workplace. Most of the studies find a higher rate of work accidents in insomniacs. The economic impact is severe in term of direct and indirect costs. Insomnia is a common problem at the workplace. The negative impact is not only on individual but also at the societal levels. More epidemiological studies appear warranted to demonstrate a reciprocal link between work conditions and sleep disorders.

Purpose: Melatonin, which is produced by the pineal gland at night, is an endogenous sleep regulator. Both sleep disorders and impaired melatonin production are common among the elderly. We examined the excretion of the major melatonin metabolite 6-sulfatoxymelatonin in insomnia patients aged >or=55 years and its relation with the subsequent response to melatonin therapy., Methods: We studied 517 insomnia patients, along with 29 age-matched and 30 younger healthy volunteers. Nocturnal urinary 6-sulfatoxymelatonin excretion was assessed between 10 pm and 10 am. Three hundred and ninety-six of the insomnia patients were treated for 2 weeks with placebo and for 3 weeks with 2 mg per night of controlled-release melatonin, of which 372 provided complete datasets. Clinical response, assessed with the Leeds Sleep Evaluation Questionnaire, was defined as an improvement of 10 mm or more on the visual analog scales., Results: Mean (+/- SD) 6-sulfatoxymelatonin excretion was lower in the insomnia patients (9.0 +/- 8.3 microg per night) than in volunteers of the same age (18.1 +/- 12.7 microg per night, P <0.05) and in younger volunteers (24.2 +/- 11.9 microg per night, P <0.05). About 30% of patients (112/372) excreted

Mutations in clock genes are associated with abnormal circadian parameters, including sleep. An association has been reported previously between a polymorphism (3111C), situated in the 3'-untranslated region (3'-UTR) of the circadian gene Clock and evening preference. In the present study, this polymorphism was assessed in: (1) 105 control subjects with defined diurnal preference, (2) 26 blind subjects with free-running circadian rhythms and characterized with regard to circadian period (tau) and (3) 16 delayed sleep phase syndrome patients. The control group was chosen from a larger population (n = 484) by Horne-Ostberg questionnaire analysis, from which three subgroups were selected (evening, intermediate and morning preference). Data from sleep diaries completed by 90% of these subjects showed a strong correlation between preferred and estimated timings of sleep and wake. The mean timings of activities for the evening group were at least 2 h later than the morning group. Genetic analysis showed that, in contrast with the previously published finding, there was no association between 3111C and eveningness. Neither was there an association between 3111C and tau, nor a significant difference in 3111C frequency between the normal and delayed sleep phase syndrome groups. To assess the effect of this polymorphism on messenger RNA (mRNA) translatability, luciferase reporter gene constructs containing the two Clock polymorphic variants in their 3'-UTR were transfected into COS-1 cells and luciferase activity measured. No significant difference was observed between the two variants. These results do not support Clock 3111C as a marker for diurnal preference, tau, or delayed sleep phase syndrome in humans.

From 1985 through 1995, 348 infants aged 3 wk-3 mo were referred to the Stanford Sleep Clinic for "apparent life-threatening events" (ALTE). A small group of 48 infants with no history of sleep-disordered breathing (SDB) was also recruited and used as controls (they comprised group C). We conducted a systematic investigation of relatives (parents, siblings, and grandparents) of the infants, including a clinical evaluation, craniofacial investigation, and the completion of an extensive (189-question) validated sleep/wake questionnaire. All data were calculated before the subdivision of ALTE infants into two groups. The subdivision was based on a blind scoring of the infants' polygraphic recordings; 42.5% of the infants were negative for SDB (Group A), whereas 57.5% of the infants were positive for SDB (Group B). Groups A and C were not significantly different from each other. Forty-three percent of the relatives of Group B infants had been treated for SDB (with nasal CPAP, surgical or dental appliance treatments) compared with 7.1% of Group A relatives. Clinical investigation indicated a significantly higher presence of small upper airways in the families of infants with SDB. About twice as many relatives reported the presence of asthma in Group B compared with Group A. Naso-oro-maxillomandibular anatomic traits that may lead to small upper airways in parents may be risk factors for abnormal breathing during sleep in their infants.

