bluuebunny/crossref_metadata_2025 huggingface dataset:
Levocetirizine has a longer duration of action on improving total nasal symptoms score than fexofenadine after single administration
Authors: Horak Friedrich , Zieglmayer Petra U. , Zieglmayer R. , Kavina A. , Lemell P.
Published: June 2005

Aims

To compare the onset and duration of action of the new antihistamine levocetirizine with that of the second‐generation antihistamine fexofenadine using the Vienna Challenge Chamber (VCC). The latter is an environment where subjects can be exposed to specific aeroallergens in controlled and reproducible conditions allowing for precise comparisons of anti‐allergic drugs.

Methods

Ninety‐four subjects received a single dose of levocetirizine 5 mg, fexofenadine 120 mg or placebo in a random order using a three‐way cross‐over design. On day 1, subjects were exposed to grass pollens (1500 grains/m3) in the VCC over a period of 4 h. Treatment was given 2 h after the start of challenge. On day 2, 22 h after drug intake, subjects were again exposed to pollens for 6 h. Specified symptoms were assessed by the subjects every 15 min using 5‐point scales. The main efficacy parameter was the change from baseline in the Major Symptom Complex Score (MSCS = sum of rhinorrhea, sneezing, itchy nose and eyes).

Results

Baseline characteristics, including symptoms scores, were similar in the three study groups. During the first 2 h after drug intake both antihistamines achieved clinically relevant and significant (P < 0.001) improvements in symptom scores. Twenty‐two to 24 h after drug intake, mean (SEM) MSCS reductions were: 1.9 (0.3) after placebo (baseline of 9.7), 3.8 (0.3) after fexofenadine (baseline of 9.9), and 5.1 (0.3) after levocetirizine (baseline of 9.8). Levocetirizine was significantly (P < 0.001) more effective than fexofenadine with a score difference of 1.3 (95% CI 0.7, 1.9). This was maintained until the end of the study (up to 28 h).

Conclusions

A rapid onset of action in alleviating seasonal allergic rhinitis (SAR) symptoms of subjects exposed to grass pollens in the VCC was observed after levocetirizine and fexofenadine. Levocetirizine was more effective than fexofenadine at and later than 22 h after drug intake, an indication of the longer‐duration of action of levocetirizine.
Association between CYP2C9 slow metabolizer genotypes and severe hypoglycaemia on medication with sulphonylurea hypoglycaemic agents
Authors: Holstein A. , Plaschke A. , Ptak M. , Egberts E.‐H. , El‐Din J. , Brockmöller J. , Kirchheiner J.
Published: June 2005

Aims

The genetically polymorphic cytochrome P450 (CYP) enzyme CYP2C9 metabolizes most sulphonylurea oral hypoglycaemic agents. The aim of this study was to test the hypothesis that individuals with genotypes predicting low CYP2C9 activity may be at a higher risk of severe drug‐associated hypoglycaemia.

Methods

In a case‐control study, 20 diabetic patients admitted to the emergency department with severe hypoglycaemia during sulphonylurea drug treatment were compared with a control group of 337 patients with type 2 diabetes but without a history of severe hypoglycaemia. A large sample of 1988 healthy Caucasian subjects served as a second control group.

Results

The CYP2C9 genotypes *3/*3 and *2/*3 that are predictive of low enzyme activity were more common in the hypoglycaemic group than in the comparison groups (10%vs <2%, respectively: odds ratio 5.2; 95% confidence interval 1.01, 27). Furthermore, the diabetic patient group with severe hypoglycaemia exhibited lower body mass indexes, higher rates of renal failure, were older compared with the diabetic group without severe hypoglycaemia, and were being treated with higher doses of glibenclamide.

Conclusions

These findings suggest that among other factors, individuals with genetically determined low CYP2C9 activity are at an increased risk of sulphonylurea‐associated severe hypoglycaemia. Thus, genotyping might be a tool for the better prediction of adverse effects caused by oral hypoglycaemic agents.
The role of CYP2C and CYP3A in the disposition of 3‐keto‐desogestrel after administration of desogestrel
Authors: Korhonen Tuomas , Tolonen Ari , Uusitalo Jouko , Lundgren Stefan , Jalonen Jorma , Laine Kari
Published: June 2005

Aims

Our objective was to study in vivo the role of CYP2C and CYP3A4 in the disposition of 3‐keto‐desogestrel after administration of desogestrel, by using the selective inhibitors fluconazole (CYP2C) and itraconazole (CYP3A4).

Methods

This study had a three‐way crossover design and included 12 healthy females, the data from 11 of whom were analyzed. In the first (control) phase all subjects received a single 150 µg oral dose of desogestrel alone. In the second and third phases subjects received a 4 day pretreatment with either 200 mg fluconazole or 200 mg itraconazole once daily in a randomized balanced order. Desogestrel was given 1 h after the last dose of the CYP inhibitor. Plasma 3‐keto‐desogestrel concentrations were determined for up to 72 h post dose.

Results

Pretreatment with itraconazole for 4 days significantly increased the area under the plasma concentration‐time curve (AUC) of 3‐keto‐desogestrel by 72.4% (95% confidence interval on the difference 12%, 133%; P = 0.024) compared with the control phase, whereas fluconazole pretreatment had no significant effect (95% CI on the difference −42%, 34%). Neither enzyme inhibitor affected significantly the maximum concentration (95% CI on the difference 14%, 124% for itraconazole and −23%, 40% for fluconazole) or elimination half‐life (95% CI on the difference −42%, 120% for itraconazole and −24%, 61% for fluconazole) of 3‐keto‐desogestrel.

