bluuebunny/crossref_metadata_2025 huggingface dataset:
Easy‐to‐use, accurate and flexible individualized Bayesian limited sampling method without fixed time points for ciclosporin monitoring after liver transplantation
Authors: Langers P. , Cremers S. C. L. M. , den Hartigh J. , Rijnbeek E. M. T. , Ringers J. , Lamers C. B. H. W. , van Hoek B.
Published: March 2005

Background : New methods to estimate the systemic exposure to ciclosporin such as the level 2 h after dosing and limited sampling formulas may lead to improved clinical outcome after orthotopic liver transplantation. However, most strategies are characterized by rigid sampling times.

Aim : To develop and validate a flexible individualized population‐pharmacokinetic model for ciclosporin monitoring in orthotopic liver transplantation.

Methods : A total of 62 curves obtained from 31 patients at least 0.5 year after orthotopic liver transplantation were divided into two equal groups. From 31 curves, relatively simple limited sampling formulas were derived using multiple regression analysis, while using pharmacokinetic software a two‐compartment population‐pharmacokinetic model was derived from these same data. We then tested the ability to estimate the AUC by the limited sampling formulas and a different approach using several limited sampling strategies on the other 31 curves. The new approach consists of individualizing the mean a priori population‐pharmacokinetic parameters of the two‐compartment population‐pharmacokinetic model by means of maximum a posteriori Bayesian fitting with individual data leading to an individualized population‐pharmacokinetic limited sampling model. From the individualized pharmacokinetic parameters, AUC0‐12h was calculated for each combination of measured blood concentrations. The calculated AUC0‐12h both from the limited‐sampling formulas and the limited‐sampling model were compared with the gold standard AUC0‐12h (trapezoidal rule) by Pearson's correlation coefficient and prediction precision and bias were calculated.

Results : The AUC0‐12h value calculated by individualizing the population‐pharmacokinetic model using several combinations of measured blood concentrations: 0 + 2 h (r2 = 0.94), 0 + 1 + 2 h (r2 = 0.94), 0 + 1 + 3 h (r2 = 0.92), 0 + 2 + 3 h (r2 = 0.92) and 0 + 1 + 2 + 3 h (r2 = 0.96) had excellent correlation with AUC0‐12h, better than limited sampling formulas with less than three sampling time points. Even trough level with limited sampling method (r2 = 0.86) correlated better than the level after 2 h of dosing (r2 = 0.75) or trough level (r2 = 0.64) as single values without limited sampling method. Moreover, the individualized population‐pharmacokinetic model had a low prediction bias and excellent precision.

Conclusion : Multiple rigid sampling time points limit the use of limited sampling formulas. The major advantage of the Bayesian estimation approach presented here, is that blood sampling time points are not fixed, as long as sampling time is known. The predictive performance of this new approach is superior to trough level and that after 2 h of dosing and at least as good as limited sampling formulas. It is of clear advantage in busy out‐patient clinics.
Upper gastrointestinal tolerability of once weekly alendronate 70 mg with concomitant non‐steroidal anti‐inflammatory drug use
Authors: Cryer B. , Miller P. , Petruschke R. A. , Chen E. , Geba G. P. , de Papp A. E.
Published: March 2005

Background : Both oral bisphosphonates and non‐steroidal anti‐inflammatory drugs have the potential to irritate the upper gastrointestinal mucosa, and are frequently used by the same patient population.

Aim : To determine the rate of upper gastrointestinal adverse events with once weekly alendronate 70 mg and concomitant non‐steroidal anti‐inflammatory drug use.

Methods : A post hoc analysis was performed on 222 patients who received both medications concomitantly during a 3‐month placebo‐controlled study. A total of 450 (224 alendronate; 226 placebo) postmenopausal women and men with osteoporosis were randomized. Concomitant non‐steroidal anti‐inflammatory drug users were defined as patients who received ≥7 continuous days of any dose of a dual cyclo‐oxygenase‐1 and cyclo‐oxygenase‐2 inhibiting non‐steroidal anti‐inflammatory drug, a selective cyclo‐oxygenase‐2 inhibitor, or aspirin. A survival analysis was performed, and significance assessed. Logistic regression was used to assess consistency of treatment effect on rate of upper gastrointestinal adverse events across non‐steroidal anti‐inflammatory drug subgroups.

Results : Similar percentages of alendronate (52.7%) and placebo (46.0%) patients used non‐steroidal anti‐inflammatory drugs regularly. Among concomitant non‐steroidal anti‐inflammatory drug users, 11 alendronate and 11 placebo patients experienced upper gastrointestinal adverse events (9.3% and 10.8%, respectively, P = 0.744). Logistic regression revealed no significant interaction (P = 0.722) between alendronate and concomitant non‐steroidal anti‐inflammatory drug use.

Conclusion : Based on this subgroup analysis, once weekly alendronate 70 mg used concomitantly with non‐steroidal anti‐inflammatory drugs, did not increase upper gastrointestinal adverse events relative to placebo over 3‐months.
Review article: psychosocial factors in the quality of life of patients with inflammatory bowel disease
Authors: Sainsbury A. , Heatley R. V.
Published: March 2005

Information on quality of life in inflammatory bowel disease is limited. Despite the clear importance of this topic to patients, quality of life measurement is seldom undertaken in day‐to‐day management of patients or included in clinical trials. Although previous reviews have dealt with quality of life, the area of psychosocial functioning has not been specifically addressed.

