bluuebunny/crossref_metadata_2025 huggingface dataset:
Axolotl (Ambystoma mexicanum) Embryonic Transplantation Methods
Authors: Nacu Eugen , Knapp Dunja , Tanaka Elly M. , Epperlein Hans H.
Published: August 2009

INTRODUCTION

A remarkable feature of axolotls (Ambystoma mexicanum) is their amenability to grafting at any stage of the lifecycle. The large size, slow development, and tensile properties of the axolotl embryo make it particularly easy to transplant different regions of the embryo at the neurula stage. Grafting of green fluorescent protein (GFP)-expressing tissue from a GFP germline transgenic animal to GFP-negative hosts has proven to be a powerful method for tracking cells during development and regeneration. In the following protocol, we describe the transplantation of epidermis, neural fold, presomitic mesoderm, and lateral plate mesoderm to produce specific labeling of limb epidermis, limb Schwann cells, limb muscle, and limb connective tissue, respectively.
Chromosome Orientation Fluorescence In Situ Hybridization (CO-FISH): Figure 1.
Authors: Williams Eli S. , Bailey Susan M.
Published: August 2009

INTRODUCTION

Chromosome orientation fluorescence in situ hybridization (CO-FISH) differs from standard FISH in its ability to make hybridizations strand-specific. The procedure works by culturing cells for a single round of replication in the presence of the thymidine analog 5-bromo-2′-deoxyuridine (BrdU), thus incorporating BrdU into the newly synthesized daughter strands. The daughter strands are then specifically removed through nuclease digestion, leaving single-stranded chromosomal DNA, which is an ideal target for hybridization of single-stranded probes. Overall, the effect is to produce single-sided signals. CO-FISH allows the investigator to determine the relative orientation of two or more DNA sequences along a chromosome. With a suitable reference probe (such as a telomere), CO-FISH can also determine the absolute 5′-to-3′ direction of a DNA sequence relative to the short-arm-to-long-arm axis of the chromosome. This protocol describes the CO-FISH procedure, which uses a peptide nucleic acid (PNA) probe.
Isolation and Cloning of High-Molecular-Weight Metagenomic DNA from Soil Microorganisms
Authors: Liles Mark R. , Williamson Lynn L. , Rodbumrer Jitsupang , Torsvik Vigdis , Parsley Larissa C. , Goodman Robert M. , Handelsman Jo
Published: August 2009

INTRODUCTION

The successful construction of large-insert community DNA (i.e., metagenomic) libraries from natural environments is dependent on several parameters, including effective cell lysis, DNA purity, and a high transformation efficiency. One problem associated with constructing metagenomic libraries from soil microbes is the co-isolation of contaminants, leading to the degradation of DNA as a result of nuclease activity. Because the isolation of intact genetic pathways from soil microbes is necessary to characterize their genetic and functional diversity, obtaining high-purity, high-molecular-weight (HMW) DNA for library construction is absolutely critical. This protocol describes the steps for the indirect extraction of bacterial DNA from soil, embedding the DNA in an agarose matrix, using a formamide and high-salt treatment to eliminate nucleases, size-selecting DNA by restriction digestion and pulsed-field gel electrophoresis (PFGE), and cloning the HMW DNA into a large-insert vector. The resulting metagenomic libraries contain high-purity, stable, HMW DNA that can be screened for various genetic loci (sequence-based) or phenotypic traits (function-based).
Preparation of Coverslips for Neuronal Cultures
Authors: Albuquerque Cristóvão , Joseph Donald J. , Choudhury Papiya , MacDermott Amy B.
Published: August 2009

INTRODUCTION

This protocol describes methods for preparing glass coverslips to use with three different types of dissociated neuronal cultures: mass culture, microisland culture, and macroisland culture. In mass culture, the entire glass coverslip is precoated with poly-D-lysine and laminin and then plated with astrocytes followed by dissociated neurons. In this system, the plated neurons tend to form an extensive and widespread network of synapses. However, depending on the origin of the neurons, proximity might not be a good predictor of the presence of synapses between any two cells. Microisland culture aims to increase the probability of identifying neurons synaptically connected to each other; its basic principle is to restrict spatially the choice of connections. This is done by plating neurons on astrocyte-seeded collagen dots on a background of a nonadhesive agarose substrate. Synaptic interactions between dorsal horn (DH) neurons or between dorsal-root ganglion (DRG) and DH neurons on the microislands are reliably found using this system, whereas they are much harder to find in mass culture. The macroisland approach is similar, but generates larger islands. It was developed specifically to improve neuronal survival in DRG/DH cocultures while still providing a high probability of connection between DRG and DH neurons. For DH-DH synapses however, microislands are still the best system.
Dissection, Plating, and Maintenance of Dorsal Root Ganglion Neurons for Monoculture and for Coculture with Dorsal Horn Neurons
Authors: Albuquerque Cristóvão , Joseph Donald J. , Choudhury Papiya , MacDermott Amy B.
Published: August 2009

INTRODUCTION

Dorsal root ganglion (DRG) neurons grow readily alone or in coculture with embryonic dorsal horn (DH) neurons and even appear to enhance survival of the DH cells. Furthermore, DRG neurons grow long neurites in the presence of nerve growth factor, forming many glutamatergic synapses onto DH neurons, if present. Otherwise (i.e., in monocultures), no synapses can be detected electrophysiologically. When preparing cocultures, use DRGs already removed from the same embryos used to prepare DH neurons, but after dissecting the dorsal horns; the DRGs are less sensitive to delay in dissection and dissociation, as long as they are left in culture medium. Microisland and mass cultures require different proportions of DRG and dorsal horn neurons. Synaptic interactions in the microisland culture of DRG and DH neurons are more intense than mass culture because the growing, branching DRG axons are confined to a limited area, and thus make many synapses onto each target DH neuron.
Assessing Significance in Genetic Association Studies: Figure 1.
Authors: Daly Mark J.
Published: August 2009

