Chirp-Evoked Auditory Brainstem Response in Children: A Review.

PURPOSE: The aim of this study was to assess the use of the chirp stimulus to record auditory brainstem responses in the pediatric population via a traditional review. METHOD: An electronic search of the literature and a hand search of the literature were conducted. Studies that utilized chirp stimuli within the pediatric population that met all of the inclusion criteria were included in this review. Qualitative synthesis and interpretation of the data were completed. RESULTS: Seven studies that met the inclusion criteria were included in the review. Chirp stimuli produce auditory brainstem response (ABR) waveform amplitudes in children similar to those in adults when presented at moderate to low frequency levels. Latency data from chirp stimuli are not consistent when stimulus presentation rates are altered. Test-retest reliability when using the chirp stimulus was found to be good, as were sensitivity and specificity of chirp-evoked ABRs utilized in a newborn hearing screening protocol. CONCLUSION: Reviewed studies indicated that when presented at 60 dB nHL or lower, broadband chirp-generated ABRs have larger amplitudes than click-generated ABRs in children with normal hearing. Utilization of chirp stimuli decreases test time because waveforms are easier to detect with increased synchronization. Further research should focus on correlating chirp thresholds with behavioral hearing thresholds. Given the variance of results in these select studies, future research should also evaluate latency findings and focus on developing normative data for infants with hearing impairment and normal hearing.

Preoperative housing in an enriched environment significantly reduces the duration of post-operative pain in a rat model of knee inflammation.

The influence of the environment on clinical post-operative pain received recently more attention in human. A very common paradigm in experimental pain research to model the effect of housing conditions is the enriched environment (EE). During EE-housing, rats are housed in a large cage (i.e. social stimulation), usually containing additional tools like running wheels (i.e. physical stimulation). Interestingly, only postsurgical housing effect on post-operative pain was developed during clinical and experimental studies while little is known on the influence of preoperative housing. In this study, our aim was to investigate the influence of housing conditions prior to an operation on the development of post-operative pain, using a rat model of carrageenan-induced inflammatory pain. Four housing conditions were used: a 3-week pre-housing in standard conditions (S-) followed by a post-housing in an EE; a 3-week pre-housing in EE followed by a post-operation S-housing; a pre- and post-housing in EE; a pre- and post-S-housing. The development of mechanical allodynia was assessed by the means of the von Frey test, preoperatively and at day post-operative (DPO) 1, 3, 7, 10, 14, 17, 21, 24 and 28. Our results show that a 3-week preoperative exposure to EE leads to a significant reduction in the duration of the carrageenan-induced mechanical allodynia, comparable with a post-operative exposure to EE. Strikingly, when rats were housed in EE prior to as well as after the carrageenan injection into the knee, mechanical allodynia lasted only 2 weeks, as compared to 4 weeks in S-housed rats.

Enriched environment and the recovery from inflammatory pain: Social versus physical aspects and their interaction.

In this study, we aimed at comparing the effect of the social versus the physical enrichment of the environment on inflammatory pain. Hence, a rat model of carrageenan-induced knee inflammation was used. Four housing conditions were investigated: a physically enriched environment (PE), a socially enriched environment (SE), an enriched environment (EE) (i.e. physically and socially enriched) and a restricted environment (RE) (i.e. non-physically or socially enriched housing). Mechanical allodynia was assessed using the von Frey test preoperatively and at day post-operative (DPO) 1, 3, 7, 10, 14, 17, 21, 24 and 28. Besides, anxiety was evaluated at DPO29, using the Elevated Plus-Maze test. Results show that RE housing resulted in a duration of mechanical allodynia of 4 weeks and of only 3 weeks in EE housing. Housing in a physically enriched environment also resulted in a reduction of the duration of mechanical allodynia of 1 week. Finally, if housed in a SE, the mechanical allodynia lasted for 3 weeks and an half. From these data, we conclude that both physical and social aspects of the environment are involved in the reduction of inflammatory pain duration, although the PE has a larger effect than the SE in this experimental setting. Interestingly, an inter-dependent relationship was noted between the PE and SE. Moreover, no significant difference in the rat anxiety was measured between groups, suggesting that the pain outcomes are likely not biased by the mean of potential housing condition-induced anxiety.