This study was an epidemiological questionnaire survey of a representative sample of the French population that included 12 778 individuals and in which adapted DSM-IV criteria for the definition of insomnia were used. Our goals were not only to assess the prevalence of 'insomnia' using these criteria, but also to compare the results obtained with those of prior studies using different definitions of 'insomnia'. The aim of this study was also to identify where areas of agreement and disagreement existed, as we believe that it is important to emphasize these points because DSM-IV recommendations are supposedly reflected in clinical practice. Seventy-three per cent of the individuals surveyed complained of a nocturnal sleep problem, but only 29% reported at least one sleep problem three times per week for a month, and 19% (2428 subjects) had at least one sleep problem three times per week for a month and complained of daytime consequences (DSM-IV criteria). Only 9% had two or more nocturnal sleep problems with daytime consequences and were classified as 'severe insomniacs'. Our study indicates that if DSM-IV criteria are used, the diagnosis of 'insomnia' is lower than in other epidemiological studies. The DSM criteria have an advantage in that they emphasize the daytime consequences of nocturnal sleep disturbances, which seem to be responsible for the most important socio-economic costs of the problem.

Blind individuals are not only handicapped by their loss of vision, but are also affected because the loss of sight may have a secondary impact on functioning of their biological clock. The objective of the present study was to determine the impact of visual loss on sleep/wake disorders. A prospective 48-item questionnaire survey was distributed to blind individuals through the French Association Valentin Haüy, which serves blind persons. A control group matched by age, sex, geographical location and professional activity/non-activity was obtained from a panel of 20000 households representative of the French population, and this group also completed the questionnaire. From a potential blind population of 1500 subjects, 1073 questionnaires (71.5%) were completed and usable for analysis, and from a potential 1000 control subjects, 794 (79. 4%) of the questionnaires were returned and analysed. Criteria outlined in the Diagnostic and Statistical Manual of Mental Disorders, 4th revision, and the International Classification of Sleep/Wake Disorders (1990) were used to determine pathology. Individuals determined to be 'totally blind' and 'almost blind' (i.e. with less than 10% vision left in only one eye) presented a significantly higher occurrence of sleep/wake disorders than controls. Nocturnal sleep disruption, daytime somnolence, and (to a lesser degree) a 'free-running' condition are significantly more common in blind individuals. There is an increased use of sleeping pills, and a higher incidence of inappropriate involuntary daily naps. In conclusion, individuals with blindness report a significant curtailment of total sleep time and hence resulting daytime somnolence, which impacts on daytime activities. A 'free-running' condition is also a common sleep/wake impairment that may compound the handicap of blindness.

Several reports indicate that use of hypnotics is significantly higher in France relative to other European countries, but few reports exist concerning the cost of this high consumption of psychotropic medications. The purpose of the present study was to estimate the direct costs that may be attributed to insomnia in France. Data were derived from previously published surveys in this field. It includes the cost of sleep medications and of substances used to promote sleep, outpatient visits to physicians or to other health professionals and sleep recordings and treatment by sleep specialists. The final estimate of the total direct cost of insomnia in France in 1995 was FF 10,232,992,500 ($2,067,271,100). Public authorities have to understand that an increase in the direct costs of insomnia may be balanced by the reduction of the daytime consequences of insomnia and then by the reduction of the indirect costs of insomnia.

