24-hour Profile Research Articles

Pharmacodynamics and Pharmacokinetics Following Once-Daily and Twice-Daily Dosing of Tiotropium Respimat® in Asthma Using Standardized Sample-Contamination Avoidance.

Background: This study was conducted to confirm the 24-hour bronchodilator efficacy and pharmacokinetic profile of once-daily tiotropium Respimat® 5 μg add-on to inhaled corticosteroids (ICS) in adults with symptomatic asthma. It used a trial protocol designed to minimize the risk of pharmacokinetic sample contamination resulting from improper sampling procedure, sample handling, or device handling during priming and subsequent inhalation procedure.Methods: A Phase II, randomized, double-blind, two-way crossover study (NCT01696071) comparing two daily dosing regimens of tiotropium for 4 weeks, once-daily 5 μg (evening dosing) or twice-daily 2.5 μg (morning and evening dosing), as add-on to maintenance therapy with ICS (400–800 μg budesonide or equivalent) as controller medication. There was no washout between treatment periods.Results: An increase in the area under the curve of the 24-hour forced expiratory volume in 1 second profile from study baseline was observed following once-daily tiotropium 5 μg (217 mL) and twice-daily 2.5 μg (219 mL), with no difference between the two regimens (−2 mL [95% confidence interval: −38, 34]). In a subset of the study population, total tiotropium exposure, expressed as area under the plasma concentration versus time curve over 24 hours, was comparable between dosing regimens. Unexpected tiotropium plasma levels were observed in two patients, possibly because of contamination.Conclusions: The observed bronchodilator efficacy over 24 hours was similar with once-daily tiotropium 5 μg and twice-daily 2.5 μg as add-on to ICS therapy, supporting the suitability of once-daily dosing to provide sustained improvements in lung function in adults with symptomatic asthma.

PP.28.12] 24-HOUR PATTERNS OF CENTRAL AORTIC AND BRACHIAL SYSTOLIC BLOOD PRESSURE IN THE VERY ELDERLY

Objective: The aim of current study was to investigate and compare 24-hour profiles of central and peripheral blood pressures in the very elderly via their simultaneous ambulatory monitoring. Design and method: Parallel 24-h ambulatory aortic and brachial blood pressure monitoring was performed in 67 treated hypertensive subjects older than 80 years (mean age 84,1 ± 3,1 years, 25,5% male, mean clinic brachial SBP 134,8 ± 23,2 mmHg) with an oscillometric cuff-based device BPLab Vasotens («Petr Telegin», Russia). Patients with ejection fraction < 40%, atrial fibrillation and severe comorbidities were not included. 24-h, awake and sleep-time systolic, diastolic and pulse blood pressure in aorta and brachial artery were compared in subgroups divided according to the diurnal pattern of brachial systolic blood pressure (SBP). Results: The diurnal profiles of central systolic and pulse BPs run in parallel with those of peripheral BPs in patients with all types of diurnal pattern and SBP amplification at night did not change significantly comparing to day-time values. Non-dipping or reverse-dipping SBP patterns appeared to be typical and were observed in 82,1% patients, while 50,7% participants had inadequate DBP dip < 10%. The proportionality of night-time SBP and DBP changes varied in different types of SBP diurnal profile. SBP and DBP decreased proportionally in dippers (ratio of DBP/SBP night-time reduction was 1,18) and disproportionately in non-dippers (the ratio was 2,6). In those patients with reverse-dipping pattern SBP and DBP changed in opposite directions at night. This disproportion in SBP and DBP night-time changes resulted in different intensity of PP night-time rise that was most evident in reverse-dippers. Relative nocturnal reduction of PP was 9,3 ± 4,72% in dippers, whereas non-dippers and reverse-dippers had relative PP increase of 6,2 ± 8,6 and 22,9 ± 12,3 %, respectively. Conclusions: The diurnal patterns of central and brachial BPs observed in very elderly treated hypertensives were almost parallel. PP amplification is similar in the day- and nighttime and this finding is different from previously described diurnal PP amplification behavior in younger subjects. Proportionality of SBP and DBP sleep-time changes depends on dipping status and results in nocturnal PP increase in non- and reverse-dippers.

