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J E Dimsdale

Publications and source records attributed to J E Dimsdale.

At least 19 recordsLinked to original sources

Severe irritability associated with statin cholesterol-lowering drugs.

BACKGROUND: As use of a drug becomes widespread, the full spectrum of its effects becomes clearer. Although a link has been suggested between low or lowered cholesterol and irritability/aggression, less is known about possible links between irritability and statins. AIM: To assess the possible connection of statin usage to severe irritability. DESIGN: Case series. METHODS: Six patients referred or self-referred with irritability and short temper on statin cholesterol-lowering drugs completed a survey providing information on character of behavioural effect, time-course of onset and recovery, and factors relevant to drug adverse effect causality. RESULTS: In each case the personality disruption, once evident, was sustained until statin use was discontinued; and resolved promptly with drug cessation. In four patients, re-challenge with statins occurred, and led to recrudescence of the problem. All patients experienced other recognized statin adverse effects while on the drug. Manifestations of severe irritability included homicidal impulses, threats to others, road rage, generation of fear in family members, and damage to property. DISCUSSION: Case series invariably raise more questions than they can answer. These case reports suggest that severe irritability may occur in some statin users. Although this adverse effect may be rare, potentially life-threatening adverse effects of drugs must be taken seriously.

Aged↗

Opioids, sleep, and cancer-related fatigue.

Oddly enough, little is known about the effects on sleep of commonly administered analgesic medications. Even less is known about their effect on next-day fatigue, mood, and cognitive functioning. We speculate that part of the fatigue typically experienced by cancer patients can be attributed to disruption of sleep by opioid medications they are taking. Fatigue and sleep are critical to the quality of life of cancer patients. Research is needed to assess the sleep and next-day consequences that can be expected from typical doses of different types of pain medications.

Fatigue↗

Types of coping strategies are associated with increased depressive symptoms in patients with obstructive sleep apnea.

STUDY OBJECTIVES: Some, but not all, researchers report that obstructive sleep apnea (OSA) patients experience increased depressive symptoms. Many psychological symptoms of OSA are explained in part by other OSA comorbidities (age, hypertension, body mass). People who use more passive and less active coping report more depressive symptoms. We examined relationships between coping and depressive symptoms in OSA. SETTING: N/A. DESIGN/PARTICIPANTS: 64 OSA (respiratory disturbance index (RDI) > or = 15) patients were studied with polysomnography and completed Ways of Coping (WC), Profile of Mood States (POMS), Center for Epidemiological Studies-Depression (CESD) scales. WC was consolidated into Approach (active) and Avoidance (passive) factors. Data were analyzed using SPSS 9.0 regression with CESD as the dependent variable and WC Approach and Avoidance as the independent variables. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: WC Approach factor (B=-1.105, beta=-.317, p=.009) was negatively correlated and WC Avoidance factor (B=1.353, beta=.376, p=.007) was positively correlated with CESD scores. These factors explained an additional 8% of CESD variance (p<.001) beyond that explained by the covariates: demographic variables, RDI, and fatigue (as measured by the POMS). CONCLUSIONS: More passive and less active coping was associated with more depressive symptoms in OSA patients. The extent of depression experienced by OSA patients may not be due solely to effects of OSA itself. Choice of coping strategies may help determine who will experience more depressive symptoms.

Adaptation, Psychological↗

Short-term hyperglycemia induces lymphopenia and lymphocyte subset redistribution.

Alterations in lymphocytes are a common finding in both type I and type II diabetes. Autoimmune phenomena in type I diabetes, the stage of the diabetic disorder and metabolic effects of therapeutic interventions may also affect actual distribution of lymphocyte phenotypes. This study investigated immunological effects specific to standardized hyperglycemia in non-diabetic individuals to exclude immunological changes potentially related to diabetes stage and treatment. 37 subjects (mean age +/- SD 39 +/- 5 years) underwent a sequence-controlled crossover with oral administration of a solution containing either 75 g glucose or artificial sweetener (i.e. placebo). At rest and at two hours, counts of white blood cells (WBC), mixed lymphocytes, mature T-cells (CD3), T-helper cells (CD4), T-suppressor/ cytotoxic cells (CD8), B-cells (CD19), natural killer cells (CD16/CD56), and interleukin-2 receptor bearing peripheral blood mononuclear cells (CD25) were measured by flow cytometry. Subjects showed a significant decrease in WBC, lymphocytes, and all lymphocyte subsets with the OGTT compared with the placebo solution (p < .05 to p < .001). In non-diabetic individuals, short-term hyperglycemia induces immunological changes that may be relevant to explain similar findings in patients with diabetes mellitus. Future studies need to validate these findings and their potential clinical implications in a diabetic population.

