bluuebunny/crossref_metadata_2025 huggingface dataset:
K‐complexes: are they signs of arousal or sleep protective?
Authors: WAUQUIER ALBERT , ALOE LOUISE , DECLERCK AUGUST
Published: January 2009

SUMMARY  The number of K‐complexes recorded at the central‐temporal EEG derivation (C3‐T3) during 5 min periods for both the ascending and descending phase of Stage 2 of NREM sleep for cycles 1,2… etc. were counted in 10 subjects for each of the following five groups: normal persons, patients with a primary generalized form of epilepsy, narcolepsy, insomnia and obstructive sleep apnoea. The differences in time spent in different stages of sleep were as expected for these types of patients. A 2‐within, 1‐between factors, repeated measure ANOVA was applied to the data on K‐complexes. Overall, there was no significant difference between the number of K‐complexes observed during the ascending and descending phases of the different sleep cycles. Patients with a sleep disorder had significantly less well‐defined K‐complexes than the normals and the patients with a primary form of generalized epilepsy: for insomnia (P= 0.035), for apnoea (P= 0.011) and for narcolepsy (P= 0.001). There was a significant, but very low correlation coefficient between the number of K‐complexes observed during Stage 2 of NREM sleep and the time spent during that stage for all groups combined (Rho 0.27, P= 0.002) and for the narcoleptic patients (Rho 0.44, P= 0.017). In all, the findings lend support to the hypothesis that a K‐complex can be seen as a ‘defensive response’, or has a sleep protective function.
Dynamic changes in hypothalamic monoamines during sleep/wake cycles assessed by parallel EEG and microdialysis in the rat
Authors: OROSCO M. , ROUGH C. , de SAINT‐HILAIRE Z. , NICOLAIDIS S.
Published: January 2009

SUMMARY Monoaminergic changes during sleep/wake cycles were investigated in the rostral hypothalamic areas since feeding, metabolism and sleep were shown to be causally related. Thus, the microdialysis probe was located stereotaxically in the ventromedial and paraventricular nuclei and cemented together with cortical electrodes for EEG sleep recordings. The monoaminergic changes were extensively investigated. Sampling of dialysates over six minutes in freely behaving rats showed an increase in 5‐HT and its metabolite 5‐HIAA during wakefulness. DOPAC rose during PS. The two other monoamines, DA and NA, remained unchanged. It appears that this method of investigation, extended in the future to other candidate areas and other dialysable substances, may provide us with a dynamic picture that characterizes the sleep/wake cycle.
Sleep habits and disorders in Finnish schoolchildren
Authors: SAARENPÄÄ‐HEIKKILÄ OUTI A. , RINTAHAKA PERTTI J. , LAIPPALA PEKKA J. , KOIVIKKO MATTI J.
Published: January 2009

SUMMARY  A variety of epidemiological sleep parameters was evaluated in 574 Finnish schoolchildren (age 7 to 17 years) and in their parents (454 mothers and 390 fathers). Three questionnaire forms were set, one for the pupil and two for his/her parents including information of sleep habits, disorders, and social background of the pupil and his/her family. The pupils were grouped by age (two preadolescent groups: 7.1–9.3 y and 9.4–13 y, adolescents 13.1–17.1 y) and sex. It was found that bedtime was more often after 22.00 hours among adolescents than preadolescents both at weekends and on weekdays. At weekends the wake‐up time was later in adolescents than preadolescents but on weekdays it was opposite in boys. On weekdays girls went earlier to bed than boys and woke up earlier than boys. Total sleep durations both on weekdays and at weekends were longer in preadolescent than in adolescent groups, and longer during weekend nights than on weekday nights in all groups. Girls experienced more dreaming and night waking, but boys snored more. Daytime sleepiness patterns were more common in adolescents than in preadolescents. Children who experienced daytime sleepiness more often had fathers with daily sleep urges.

An association was found between age and sleep habits and some daytime sleepiness patterns; adolescents went to bed later and slept less, and had more problems with alertness during daytime than preadolescents. Some differences were also found between boys and girls. The daytime sleepiness of pupils correlated with the same symptom in fathers.
Pre‐sleep behaviour in normal subjects
Authors: ELLIS CATHY , LEMMENS GILBERT , PARKES DAVID
Published: January 2009

SUMMARY  Behaviour in the 2‐h period before sleep onset was evaluated in 90 subjects with normal sleep/wake habits using an anonymous self‐report questionnaire. This determined the timing of events from the initial preparation for sleep. The nature of the pre‐sleep environment, the level of physical activity, and patterns of feeding behaviour were recorded together with self‐ratings of tiredness, mood and security. Estimated sleep duration and sleep quality were determined. Ninety of 120 subjects responded. Sleep ‘preparatory latency’, from the time of initial sleep preparation to sleep onset, was 77 ± 48 min; bed time to sleep onset time (sleep latency) was 41 ± 42 min; lights out to sleep onset latency was 26 ± 45 min. The estimated total sleep time was 7 ± 1 h. In the pre‐sleep period, mean noise and illumination levels were low and environmental temperature rating was at the median point on a very cold‐very hot scale (mean scale scores: 23, 28 and 50, respectively). All subjects went to the bathroom before going to bed. Twenty‐five percent of normal subjects had a snack or meal in the 2‐h period before sleep onset. Sixty percentage recorded setting an alarm, 27% had a bath or shower, 23% checked door locks or windows and 49% read in bed. Nine percent of subjects slept with a cat on the bed.