The relation between adult perception of emotion intensity in the cries of 1- and 6-month-old infants and the acoustic characteristics of the cries was examined. In the first study, adults who were inexperienced in child care rated 40 cries on 3 emotion intensity scales: anger, fear, and distress. The cries of 6-month-olds were rated as being significantly more intense. Different acoustic variables accounted for emotion intensity ratings for the 2 infant ages. Peak amplitude and noisiness of the cry predicted adult judgments of intensity ratings of 1-month-olds' cries; a measure of amplitude ratio (in 2 frequency bands) was the best predictor of intensity ratings of 6-month-olds' cries. In the second study, parents of infants rated the same cries on the same scales. They also rated the older infants' cries as being more intense. The 2 adult groups did not differ on their ratings, and a regression equation derived from one adult group predicted the other adult group's rating of the same infant age better than it predicted its own ratings for the other infant age. Infant age, and its associated acoustic features, seems to be a more important determinant of adults' perception of emotion intensity than are such adult characteristics as gender or infant-care experience.

Objective: To determine whether upper airway resistance syndrome (UARS) can be recognized and distinguished from obstructive sleep apnea syndrome (OSAS) in prepubertal children based on clinical evaluations, and, in a subgroup of the population, to compare the efficacy of esophageal pressure (Pes) monitoring to that of transcutaneous carbon dioxide pressure (tcPCO2) and expired carbon dioxide (CO2) measurements in identifying UARS in children., Study Design: A retrospective study was performed on children, 12 years and younger, seen at our clinic since 1985. Children with diagnoses of sleep-disordered breathing were drawn from our database and sorted by age and initial symptoms. Clinical findings, based on interviews and questionnaires, an orocraniofacial scale, and nocturnal polygraphic recordings were tabulated and compared. If the results of the first polygraphic recording were inconclusive, a second night's recording was performed with the addition of Pes monitoring. In addition, simultaneous measurements of tcPCO2 and endtidal CO2 with sampling through a catheter were performed on this second night in 76 children. These 76 recordings were used as our gold standard, because they were the most comprehensive. For this group, 1848 apneic events and 7040 abnormal respiratory events were identified based on airflow, thoracoabdominal effort, and Pes recordings. We then analyzed the simultaneously measured tcPCO2 and expired CO2 levels to ascertain their ability to identify these same events., Results: The first night of polygraphic recording was inconclusive enough to warrant a second recording in 316 of 411 children. Children were identified as having either UARS (n = 259), OSAS (n = 83), or other sleep disorders (n = 69). Children with small triangular chins, retroposition of the mandible, steep mandibular plane, high hard palate, long oval-shaped face, or long soft palate were highly likely to have sleep-disordered breathing of some type. If large tonsils were associated with these features, OSAS was much more frequently noted than UARS. In the 76 gold standard children, Pes, tcPCO2, and expired CO2 measurements were in agreement for 1512 of the 1848 apneas and hypopneas that were analyzed. Of the 7040 upper airway resistance events, only 2314 events were consonant in all three measures. tcPCO2 identified only 33% of the increased respiratory events identified by Pes; expired CO2 identified only 53% of the same events., Conclusions: UARS is a subtle form of sleep-disordered breathing that leads to significant clinical symptoms and day and nighttime disturbances. When clinical symptoms suggest abnormal breathing during sleep but obstructive sleep apneas are not found, physicians may, mistakenly, assume an absence of breathing-related sleep problems. Symptoms and orocraniofacial information were not useful in distinguishing UARS from OSAS but were useful in distinguishing sleep-disordered breathing (UARS and OSAS) from other sleep disorders. The analysis of esophageal pressure patterns during sleep was the most revealing of the three techniques used for recognizing abnormal breathing patterns during sleep.

Insomnia can cause impaired productivity and absenteeism from work, increased risk of accidents, and impaired quality of family and social life. Thus, it can compromise quality of life in affected individuals and result in costs to society as a whole. The nonbenzodiazepine hypnotic zopiclone is effective and well tolerated in the treatment of insomnia. Importantly, it also has minimal effects on next-day performance and psychological function. 458 patients treated with zopiclone for 14 days showed significantly greater improvement compared with placebo recipients in sleep evaluation questions and scores for activity, social and professional quality-of-life aspects. After 8 weeks, the improvement in scores for sleep, activity and social questions remained significantly higher in patients who had received zopiclone compared with placebo recipients. No significant differences were observed between 167 patients who had been taking zopiclone for at least 12 months and a control group of 381 persons with no sleep problems in virtually all of the 5 aspects of the quality-of-life questionnaire. Some important aspects such as relationships and professional life were not modified by zopiclone. When insomnia is treated appropriately, compared with no treatment, patients' feelings about their quality of life are improved and, furthermore, do not appear to differ significantly from perceptions of quality of life in those without sleep-related problems.