Adult↗

Sleep quality and blood pressure dipping in obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with poor sleep quality and a high incidence of nondipping. The aim of this study was to determine the association of sleep quality and nocturnal blood pressure (BP) dipping in an OSA population. METHODS: A total of 44 untreated subjects with mild to severe OSA underwent overnight-attended polysomnography and 24-h ambulatory BP monitoring. Subjects were off antihypertensive medication. The percentage of slow wave sleep, percentage of time awake after sleep onset during the sleep period, sleep efficiency, and arousal index were chosen as measurements of sleep quality. Dipping was evaluated using the change in systolic BP, diastolic BP, and mean arterial pressure. Patients were classified as dippers and nondippers based on a nocturnal drop in mean arterial pressure > 10%. Differences between groups were evaluated by independent sample t tests. Pearson correlation and linear regression were used to evaluate the association of sleep quality and dipping. RESULTS: There were no differences between dippers and nondippers with regard to body mass index, age, or respiratory disturbance index. A total of 84% were nondippers. No difference was found between dippers and nondippers in sleep quality. None of the sleep quality measures correlated with the measurements of dipping. In multiple regression analyses, the percentage of slow wave sleep and arousal index each independently predicted only a small percentage of the variance (approximately 10%) of nocturnal DBP dipping. CONCLUSIONS: The prevalence of nondipping was very high in a population of untreated patients with mild to severe OSA. Nonetheless, sleep quality did not appear to be related to BP dipping.

Adult↗

Association between polysomnographic sleep measures and health-related quality of life in obstructive sleep apnea.

Many facets of health-related quality of life are diminished in obstructive sleep apnea (OSA) as they are in other chronic medical conditions. We speculated that impairment in health-related quality of life (HRQoL) might result from the fatigue and daytime somnolence associated with the sleep disorder, as an indirect result from the fragmentation of night-time sleep in OSA. Our hypothesis was that sleep fragmentation measures would correlate with poorer HRQoL measured by medical outcomes study (MOS) subscales. Thirty-nine patients with polysomnographically-confirmed OSA participated in this study. Pearson's correlations were performed with the following sleep architecture variables: wake after sleep onset, the total number of brief arousals, the number of respiratory-related arousals, the rate of respiratory events per hour, and total sleep time. To our surprise, although the total number of arousals was associated with health distress (r=-0.481, P < 0.005), it did not correlate with any other subscales indicating poorer physical and mental health. The relatively insensitive measure of total sleep time (TST) correlated in the expected direction with most subscales. However, after controlling for age and gender, respiratory disturbance indices (RDI) and/or number of arousals emerged as significantly associated with mobility, cognitive functioning, social functioning, energy and fatigue, and health distress. Our findings suggest that polysomnographic indicators of sleep quality and sleep continuity may be an important influence determining many aspects of HRQoL in OSA patients.

Adult↗

Decrease in the plasma von Willebrand factor concentration following glucose ingestion: the role of insulin sensitivity.

Elevated plasma von Willebrand factor (vWF) concentration is thought to be associated with increased prevalence of cardiovascular events in the insulin resistance syndrome. We examined the effects of oral glucose challenge and accompanying metabolic and hemodynamic changes on vWF levels with respect to insulin sensitivity. Forty normotensive and hypertensive subjects (mean age +/- SD, 40 +/- 5 years) underwent a standard oral glucose tolerance test (OGTT). Plasma vWF antigen, glucose, insulin, catecholamines, and hemodynamics were measured at rest, and at 30, 60, 90, and 120 minutes after glucose intake. Insulin sensitivity was determined by the insulin sensitivity index (ISI(0,120)). Resting plasma vWF concentration was associated with screening systolic blood pressure (BP) (r =.43, P =.005). There were time effects for all variables of interest. While vWF antigen (P =.044), epinephrine (P =.003), and diastolic BP (P =.001) decreased after glucose challenge, norepinephrine (P =.009), systolic BP (P =.022), and heart rate (P <.001) increased. Decline in vWF (area under the curve) was associated with decrease in epinephrine (r =.46, P =.004) and with screening systolic BP (r =.45, P =.004). However, neither resting plasma vWF levels nor vWF decrease following glucose ingestion were significantly associated with the ISI(0,120.) The plasma vWF concentration decreases following glucose ingestion. While mechanisms underlying this phenomenon may relate to sympathetic nervous system function, they seem not related to insulin sensitivity. Endothelial dysfunction such as caused by hypertension rather than metabolic dysregulation per se may underlie the elevated plasma vWF concentration found with insulin resistance.