Comparison of Bruch's Membrane Opening Minimum Rim Width and Peripapillary Retinal Nerve Fiber Layer Thickness in Early Glaucoma Assessment.

To compare the diagnostic value of Bruch's membrane opening minimum rim width (BMO-MRW) and retinal nerve fiber layer thickness (RNFLT) in patients with ocular hypertension, preperimetric, and perimetric glaucoma. One hundred eighty-one eyes consisting of 40 healthy controls, 41 ocular hypertensive subjects, 50 subjects with preperimetric glaucoma and 50 with perimetric glaucoma were included. One randomly selected eye was included. All patients underwent slit-lamp examination, funduscopy, achromatic perimetry, and 24-hour IOP profile. Bruch's membrane opening-MRW and RNFLT (3 peripapillary circle scans, 12°/14°/16°) data were obtained using spectral domain optical coherence tomography. Areas under the receiver operating characteristics curves (AUROC) as well as sensitivity at fixed specificity were computed globally and for six vertical split sectors. Venn diagrams were plotted to identify patients that were diagnosed by one of the two parameters only. For RNFLT the smallest circle diameter showed highest diagnostic accuracy and was used for comparison with BMO-MRW. Distinguishing perimetric glaucoma, RNFLT and BMO-MRW showed comparable AUROCs in global (AUROC, 95% confidence interval: 0.954, 0.911-0.996 and 0.929, 0.872-0.986) and sectoral (0.929, 0.877-0.981 and 0.946, 0.904-0.996) analysis. For preperimetric glaucoma BMO-MRW and RNFLT also demonstrated comparable performance in global (0.839, 0.757-0.921 and 0.821, 0.731-0.912) and sectoral (0.860, 0.782-0.938 and 0.835, 0.750-0.920) analysis. When identifying ocular hypertensive eyes AUROCs were lower for global RNFLT and BMO-MRW (0.493, 0.365-0.621 and 0.562, 0.433-0.691). A combined parameter showed an AUROC of 0.959, 0.921 to 0.996 for perimetric and 0.849, 0.770 to 0.929 for preperimetric glaucoma. Bruch's membrane opening-MRW and RNFLT are comparably useful parameters for discrimination of preperimetric and perimetric glaucomatous eyes and show potential to assist each other in glaucoma diagnosis. (www.ClinicalTrials.gov number, NTC00494923; Erlangen Glaucoma Registry.).

Ultrasonic indicators of the heart and carotid arteries in arterial hypertension development in patients with chronic obstructive pulmonary disease

Aim. To specify the sequence of changes in the functional parameters of arterial hypertension in patients with chronic obstructive pulmonary disease and asthma according to the results of echocardiography, carotid arteries duplex scan and ambulatory blood pressure monitoring.Methods. Ambulatory blood pressure monitoring, tissue Doppler echocardiography and carotid artery duplex scan were performed in 160 patients with chronic obstructive pulmonary disease, arterial hypertension, asthma, and 33 apparently healthy volunteers of both sexes aged 39-70 years.Results. In patients with chronic obstructive pulmonary disease, an increase in hypertensive indices of time and area with the development of non-dipper or inverse-dipper 24-hour blood pressure profile disturbances is registered only at night hours. In chronic obstructive pulmonary disease, unlike asthma, carotid arteries thickening, combined hypertrophy and diastolic dysfunction of both ventricles develop. The prevalence of the thickening of «intima-media» complex and atherosclerotic plaques among patients with comorbid pathology (chronic obstructive pulmonary disease + arterial hypertension) occurs significantly more frequently than in the groups with hypertension or chronic obstructive pulmonary disease, confirming the synergistic effect of the considered nosologies on the atherosclerotic process.Conclusion. In patients with chronic obstructive pulmonary disease changes of the ultrasonic and functional indicators of the cardiovascular system, typical for arterial hypertension are registered starting with stage I and amplified with increase in the disease severity, leading to the need of diagnostic and therapeutic management correction.

Effect of Breakfast on the Exposure of the Once-Daily Tacrolimus Formulation in Stable Kidney Transplant Recipients.