Conclusions

According to the present study, the biotransformation of desogestrel to 3‐keto‐desogestrel did not appear to be mediated by CYP2C9 and CYP2C19 as suggested earlier. However, the further metabolism of 3‐keto‐desogestrel seems to be catalyzed by CYP3A4.
Dexamethasone as a probe for vinorelbine clearance
Authors: Puisset Florent , Dalenc Florence , Chatelut Etienne , Cresteil Thierry , Lochon Isabelle , Tisnes Pierre , Roché Henri
Published: June 2005

Aim

To assess the value of using dexamethasone as an in vivo probe for predicting vinorelbine clearance (CL).

Methods

A population approach (implemented with NONMEM) was used to analyse blood vinorelbine pharmacokinetic data from 20 patients who received a 20‐min intravenous infusion of vinorelbine (from 20 to 30 mg m−2). Selected patient clinical data as well as known functional single CYP3A5 and ABCB1 genotype were also tested as covariates.

Results

The best covariate model (with ± 95% confidence intervals) was based on dexamethasone plasma clearance (DPC) and alkaline phosphatase (ALP): vinorelbine blood CL (l h−1) = 39.8(± 4.0) × (DPC/13.2)0.524(±0.322) × (ALP/137)−0.198(±0.158). Interindividual variability in vinorelbine CL decreased from 29.7% (model without covariate) to 14.7% when including DPC and ALP. Vinorelbine CL was not correlated with body surface area (BSA) or associated with CYP3A5 and ABCB1 genotype.

Conclusions

These results indicate that individualization of vinorelbine dose would be improved by using dexamethasone clearance rather than BSA. Dexamethasone merits further evaluation as a probe of CYP3A metabolism.
Queen Mary Utilization of Antihypertensive Drugs Study: use of antihypertensive drug classes in the Hypertension Clinic 1996–2004
Authors: Cheung Bernard M. Y. , Wong Yuk Lin , Lau Chu Pak
Published: June 2005

Background

Utilization of antihypertensive drugs in the hypertension outpatient clinic is surveyed periodically in the Queen Mary Utilization of Antihypertensive Drugs Study (QUADS).

Methods

Two hundred and fifty‐one patients (123 men, 128 women) were interviewed in April to December 1996, 439 patients (232 men, 207 women) in January to December 99 and 228 patients (109 men, 119 women) in April to May 2004. Their case notes were reviewed.

Results

The percentages of patients receiving no drug (lifestyle modification), one, two, three and over three drugs were 7%, 48%, 36%, 7%, 3%, respectively, in 1996; 14%, 34%, 36%, 13% and 1%, respectively, in 1999; and 3%, 30%, 40%, 22% and 6%, respectively, in 2004. The number of drugs correlated with age and overweight. In 1996, 51% patients received calcium channel blockers (CCB); 46%β‐blockers (BB); 32% angiotensin‐converting enzyme inhibitors (ACEI); 15% thiazide diuretics; 5%α‐blockers; and 0% angiotensin receptor blockers (ARB). In 1999, the respective figures were 52% CCB, 49% BB, 24% ACEI, 22% thiazide diuretics, 4%α‐blockers and 2% ARB. In 2004, the respective figures were 65% CCB, 64% BB, 33% ACEI, 24% thiazide diuretics, 4%α‐blockers and 7% ARB. Fewer patients on BBs reported side‐effects. Only 11% were on α statin and 9% on aspirin. Blood pressure on treatment was 147 ± 21/84 ± 11 mmHg in 1999 and 144 ± 21/82 ± 11 mmHg in 2004.

Conclusions

Increasingly, multiple drugs were used for blood pressure control. Blood pressure control needs improvement, especially in diabetics. CCBs and BBs were consistently popular. Thiazide diuretics, ARBs, statins and aspirin were underused, despite favourable clinical trial evidence.
Cytochromes P450 and MDR1 mRNA expression along the human gastrointestinal tract
Authors: Thörn Mari , Finnström Niklas , Lundgren Stefan , Rane Anders , Lööf Lars
Published: June 2005

Aim

The aim of this study was to quantify the mRNA expression of three cytochromes P450 (CYP) and P‐glycoprotein (P‐gp) in the human gastrointestinal (GI) tract.

Method

Biopsies were obtained from gastric, duodenal, colonic and rectal mucosa during routine gastro‐colonoscopy in 27 patients. The biopsies were snap‐frozen in liquid nitrogen. Real‐time reverse transcriptase‐polymerase chain reaction (RT‐PCR) was used for the quantitative analyses of mRNA expressed by the CYP2E1, CYP3A4 and CYP3A5 genes, and the MDR1 gene coding for P‐gp protein. The mRNA expression of b‐actin was used as an internal standard for comparisons between samples.

Results

All CYP genes were expressed at all locations throughout the GI tract, although all showed substantial interindividual variation. CYP2E1 had the highest expression at all locations (P < 0.05 to P < 0.0001), except in the right colon. CYP3A4 and CYP3A5 had their highest mRNA expression in the duodenum (P < 0.001 and P < 0.000 001, respectively) and CYP2E1 in the stomach (P < 0.01). MDR1 mRNA concentrations increased along the GI tract with the highest expression being in the left colon (P < 0.000001).