INTRODUCTION

A critical step in every genetic association study is the estimation of statistical significance. It is on the basis of these estimates, frequently in the form of the traditionalP-value, that most studies attempt to draw a qualitative conclusion regarding the association, or lack of association, of the tested genetic variants. This article introduces basic concepts and fundamental considerations relevant to designing appropriate significance tests and discusses what these tests can and cannot tell us about genetic association.
Varenicline in prevention of relapse to smoking: effect of quit pattern on response to extended treatment
Authors: Hajek Peter , Tønnesen Philip , Arteaga Carmen , Russ Cristina , Tonstad Serena
Published: August 2009

Aim  While older behavioural and pharmacological approaches to preventing relapse to smoking show little efficacy, a recent randomized trial of an extended course of varenicline reported positive results. In this secondary analysis, trial data were examined to see whether smokers who manage to achieve abstinence only later in the original course of treatment are more likely to benefit from having the course extended.

Methods  A total of 1208 patients abstinent for at least the last week of 12 weeks' treatment with varenicline were randomized to 3 months continued varenicline or placebo. Overall, 44% of the 12‐week abstainers were abstinent from the target quit date (TQD), while the rest stopped smoking later. We examined the relationship between quit pattern and the varenicline versus placebo difference in continuous abstinence rates at week 52 and contributions of baseline patient characteristics.

Results  With increasing delay in initial quitting, 12‐month success rates declined. Participants who had their last cigarette at week 11 of open‐label treatment had quit rates at 52 weeks of 5.7% compared with 54.9% in those who last smoked in week 1 [odds ratio (OR) 20.3 (6.3, 65.9); P < 0.0001]. Patients who failed to initiate abstinence in the first week benefited more from extended treatment than patients continuously abstinent from week 1 [OR 1.7 (1.2, 2.4); P = 0.0015 versus OR 1.1 (0.8, 1.5); P = 0.6995, respectively; with the interaction of the quit pattern with treatment effect reaching borderline significance (P = 0.0494)]. No other patient characteristics were related to treatment effect.

Conclusions  Compared with smokers who quit smoking on their TQD, those who have an initial delay in achieving sustained abstinence have increased risk of relapse even several months later, and may be more likely to benefit from extended treatment with varenicline.
The association of snus and smoking behaviour: a cohort analysis of Swedish males in the 1990s
Authors: Stenbeck Magnus , Hagquist Curt , Rosén Måns
Published: August 2009

Background  The European Union has banned sales of moist snuff (snus) in all member states, with the exception of Sweden. The ban is motivated by the potential adverse health effects of snus, but snus may also help people to avoid smoking or stop tobacco use.

Aims  The purpose of this study is to investigate the association between snus and smoking behaviour.

Measurements  The Swedish Survey of Living Conditions (ULF) health interview panel running from 1988/9 to 1996/7 was used to examine the gross and net flows between smoking and snus among Swedish males. Females were excluded from the analysis due to low snus prevalence. Contingency table models were used to investigate several hypotheses about the relationships between snus and smoking behaviour.

Findings  We found clear associations between the two habits. For the younger cohort (age 16–44 years), snus use contributed to approximately six smoking quitters per smoking starter attributable to snus. For the older cohort (age 45–84) there were slightly more than two quitters per starter. In terms of odds ratios, in the younger group smoking cessation attributable to snus was twice as common as smoking initiation, but in the older group the odds of starting smoking attributable to snus was 2.5 times higher than for quitting.

Conclusions  Snus contributed to the reduction of smoking among Swedish males in the 1990s. Snus had different effects among non‐smokers and smokers in different age groups.
Gender and alcohol consumption: patterns from the multinational GENACIS project
Authors: Wilsnack Richard W. , Wilsnack Sharon C. , Kristjanson Arlinda F. , Vogeltanz‐Holm Nancy D. , Gmel Gerhard
Published: August 2009

Aims  To evaluate multinational patterns of gender‐ and age‐specific alcohol consumption.

Design and participants  Large general‐population surveys of men's and women's drinking behavior (n's > 900) in 35 countries in 1997–2007 used a standardized questionnaire (25 countries) or measures comparable to those in the standardized questionnaire.

Measurements  Data from men and women in three age groups (18–34, 35–49, 50–65) showed the prevalence of drinkers, former drinkers, and lifetime abstainers; and the prevalence of high‐frequency, high‐volume, and heavy episodic drinking among current drinkers. Analyses examined gender ratios for prevalence rates and the direction of changes in prevalence rates across age groups.

Findings  Drinking per se and high‐volume drinking were consistently more prevalent among men than among women, but lifetime abstention from alcohol was consistently more prevalent among women. Among respondents who had ever been drinkers, women in all age groups were consistently more likely to have stopped drinking than men were. Among drinkers, the prevalence of high‐frequency drinking was consistently greatest in the oldest age group, particularly among men. Unexpectedly, the prevalence of drinking per se did not decline consistently with increasing age, and declines in high‐volume and heavy episodic drinking with increasing age were more typical in Europe and English‐speaking countries.