The once-daily Tacrolimus formulation (Tac ONCE-DAILY) has to be taken on an empty stomach. This is inconvenient for patients and may hamper compliance. The influence of food intake on the exposure of Tac ONCE-DAILY is unknown in transplant recipients. We compared the pharmacokinetics (PKs) of Tac ONCE-DAILY in stable kidney transplant recipients under fasted and fed conditions. In an open-label, single-center, cross-over PK study, 27 stable kidney white transplant recipients (17 male, 10 female) treated with Tac ONCE-DAILY under fasted conditions were enrolled. Two 10-point 24-hour blood concentration time profiles [area under the blood concentration time curve from time 0 to 24 hours (AUC0-24)] were collected under steady state conditions. The primary objective was to investigate the effect of food on the PKs and relative bioavailability of Tac ONCE-DAILY. Twenty-seven stable renal transplant patients provided 1 AUC0-24 under fasted and fed conditions, respectively. AUC0-24, C24, and Cmax, were lower in the fed state and Tmax was 1 hour postponed. The 90% confidence interval ratio (fed: fasted) for AUC0-24 was 0.81-0.91 and for C24 0.82-0.92 (both P < 0.001). The majority (60%) had no significant change, but the change in AUC0-24 ranged from -38% to +29%. One trough level was below the target range after fed intake. When Tac ONCE-DAILY is ingested with standard continental breakfast, AUC0-24 and C24 decrease overall, with C24 in the therapeutic range in almost all patients. The convenient fed intake could promote therapy adherence. Given the possible significant change in exposure, we advise monitoring of the tacrolimus trough level 1 week after fed ingestion of Tac ONCE-DAILY.

Hypertension in Chronic Kidney Disease Part 2: Role of Ambulatory and Home Blood Pressure Monitoring for Assessing Alterations in Blood Pressure Variability and Blood Pressure Profiles.

Blood pressure (BP) is characterized by high variability, including changes beat-to-beat (very short term), within 24 hours (short term), from day to day (midterm), and between visits spaced by weeks, months, seasons, and even years (long term). These variations can be estimated by means of continuous beat-to-beat BP recordings, repeated conventional office BP measures, 24-hour ambulatory BP monitoring (ABPM), or home BP monitoring (HBPM) over longer time windows (Table). A main advantage of ABPM over other BP measurement techniques is represented by its ability to track BP changes occurring in daily life conditions and during 24 hours, thus allowing assessment of overall BP variability (BPV) as well as identification of its specific components, such as nocturnal hypertension and altered day-to-night BP profiles (ie, morning BP rise, nondipping pattern of BP) which become manifest early in the course of chronic kidney disease (CKD). These alterations are even more significant in subjects with end-stage renal disease (ESRD) mainly, but not exclusively, because of the marked reduction in intravascular volume immediately after hemodialysis followed by the progressive increase in volemia throughout the interdialytic period,2 combined with an enhanced sympathetic activity. The higher frequency of alterations in 24-hour BP profiles and BPV in subjects with CKD and in those with ESRD not only makes a proper assessment and achievement of BP control more difficult in these subjects but may be prognostically relevant on the background of the evidence from longitudinal and observational studies indicating that increased BPV may predict the development of cardiovascular and renal disease, over and above the contribution of elevated mean BP levels per se3–11 (Figure 1). The purpose of this review is to address the currently available evidence on the role of ABPM and HBPM for the assessment and management of alterations in circadian BP profiles …

The impact of a low glycaemic index (GI) diet on simultaneous measurements of blood glucose and fat oxidation: A whole body calorimetric study