Association between white-coat effect and blunted dipping of nocturnal blood pressure.

BACKGROUND: In this study, we assessed whether the white-coat effect (difference between office and daytime blood pressure (BP)) is associated with nondipping (absence of BP decrease at night). METHODS: Data were available in 371 individuals of African descent from 74 families selected from a population-based hypertension register in the Seychelles Islands and in 295 Caucasian individuals randomly selected from a population-based study in Switzerland. We used standard multiple linear regression in the Swiss data and generalized estimating equations to account for familial correlations in the Seychelles data. RESULTS: The prevalence of systolic and diastolic nondipping (<10% nocturnal BP decrease) and white-coat hypertension (WCH) was respectively 51, 46, and 4% in blacks and 33, 37, and 7% in whites. When white coat effect and nocturnal dipping were taken as continuous variables (mm Hg), systolic (SBP) and diastolic BP (DBP) dipping were associated inversely and independently with white-coat effect (P < 0.05) in both populations. Analogously, the difference between office and daytime heart rate was inversely associated with the difference between daytime and night-time heart rate in the two populations. These results did not change after adjustment for potential confounders. CONCLUSIONS: The white-coat effect is associated with BP nondipping. The similar associations between office-daytime values and daytime-night-time values for both BP and heart rate suggest that the sympathetic nervous system might play a role. Our findings also further stress the interest, for clinicians, of assessing the presence of a white-coat effect as a means to further identify patients at increased cardiovascular risk and guide treatment accordingly.

Environmental housing affects the duration of mechanical allodynia and the spinal astroglial activation in a rat model of chronic inflammatory pain.

In this study, we aimed at investigating the effect of an enriched environment (EE) on the recovery from chronic inflammatory pain. Inflammatory pain was induced by the injection of 2 mg of carrageenan (CAR) into the right knee of male Sprague-Dawley rats (n=34). Rats were housed either singly (S-housed) or in an EE (EE-housed). The EE consisted of a large cage (L x W x H=2.0 x 1.0 x 0.8 m) containing various attributes (e.g. running wheels, shelter house, climbing frame). Withdrawal response to von Frey filament was used to assess mechanical allodynia at days post-operative (DPO) -1, 1, 7, 14, 21 and 28. S-housed animals showed a marked tactile sensitivity in the ipsilateral paw from DPO1 to DPO21. Four weeks after the CAR injection, S-housed rats were no longer allodynic. In contrast, EE-housed rats showed a significantly faster recovery: already at DPO21, they were no longer allodynic. In a first attempt to analyse the possible role of astroglial cells in the EE-induced effect, histological analysis at DPO21 was performed. Immunohistochemical staining of the spinal dorsal horn at L3-L5 indeed showed that spinal levels of astroglial activation are different between the two housing groups and therefore may play a role in the EE-induced effect on the duration of mechanical allodynia. In conclusion, our results showed that EE-housing results in a reduced duration of mechanical allodynia in chronic inflammatory pain in rats. Astroglial activation is suggested to be involved in this housing effect.

The CatWalk method: assessment of mechanical allodynia in experimental chronic pain.

The CatWalk gait analysis system has recently been suggested as a rapid and objective alternative method over the von Frey test to assess mechanical allodynia in chronic neuropathic pain models. Our results demonstrate that no correlation exists between the development of mechanical allodynia and changes in CatWalk-gait parameters in a chronic inflammatory pain model. Hence, the use of the CatWalk in assessment of experimental chronic pain is discussed.

Association of ABCB1 genetic variants with renal function in Africans and in Caucasians.

