bluuebunny/crossref_metadata_2025 huggingface dataset:
Low‐dose and short‐term cyclosporine treatment in patients with chronic idiopathic urticaria: A clinical and immunological evaluation
Authors: SERHAT INALOZ H. , OZTURK Savas , AKCALI Cenk , KIRTAK Necmettin , TARAKCIOGLU Mehmet
Published: May 2008

The present study aimed to evaluate the effectiveness of 2.5 mg/kg/day cyclosporin (CsA) treatment in patients with severe chronic idiopathic urticaria (CIU) and the impact of CsA treatment on several cytokines involved in the etiopathogenesis of CIU. Twenty‐seven CIU patients and 24 healthy control subjects were included in the study. The autologous serum skin test (ASST) for autoantibodies and urticaria activity scoring (UAS) were measured for the evaluation of the clinical severity and the response to therapy, and the serum levels of interleukin (IL)‐6, IL‐8, IL‐2 receptor, IL‐1β, tumor necrosis factor (TNF)‐α and IL‐5 were measured. The mean UAS score was 32.07 ± 7.05 and 6.22 ± 3.84 before and after CsA treatment, respectively. The serum IL‐2 receptor, TNF‐α and IL‐5 levels of patients before CsA treatment were statistically higher than those of the control group (P = 0.001), and after 4 weeks of CsA therapy the mean IL‐2R, TNF‐α and IL‐5 levels were significantly decreased. The data from this study demonstrate that CsA therapy is efficient and safe for CIU patients. Increase in clinical efficacy and marked decreases in serum cytokine levels suggest that inhibition of cytokine generation is involved in the action of the drug in this clinical setting.
Seborrheic keratosis that follows Blaschko's lines
Authors: MABUCHI Tomotaka , AKASAKA Emiko , KONDOH Akio , UMEZAWA Yoshinori , MATSUYAMA Takashi , OZAWA Akira
Published: May 2008

A 66‐year‐old Japanese man had skin lesions on the left side of his trunk and the left upper extremity for approximately 10 years. The skin lesions were asymptomatic but increased gradually, which brought the patient to our hospital. On the initial examination, we noticed 5 mm × 5 mm to 15 mm × 5 mm, round or oval, light to dark brown keratotic papules on the left side of chest and abdomen and the left upper extremity. The papules were aligned in an S‐shaped line on the trunk and in a straight line on the upper extremity. Clinical and histopathological findings led to a diagnosis of seborrheic keratosis that followed Blaschko's lines. To our knowledge, no such a case has been reported previously. Our case supports the hypothesis that seborrheic keratosis can be associated with genetic mosaicism.
Perspectives in treatment of AL amyloidosis
Authors: Wechalekar Ashutosh D. , Hawkins Philip N. , Gillmore Julian D.
Published: May 2008

Light chain (AL) amyloidosis is the most frequently diagnosed form of systemic amyloid in the western world. The historically poor prognosis of AL amyloidosis appears to be improving with currently reported median survival of c. 40 months compared to 13 months in the early 1990s when low‐dose oral melphalan was the mainstay of treatment. Autologous stem cell transplantation (ASCT) achieves the highest rates of complete clonal response but is confounded by substantial treatment‐related mortality in AL amyloidosis unless it is restricted to highly selected patients. Newer chemotherapy regimens appear to have a balance of better safety and respectable efficacy with overall outcomes nearly similar to ASCT, but which may be used more widely. There are few data comparing durability, depth of clonal response, rate of organ response and overall survival following ASCT or chemotherapy, but a recent small, randomized trial did not suggest superiority of ASCT to oral melphalan and dexamethasone. There is a compelling need for further and larger randomized trials in this context. At the same time, various new specific anti‐amyloid drugs have shown (in early phase studies or animal models) some very promising results. This review attempts to highlight the challenges, controversies and progress in AL amyloidosis.
Arsenic trioxide induces de novo protein synthesis of annexin‐1 in neutrophils: association with a heat shock‐like response and not apoptosis
Authors: Binet François , Chiasson Sonia , Girard Denis
Published: May 2008

