Sleep-wake pattern of medical students: early versus late class starting time

The sleep-wake cycle of students is characterized by delayed onset, partial sleep deprivation and poor sleep quality. Like other circadian rhythms, the sleep-wake cycle is influenced by endogenous and environmental factors. The aim of the present study was to determine the effects of different class starting times on the sleep-wake pattern of 27 medical students. The data were collected during two medical school semesters having different class starting times. All subjects answered the Portuguese version of the Horne and Östberg Morningness/Eveningness Questionnaire, the Pittsburgh Sleep Quality Index (PSQI) and kept a sleep diary for two weeks during each semester. Better sleep quality (PSQI = 5.3 vs 3.4), delayed sleep onset (23:59 vs 0:54 h) and longer sleep duration (6 h and 55 min vs 7 h and 25 min) were observed with the late schedule. We also found reduced sleep durations during weekdays and extended sleep durations during weekends. This pattern was more pronounced during the semester with the early class schedule, indicating that the students were more sleep deprived when their classes began earlier in the morning. These results require further investigation regarding the temporal organization of our institutions.

Infrared coagulation versus rubber band ligation in early stage hemorrhoids

The ideal therapy for early stages of hemorrhoids is always debated. Some are more effective but are more painful, others are less painful but their efficacy is also lower. Thus, comfort or efficacy is a major concern. In the present randomized study, a comparison is made between infrared coagulation and rubber band ligation in terms of effectiveness and discomfort. One hundred patients with second degree bleeding piles were randomized prospectively to either rubber band ligation (N = 54) or infrared coagulation (N = 46). Parameters measured included postoperative discomfort and pain, time to return to work, relief in incidence of bleeding, and recurrence rate. The mean age was 38 years (range 19-68 years). The mean duration of disease was 17.5 months (range 12 to 34 months). The number of male patients was double that of females. Postoperative pain during the first week was more intense in the band ligation group (2-5 vs 0-3 on a visual analogue scale). Post-defecation pain was more intense with band ligation and so was rectal tenesmus (P = 0.0059). The patients in the infrared coagulation group resumed their duties earlier (2 vs 4 days, P = 0.03), but also had a higher recurrence or failure rate (P = 0.03). Thus, we conclude that band ligation, although more effective in controlling symptoms and obliterating hemorrhoids, is associated with more pain and discomfort to the patient. As infrared coagulation can be conveniently repeated in case of recurrence, it could be considered to be a suitable alternative office procedure for the treatment of early stage hemorrhoids.

Interruption of the blood-stage cycle of the malaria parasite, Plasmodium chabaudi, by protein tyrosine kinase inhibitors

Malaria is a devastating disease caused by a unicellular protozoan, Plasmodium, which affects 3.7 million people every year. Resistance of the parasite to classical treatments such as chloroquine requires the development of new drugs. To gain insight into the mechanisms that control Plasmodium cell cycle, we have examined the effects of kinase inhibitors on the blood-stage cycle of the rodent malaria parasite, Plasmodium chabaudi. In vitro incubation of red blood cells for 17 h at 37ºC with the inhibitors led to a decrease in the percent of infected cells, compared to control treatment, as follows: genistein (200 µM - 75%), staurosporine (1 µM - 58%), R03 (1 µM - 75%), and tyrphostins B44 (100 µM - 66%) and B46 (100 µM - 68%). All these treatments were shown to retard or prevent maturation of the intraerythrocytic parasites. The diverse concentration ranges at which these inhibitors exert their effects give a clue as to the types of signals that initiate the transitions between the different developmental stages of the parasite. The present data support our hypothesis that the maturation of the intraerythrocytic cycle of malaria parasites requires phosphorylation. In this respect, we have recently reported a high Ca2+ microenvironment surrounding the parasite within red blood cells. Several kinase activities are modulated by Ca2+. The molecular identification of the targets of these kinases could provide new strategies against malaria.