Humans, like other animal species, show a complex behavioural sequence in the 2‐h period before falling asleep. A constant environment with limited metabolic activity may predispose to thermoregulatory changes prior to sleep onset.
Modafinil, d‐amphetamine and placebo during 64 hours of sustained mental work. I. Effects on mood, fatigue, cognitive performance and body temperature
Authors: PIGEAU R. , NAITOH P. , BUGUET A. , McCANN C. , BARANSKI J. , TAYLOR M. , THOMPSON M. , MACK I.
Published: January 2009

SUMMARY  Modafinil is an alerting substance that is considered safer than amphetamine with fewer side effects. Although modafinil has been used successfully to treat narcolepsy, relatively little is known about its ability to ameliorate fatigue and declines in mental performance due to sleep deprivation (SD) in a normal population. Forty‐one military subjects received either 300 mg of modafinil, 20 mg of d‐amphetamine, or placebo on 3 separate occasions during 64 hours of continuous cognitive work and sleep loss. Three drug treatments were given: at 23.30 hours and 05.30 hours during the first and second SD nights, respectively, and once at 15.30 hours during the third day of continuous work. Subjective estimates of mood, fatigue and sleepiness, as well as objective measures of reaction time, logical reasoning and short‐term memory clearly showed better performance with both modafinil and amphetamine relative to placebo. Both modafinil and amphetamine maintained or increased body temperature compared to the natural circadian cycle observed in the placebo group. Also, from subject debriefs at the end of the study, modafinil elicited fewer side‐effects than amphetamine, although more than the placebo group. Modafinil appears to be a good alternative to amphetamine for counteracting the debilitating mood and cognitive effects of sleep loss during sustained operations.
Blood pressure analysis
Authors: PENZEL THOMAS
Published: January 2009

SUMMARY  Arterial blood pressure is influenced by sleep‐related breathing disorders. As cardiovascular consequences can be diagnosed by an accurate recording and analysis of blood pressure, new recording methodologies and an approach to analysis are presented here. Invasive continuous blood pressure recording is the common reference for all methodologies. As blood pressure varies rapidly in parallel with sleep‐related breathing disorders it is indispensible to record blood pressure continuously. To introduce non‐invasive methodology the Finapres system was used during sleep studies; a validation study showed severe limitations. This study was followed by the validation of an improved system called Portapres, which is portable, has two finger cuffs and a hydrostatic height compensation.

Analysis of continuous blood pressure in patients with sleep apnoea is carried out to detect mechanisms which influence the cardiovascular risk. Spectrum analysis of systolic blood pressure showed two different major oscillations present in patients with obstructive sleep apnoea. One oscillation (<0.06 Hz) occurs in parallel with each apnoeic episode and the other oscillation (0.2‐0.4 Hz) occurs in parallel with the obstructive efforts during each apnoea and in parallel with respiration during periods of snoring. These two oscillations were so specific that the use of non‐invasive continuous blood pressure recording allowed an estimation of the extent of underlying breathing disorders, and assessment of cardiovascular risk in a patient with obstructive apnoea in terms of hypertension and on the basis of ambulatory monitoring.
Regulation of blood volume—implications for cardiovascular pathophysiology in sleep apnoea
Authors: EHLENZ KLAUS
Published: January 2009

SUMMARY  Volume homeostasis plays an important role in the regulation of the cardiovascular system and maintenance of haemodynamics. The heart‐kidney axis represents the central part of the volume regulating system: the heart senses changes in the volume status and influences renal function via neural and humoral pathways in order to compensate for disturbances in volume homeostasis and prevent under‐ or overfilling of the heart. An undisturbed circadian rhythmicity of volume homeostasis, renal function and secretory pattern of volume regulating hormones may be of physiological importance. Disturbances in volume regulation are involved in the pathogenesis of cardiovascular diseases, e.g. arterial hypertension and heart failure. Nocturia in sleep apnoea (suggesting heart failure) may be explained by changes in volume‐regulating hormones indicating hypervolaemia of the central part of the cardiovascular system (‘central hypervolaemia’) caused by exaggerated venous return during repetitive Muller manoeuvres. Treatment of sleep apnoea abolishes nocturia and restores normal circadian rhythm of volume homeostasis and secretion of volume‐regulating hormones. Chronic cardiac volume overload during sleep may be implicated in the pathogenesis of cardiovascular sequelae in sleep apnoea: cardiac hypertrophy and heart failure. Central hypervolaemia during sleep can cause long‐term disturbances in blood pressure control by different mechanisms and may be in part responsible for the development of daytime hypertension in sleep apnoea. In summary, volume homeostasis is controlled by a complex interaction of heart and kidney. Disturbances may reflect cardiovascular diseases or may even be the cause. In sleep apnoea disturbances in volume regulation may be important for the development of cardiovascular sequelae.
Effects of (nCPAP) on cardiac function awake and asleep
Authors: DEEGAN PAUL C. , McNICHOLAS WALTER T.
Published: January 2009

SUMMARY  Continuous positive airway pressure (CPAP) leads to a fall in cardiac output (CO) when applied to individuals with normal cardiac function. However, some reports indicate that CPAP improves CO in selected patients with congestive heart failure, although other reports disagree. Nasal CPAP effectively reverses obstructive sleep apnoea, a condition in which vigorous inspiratory efforts against an occluded upper airway can induce falls in CO. The cardiovascular effects of CPAP in such patients will depend on the balance between the indirect cardiac benefits resulting from relief of apnoeas, and the direct effects of positive pressure on the heart itself.
Pulmonary haemodynamics in obstructive sleep apnoea
Authors: MARRONE ORESTE , BONSIGNORE MARIA ROSARIA
Published: January 2009