Adult↗

Obstructive sleep apnea and hypertension: are peripheral chemoreceptors involved?

The mechanism of pathogenesis of hypertension in patients with obstructive sleep apnea (OSA) is unknown. Many investigators point to the high sympathetic nervous system activity (SNS) observed in OSA patients. However, there is no clear explanation as to the mechanism for the development of SNS hyperactivity in these patients. A common feature of patients with OSA is repetitive bouts of transient hypoxemia during sleep. Repetitive transient hypoxemia in rats has resulted in hypertension. In OSA patients, resolution of nocturnal hypoxemia with CPAP has corrected nocturnal and diurnal hypertension. Also, exposure to hyperoxia reduces blood pressure and sympathetic activity in OSA patients, but not in normals. These data suggest a significant role of peripheral chemoreceptors in the regulation of vascular tone. We hypothesize that peripheral chemoreceptors significantly contribute to the pathogenesis of hypertension in patients with OSA and that this is associated with chemoreceptor hyperactivity. This implies that correcting the intermittent nocturnal hypoxemia alone may prevent the cardiovascular morbidity associated with obstructive sleep apnea.

Animals↗

The hypercoagulable state in sleep apnea is related to comorbid hypertension.

OBJECTIVE: Obstructive sleep apnea (OSA) is associated with increased prevalence of atherosclerotic disease. A hypercoagulable state thought to underly atherosclerosis has been described in both OSA and systemic hypertension. We wondered about the respective contribution of apnea and hypertension to a hypercoagulable state. DESIGN: Eighty-seven subjects with symptoms suggestive of OSA, mean age 47 years (range 32-64 years), underwent polysomnography and blood pressure (BP) screening. OSA was diagnosed when respiratory disturbance index (RDI) > or = 15. Subjects having systolic BP (SBP) > 140 mmHg and/or diastolic BP (DBP) > 90 mmHg were classified as having hypertension. Three hypercoagulability markers were measured: thrombin/antithrombin III complex (TAT), fibrin D-dimer (DD), and von Willebrand factor antigen (vWF:ag). RESULTS: Analysis of variance and multiple linear regression were performed on the following four subject groups: (1) normotensive non-apneics (n = 19), (2) normotensive apneics (n = 38), (3) hypertensive non-apneics (n = 11), and (4) hypertensive apneics (n = 19). OSA (groups 2 and 4) had no significant main effect on hemostasis. Hypertensives (groups 3 and 4) had higher plasma levels of TAT (median/inter-quartile range, 148/59-188 versus 77/53-108 pmol/l; P = 0.009) and of DD (376/265-721 versus 303/190-490 ng/ml; P = 0.040) than normotensives (groups 1 and 2). Across all subjects, SBP was the only significant predictor of TAT (P = 0.001) and of DD (P = 0.004), whereas DBP was the only significant predictor of vWF:ag (P = 0.029). These findings persisted even after controlling for gender, age, body mass index, RDI, mean SaO2, and hematocrit. CONCLUSION: Hypercoagulability in OSA is mediated by comorbid hypertension and might account for high cardiovascular morbidity in OSA in general.

Adult↗

Mood states and impedance cardiography-derived hemodynamics.

OBJECTIVE: This exploratory study investigated the relation between psychological mood states and hemodynamic variables obtained at rest. METHODS: We measured resting hemodynamic variables using impedance cardiography, blood pressure, heart rate, and the Profile of Mood States (POMS) in 71 participants. RESULTS: Mood states were not significantly associated with heart rate, systolic, diastolic, or mean arterial pressure. In comparison with these basic measures of physiology, a number of impedance derived measures of hemodynamics were associated with mood states. Log stroke volume was negatively correlated with POMS tension-anxiety (r = -.319, p = .009) and fatigue-inertia (r = -. 316, p = .009). Log cardiac output was negatively associated with fatigue-inertia (r = -.346, p < .01). Log total peripheral vascular resistance was positively correlated with POMS fatigue-inertia (r = .276, p = .024). CONCLUSIONS: Our findings suggest that mood states are associated with hemodynamic variables underlying blood pressure.

Adult↗

Response bias influences mental health symptom reporting in patients with obstructive sleep apnea.