Transitory increased blood pressure after upper airway surgery for snoring and sleep apnea correlates with the apnea-hypopnea respiratory disturbance index

A transitory increase in blood pressure (BP) is observed following upper airway surgery for obstructive sleep apnea syndrome but the mechanisms implicated are not yet well understood. The objective of the present study was to evaluate changes in BP and heart rate (HR) and putative factors after uvulopalatopharyngoplasty and septoplasty in normotensive snorers. Patients (N = 10) were instrumented for 24-h ambulatory BP monitoring, nocturnal respiratory monitoring and urinary catecholamine level evaluation one day before surgery and on the day of surgery. The influence of postsurgery pain was prevented by analgesic therapy as confirmed using a visual analog scale of pain. Compared with preoperative values, there was a significant (P < 0.05) increase in nighttime but not daytime systolic BP (119 ± 5 vs 107 ± 3 mmHg), diastolic BP (72 ± 4 vs 67 ± 2 mmHg), HR (67 ± 4 vs 57 ± 2 bpm), respiratory disturbance index (RDI) characterized by apnea-hypopnea (30 ± 10 vs 13 ± 4 events/h of sleep) and norepinephrine levels (22.0 ± 4.7 vs 11.0 ± 1.3 µg l-1 12 h-1) after surgery. A positive correlation was found between individual variations of BP and individual variations of RDI (r = 0.81, P < 0.01) but not between BP or RDI and catecholamines. The visual analog scale of pain showed similar stress levels on the day before and after surgery (6.0 ± 0.8 vs 5.0 ± 0.9 cm, respectively). These data strongly suggest that the cardiovascular changes observed in patients who underwent uvulopalatopharyngoplasty and septoplasty were due to the increased postoperative RDI.

A comparison of public and private obstructive sleep apnea clinics

The aim of the present study was to compare the clinical findings and polysomnography results obtained at public and private clinics in Brazil, the follow-up after diagnosis, and the therapeutic aspects related to continuous positive airway pressure. Patients who snore and who have obstructive sleep apnea were retrospectively divided into two groups, i.e., public clinic (N = 307) and private clinic (N = 317). Data concerning age, sex, body mass index (BMI), neck circumference, medical history, sleepiness scale, follow-up after diagnosis, and acceptance of continuous positive airway pressure therapy were collected. Mean age was 50 ± 12 (range: 15-80) for public patients and 48 ± 12 years (range: 19-91) for private patients. Mean BMI was 30 ± 6 (range: 19-67) for public patients and 31 ± 6 kg/m² (range: 21-59) for private patients. The public clinic had a significantly higher frequency of women than the private clinic (M:F ratio of 2.0:1 and 6.9:1, respectively). The condition of private patients (apnea-hypopnea index = 31 ± 25) was more severe than that of public patients (apnea-hypopnea index = 25 ± 24 events/h; P = 0.0004). In the public and private clinics, 19 and 15% of patients were snorers, respectively, and 81 and 85% of them had sleep apnea. After diagnosis, follow-up was longer in the private group. The continuous positive airway pressure acceptance was similar for both groups (32 vs 35%), but patients from the public clinic abandoned treatment more than private ones (65 vs 13%). Social status was significant in terms of the severity of obstructive sleep apnea age and gender distribution. Private patients look for a diagnosis earlier in the course of the disease than public patients, adhere more to follow-up, and abandon continuous positive airway pressure treatment less than public patients do.

The mental health of graduate students at the Federal University of São Paulo: a preliminary report

We present data regarding the care provided to graduate level health professionals at the mental health center of the Federal University of São Paulo. From September 1996 to September 2003, 146 graduate students (99 in the Master's degree program and 47 in the Doctoral program) were attended. This population was predominantly female (68.5%), with a mean (± SD) age of 28.6 ± 4.42 years, not married (71.9%). Most of the subjects were professionals who had not graduated from the Federal University (78.1%). The students who sought help for psychological and/or psychiatric problems were classified into two categories: situational-adaptive crises and psychopathological crises. The main diagnoses were depression and anxiety disorders (44%) causing 4.5% of the subjects to be temporarily suspended from their graduate studies; 19.2% reported that they had used psychotropic drugs within the previous month, and 47.9% referred to sleep disturbances. Suicidal tendencies were mentioned by 18% of those interviewed. Students with emotional disturbances and academic dysfunctions should be recognized at an early stage, and it is fundamental for them to have access to mental health programs that provide formal, structured and confidential care. Thus, it is important that professors and advisors in graduate programs build a warm and affective learning environment. If we consider the expressive growth in Brazilian scientific production resulting from the implementation of an extensive national system of graduate education, it is important to focus efforts on enhancing and upgrading the mental health care system.

