[Screening of occupational exposure to asbestos and silica by job-exposure matrix among patients with lung cancer and mesothelioma]. / Dépistage des expositions professionnelles à l'amiante et à la silice par matrice emplois-expositions auprès de patients atteints de cancer bronchopulmonaire et de mésothéliome.

INTRODUCTION: In the context of underreporting of occupational diseases, the aim was to study the validity of silica and asbestos job-exposure matrices in screening occupational exposure in the field of thoracic oncology. METHODS: Fifty patients hospitalized with primitive lung cancer or mesothelioma in a university hospital center in the Hauts-de-Seine department of France were included between November 2016 and September 2017. For each patient 1/the job history was collected, from which data was entered single-blindly into the job-exposure matrices by a resident in occupational medicine, 2/a questionnaire (Q-SPLF) was completed similarly, and 3/the patients also had a consultation with a chief resident in occupational medicine, considered the gold standard. The main outcome was the diagnostic performance of the matrices. The Q-SPLF diagnostic performance was also studied. RESULTS: The asbestos and silica matrices had sensitivities of 100%, specificities of respectively 76.1% and 87.8%, the positive likelihood ratios were at 4.19 [2.5-6] and 8.17 [3.8-10], and the negative likelihood ratios were at 0. The Q-SPLF diagnostic performance was comparable to that of the matrices. CONCLUSIONS: The matrices and the questionnaire have a great diagnostic performance which seems interesting for a use as a screening tool for occupational exposures. These results have yet to be confirmed by large-scale studies.

Circulating leptin levels are associated with increased craving to smoke in abstinent smokers.

The adipocyte hormone leptin regulates satiety and energy expenditure. Recent evidence suggests that leptin is associated with increased craving for alcohol and with shorter length of abstinence during alcohol treatment. This study examined leptin's associations with craving for cigarettes and smoking relapse among smokers interested in cessation. Participants (32 smokers; 14 women) attended a laboratory session 24h following their designated quit day where circulating leptin levels and craving for smoking were assessed. Other measures of withdrawal symptoms, affect, physical symptoms, as well as neuroendocrine and cardiovascular measures were collected before and after performing two stress tasks (public speaking and cognitive tasks). High circulating leptin levels were associated with increased craving, withdrawal symptoms, negative affect, physical symptoms, and reduced positive affect. Circulating leptin levels were not related to cardiovascular and neuroendocrine measures, responses to acute stressors, or to smoking relapse. These results indicate that circulating leptin is a promising biological marker of craving for smoking and warrant further investigation of the links between appetite regulation and nicotine dependence.

Blunted opiate modulation of hypothalamic-pituitary-adrenocortical activity in men and women who smoke.

OBJECTIVE: To examine the extent to which nicotine dependence alters endogenous opioid regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis functions. Endogenous opiates play an important role in regulating mood, pain, and drug reward. They also regulate the HPA functions. Previous work has demonstrated an abnormal HPA response to psychological stress among dependent smokers. METHODS: Smokers and nonsmokers (total n = 48 participants) completed two sessions during which a placebo or 50 mg of naltrexone was administered, using a double-blind design. Blood and saliva samples, cardiovascular and mood measures were obtained during a resting absorption period, after exposure to two noxious stimuli, and during an extended recovery period. Thermal pain threshold and tolerance were assessed in both sessions. Participants also rated pain during a 90-second cold pressor test. RESULTS: Opioid blockade increased adrenocorticotropin, plasma cortisol, and salivary cortisol levels; these increases were enhanced by exposure to the noxious stimuli. These responses were blunted in smokers relative to nonsmokers. Smokers tended to report less pain than nonsmokers, and women reported more pain during both pain procedures, although sex differences in pain were significant only among nonsmokers. CONCLUSIONS: We conclude that nicotine dependence is associated with attenuated opioid modulation of the HPA. This dysregulation may play a role in the previously observed blunted responses to stress among dependent smokers.

Nociceptive flexion reflex and pain rating responses during endogenous opiate blockade with naltrexone in healthy young adults.

The effect of opioid blockade on nociceptive flexion reflex (NFR) activity and subjective pain ratings was examined in 151 healthy young men and women. Using a within-subjects design, NFR threshold was assessed on 2 days after administration of either placebo or a 50mg dose of naltrexone. Electrocutaneous pain threshold and tolerance levels were measured after NFR threshold assessment on each day. Results indicated that administration of naltrexone was consistently associated with hypoalgesic responding. Specifically, participants exhibited lower levels of NFR activity and reported lower pain ratings for electrocutaneous stimulation delivered at pain threshold and tolerance levels following administration of naltrexone as compared to placebo. These findings indicate that opiate blockade using the current standard dose may elicit hypoalgesia. A potential moderating effect of dose of opiate-blockade medication and level of endogenous opioid activation should be carefully examined in future research.