The aim of this study was to review the psychosocial factors affecting quality of life in patients with inflammatory bowel disease, using an electronic search of MEDLINE, EMBASE, CINAHL and psycINFO. Of the 751 articles identified by the search, 107 were considered relevant and included in the review.

A number of psychosocial factors appear to be important, including gender, socioeconomic status, ethnicity and perceived stress. To improve the quality of life in patients with inflammatory bowel disease, clinicians’ attention needs to be drawn towards this subject, with an awareness of those patient groups more vulnerable to impaired quality of life. These identified variables also represent important factors, which should be adjusted for when conducting research into quality of life in these patients.
Meta‐analysis: upper gastrointestinal tolerability of valdecoxib, a cyclooxygenase‐2‐specific inhibitor, compared with nonspecific nonsteroidal anti‐inflammatory drugs among patients with osteoarthritis and rheumatoid arthritis
Authors: Eisen G. M. , Goldstein J. L. , Hanna D. B. , Rublee D. A.
Published: March 2005

Aim : To compare the incidence of abdominal pain, dyspepsia and/or nausea associated with valdecoxib, nonspecific nonsteroidal anti‐inflammatory drugs and placebo in patients with rheumatoid arthritis and osteoarthritis.

Methods : Data from five randomized, double‐blind 12‐week trials were pooled. Independent risk factors for abdominal pain, dyspepsia and/or nausea were also determined.

Results : The final analysis consisted of 4394 patients. Nonspecific nonsteroidal anti‐inflammatory drug users (n = 1185) received naproxen 1000 mg/day (n = 766), ibuprofen 2400 mg/day (n = 207) or diclofenac sodium 150 mg/day (n = 212). Valdecoxib users received 10 mg/day (n = 955), 20 mg/day (n = 851) or 40 mg/day (n = 430). A total of 973 patients received placebo. The nonspecific nonsteroidal anti‐inflammatory drug group was most likely to report abdominal pain or dyspepsia, while the placebo group reported the highest incidence of nausea. The most important risk factors for abdominal pain, dyspepsia and/or nausea were nonspecific nonsteroidal anti‐inflammatory drug use, gastrointestinal history of nonspecific nonsteroidal anti‐inflammatory drug‐related intolerance or gastroduodenal ulcers, osteoarthritis diagnosis, female gender and age <65 years.

Conclusion : This pooled analysis demonstrates a clear decrease in dyspepsia and an improvement in upper gastrointestinal tolerability for patients with osteoarthritis and rheumatoid arthritis taking valdecoxib, even at supratherapeutic doses, compared with those taking nonspecific nonsteroidal anti‐inflammatory drugs over 12 weeks.
Impact of pregnancy on the clinical activity of Crohn's disease
Authors: Agret F. , Cosnes J. , Hassani Z. , Gornet J.‐M. , Gendre J.‐P. , Lémann M. , Beaugerie L.
Published: March 2005

Background : The impact of pregnancy on Crohn's disease activity has been poorly investigated.

Aim : To determine the effect of pregnancy on Crohn's disease activity from the retrospective analysis of a cohort of women who had a regular clinical follow‐up.

Methods : Seventy pregnancies occurring in 61 women were studied. The Harvey–Bradshaw index was determined during the four quarters preceding each pregnancy, the three quarters of pregnancy and the four quarters following delivery.

Results : The mean Harvey–Bradshaw index during pregnancy [0.68 (0.18), mean (S.E.M.)] was significantly lower than that of the year preceding pregnancy [0.98 (0.16), P = 0.03] and that of the year following delivery [1.10 (0.17), P = 0.04]. In non‐smoking women (48 pregnancies), there was no significant change of Harvey–Bradshaw index between these intervals. Whereas in those who smoked (22 pregnancies), most of whom reduced tobacco consumption during pregnancy, the mean Harvey–Bradshaw index during pregnancy was significantly reduced compared with that of the year following delivery [0.58 (0.20) vs. 1.60 (0.33), P = 0.01]. The use of drugs was significantly lower during pregnancy.

Conclusions : Crohn's disease activity is mildly but significantly lower during pregnancy. The reduction of tobacco consumption during pregnancy in smoking women may play an important role in this improvement.
Severe haemorrhage following abdominal paracentesis for ascites in patients with liver disease
Authors: Pache I. , Bilodeau M.
Published: March 2005

Background : Bleeding is a recognized complication of abdominal paracentesis. Special concern has been raised when it is performed in patients with liver failure because of coagulation disorders and collaterals in the abdominal wall.

Aim : To assess the clinical characteristics of patients who developed haemorrhagic complications after paracentesis.

Methods : We reviewed all cases of severe haemorrhage occurring after paracentesis in patients admitted to the Liver Unit of our institution between 1994 and 2004.

Results : Nine cases were identified among 4729 procedures. The occurrence of severe haemorrhage represented 0.19% of all procedures with a death rate of 0.016%. Bleeding was not related to operator experience, elevated international normalized ratio or low platelets. It occurred in patients with high model for end‐stage liver disease and Child‐Pugh scores. Furthermore, some degree of renal failure was present in all but one patient.