Conclusions  As expected, men still exceed women in drinking and high‐volume drinking, although gender ratios vary. Better explanations are needed for why more women than men quit drinking, and why aging does not consistently reduce drinking and heavy drinking outside Europe and English‐speaking countries.
Estimating the burden of disease attributable to illicit drug use and mental disorders: what is ‘Global Burden of Disease 2005’ and why does it matter?
Authors: Degenhardt Louisa , Whiteford Harvey , Hall Wayne , Vos Theo
Published: August 2009

Background  The estimated impact of illicit drug use and mental disorders upon population health needs to be understood because there is evidence that they produce substantial loss of life and disability, and information is needed on the comparative population health impact of different diseases and risk factors to help focus policy, service and research planning and execution.

Aims  To provide an overview of a global project, running since the end of 2007—Global Burden of Disease (GBD) 2005.

Methods  The new GBD aims to update comprehensively the findings of the first GBD exercise. It aims to provide regional and global estimates of the burden of disease attributable to hundreds of diseases, injuries and their risk factors. Groups have been assembled to provide expert advice on the parameters needed to inform these estimates; here, we provide a brief summary of the broad range of work being undertaken by the group examining illicit drug use and mental disorders.

Discussion  The estimates of the contribution of mental disorders and illicit drugs to GBD will inform and potentially shape the focus of researchers, clinicians and governments in the years to come. We hope that interested readers might be encouraged to submit new data or feedback on the work completed thus far, as well as the work that is still under way and yet to be completed.
Acquired factor V inhibitor in a critically ill patient
Authors: Morris C. J. , Curry N.
Published: August 2009

Acquired inhibitor of factor V is a rare condition with a variety of clinical manifestations, from extremely mild to life threatening haemorrhage. We present a case from our intensive care unit as a reminder of the less common causes of elevated prothombin and activated partial thromboplastin times, and how knowledge of the variable presentation may aid management.
A comparison of volatile and non volatile agents for cardioprotection during on‐pump coronary surgery
Authors: De Hert S. , Vlasselaers D. , Barbé R. , Ory J‐P. , Dekegel D. , Donnadonni R. , Demeere J‐L. , Mulier J. , Wouters P.
Published: August 2009

A randomised study of 414 patients undergoing coronary artery surgery with cardiopulmonary bypass was conducted to compare the effects of a volatile anaesthetic regimen with either deesflurane or sevoflurane, and a total intravenous anaesthesia (TIVA) regimen on postoperative troponin T release. The primary outcome variable was postoperative troponin T release, secondary outcome variables were hospital length of stay and 1‐year mortality. Maximal postoperative troponin T values did not differ between groups (TIVA: 0.30 [0.00–4.79] ng.ml−1 (median [range]), sevoflurane: 0.33 [0.02–3.68] ng.ml−1, and desflurane: 0.39 [0.08–3.74] ng.ml−1). The independent predictors of hospital length of stay were the EuroSCORE (p < 0.001), female gender (p = 0.042) and the group assignment (p < 0.001). The one‐year mortality was 12.3% in the TIVA group, 3.3% in the sevoflurane group, and 6.7% in the desflurane group. The EuroSCORE (p = 0.003) was the only significant independent predictor of 1‐year mortality.
A comparison of stroke volume variation measured by the LiDCOplus and FloTrac‐Vigileo system
Authors: De Wilde R. B. P. , Geerts B. F. , Van Den Berg P. C. M. , Jansen J. R. C.
Published: August 2009

The aim of this study was to compare the accuracy of stroke volume variation (SVV) as measured by the LiDCOplus system (SVVli) and by the FloTrac‐Vigileo system (SVVed). We measured SVVli and SVVed in 15 postoperative cardiac surgical patients following five study interventions; a 50% increase in tidal volume, an increase of PEEP by 10 cm H2O, passive leg raising, a head‐up tilt procedure and fluid loading. Between each intervention, baseline measurements were performed. 136 data pairs were obtained. SVVli ranged from 1.4% to 26.8% (mean (SD) 8.7 (4.6)%); SVVed from 2.0% to 26.0% (10.2 (4.7)%). The bias was found to be significantly different from zero at 1.5 (2.5)%, p < 0.001, (95% confidence interval 1.1–1.9). The upper and lower limits of agreement were found to be 6.4 and −3.5% respectively. The coefficient of variation for the differences between SVVli and SVVed was 26%. This results in a relative large range for the percentage limits of agreement of 52%. Analysis in repeated measures showed coefficients of variation of 21% for SVVli and 22% for SVVed. The LiDCOplus and FloTrac‐Vigileo system are not interchangeable. Furthermore, the determination of SVVli and SVVed are too ambiguous, as can be concluded from the high values of the coefficient of variation for repeated measures. These findings underline Pinsky’s warning of caution in the clinical use of SVV by pulse contour techniques.
Increased levels of T cell granzyme b in bronchiolitis obliterans syndrome are not suppressed adequately by current immunosuppressive regimens
Authors: Hodge S , Hodge G , Ahern J , Liew C-L , Hopkins P , Chambers D C , Reynolds P N , Holmes M
Published: August 2009

