Characterization of proteinuria in treated and untreated dogs naturally infected with Leishmania sp / Caracterização da proteinúria de cães tratados e não tratados, naturalmente infectados com Leishmania sp

In the search for an early biomarker of renal injury, this study aimed to determine the urinary protein profile of dogs with leishmaniasis without treatment and treated as determined by Brazilian legislation. The identification of proteinuria, its classification and the circumstances in which it takes place instigated this study. For this, 30 dogs from an outpatient clinic at a Veterinary Hospital in Belo Horizonte were evaluated. All animals underwent clinical and laboratory tests, which included renal biomarkers. The proteins were characterized using the SDS-page electrophoresis technique, and thus, a urinary protein profile was developed comparing patients considered clinically healthy with dogs infected with leishmaniasis that were under treatment and with untreated infected dogs. The results showed that the hematological and biochemical parameters showed similar behavior between the groups of healthy dogs and dogs with leishmaniasis treated, however a very heterogeneous pattern of urinary proteins can be observed and differed between healthy animals and animals with leishmaniasis, as well as between treated and untreated animals. The results suggest that the classification of proteinuria can be a tool that helps in the staging of animals infected with L. infantum and can differentiate them as to the severity of existing kidney injuries.(AU)

Na busca por um biomarcador precoce de injúria renal, este trabalho teve como objetivo determinar o perfil proteico urinário de cães infectados com leishmaniose sem tratamento e tratados conforme determina a legislação brasileira. A identificação da proteinúria, sua classificação e as circunstâncias em que ocorrem instigaram este estudo. Para tanto, foram avaliados 30 cães oriundos do atendimento clínico ambulatorial de um Hospital Veterinário em Belo Horizonte. Todos os animais passaram por exame clínico e laboratorial, que incluíram biomarcadores renais. As proteínas foram caracterizadas através da técnica de eletroforese por SDS-PAGE, e assim, foi elaborado um perfil proteico urinário comparando pacientes considerados clinicamente hígidos, com cães infectados por Leishmania (L.) infantum e que estavam sob tratamento e cães infectados não tratados. Os resultados demonstraram que os parâmetros hematológicos e bioquímicos apresentaram comportamento semelhante entre os grupos de cães hígidos e de cães infectados com L. infantum tratados, entretanto um padrão muito heterogêneo de proteínas urinárias pode ser observado e diferiu entre animais hígidos e animais com leishmaniose, assim como entre os animais tratados e não tratados. Os resultados sugerem que a classificação da proteinúria pode ser uma ferramenta que auxilia no estadiamento de animais infectados por L. infantum podendo diferenciá-los quanto à gravidade de lesões renais existentes.(AU)

Characterization of proteinuria in treated and untreated dogs naturally infected with Leishmania sp

ABSTRACT: In the search for an early biomarker of renal injury, this study aimed to determine the urinary protein profile of dogs with leishmaniasis without treatment and treated as determined by Brazilian legislation. The identification of proteinuria, its classification and the circumstances in which it takes place instigated this study. For this, 30 dogs from an outpatient clinic at a Veterinary Hospital in Belo Horizonte were evaluated. All animals underwent clinical and laboratory tests, which included renal biomarkers. The proteins were characterized using the SDS-page electrophoresis technique, and thus, a urinary protein profile was developed comparing patients considered clinically healthy with dogs infected with leishmaniasis that were under treatment and with untreated infected dogs. The results showed that the hematological and biochemical parameters showed similar behavior between the groups of healthy dogs and dogs with leishmaniasis treated, however a very heterogeneous pattern of urinary proteins can be observed and differed between healthy animals and animals with leishmaniasis, as well as between treated and untreated animals. The results suggest that the classification of proteinuria can be a tool that helps in the staging of animals infected with L. infantum and can differentiate them as to the severity of existing kidney injuries.