SUMMARY  The time course of right ventricular output (RVO) and transmural pulmonary artery pressure (PAP) changes, detected beat‐by‐beat, were analysed in a sample of obstructive sleep apnoea (OSA) episodes recorded in six patients with OSA syndrome. RVO showed a trend to a decrease during apnoeas, due to a decrease in heart rate, and decreased further in the immediate post‐apnoeic period, due to a decrease in right ventricular stroke volume [post‐apnoeic RVO = 82.6 ± 9.3 (SD) % of the value in the immediate pre‐apnoeic period; P<0.01]. Both systolic and diastolic transmural PAP showed a progressive increase throughout apnoeas (from 23.7 ± 7.3 to 29 ± 6.9 and from 9.1 ± 4.4 to 14.3 ± 3.3 mmHg, respectively, from early to late apnoeic period; P<0.01), and similarly high values in the late apnoeic and in the immediate post‐apnoeic period. Therefore, cardiac output and arterial pressure in the pulmonary circulation undergo simultaneous inverse changes in OSA, similar to what was previously shown in the systemic circulation. Although these data cannot define accurately the behaviour of pulmonary vascular resistance, they suggest that pulmonary vascular resistance could also undergo continuous oscillations in OSA, with recurring peaks detectable between apnoea termination and the immediate post‐apnoeic period.
Respiratory sinus arrhythmia during obstructive sleep apnoeas in humans
Authors: BONSIGNORE MARIA R. , ROMANO S. , MARRONE O. , INSALACO G.
Published: January 2009

SUMMARY  Respiratory sinus arrhythmia (RSA) reflects parasympathetic modulation of heart rate (HR) during the respiratory cycle. Since the time‐course of RSA during obstructive sleep apnoea (OSA) is not known, an analysis was made of ECG in samples of consecutive OSA recorded in 5 patients during NREM sleep while breathing room air (OSA‐AIR, mean lowest SaO2 83.0 ±6.5%) or supplemental oxygen (OSA + O2, mean lowest SaO2 91.7 ± 2.2%), respectively. For each breath, HR at the transition from expiration to inspiration (HRei), and HR at maximal inspiration (HRie) were calculated, and the inspiratory increase in HR estimated as the ratio: HRei/subsequent HRie. Similarly, the expiratory decrease in HR was estimated as: HRie/subsequent HRei. RSA was identified by an inspiratory increase in HR (HRei/HRie<1), and an expiratory decrease in HR (HRie/HRei > 1). OSA‐AIR and OSA + O2 did not differ for duration or oesophageal pressure nadir. During OSA‐AIR, the inspiratory increase in HR became progressively more marked from the first occluded to the first open breath, whereas during OSA + O2 it remained stable throughout the apnoeic cycle. The expiratory decrease in HR remained constant during the apnoeic phase, but was blunted in the first open breaths irrespective of O2 administration. In summary, hypoxia appeared to affect inspiratory, but not expiratory HR. Instead, the expiratory slowing of HR transiently disappeared in the immediate post‐apnoeic phase, suggesting a possible effect of arousal or pulmonary inflation. These data suggest that the parasympathetic system may contribute to cardiovascular regulation during OSA.
Obstructive sleep apnoea as a risk factor for hypertension
Authors: GRUNSTEIN RONALD
Published: January 2009

SUMMARY  It is controversial whether obstructive sleep apnoea (OSA) is a risk factor for hypertension as previous reviews of the subject have emphasized the confounding effect of obesity. We examined evidence from recent studies to reassess this debate. Cross‐sectional studies from sleep clinic population (Sydney Sleep Cohort, Gothenburg Sleep Clinic Cohort), community sample (Busselton Sleep Survey, Wisconsin Sleep Cohort) and obese population (Swedish Obese Subjects Study) provide stronger evidence that the relationship between sleep apnoea and hypertension is an independent one. Moreover recent studies looking at the effect of sleep apnoea treatment have demonstrated a fall in blood pressure independent of weight change. More definitive studies are required but recent data provide increasing evidence that OSA is an independent risk factor for hypertension.
Jet lag and sleepiness In aircrew
Authors: SAMEL A. , WEGMANN H. M. , VEJVODA M.
Published: January 2009

SUMMARY  Jet‐lag and day‐time sleepiness cannot be avoided in transmeridian operations, because work hours of aircrews interfere with the circadian system through irregular work‐rest schedules and rapid time‐zone transitions. Although the primary cause of accidents is usually the human factor, jet lag and sleepiness have seldom been officially identified as causes of inadequate functioning in the cockpit. However, research clearly indicates that flights at night and/or across time zones will impair performance and reduce safety. Research on countermeasures have focused on on‐board napping, crew augmentation, behavioural strategies against jet‐lag, light treatment and melatonin administration. Regrettably, scientific knowledge has been successfully transmitted to only a very few national authorities responsible for work hours of aircrews.
Effects of timing of shifts on sleepiness and sleep duration
Authors: KECKLUND GÖRAN , ÅKERSTEDT TORBJÖRN
Published: January 2009

SUMMARY  This review summarizes the effects on sleep duration and sleepiness of (1) the timing of shifts (start and finishing times) and (2) the scheduling of free time between shifts. The results from the few studies available show that sleep duration is clearly determined by the change over time between the night and the morning shift—no more than 5 or 6 hours of sleep is obtained before the morning shift if the shift starts at 06.00 hours or earlier. Therefore, it is suggested that the morning shift should not start before 07.00 hours. A late start of the morning shift will however, increase the sleepiness at the end of the night shift, as well as decrease the duration of the daysleep after the night shift. On the other hand, one may argue that the short daysleep after a night shift may be compensated for by an evening nap, whereas a short night sleep before a morning shift cannot (no time for nap). The review of studies concerning free time between shifts suggests that at least 16 hours is needed and that quick change‐overs should be avoided. The free time after a spell of night shifts should be at least 48 hours since the shiftworker needs two main sleep episodes to recover from night work.
Sleepiness and shiftwork: individual differences
Authors: HÄRMÄ MIKKO
Published: January 2009