Twelve full-term infants (7 girls and 5 boys) with normal neurological, behavioral and somatic development were followed at regular intervals during the first 5 months of life to appreciate the development of circadian rectal temperature rhythmicity. Activity and temperature (oral at birth, rectal thereafter) were monitored for a minimum of 60 hours on seven separate occasions: at birth, 3 weeks, 6 weeks, 8 weeks, 10 weeks, 16 weeks and 20 weeks of age. Activity was measured using an actigraph worn on the infant's wrist, and rectal temperature was measured using a rectal probe attached to a portable microprocessor (Vitalog TM). Data points were collected every 2 minutes. No fewer than ten infants were monitored at each session, and no infant missed more than one session. Missing recordings were due to equipment malfunctions, probe expulsions and minor health problems. Six infants out of 12 were successfully monitored at each of the first four sessions, from birth to 8 weeks of age inclusively, and two subjects were successfully monitored at all seven sessions. Periodic regression analysis was performed by least squares curve fit with secondary analysis of variance. Analysis of covariance was performed on repeated measures. There was no evidence of rectal temperature circadian rhythmicity at 3 weeks. Two infants demonstrated a circadian rhythmicity at 6 weeks, and all infants had a circadian rhythmicity at 10 weeks post-natal age. At the time of the first observance of circadian rhythmicity of rectal temperature, the mean delta in temperature from peak to trough was 0.6 +/- 0.3 degrees C. This delta was greater at the 16th week, with a mean value of 1.2 +/- 0.3 degrees C. The trough was seen during the first part of the long nocturnal inactivity period. Circadian rhythmicity of rectal temperature was always observed in the studied subjects before the establishment of a consolidated, long daytime wake period.

Objective: To review our experience with home nasal continuous positive airway pressure (CPAP) in infants with small upper airways and abnormal breathing during sleep., Study Design: Seventy-four infants with sleep-disordered breathing and narrow upper airways, as identified by nocturnal polygraphic recording and endoscopic evaluation, were treated at home with nasal CPAP. Infants with craniofacial anomalies and trisomy 21, and infants who had been referred to us as having had "apparent life-threatening events," made up the majority of the population. Because of the rapid growth of infants, regular follow-up visits were scheduled to adjust CPAP and mask size., Results: Seventy-two infants were successfully treated at home with nasal CPAP; there were two failures. Follow-up lasted from 5 months to 12 years. Compliance was not a problem, but home nasal CPAP was prescribed only for infants who lived close to our center and whose families and pediatricians were willing to support compliance., Comments: Home nasal CPAP requires careful, in-laboratory titration and regular follow-up to adjust both pressure and mask size. With the support of families and pediatricians, home nasal CPAP can be an effective treatment for infants with upper airway respiratory problems during sleep. In many cases, it can provide an interim solution, enabling physicians to plan surgery at an appropriate time and giving infants time to grow before having to undergo surgical stress.

Forty-one subjects between 12 and 63 years of age with a complaint of nocturnal wandering were reviewed retrospectively, and a prospective investigation of their compliance to treatment was performed. Twenty-nine of 41 subjects committed violence against themselves or others ("violent group"). Clinical investigation of their problem involved polysomnography, wake and sleep EEGs and ambulatory EEG recording in the home environment. The nocturnal wandering may have started from NREM sleep or REM sleep, and violence was observed in both of these sleep states. Arousal from sleep may have been triggered by sleep-disordered breathing or may have been related to temporal lobe abnormalities, and, in some cases, no abnormal polygraphic features were noted. Violence was always preceded by many instances of nocturnal wandering that had received little clinical attention. Temporal lobe abnormalities, a rare cause of nocturnal wandering, were present only in the "violent" group. This group also had a higher percentage of men than the "nonviolent" group. In both groups, the frequency of nocturnal wandering increased with an increase in daytime stressors. Pharmacological and psychiatric treatment approaches were beneficial in both groups.