RESUMO: Na busca por um biomarcador precoce de injúria renal, este trabalho teve como objetivo determinar o perfil proteico urinário de cães infectados com leishmaniose sem tratamento e tratados conforme determina a legislação brasileira. A identificação da proteinúria, sua classificação e as circunstâncias em que ocorrem instigaram este estudo. Para tanto, foram avaliados 30 cães oriundos do atendimento clínico ambulatorial de um Hospital Veterinário em Belo Horizonte. Todos os animais passaram por exame clínico e laboratorial, que incluíram biomarcadores renais. As proteínas foram caracterizadas através da técnica de eletroforese por SDS-PAGE, e assim, foi elaborado um perfil proteico urinário comparando pacientes considerados clinicamente hígidos, com cães infectados por Leishmania (L.) infantum e que estavam sob tratamento e cães infectados não tratados. Os resultados demonstraram que os parâmetros hematológicos e bioquímicos apresentaram comportamento semelhante entre os grupos de cães hígidos e de cães infectados com L. infantum tratados, entretanto um padrão muito heterogêneo de proteínas urinárias pode ser observado e diferiu entre animais hígidos e animais com leishmaniose, assim como entre os animais tratados e não tratados. Os resultados sugerem que a classificação da proteinúria pode ser uma ferramenta que auxilia no estadiamento de animais infectados por L. infantum podendo diferenciá-los quanto à gravidade de lesões renais existentes.

Characteristics and Trends in Hypnotics Consumption in the Largest Health Care System in Israel.

Objectives. To quantify and characterize hypnotics consumption habits among adult patients insured by Clalit Health Services (CHS), the largest health care provider in Israel, in 2000 and 2010. Methods. A retrospective analysis of CHS computerized pharmacy records. Data were collected for all patients over the age of 18 years who were prescribed hypnotics in 2000 and in 2010. Results. Sleep medications were consumed by 8.7% of the adult CHS population in 2000 and by 9.6% in 2010. About one-quarter of consumers were treated for more than 6 months in both years. Multiple sleeping drugs were consumed more often in 2010 (45.2%) than a decade before (22%). While in 2000 benzodiazepines accounted for 84.5% of hypnotics, in 2010 this was reduced to 73.7% (p < 0.05). Of all patients treated for longer than 6 months only 11% in 2000 and 9% in 2010 required a dose escalation suggesting the absence of tolerance. Conclusions. Nine percent of the Israeli population consumes hypnotics. There is a major increase in prescription of combination of medications between 2000 and 2010, with an increase in Z class medications use and reduction in benzodiazepines. Most patients chronically treated did not escalate dosage, suggesting the absence of tolerance.

The effect of medical clowning on reducing pain, crying, and anxiety in children aged 2-10 years old undergoing venous blood drawing--a randomized controlled study.