ObjectiveLow glycaemic index (GI) foods are known to minimize large fluctuations in blood glucose levels and have been suggested to increase fat oxidation. The objective of this study was to simultaneously investigate glucose excursion and substrate oxidation in a whole body calorimetre when Chinese male subjects were provided a low or high GI meal. Materials/MethodsIn a randomized, controlled crossover non blind design, 12 healthy Chinese male adults (BMI 21.8 ± 1.3 kgm−2) attended two sessions consisting of either four low or high glycaemic meals (LGI vs HGI). Breakfast, lunch and snack were consumed in a whole body calorimetre while dinner was consumed at home. Daily changes in glycaemic response (GR) and postprandial GR responses were measured using a continuous glucose monitoring system. The GR was further calculated to obtain the incremental area under the curve (iAUC) for glucose concentrations. Glycaemic variability was calculated as mean amplitude of glycaemic excursion (MAGE). Substrate oxidation was calculated by measuring respiratory quotient and urine nitrogen excretion. ResultsAfter LGI meals in the whole body calorimetre, iAUC for glucose (P = 0.008) was lower compared to the HGI session. The HGI treatment produced a significantly greater MAGE than the LGI treatment over the 24 hour period (P < 0.001). Additionally, higher fat oxidation and lower carbohydrate oxidation were observed following breakfast and lunch when comparing LGI to HGI (P < 0.05) ConclusionsConsumption of LGI meals was capable of attenuating 24-hour blood glucose profiles and decreasing postprandial glucose excursions in healthy Asian males. Additionally, LGI mixed meals were able to promote fat oxidation over carbohydrate oxidation when compared to HGI mixed meals. The consumption of low GI meals may be a strategic approach in improving overall glycaemia and increasing fat oxidation in Asians consuming a high carbohydrate diet.

Risk of nephrolithiasis, hyperoxaluria, and calcium oxalate supersaturation increased after Roux-en-Y gastric bypass surgery: a systematic review and meta-analysis

BackgroundEarlier publications have shown renal stone complications after bariatric surgery. Multiple reports have also linked metabolic changes that alter the urinary chemistry profiles, especially hyperoxaluria, after bariatric surgery. However, evidence on change of other urine chemistry studies and type of bariatric surgery and risk of stone has been inconclusive so far. ObjectivesTo explore the association between bariatric surgery and postoperative urinary chemistry change and risk of stone formation SettingA systematic review and meta-analysis. MethodsWe comprehensively searched the databases of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from their dates of inception to January 2016. The inclusion criteria were published studies of association between bariatric surgery and postoperative renal stone formation or urine chemistry profiles. We used random-effects model meta-analysis and calculated the pooled risk of renal stone and difference in 24-hour urine chemistry profiles. ResultsTwelve observational studies were included in the meta-analysis. There was significantly higher risk of stone formation after Roux-en-Y gastric bypass surgery with pooled relative risk = 1.79 (95% CI: 1.54–2.10). In the analysis of urine chemistry profiles, there was significantly higher calcium oxalate supersaturation, lower citrate, and lower volume postoperatively compared with preoperatively. There was also higher urine oxalate in patients who had bariatric surgery compared with nonsurgery controls. ConclusionsRoux-en-Y gastric bypass surgery is associated with higher risk of renal stone and increased urine oxalate and calcium oxalate supersaturation.

Confocal Laser Scanning Tomography to Predict Visual Field Conversion in Patients With Ocular Hypertension and Early Glaucoma.

To compare Moorfields regression analysis (MRA), Glaucoma probability score (GPS), and different discriminant functions to predict future visual field conversion of patients with ocular hypertension and early glaucoma. The study included 120 eyes of patients with ocular hypertension and 110 eyes of patients with early glaucoma from the Erlangen glaucoma registry. Annually, all patients underwent standard automated perimetry, 24-hour intraocular pressure profile, optic disc photography, and HRT (Heidelberg Retina Tomograph I-III; Heidelberg Engineering) measurements. The cohort was divided into 2 groups based on the development of repeatable glaucomatous visual fields. Positive predictive values and negative predictive values were compared for MRA, GPS, and the classification of Bathija, Iester, Mardin, and Mikelberg at baseline. Kaplan-Meier Survival curves and Logrank tests were used to evaluate equality of survival distributions for different test results. Median follow-up was 9.04 years. 26 eyes (11.3%) demonstrated glaucomatous visual field loss in the follow-up. MRA temporal-superior and temporal-inferior outside normal limits were predictive of future visual field loss with positive predictive values of 33.3% and 28.6%. Normal GPS Temporal Sector demonstrated a negative predictive value of 96.4% and normal results in discriminant functions between 94.7% and 95.5%. Confocal scanning laser tomography is a useful imaging modality to predict future visual field conversion. Development of visual field defects in 10 years is highly unlikely, if GPS classification and/or classification of discriminant analysis at baseline are normal. MRA temporal-superior and temporal-inferior outside normal limits are associated with future VF conversion (ClinicalTrials.gov number, NCT00494923).