Synopsis The analysis of the lipids extracted from human hair by silica-gel-column liquid chromatography permitted an isolation of the fraction enriched in free ceramides. These were identified by GC/MS and are related to ceramide classes 2 and 5 in which the long-chain base was predominantly sphinganine. This differs from that observed in the free ceramides found within the stratum corenum.

This report, prepared for the National Commission on Sleep Disorders Research, explores the economic implications of sleepiness in relation to accidents. In Part One, I describe the frequency of accidents in the United States and explain a method for estimating the economic cost of these of accidents. Accidents are the fourth leading cause of mortality in the United States, and motor-vehicle accidents represent 51% of total deaths caused by accidents. The method used for calculating the cost of accidents is called "the human capital approach". It is based on the principle that "one person produces a sum of output during his/her life-time, which can be approximated by his/her earnings". It is necessary to understand that this estimate of human value is not intended to reduce human beings to a sum of earnings during his/her lifetime. It does, however, serve as a useful indicator in making decisions regarding public health policy for the country. The results of the total cost of accidents and the relative costs for work-related, home-based and public accidents in 1988 are discussed. In Part Two, I explore the role sleepiness plays in contributing to the total number of accidents. The difficulty of researching this subject is compounded by the fact that reports of rates of accidents related to sleepiness differ significantly from author to author. This is true both for drivers with sleep disorders and those without. We have calculated two different rates for estimating the number of motor-vehicle accidents caused by sleepiness.(ABSTRACT TRUNCATED AT 250 WORDS)

The response of signal recipients depends on information found in the signal itself and on other information sources known collectively as context. Context is the set of events, conditions, and changeable recipient characteristics that modify the effect of a signal on recipients' behavior. Sources of contextual information include (a) the characteristics of the recipient and (b) sources external to the recipient (the signaler and the setting). Contextual information is most commonly used when the signal itself does not provide enough information for the recipient to behave adaptively. The signal's referent may be ambiguous or deceptive, or recipients may need additional information to fine-tune their responses. When animal signals were thought to be information poor, contextual information was seen as being critically informative. Animal signals are now known to be much more informative, but even information-rich systems, such as human language, depend heavily on contextual sources of information.

We report the results of 2 studies on food-elicited vocalizations in golden lion tamarins (Leontopithecus rosalia). First, we investigated the preferences of 10 golden lion tamarins for 6 foods. Tamarins prefer mealworms and raisins significantly more than apple, egg, carrot, or marmoset diet. Food preference rank was significantly and positively correlated with the rank of latency to choose a particular food. Second, we investigated the relation between food preference and 15 vocal parameters measured from the calls emitted by 5 tamarins to a subset of the foods. Only 1 parameter was significantly correlated with food preference across animals. Within-subjects multivariate analysis of variance showed that the vocalizations to foods are significantly different. Our results support an hypothesis that food-elicited vocalizations vary in ways that correspond to the caller's preference but not in a manner that labels food type.

Examination of perceptions of human facial attributes revealed that individual attributes are similarly perceived by males and females. However, patterns of attribute interrelationships differ as a function of gender of the face. Undergraduate students (N = 280) rated pictures of 40 male or female Caucasians on 12 physical attributes (e.g., nose size, face width) and overall attractiveness. The four sets of attribute ratings (defined by rater gender and picture gender) were submitted to principal components analyses, and five-factor solutions were found for each condition (accounting for about 76% of the variance). Comparisons of the four component solutions using confirmatory factor procedures revealed that male and female raters share one factor structure when rating photographs of female faces and another factor structure when rating photographs of male faces. Multiple regression analyses revealed that the patterns of attribute interrelationships were not "perceptual units" in the perception of attractiveness, and that different "rules" are used to assess the attractiveness of male and female stimuli faces. The importance of these results for models of facial attractiveness and interfacial similarity judgements are discussed.