Assessment of opiate modulation of pain and nociceptive responding in young adults with a parental history of hypertension.

This double blind, placebo-controlled study examined the effects of an opiate antagonist, naltrexone, on nociceptive flexion reflex (NFR) thresholds and subjective pain in individuals with and without a parental history of hypertension. Using a repeated measures design, NFR threshold was repeatedly assessed on two testing days after administration of either placebo or naltrexone. Immediately after NFR threshold was determined, participants rated the level of pain experienced during the preceding NFR assessment, and at the end of each session participants' electrocutaneous pain threshold was assessed. Two primary findings were obtained. First, individuals with a parental history of hypertension exhibited attenuated pain sensitivity. Second, endogenous opioid blockade was associated with increased pain ratings in women but with increased pain threshold in men. In sum, the present study did not support a direct involvement of the endogenous opioid system in the attenuated pain sensitivity observed in individuals at increased risk for hypertension.

Nociception and baroreceptor stimulation in hypertension-prone men and women.

We examined the effects of baroreceptor stimulation on nociceptive responding in men and women with a positive or negative parental history of hypertension. The effects of three baroreceptor conditions (stimulation, inhibition, and control) on subjective pain and nociceptive responding were evaluated during electrocutaneous sural nerve stimulation. Pain ratings were lower in men with positive parental history relative to men with negative parental history, but this difference was not found in women. Both stimulatory and inhibitory baroreceptor conditions were associated with reduced pain reports compared to the control condition. There were no significant differences in nociceptive responding as a function of parental history of hypertension. Although this study confirms a link between hypoalgesia and risk for hypertension in men, it does not support the hypothesis that this attenuated pain perception is due to enhanced baroreceptor activity.

Sex differences in pain and hypothalamic-pituitary-adrenocortical responses to opioid blockade.

OBJECTIVE: Sex differences in pain sensitivity and stress reactivity have been well documented. Little is known about the role of the endogenous opioid system in these differences. This study was conducted to compare adrenocortical, pain sensitivity, and blood pressure responses to opioid blockade using naltrexone in men and women. METHODS: Twenty-six participants completed 2 sessions during which placebo or 50 mg of naltrexone was administered, using a double-blind, counterbalanced design. Thermal pain threshold and heat tolerance were assessed. Participants also rated pain during a 90-second cold pressor test (CPT) and completed the McGill Pain Questionnaire (MPQ) after each pain challenge. Blood and saliva samples and cardiovascular and mood measures were obtained throughout the sessions. RESULTS: Plasma cortisol, adrenocorticotropin, beta endorphin, prolactin, and salivary cortisol levels increased similarly in men and women after naltrexone administration compared with placebo. Women reported more pain during both pain procedures and had lower thermal pain tolerance. In response to naltrexone, women exhibited reduced blood pressure responses and reduced MPQ pain ratings after CPT. No effects of naltrexone on these measures were found in men. CONCLUSIONS: Although men and women exhibited similar hormonal responses to opioid receptor blockade, women reported less pain and showed smaller blood pressure responses during CPT. Results suggest differential effects of the endogenous opioid system on pain perception and blood pressure in men and women.

Prospective examination of effects of smoking abstinence on cortisol and withdrawal symptoms as predictors of early smoking relapse.

This study addressed the hypothesis that exaggerated mood and cortisol changes during the first 24h of smoking abstinence are associated with early relapse. Salivary cortisol levels and mood reports were measured during 24-h ad libitum smoking and the first 24-h abstinence period of a quit attempt. Seventy-two habitual smokers (34 women and 38 men) who were interested in smoking cessation participated. Cotinine concentrations in saliva and expired carbon monoxide were measured before and after abstinence and 1 week after the quit date to verify smoking status. Abstinence produced significant withdrawal symptoms in all participants and reduced cotinine and carbon monoxide levels. While participants showed the expected diurnal changes in cortisol levels, those who relapsed within the first week post quitting exhibited a greater drop in morning cortisol concentrations during abstinence relative to their ad libitum smoking levels. Participants who relapsed reported greater withdrawal symptoms, craving for cigarettes, and distress, and they also reported greater reduction in positive affect during the first 24-h period of abstinence than those who maintained abstinence. These results support the hypothesis that early relapse is associated with exaggerated mood and adrenocortical perturbations observed during the first day of abstinence.

A 9,000-year record of Chagas' disease.