UNLABELLED: Recently, the utilization of medical clowns to reduce anxiety, stress, and even pain associated with hospitalization has become popular. However, the scientific basis of this benefit and outcome is scant. Venipuncture and IV cannulation are very common sources of pain in ill children. To reduce pain, one common approach is to apply a local anesthetic prior to the procedure. In the current study, we sought to compare the utilization of medical clowning in this process with two control groups: (1) local anesthetic cream (EMLA®, Astrazeneca, London, UK) applied prior to the procedure (active control) and (2) the procedure performed with neither clown nor EMLA (control group). We hypothesized that a medical clown will reduce pain, crying, and anxiety in children undergoing this procedure.Children aged 2-10 years who required either venous blood sampling or intravenous cannulation were recruited and randomly assigned to one of the three groups. Outcome measures consisted of the duration of the whole procedure (measured objectively by an independent observer), the duration of crying (measured objectively by an independent observer), subjective assessment of pain level (a commonly used validated scale), and anxiety level regarding future blood exams (by questionnaire). Analysis of variance (ANOVA) was used to compare between the groups. p < 0.05 was considered statistically significant.One hundred children participated. Mean age was 5.3 ± 2.5 years (range 2-10 years). The duration of crying was significantly lower with clown than in the control group (1.3 ± 2.0 vs 3.8 ± 5.4 min, p = 0.01). With EMLA, this duration was 2.4 ± 2.9 min. The pain magnitude as assessed by the child was significantly lower with EMLA than in the control group (2.9 ± 3.3 vs 5.3 ± 3.8, p = 0.04), while with clown it was 4.1 ± 3.5, not significant when compared with the other two modalities. Hence, duration of crying was shortest with clown while pain assessment was lowest with EMLA. Furthermore, with clown duration of cry was significantly shorter than in controls, but pain perception did not significantly differ between these groups. As expected, the duration of the entire process was shortest in the control group (5.0 ± 3.8 min), moderate with clown (19.3 ± 5.8 min), and longest with EMLA (63.2 ± 11.4 min, p < 0.0001 between all). Parental reporting of a beneficial effect was greater with clown than with EMLA (3.6 ± 0.8 vs 3.0 ± 1.1, p = 0.02). Parental assessment of child's anxiety related to future blood tests as evaluated by telephone the following day revealed that it was significantly lower with clown than in the control group or EMLA (2.6 ± 1.2 vs 3.7 ± 1.3 or 3.8 ± 1.6, p < 0.01 for both). CONCLUSIONS: Distraction by a medical clown is helpful in children undergoing blood tests or line insertion. Although pain reduction was better with EMLA, both duration of cry and anxiety were lower with a medical clown. These results strongly encourage and support the utilization of medical clowns while drawing blood in children.

The SomnuSeal Oral Mask Is Reasonably Tolerated by Otherwise CPAP Noncompliant Patients with OSA.

Compliance with CPAP is the major limiting factor in treating patients with OSA. The novel SomnuSeal mask is an oral self-adaptable mask located between the teeth and the lips ensuring that there are no air leaks or skin abrasions. Fifty patients with AHI > 20, who failed previous CPAP trials, were asked to sleep with the mask for one month. In all patients, the mask was connected to an AutoPAP machine with a heated humidifier. Efficacy, convenience, and compliance (average usage for 4 or more hours per night) were monitored. Fifty patients (41 m and 9 f, mean age 57 ± 12 years, BMI 33.6 ± 4.9 kg/m(2), and AHI 47 ± 23/h) participated. Eleven were classified as compliant (average mask usage of 26 nights, 4.7 hours per night), five were only partially compliant (average usage of 13 nights, 2.9 hours per night), and 34 could not comply with it. In all patients who slept with it, the efficacy (assessed by residual AHI derived from the CPAP device) was good with an AHI of less than 8/hour. Interestingly, the required optimal pressure decreased from an average of 9.3 cmH2O to 4.6 cmH2O. The SomnuSeal oral interface is effective and may result in converting noncompliant untreated patients with OSA into well-treated ones.

Orexin receptor antagonism, a new sleep-enabling paradigm: a proof-of-concept clinical trial.

The orexin system is a key regulator of sleep and wakefulness. In a multicenter, double-blind, randomized, placebo-controlled, two-way crossover study, 161 primary insomnia patients received either the dual orexin receptor antagonist almorexant, at 400, 200, 100, or 50 mg in consecutive stages, or placebo on treatment nights at 1-week intervals. The primary end point was sleep efficiency (SE) measured by polysomnography; secondary end points were objective latency to persistent sleep (LPS), wake after sleep onset (WASO), safety, and tolerability. Dose-dependent almorexant effects were observed on SE , LPS , and WASO . SE improved significantly after almorexant 400 mg vs. placebo (mean treatment effect 14.4%; P < 0.001). LPS (­18 min (P = 0.02)) and WASO (­54 min (P < 0.001)) decreased significantly at 400 mg vs. placebo. Adverse-event incidence was dose-related. Almorexant consistently and dose-dependently improved sleep variables. The orexin system may offer a new treatment approach for primary insomnia.

Pre-eclampsia is associated with sleep-disordered breathing and endothelial dysfunction.