Conclusion

Multiple sampling within the same individual enabled us to study the intraindividual variation in expression of CYP and MDR1 genes along the GI tract. We find that CYP2E1 mRNA expression is higher than that of the other CYPs. CYP3A expression is highest in the duodenum and that of MDR1 increases from stomach and duodenum to colon.
The effects of growth hormone status on circulating levels of vascular growth factors
Authors: Silha Josef V. , Krsek Michal , Hana Vaclav , Marek Josef , Weiss Vladimir , Jezkova Jana , Rosicka Martina , Jarkovska Zuzana , Murphy Liam J.
Published: June 2005

Background  Vascular growth factors are important not only in angiogenesis but also for the maintenance of normal endothelial integrity and function. Elevated levels of vascular endothelial growth factor (VEGF), angiopoietin‐2, hepatocyte growth factor (HGF), endostatin and angiogenin have been associated with endothelial dysfunction and atherosclerosis. Both acromegaly and growth hormone deficiency (GHD) are associated with endothelial dysfunction and changes in blood vessel morphology.

Aim  To investigate the effect of GH status on the circulating levels of angiogenic factors.

Design  We measured the levels of six endothelial growth modulators, four angiogenic growth factors and two inhibitors of angiogenesis in 35 untreated acromegalics, 36 untreated GH‐deficient subjects and 101 normal control subjects. Fifteen GH‐deficient subjects were also studied before and 1 year after treatment with GH.

Results  Mean angiogenin concentrations were increased in acromegaly and decreased in GH‐deficient subjects compared to control subjects. Endostatin levels showed a similar pattern although the elevated levels in acromegalic subjects did not achieve statistical significance. Angiogenin and endostatin levels both correlated significantly with IGF‐I levels (R = 0·61, P < 0·001 and R = 0·22, P < 0·01, respectively). The relationship between angiogenin and IGF‐I levels remained significant even after correction for gender, age, body mass index (BMI) and insulin resistance. There were no significant differences in the levels of HGF, VEGF, VEGF‐C or angiopoietin‐2 between the three groups. VEGF‐D levels were elevated in both acromegalic and GH‐deficient male subjects. A similar pattern was apparent in female subjects. After GH treatment, a significant reduction in VEGF‐D levels and a significant rise in endostatin levels were observed in GH‐deficient subjects. A nonsignificant increase in angiogenin levels was also observed.

Conclusion  These data indicate that significant perturbations in the levels of vascular growth modulators are present in both acromegaly and GHD. While changes in endostatin and angiogenin levels appear to correlate with IGF‐I levels, VEGF‐D levels show similar perturbations in both acromegaly and GHD. Further studies are required to determine the relationship of the perturbations to endothelial dysfunction in these conditions.
Fhos2, a novel formin‐related actin‐organizing protein, probably associates with the nestin intermediate filament
Authors: Kanaya Hideki , Takeya Ryu , Takeuchi Kosei , Watanabe Norinobu , Jing Naihe , Sumimoto Hideki
Published: June 2005

Fhos1 is a mammalian formin‐family protein, and functions as an organizer of the actin microfilament. Here we have cloned human and mouse cDNAs for a novel Fhos homolog, designated Fhos2. The messages for Fhos2 are expressed in the heart, kidney, and brain, where the Fhos1 mRNAs are not abundant. Two splice variants of Fhos2 exist in a tissue‐specific manner; the longer variant Fhos2L is the major form in the heart, whereas the kidney and brain predominantly express Fhos2S that encodes a shorter protein. Over‐expression of an active form of the two Fhos2 variants, as well as that of Fhos1, induces the formation of actin stress fibers in HeLa cells, suggesting that Fhos2 acts as an actin‐organizing protein. Biochemical analysis using rat cardiomyoblastic H9c2 (2‐1) cells reveals that endogenous Fhos2 is enriched in the intermediate filament fraction. Consistent with this, Fhos2 localizes to the nestin intermediate filament but not to other cytoskeletons, as demonstrated by staining of H9c2 (2‐1) cells with anti‐Fhos2 antibodies. Furthermore, Fhos2 is present in nestin‐expressing neuroepithelial cells of the fetal rat brain. Thus, Fhos2 not only has the actin‐organizing activity but also associates with nestin, which may imply a Fhos2‐mediated link between the nestin intermediate filament and actin microfilament.
DNA polymerase lambda directly binds to proliferating cell nuclear antigen through its confined C‐terminal region
Authors: Shimazaki Noriko , Yazaki Takaya , Kubota Takashi , Sato Asami , Nakamura Ayako , Kurei Shunsuke , Toji Shingo , Tamai Katsuyuki , Koiwai Osamu
Published: June 2005

DNA polymerase lambda (Pol λ) was recently identified as a new member of the family X of DNA polymerases. Here, we show that Pol λ directly binds to proliferating cell nuclear antigen (PCNA), an auxiliary protein for DNA replication and repair enzymes, both in vitro and in vivo. A pull‐down assay using deletion mutants of Pol λ showed that the confined C‐terminal region of Pol λ directly binds to PCNA. Furthermore, a synthetic peptide of 20‐mers derived from the C‐terminal region of Pol λ competes with full‐length Pol λ for binding to PCNA. The residues between amino acids 518 and 537 of Pol λ are required for binding to PCNA, and are different from the consensus PCNA interacting motif (PIM). Pol λ associates with PCNA in vivo by immunoprecipitation analysis and EGFP‐tagged Pol λ co‐localizes with PCNA as spots within a nucleus using fluorescent microscopy. Through direct binding, PCNA suppressed the distributive nucleotidyltransferase activity of Pol λ. Pol µ, which also belongs to the family X of DNA polymerases, binds to PCNA by a pivotal amino acid residue.
Over‐expression of Aurora‐A targets cytoplasmic polyadenylation element binding protein and promotes mRNA polyadenylation of Cdk1 and cyclin B1
Authors: Sasayama Takashi , Marumoto Tomotoshi , Kunitoku Naoko , Zhang Dongwei , Tamaki Norihiko , Kohmura Eiji , Saya Hideyuki , Hirota Toru
Published: June 2005