SUMMARY  On‐site studies of shiftwork show considerable differences in sleepiness between workers. Variation between individuals depends on different sleeping, coping and living habits of the workers, on possible sleep disorders, but also on more ‘permanent’ inter‐individual factors that may influence sleepiness by changing either the circadian or homeostatic factors of sleep. The effects of circadian phase, age, sex, physical fitness, domestic and personality factors on shiftworkers' sleepiness and work‐related accidents are reviewed. It is concluded that only a minor part of the variation in sleepiness between individuals can be explained. The present knowledge is not sufficient to carry out reliable ‘selection’ of individuals suitable for shiftwork. However, preventive advice and medical surveillance focusing on individual differences in sleepiness are recommended.
Use of bright light to treat maladaptation to night shift work and circadian rhythm sleep disorders
Authors: CZEISLER CHARLES A. , DIJK DERK‐JAN
Published: January 2009

SUMMARY  Night work is associated with increased sleepiness and disturbed sleep. Maladaptation of the circadian system, which is phase‐adjusted to day time work and thus promotes sleepiness during its nadir at night and wakefulness (or disturbed sleep) during the day, contributes substantially to this problem. A major cause of suboptimal circadian phase adjustment among night workers is the exposure to morning light, which prevents the delay needed for optimal adjustment to night work. Several laboratory studies indicate that careful application of bright light may cause the circadian system to shift to any desired phase. Furthermore, studies of simulated night work demonstrate that night exposure to bright light can virtually eliminate circadian maladjustment among night workers. While the results are promising, there is still, however, an urgent need for longitudinal studies of bright light application in. real‐life settings.
Variable extent of hybridization between invasive sika (Cervus nippon) and native red deer (C. elaphus) in a small geographical area
Authors: SENN HELEN V. , PEMBERTON JOSEPHINE M.
Published: January 2009

Instances of hybridization between endemic and alien species pose a threat to species integrity but also provide us with an opportunity to study the dynamics of gene flow between two species as they first meet. Here, we used variation at 22 highly differentiated microsatellite loci and one mitochondrial DNA (mtDNA) marker in a sample of 735 individuals, to investigate the genetic consequences of an introduction of Japanese sika deer (Cervus nippon) for native red deer (C. elaphus) on the Kintyre Peninsula in Scotland. We investigated population structure, estimated null‐allele frequency and assigned individual hybrid scores using a Bayesian clustering algorithm implemented in structure 2.2. The dataset clearly divided into two clusters and generally, introgression into red and sika was low. However at one site, West Loch Awe, 43% of individuals were hybrids. MtDNA introgression indicated that hybridization was occurring between red‐deer hinds and sika‐deer stags. We argue that the pattern of differential introgression across the study area is primarily due to the rarity of hybridization events between the two species and the limited time the two species have been in contact (< 120 years). This contrasts with the causes of classic mosaic hybrid zones (selection induced by habitat variability). Currently, it seems possible that, in time, the level of hybridization found at West Loch Awe could also be found across the whole of the peninsula.
Calcium homeostasis is required for contact‐dependent helical and sinusoidal tip growth in Candida albicans hyphae
Authors: Brand Alexandra , Lee Keunsook , Veses Veronica , Gow Neil A. R.
Published: January 2009

Hyphae of the dimorphic fungus, Candida albicans, exhibit directional tip responses when grown in contact with surfaces. On hard surfaces or in liquid media, the trajectory of hyphal growth is typically linear, with tip re‐orientation events limited to encounters with topographical features (thigmotropism). In contrast, when grown on semisolid surfaces, the tips of C. albicans hyphae grow in an oscillatory manner to form regular two‐dimensional sinusoidal curves and three‐dimensional helices. We show that, like thigmotropism, initiation of directional tip oscillation in C. albicans hyphae is severely attenuated when Ca2+ homeostasis is perturbed. Chelation of extracellular Ca2+ or deletion of the Ca2+ transporters that modulate cytosolic [Ca2+] (Mid1, Cch1 or Pmr1) did not affect hyphal length but curve formation was severely reduced in mid1Δ and cch1Δ and abolished in pmr1Δ. Sinusoidal hypha morphology was altered in the mid1Δ, chs3Δ and heterozygous pmr1Δ/PMR1 strains. Treatments that affect cell wall integrity, changes in surface mannosylation or the provision of additional carbon sources had significant but less pronounced effects on oscillatory growth. The induction of two‐ and three‐dimensional sinusoidal growth in wild‐type C. albicans hyphae is therefore the consequence of mechanisms that involve Ca2+ influx and signalling rather than gross changes in the cell wall architecture.
Echinococcosis, toxocarosis and toxoplasmosis screening in a rural community in eastern Kazakhstan
Authors: Torgerson Paul R. , Rosenheim Kathy , Tanner Isabelle , Ziadinov Iskender , Grimm Felix , Brunner Matthias , Shaiken Sholpan , Shaikenov Blok , Rysmukhambetova Aizhan , Deplazes Peter
Published: January 2009

Objective  To determine the extent of carnivore‐transmitted parasitic zoonoses in a community in eastern Kazakhstan, a region where cystic echinococcosis (CE) re‐emerged in recent years.