Smart Hybrid Energy Storage for Stand-Alone PV Microgrid: Optimization of Battery Lifespan through Dynamic Power Allocation

Battery as the key component in stand-alone PV microgrid system tends to be the most vulnerable element in terms of durability. Poorly managed battery charge/discharge process turns out to be one of the main life-limiting factors. To improve the longevity of battery storage system, a novel energy storage system topology and its smart power management strategy is presented in this paper. This paper proposes a stand-alone 6 kW PV microgrid system with hybrid energy storage system that combines supercapacitors and batteries. Smart power allocation strategy among the SC and the battery modules is designed to dynamically allocate the power to optimally charge/discharge the batteries while fulfilling the variations in supply and load. The performance of the proposed system is evaluated via model simulation using Matlab/Simulink. The system is simulated under a typical 24-hours residential load profile and the results proved that the proposed system can provide sufficient power to regulate the fluctuations in supply and load. During the process, the batteries are charged / discharged with ideal charge rate and operated under a low depth-of-discharge that have proven to prolong the battery lifetime.

Optimizing Blood Sampling Protocols in Patients With Acromegaly for the Estimation of Growth Hormone Secretion.

Optimal blood sampling schemas of GH for the estimation of the 24-hour secretion rate have not been established in acromegalic patients. By censoring available 24-hour GH serum profiles, we investigated the reliability of such simplified schemas. Design, Subjects, and Methods: We used 24-hour serum GH concentration profiles obtained with 10-minute sampling in a large cohort of healthy subjects (n = 130; mean age, 42; range, 18-77 years) and acromegalic patients (n = 87; mean age, 48; range 18-72 years). Patient categories were active disease, surgically cured, and somatostatin analog-treated individuals. The regression coefficients of determination (R(2)) and the linear slopes (β) between 24-hour secretion rates or mean concentrations (144 samples) on the one hand and mean values with less frequent sampling on the other, decreased in controls and in patients a short (1-2 weeks) or long (2-5 years) time after successful surgery. By contrast, the regression parameters remained essentially unchanged in patients with active acromegaly and those under GH suppressive treatment. Excellent correlations (R(2) ≥ 0.90) without GH underestimation existed between mean GH of daytime profiles and mean GH of 24-hour profiles and GH secretion rates estimated by deconvolution in patients with active acromegaly and patients treated with somatostatin analogs. Simplified sampling schemes, particularly a day profile, can be used for the estimation of GH secretion in patients with active acromegaly and under medical treatment. However, in healthy controls and patients after successful surgery, prolonged and frequent sampling schemes, at least at 2-hour intervals, reliably reflect 24-hour secretion.

The Effect of Long-term Antiglaucomatous Drug Administration on Central Corneal Thickness.

To evaluate rates of changes per year of central corneal thickness after antiglaucomatous drug administration with β-blockers, prostaglandin analogs, and carbonic anhydrase inhibitors monotherapy and combined topical antiglaucomatous therapy, in a cohort of patients with ocular hypertension, glaucoma suspects, and patients with perimetric glaucoma as compared with normal controls. This retrospective single-center study included 130 eyes as healthy controls, 121 eyes of ocular hypertensive patients, 105 eyes of glaucoma suspects, and 49 eyes of perimetric glaucoma patients. All patients underwent standard automated perimetry, 24-hour intraocular pressure profile, optic disc photography, and optical coherence pachymetry (OCP; Heidelberg Engineering). The cohort was divided into 8 groups on the basis of topical antiglaucomatous medication. Linear regression analysis was conducted to analyze the relationship between central corneal thickness and exposure to antiglaucomatous medication during the follow-up. Central corneal thickness did not change during the follow-up for investigated diagnostic subgroups. There was a statistically significant decrease in central corneal thickness for eyes treated with prostaglandin monotherapy (-3.1 μm/y for left eye), and a combined therapy with prostaglandins, carbonic anhydrase inhibitors, and β-blockers (-5.8 and -3.8 μm/y for right and left eye, respectively). We recommend regular measurements before and during therapy with prostaglandin monotherapy and a combined therapy with prostaglandins, carbonic anhydrase inhibitors, and β-blockers. Follow-up intraocular pressure measurements may be underestimated for eyes treated with the aforementioned treatment regimens if central corneal thickness is not measured on a regular basis.