Aurora‐A is a centrosomal serine‐threonine kinase that regulates mitosis. Over‐expression of Aurora‐A has been found in a wide range of tumors and has been implicated in oncogenic transformation. However, how Aurora‐A over‐expression contributes to promotion of carcinogenesis remains elusive. Immunohistochemical analysis of breast tumors revealed that over‐expressed Aurora‐A is not restricted to the centrosomes but is also found in the cytoplasm. This over‐expressed Aurora‐A appeared to be phosphorylated on Thr288, which is known to be required for its enzymatic activation. In analogy to Aurora‐A's role in oocyte maturation and the early embryonic cell cycle, here we investigated whether ectopically over‐expressed Aurora‐A can similarly stimulate polyadenylation of mRNA in human somatic cultured cells by interacting with a human ortholog of cytoplasmic polyadenylation element binding protein, h‐CPEB. In vitro experiments revealed that Aurora‐A binds directly to, and phosphorylates, h‐CPEB. We found that polyadenylation of mRNA tails of cyclin B1 and Cdk1 was synergistically stimulated when Aurora‐A and h‐CPEB were over‐expressed, and they were further promoted in the presence of an Aurora‐A activator Ajuba. Our results suggest a function of ectopically over‐expressed Aurora‐A that might be relevant for carcinogenesis.
GABP, HCF‐1 and YY1 are involved in Rb gene expression during myogenesis
Authors: Deléhouzée Sophie , Yoshikawa Tatsufumi , Sawa Chika , Sawada Jun‐ichi , Ito Takumi , Omori Masashi , Wada Tadashi , Yamaguchi Yuki , Kabe Yasuaki , Handa Hiroshi
Published: June 2005

Muscle cell differentiation, or myogenesis, is a well‐characterized process and involves the expression of specific sets of genes in an orderly manner. A prerequisite for myogenesis is the exit from the cell cycle, which is associated with the up‐regulation of the tumor suppressor Rb. In this study, we set to investigate the regulatory mechanism of the Rb promoter that allows adequate up‐regulation in differentiating myoblasts. We report that Rb expression is regulated by the transcription factors GABP, HCF‐1 and YY1. Before induction of differentiation, Rb is expressed at a low level and GABP and YY1 are both present on the promoter. YY1, which exerts an inhibitory effect on Rb expression, is removed from the promoter as cells advance through myogenesis and translocates from the nucleus to the cytoplasm. On the other hand, upon induction of differentiation, the GABP cofactor HCF‐1 is recruited to and coactivates the promoter with GABP. RNAi‐mediated knock‐down of HCF‐1 results in inhibition of Rb up‐regulation as well as myotube formation. These results indicate that the Rb promoter is subject to regulation by positive and negative factors and that this intricate activation mechanism is critical to allow the accurate Rb gene up‐regulation observed during myogenesis.
Quality of life of patients having renal replacement therapy
Authors: Niu Shu‐Fen , Li I.‐Chuan
Published: June 2005

Aim.  This paper reports a study to compare the quality of life and its correlates for patients undergoing various types of renal replacement therapy.

Background.  Patients with end stage renal disease need renal replacement therapy as a substitute for their original kidneys. Different renal replacement therapies have different levels of impact on physical, psychological and social health. Quality of life as perceived by patients with end‐stage renal disease is an important measure of patient outcome.

Methods.  A cross‐sectional, descriptive, correlational study was carried out in 2002. A total of 240 patients were recruited from two medical centres in northern Taiwan. These patients were currently undergoing one of following types of renal replacement therapies: haemodialysis, continuous ambulatory peritoneal dialysis or transplantation. The study instrument used was the WHOQOL‐BREF‐TAIWAN. Data were analysed using descriptive and inferential statistics.

Results.  The scores for quality of life of transplantation patients were higher than those for both haemodialysis and continuous ambulatory peritoneal dialysis patients. The lowest scores for all three groups were in the psychological domain. The mean age for haemodialysis and continuous ambulatory peritoneal dialysis patients was significantly higher than that for transplant patients. The educational level, proportion of single people, and employment status of transplant patients were significantly higher than those of haemodialysis and continuous ambulatory peritoneal dialysis patients. Perception of economic status as ‘balanced’ or ‘proficient’ for transplant patients was significantly higher than for continuous ambulatory peritoneal dialysis and haemodialysis patients.

Conclusion.  Information about the quality of life of patients having various types of renal replacement therapy will assist physicians, nurses, patients and their families to make decisions on treatment selection. There is a need to establish support groups for patients having renal replacement therapy in order to enhance their quality of life, especially in the psychological domain.
The development of a new measure for the assessment of psychopathology in adults with intellectual disability
Authors: Mohr C. , Tonge B. J. , Einfeld S. L.
Published: June 2005

Background  People with intellectual disability (ID) and untreated psychiatric disorder lead unnecessarily difficult and unhappy lives. The prevalence of mental illness in children and adults with ID is greater than that found in the general population. A carer‐completed checklist of psychopathology that could be used with both children and adults would help identify those individuals with ID most likely to have a mental health problem, help ensure that they receive the limited services that are usually available and also assist the process of clinical assessment, diagnosis and management.