Conclusion : Severe haemorrhage after abdominal paracentesis in patients with liver disease occurs in 0.2% of cases. It occurs in patients with severe liver failure and is often associated with significant pre‐existing renal dysfunction.
Adefovir dipivoxil added to ongoing lamivudine therapy in patients with lamivudine‐resistant hepatitis B e antigen‐negative chronic hepatitis B
Authors: Vassiliadis T. , Nikolaidis N. , Giouleme O. , Tziomalos K. , Grammatikos N. , Patsiaoura K. , Zezos P. , Gkisakis D. , Theodoropoulos K. , Katsinelos P. , Orfanou‐Koumerkeridou E. , Eugenidis N.
Published: March 2005

Background : Long‐term treatment with lamivudine is required to control viral replication in patients with hepatitis B e antigen‐negative chronic hepatitis B, but is associated with a high rate of viral resistance. The role of adefovir dipivoxil in these patients has not been definitively evaluated.

Aim : To address the role of adefovir in the management of patients with lamivudine‐resistant hepatitis B e antigen‐negative chronic hepatitis B.

Methods : Patients were assigned to receive adefovir 10 mg once daily plus ongoing lamivudine 100 mg once daily for 52 weeks. The primary end point was reduction in serum hepatitis B virus DNA level (hepatitis B virus DNA response). Secondary end points included the proportion of patients with undetectable hepatitis B virus DNA at week 52 (complete virological response) and the percentage of patients with normalization of alanine transferase level at week 52 (biochemical response).

Results : A total of 49 consecutive patients were enrolled in this study. After 52 weeks of treatment, all patients had an hepatitis B virus DNA response and 57.1% had complete virological response. Biochemical response occurred in 75.6% of patients.

Conclusions : Administration of adefovir in patients with lamivudine‐resistant chronic hepatitis B results in significant suppression of viral replication. Nevertheless, continuous therapy will probably be needed in order to maintain remission in these patients.
Feature
Authors: Horne David J.
Published: March 2005

NASA lander Opportunity is achieving something that no previous planetary explorer has ever managed: field mapping and logging of exposed bedrock on another planet, in the Terra Meridiani (the Land of the Meridian) of Mars.
The Asian Tsunami disaster, December 2004
Authors: Waltham Tony
Published: March 2005

The tragic scenes of human suffering in the wake of the Asian tsunami in late December 2004 have thrown into sharp relief the Earth's destructive power (Fig. 1). Caused by a tectonic event off the coast of Sumatra, it could be described as a very large earthquake, an unusual tsunami and a massive disaster. Or, with a longer view, it could be considered a normal feature of a convergent plate boundary. Both views are correct.

Mass destruction after the tsunami hit the village on the sand bar at Phi Phi Island, Thailand, with unscathed limestone hills behind (Rex Features).

image
Difference in root canal length between Asians and Caucasians
Authors: Kim E. , Fallahrastegar A. , Hur Y.‐Y. , Jung I.‐Y. , Kim S. , Lee S.‐J.
Published: March 2005

Aim  To investigate whether there is a racial difference in canal length between the Asians and Caucasians.

Methodology  Five hundred and fifteen Asian patients who had received root canal treatment at the Yonsei University Hospital, Korea between 1995 and May 2001 and 324 Caucasoid patients who had received root canal treatment at the Graduate Endodontic Clinic at the University of Pennsylvania, US were selected. The clinical endodontic procedures at both clinics were similar. An electronic apex locator (Root‐ZXTM; J. Morita Co., Kyoto, Japan) was used to measure the initial working lengths and this was verified by conventional radiography. The measurements from both Asian and Caucasian teeth were compared using a Student's t‐test and a Mann–Whitney test.

Results  The mean difference in canal length of pooled teeth between the Asian and Caucasian teeth was 1.2 mm, with a range from 0 to 2.5 mm. The greatest difference was in the distobuccal canal (2.5 mm) of maxillary first molar teeth followed by the mesiolingual canal (2.3 mm) of mandibular second molar, the buccal canal (2.1 mm) of the maxillary second premolar, the maxillary first molar and the mandibular second molar.

Conclusion  Tooth lengths in Asians were shorter than Caucasians.
Influence of the pulpal components on human dentine permeability in vitro
Authors: Puapichartdumrong P. , Ikeda H. , Suda H.
Published: March 2005

Aim  To examine the influence of the retained pulpal components on permeability of human dentine by monitoring drug diffusion.

Methodology  Twelve intact dentine discs were prepared from freshly extracted human third molars. The dentine surface on the enamel side was etched with 10% polyacrylic acid for 30 s. The drug diffusion test was carried out before and after removal of the retained pulpal components. Each dentine disc was inserted between two plastic chambers; enamel‐ and pulpal‐side chambers, which were filled with 0.05 mol L−1 naproxen sodium (NA) and phosphate‐buffered saline (PBS), respectively. After 10 min, the solution on the pulpal‐side chamber was collected to determine the concentration of NA using a spectrophotometer. To remove the retained pulpal components and residual NA, the pulp chamber of each disc was washed out with PBS and placed in an ultrasonic cleaner. After removal of these components and the residual NA, the drug diffusion test was repeated. The inner surface of the pulp chamber was observed using scanning electron microscopy (SEM) before and after the removal of the retained pulpal components.

Results  The amount of NA that diffused through dentine into the pulp was significantly higher after the pulp chamber was washed out with PBS (paired t‐test, P < 0.05). SEM observation demonstrated the presence of the retained pulpal components, odontoblastic layer and some parts of subodontoblastic zone, covering the surface of predentine. These components were removed after the pulp chamber was washed out with PBS followed by cleaning in an ultrasonic cleaner.