Sleep disorders, sleepiness and traffic safety: a public health menace

Sleep disorders are not uncommon and have been widely reported throughout the world. They have a profound impact on industrialized 24-h societies. Consequences of these problems include impaired social and recreational activities, increased human errors, loss of productivity, and elevated risk of accidents. Conditions such as acute and chronic insomnia, sleep loss, excessive sleepiness, shift-work, jet lag, narcolepsy, and sleep apnea warrant public health attention, since residual sleepiness during the day may affect performance of daily activities such as driving a car. Benzodiazepine hypnotics and zopiclone promote sleep, both having residual effects the following day including sleepiness and reduced alertness. In contrast, the non-benzodiazepine hypnotics zolpidem and zaleplon have no significant next-day residual effects when taken as recommended. Research on the effects of wakefulness-promoting drugs on driving ability is limited. Countermeasures for excessive daytime sleepiness have a limited effect. There is a need for a social awareness program to educate the public about the potential consequences of various sleep disorders such as narcolepsy, sleep apnea, shift-work-related sleep loss, and excessive daytime sleepiness in order to reduce the number of sleep-related traffic accidents.

Repercussions of a sleep medicine outreach program

Despite the high prevalence of sleep disorders, many healthcare professionals and lay people have little knowledge of Sleep Medicine. Mindful of such a reality, in 2001 the Sleep Institute of the Associação Fundo de Incentivo à Psicofarmacologia launched a campaign to increase Sleep Medicine awareness. Media features, exhibitions, inserts, and classes were used to reach 2,000,000 people and 55,000 healthcare professionals during the period from 2001 to 2004. To evaluate this program, we compared data for polysomnography referrals to the Institute in 2000 and in 2004. A total of 8805 referrals were evaluated (2000: 2164; 2004: 6641). Over the 4 years of the program, the number of beds increased by 43%; more women were referred (31 vs 37%; P < 0.001), mainly with a diagnostic hypothesis of sleep-disorder breathing (SDB). SDB was the most frequent diagnostic hypothesis in 2000 and 2004. In 2004 there were fewer referrals without a diagnostic hypothesis (27 vs 21%; P < 0.001) and for controlling surgically treated SDB (2.3 vs 1.6%; P < 0.05), and an increase in the following diagnostic hypotheses: non-invasive treatment of SDB (8.3 vs 12.3%; P < 0.001) and insomnia (3.5 vs 6.5%; P < 0.001). Insomnia diagnostic hypothesis was better correlated with SDB on referral documents in 2004 and less with a diagnostic hypothesis of limb movement disturbance. The program helped increase polysomnography referrals, particularly among women. Healthcare professionals appear to have a more developed understanding of sleep disorders.

Obese obstructive sleep apnea patients with tonsil hypertrophy submitted to tonsillectomy

The physiopathology of obstructive sleep apnea-hypopnea syndrome (OSAHS) is multifactorial and obesity has been shown to be one of the main factors correlated with its occurrence. In obese patients with anatomical alterations of the upper airways it is often difficult to predict success for surgical correction since obesity is a limiting factor. Therefore, the aim of the present study was to evaluate the results of tonsillectomy in a specific group of patients, i.e., obese OSAHS patients with tonsil hypertrophy. Seven OSAHS patients with moderate obesity with obstructive palatine tonsil hypertrophy were submitted to tonsillectomy. All patients were submitted to pre- and postoperative appraisal of body mass index, otorhinolaryngology examination and polysomnography. Patients' average age was 36.4 ± 10.3 years and average preoperative body mass index was 36.6 ± 6.3 kg/m². Postoperative weight did not differ significantly from preoperative weight (P = 0.27). Average preoperative apnea and hypopnea index (AHI) was 81 ± 26/h and postoperative AHI was 23 ± 18/h (P = 0.0005). Average preoperative minimum oxyhemoglobin saturation (SaO2 min) was 69 ± 14% and the postoperative value was 83 ± 3% (P = 0.038). In relation to AHI, 6 (86%) of the 7 patients studied showed a reduction of 50% in relation to preoperative level and of these, 4 (57%) presented AHI of less than 20%. Only one patient presented a reduction of less than 50% in AHI, but even so showed improved SaO2 min. Tonsillectomy treatment for OSAHS in obese patients with obstructive palatine tonsil hypertrophy caused a significant reduction in AHI, with improvement in SaO2 min. This procedure could be eventually considered as an option of treatment for obese OSAHS patients with significant tonsil hypertrophy when continuous positive air pressure therapy is not possible as the first choice of treatment.