Method  This research aimed to develop a reliable and valid carer‐completed checklist of psychopathology for adults with ID by redeveloping an existing measure for children with ID, the Developmental Behaviour Checklist (DBC‐P). The new checklist, The Developmental Behaviour Checklist for Adults (DBC‐A) was devised by changing, deleting and adding to DBC‐P items. Reliability studies were conducted with paid and family carers, and DBC‐A scores were compared with the results from two other measures of psychopathology.

Results  One DBC‐P item was deleted, seven items changed and 12 items added. The psychometric properties of this new checklist, the DBC for Adults with ID (DBC‐A), were investigated and found to be satisfactory. Intraclass correlations for test‐retest and inter‐rater reliability ranged from 0.72 to 0.85, and concurrent validity with two measures of emotional and behavioural disturbance was satisfactory.

Conclusions  The carer‐completed DBC‐A provides a broad and comprehensive survey of the emotional and behavioural problems of adults with ID. It has satisfactory psychometric properties and therefore can be used with confidence in clinical, research and service settings, and its development allows continuous assessment of psychopathology across the lifespan for all people with ID.
Is Post‐Traumatic Stress Disorder a helpful concept for adults with intellectual disability?
Authors: Mitchell A. , Clegg J.
Published: June 2005

Background  Research using the concept of Post‐Traumatic Stress Disorder (PTSD) with adults with intellectual disability (ID)assumes they perceive and react to traumatic events in a similar way to non‐disabled adults. Reactions to trauma displayed by children may be relevant to adults with ID as well.

Methods  Two focus groups were held with professionals and practitioners to explore the relevance of criteria from child as well as adult literature to adults with ID who experience trauma. Descriptive thematic analysis was carried out.

Results  Abuse, parental bereavement, and having children removed were considered common sources of trauma. Similarities identified between disabled and non‐disabled adults were flashbacks and nightmares; distressed by reminders; avoidance; hypervigilance and increased arousal. Differences were the frequent occurrence of multiple rather than single events, which were considered significant in generating chronic problems similar to those described as PTSD; also the occurrence of physical health problems and behavioural re‐enactments.

Discussion and conclusions  Experienced professionals and practitioners considered most of the ideas from PTSD research with non‐disabled adults to be relevant to adults with ID who experience trauma, but that some behaviour reported in research with children was also relevant. Topics and questions for use in clinical and research practice with individuals who have experienced trauma were proposed.
Randomized controlled trial of assertive community treatment in intellectual disability: the TACTILD study
Authors: Oliver P. C. , Piachaud J. , Tyrer P. , Regan A. , Dack M. , Alexander R. , Bakala A. , Cooray S. , Done D. J. , Rao B.
Published: June 2005

Background  There has been a policy shift away from hospital to community in the services of all those with psychiatric disorders, including those with intellectual disability (ID), in the last 50 years. This has been accompanied recently by the growth of assertive outreach services, but these have not been evaluated in ID services.

Method  In a randomized controlled trial we compared assertive outreach with ‘standard’ community care, using global assessment of function (GAF) as the primary outcome measure, and burden and quality of life as secondary measures.

Results  We recruited 30 patients, considerably less than expected; no significant differences were found between the primary and secondary outcomes in the two groups. The differences were so small that a Type II error was unlikely.

Conclusions  Reasons for this lack of specific efficacy of the assertive approach are discussed and it is suggested that there is a blurring of the differences between standard and assertive approaches in practice.
An exploratory study of assertive community treatment for people with intellectual disability and psychiatric disorders: conceptual, clinical, and service issues
Authors: Martin G. , Costello H. , Leese M. , Slade M. , Bouras N. , Higgins S. , Holt G.
Published: June 2005

Background  Assertive community treatment (ACT) has been applied to a number of disorders in the adult population, such as schizophrenia, with some degree of success; its use in the treatment of people with intellectual disability (ID) and mental illness has received little attention. Despite the high costs of ID in health and social care, there has been very little evidence‐based practice for people with ID and mental illness, and it remains a neglected area of research.

Aims  The aims of this study were an exploratory comparison of the effectiveness of an ACT model for the treatment of mental illness in people with ID (ACT‐ID) with a standard community treatment (SCT‐ID) approach.

Method  A Randomized controlled trial design was adopted and allocation was made by stratified randomization by an independent statistician. The prognostic factors used in the randomization were gender and psychiatric diagnosis (psychosis vs. affective). Service users were randomly allocated to either ACT‐ID or SCT‐ID.