Bronchiolitis obliterans syndrome (BOS) is characterized by persistent alloreactive, infective and non-specific epithelial injury, loss of epithelial integrity and dysregulated repair. We have reported increased apoptosis of epithelial cells collected from the large airway in lung transplant recipients. As part of the alloreactive response, T cells induce apoptosis of target epithelial cells by secreting granzyme b. We hypothesized that granzyme b would be increased in lung transplant patients with acute rejection and BOS and that commonly used immunosuppressive agents would fail to suppress this serine protease adequately. We investigated intracellular T cell granzyme b in blood, bronchoalveolar lavage (BAL) and large airway brushing (23 controls, 29 stable transplant, 23 BOS, 28 acute rejection, 31 infection) using flow cytometry and assessed the effect of clinically relevant concentrations of cyclosporin A, tacrolimus, methylprednisolone and a protease inhibitor, gabexate mesilate, on in vitro granzyme b production. Granzyme b was increased significantly in all compartments of all transplant groups compared to controls. Surprisingly, granzyme b was even higher in patients with BOS than in patients with acute rejection. In longitudinal analysis in three patients, blood granzyme b increased prior to or at the onset of BOS. In vitro, methylprednisolone and gabexate mesilate had no effect and cyclosporin A and tacrolimus only a moderate effect on production of granzyme b by CD8+ T cells. Increased T cell granzyme b production may contribute to BOS pathogenesis and is not curtailed by current immunosuppressants. Longitudinal investigation of granzyme b in blood may provide an adjunctive non-invasive method for predicting BOS/OB.
Feasibility of joint 1D velocity model and event location inversion by the Neighbourhood algorithm
Authors: Jansky Jaromir , Plicka Vladimir , Eisner Leo
Published: August 2009

Using a set of synthetic P‐ and S‐wave onsets, computed in a 1D medium model from sources that mimic a distribution of microseismic events induced by hydrofrac treatment to a monitoring geophone array(s), we test the possibility to invert back jointly the model and events location. We use the Neighbourhood algorithm for data inversion to account for non‐linear effects of velocity model and grid search for event location. The velocity model used is composed of homogeneous layers, derived from sonic logging. Results for the case of one and two monitoring wells are compared. These results show that the velocity model can be obtained in the case of two monitoring wells, if they have optimal relative position. The use of one monitoring well fails due to the trade‐off between the velocity model and event locations.
Pharmacokinetics, coagulation factor consumption and clinical efficacy in patients being switched from full‐length FVIII treatment to B‐domain‐deleted r‐FVIII and back to full‐length FVIII
Authors: REA C. , DUNKERLEY A. , SØRENSEN B. , RANGARAJAN S.
Published: August 2009

Summary.  Concerns have been raised regarding pharmacokinetic performance, efficacy and safety of B‐domain‐deleted recombinant FVIII (BDD rFVIII). The objective of this study was to perform a retrospective survey of half‐life measurements, efficacy and safety in patients with severe haemophilia A, switching treatment from full‐length factor VIII (FL FVIII) to BDD rFVIII and then back to FL FVIII. We hypothesized that half‐life of FVIII would be equal regardless of product and that total factor consumption and bleeding frequency would be indistinguishable. We report on inhibitor development and outcome following surgery. Patients with severe haemophilia A, exposed to BDD rFVIII were identified from a database. A retrospective analysis of laboratory data and medical notes was undertaken. No significant difference was detected between the half‐life measurements during the switch from FL FVIII (T/2 median 9.15 h, range 6.4–22) to BDD rFVIII (T/2 median 9.7, range 4.7–16.8) and back to FL FVIII (T/2 median 9.0, range 5.0–19.5). There was no significant difference in coagulation factor usage (BDD rFVIII median 4803 IU kg−1 year−1, range 659–11 304; FL FVIII median 5349, range 1691–10 146), nor bleeds. Eleven received BDD rFVIII to cover surgical procedures, with no reports of excess bleeding. Thirty‐three patients received significant exposure to BDD rFVIII and one developed a low titre inhibitor. BDD rFVIII was found to be equivalent to other FVIII products in terms of pharmacokinetics, clinical efficacy and safety in this study group.
Gynaecological and obstetrical problems in women with different bleeding disorders
Authors: SIBONI S. M. , SPREAFICO M. , CALÒ L. , MAINO A. , SANTAGOSTINO E. , FEDERICI A. B. , PEYVANDI F.
Published: August 2009

Summary.  The aim of this case–control study was to analyse the prevalence of gynaecological, obstetrical and other more general bleeding symptoms in 114 women affected by various inherited bleeding disorders, who were compared with 114 apparently healthy women. Retrospective information were collected by means of two specific questionnaires, one on gynaecological and obstetrical bleeding symptoms, with special focus on the presence of menorrhagia as defined by a pictorial blood loss assessment chart (PBAC); and the other on general bleeding symptoms, whose severity was graded by means of the bleeding score (BS). Compared to normal women, the whole group of women with inherited bleeding disorders had a higher prevalence of excessive bleeding at menarche (25% vs. 5%, P < 0.0001) and menorrhagia (59% vs. 46%, P = 0.06). Affected women also had a higher frequency than controls of general bleeding symptoms that scored as severe by a BS ≥ 12 (49% vs. 0%, P < 0.0001). In affected women, the BS increased according to the severity of the haemostasis defect. In conclusions, the BS and the PBAC are simple tools to evaluate the severity of general bleeding symptoms and menorrhagia in women with inherited bleeding disorders. These instruments may help to identify those women for whom a therapeutic intervention is warranted.
A species well travelled – the Dodonaea viscosa (Sapindaceae) complex based on phylogenetic analyses of nuclear ribosomal ITS and ETSf sequences
Authors: Harrington Mark G. , Gadek Paul A.
Published: August 2009

Aim  To determine the evolutionary history of the widely studied, cosmopolitan polymorphic species Dodonaea viscosa (hop bush, varnish tree).