Methods  Cross sectional ultrasound study of 3126 human subjects to determine the extent of human cystic and alveolar echinococcosis (AE). Blood samples were taken from each subject and analysed for antibodies against Echinococcus, Toxocara and Toxoplasma spp. Each subject was questioned about possible risk factors that might be associated with zoonotic transmission. Analysis employed a mixed modelling approach based on the results of the ultrasound study, the serological results and the results of the questionnaire. Bayesian techniques were employed to estimate diagnostic performance. A helminthological study of the local dog population was also undertaken.

Results  A total of 23 subjects tested positive for CE on ultrasound and a further three individuals had strong serological evidence of infection. Another 24 reported treatment for CE. Ultrasound lesions or treatment for CE were associated with poverty. No ultrasound evidence of AE was found, but one individual had strong serological evidence of exposure to Echinococcus multilocularis. Toxoplasma seropositivity (16%; 504 individuals) increased with age. Household level Toxoplasma‐seropositivity was associated with unsafe drinking water. Toxocara seropositivity (11%; 349 individuals) was more frequent in children and in individuals who disposed of dog faeces on the vegetable garden. A purgation study of dogs indicated that 13% of dogs in the community were infected with Echinococcus granulosus, 5% with E. multilocularis and 2% with Toxocara canis respectively.

Conclusions  There is significant transmission of E. granulosus to humans in this community. Transmission may be associated with poverty. There is little evidence of E. multilocularis transmission to humans, despite the presence in the parasite in the domestic dog population. Toxoplasma is actively transmitted and there is evidence for transmission by the water supply. Children are at highest risk of exposure to Toxocara.
Medication history of a series of patients with bullous pemphigoid from northern Greece – observations and discussion
Authors: Patsatsi Aikaterini , Vyzantiadis Timoleon‐Achilleas , Chrysomallis Fotis , Devliotou‐Panagiotidou Despina , Sotiriadis Dimitrios
Published: January 2009

Background  Bullous pemphigoid (BP) is an autoimmune bullous disease that mainly affects elderly patients. In this retrospective study, in a series of patients with BP, data on systemic medications were collected in order to investigate a possible association with active BP.

Methods  Thirty‐four patients with BP were studied in two groups. Group A contained patients who were receiving systemic medications and group B contained patients receiving no medications. All sera were examined by immunoassay for the possible existence of anti‐BP180NC16a and anti‐BP230, prior to the initiation of steroid treatment.

Results  Patients were of a similar age in both groups (P = 0.07). Anti‐BP180NC16a autoantibodies were detected in 80% of patients in group A and in 14% of patients in group B. Anti‐BP230 autoantibodies were detected in 25% of patients in group A and in 50% of patients in group B. Levels of circulating anti‐BP180NC16a autoantibodies were statistically significantly higher in group A than in group B (P = 0.04).

Conclusions  Patients who were receiving systemic medications seemed to be more susceptible to the development of BP. Should we consider drug exposure as one of the reasons for the increased prevalence of BP in the elderly? It is important to be more vigilant with this category of patients in order to provide an early diagnosis of the disease.
Kindler syndrome: report of three cases in a family and a brief review
Authors: Yazdanfar Ameneh , Hashemi Banafsheh
Published: January 2009

Background  Kindler syndrome is an autosomal recessive disorder with neonatal blister formation, photosensitivity, atrophy, abnormal pigmentation, and fragility of the skin. Skin atrophy is more prominent on the extremities and the skin manifestations improve with age.

Methods  We report three cases in a family which present the clinical and pathologic manifestations of Kindler syndrome.

Results  All of the three cases reported here present skin changes on the extremities, face, and neck, including hyper‐ and hypopigmentation, atrophy, and telangiectasia. The condition in these cases started soon after birth. Two of these cases also had mucosal involvement.

Conclusion  Increased photosensitivity and sunburn after minimal sun exposure should lead physicians to examine the skin for poikiloderma and the mouth for fragility of the gums, periodontitis and other associated findings. Also, patients should be questioned about any history of blister formation as well as family history.
Gambogic acid induces apoptosis by regulating the expression of Bax and Bcl‐2 and enhancing caspase‐3 activity in human malignant melanoma A375 cells
Authors: Xu Xiaoyuan , Liu Yeqiang , Wang Ling , He Jun , Zhang Hongfeng , Chen Xinxiang , Li Yan , Yang Jing , Tao Juan
Published: January 2009

Objectives  To investigate the effect of a Chinese traditional medicine, gambogic acid (GA), on human malignant melanoma (MM) A375 cells and to study the mechanism of apoptosis induced by GA.

Methods  A375 cells were treated with GA at different doses and for different times, and their proliferation and viability were detected by 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide (MTT) assay. Apoptosis induced by GA in A375 cells was observed by annexin‐V/propidium iodide doubling staining flow cytometry assay and Hoechst staining. To further determine the molecular mechanism of apoptosis induced by GA, the changes in expression of Bcl‐2 and Bax were detected by real‐time reverse transcriptase‐polymerase chain reaction (RT‐PCR) and Western blot, and caspase‐3 activity was measured by fluorescence resonance energy transfer (FRET) probe.

Results  After incubation with GA, A375 cell proliferation was dramatically inhibited in a dose‐dependent manner. After these cells had been exposed to GA for 24, 36 and 48 h, the IC50 values were 1.57 ± 0.05, 1.31 ± 0.20, and 1.12 ± 0.19 µg/mL, respectively. Treatment of A375 cells with GA (2.5–7.5 µg/mL) for 36 h resulted in an increased number of early apoptotic cells, which ranged from 27.6% to 41.9%, in a dose‐dependent manner, compared with only 3.5% apoptotic cells in the non‐GA‐treated group. An increase in Bax and decrease in Bcl‐2 expression were found by real‐time RT‐PCR and Western blot. Caspase‐3 activity was increased in a dose‐dependent manner, observed by FRET probe.