BACKGROUND: The P-glycoprotein, encoded by the ABCB1 gene, is expressed in human endothelial and mesangial cells, which contribute to control renal plasma flow and glomerular filtration rate. We investigated the association of ABCB1 variants with renal function in African and Caucasian subjects. METHODS: In Africans (290 subjects from 62 pedigrees), we genotyped the 2677G>T and 3435 C>T ABCB1 polymorphisms. Glomerular filtration rate (GFR) was measured using inulin clearance and effective renal plasma flow (ERPF) using para-aminohippurate clearance. In Caucasians (5382 unrelated subjects), we analyzed 30 SNPs located within and around ABCB1, using data from the Affymetrix 500 K chip. GFR was estimated using the simplified Modification of the Diet in Renal Disease (MDRD) and Cockcroft-Gault equations. RESULTS: In Africans, compared to the reference genotype (GG or CC), each copy of the 2677T and 3435T allele was associated, respectively, with: GFR higher by 10.6 +/- 2.9 (P < 0.001) and 4.4 +/- 2.3 (P = 0.06) mL/min; ERPF higher by 47.5 +/- 11.6 (P < 0.001) and 28.1 +/- 10.5 (P = 0.007) mL/min; and renal resistances lower by 0.016 +/- 0.004 (P < 0.001) and 0.011 +/- 0.004 (P = 0.004) mm Hg/mL/min. In Caucasians, we identified 3 polymorphisms in the ABCB1 gene that were strongly associated with all estimates of GFR (smallest P value = 0.0006, overall P = 0.014 after multiple testing correction). CONCLUSION: Variants of the ABCB1 gene were associated with renal function in both Africans and Caucasians and may therefore confer susceptibility to nephropathy in humans. If confirmed in other studies, these results point toward a new candidate gene for nephropathy in humans.

Secular trends in height and weight among children and adolescents of the Seychelles, 1956-2006.

BACKGROUND: Height of individuals has long been considered as a significant index of nutrition and health of a population; still, there is little information regarding the trends of height and weight among developing or transitional countries. We assessed the secular trends in height and weight in children of the Seychelles, a rapidly developing island state in the Indian Ocean (African region). METHODS: Height and weight were measured in all students of all schools in four selected school grades (kindergarten, 4th, 7th and 10th grades) for the periods 1998-9 (6391 children) and 2005-6 (8582 children). Data for 1956-7 was extracted from a previously published report. RESULTS: At age 15.5 years, boys/girls were on average 10/13 cm taller and 15/9 kg heavier in 2005-6 than in 1956-7. Height increased in boys/girls by 1.62/0.93 cm/decade between 1956-7 and 1998-9 and by 1.14/1.82 cm/decade between 1998-9 and 2005-6. For weight, the linear increase in boys/girls was 1.38/1.10 kg/decade between 1956-7 and 1998-9 and 2.21/2.50 kg/decade between 1998-9 and 2005-6. Overall, the relative increase in weight between 1956-7 and 2005-6 was 5-fold higher than the relative increase in height. CONCLUSION: Height and weight increased markedly over time in children aged <16 years in the Seychelles, consistent with large changes in socio-economic and nutritional indicators in the considered 50-year interval. The markedly steeper increase in weight than height over time is consistent with an epidemic of overweight and obesity.

Nighttime blood pressure and nocturnal dipping are associated with daytime urinary sodium excretion in African subjects.

Blood pressure (BP) follows a circadian rhythm, with 10% to 15% lower values during nighttime than during daytime. The absence of a nocturnal BP decrease (dipping) is associated with target organ damage, but the determinants of dipping are poorly understood. We assessed whether the nighttime BP and the dipping are associated with the circadian pattern of sodium excretion. Ambulatory BP and daytime and nighttime urinary electrolyte excretion were measured simultaneously in 325 individuals of African descent from 73 families. When divided into sex-specific tertiles of day:night ratios of urinary sodium excretion rate, subjects in tertile 1 (with the lowest ratio) were 6.5 years older and had a 9.8-mm Hg higher nighttime systolic BP (SBP) and a 23% lower SBP dipping (expressed in percentage of day value) compared with subjects in tertile 3 (P for trend <0.01). After adjustment for age, the SBP difference across tertiles decreased to 5.4 mm Hg (P=0.002), and the SBP dipping difference decreased to 17% (P=0.05). A similar trend across tertiles was found with diastolic BP. In multivariate analyses, daytime urinary sodium and potassium concentrations were independently associated with nighttime SBP and SBP dipping (P<0.05 for each). These data, based on a large number of subjects, suggest that the capacity to excrete sodium during daytime is a significant determinant of nocturnal BP and dipping. This observation may help us to understand the pathophysiology and clinical consequences of nighttime BP and to develop therapeutic strategies to normalize the dipping profile in hypertensive patients.