Location  All continents except Antarctica, extending from 44° S (in the South Island of New Zealand) to 33° N (in California and Arizona).

Methods  For 50 samples across the worldwide distribution, Bayesian analyses of nuclear ribosomal transcribed spacers (ITS 1, ITS 2 and partial ETS) were performed. The alignment was partitioned by secondary structure and analysed using separate models of sequence evolution for each spacer’s stem and loop partition. Bayesian relaxed‐clock estimations of divergence times were used to investigate the tempo of the transoceanic dispersal history of Dodonaea viscosa.

Results  The widely distributed Dodonaea viscosa evolved in Australia from its most recent common ancestor in the Late Pliocene to Early Pleistocene and subsequently split into two distinct, geographically based, intraspecific lineages. There are a number of regional subclades that are also supported by specific molecular elements.

Main conclusions  Dodonaea viscosa is not an old lineage, as has often been speculated based primarily on its vast distribution. It diverged from its most recent common ancestor and subsequently dispersed and established around the world within the last 2 Myr. Two distinct lineages within Dodonaea viscosa, which have been shaped by Quaternary climatic change, have separate dispersal histories. The molecular investigations have identified that, although there are least two evolutionary lineages within the complex, they do not correlate with any distinct morphological subunits. It is proposed that Dodonaea viscosa (including D. biloba and D. procumbens) be recognized as an ochlospecies.
Neuropsychological effects of subsequent exposure to phenylalanine in adolescents and young adults with eariy‐treated phenylketonuria
Authors: Griffiths P. , Paterson L. , Harvie A.
Published: August 2009

Severe mental handicap in phenytketonuHa (PKU) can be prevented if dietary treatment is implemented at birth. Controversy remains about the optimum age for terminating treatment, A group of adolescents and young adults with PKU from the West of Scotland Register was identified which had received early treatment, been well‐controlled on diet, ceased treatment at 10 years old and subsequently were hyperphenyialaninaemic for 3 years or more. They were given a battery of neuropsychologcal tests and their results were compared with those of onndiet subjects with PKU and normal controls. The findings generally supported the view that dietary cessation at age 10 is sufficient to prevent a substantial reduction of cognitive and motor ability, and that the central nervous system is probably mature enough to withstand the toxic effects of high blood phenylaianine by then. However, there were minor indications, in keeping with Welsh et al.'s hypothesis [M.C. Welsh. B.F. Pennington. S. Ozonoff. B. Rouse E.R.B. McCabe (1990) Neuropsychology of early‐treated phenylketonuria: specific executive function deficits. Child Development 61, 1697–713], that subtle intelleaual deficiencies might arise both during and after treatment, possibly in the realm of frontal‐executive functions.
Characteristics of the eating disorder in Prader‐Willi syndrome: implications for treatment
Authors: Holland A. J. , Treasure J. , Coskeran P. , Dallow J.
Published: August 2009

Over‐eating and resultant obesity is well recognized as a central feature of the Prader–Willi Syndrome (PWS). The eating behaviour of 13 subjects with PWS was been studied retrospectively over a 28‐day period and also by direct observation when given free access to food. Changing cognitions normally associated with food intake (e.g. changes in hunger) were assessed using visual analogue scales (VAS) and by asking subjects to rate photographs of particular foods. Eight out of 13 subjects (61 %) with PWS had to have their access to food severely restricted. Ten (77%) ate excessive amounts when given free access to food, and although feelings of ‘hunger',‘desire to eat’ and ‘fullness’ changed in the expected direaion. these changes were delayed, compared to a control group, and only occurred after eating a significantly greater amount of food. Ratings of ‘hunger’ and ‘fullness’ started to return to pre‐meal levels sooner than in the controls. The present authors consider that PWS is an example of genetic obesity secondary to an impaired satiety response. These observations have important implications for treatment.
Sexual abuse of adults with learning disabilities
Authors: Beail N. , Warden S.
Published: August 2009

This paper reports a clinical study of reported or disclosed sexual abuse of adults with learning disabilities. The findings support the results of a recent survey [V. Turk & H. Brown (1993) Sexual abuse of adults with learning disabilities: results of a two‐year incidence survey. Mental Handicap Research 6, 193–216] but some differences were found, particularly with regard to sex of the survivors. The study also illustrates more than previous studies a link Isetween sexual abuse and sexualized and Inappropriate sexual behaviour and other challenging behaviours in men with learning disabilities.
Ageing in adults with Down's syndrome in institutionally based and community‐based residences
Authors: Roeden J. M. , Zitman F. G.
Published: August 2009

Seventy‐one subjects with Down's syndrome (DS), between the ages of 29 and 68 years, and 46 matched controls (without DS) were examined for intelligence, memory (short‐ and long‐term memory, and spatial and temporal orientation), communication (receptive, expressive and written language) and daily living skills (personal, domestic and community daily living skills). All subjects were screened on hearing and visual functions, thyroid functions; depression and dementia. DS‐subjects and controls were matched on chronological age, mental age, living conditions and male/female ratio. Comparisons were made between five subgroups (I) non‐demented institutionalized subjects with DS (DSI‐group; n=35); (2) non‐demented institutionalized controls without DS (Ci‐group; n=22); (3) demented institutionalized subjects with DS (n= 10); (4) non‐demented subjects with DS living in group homes (DSg; n=26); and (5) non‐demented controls without DS living in group homes (Cg; n=24). Institutionalized and non‐institutionalized subjects, as well as demented and non‐demented subjects differed significantly on all functions measured. Multiple regression analysis was performed to examine the influence of age and sensory deficits on adaptive and cognitive functioning. In DSg subjects, significant associations were found between age and mental age, and between age and performances on written language. In (non‐demented) DSi subjects, significant relations were found between age and memory functions observed in daily circumstances. Moreover, in the (non‐demented) DSi elderly, visual impairment was significantly related to depressed performance on daily living skills. No age effects were seen in control subjects. Infirmities of old age like dementia and sensory deficits were far more common in people with DS than in controls. Psychiatric and diagnostic aspects of clinical depression and dementia were emphasized in particular.
Two longitudinal studies of the abilities of people with Down's syndrome
Authors: Shepperdson B.
Published: August 2009