Conclusion  GA can inhibit the proliferation of A375 cells and induce their apoptosis, which may be related to the up‐regulation of the Bax/Bcl‐2 ratio and caspase‐3 activity.
PEP005 (ingenol mebutate) gel, a novel agent for the treatment of actinic keratosis: Results of a randomized, double‐blind, vehicle‐controlled, multicentre, phase IIa study
Authors: Siller Greg , Gebauer Kurt , Welburn Peter , Katsamas Janelle , Ogbourne Steven M
Published: January 2009

The sap of the plant Euphorbia peplus is a traditional remedy for skin conditions, including actinic keratosis. The active constituent of the sap is ingenol mebutate (ingenol‐3‐angelate), formerly known as PEP005. This randomized, double‐blind, vehicle‐controlled, phase IIa study investigated the safety (and secondarily the efficacy) of two applications of ingenol mebutate gel in 58 patients with biopsy‐confirmed actinic keratosis. Five preselected lesions were treated with ingenol mebutate gel, 0.0025%, 0.01% or 0.05%, or vehicle gel, on days 1 and 2 (Arm A) or days 1 and 8 (Arm B). There were no significant differences in tolerability or efficacy between Arms A and B. Treatment was well tolerated. The most common local skin responses were dose‐related erythema, flaking/scaling/dryness and scabbing/crusting. Efficacy was greatest with ingenol mebutate gel, 0.05%, which resulted in complete clinical clearance of 71% of treated lesions (P < 0.0001 vs vehicle gel). In addition, 67% of patients treated with ingenol mebutate gel, 0.05% had clinical clearance of at least four of five treated lesions (P = 0.0185 vs vehicle gel). Ingenol mebutate gel is being developed as a short‐course topical therapy for actinic keratosis and non‐melanoma skin cancer.
Cardiovascular risk factors in Australian indigenous and non‐indigenous children: A population‐based study
Authors: Haysom Leigh , Williams Rita E , Hodson Elisabeth M , Lopez‐Vargas Pamela , Roy L Paul , Lyle David M , Craig Jonathan C
Published: January 2009

Aim:  Indigenous people have a two‐ to tenfold increased risk of premature death from cardiovascular disease. We aimed to determine whether some key risk factors for cardiovascular disease occur more commonly in Aboriginal than non‐Aboriginal Australian children.

Methods:  Children were enrolled from primary schools throughout New South Wales, the state with the highest number of Aboriginal people. Associations between ethnicity, gender, birthweight, socio‐demographic status and hypertension, obesity, baseline and persistent albuminuria were determined.

Results:  A total of 2266 children (55% Aboriginal) were enrolled. Mean age was 8.9 years (±3.8 years). Obesity (body mass index ≥2 standard deviations) was detected in 7.1%, systolic hypertension (blood pressure >90th percentile) in 7.2%, diastolic hypertension in 5.9%, baseline albuminuria (albumin : creatinine ≥3.4 mg/mmol) in 7.3% and persistent albuminuria in 1.5% with no differences between Aboriginal and non‐Aboriginal children. Hypertension was less common with increasing social disadvantage (trend P < 0.02). Increasing body mass index standard deviation was strongly associated with systolic and diastolic hypertension (both P < 0.0001).

Conclusions:  Many risk factors for cardiovascular disease are already common in young children but not more prevalent in Aboriginal than in non‐Aboriginal children. In all children, overweight and obesity have the strongest association with hypertension, but social disadvantage appears protective for hypertension. Our findings suggest that risk for cardiovascular health disparities seen in indigenous adults manifests beyond childhood and that a window of opportunity exists to prevent some of these outcomes.
Referrals for tall stature in children: A 25‐year personal experience
Authors: Thomsett Michael J
Published: January 2009

Aim:  Extreme tall stature may lead to a variety of concerns in tall children and their parents, leading to requests for treatment to reduce final height in some children. This study reviews referrals for tall stature to a single pediatric endocrinologist and results of treatment over 25 years from 1980 to 2004.

Methods:  Diagnoses, heights, target heights and estimated final heights at presentation, and final heights and complications in treated patients, were examined by retrospective chart review.

Results:  Of 345 referrals, 244 (71%) were girls and 101 (29%) were boys. Of the 68 (19.7%) treated, 53 (78%) were girls and 15 (22%) were boys. Most children had familial tall stature. Treated children were tall for their already tall families. Treatment reduced final heights compared with estimated final heights by (mean +/− standard error of the mean) 4.2 +/− 0.5 cm (P = 0.001) in girls and 5.1 +/− 0.8 cm (P < 0.001) in boys. Minor complications occurred in 27 (51%) girls, including 5 (9.4%) who stopped treatment because of weight gain, and 5 (33%) of boys. In more recent years, girls (but not boys) presented less frequently, were taller at presentation and opted for treatment less often, and at taller estimated final heights than in the earlier years.

Conclusions:  Any benefits of high‐dose sex steroid treatment of tall children in terms of reduced final height and improved self‐image are at the expense of complications in many. Fewer tall girls being referred and treated probably reflects altered attitudes to tallness in society. Such treatment should seldom – if ever – be used in the future.
The development and evaluation of a simple method of gestational age estimation
Authors: Allan Rachel C , Sayers Susan , Powers Jennifer , Singh Gurmeet
Published: January 2009

Aims:  The aims of this study were to develop and evaluate a shorter gestational age estimation method based on the Dubowitz scoring system (DSS) that could be taught easily to untrained health‐care workers.