In silico diabetology

Simulation models can contribute substantially to our understanding and ability to control the dynamic processes underlying impaired glucose metabolism in diabetic patients. The aim of this paper is to outline a new comprehensive, physiologically-based dynamic model of glucose homeostasis incorporating up-to-date quantitative knowledge about glucose metabolism and its control by insulin and glucagon. The model is composed of three submodels for glucose, insulin, and glucagon. The glucose submodel specifies the dynamics of glucose absorption following meals, hepatic glucose production and uptake, peripheral glucose uptake, kidney excretion, and insulin-independent uptake of glucose in the brain and red blood cells. The insulin submodel includes equations for insulin absorption, pancreatic insulin release and insulin clearance. The glucagon model specifies the hormone secretion and elimination kinetics. Algebraic equations are used to specify (i) how the hormones affect glucose production and utilisation in various compartments such as liver, muscle and fat tissues, and (ii) how glucose levels modify insulin and glucagon release from the pancreas. Setting the values of various model parameters is used to generate virtual individual patients. The model allows the simulation of 24-hour blood glucose profiles for both insulin-dependent non-insulin dependent diabetic patients.

Prevalencia y percepción de la variabilidad diaria de los síntomas en pacientes con enfermedad pulmonar obstructiva crónica estable en España

IntroductionFew studies have examined the 24-hour symptom profile in patients with chronic obstructive pulmonary disease (COPD). The main objective of this study was to determine daily variations in the symptoms of patients with stable COPD in Spain, compared with other European countries. MethodsObservational study conducted in 8 European countries. The results from the Spanish cohort (n=122) are compared with the other European subjects (n=605). We included patients with COPD whose treatment had been unchanged in the previous 3months. Patients completed questionnaires on morning, day-time, and night-time symptoms of COPD, the COPD assessment test (CAT), the hospital anxiety and depression scale (HADS), and the COPD and asthma sleep impact scale (CASIS). ResultsMean age: 69 (standard deviation [SD]=9) years; mean post-bronchodilator FEV1: 50.5 (SD=19.4)% (similar in Spanish and European cohorts). The proportion of men among the Spanish cohort was greater (91.0% versus 60.7%, P<.0001). A total of 52.5% patients experienced some type of symptom throughout the day, compared to 57.5% of the other Europeans, P<.001). Patients with symptoms throughout the day had poorer health-related quality of life (HRQoL) and higher levels of anxiety/depression than patients without symptoms. Patients with night-time symptoms had a poorer quality of sleep. Spanish patients with symptoms throughout the day had higher CAT scores (16.9 versus 20.5 in the other Europeans, P<.05). ConclusionsDespite receiving treatment, more than half of patients report symptoms throughout the day. These patients have poorer HRQoL and higher levels of anxiety/depression. Among patients with similar lung function, the Spanish cohort was less symptomatic and reported better HRQoL than other Europeans.