Conclusions  The presence of retained pulpal components had a significant influence on drug diffusion through dentine discs.
Frequency and type of canal isthmuses in first molars detected by endoscopic inspection during periradicular surgery
Authors: Von Arx T.
Published: March 2005

Aim  To analyse the occurrence of canal isthmuses in molars following root‐end resection.

Methodology  The material consisted of 56 mandibular and 32 maxillary first molars subjected to periradicular surgery. Based on radiographic, clinical, as well as intraoperative status, only roots with associated pathological lesions were treated. In total, 124 roots were resected (80 mandibular and 44 maxillary molar roots). The cut root faces were inspected with a rigid endoscope following apical root‐end resection. The number of canals as well as the presence and type of canal isthmuses were recorded.

Results  In maxillary first molars, 76% of resected mesio‐buccal roots had two canals and an isthmus, 10% had two canals but no isthmus, and 14% had a single canal. All disto‐buccal and palatal roots had one canal. In mandibular first molars, 83% of mesial roots had two canals with an isthmus. In 11%, two canals but no isthmus were present, and 6% demonstrated a single canal. Sixty‐four per cent of distal roots had a single canal and 36% had two canals with an isthmus.

Conclusions  This clinical study during periradicular surgery and intraoperative endoscopic examination of first permanent molars found a high frequency of canal isthmuses at the resection level. Endoscopic inspection also demonstrated that none of the isthmuses were filled, emphasizing the difficulty of orthograde instrumentation and root filling of canal isthmuses.
Prevalence of persistent pain after endodontic treatment and factors affecting its occurrence in cases with complete radiographic healing
Authors: Polycarpou N. , Ng Y.‐L. , Canavan D. , Moles D. R. , Gulabivala K.
Published: March 2005

Aims  To (i) determine the prevalence of persistent dento‐alveolar pain following nonsurgical and/or surgical endodontic treatment conducted in a teaching dental hospital and (ii) identify the risk factors associated with persistent pain after apparently successful root canal treatment.

Study design  A total of 175 patients/teeth were reviewed 12–59 months following treatment. The patients were examined clinically and radiographically and a detailed pain history obtained. Multiple logistic regression analysis was used to investigate the association between potential risk factors and persistent pain after successful endodontic treatment.

Results  The prevalence of persistent pain after successful root canal treatment was 12% (21/175). Treatment success was determined by the absence of clinical and radiographic signs of dental disease. The factors that were significantly (P < 0.05) associated with persistent pain following endodontic treatment were: ‘duration of preoperative pain’ [odds ratio (OR) = 8.6], ‘preoperative pain from the tooth’ (OR = 7.8), ‘preoperative tenderness to percussion’ (OR = 7.8), ‘previous chronic pain problems’ (OR = 4.5), ‘gender’ (OR = 4.5) and ‘history of painful treatment in the orofacial region’ (OR = 3.8). ‘Type of treatment received (surgical or nonsurgical treatment)’ showed borderline significance at the 10% level.

Conclusions  The presence and duration of preoperative pain from the tooth site, lasting at least 3 months, a positive history of previous chronic pain experience or painful treatment in the orofacial region, and female gender were important risk factors associated with persistent pain after successful endodontic treatment.
Outcome of root canal treatment using Thermafil and cold lateral condensation filling techniques
Authors: Chu C. H. , Lo E. C. M. , Cheung G. S. P.
Published: March 2005

Aim  To evaluate the outcome of root canal treatment (RCT) using either Thermafil (TF) or lateral condensation (LC) as filling technique, and to compare the time required for the treatment when either filling technique was used.

Methodology  This study involved all patients attending the dental clinic of a university in Hong Kong who required primary, nonsurgical RCT. It was a prospective clinical trial involving 85 teeth in 79 patients aged 15–69 years (mean 48 ± 12 years), which required root treatment and finally filling with either TF or LC by one of four dentists following a standard treatment protocol. The time used for the entire course of treatment was recorded. The treated teeth were examined both clinically and radiographically 3 years after the treatment by a single examiner who did not know their group assignment.

Results  A total of 85 teeth from 79 patients were included in this study and 71 teeth from 64 patients were examined after 3 years. Thirty‐four teeth were root filled with LC and 37 with TF. The overall attrition rate was 16% (14/85). There were 22 incisors and canines, 21 premolars and 28 molars for evaluation. Post‐treatment disease with clinical symptoms and/or radiographic radiolucency was observed in seven teeth (21%) of the LC group and in seven teeth (19%) in the TF group. There was no statistically significant difference (P > 0.05) for the presence of disease between the two groups. It was found that irrespective of the filling method used, teeth later restored with extracoronal restorations had a lower association with disease than those receiving intracoronal restorations (7% vs. 30%; P = 0.037). RCT took, on average, 20 min less when TF was used for filling compared with LC (98 min vs. 78 min, P = 0.003).