A double-blind comparison of the effect of the antipsychotics haloperidol and olanzapine on sleep in mania

The effects of haloperidol and olanzapine on polysomnographic measures made in bipolar patients during manic episodes were compared. Twelve DSM-IV mania patients were randomly assigned to receive either haloperidol (mean ± SD final dosage: 5.8 ± 3.8 mg) or olanzapine (mean ± SD final dosage: 13.6 ± 6.9 mg) in a 6-week, double-blind, randomized, controlled clinical trial. One-night polysomnographic evaluation was performed before and after the haloperidol or olanzapine treatment. Psychopathology and illness severity were rated respectively with the Young Mania Rating Scale (YMRS) and the Clinical Global Impressions - Bipolar version (CGI-BP). There was a significant improvement in the YMRS and CGI-BP scores at the end of the study for both groups. Mixed ANOVA used to compare the polysomnographic measures of both drugs demonstrated significant improvement in sleep measures with olanzapine. In the olanzapine group, statistically significant time-drug interaction effects on sleep continuity measures were observed: sleep efficiency (mean ± SEM pre-treatment value: 6.7 ± 20.3%; after-treatment: 85.7 ± 10.9%), total wake time (pre-treatment: 140.0 ± 92.5 min; after-treatment: 55.2 ± 44.2 min), and wake time after sleep onset (pre-treatment: 109.7 ± 70.8 min; after-treatment: 32.2 ± 20.7 min). Conversely, improvement of polysomnographic measures was not observed for the haloperidol group (P > 0.05). These results suggest that olanzapine is more effective than haloperidol in terms of sleep-promoting effects, although olanzapine is comparatively as effective as haloperidol in treating mania. Polysomnography records should provide useful information on how manic states can be affected by psychopharmacological agents.

Sleep deprivation reduces the lymphocyte count in a non-obese mouse model of type 1 diabetes mellitus

The objective of the present study was to determine whether sleep deprivation (SD) would promote changes in lymphocyte numbers in a type 1 diabetes model (non-obese diabetic, NOD, mouse strain) and to determine whether SD would affect female and male NOD compared to Swiss mice. The number of lymphocytes in peripheral blood after 24 and 96 h of SD (by multiple platform method) or equivalent period of time in home-cage controls was examined prior to the onset of diabetes. SD for 96 h significantly reduced lymphocytes in male Swiss mice compared to control (8.6 ± 2.1 vs 4.1 ± 0.7 10³/µL; P < 0.02). In male NOD animals, 24- and 96-h SD caused a significant decrease of lymphocytes compared to control (4.4 ± 0.3 vs 1.6 ± 0.5; P < 0.001 and 4.4 ± 0.3 vs 0.9 ± 0.1 10³/µL; P < 0.00001, respectively). Both 24- and 96-h SD induced a reduction in the number of lymphocytes in female Swiss (7.5 ± 0.5 vs 4.5 ± 0.5, 4.4 ± 0.6 10³/µL; P < 0.001, respectively) and NOD mice (4 ± 0.6 vs 1.8 ± 0.2, 1.2 ± 0.4 10³/µL; P < 0.01, respectively) compared to the respective controls. Loss of sleep induced lymphopenia in peripheral blood in both genders and strains used. Since many cases of autoimmunity present reduced numbers of lymphocytes and, in this study, it was more evident in the NOD strain, our results suggest that SD should be considered a risk factor in the onset of autoimmune disorders.

Sleep habits and complaints of adults in the city of São Paulo, Brazil, in 1987 and 1995

This study compares the prevalence of complaints of insomnia, excessive diurnal sleepiness, parasomnias, and sleep habits of the adult population in the city of São Paulo, Brazil, estimated in surveys carried out in 1987 and 1995. Representative samples of 1000 adult residents per survey were interviewed using a validated structured sleep questionnaire, the "UNIFESP Sleep Questionnaire". Difficulty maintaining sleep, difficulty initiating sleep and early morning awakening, occurring at least three times a week, were reported in 1987 and 1995, by 15.8/27.6, 13.9/19.1, and 10.6/14.2% of the interviewees, respectively, significantly increasing throughout time. These sleep problems were more often found among women. Frequencies of excessive diurnal sleepiness and sleep attacks were unchanged comparing 1987 with 1995 (4.5 vs 3.8 and 3.1 vs 3.0%, respectively). Parasomnia complaints remained unchanged, with the exception of leg cramps, which doubled in prevalence from 1987 to 1995 (2.6 to 5.8%). Snoring was the most common parasomnia (21.5% in 1995), reported more often by men than by women, and somnambulism was the least common (approximately 1%). Besides sleeping slightly less, interviewees went to bed and woke up later in 1995. Approximately 12% of the subjects in both surveys had consulted a physician due to sleep problems and 3.0% reported habitual use of sleep-promoting substances in 1995. Overall, there was a significant increase in insomnia complaints from 1987 to 1995 in the general population of the city of São Paulo. This major change over a little under a decade should be considered as an important public health issue.