New fatty polyenic (linoleic, linolenic, arachidonic, linoelaidic) mono esters of erythromycin A have been synthesized by using various reagents such as acyl chloride, carboxylic acid anhydride, and mixed carbonic anhydride. These different ways of activating the fatty acid allowed a regioselectivity of esterification at position 2' of the desosamine ring or position 4" of the cladinose ring of erythromycin A. The in vitro antibacterial properties of these new esters against members of the resident flora of the human skin were determined and compared with those of erythromycin A. The number and the stereochemistry of the double bonds seem to play a crucial role in the expression of the in vitro antibacterial activity.

Changes in the composition of human stratum corneum lipids (SCL) were studied at various times after an induced inflammatory reaction. Three kinds of injury were inflicted: 3 MED of ultraviolet radiation, 3 MED of solar radiation or 30 strippings of the horny layer with plastic tape. The SCL were evaluated qualitatively and quantitatively at short intervals. Marked changes in the SCL were detected between the 9th and the 11th day. With all 3 insults, the SCL increased quantitatively and showed a more polar pattern, i.e. a decrease in neutral fractions and an increase in the polar ones. These changes were synchronous with the marked shedding which occurs between the 9th and the 11th day. These findings have implications for the role of lipids in stratum corneum cohesiveness.

Four types of calls (long calls, chirps, chucks, and trills) from Golden Lion Tamarins (Leontopithecus rosalia) were analyzed for sex differences in structure. Six or more acoustic variables were analyzed for each call type. One or more variables from each call category differed significantly between the sexes. In addition, discriminant function analyses were conducted on male vs. female data for each call type. Long calls, chirps, and chucks from males and females were quite discriminable, but trills were not. That these differences exist is surprising given that callitrichid primates are otherwise quite monomorphic in structure and behavior. Possible functions served by sex differences in call structure include group censusing or assessing the sex of transient individuals., (Copyright © 1990 Wiley‐Liss, Inc., A Wiley Company.)

A modified photometric technique has shown considerable differences between the refatting kinetics of the scalp and forehead. The refatting on the forehead occurs rapidly, probably due to the large follicular reservoir. The follicular reservoir of the scalp, which bears a large terminal hair, is much smaller and so the refatting time is longer. Thus, sebum excretion and sebum production rates probably correlate better on the scalp than on the forehead, and we suggest that the scalp may be a better site than the forehead for investigating sebaceous gland physiology.

An in vitro study of the oxidation of squalene, and a description of factors acting on this transformation are presented. Thin layer chromatography was used to quantify the products generated by different oxidation processes. The results clearly show that squalene is a highly effective oxygen-scavenging agent. Its oxidation may first induce comedogenesis and, as a secondary event, cause a large reduction in oxygen tension in the human pilo-sebaceous duct. Porphyrins were confirmed to be highly efficient catalytic factors in the squalene oxidation process. The relationships between comedogenesis, bacterial colonization, and the role of sebum in the pathogenesis of acne are discussed in the light of these findings.