Conclusions  Using TF or LC in the filling of root canals did not result in significant difference in the clinical treatment outcome. TF consumed significantly less time than LC. The type of postendodontic restoration had a significant association with the presence of post‐treatment disease.
CSF iron, ferritin and transferrin levels in restless legs syndrome
Authors: MIZUNO SOICHI , MIHARA TAKUMI , MIYAOKA TSUYOSHI , INAGAKI TAKUZI , HORIGUCHI JUN
Published: March 2005

The aim of this study is evaluating iron, ferritin, and transferrin in both serum and CSF in patients of restless legs syndrome (RLS), based on the hypothesis that iron deficiency in the central nervous system (CNS) causes the symptoms as a result of the dysfunction of dopaminergic systems. These parameters, polysomnographic sleep measures, and subjective evaluation of the sleep quality were compared in 10 patients of idiopathic RLS (RLS group) and 10 age‐matched patients of psychophysiological insomnia without RLS symptoms (non‐RLS group). With sleep patterns, sleep latency was longer and sleep efficiency was lower in the RLS group than those in the non‐RLS group. Periodic leg movement index in the RLS group was higher than that of the non‐RLS group. With serum examination, there were no significant differences for the iron, ferritin, and transferrin values between the both groups. With CSF examination, the iron and ferritin values were lower and the transferrin values were higher in the RLS group than those in the non‐RLS group. There was positive correlation between the serum and CSF ferritin levels in the both groups, but the slope of the regression lines for the RLS group was lower than that for the non‐RLS group. These results indicate low brain iron concentration caused by the dysfunction of iron transportation from serum to CNS in patients with idiopathic RLS.
Chronic insomnia and performance in a 24‐h constant routine study
Authors: VARKEVISSER MICHAEL , KERKHOF GERARD A.
Published: March 2005

Insomniacs report daytime functioning problems, but studies of neurobehavioral functioning in insomniacs have shown little objective evidence of impairment. In addition, very little is known about the influence of the circadian clock on performance in chronic insomniacs. In the present study, we investigated whether chronic insomnia is associated with an overall performance deficit, and what the effect is of circadian rhythmicity, under strictly controlled laboratory conditions. A 24‐h experiment was carried out under constant routine conditions. Psychomotor performance, body temperature, and subjective functioning of 11 insomniacs and 13 healthy subjects were assessed. The insomniacs showed significant overall performance impairments in vigilance, working memory, and motor control. In addition, body temperature, performance and subjective functioning showed a circadian pattern similar to healthy subjects, with trough values in the late night/early morning and peak values in the early evening. Self‐reported functioning among the insomniacs indicated mood disturbances, concentration problems, elevated fatigue and elevated sleepiness. The results indicated that chronic insomnia is associated with a substantial lowering of the 24‐h level of performance and subjective functioning, irrespective of the type of task and/or the particular parameter, and without differential effects of circadian rhythmicity. Apparently, chronic insomnia has a negative impact upon performance as measured under strictly controlled, unmasked conditions.
The scoring of arousals in healthy term infants (between the ages of 1 and 6 months)
Authors:   THE INTERNATIONAL PAEDIATRIC WORK GROUP ON AROUSALS
Published: March 2005

Various definitions of arousals have been used in infants. An international group of experts has worked on a consensus for the scoring of arousals in healthy infants, aged between 1 and 6 months. This opinion paper summarizes the consensus statement on the scoring of arousal. The paper reviews recommended techniques for the recording of arousal in infants. Scoring includes the differentiation between subcortical activation, with no visible change n the electroencephalograph (EEG) recording, and cortical arousals associated with EEG changes. The arousals are further scored as spontaneous or induced, according to environmental conditions. Potential limitations to the method are discussed, with the hope that this document could contribute to promote further progresses in the scoring of infants arousals from sleep.
Endocrinological and catecholaminergic alterations during sleep deprivation and recovery in male rats
Authors: ANDERSEN MONICA L. , MARTINS PAULO J. F. , D'ALMEIDA VÂNIA , BIGNOTTO MAGDA , TUFIK SERGIO
Published: March 2005

Since previous data of our group showed increased concentrations in HPA axis hormones in sleep deprived rats, we hypothesized that this augmentation could produce effects in other hormonal systems, particularly in the sexual system. Considering that little is known about how the hormonal system changes during the recovery period after sleep deprivation (SD), our objective was to examine from what point SD alters sexual and stress‐related hormones along with plasma catecholamine concentrations during 4 days. We also sought to verify the time course of their recovery after an equivalent period of recovery sleep. Rats were deprived of sleep by the platform technique for 1–4 days and were allowed to recover for the same period. Plasma catecholamines [dopamine (DA) and noradrenaline (NOR)], testosterone, estrone, progesterone, prolactin, corticosterone and adrenocorticotropic hormone (ACTH) concentrations were measured. Comparisons between groups showed that the SD procedure used in the present study produced marked alterations in almost all studied hormones from 24 h of SD, except for estrone and prolactin (which required 96 h of SD to become altered). Testosterone and estrone decreased, whereas progesterone, prolactin, corticosterone, ACTH, DA and NOR increased. During recovery period, progesterone, prolactin and corticosterone concentrations returned to control levels, whereas testosterone, estrone, NOR and DA did not. In addition, after 48 h of recovery ACTH and NOR decreased below control concentrations, remaining low until 96 h of sleep recovery. Thus, SD showed long lasting, differential effects upon these neurochemicals suggesting that each has its own pattern of responses to SD as well as variable periods of recovery.
Circadian activity rhythm in demented and non‐demented nursing‐home residents measured by telemetric actigraphy
Authors: PAAVILAINEN PAULA , KORHONEN ILKKA , LÖTJÖNEN JYRKI , CLUITMANS LUC , JYLHÄ MARJA , SÄRELÄ ANTTI , PARTINEN MARKKU
Published: March 2005