Methods:  Using the DSS, seven criteria were identified that explained 90% of the variance in gestational age estimation. Ventral suspension was excluded, skin texture was substituted for skin colour and ear bending was for ear firmness. The final six criteria comprise the short DSS (SDSS). The study population was 100 babies, 51 Caucasian, 34 Aboriginal. Birth weight ranged from 1351 to 5430 g. The gestational age range was 29.6–41.7 weeks. Three researchers (medical student 1 (MS1), medical student 2 (MS2) and a paediatrician) who were blind to other available gestational age estimations assessed babies within 72 h of birth using the DSS and SDSS.

Results:  MS1 found the 95% limits of agreement (LOA) between SDSS and DSS to be −1.1 to 1.7 weeks. In the 27 babies who had first trimester foetal ultrasound (USS), the LOA between USS and SDSS were −1.9 to 1.4 weeks and −2.3 to 1.9 weeks, respectively. Using the SDSS, the LOA for the three researchers were within ±2 weeks.

Conclusion:  The data presented suggest that the SDSS is approximately equivalent to the DSS in the relatively limited population studied, and within these limitations appears to be a simple alternative to the DSS. Further evaluation is needed before firm conclusions about the accuracy and clinical utility of the SDSS can be made.
Adherence to physical activity and electronic media guidelines in Australian pre‐school children
Authors: Okely Anthony D , Trost Stewart G , Steele Julie R , Cliff Dylan P , Mickle Karen
Published: January 2009

The aim of this study was to determine compliance with the National Association for Sport and Physical Education (NASPE) guideline for physical activity and American Academy of Pediatrics (AAP) recommendation for electronic media use among urban pre‐school children in two large cities on the East Coast of Australia. Cross‐sectional data were collected from 266 parents. Time spent using electronic media (watching television, DVDs or on the computer) and in physical activity were parent reported. The proportion who met each guideline was calculated. 56 per cent and 79% of children met the NASPE guideline on weekdays and weekends, respectively, while 73% and 70% met the AAP recommendation on weekdays and weekends, with no difference between boys and girls. A substantial minority do not meet physical activity and electronic media use recommendations, highlighting the need to better understand what factors contribute to physical activity and electronic media use among this group of pre‐schoolers.
Traumatic bleeding at birth treated with Factor VII
Authors: Carmo Kathryn A Browning , O'Brien Karen , Teo Juliana , Schell David
Published: January 2009

We report 36 week gestation twins born following a traumatic delivery. Twin 2 had profuse haemorrhage where haemostasis was achieved with recombinant Factor VIIa (rFVIIa – NovoSeven®;Novo Nordisk A/S, Bagsværd, Denmark)
A low‐GI diet is associated with a short‐term improvement of glycaemic control in Asian patients with type 2 diabetes
Authors: Yusof B. N. M. , Talib R. A. , Kamaruddin N. A. , Karim N. A. , Chinna K. , Gilbertson H.
Published: January 2009

Aims:  The aim of this study is to compare the efficacy of low glycaemic index (GI) vs. conventional carbohydrate exchange (CCE) dietary advice on glycaemic control and metabolic parameters in patients with type 2 diabetes.

Methods:  A total of 104 patients with type 2 diabetes were randomly assigned to either a low GI (GI) or CCE dietary advice over a 12‐week period. The primary end‐point was glycaemic control as assessed by glycated haemoglobin A1c (HbA1c), fructosamine level and plasma glucose. The secondary end‐points were anthropometric measurements and metabolic parameters that include blood pressure, lipid profile and insulin levels. The oral antidiabetic medications remained unchanged throughout the duration of the study.

Results:  A low‐GI diet was associated with significant changes in the fructosamine level (ΔGI = −0.20 ± 0.03; ΔCCE = −0.08 ± 0.03 mmol/l, p < 0.01) and waist circumference (ΔGI group = −1.88 ± 0.30 cm; ΔCCE group: −0.36 ± 0.4 cm, p < 0.05) at week 4. At week 12, the changes in fasting glucose (ΔGI = −0.03 ± 0.3; ΔCCE = 0.7 ± 0.3 mmol/l; p < 0.05) and waist circumference (ΔGI = −2.35 ± 0.47 cm; ΔCCE group = −0.66 ± 0.46 cm; p < 0.05) in the GI group was significantly lower than the CCE group. With the low‐GI diet, the changes in postprandial glycaemia at time 0, 60, 150 and 180 min after consuming the standard test meal was lower than with the CCE diet (p < 0.05). No significant differences were found between the groups for the remaining parameters that were measured.

Conclusions:  Use of a low‐GI diet resulted in significant changes of serum fructosamine level, plasma glucose and waist circumference in Asian patients with type 2 diabetes over a 12‐week period compared with those following a CCE diet. The effect on HbA1c and other metabolic parameters was not significantly different between the two study groups but the improvement within the GI group was more pronounced and of clinical benefit.
Fixed‐dose single tablet antidiabetic combinations
Authors: Bailey C. J. , Day C.
Published: January 2009

Combinations of two or more oral agents with different mechanisms of action are often used for the management of hyperglycaemia in type 2 diabetes. While these combinations have customarily been taken as separate tablets, several fixed‐dose single tablet combinations are now available. These are based on bioequivalence with the separate tablets, giving similar efficacy to the separate tablets and necessitating the same cautions and contraindications that apply to each active component. Fixed‐dose combinations can offer convenience, reduce the pill burden and simplify administration regimens for the patient. They increase patient adherence compared with equivalent combinations of separate tablets, and this is associated with some improvements in glycaemic control. Presently available antidiabetic fixed‐dose combinations include metformin combined with a sulphonylurea, thiazolidinedione, dipeptidylpeptidase‐4 inhibitor or meglitinide as well as thiazolidinedione–sulphonylurea combinations, each at a range of dosage strengths to facilitate titration. Anticipated future expansion of multiple drug regimens for diabetes management is likely to increase the use of fixed‐dose single tablet combinations.
The prognostic significance of advanced age in patients with bladder cancer treated with radical cystectomy
Authors: Resorlu Berkan , Beduk Yasar , Baltaci Sumer , Ergun Gul , Talas Halit
Published: January 2009

OBJECTIVE

To evaluate the association of patient age with pathological and long‐term oncological outcomes after radical cystectomy (RC) for bladder carcinoma, as this disease, like many others, increases in incidence with age.