Ethoxyformylation of sarcoplasmic reticulum vesicles is performed to study a possible role of histidine residues in the calcium translocation process. The influence of the chemical modification is evaluated on the Ca2+-dependent ATPase activity, and on the Ca2+ uptake parameters: VCa (initial rate of calcium uptake) and CCa (amount of cation accumulated at the steady state). The substitution of the amino acids is monitored by three different techniques: (a) by amino acid analysis of the ethoxyformylated material further submitted to modification by diazonium-1-H-tetrazole, or by sulfhydryl titration using 5-5'-dithiobis (2-nitrobenzoic acid); (b) by 14C labeling followed by the removing of labels after NH2OH or imidazole treatment at pH 7; (c) by spectrophotometric measurements at 230 nm. The ethoxyformylation reaction is not specific for histidine at pH 6.1 and 10 degrees. About 1 lysyl group/mol of ATPase is first modified. Then 1 (with a pseudo-first order rate constant of 240 (+/- 20) 10(-3) min-1) or 2 histidines are modified. No substitution of tyrosine or sulfhydryl groups can be detected under our experimental conditions. A decrease of the Ca2+-dependent ATPase activity correlated with the inhibition of both VCa and Cca corresponds to the chemical substitution of the histidine. No direct correlation between the decrease of the activities and the modification of the lysine can be found. After removing the ethoxyformyl group from the histidine, only the Ca2+-dependent ATPase activity is restored to its initial value. No protection is found when the reaction is performed in the presence of ATP or p-nitrophenylphosphate. These results can be explained if one assumes that the ethoxyformylation of the histidine residue(s) induces a conformational change modifying the affinity of the membrane for nucleotides.

The culture medium of bovine aortic endothelial cells contains proteins which inhibit the aggregation of platelets induced by aortic microfibrils but not by type III collagen. From this medium, fibronectin, thrombospondin and a glycoprotein with MW of 128 Kd (GP 128), similar to a glycoprotein described in a microfibrillar extract from bovine aorta were separated by affinity and ion exchange chromatography. GP 128 was further purified by molecular sieve chromatography on SW 3000 column. GP 128 inhibited the aggregation of platelets by microfibrils. This suggests a role of GP 128 in the platelet/subendothelium interaction.

Measurement of Sebum Excretion Rate (SER) in patients is a time-consuming test. It is now possible to measure SER 1 h after having degreased the forehead with a 70% ethanol solution. The skin surface lipids (SSL) collected during this time have similar composition to those collected for up to 7 h. A qualitative and quantitative study of sebaceous excretion, on 18 volunteers, from 1 to 7 h after having cleansed the forehead, showed that the refatting kinetics, in all subjects, obeyed the same mathematical law, independent of the subjects' individual SER.

The metabolic changes in carbohydrate (fasting blood sugar and blood sugar levels two hours after taking 70 g of glucose orally as well as insulin and glycosylated A1c haemoglobin) and also lipid metabolism as total and fractional HDL, triglycerides and alphaprotein B, were compared in 43 patients of a mean age of 48.6 years who had hysterectomy with castration. These patients were divided into two random groups: the first group (23 women) received hormone replacement treatment in a dose of 1.5 mg of oestradiol percutaneously, the second group of 20 women received 2 mg of oestradiol specially prepared for oral administration. Biological control was carried out immediately after the treatment and 3 and 6 months later. It consisted of levels of carbohydrates and of lipids and of oestriol, oestradiol and FSH. Both treatments, whether percutaneous or oral, were similar in their beneficial action on the changes brought about by castration. When 17 Beta oestradiol was administered percutaneously a better control over the carbohydrate and lipid (triglyceride) metabolism was obtained. This confirms that when oestradiol is administered orally the same respect has to be given to the contrary indications to its administration and to controlling the metabolic effects as when any other form of oestrogen therapy is administered orally.

1. Serial bronchoalveolar lavages (BAL) were performed on a subhuman primate (Macacus cynomolgus) in order to give an experimental model for silicosis. 2. We have identified and quantified some plasma proteins of monkey BAL fluid. 3. The results were compared to those previously obtained in humans. 4. Two proteins previously detected in human BAL fluid (alpha 1 acid glycoprotein, alpha 1 antichymotrypsin) were not detected in monkey control BAL fluid. 5. Two kinds of transferrins were detected in monkey BAL fluids while only one is described in human. 6. The present results will now permit sequential follow up studies during the course of experimental silicosis.

Images of the hamster flank organ were obtained in vivo by high resolution ultrasound (B-scan). The planimetric measurements of the ultrasonic image that determined the size of the flank organ, with a reproducibility of about 10%, highly correlated with the measurements of histological sections. This new method provides a simple and non-invasive method for determining the size of the hamster flank organ after various treatments which does not involve the killing of the animal under investigation.