There is a need to develop unobtrusive methods for long‐term monitoring of sleep/wake and circadian activity patterns in the elderly both in nursing homes and at home settings as sleep is important for health and well‐being. The IST Vivago® WristCare is an active social alarm system, which provides continuous telemetric monitoring of the user's activity. We examined how the activity signal measured by IST Vivago differed between demented and non‐demented subjects living in a nursing home, and how it correlated with the subjective assessment of sleep quality and daytime alertness. The activity signal data together with subjective assessments of sleep quality and daytime vigilance were collected from 42 volunteers (aged 56–97 years; 23 demented and 19 non‐demented) for at least 10 days. The demented subjects had lower daytime activity and higher nocturnal activity than the non‐demented subjects. Correlations between the activity parameters and self‐assessments were weak but statistically significant. We also found correlation between functional ability and diurnal activity. The results are in line with previous studies with demented and non‐demented elderly subjects and suggest that the IST Vivago system provides a valid instrument for unobtrusive continuous long‐term monitoring of the circadian rhythm and sleep/wake patterns in the elderly.
Sleep apnea‐related cognitive deficits and intelligence: an implication of cognitive reserve theory
Authors: ALCHANATIS MANOS , ZIAS NIKOLAOS , DELIGIORGIS NIKOLAOS , AMFILOCHIOU ANASTASIA , DIONELLIS GIORGOS , ORPHANIDOU DORA
Published: March 2005

Cognitive deficits in patients with obstructive sleep apnea syndrome (OSAS) are well demonstrated, but the pathophysiology of these deficits is still controversial, as the relationship between OSA severity and cognitive deficits is usually weak. Our study considers the possible relationship between OSA‐related cognitive deficits and the overall intellectual function of OSA patients. Forty‐seven OSA patients and 36 normal individuals underwent a neuropsychological battery test assessing attention and alertness. According to the resulting IQ score, patients and controls were divided into a high‐intelligence group (IQ ≥ 90th percentile) and a normal‐intelligence group (50 ≤ IQ < 90%ile). Between the two patient groups there were no significant differences noticed, regarding OSA severity or sleepiness. High‐intelligence patients showed the same attention/alertness performance compared with the high‐intelligence controls. On the contrary, patients with normal‐intelligence showed attention/alertness decline compared with the normal‐intelligence control group. The two patient groups were re‐examined with the same battery test after at least 1 year of CPAP treatment. At re‐examination neither patient group showed any differences regarding attention and alertness compared with the control groups. We assume that high‐intelligence may have a protective effect against OSA‐related cognitive decline, perhaps due to increased cognitive reserve.
Fatigue‐related impairment in the speed, accuracy and variability of psychomotor performance: comparison with blood alcohol levels
Authors: MARUFF PAUL , FALLETI MARINA G. , COLLIE ALEX , DARBY DAVID , MCSTEPHEN MICHAEL
Published: March 2005

Cognitive performance is impaired by fatigue arising from sustained wakefulness and alcohol. Three recent papers directly compared the effects of increasing fatigue and blood alcohol concentration (%BAC) to provide a framework for understanding fatigue‐related cognitive impairment. While the expression of fatigue‐related cognitive impairments in terms of %BAC equivalents is sound, the methodology in each study was flawed in that the statistics used to compare the effects of %BAC and fatigue on cognition did not account for variation between or within each condition. The point estimates of the difference between a baseline and any level of fatigue or %BAC provided no indication of the size of difference that could reasonably be expected by chance. Importantly, all studies showed that variation increased as cognitive performance declined because of both increasing fatigue and %BAC. The current study compared the effect of increasing levels of %BAC and fatigue on the simple reaction task from the CogState test battery on 40 healthy adults using statistical methods that account for intra‐individual and within‐group variability in performance. After 24 h of sustained wakefulness and with 0.08%BAC, individuals showed maximal cognitive impairment; however, the magnitude of impairment found for fatigue was equivalent only to that observed for 0.05%BAC. Re‐analysis of the data using percentage change scores indicated that the magnitude of fatigue‐related cognitive impairment was much greater than that detected for 0.08%BAC. This suggests that previous studies that have not accounted for variability in the performance data have overestimated the effect of fatigue on cognitive performance.
Mutations in Arabidopsis acyl‐CoA oxidase genes reveal distinct and overlapping roles in β‐oxidation
Authors: Adham A. Raquel , Zolman Bethany K. , Millius Arthur , Bartel Bonnie
Published: March 2005

Indole‐3‐butyric acid (IBA) is an endogenous auxin used to enhance rooting during propagation. To better understand the role of IBA, we isolated Arabidopsis IBA‐response (ibr) mutants that display enhanced root elongation on inhibitory IBA concentrations but maintain wild‐type responses to indole‐3‐acetic acid, the principle active auxin. A subset of ibr mutants remains sensitive to the stimulatory effects of IBA on lateral root initiation. These mutants are not sucrose dependent during early seedling development, indicating that peroxisomal β‐oxidation of seed storage fatty acids is occurring. We used positional cloning to determine that one mutant is defective in ACX1 and two are defective in ACX3, two of the six Arabidopsis fatty acyl‐CoA oxidase (ACX) genes. Characterization of T‐DNA insertion mutants defective in the other ACX genes revealed reduced IBA responses in a third gene, ACX4. Activity assays demonstrated that mutants defective in ACX1, ACX3, or ACX4 have reduced fatty acyl‐CoA oxidase activity on specific substrates. Moreover, acx1 acx2 double mutants display enhanced IBA resistance and are sucrose dependent during seedling development, whereas acx1 acx3 and acx1 acx5 double mutants display enhanced IBA resistance but remain sucrose independent. The inability of ACX1, ACX3, and ACX4 to fully compensate for one another in IBA‐mediated root elongation inhibition and the ability of ACX2 and ACX5 to contribute to IBA response suggests that IBA‐response defects in acx mutants may reflect indirect blocks in peroxisomal metabolism and IBA β‐oxidation, rather than direct enzymatic activity of ACX isozymes on IBA‐CoA.
Genomics‐based selection and functional characterization of triterpene glycosyltransferases from the model legume Medicago truncatula
Authors: Achnine Lahoucine , Huhman David V. , Farag Mohamed A. , Sumner Lloyd W. , Blount Jack W. , Dixon Richard A.
Published: March 2005