COMPARISON OF EFFECTIVENESS OF COMBINATION ANTIHYPERTENSION THERAPY IN WOMEN WITH ABDOMINAL OR GLUTEO-FEMORAL OBESITY

Aim. To study the influence of combinational antihypertension therapy including inhibitor of angiotensin converting enzyme (ACEi) or direct renin inhibitor (DRI) on the parameters of 24-hour blood pressure monitoring (ABPM) in postmenopausal women in different obesity patterns. Material and methods. Totally, 168 women studied with arterial hypertension (AH) in postmenopause: 97 with abdominal obesity (AO) and 71 with gluteofemoral (GFO). Patients were randomized to groups of ACEi therapy and diuretic or DRI and diuretic. Follow-up lasted for 24 weeks. Results. In 4 weeks of therapy with the usage of maximal ACEi dosages, target level of blood pressure (BP) was reached in 30 from 42 (71,4%) women with AO and 27 from 32 (84,4%) with GFO, and maximum dose of DRI led to target pressure achievement in 37 from 41 (90,2%) women with AO and 30 from 33 (90,9%) with GFO. Others required addition to the therapy a dihydropyridine calcium antagonist. In 6 months of therapy in all groups of patients there was positive dynamics of the main 24-hour profile parameters. Conclusion . Combination of ACEi or DRI with indapamide retard have significant antihypertension effect in women with AH in AO and GFO. In addition, combination of DRI with diuretic is better than of ACEi that was showed by the prevalence and speed of target BP achievement, more significant dynamics of ABPM parameters and positive changes in patients spread upon physiologic and pathologic types of 24-hour profile in 24-week therapy, especially in AO.

Contact Lens Sensor Triggerfish – What Do We Know?

Multiple measurements of the intraocular pressure (IOP) at different times during the day and at night provide information on the peak and trough values, and the number and magnitude of short- and long-term fluctuations. Goldmann applanation tonometry (GAT) is generally used only once or a few times during office hours. The ideal would be a safe, well-tolerated, and valid 24- hour measurement. The contact lens sensor Triggerfish® (SENSIMED AG, Lausanne, Switzerland) is claimed to measure changes in corneal curvature induced by changes in IOP. After animal experiments, multiple studies in healthy and glaucoma patients were performed, in some cases revealing good correlation with tonometer values, in others poor or no correlation at all. The interpretation of the 24-hour profiles is not standardised, and there is no agreement upon definition of a fluctuation. Comparability between mmHg and an electrically measured value cannot be established. Despite the fact that safety and tolerability of the device are good, the absence of definitive validation of the results means that the product cannot yet be recommended for daily clinic or office use. This product is also no longer marketed as providing ‘24- hour IOP profile’ or ‘continuous monitoring of IOP fluctuation’, but now rather as recording a ‘24-hour profile of ocular dimensional changes’.

Betel Nut Chewing: An Unrecognized Cause of Milk Alkali Syndrome

ABSTRACT Objective: To describe an uncommon case of milk alkali syndrome from betel nut chewing. A 60-year-old Pakistani woman was referred to the Endocrinology Clinic for hypercalcemia. She reported a history of type 2 diabetes mellitus, hypothyroidism, anxiety, and renal stones. She denied symptoms of hypercalcemia. However, her serum calcium levels were noted to be above the upper end of reference range but consistently below 11 mg/dL. She was noted to have alkalosis and low parathyroid hormone levels, despite a normal renal function. A 24-hour urine stone profile revealed high-normal urine calcium and low urine citrate levels. Upon further history, it was noted that she avidly chewed betel nut up to 15 times a day, along with lime paste and tobacco paste. She was physically and psychologically addicted to this process. She was also taking calcium supplementations. On exam, she was noted to have dark pigmentation of her tongue from chronic use of lime paste and retention of betel nut in her mouth. Meth...

The Protective Effect of Beraprost Sodium on Diabetic Nephropathy by Inhibiting Inflammation and p38 MAPK Signaling Pathway in High-Fat Diet/Streptozotocin-Induced Diabetic Rats.

Background. p38 mitogen-activated protein kinase (MAPK) plays a crucial role in regulating signaling pathways implicated in inflammatory processes leading to diabetic nephropathy (DN). This study aimed to examine p38 MAPK activation in DN and determine whether beraprost sodium (BPS) ameliorates DN by inhibiting inflammation and p38 MAPK signaling pathway in diabetic rats. Methods. Forty male Sprague Dawley (SD) rats were randomly divided into the normal control group, type 2 diabetic group, and BPS treatment group. At the end of the 8-week experiment, we measured renal pathological changes and the activation of the p38 MAPK signaling pathway and inflammation. Result. After BPS treatment, renal function, 24-hour urine protein, lipid profiles, and blood glucose level were improved significantly; meanwhile, inflammation and the expression of p38 MAPK signaling pathway in the diabetic kidney were attenuated. Conclusions. BPS significantly prevented type 2 diabetes induced kidney injury characterized by renal dysfunction and pathological changes. The protective mechanisms are complicated but may be mainly attributed to the inhibition of the p38 MAPK signaling pathway and inflammation in the diabetic kidney.