Microalbuminuria, but not cystatin C, is associated with carotid atherosclerosis in middle-aged adults.

BACKGROUND: Cystatin C, a marker of renal function, has been shown to be an independent predictor of cardiovascular disease (CVD) in older adults, but few data are available in middle-aged adults. Moreover, no study has compared cystatin C and microalbuminuria as risk factors for CVD outcomes in middle-aged adults, and it is not known whether cystatin C is related to an early stage of atherosclerosis. METHODS: We evaluated the relationships between serum creatinine, estimated glomerular filtration rate (GFR), serum cystatin C (all divided into tertiles), microalbuminuria and carotid atherosclerosis in a population-based random sample of 523 adults aged 35-64 years from the Seychelles (Indian Ocean). GFR was estimated using the modification of diet in renal disease (MDRD) equation. Intima-media thickness (IMT) was assessed by B-mode ultrasound. RESULTS: The mean age of the study sample was 52 years, and 55% were women. Carotid IMT was higher in participants with microalbuminuria (802 vs 732 microm, P<0.001) and was inversely associated with GFR tertiles (from 728 to 809 microm, P for trend=0.002). IMT was not associated with cystatin C or creatinine (P for trend=0.10 and 0.16, respectively). In multivariate analyses adjusted for cardiovascular risk factors, the association between microalbuminuria and IMT remained (P=0.047), while the association between GFR and IMT disappeared (P for trend=0.33). CONCLUSIONS: Microalbuminuria, but not cystatin C, is associated with carotid atherosclerosis beyond traditional cardiovascular risk factors among middle-aged adults. Cystatin C does not have a stronger relationship with carotid atherosclerosis in middle-aged adults than creatinine.

Prevalence of cardiovascular risk factors in a middle-income country and estimated cost of a treatment strategy.

BACKGROUND: We assessed the prevalence of risk factors for cardiovascular disease (CVD) in a middle-income country in rapid epidemiological transition and estimated direct costs for treating all individuals at increased cardiovascular risk, i.e. following the so-called "high risk strategy". METHODS: Survey of risk factors using an age- and sex-stratified random sample of the population of Seychelles aged 25-64 in 2004. Assessment of CVD risk and treatment modalities were in line with international guidelines. Costs are expressed as USD per capita per year. RESULTS: 1255 persons took part in the survey (participation rate of 80.2%). Prevalence of main risk factors was: 39.6% for high blood pressure (> or =140/90 mmHg or treatment) of which 59% were under treatment; 24.2% for high cholesterol (> or =6.2 mmol/l); 20.8% for low HDL-cholesterol (<1.0 mmol/l); 9.3% for diabetes (fasting glucose > or =7.0 mmol/l); 17.5% for smoking; 25.1% for obesity (body mass index > or =30 kg/m2) and 22.1% for the metabolic syndrome. Overall, 43% had HBP, high cholesterol or diabetes and substantially increased CVD risk. The cost for medications needed to treat all high-risk individuals amounted to USD 45.6, i.e. 11.2 dollars for high blood pressure, 3.8 dollars for diabetes, and 30.6 dollars for dyslipidemia (using generic drugs except for hypercholesterolemia). Cost for minimal follow-up medical care and laboratory tests amounted to 22.6 dollars. CONCLUSION: High prevalence of major risk factors was found in a rapidly developing country and costs for treatment needed to reduce risk factors in all high-risk individuals exceeded resources generally available in low or middle income countries. Our findings emphasize the need for affordable cost-effective treatment strategies and the critical importance of population strategies aimed at reducing risk factors in the entire population.