Pre-eclamptic toxaemia (PET) may be associated with both endothelial dysfunction (ED) and sleep-disordered breathing (SDB). It was hypothesised that females with PET would demonstrate both SDB and ED, and that a correlation between these two would suggest a potential causative association. A total of 17 females with PET and 25 matched females with uncomplicated pregnancy were studied. They underwent a nocturnal ambulatory sleep study (using Watch_PAT100) and noninvasive evaluation of endothelial function utilising the reactive hyperaemia test (using Endo_PAT 2000). A higher ratio of post- to pre-occlusion pulse-wave amplitude (endothelial function index (EFI)) indicated better endothelial function. Females with PET had a significantly higher respiratory disturbance index (RDI) and lower EFI than controls (18.4+/-8.4 versus 8.3+/-1.3.h(-1), and 1.5+/-0.1 versus 1.8+/-0.1, respectively). Blood pressure significantly correlated with RDI and with EFI. EFI tended to correlate with RDI. In conclusion, these results suggest that both sleep-disordered breathing and endothelial dysfunction are more likely to occur in females with pre-eclamptic toxaemia than in females with uncomplicated pregnancies. The current authors speculate that respiratory disturbances contribute to the functional abnormality of the blood vessels seen in females with pre-eclamptic toxaemia, although causality cannot be determined based on this study.

Predictors of erectile function improvement in obstructive sleep apnea patients with long-term CPAP treatment.

The long-term effect of treatment with continuous positive airway pressure (CPAP) on erectile function was assessed in 60 patients with obstructive sleep apnea syndrome (OSAS). Severity of OSAS was evaluated by respiratory disturbance index (RDI) and minimal oxygen saturation (OxiMin). Severity of erectile dysfunction (ED) was assessed with the five question International Index of Erectile Function (IIEF-5) before and after CPAP treatment. Subjects were categorized into three groups on the basis of the change in IIEF-5 score: Group 1, no change (n=37); Group 2, improvement from 10+/-5.65 to 19.1+/-5.7, P<0.01 (n=12); Group 3, worsening from 19.9+/-4.7 to 9.5+/-7.8, P<0.01 (n=11). Group 2 had significantly higher RDI and lower OxiMin than the other groups, and was also more compliant and satisfied with CPAP. Change in IIEF-5 with CPAP treatment was negatively correlated (Pearson coefficient) with OxiMin (r=-0.374), and positively correlated with adherence to CPAP treatment (r=0.689). In conclusion, in selected patients, CPAP treatment for OSAS may by itself have a positive effect on erectile function by improving respiration during sleep. Predictors of erectile improvement include high RDI, low OxiMin, and CPAP compliance.

Bilateral mandibular distraction for patients with compromised airway analyzed by three-dimensional CT.

The purpose of this study was to present the method of mandibular distraction osteogenesis in order to improve airway to respiratory distressed patients due to significant mandibular deficiency, and to present the quantitative volumetric evaluation of mandible and upper airway using three-dimensional-CT (3D-CT) before and after distraction. This study involved 12 patients aged 12 months to seven years with various complaints of Obstructive Sleep Apnea (OSA) such as noisy breathing during sleep, waking episodes, pauses in respiration and daytime somnolence. Some of them were considered tracheostomy candidates. All the patients underwent bilateral mandibular distraction under general anesthesia. 3D-CT of face and neck was performed before and after distraction and a quantitative volumetric evaluation of mandibular volume and airway volume was performed. The results reveal successful mandibular advancement with increase of mandibular volume by an average of 28.24% and increase of upper airway volume with a mean of 71.92%. Moreover, there were improved apnea index and oxygen saturation and elimination of OSA symptoms. In conclusion, the results demonstrate that following distraction osteogenesis of hypoplastic mandible the volume of the mandible and upper airway increases, eliminating symptoms of OSA and preventing tracheostomy.

Sleep patterns in children and adolescents with functional recurrent abdominal pain: objective versus subjective assessment.