The Medical Outcomes Study (MOS) inventory is widely used to assess quality of life in chronically ill patients. Although response bias was addressed during its initial validation, we are unaware ofsubsequent studies examining how personality characteristics influence responses on this instrument. We examined the impact of response bias on MOS data reported by 44 obstructive sleep apnea (OSA) outpatients who completed the MOS and Marlowe-Crowne Social Desirability Scale (MC). Social desirability implies responding in a way that the participant believes will be viewed favorably; MC is often used to statistically controlfor this form of response bias on self-report measures. The MOS yielded 2 summary scales (Mental and Physical Health) and 8 dimensions (based on Short Form-36 [SF-36]). Data were analyzed using multiple regression analyses. Results show that there is a significant relation between MC and the Mental and Physical Health factors (R2 = .194, F = 5.069, p = .011) and the eight SF-36 dimensions (R2 = .359, F= 2.448, p = .032). Post hoc analyses did not reveal that any one independent variable was a superior predictor of the MC. Participants scoring high on the MC reported 31% greater health than participants scoring low on the MC. Findings suggest that response bias has a significant influence on MOS data from OSA patients, with the greatest impact on mental health indexes. Controlling for response bias on the MOS and other self-report measures is important in both research and clinical situations with OSA and potentially other chronically ill patients.

Adult↗

Continuous positive airway pressure normalizes cardiac autonomic and hemodynamic responses to a laboratory stressor in apneic patients.

OBJECTIVES: We examined the effect of continuous positive airway pressure (CPAP) treatment for sleep apnea on cardiac contractility, heart rate variability, and hemodynamics at rest and in response to a laboratory stressor. SUBJECTS AND INSTRUMENTATION: Forty-one apneic patients were studied on three occasions: before treatment, after 1 full night of CPAP treatment, and after 1 week of CPAP treatment. The subjects were randomly assigned to receive effective treatment or placebo. Contractility and hemodynamics were determined with impedance cardiography, and parasympathetic activity was assessed by analysis of heart rate variability. Measures were determined at rest and in response to a stressor. DESIGN AND RESULTS: For the cardiac sympathetic (contractility) measures (preejection period, cardiac acceleration index [CAI], and low-frequency/high-frequency ratio) significant interactions were found in the combination treatment (CPAP vs placebo) by study day (day 1, day 3, day 11) by test period (baseline, preparation, talking) [p < 0.01]. For these measures, there were no differences between the treatment groups or responses to the stressor on day 1. Levels in placebo-treated subjects did not change or respond on the subsequent study days. In the CPAP-treated subjects, there was a decrease in these indexes at baseline, which became significantly lower by day 11 (ie, CAI levels were 24 Omega/s(2), 22 Omega/s(2), and 14 Omega/s(2) on day 1, day 3, and day 11, respectively). These measures also became responsive to the stressor by showing increased sympathetic activity (CAI levels on day 11 were 14 Omega/s(2) at baseline, 32 Omega/s(2) during speech preparation, and 36 Omega/s(2) while speaking). The parasympathetic indexes, such as high-frequency power or band of heart rate variability as determined by spectral analysis, showed a significant day-by-treatment interaction (p < 0.005), whereas the CPAP- treated group had significantly more parasympathetic activity after 1 week of treatment. For the hemodynamic measures (stroke volume [SV], cardiac output, and systemic vascular resistance [SVR]), there were significant treatment-by-study day-by-test-period interactions (p < 0.01). SV and cardiac output increased across days, and SVR decreased in the CPAP-treated patients. CONCLUSIONS: These results indicate that CPAP normalizes contractility, increases cardiac vagal tone, and changes hemodynamic regulation from being resistance dominated to being cardiac dominated. Thus, after 1 week of treatment with CPAP, many of the indicators of poor cardiac functioning in apnea patients are improved.

Adult↗

Effect of continuous positive airway pressure and placebo treatment on sympathetic nervous activity in patients with obstructive sleep apnea.