A cohort of subjects with Down's syndrome born in South Wales, UK, in 1964, 1965 and 1966, and living at home, was studied as infants, teenagers and young adults (the original cohort). Carers were interviewed and the abilities of the subjects assessed, using a variety of measures. Average scores of the cohort improved over the years, although the rate of progress slowed down between the teenage and adult years. Scores were related to social class, stimulation given in the home, and at older ages, maternal age at the birth of the subject. This latter finding was unexpected. A comparative cohort of subjects with Down's syndrome from South Wales born in 1973, 1974 and 1975 was studied as infants and teenagers. They were at the same stage as the original cohort as infants and teenagers, but living 9 years later. In spite of the comparative cohort coming from a favoured background, in terms of social class and having access to improved services, mean scores at the teenage stage were only significantly better on one test of language than those of the original cohort at the same age. Most studies find that females with Down's syndrome have higher abilities than males: this was the case for the original cohort, but not for the comparative cohort.
Catatonic syndrome following recovery from neuroleptic malignant syndrome
Authors: Dent J.
Published: August 2009

In June 1992, a 51 ‐year‐old Caucasian man with a mild learning disability was prescribed chlorpromazine and thioridazine for sleeplessness and agitation. He developed neuroleptic malignant syndrome (NMS) which was treated successfully with Intravenous diazepam. Without further exposure to neuroleptics, the patient became acutely unwell with signs of catatonic syndrome in March 1993 and responded to oral diazepam. When the dose of diazepam was reduced in August 1993, the catatonic syndrome recurred and responded to an increase in his oral diazepam. In the past, the patient had been admitted to hospital in 1983 and 1986 with severe extrapyramidal symptoms and parkinsonism following prescription of neuroleptics for agitation. This case provides evidence that patients with a predisposition to catatonic syndrome may be at increased risk of developing NMS, and therefore, should not be treated with neuroleptics.
Hepatitis C in chronic liver disease: an epidemiological study based on 566 consecutive patients undergoing liver biopsy during a 10‐year period
Authors: VERBAAN H. , WIDELL A. , LINDGREN S. , LINDMARK B. , NORDENFELT E. , ERIKSSON S.
Published: August 2009

We analysed the presence of hepatitis C virus (HCV) antibodies in 566 patients undergoing liver biopsy. While over 20% of the patients were anti‐HCV positive according to elisa, only 13.8% had HCV antibodies when tested with a four‐antigen recombinant immunoblot assay (RIBA 2). At the time of inclusion in the study, most patients were asymptomatic, irrespective of whether they were HCV‐positive. Histological findings in anti‐HCV‐positive patients were chronic persistent hepatitis, chronic active hepatitis or cirrhosis in > 75% of cases. Only four of the patients who were anti‐HCV‐positive according to the RIBA 2 had autoimmune chronic active hepatitis. Risk behaviour could be identified in the majority of cases. Community‐acquired sporadic cases were rare (12%). Of the 153 patients who died during follow‐up, 23 subjects were anti‐HCV positive. Although age‐ and sex‐adjusted survival was not shorter in anti‐HCV‐positive patients than in anti‐HCV‐negatives, the risk of hepatocellular cancer was higher (P = 0.01). We conclude that HCV infection is associated with chronic liver disease, even when critical evidence of viral aetiology is slight. Truly sporadic cases are rare. Patients infected with HCV are at increased risk of developing hepatocellular cancer.
Close correlation between high‐density lipoprotein and triglycerides in normotriglyceridaemia
Authors: JOHANSSON J. , WALLDIUS G. , CARLSON L. A.
Published: August 2009

The relationship between high‐density‐lipoprotein (HDL) particle size subclasses and the levels of the major lipoprotein lipids was studied in 74 men consecutively referred to the lipid clinic. HDL (density 1.070‐1.21 kg l−1) was separated by polyacrylamide gradient gel electrophoresis (GGE) into five size‐defined subclasses, in order of decreasing size as follows: HDL2b, HDL2a, HDL3a, HDL3b and HDL3c. Cholesterol and triglyceride concentrations in very‐low‐density (VLDL), low‐density (LDL) and high‐density (HDL) lipoproteins were determined. The level of VLDL triglycerides was negatively correlated with HDL2b (r = − 0.66. P < 0.0001), and positively correlated with HDL3b concentrations (r = 0.65, P < 0.0001). Both correlations were restricted to subjects with VLDL triglyceride concentrations of < 1.80 mmol l−1, i.e. those with normotriglyceridaemia. Patients with a history of myocardial infarction and/or angina pectoris (n = 18) had significantly lower HDL2b levels than subjects with asymptomatic hyperlipidaemia (n = 50), i.e. 0.16 vs. 0.22 mg protein ml−1 (P < 0.05), despite essentially similar cholesterol and triglyceride levels in the VLDL, LDL and HDL fractions, including HDL2 and HDL3 cholesterol.
Function of terminal ileum in patients with Yersinia‐triggered reactive arthritis
Authors: SAARIO R. , LEINO R. , LAHESMAA R. , GRANFORS K. , TOIVANEN A.
Published: August 2009