Melatonin and cortisol profiles in late midlife and their association with age-related changes in cognition.

Previous studies have reported an association between circadian disturbances and age-related cognitive impairment. The aim was to study the 24-hour profiles of melatonin and cortisol in relation to cognitive function in middle-aged male subjects. Fifty healthy middle-aged males born in 1953 were recruited from a population-based cohort based on previous cognitive assessments in young adulthood and late midlife. The sample included 24 cognitively high-functioning and 26 cognitively impaired participants. Saliva samples were collected every 4 hours over a 24-hour period and analyzed for cortisol and melatonin levels by immunoassay. All participants exhibited clear circadian rhythms of salivary melatonin and cortisol. Salivary melatonin concentrations had a nocturnal peak at approximately 4 am. The median nocturnal melatonin response at 4 am was significantly lower in the cognitively impaired group than in the high-functioning group (−4.6 pg/mL, 95% CI: −7.84, −1.36, P=0.006). The 24-hour mean melatonin concentration (high-functioning group: 4.80±0.70 pg/mL, vs cognitively impaired group: 4.81±0.76 pg/mL; P>0.05) (or the area under the curve, AUC) was not significantly different between the two groups. Cortisol levels were low during the night, and peaked at approximately 8 am. Median cortisol concentrations were similar at all times, as were the 24-hour mean cortisol concentrations and AUC. To the best of our knowledge, ours is the first study to assess circadian measures (ie, melatonin and cortisol) in healthy middle-aged men with different cognitive trajectories in midlife. We found evidence of altered circadian rhythms with a reduced nocturnal melatonin response at 4 am in men with cognitive impairment. The 24-hour concentration and AUC of melatonin and cortisol were similar in the cognitively high-functioning group and in the cognitively impaired.

EPIDEMIOLOGY OF ISCHEMIC HEART DISEASE AND ATHEROSCLEROSIS RISK FACTORS IN IMPRISONED MEN

Aim. To reveal prevalence of coronary heart disease (CHD), arterial hypertension (AH) and risk factors for atherosclerosis (RFA) in men sentenced to imprisonment and to evaluate efficacy of secondary prevention for those with CHD and AH. Material and methods. An epidemiological study conducted with 986 imprisoned men at the age 21-69 y.o., included 24-hour blood pressure monitoring (APBM) and ECG monitoring (Holter) within random selection; evaluation of efficacy of complex medical-psychological monitoring (pharmacotherapy + medical enlightenment) in 46 persons with CHD and AH. Results. A high prevalence of CHD was established (15,6%), myocardial infarction (7,6%), AH (49,8%), cardiac rhythm disorders (CRD, 35,3%), borderline psychic disorders (89,2%), smoking (96,0%), alcohol consumption (AC, 96,9%), low physical activity (89,2%), left ventricle hypertrophy (52,3%), anxiety (49,7%), depression (39,5%) and their concomitance (85,0-92,0%); very low level of an existence of AH acknowledgement (10,3%), of CHD (1,6%) and CRD (4,7%). In ABPM and Holter first time were found disorders of 24-hour profile in all persons with AH and also hypertension reactions (66,6%) in normal BP, as deviations of coronary flow — episodes of transient myocardial ischemia (66,6%) and CRD (33,3%). Thanks to the treatment-educational complex, efficacy was marked in 80,0% prisoners of the 1st group, 87,5% — of the 2nd group and 93,3% — of the 3rd. Conclusion. First time a significant prevalence revealed of CHD and AH, of CRD and RFA, significant deviations of peripheral and coronary flow in isolated persons, therapeutical efficacy of secondary prevention (80,0%-93,3%) among prisoners with CHD and AH.