STUDY OBJECTIVES: We studied the effect of continuous positive airway pressure (CPAP) treatment on sympathetic nervous activity in 38 patients with obstructive sleep apnea. DESIGN: Randomized, placebo-controlled trial. SETTING: Patients underwent polysomnography on three occasions in a clinical research center, and had BP monitored over 24 h at home. All of the patients had sleep apnea with a respiratory disturbance index (RDI) > 15. INTERVENTIONS: The patients were randomized blindly to CPAP or placebo (CPAP at ineffective pressure) treatment. MEASUREMENTS AND RESULTS: Prior to therapy, the number of apneas and the severity of nocturnal hypoxia correlated significantly with daytime urinary norepinephrine (NE) levels, but not nighttime urinary NE levels. CPAP treatment lowered daytime BP from 99 +/- 2 mm Hg to 95 +/- 3 mm Hg (mean +/- SEM) and nighttime BP from 93 +/- 3 mm Hg to 88 +/- 3 mm Hg. Placebo CPAP treatment decreased both day and night mean BP only 2 mm Hg. CPAP, but not placebo, treatment lowered daytime plasma NE levels by 23%, daytime urine NE levels by 36%, daytime heart rate by 2.6 beats/min, and increased lymphocyte beta(2)-adrenergic receptor sensitivity (all p < 0.05). The effect of CPAP treatment on nighttime urine NE levels and heart rate did not differ from placebo treatment. There was a suggestion of an effect of placebo CPAP treatment on nighttime measures, but not on daytime measures. CONCLUSION: We conclude that daytime sympathetic nervous activation is greater with more severe sleep apnea. CPAP treatment diminished the daytime sympathetic activation; the potential nighttime effect of CPAP treatment was obscured by a small placebo effect.

Female↗

Does obstructive sleep apnea confound sleep architecture findings in subjects with depressive symptoms?

BACKGROUND: Compared with normal subjects, depressed patients have shorter rapid eye movement sleep latency (REML), increased REM and decreased slow wave sleep as a percentage of total sleep time (REM%, SWS%), and longer sleep latency (SL). Obstructive sleep apnea (OSA) patients experience longer REML, decreased REM% and SWS%, and shorter SL. We examined the interplay of depressive symptoms, OSA, and sleep architecture. METHODS: Subjects (n = 106) were studied with polysomnography. OSA was defined as a Respiratory Disturbance Index > or = 15. Subjects were divided into Hi/Lo groups using a Center for Epidemiological Studies-Depression (CES-D) score of 16. RESULTS: OSA patients had shorter SL than non-OSA patients (14.5 vs. 26.8 min, p <.001); Hi CES-D subjects showed a trend toward longer SL than Lo CES-D subjects (23.7 vs. 17.5 min, p =.079). Significant OSA x CES-D interactions emerged, however, for REM% (p =.040) and SL (p =.002): OSA/Hi CES-D subjects had higher REM% than OSA/Lo CES-D subjects (19.3% vs. 14.3%, p =.021); non-OSA/Hi CES-D subjects had SL (35.3 min) 2-3 times as long as other subjects (p =.002-.012). CONCLUSIONS: Because of the high prevalence of OSA and depression, findings suggest that OSA must be considered in studies of mood and sleep architecture. Conversely, depressive symptoms must be considered in studies of OSA and sleep architecture.

Adult↗

Plasma epinephrine levels in hypertension and across gender and ethnicity.

Epinephrine (E) infusions raise blood pressure and there is an excess incidence of hypertension among males and blacks. However, reports of E levels by ethnicity, gender, and blood pressure status are inconsistent. Insensitive assays, variability in plasma E levels within individuals, and the small size of most studies have contributed to these conflicting reports. We measured plasma E levels in a large diverse sample of subjects, using a highly sensitive assay. A total of 361 individuals participated in the study: 61% were men and 39% women, 74% were normotensive and 26% hypertensive, 59% were white and 41% were black. Except for difference in blood pressure and body mass index between the normotensives and hypertensives, subjects had similar baseline characteristics and took no antihypertensive medications for at least five days prior to sampling. All blood samples were collected after resting for a least 30 minutes following the insertion of an indwelling i.v. catheter. Catecholamine levels were determined using a radioenzymatic assay (assay sensitivities for E and norepinephrine were 6 pg/ml and 10 pg/ml, respectively). An ethnicity by gender interaction was found (F(1,315) = 5.126, p = .024). Subsequent analysis revealed that white women had significantly lower basal plasma E levels than white men (p <0.001) and black women (p = 0.036). There were no significant differences in E levels between black men and women or between white men and black men. Uncorrected E levels were lower in normotensive than hypertensive subjects (p = .009) but this difference was not significant when corrected for body mass index (BMI). Uncorrected norepinephrine levels were higher in women than men (p = .03) but the difference was no longer significant when corrected for BMI. Plasma E levels were significantly lower among white women than men or black women. In contrast to prior studies, E levels were lower in hypertensives, but this may reflect obesity among hypertensives.

Adult↗