In order to study the function of the intestinal epithelium in the terminal ileum, the Schilling test was performed in 10 patients with Yersinia‐triggered reactive arthritis, in 10 patients who had recovered from Yersinia enteritis without complications, and in five patients with rheumatoid arthritis treated with non‐steroidal anti‐inflammatory agents. The Schilling test indicates absorption of vitamin B12 in the terminal ileum, i.e. the area affected by Yersinia and inflamed in patients with reactive arthritis. The findings obtained demonstrate increased uptake through the epithelium in this area of the intestine in patients with Yersinia‐triggered reactive arthritis. There are two possible explanations. First, Yersinia infection may have a long‐term effect on the gut mucosa. Secondly, some individuals may, at the level of the terminal ileum, show enhanced absorption of vitamin B12 and/or other substances such as microbes or their components, resulting in increased susceptibility to certain infections.
Influence of a meat‐free diet on the urinary excretion of 3‐methylhistidine and creatinine in chronic renal failure
Authors: GUTIERREZ A. , ALVESTRAND A. , QURESHI G. A. , BERGSTRÖM J.
Published: August 2009

Urinary excretion of 3‐methylhistidine has been proposed as an index of internal protein breakdown provided that the intake of exogenous 3‐methylhistidine (meat) is excluded. To evaluate the potential use of 3‐methylhistidine in the metabolic assessment of patients with advanced renal failure, we studied a group of 11 patients with markedly reduced renal function who were put on a meat‐free diet (the protein intake was kept constant). Steady‐state plasma concentration and urinary excretion of 3‐methylhistidine were not achieved until 14 d after exclusion of meat from the diet. At that time the plasma concentration and urinary excretion of 3‐methylhistidine had decreased by 43% and 60%, respectively. We conclude that the delay in reaching steady state makes the clinical use of urinary excretion of 3‐methylhistidine in patients with advanced renal failure unpracticable as an index of protein breakdown. The exclusion of meat also resulted in a continuous decrease in the plasma level and urinary excretion of creatinine, with the result that plasma creatinine or its reciprocal become misleading for evaluation of changes in renal function until a new steady state has been reached.
Treatment of orthostatic hypotension with sleeping in the head‐up tilt position, alone and in combination with fludrocortisone
Authors: HARKEL A. D. J. TEN , VAN LIESHOUT J. J. , WIELING W.
Published: August 2009

We studied the effect of sleeping in the head‐up tilt (HUT) position, alone and in combination with fludrocortisone, on orthostatic tolerance and blood pressure (BP) in six patients with hypoadrenergic orthostatic hypotension. A high salt diet of 150–200 mmol Na+ d−1 was also administered. Combined treatment reduced orthostatic dizziness in all patients (P < 0.001), and increased the maximal standing period to at least 10 min. HUT alone (n = 4) reduced the BP decrease after 1 min of standing from −64/‐42/‐25 ± 29/21/17mmHg to −53/‐37/‐23 ± 31/24/20 mmHg (P < 0.01 for systolic BP). Addition of fludrocortisone to HUT (HUT/fludro) (n = 5) further reduced the BP decrease after 1 min of standing from −63/ −40/ −24 ± 20/12/11 mmHg to −21/‐19/‐8 ± 12/10/5 mmHg (P < 0.05 for systolic, mean and diastolic BP, respectively). BP at maximal standing time increased from 58/47/42 ± 9/8/7 mmHg initially to 95/69/57 ± 27/22/20 mmHg during combined treatment (P < 0.05 for systolic and mean BP), and remained unchanged during the 14‐month (range 8–70 month) follow‐up period. Nocturnal sodium excretion decreased from 8.0 ± 2.3 mmol h−1 to 5.9 ± 1.9 mmol h−1 with combined treatment; body weight increased by 1.6 kg on average (range 0.5‐2.4 kg) (P < 0.01). We conclude that the combination of HUT and fludrocortisone effectively minimizes orthostatic symptoms and increases orthostatic BP in patients with hypo‐adrenergic orthostatic hypotension.
Acute myelomonocytic leukaemia with infiltrative peripheral neuropathy
Authors: BILLSTRÖM R. , LUNDQUIST A.
Published: August 2009

The case of a 71‐year‐old woman with acute myelomonocytic leukaemia and severe pains in her arms, legs and back during treatment is described. Signs of a generalized polyneuropathy subsequently developed. Autopsy revealed massive leukaemic infiltration of peripheral nerves. Peripheral nerve involvement in acute leukaemia appears to be rare as judged from the very few previously reported cases. The condition should be suspected whenever inexplicable pain problems and signs of peripheral neuropathy occur in patients with acute leukaemia.
Anaemia, iron‐related measurements and erythropoietin levels in untreated patients with active leprosy
Authors: LAPINSKY S. E. , BAYNES R. D. , SCHULZ E. J. , MACPHAIL A. P. , MENDELOW B. , LEWIS D. , BOTHWELL T. H.
Published: August 2009