PATIENTS AND METHODS

We retrospectively reviewed 241 consecutive patients with invasive bladder cancer who had RC between 1990 and 2007. The age at RC was analysed both as a continuous and categorical (≤50 years, 38 patients; 51–69, 172; or ≥70, 31) variable. Survival was also analysed.

RESULTS

Increasing age, analysed as a continuous and categorical variable, was associated with advanced pathological stage (P = 0.009 and 0.006, respectively). The 5‐year cancer‐specific survival rates for patients according to the age groups were 78.5%, 44.9% and 28.1%, respectively, and Kaplan‐Meier analysis showed an increased risk of bladder cancer‐specific death with advancing age (P < 0.001). Being older at RC was an important prognostic factor for disease‐specific survival in a multivariate Cox regression model. Patients aged ≥70 years had a significantly higher risk of disease than patients aged ≤50 years (P = 0.002).

CONCLUSIONS

Higher age at RC is significantly associated with the risk of pathologically advanced disease and poorer cancer‐specific survival. More prospective work is needed to examine the impact of age on tumour biology and cancer‐specific survival.
Prognostic significance of microscopic bladder neck invasion in prostate cancer
Authors: Rodríguez‐Covarrubias Francisco , Larré Stéphane , Dahan Mickael , De La Taille Alexandre , Allory Yves , Yiou René , Vordos Dimitri , Hoznek Andras , Abbou Claude‐Clément , Salomon Laurent
Published: January 2009

OBJECTIVE

To assess the prognostic significance of microscopic bladder neck invasion (BNI+) after radical prostatectomy (RP).

PATIENTS AND METHODS

From January 1988 to December 2006, 1480 patients with clinically localized prostate cancer were surgically treated at one tertiary university hospital. The risk of biochemical progression, defined as a prostate‐specific antigen (PSA) level after RP of >0.2 ng/mL, was assessed with univariate and multivariate analyses for clinical and pathological variables. We compared the biochemical progression‐free survival (bPFS) of patients with BNI+ vs stages pT2, pT3a, pT3b and positive lymph nodes (N+). In a second analysis, we evaluated the bPFS of patients in different stages associated with BNI+ and compared them with those in the same stages with no BNI.

RESULTS

BNI+ was found in 132 (9%) patients; the 5‐year bPFS was 86%, 54%, 26% and 10% for stages pT2, pT3a, pT3b and N+, respectively, while it was 30% for BNI+ (P < 0.001). There was no difference in the 5‐year bPFS between stage pT2 and pT2 + BNI (P = 0.32). Stages pT3a and pT3b had a better 5‐year bPFS than stage pT3a + BNI (P = 0.003) and pT3b + BNI (P = 0.001), respectively. In the univariate analysis all variables were associated with BP. In the multivariate analysis, only BNI+ had no association with BP (odds ratio 1.14, 95% confidence interval 0.70–1.85; P = 0.59).

CONCLUSIONS

Microscopic BNI+ in prostate cancer is not an independent risk factor for biochemical progression and should be regarded as a factor that worsens the prognosis of the underlying tumour stage. A longer follow‐up is necessary to confirm these findings.
Heparin‐binding epidermal growth factor‐like growth factor functionally antagonizes interstitial cystitis antiproliferative factor via mitogen‐activated protein kinase pathway activation
Authors: Kim Jayoung , Keay Susan K. , Freeman Michael R.
Published: January 2009

OBJECTIVE

To delineate the mechanism underlying the potential functional relationship between interstitial cystitis antiproliferative factor (APF) and heparin‐binding epidermal growth factor‐like growth factor (HB‐EGF), as APF has previously been shown to decrease the proliferation rate of normal bladder epithelial cells and the amount of HB‐EGF produced by these cells.

MATERIALS AND METHODS

APF‐responsive T24 transitional carcinoma bladder cells were treated with high‐pressure liquid chromatography‐purified native APF with or without HB‐EGF to determine the involvement of signalling pathways and proliferation by Western blot analysis, p38 mitogen‐activated protein kinase (MAPK) and extracellular signal‐regulated kinase (Erk)/MAPK assays, and 3‐(4,5‐dimethylthiazolyl‐2)‐2,5‐diphenyltetrazolium bromide (MTT) assay.

RESULTS

Cyclic stretch induced the secretion of HB‐EGF from T24 cells overexpressing the HB‐EGF precursor, resulting in enhanced proliferation. T24 cells treated with APF had increased p38MAPK activity and suppressed cell growth, events that were both reversed by treatment with a p38MAPK‐selective inhibitor. Activation of Erk/MAPK by HB‐EGF was inhibited by APF, and APF did not stimulate p38MAPK in the presence of soluble HB‐EGF or when cells overexpressed constitutively secreted HB‐EGF. Lastly, APF inhibitory effects on cell growth were attenuated by HB‐EGF.

CONCLUSIONS

These results indicate that HB‐EGF and APF are functionally antagonistic and signal through parallel MAPK signalling pathways in bladder cells.