Results  There were no statistically significant differences between ACT‐ID and SCT‐ID in terms of the level of unmet needs, carer burden, functioning and quality of life, but borderline evidence of a difference between treatment groups in quality of life in favour of SCT‐ID. Both SCT‐ID and ACT‐ID groups decreased level of unmet needs and carer burden, and increased functioning. SCT‐ID also led to a small increase in quality of life.
Antenatal therapeutic drug exposure and fetal/neonatal tumours: review of 89 cases
Authors: Satgé  , Sasco  , Little
Published: June 2005

Summary.
 Although case reports on the association between neonatal tumours and maternal therapeutic drug use during pregnancy are cited regularly, no systematic review has been published. In a systematic search of the literature on fetal and neonatal tumours, we identified 36 malignant and 54 benign tumours in 89 fetuses and neonates prenatally exposed to various drugs. Six associations with in utero exposure are noteworthy: (1) phenytoin and neuroblastoma, as already suspected; (2) antibiotics and leukaemias; (3) hormonal treatment and vascular tumours; (4) acetaminophen (paracetamol) and fusocellular sarcoma; (5) acetaminophen in combination with petroleum products and hepatoblastoma; and (6) dicyclomine hydrochloride and teratomas. In view of the high level of consumption of drugs by pregnant women and the rarity of neonatal tumours, a possible carcinogenic effect is difficult to establish. However, some associations already observed in older infants, children and adults after antenatal and postnatal exposure to the same drugs are of note. We suggest that these drugs may act as carcinogens or as co‐carcinogens in association with other physical and chemical agents and/or a particular genetic background. We therefore feel it is important to encourage the systematic collection, registration and publication of case reports on this subject. The hypotheses generated thereby could then be tested by formal epidemiological studies.
Smoking during pregnancy and babbling abilities of the 8‐month‐old infant
Authors: Obel  , Henriksen  , Hedegaard  , Secher  , Østergaard
Published: June 2005

Summary.
 Animal experiments suggest that the fetal brain is sensitive to nicotine. Although much attention has been given to the relation between cigarette smoking during pregnancy and neurodevelopment in children, this remains controversial. Our study describes the relationship between maternal cigarette smoking during pregnancy and babbling abilities of the 8‐month‐old infant. In a longitudinal cohort, information was collected at the 16th week of gestation, at delivery and when the infant was about 8 months old. At this age babbling abilities of the infant were evaluated by a health visitor during a home visit. Singleton infants without any disability born at Aarhus University Hospital, Denmark, 1991–92 and still living in the Community of Aarhus at the age of 8 months were eligible (n = 2302). Complete follow‐up was obtained for 1871 children (81.3%). A dose–response‐like relationship between number of cigarettes smoked per day during pregnancy and babbling abilities was found after controlling for potential confounders. Smoking 10 or more cigarettes per day during pregnancy almost doubled the risk (odds ratio [OR] = 2.0, 95% confidence interval [CI] 1.1–3.6) of the infant being a non‐babbler at the examination at 8 months. Among children who were breast fed for less than 4 months this risk was even higher (OR = 2.7, CI 1.3–5.8).
Dense membrane formation after combined phacoemulsification–trabeculectomy surgery
Authors: Chan Colin CK , Goldberg Ivan
Published: June 2005

Abstract

A case is reported of formation of a dense intraocular membrane following combined phacoemulsification–trabeculectomy surgery. The membrane might have originated from a loose piece of pigment epithelium or might have resulted from dense pigment deposition on a postoperative pupillary membrane. Postoperative membranes have been reported particularly after combined procedures. A combination of intensive topical dexamethasone, homatropine and a Nd:YAG laser was used to speed resolution of the membrane.
Unusual cause for non‐detection of retained metallic foreign body on ocular ultrasonography
Authors: Prakash Gunjan , Venkatesh Pradeep , Garg Satpal
Published: June 2005

Ultrasound biomicroscopy has become a valuable adjunct in the evaluationof occult ocular foreign bodies. An unusual cause for non‐detectionof a metallic retained intraocular foreign body is described. Inthis case, the usual ‘shadowing’ was not discernibleas the foreign body was lying just over the optic disc.
Choroidal neovascularization after accidental macular damage by laser
Authors: Nehemy MárcioB , Torqueti‐Costa Leonardo , Magalhães Érika P , Vasconcelos‐Santos Daniel Vítor , Vasconcelos AdoJório
Published: June 2005

A 30‐year‐old male physics professor was examined 2 months afterbeing accidentally hit by a laser beam in his left eye. He complainedof abrupt vision loss and central scotoma after the laser accident,with stabilization of the vision thereafter. At presentation, hepresented best‐corrected visual acuity of 6/18 in the lefteye. Fundoscopy disclosed a slightly elevated foveal brownish lesion,surrounded by a subtle subretinal haemorrhage. Fluorescein angiographydemonstrated a hyperfluorescent foveal lesion with stainingand a slight leakage in the late phase, characterizing a fibrovascularchoroidal neovascularization (CNV). Optical coherence tomography showeda discrete increase in retinal thickness and a subretinalfibrotic CNV. Visual acuity remained stable during the follow up(4 months). CNV after laser injury is rare. The evolutionof this case suggests that CNV, after an accidental laser injury,in a healthy macula of a young patient might have a self‐limitedcourse and a relatively good prognosis.
Bilateral benign lymphoid hyperplasia of the conjunctiva in a paediatric patient
Authors: Kim Peter , Macken Peter L , Palfreeman Simon , Rawlinson William D , Martin Frank
Published: June 2005

Abstract

A 14‐year‐old boy presented with a 6‐month history of bilateral slowly enlarging conjunctival lesions. There was no associated ocular or systemic symptomatology. Examination revealed bilateral salmon‐coloured nodular lesions of the bulbar conjunctiva. The remainder of his ophthalmic and general examinations were normal. Extensive investigation excluded regional or systemic involvement. Excision biopsy of the lesions showed a predominantly mature B lymphocyte infiltrate with immunohistochemistry and flow cytometry consistent with reactive lymphoid hyperplasia. Polymerase chain reaction testing for Epstein–Barr virus was negative. At 2 years follow‐up, the patient remained healthy and there was no evidence of recurrence. Benign lymphoid hyperplasia of the conjunctiva with bilateral involvement is extremely rare in children. Only a few case reports have been documented in the literature.
Suprachoroidal haemorrhage following Nd:YAG laser posterior capsulotomy
Authors: Chan Wing C , McGimpsey Stuart J , Murphy Martin F , Best Richard M
Published: June 2005