AIM: To document objective sleep patterns of children and adolescents with functional recurrent abdominal pain (RAP), and to compare them with subjective sleep assessments and sleep patterns of healthy controls. METHODS: Subjective sleep reports and sleep habit assessments were obtained from 25 adolescents with functional RAP and from 15 age- and gender-matched healthy volunteers, and were compared with continuous movement monitoring using the Actigraph for 7 consecutive days. RESULTS: Abdominal pain before falling asleep was a unanimous complaint in the RAP group, with 29% reporting awakening from sleep by the pain. Only 25% of RAP patients assessed their sleep quality as good, compared with 87% of the control group. Objective sleep patterns measurements of the RAP patients were similar to those of the control group as well as to measurements observed in a large population of school-aged children and adolescents. CONCLUSION: This study of a small group of children and adolescents with functional RAP provides objective evidence that their sleep patterns do not differ from those of normal peers, despite their subjective complaints.

Long-term follow-up of untreated patients with sleep apnoea syndrome.

Obstructive sleep apnoea (OSA) is a common disorder with numerous potential sequelae. Although the majority of these consequences can be reduced with appropriate treatment, only limited data exist regarding the natural progression ofthis disorder in untreated individuals. We hereby report a long-term follow-up of all untreated patients (n = 40) followed-up in the Technion Sleep Clinic, using both subjective and objective measurements. In addition, we report a long-term follow-up of 11 patients who attempted dietary weight loss. The average time interval between the first and second polysomnographies for the untreated group was 5.0 +/- 2.8 yrs, and 2.5 +/- 2.3 yrs for the weight reduction group. There was no significant change in Body Mass Index (BMI) or Respiratory Disturbance Index (RDI) between the two Polysomnographic (PSG) evaluations in the untreated patients. However, eight patients developed hypertension (n=5) or ischaemic heart disease (IHD) (n=3) between the two evaluations. RDI, age and BMI at the time ofthe initial evaluation were not predictive of changes in RDI, snoring intensity or minimal oxygen saturation. However, the patients who developed hypertension/IHD had significantly higher RDI than the patients who did not (46 +/- 27 vs. 23 +/- 17 h(-1), P < 0.005). In the weight-loss group, BMI decreased by a mean of 3.1 kg m(-2), and RDI decreased by 20events h(-1), P<0.05 for both. There was a significant correlation between the weight loss and improvement in RDI (R = 0.75, P = 0.005). We conclude that in untreated obstructive sleep apnoea patients RDI does not necessarily increase over time, but associated hypertension or ischaemic heart disease may develop. When weight loss is successfully achieved, sleep apnoea significantly improves with a high correlation between the extent of weight loss and the improvement in apnoea status.

Genioglossal activation in patients with obstructive sleep apnea versus control subjects. Mechanisms of muscle control.

Pharyngeal dilator muscle activation (GGEMG) during wakefulness is greater in patients with obstructive sleep apnea (OSA) than in healthy control subjects, representing a neuromuscular compensatory mechanism for a more collapsible airway. As previous work from our laboratory has demonstrated a close relationship between GGEMG and epiglottic pressure, we examined the relationship between genioglossal activity and epiglottic pressure in patients with apnea and in control subjects across a wide range of epiglottic pressures during basal breathing, negative-pressure (iron-lung) ventilation, heliox breathing, and inspiratory resistive loading. GGEMG was greater in the patients with apnea under all conditions (p < 0.05 for all comparisons), including tonic, phasic, and peak phasic GGEMG. In addition, patients with apnea generated a greater peak epiglottic pressure on a breath-by-breath basis. Although the relationship between GGEMG and epiglottic negative pressure was tight across all conditions in both groups (all R values > = 0.69), there were no significant differences in the slope of this relationship between the two groups (all p values > 0.30) under any condition. Thus, the increased GGEMG seen in the patient with apnea during wakefulness appears to be a product of an increased tonic activation of the muscle, combined with increased negative-pressure generation during inspiration.

Melatonin effect on seizures in children with severe neurologic deficit disorders.