The mechanisms responsible for anaemia in leprosy were studied prior to the institution of therapy in 56 patients with active disease. Haematological indices, iron‐related measurements, inflammatory markers and erythropoietin levels were assessed, with bone‐marrow studies being performed on anaemic patients. Anaemia was more common in the patients with lepromatous leprosy (85.7%) than it was in the rest of the group (19%). The lepromatous group exhibited the disordered iron transport of the anaemia of chronic disorders in that they had a significantly lower mean serum iron level (P< 0.05), and a mildly raised serum ferritin concentration. Anaemic lepromatous patients also showed a blunted erythropoietin response compared with controls with noninflammatory anaemia. A subgroup of five anaemic subjects displayed apparently adequate transport of iron to the erythroid marrow (normal percentage transferrin saturations and appropriate sideroblast counts) and the blunted erythropoietin response appeared to be the dominant factor in the pathogenesis of their anaemia. Analysis of inflammatory markers revealed that while the erythrocyte sedimentation rate was very high in the lepromatous subjects, there was no concomitant rise in C‐reactive protein concentration. This suggests the presence of a disordered cytokine‐mediated acute phase response in the condition.
Hyponatraemia in acute brain disease
Authors: KRÖLL M. , JUHLER M. , LINDHOLM J.
Published: August 2009

Hyponatraemia (HN) can result from a wide range of mechanisms, and therapy must be individualized. Two theories of the origin of HN in acute brain disease have prevailed. The first is the cerebral salt wasting syndrome (CSWS), where excessive natriuresis caused by some unknown cerebral natriuretic factor lowers the total sodium pool of the body and hence the plasma concentration. The second theory is the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), where an increase in total body water is caused by unphysiological secretion of ADH, lowering the concentration of sodium in the plasma. A third possibility is ‘sodium shift’, i.e. a displacement of sodium from the extracellular to the intracellular space with a simultaneous movement of potassium in the opposite direction. The morbidity and mortality associated with HN only arise in cases where the rate of development of HN was 0.5 mmol h−1 or more. Symptoms respond promptly when the HN is quickly corrected with furosemide and 3% sodium chloride.
Metabolism of plasma low density lipoproteins in familial combined hyperlipidaemia: effect of acipimox therapy
Authors: ERICSSON S. , ERIKSSON M. , BERGLUND L. , ANGELIN B.
Published: August 2009

Ten male patients with familial combined hyperlipidaemia (FCHL) were studied with regard to LDL metabolism and composition. The FCHL patients had higher LDL levels than healthy controls (5.4 ± 1.4 vs. 3.7 ± 0.7 mmol l−1; P < 0.005) and a higher rate of production of the lipoprotein (15.8 ± 3.1 mg kg−1 d−1 in FCHL vs. 13.1 ± 1.8 mg kg−1 d−1 in the normals; P < 0.005). The fractional catabolic rate of LDL was low‐normal in the FCHL patients, with a high level of interindividual variation. The actual individual LDL cholesterol level within the FCHL patient group appeared to be more closely associated with the LDL apoB FCR value than the rate of production of the particle. Analysis of the LDL particles from FCHL patients revealed a relative enrichment in triglycerides, while the cholesterol content of the lipoprotein was normal. Institution of acipimox therapy in 8 patients reversed the high rate of synthesis of LDL (15.2 ± 3.5 mg kg−1 d−1) to a more normal level (13.9 ± 4.0 mg kg−1 d−1; P = 0.08), while the FCR did not change significantly. In conclusion, patients with FCHL show an apparent overproduction of LDL apoB, while the actual degree of LDL elevation appears to be dependent on the clearance capacity of the lipoprotein, measured as LDL apoB FCR. The overproduction defect of LDL apoB can, at least in part, be managed by treatment with the nicotinic acid analogue acipimox.
Use of smokeless tobacco: blood pressure elevation and other health hazards found in a large‐scale population survey
Authors: BOLINDER G. M. , AHLBORG B. O. , LINDELL J. H.
Published: August 2009

Health hazards associated with the use of smokeless tobacco were evaluated in a cross‐sectional study of 97 586 Swedish construction workers undergoing health examinations in 1971–74. All users of smokeless tobacco only (5014 subjects) and all exclusive smokers of ≥ 15 cigarettes daily (8823 subjects) were compared with all non‐users of any tobacco (23 885). Both smokeless tobacco users and smokers showed higher prevalences of circulatory and respiratory disorders. Hypertension was most common in smokeless tobacco users. In the 45‐ to 56‐years age group, the odds ratio for a diastolic blood pressure of > 90 mmHg was 1.8 (95% CI, 1.5–2.1), and for a systolic blood pressure > 160 mmHg, 1.7 (95% CI, 1.3–2.1). Smokers showed the lowest prevalence of hypertension. Disability pensions due to cardiovascular disease were nearly 50% more frequent in both smokeless tobacco users and smokers. These findings indicate that an increased cardiovascular risk is also associated with the use of smokeless tobacco.
Hypersensitivity reaction associated with acute hepatic dysfunction following a single intravenous dose of procainamide
Authors: WORMAN H. J. , IP J. H. , WINTERS S. L. , TEPPER D. C. , GOMES A. J.
Published: August 2009

Rare cases of hepatotoxicity have been attributed to the antiarrhythmic agent procainamide. We here describe the case of a patient who had a hypersensitivity reaction to procainamide with fever, chills, arthralgia, abdominal pain and acute elevations of serum aminotransferase activities and bilirubin concentration. The reaction occurred after the patient had received a large intravenous dose during cardiac electrophysiological testing. This case should alert physicians to potential hepatotoxic reactions to procainamide, particularly with the increasing popularity of cardiac electrophysiological testing, during which this drug is commonly used.