Nd:YAG laser posterior capsulotomy is the commonest procedurefor posterior capsule thickening following cataract surgery. Complicationsfollowing this laser surgery are relatively few, and this is ordinarilya safe and effective procedure. Herein a case is described of suprachoroidalhaemorrhage following Nd:YAG laser posterior capsulotomy. To thebest of the authors' knowledge, this is the first report of this complication.Patients undergoing this procedure should be warned of this rarebut potentially devastating complication.
Effects of pars plana vitrectomy on retrobulbar haemodynamics in diabetic retinopathy
Authors: Sullu Yuksel , Hamidova Reyhan , Beden Umit , Yakupov Kamuran , Canbaz Sevgi , Danaci Murat
Published: June 2005

Abstract

Background:  The purpose of the present study was to determine the effects of pars plana vitrectomy on retrobulbar haemodynamics in patients with proliferative diabetic retinopathy (PDR).

Methods:  Colour Doppler imaging was used for measurement of blood flow velocities and resistive index of the ophthalmic artery (OA), posterior ciliary arteries (PCA) and central retinal artery (CRA) in 14 eyes of 14 patients with PDR before pars plana vitrectomy and at the 1 and 6 months after operation. The patients were also treated by laser photocoagulation before or during surgery. Twenty age‐ and sex‐matched healthy subjects were used as control group.

Results:  Mean peak systolic velocity and the end diastolic velocity of the CRA in the patients with PDR were lower and the mean resistive index was higher than in those of the control group (P < 0.05). The mean end diastolic velocity of OA in the patients was lower and the mean resistive index was higher than in the control group (P < 0.05). The peak systolic velocity of the OA and the end diastolic velocity of the CRA were significantly increased (P = 0.043 and P = 0.018, respectively) and the mean resistive index of the CRA was significantly decreased after pars plana vitrectomy (P = 0.043). No significant changes were detected among preoperative and postoperative values of peak systolic velocity, end diastolic velocity, and resistive index of the PCA and the mean velocity of the central retinal vein (P > 0.05).

Conclusions:  The blood flow velocities of OA and CRA are decreased but the resistive index is increased significantly in patients with PDR. Pars plana vitrectomy in patients with PDR may decrease resistive index and improve blood flow in the CRA.
Accounting and the Construction of Taste: Standard Labour Costs and the Georgian Cabinet‐Maker
Authors: Jeacle Ingrid
Published: June 2005

The article examines the role of accounting in the dissemination of a classical taste in British furniture during the Georgian era. This is a celebrated period in furniture design, to which the fame of some of its key participants, such as Thomas Chippendale, still bears testimony. It is also a period in which the notion of interior decoration comes to prominence. Furniture and room arrangement began to mirror the taste in classical antiquity already evident in the architectural landscape. The dissemination of taste to the mass populace took the form of pattern books comprising easily replicated designs of household furniture. Regional versions of these books also contained detailed standard labour costs for every furniture design. In pre‐empting conflict over piece‐work pay these standards regulated the cabinet‐making trade and, the article shows, encouraged a stability in labour relations conducive to the spread of a national taste in classicism.
Instabilities of Multihump Vector Solitons in Coupled Nonlinear Schrödinger Equations
Authors: Pelinovsky Dmitry E. , Yang Jianke
Published: June 2005

Spectral stability of multihump vector solitons in the Hamiltonian system of coupled nonlinear Schrödinger (NLS) equations is investigated both analytically and numerically. Using the closure theorem for the negative index of the linearized Hamiltonian, we classify all possible bifurcations of unstable eigenvalues in the systems of coupled NLS equations with cubic and saturable nonlinearities. We also determine the eigenvalue spectrum numerically by the shooting method. In case of cubic nonlinearities, all multihump vector solitons in the nonintegrable model are found to be linearly unstable. In case of saturable nonlinearities, stable multihump vector solitons are found in certain parameter regions, and some errors in the literature are corrected.
Uniform Asymptotics for Orthogonal Polynomials with Exponential Weights—the Riemann–Hilbert Approach
Authors: Wang Z. , Wong R.
Published: June 2005

Let Q(x) =q2mx2m+q2m−1x2m−1+⋯ be a polynomial of degree 2m with q2m > 0, and let {πn(x)}n≥1 be the sequence of monic polynomials orthogonal with respect to the weight w(x) =e−Q(x) on . Furthermore, let αn and βn denote the Mhaskar–Rakhmanov–Saff (MRS) numbers associated with Q(x). By using the Riemann–Hilbert approach, an asymptotic expansion is constructed for πn(cnz+dn), which holds uniformly for all z bounded away from (−∞, −1), where and .
The Effect of the Estimation on Goodness‐of‐Fit Tests in Time Series Models
Authors: Fang Yue
Published: June 2005

Abstract. We analyze, by simulation, the finite‐sample properties of goodness‐of‐fit tests based on residual autocorrelation coefficients (simple and partial) obtained using different estimators frequently used in the analysis of autoregressive moving‐average time‐series models. The estimators considered are unconditional least squares, maximum likelihood and conditional least squares. The results suggest that although the tests based on these estimators are asymptotically equivalent for particular models and parameter values, their sampling properties for samples of the size commonly found in economic applications can differ substantially, because of differences in both finite‐sample estimation efficiencies and residual regeneration methods.
Mixed Portmanteau Tests for Time‐Series Models
Authors: Wong Heung , Ling Shiqing
Published: June 2005