PURPOSE: Recently, melatonin has been associated with antiepileptic activity, most probably because of its antioxidant activity as a free radical scavenger. This study aimed to expand the clinical experience with melatonin as an antiepileptic drug (AED) in humans. METHODS: Six children (aged 2-15 years), with severe intractable seizures, were treated with 3 mg of oral melatonin 30 min before bedtime, in addition to their previous AED treatment for 3 months. A diary of clinical seizure activity (time of day, duration, and type) was kept by parents for a month before and during treatment. Five patients underwent a baseline polysomnography, and three also were monitored during melatonin treatment. RESULTS: With the exception of the parents of one child, all reported a significant clinical improvement in seizure activity during treatment, particularly during the night. Sleep studies showed a decrease in epileptic activity in two of the three patients who were monitored during treatment, and a change of sleep efficiency from 84.2% to 89.7% (NS). Improvement in daytime behavior and in communication abilities was reported by parents, although it was not objectively measured. CONCLUSIONS: This clinical observation adds to the growing data showing the antiepileptic effect of melatonin. However, owing to the paucity of well-controlled studies, using melatonin as an AED should be limited to this specific group of patients with intractable seizures.

Sublingual electrical stimulation of the tongue during wakefulness and sleep.

Pharyngeal obstruction in patients with obstructive sleep apnea (OSA) is thought to result from decreased upper airway muscle tone during sleep. The goal of the present study was to estimate the role of the tongue muscles in maintaining pharyngeal patency during sleep. Using non-invasive, sub-lingual surface electrical stimulation (ES), we measured tongue protrusion force during wakefulness and upper airway resistance during sleep in seven healthy subjects and six patients with OSA. During wakefulness, ES produced similar protrusion forces in healthy subjects and patients with OSA. ES of the anterior sublingual surface, causing preferential contraction of the genioglossus, resulted in smaller effects than combined ES of the anterior and lateral surface, which also stimulated tongue retractors. During sleep, trans-pharyngeal resistance decreased and peak inspiratory flow rate increased from 319+/-24 to 459+/-27 and from 58+/-16 to 270+/-35 ml/sec for healthy subjects and OSA patients, respectively (P<0.001). However, ES was usually unsuccessful in reopening the upper airway in the presence of complete apneas. We conclude that non-invasive ES of the tongue improves flow dynamics during sleep. Combined activation of tongue protrusors and retractors may have a beneficial mechanical effect. The magnitude of responses observed suggests that in addition to the stimulated muscles, other muscles and/or forces have a substantial impact on pharyngeal patency.

Genioglossal inspiratory activation: central respiratory vs mechanoreceptive influences.

Upper airway dilator muscles are phasically activated during respiration. We assessed the interaction between central respiratory drive and local (mechanoreceptive) influences upon genioglossal (GG) activity throughout inspiration. GG(EMG) and airway mechanics were measured in 16 awake subjects during baseline spontaneous breathing, increased central respiratory drive (inspiratory resistive loading; IRL), and decreased respiratory drive (hypocapnic negative pressure ventilation), both prior to and following dense upper airway topical anesthesia. Negative epiglottic pressure (P(epi)) was significantly correlated with GG(EMG) across inspiration (i.e. within breaths). Both passive ventilation and IRL led to significant decreases in the sensitivity of the relationship between GG(EMG) and P(epi) (slope GG(EMG) vs P(epi)), but yielded no change in the relationship (correlation) between GG(EMG) and P(epi). During negative pressure ventilation, pharyngeal resistance increased modestly, but significantly. Anesthesia in all conditions led to decrements in phasic GG(EMG), increases in pharyngeal resistance, and decrease in the relationship between P(epi) and GG(EMG). We conclude that both central output to the GG and local reflex mediated activation are important in maintaining upper airway patency.