Effect of sildenafil (Viagra®) on the genital reflexes of paradoxical sleep-deprived male rats

Since there is evidence that paradoxical sleep deprivation (PSD) elicits penile erection (PE) and ejaculation (EJ), and that the erectile response of rats is mediated by nitric oxide, the present study sought to extend the latter finding by assessing the effects of sildenafil on the genital reflexes of male Wistar rats subjected to PSD. We also determined the influence of sildenafil on hormone concentrations. In the first experiment, sildenafil at doses ranging from 0.08 to 0.32 mg/kg was administered intraperitoneally to rats that had been deprived of sleep for 4 days and to home cage controls (N = 8-10/group). The frequency of PE and EJ was measured for 60 min. PSD alone induced PE in 50% of the animals; however, a single injection of sildenafil did not significantly increase the percentage of rats displaying PE compared to PSD-saline or to home cage groups. PSD alone also induced spontaneous EJ, but this response was not potentiated by sildenafil in the dose range tested. Testosterone concentrations were significantly lower in PSD rats (137 ± 22 ng/dL) than in controls (365 ± 38 ng/dL), whereas progesterone (0.9 ± 0.1 vs 5.4 ± 1 ng/mL) and plasma dopamine (103.4 ± 30 vs 262.6 ± 77 pg/mL) increased. These changes did not occur after sildenafil treatment. The data show that although sildenafil did not alter the frequency of genital reflexes, it antagonized hormonal (testosterone and progesterone) and plasma dopamine changes induced by PSD. The stimulation of the genital reflexes by sildenafil did not result in potentiating effects in PSD rats.

The reciprocal interaction between sleep and type 2 diabetes mellitus: facts and perspectives

Type 2 diabetes mellitus is a systemic disease characterized by intolerance to glucose and peripheral resistance to insulin. This endocrine disease affects fundamental mechanisms of the central nervous system and jeopardizes the balance of vital functions such as the cardiovascular and circadian rhythm. The increased prevalence of metabolic disorders in our society is aggravated by endemic voluntary postponement of bedtime and by the current sedentary lifestyle, leading to epidemic proportions of obese people. Diabetes and chronic loss of sleep share the fact that both affect millions and one is detrimental to the other. Indeed, sleep deficits have marked modulatory effects on glucose metabolism and insulin sensitivity and foster metabolic syndrome that culminates in sleep disorders like restless syndrome and sleep apnea, which in turn lead to poor sleep quality. We examine the hypothesis that these two worldwide emerging disorders are due to two interlinked cycles. In our paradigm, we establish an intimate relationship between diabetes and sleep disturbances and postulate possible mechanisms that provide support for this conjecture. In addition, we propose some perspectives about the development of the reciprocal interaction between predictor components of metabolic syndrome and sleep disturbances that lead to poor sleep quality. The ability to predict the development and identify or associate a given mode of sleep disturbance to diabetes would be a valuable asset in the assessment of both. Furthermore, major advances in care coupled with healthy lifestyles can ensure a higher quality of life for people with diabetes.

Effects of cocaine, methamphetamine and modafinil challenge on sleep rebound after paradoxical sleep deprivation in rats

Sleep loss is both common and critically relevant to our society and might lead to the abuse of psychostimulants such as amphetamines, cocaine and modafinil. Since psychoactive substance abuse often occurs within a scenario of sleep deficit, the purpose of this investigation was to compare the sleep patterns of rats challenged with cocaine (7 mg/kg, ip), methamphetamine (7 mg/kg, ip), or modafinil (100 mg/kg, ip) subsequent to paradoxical sleep deprivation (PSD) for 96 h. Our results show that, immediately after 96 h of PSD, rats (10 per group) that were injected with a psychostimulant presented lower percentages of paradoxical sleep compared to those injected with saline (P < 0.01). Regarding slow wave sleep (SWS), rats injected with psychostimulants after PSD presented a late rebound (on the second night subsequent to the injection) in the percentage of this phase of sleep when compared to PSD rats injected with saline (P < 0.05). In addition, the current study has produced evidence of the characteristic effect of each drug on sleep architecture. Home cage control rats injected with modafinil and methamphetamine showed a reduction in SWS compared with the saline group. Methamphetamine affected sleep patterns most, since it significantly reduced paradoxical sleep, SWS and sleep efficiency before and after PSD compared to control (P < 0.05). Cocaine was the psychostimulant causing the least changes in sleep pattern in relation to those observed after saline injection. Therefore, our results suggest that abuse of these psychostimulants in a PSD paradigm aggravates their impact on sleep patterns.