Marked increase in the prevalence of obesity in children of the Seychelles, a rapidly developing country, between 1998 and 2004.

BACKGROUND: There are few data on overweight in children in developing countries. Such data are important to guide public health policy. We assessed trends in the prevalence of overweight and obesity in children from the Seychelles, a middle-income island state in the Indian Ocean. METHODS: Multiple cross-sectional surveys were conducted each year between 1998 and 2004 on all students of all schools in four selected school grades (creche, 4th, 7th and 10th years of mandatory school). Weight and height were measured and children were asked about walking time and frequency of physical exercise at leisure time. Excess weight categories were defined according to the criteria of the International Obesity Task Force (IOTF) and the U.S. Centers for Disease Control and Prevention (CDC). RESULTS: Data were available for 33 340 observations in 1998-2004, corresponding to 23,459 individual children measured once or several times. Based on IOTF criteria, the prevalence of 'overweight' or 'obesity' increased from 8.7% to 13.5% in boys, and from 11.8% to 18.6% in girls from 1998 to 2004 (P < 0.001). The prevalence of 'obesity' increased from 2.1% to 5.2% in boys and from 3.1% to 6.2% in girls (P < 0.001). Using CDC criteria, the prevalence of 'at risk of overweight' and 'overweight' increased by similar proportions. The shift towards higher values over time was larger in the upper than the lower tail of the BMI distribution. Physical activity decreased over calendar years and was inversely associated with excess weight. CONCLUSIONS: The prevalence of excess weight increased markedly over a seven-year period in children in the Seychelles. This is likely to reflect a rapid nutrition transition with increasingly positive energy balance. These findings stress the need for programs and policies aimed at promoting physical activity and healthy nutrition in countries in epidemiological transition.

Interaction of ochratoxin A with human intestinal Caco-2 cells: possible implication of a multidrug resistance-associated protein (MRP2).

Ochratoxin A (OTA), a nephrotoxic mycotoxin, is absorbed from small intestine and, in plasma, binds to serum albumin. Prolonged half-live results from reabsorption by proximal tubules and enterohepatic circulation. The mechanism whereby OTA crosses intestine was investigated by means of a cell culture system consisting of Caco-2 cells, as in vitro model of human intestinal epithelium. Cytotoxicity assays on proliferating Caco-2 cells showed that 0.4 microM OTA inhibits MTT reduction by 50%. Transepithelial transport and intracellular accumulation of OTA were studied in Caco-2 cells, differentiated in bicameral inserts. At pH 7.4, OTA is transported preferentially in basolateral (BL) to apical (AP) direction, suggesting a net secretion. Conditions closer to in vivo situation in duodenum (AP pH 6.0, BL pH 7.4) increase intracellular accumulation and transepithelial transport. AP to BL transport becomes higher than BL to AP transport, suggesting OTA absorption. Addition of serum albumin in BL compartment further increases OTA absorption across Caco-2 cells and suggests that in vivo OTA transport from serosal to luminal side of enterocytes is prevented, due to its binding to plasma proteins. Competition experiments showed that carrier systems for large neutral amino acids, H(+)/dipeptides cotransporter, organic anion (p-aminohippurate) carrier and organic anion transporter (oatp) are not implicated in OTA transport across Caco-2 cells, in contrast to what was reported in kidney and liver. AP and BL transport and intracellular accumulation of OTA are increased in the presence of non specific inhibitors of MRPs (indomethacin, genistein and probenecid) and of 1-chloro-2,4-dinitrobenzene (biotransformed into 2,4-dinitrophenyl-gluthatione, a specific inhibitor of MRPs), but are affected by verapamil, an inhibitor of P-gp. This suggests that the multidrug resistance-associated protein (MRP2) could be implicated in transepithelial transport. Therefore, absorption of OTA across the intestinal mucosa would be limited thanks to its excretion through MRP2 at the apical pole of enterocytes.