Upper-airway collapsibility: measurements and sleep effects.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is characterized by repetitive pharyngeal collapse during sleep. Several techniques have been proposed to assess the collapsibility of the upper airway in awake humans, but sleep-wake comparisons have rarely been attempted and there are few studies comparing OSA patients to control subjects. We sought to compare two collapsibility measurement techniques between normal and apneic subjects, and between wakefulness and sleep. DESIGN: We conducted three studies. First, we examined whether collapsibility assessed by negative pressure pulses (NPPs) during wakefulness reflected values during sleep in 21 normal subjects. Second, we determined in these normal subjects whether collapsibility during sleep assessed by NPPs was predictive of collapsibility measured by inspiratory resistive loading (IRL). Finally, we compared upper-airway collapsibility between apnea patients (n = 22) and normal volunteers (n = 38) during wakefulness by NPPs. SETTING: Clinical and research laboratories at the Brigham and Women's Hospital. PARTICIPANTS: Two populations of normal subjects (n = 21 and n = 38) and OSA patients (n = 22). MEASUREMENTS AND RESULTS: Collapsibility during wakefulness, as measured by NPPs, correlated significantly with collapsibility during sleep (r = 0.62; p = 0.003). There was also a significant correlation between the two measures of collapsibility (IRL and NPP) during sleep (r = 0.53; p = 0.04). Both measures revealed a significant increase in pharyngeal collapsibility during sleep as compared to wakefulness. Finally, apnea patients had significantly greater pharyngeal collapsibility than control subjects during wakefulness (p = 0.017). CONCLUSIONS: These data suggest that upper-airway collapsibility measured during wakefulness does provide useful physiologic information about pharyngeal mechanics during sleep and demonstrates clear differences between individuals with and without sleep apnea.

Peripheral arterial responses to treadmill exercise among healthy subjects and atherosclerotic patients.

UNLABELLED: BACKGROUND-Peripheral cutaneous vascular beds, such as the fingertips, contain a high concentration of arteriovenous anastomoses, richly innervated by a-adrenergic nerve fibers, to control heat regulation. Nevertheless, for a variety of technical reasons, finger blood flow responses to exercise have not been well studied in health and disease. Hence, we compared finger pulse-wave amplitude (PWA) responses to exercise among 50 normal volunteers and 57 patients with atherosclerotic coronary artery disease (CAD) using a robust, modified form of volume plethysmography. METHODS AND RESULTS: PWA was quantified for each minute of exercise as a ratio relative to baseline. Exercise PWA responses were compared with clinical, hemodynamic, ECG, and myocardial single photon emission computed tomography parameters. Among normal subjects, 38 (76%) manifested vasodilation throughout exercise and 12 (24%) manifested initial vasodilation followed by vasoconstriction at high heart rate thresholds. None manifested vasoconstriction throughout exercise. By contrast, 20 CAD patients (35%) manifested progressive vasoconstriction from the onset of exercise, and 10 others (18%) manifested vasoconstriction at low heart rate thresholds (P < 0.001 versus normals) after initial vasodilation with exercise. Patients exhibiting vasodilation versus vasoconstriction during exercise had similar clinical and exercise profiles, except for a greater use of ACE inhibitors and a greater level of achieved metabolic equivalents among the former (P<0.05 for both). CONCLUSIONS: Half of our CAD patients manifested diminution in PWA that was consistent with peripheral arterial vasoconstriction during the early phases of treadmill exercise. Such paradoxical vasoconstrictive responses were not observed in normal subjects and, therefore, they may represent generalized vascular pathology secondary to atherosclerosis.

Long-term sleep disturbances in adolescents after minor head injury.