Previous works demonstrated that microfibrils stimulate blood platelets to aggregate. The present study compares the activation of platelets by human placental and bovine aortic microfibrils and by type III collagen. We studied the morphological changes occurring in in platelets during their activation and aggregation, as well as the kinetics of the release reaction and thromboxane B2 formation. As for collagen, the microfibrils-induced platelet aggregation followed a lag phase, during which progressive emission of pseudopodes and centralization of organelles occurred. Aggregation was associated with secretion of beta-thromboglobulin and adenylic adenylic nucleotides, and with formation of thromboxane B2; it was established that the kinetics of secretion and the aggregation curve were parallel. Microfibrils-induced aggregation was also inhibited by ethylenediamine tetraacetic acid, creatine phosphate-creatine phosphokinase, and aspirin, showing that it was calcium-dependent and required a secretion of ADP and formation of endoperoxide and thromboxane. The response to microfibrils was much more rapid than to collagen; placental microfibrils reacted faster than aortic microfibrils. The requirement of plasma in the microfibrils platelets interaction was confirmed: 10 microliters is the minimal amount of plasma necessary for an aggregation of platelets in 400 microliters of buffer. This fact supports the idea of the existence of two different pathways in the interaction between platelet and the subendothelium, depending on the vascular structure (microfibrils or collagen) involved, even though the sequence of events leading to the formation of an aggregate is similar.

This paper describes an original in vivo device to investigate and quantify cutaneous resorption of sebum. Such a phenomenon was explored using a photometric determination of residual skin surface lipids at different times following initial deposits of known amounts of artificial sebum on demarcated areas. The technique was carried out on seven healthy subjects. The chosen area was the anterior aspect of the forearm, owing to the very low sebum production of this site, less than the sensitivity of the measuring instrument. The kinetics of absorption of applied sebum turned out to be hyperbolic-like and well correlated with experimental results (r = 0.992), allowing a mathematical determination of the initial velocity of penetration of sebum into the skin, reaching 20 micrograms/cm2.min for a standard program including a mean initial deposit of 116 micrograms/cm2. This kinetics actually does not fit with a true percutaneous absorption of lipids but is compatible with that of absorption into the stratum corneum. It conveys the faster absorption of the latter for sebum, a well-known but not so far quantified property of stratum corneum. The model here described is not at once transposable to skin areas with high sebum production since, quite obviously in such zones, the stratum corneum is permanently saturated with skin surface lipids. Therefore, the conclusions of this work cannot be correlated with the regreasing parameters studied so far on the forehead, but they provide interesting data about the evolution of sebum following its output onto the skin surface and therefore a better understanding of sebaceous physiology.

Skin surface lipids and lipids from open and closed comedones in acne patients were analysed by thin layer chromatography. The results showed that these lipids were enriched in polar lipids, as compared with the skin surface lipids obtained from controls without acne. In both open and closed comedones, these polar lipids appeared to be derived mainly from the oxidation of squalene, which is in agreement with our previous in vitro results. We suggest that squalene oxidation is the link between comedogenesis and bacterial colonization, and based on this, we propose a hypothesis of the pathogenesis of acne.

The purpose of this study is to present a rapid, simple, and accurate method for quantitation of SSL in man. The technique which is derived from the works by Schaefer and Kuhn-Bussius, employs a series of clearn ground glass plates, and an apparatus, the Lipometre, for the determination of the variation of light transmission across the plates as a function of the fat deposited on them. Results on 32 adults, males and females, show that the first four iterative samplings, at constant pressure, on the same forehead area follow an identical physical law independently of whether the skin is fatty or dry. This law affords a precise definition of the Casual-Level, its quantification and its correlation with skin patterns. It is consequently possible, either as an investigative or a routine technique, to predict the total amount of SSL with good accuracy within 2 min. The SSL, for non-pathological skins, fall within the range 150 microgram/cm2 to 900 microgram/cm2 which is in good agreement with values quoted in the literature.