Abstract. This paper obtains the joint limiting distribution of residuals and squared residuals of a general time‐series model. Based on this, we propose a mixed portmanteau statistic for testing the adequacy of fitted time‐series models. In some cases, it is shown that this statistic can be simply approximated by the sum of well‐known portmanteau statistics. The finite‐sample performance of the new test is compared with those of well‐known tests through simulations.
A Simple Gait‐Stabilizing Device Reduces Outdoor Falls and Nonserious Injurious Falls in Fall‐Prone Older People During the Winter
Authors: McKiernan Fergus Eoin
Published: June 2005

Objectives: To determine whether Yaktrax Walker (YW), a nonmedical gait‐stabilizing device, prevents outdoor falls and injurious falls in fall‐prone older people during the winter.

Design: Prospective, randomized, interventional trial.

Setting: Community‐based, northern United States, winter, outdoors.

Participants: Ambulatory, community‐dwelling, fall‐prone people aged 65 and older.

Intervention: Participants were randomized to wear YW or their usual winter footwear (UWF) outdoors during the winter of 2003/2004.

Measurements: The number of indoor and outdoor slips, falls, and injurious falls was recorded daily in a fall diary. Winter footwear satisfaction survey was completed after study completion.

Results:
One hundred nine subjects completed 10,724 diary days. Mean age was 74.2. There were 93 indoor slips, 13 indoor falls, 714 outdoor slips, and 62 outdoor falls. The tendency for both groups to slip/fall indoors was comparable. The relative risk (RR) of outdoor slip for YW was 0.50 (P<.04) for all diary days and 0.61 (P=.14) when only days walked on snow and ice was the exposure variable. The RR of outdoor fall for YW was 0.42 (P<.03) when only days walked on snow and ice was the exposure variable. RR of injurious falls per day walked on snow and ice for YW was 0.13 (P<.02). Twelve of 19 outdoor falls occurred when YW subjects were not wearing their assigned device. No serious injury or fracture occurred in either group. The number needed to treat for the YW to prevent one nonserious injurious fall in one winter was six.

Conclusion: YW may reduce the risk of outdoor winter falls, and of nonserious injurious falls, in older community‐dwelling people with a history of previous falls.
Medication Safety in Older Adults: Home‐Based Practice Patterns
Authors: Metlay Joshua P. , Cohen Abigail , Polsky Dan , Kimmel Stephen E. , Koppel Ross , Hennessy Sean
Published: June 2005

Objectives: To identify the current state of medication‐taking practices of community‐dwelling older adults on high‐risk medications.

Design: Telephone survey of older adults filling prescriptions for warfarin, digoxin, or phenytoin from May 2, 2002, through June 30, 2003.

Setting: The Pennsylvania Pharmacy Assistance Contract for the Elderly (PACE) Program, a state‐run program providing prescription drug coverage for poor older adults.

Participants: PACE members.

Measurements: Patients self‐reported sources of information on current medications as well as home‐based practices for organizing medication regimens.

Results: Four thousand nine hundred fifty‐five PACE members were interviewed. Thirty‐two percent of the sample reported that they had not received any specific instructions about their medications, 35% reported that they received instructions from their primary care provider, and 46% indicated they received them from a pharmacist. Fifty‐four percent of participants indicated that they used a pillbox for organizing their medications. Older adults prescribed warfarin were more likely to report receiving instructions than those prescribed digoxin or phenytoin.

Conclusion: A substantial proportion of older adults on high‐risk medications do not recall receiving instructions for the use of their medications and do not take advantage of existing systems for organizing medication regimens. Improved patient education and delivery of medication organization systems are immediate opportunities to potentially reduce the risk of medication errors in older people.
The Challenge of Diagnosing Pulmonary Embolism in Elderly Patients: Influence of Age on Commonly Used Diagnostic Tests and Strategies
Authors: Righini Marc , Le Gal Grégoire , Perrier Arnaud , Bounameaux Henri
Published: June 2005

Pulmonary embolism (PE) is a potentially fatal disease if left untreated. The prevalence of PE increases markedly with age, and its diagnosis in elderly people is difficult because many cardiopulmonary conditions may mimic clinical presentation of PE, and age may unfavorably influence the characteristics of diagnostic tests for PE. The modern approach to PE is based on sequential diagnostic strategies based on clinical probability, D‐dimer measurement, lower limb compression ultrasonography, ventilation‐perfusion lung scan, and helical computed tomography (hCT). Pulmonary angiogram is rarely necessary because the noninvasive diagnostic evaluation is usually conclusive. Age reduces the clinical usefulness of D‐dimer and ventilation‐perfusion lung scan. D‐dimer allows excluding PE in only 5% of patients aged 80 and older, compared with 60% younger than 40. Similarly, the rate of inconclusive ventilation‐perfusion lung scans is almost twice as high (58%) in patients older than 70 and in patients younger than 40 (32%). In contrast, aging does not change the diagnostic accuracy of clinical probability assessment, whether empirical or as determined by prediction rules, nor appear to influence the diagnostic characteristics of lower limb compression ultrasonography and hCT. Therefore, a rational diagnostic approach to PE in older people should rest mainly on the sequential use of those tests that have demonstrated strong diagnostic yield, accuracy, and safety in this population.