It has been demonstrated that patients in the acute phase after minor head injury (MHI) complain of sleep disturbances. The purpose of the present study was to characterize the long-term effects of MHI on sleep in adolescents. Nineteen adolescents who had suffered MHI 3 years before the study and had complained of sleep disturbances completed a sleep questionnaire and were investigated in the sleep laboratory by whole-night polysomnographic recordings and were actigraphically monitored for 5 days at home. Questionnaire results revealed severe complaints regarding sleep behavior. Polysomnographic recordings revealed that in comparison with controls, MHI was associated with lower sleep efficiency (79.8 +/- [9.8]% vs 87.7 +/- [6.8]%; P < 0.005), with more wake time (10.6 +/- [9.0]% vs 3.4 +/- [4.4]%; P < 0.005), and with more awakenings lasting more than 3 minutes (2.1 +/- [1.5] vs 0.6 +/- [0.8]; P < 0.005). These findings were confirmed by actigraphic monitoring that revealed lower sleep efficiency (90 +/- [5]% vs 94 +/- [3]%; P < 0.05), more minutes of wake time (49 +/- [21] min vs 28 +/- [15] min; P < 0.05), and a trend toward more awakenings longer than 5 minutes (1.8 +/- [0.8] vs 1.2 +/- [0.8]; P = 0.063). Our data demonstrated that 3 years after MHI without any discernible clinical sequel, adolescents still complain of sleep disturbances that could be confirmed by both polysomnographic and actigraphic monitoring.

Increased prevalence of obstructive sleep apnea syndrome in obese women with polycystic ovary syndrome.

Obstructive Sleep Apnea (OSA) is considerably more common in men than women. Preliminary data suggest that androgens may play a role in the male predominance of apnea. Polycystic Ovary Syndrome (PCOS) is characterized by menstrual disturbances, androgen excess, and frequently obesity. These features suggest that women with PCOS may be at increased risk for OSA. To determine whether obese women with PCOS have an increased prevalence of sleep apnea compared with age and weight-matched reproductively normal women, we performed overnight polysomnography for determination of the apnea-hypopnea index (AHI) in 18 obese women with PCOS and age and weight-matched control women. Additional measurements included waist, hip, and neck circumferences, serum total testosterone, unbound testosterone, and DHEAS. Women with PCOS had a higher AHI than controls (22.5 +/- 6.0, vs. 6.7 +/- 1.0, P = 0.008). Women with PCOS were also more likely to suffer from symptomatic OSA syndrome (44.4% vs. 5.5%, P = 0.008). AHI correlated with waist-hip ratio (r = 0.51, P < 0.03), serum testosterone (r = 0.52, P < 0.03) and unbound testosterone (r = 0.50, P < 0.05) in women with PCOS. We conclude that obese women with PCOS are at increased risk of OSA when compared with matched reproductively normal women. Women with PCOS should be carefully questioned regarding symptoms of sleep apnea.

Airway mechanics and ventilation in response to resistive loading during sleep: influence of gender.

The male predominance in obstructive sleep apnea (OSA) is currently poorly understood although differences in pharyngeal airway anatomy and physiology have been proposed. As the response to inspiratory resistive loading (IRL) provides important information on both airway collapsibility (mechanics) and ventilatory control, we compared this respiratory response in eight normal women and eight age and body mass index (BMI)-matched men, during stable nonrapid eye movement (NREM) sleep. Upper airway mechanics, ventilation, plus activation of two dilator muscles (genioglossus [GG] and tensor palatini [TP]) were monitored during basal breathing (BL), followed by four sequentially applied loads (5, 10, 15, 25 cm H(2)O/L/s) for three breaths each. Men developed more severe hypopnea in response to identical applied external loads than did women. At a resistance of 25 cm H(2)O/L/s, VT decreased by 26 +/- 1% in women compared with 44 +/- 1% in men (differences between sexes p < 0.05). Pharyngeal resistance (Rpha) in response to IRL increased significantly more in men than women (37.3 +/- 11.2 cm H(2)O/L/s in men at maximal load, compared with an increase of 6.6 +/- 3.9 cm H(2)O/L/s in women, p < 0.05). Men and women had near identical minute ventilation responses to total load (applied extrinsic plus measured intrinsic), implying no differences in central drive or load response. There were no significant increases in GG or TP activation in response to IRL in either sex. We conclude that normal men are more vulnerable to load-induced hypoventilation than women, due to increased upper airway collapse, which could not be explained by differences in dilator muscle activation. This implies a fundamental difference in the upper airway anatomy and/or tissue characteristics between the two sexes.