Tissue specimens from 283 principally spontaneously (naturally) desiccated human mummies from coastal and low valley sites in northern Chile and southern Peru were tested with a DNA probe directed at a kinetoplast DNA segment of Trypanosoma cruzi. The time interval spanned by the eleven major cultural groups represented in the sample ranged from approximately 9,000 years B.P. (7050 B.C.) to approximately the time of the Spanish conquest, approximately 450 B.P. ( approximately 1500 A.D.). Forty-one percent of the tissue extracts, amplified by the PCR reacted positively (i.e., hybridized) with the probe. Prevalence patterns demonstrated no statistically significant differences among the individual cultural groups, nor among subgroups compared on the basis of age, sex, or weight of specimen tested. These results suggest that the sylvatic (animal-infected) cycle of Chagas' disease was probably well established at the time that the earliest humans (members of the Chinchorro culture) first peopled this segment of the Andean coast and inadvertently joined the many other mammal species acting as hosts for this parasite.

Enhanced adrenocortical responses to stress in hypertension-prone men and women.

Hypertension risk may be associated with increased adrenocortical activity, but the extent to which this enhanced activation differs between men and women at rest and in response to psychological stress is not known. This study examined gender differences in adrenocortical responses to an extended public-speaking stressor in persons at high (resting systolic blood pressure > median; n = 21) or low risk (negative parental history and < or = median systolic blood pressure; n = 26). Salivary cortisol levels were assessed at rest and in response to public speaking in a repeated measure design on two test sessions held on separate days. Heart rate, systolic blood pressure, and diastolic blood pressure were obtained at 3-min intervals before, during, and after the task. High-risk participants showed greater cortisol, blood pressures, and heart rate responses to the public-speaking stressor than the low-risk group (ps < .01). Men showed greater cortisol concentrations than women (p < .05), independent of hypertension risk status. Cardiovascular measures during the acute stressor predicted subsequent cortisol production, but only in the high-risk group. Results suggest that hypertension risk is associated with enhanced physiological reactivity across sympathetic and adrenocortical systems, supporting the possibility that this exaggerated reactivity may represent a marker of risk in hypertension-prone men and women.

Attenuated adrenocortical and blood pressure responses to psychological stress in ad libitum and abstinent smokers.

Chronic smoking may alter physiological systems involved in the stress response. This study was designed to examine the effects of ad libitum smoking and abstinence on adrenocortical and cardiovascular responses to acute psychological stress in dependent cigarette smokers. We evaluated differences among abstinent smokers, smokers who continued to smoke at their normal rate, and nonsmokers in salivary cortisol concentrations, systolic and diastolic blood pressure (BP), heart rate (HR), and mood reports. Measurements were obtained during rest and in response to acute psychological stress (public speaking) in one session (stress session) and during continuous rest in a control session. Thirty-eight smokers (21 women) and 32 nonsmokers (18 women) participated. Smokers were assigned to either abstain from smoking the night prior to and the day of each session, or to continue smoking at their normal rate before each session. All groups showed significant stress-induced changes in BP and HR. Smokers, regardless of their assigned condition, showed attenuated systolic BP responses to the public-speaking stressor when compared to nonsmokers. While resting cortisol levels were greater among smokers than nonsmokers, no cortisol response to the acute stressor was demonstrated in either ad libitum or abstinent smokers. These results indicate that chronic smoking diminishes adrenocortical and cardiovascular responses to stress, and that short-term abstinence does not correct these alterations.

Psychophysiological effects of nicotine abstinence and behavioral challenges in habitual smokers.

We tested the hypothesis that psychophysiological responses to behavioral challenges are enhanced by short-term abstinence from smoking. Blood pressure (BP), salivary cortisol levels, and withdrawal symptoms were measured after a period of smoking abstinence (18 h) or ad libitum smoking, during rest, and in response to acute behavioral challenges. Thirty habitual smokers (15 women and 15 men) participated in two laboratory sessions conducted on two separate days (after abstinence or ad libitum smoking). Cotinine concentrations in saliva and expired carbon monoxide were measured in both conditions. Abstinence produced significant withdrawal symptoms in all participants, with women reporting greater desire to smoke than men. Participants showed greater systolic BP responses to the behavioral challenges in the abstinence condition than the control condition. They also showed worse cognitive performance on the challenges in the abstinence than in the ad libitum condition. Men had greater salivary cortisol levels than women, and both men and women showed the expected decline in cortisol levels across time, but showed no difference between the abstinence and ad libitum smoking conditions in the laboratory or during ambulatory measurements. These results indicate that abstinence alters mood, performance, and BP responses to acute challenges but not adrenocortical responses. It is possible that these changes mediate stress-related vulnerability to smoking relapse.

Adrenocortical and hemodynamic predictors of pain perception in men and women.