The biosynthesis of triterpene saponins is poorly characterized in spite of the importance of these glycosylated secondary metabolites for plant defense and animal health. The model legume Medicago truncatula synthesizes more than 30 different saponins based on at least five triterpene aglycones; soyasapogenols B and E, medicagenic acid, hederagenin and bayogenin. We have employed an inducible cell culture system, DNA array‐based and in silico transcript profiling, and targeted metabolite profiling, to identify triterpene glycosyltransferases (GTs) from among the more than 300 GTs expressed in M. truncatula. Two uridine diphosphate glucosyltransferases were functionally characterized; UGT73K1 with specificity for hederagenin and soyasapogenols B and E, and UGT71G1 with specificity for medicagenic acid. The latter enzyme also glycosylated certain isoflavones and the flavonol quercetin with higher efficiency than triterpenes; however, integrated transcript and metabolite profiling supported a function for UGT71G1 in terpenoid but not (iso)flavonoid biosynthesis in the elicited cell cultures.
Silencing the nuclear actin‐related protein AtARP4 in Arabidopsis has multiple effects on plant development, including early flowering and delayed floral senescence
Authors: Kandasamy Muthugapatti K. , Deal Roger B. , McKinney Elizabeth C. , Meagher Richard B.
Published: March 2005

Actin‐related proteins (ARPs) share moderate sequence homology and basal structure with conventional actins and are found in all eukaryotes. While the functions of most of the divergent ARPs are not clear, several of them are localized to the nucleus and have been identified as components of various chromatin‐modifying complexes. Using an antibody to Arabidopsis AtARP4, we found this conserved homolog of human BAF53 and yeast Arp4 is concentrated in the nucleoplasm of Arabidopsis, Brassica, and tobacco cells. To gain further insight into the role of ARP4, we have examined Arabidopsis plants that are defective in AtARP4 expression. Phenotypic analysis of the arp4‐1 mutant allele, which has a T‐DNA insertion in the promoter region and a moderate reduction in the level of AtARP4 protein expression, revealed partial sterility due to defects in anther development. Targeting the distinct, 3′ UTR of AtARP4 transcripts with RNA interference caused a drastic reduction in the level of AtARP4 protein expression in several independent transgenic lines, and resulted in strong pleiotropic phenotypes such as altered organization of plant organs, early flowering, delayed flower senescence and high levels of sterility. Western blot analysis and immunolabeling demonstrated a clear correlation between reductions in the level of AtARP4 expression and severity of the phenotypes. Based on our results and data on the orthologs of AtARP4 in yeast and other organisms, we suggest that AtARP4 is likely to exert its effects on plant development through the modulation of chromatin structure and subsequent changes in gene regulation.
Arabidopsis mutants Atisa1 and Atisa2 have identical phenotypes and lack the same multimeric isoamylase, which influences the branch point distribution of amylopectin during starch synthesis
Authors: Delatte Thierry , Trevisan Martine , Parker Mary L. , Zeeman Samuel C.
Published: March 2005

The aim of this work was to evaluate the function of isoamylase in starch granule biosynthesis in Arabidopsis leaves. A reverse‐genetic approach was used to knockout AtISA1, one of three genes in Arabidopsis encoding isoamylase‐type debranching enzymes. The mutant (Atisa1‐1) lacks functional AtISA1 transcript and the major isoamylase activity (detected by native gels) in crude extracts of leaves. The same activity is abolished by mutation at the DBE1 locus, which encodes a second isoamylase‐type protein, AtISA2. This is consistent with the idea that ISA1 and ISA2 proteins are subunits of the same enzyme in vivo. Atisa1‐1, Atisa2‐1 (dbe1), and the Atisa1‐1/Atisa2‐1 double mutant all have identical phenotypes. Starch content is reduced compared with the wild type but substantial quantities of the soluble glucan phytoglycogen are produced. The amylopectin of the remaining starch and the phytoglycogen in the mutants are structurally related to each other and differ from wild‐type amylopectin. Electron micrographs reveal that the phytoglycogen‐accumulating phenotype is highly tissue‐specific. Phytoglycogen accumulates primarily in the plastids of the palisade and spongy mesophyll cells. Remarkably, other cell types appear to accumulate only starch, which is normal in appearance but is altered in structure. As phytoglycogen accumulates during the day, its rate of accumulation decreases, its structure changes and intermediates of glucan breakdown accumulate, suggesting that degradation occurs simultaneously with synthesis. We conclude that the AtISA1/AtISA2 isoamylase influences glucan branching pattern, but that this may not be the primary determinant of partitioning between crystalline starch and soluble phytoglycogen.
Greater early pancreas graft loss in women compared with men after simultaneous pancreas–kidney transplantation
Authors: Colling Christopher , Brian Stevens R , Lyden Elizabeth , Lane James , Mack‐Shipman Lynn , Wrenshall Lucile , Larsen Jennifer
Published: March 2005

Abstract: Background:  Gender differences in graft survival has been reported after some types of organ transplantation, but not after pancreas transplantation. This study compares graft survival between women and men after simultaneous pancreas–kidney transplantation (SPK).