Research has demonstrated that women report more pain than men, and clinical observations suggest that attenuated adrenocortical activity is associated with high pain sensitivity. The extent to which cortisol concentrations and hemodynamics contribute to gender differences in pain sensitivity has not been investigated. Thirty-four women and 31 men performed the hand cold pressor test (CPT). Participants rated their pain every 15 s during a 90-s CPT and a 90-s post-CPT recovery period and reported pain using the McGill Pain Questionnaire (MPQ). Salivary cortisol samples and cardiovascular measures were collected prior to, during, and after the CPT. Women reported greater pain than men during and after the CPT and on the MPQ (Ps<0.01). CPT disrupted the expected diurnal decline in cortisol, as shown by a significant increase in cortisol concentration post-CPT (P<0.01) in men and women. Regression analyses revealed that pre-CPT cortisol concentrations predicted lower pain reports during and after CPT in men only (P<0.01). Systolic blood pressure (BP) and stroke volume correlated negatively with pain reports only in women (Ps<0.05). Controlling for potential confounding variables did not alter these relationships. The negative association between pre-CPT cortisol and pain perception in men and the association between BP and pain in women demonstrate different physiological predictors of pain perception in men and women.

Blood pressure but not parental history for hypertension predicts pain perception in women.

Previous work has suggested an attenuated sensitivity to painful stimulation in hypertensive men. We recently reported that, compared with persons with negative parental history, men, but not women, with a positive history for hypertension showed attenuated pain perception. This study specifically addressed factors that predict pain perception in women, including blood pressure, parental history and mood states. Fifty-four normotensive women with positive (PH+; n = 20) or negative parental history (PH-; n = 34) for hypertension and high or low casual systolic blood pressure (BP) performed the cold pressor (CP) test. Participants rated their pain every 15 s during a 90-s hand CP (0-4 degrees C) and a 90-s post-CP rest period. Detailed mood ratings were obtained immediately before the CP test. Data were evaluated using multivariate repeated measure analyses of variance and regression analyses. PH+ and PH- women did not differ in age, height, weight, education, resting BP, or heart rate. PH+ and PH- women did not differ in pain ratings during or after the CP, or pain ratings using the McGill Pain Questionnaire (MPQ), and they did not differ in their cardiovascular responses to the CP, confirming our earlier study in a separate sample. Women with high casual systolic BP reported significantly less pain, especially after the CP (P < 0.01). MPQ total scores confirmed this finding with high BP women reporting less pain than low BP women (P < 0.05). Regression analyses confirmed these effects. Controlling for potential confounding variables did not alter these relationships. These findings suggest that in women, phenotype systolic BP may be a better predictor of hypoalgesia than parental history of hypertension.

Riboflavin and riboflavin-derived cofactors in adolescent girls with anorexia nervosa.

BACKGROUND: Thyroid hormones, riboflavin, riboflavin cofactors, and organic acids were assessed in girls with anorexia nervosa. OBJECTIVE: The objective was to examine the effect of malnutrition and low thyroid hormone concentrations on erythrocyte and plasma riboflavin metabolism and their relation with urinary organic acid excretion. DESIGN: Seventeen adolescent girls with anorexia nervosa [body mass index (BMI; in kg/m2): 14.8 +/- 2.2] and 17 age-matched, healthy girls (control subjects; BMI: 20.5 +/- 2.2) took part in the feeding study. Erythrocyte and plasma riboflavin as well as riboflavin cofactors (flavin mononucleotide and flavin adenine dinucleotide) were assessed by HPLC, whereas urinary organic acids were assessed by gas chromatography-mass spectrometry. RESULTS: Anorectic patients who began a feeding program had higher erythrocyte riboflavin (3.5 +/- 2.2 compared with <0.1 nmol/mol hemoglobin; P < 0.001), lower plasma flavin adenine dinucleotide (57.8 +/- 18.5 compared with 78.5 +/- 54.3 nmol/L; P < 0.05), and higher urinary ethylmalonic acid (7.12 +/- 4.39 compared with 1.3 +/- 2.8 micromol/mmol creatinine; P < 0.001) and isovalerylglycine (7.65 +/- 4.78 compared with 3.8 +/- 0.9 micromol/mmol creatinine; P < 0.05) concentrations than did control subjects. Triiodothyronine concentrations were low and negatively correlated with plasma riboflavin concentrations (r = -0.69, P < 0.01). Not all patients showed improvements in these biochemical indexes after 30 d of refeeding. CONCLUSIONS: The low triiodothyronine concentrations observed in anorexia nervosa could alter the extent of riboflavin conversion into cofactors, thus leading to high erythrocyte riboflavin concentrations, low plasma flavin adenine dinucleotide concentrations, and high rates of ethylmalonic acid and isovalerylglycine excretion.

[Malignant melanoma of the larynx (author's transl)]. / Das maligne Melanom des Kehlkopfes.

Three instances of malignant melanoma of the larynx are reported. Tumour localization and infiltration are described and the differentiation from normal and pathological tissue changes is discussed. It is noted that distant metastases present late.