Methods:  All first time SPK (n = 163) transplants (109 M/54 F) performed between 1989 and 2000 at University of Nebraska Medical Center, where data was available, were analyzed for overall graft and patient survival. Graft failure was then subdivided into early (<6 months), and late (>6 months), and compared between women and men.

Results:  The 5‐yr pancreas and kidney graft survival rates for all SPK recipients was 86% [95% confidence interval (CI) = 81–92%] and 87% (95% CI = 82–93%), respectively. While overall pancreas graft survival in women was similar to men (p = 0.16), early pancreas graft failure was greater in women than men (p = 0.010) with no one cause for failure predominant. There was no gender difference in late pancreas graft failure or in early, or late kidney graft failure in the same recipients. The gender difference was unexplained by differences in age, immunosuppression, body mass index (BMI), or diabetes duration between women and men.

Conclusions:  This is the first report of a gender difference in pancreas graft survival after SPK with greater early (<6 months) pancreas graft failure in women than men. With no gender difference in kidney graft failure in the same individuals, gender differences in immune responses are unlikely to be the cause. Multiple variables likely contribute.
Hypertension, antihypertensive agents and outcomes following renal transplantation
Authors: Tutone VK , Mark PB , Stewart GA , Tan CC , Rodger RSC , Geddes CC , Jardine AG
Published: March 2005

Abstract:  Hypertension is common following renal transplantation and adversely affects graft and patient survival. However, strategies for antihypertensive drug therapy and target blood pressure have not been clearly defined.

Aim:  To assess the influence of achieved blood pressure and antihypertension drug therapy on graft and patient survival with the aim of identifying targets and event rates for future intervention studies.

Methods:  We undertook a longitudinal follow up study of 634 renal transplant patients. Patients were surveyed in December 1994 and followed up after 102 months. Blood pressure (BP) was determined from the mean of three clinic readings and antihypertensive drug therapy recorded.

Results:  Complete follow up data were available for analysis on 622 patients (57.2% male; mean age: 45.2 ± 13.0 yr. There were 158 (25.4%) deaths and 115 (18.5%) death‐censored graft failures. Lower systolic and diastolic blood pressure were associated with better graft survival in the Kaplan–Meier analysis. Univariate analysis showed serum creatinine (HR 1.012, p < 0.001), duration of renal replacement therapy (HR 0.946, p = 0.012), age (HR 0.979, p = 0.014) and pulse pressure (HR 1.017, p = 0.044) to be predictors of graft survival with serum creatinine and duration of renal replacement therapy as the only significant factors in the multivariate analysis. Lower systolic and pulse pressure were associated with better patient survival in the Kaplan–Meier analysis. Age (HR) 1.062, p < 0.0001), serum creatinine (HR 1.002, p = 0.021), diabetes (HR 3.371, p < 0.0001), and pulse pressure (HR 1.013, p = 0.036) were significant predictors of patient survival in the univariate and multivariate analysis. Patient survival was reduced with increasing number of antihypertensives (p < 0.05), as was graft survival (p < 0.05). Reduced patient and graft survival were seen in patients prescribed calcium channel antagonists (p < 0.01). There was no increased patient mortality in those patients on beta‐blockers or angiotensin converting enzyme (ACE) inhibitors.

Conclusion:  Hypertension is a risk factor, which remains despite the use of anti‐hypertensives, for reduced patient and graft survival. The risk was not significant when blood pressure was entered together with serum creatinine in the multivariate analysis. Beta‐blockers may have a beneficial effect on cardiovascular mortality, and ACE inhibitors a beneficial effect on both patient and graft survival. There is a pressing need for interventional studies to assess the impact of blood pressure targets on patient and graft survival and the effect of individual agents on these outcomes.
Predictors of improvement in renal function after calcineurin inhibitor withdrawal for post‐liver transplant renal dysfunction
Authors: Hong Matthew KH , Angus Peter W , Jones Robert M , Vaughan Rhys B , Gow Paul J
Published: March 2005

Abstract:  Background:  Renal dysfunction after liver transplantation is a major management problem. Predictors of improvement in renal dysfunction after calcineurin inhibitor therapy (CNI) withdrawal and replacement with either mycophenolate mofetil (MMF) or azathioprine (AZA) have not previously been examined.

Methods:  Retrospective analysis of 33 post‐transplant patients with creatinine clearance (CrCl) below 50 mL/min who were changed from CNI to either MMF or AZA. Following CNI withdrawal patients were divided into two groups: those with improved CrCl after switching and those without, to identify the variables associated with improved renal function.

Results:  Variables associated with improved CrCl were: absence of hypertension or diabetes, shorter time between transplantation and switch, deterioration in CrCl in months prior to switch and treatment with MMF (compared with AZA).

Conclusions:  Our findings suggest CNI withdrawal should be targeted to a subgroup of patients whose renal function is most likely to improve.