We recently demonstrated that arsenic trioxide (ATO) induced apoptosis in human neutrophils and increased de novo protein synthesis. Here, we identified one of these newly synthesized proteins as annexin‐1 (AnxA1), a protein recently found to be proapoptotic in neutrophils when added exogenously. AnxA1 was detected at the cell membrane of ATO‐induced neutrophils as well as in the supernatants. Using neutrophils harvested from AnxA1 knockout mice, we found that the proapoptotic activity of ATO was similar in neutrophils, regardless of AnxA1 levels. A second protein was identified as heat shock protein (Hsp) 89α. Because ATO is known to induce a HS‐like response in a variety of cells, we investigated its ability to induce gene expression of Hsp in neutrophils and found that ATO increases HSP90AA1, HSPA1 and HSPB1 mRNA in these cells. We conclude that ATO‐induced neutrophil apoptosis by an AnxA1‐independent mechanism. Our data provide the first evidence that ATO induces a stress response in human neutrophils and that de novo synthesis of AnxA1 is related to this event rather than to the proapoptotic activity of ATO.
Testing for tree‐ring divergence in the European Alps
Authors: BÜNTGEN ULF , FRANK DAVID , WILSON ROB , CARRER MARCO , URBINATI CARLO , ESPER JAN
Published: May 2008

Evidence for reduced sensitivity of tree growth to temperature has been reported from multiple forests along the high northern latitudes. This alleged circumpolar phenomenon described the apparent inability of temperature‐sensitive tree‐ring width and density chronologies to parallel increasing instrumental temperature measurements since the mid‐20th century. In addition to such low‐frequency trend offset, the inability of formerly temperature‐sensitive tree growth to reflect high‐frequency temperature signals in a warming world is indicated at some boreal sites, mainly in Alaska, the Yukon and Siberia. Here, we refer to both of these findings as the ‘divergence problem’ (DP), with their causes and scale being debated. If DP is widespread and the result of climatic forcing, the overall reliability of tree‐ring‐based temperature reconstructions should be questioned. Testing for DP benefits from well‐replicated tree‐ring and instrumental data spanning from the 19th to the 21st century. Here, we present a network of 124 larch and spruce sites across the European Alpine arc. Tree‐ring width chronologies from 40 larch and 24 spruce sites were selected based on their correlation with early (1864–1933) instrumental temperatures to assess their ability of tracking recent (1934–2003) temperature variations. After the tree‐ring series of both species were detrended in a manner that allows low‐frequency variations to be preserved and scaled against summer temperatures, no unusual late 20th century DP is found. Independent tree‐ring width and density evidence for unprecedented late 20th century temperatures with respect to the past millennium further reinforces our results.
Persistent effects of a discrete warming event on a polar desert ecosystem
Authors: BARRETT J. E. , VIRGINIA R. A. , WALL D. H. , DORAN P. T. , FOUNTAIN A. G. , WELCH K. A. , LYONS W. B.
Published: May 2008

A discrete warming event (December 21, 2001–January 12, 2002) in the McMurdo Dry Valleys, Antarctica, enhanced glacier melt, stream flow, and melting of permafrost. Effects of this warming included a rapid rise in lake levels and widespread increases in soil water availability resulting from melting of subsurface ice. These increases in liquid water offset hydrologic responses to a cooling trend experienced over the previous decade and altered ecosystem properties in both aquatic and terrestrial ecosystems. Here, we present hydrological and meteorological data from the McMurdo Dry Valleys Long Term Ecological Research project to examine the influence of a discrete climate event (warming of >2 °C) on terrestrial environments and soil biotic communities. Increases in soil moisture following this event stimulated populations of a subordinate soil invertebrate species (Eudorylaimus antarcticus, Nematoda). The pulse of melt‐water had significant influences on Taylor Valley ecosystems that persisted for several years, and illustrates that the importance of discrete climate events, long recognized in hot deserts, are also significant drivers of soil and aquatic ecosystems in polar deserts. Thus, predictions of Antarctic ecosystem responses to climate change which focus on linear temperature trends may miss the potentially significant influence of infrequent climate events on hydrology and linked ecological processes.
Molecular analysis of F8 in Lebanese haemophilia A patients: novel mutations and phenotype–genotype correlation
Authors: DJAMBAS KHAYAT C. , SALEM N. , CHOUERY E. , CORBANI S. , MOIX I. , NICOLAS E. , MORRIS M.A. , DE MOERLOOSE P. , MÉGARBANÉ A.
Published: May 2008

Summary.  Haemophilia A (HA) is an X‐linked recessive hereditary bleeding disorder affecting one in 5000 men, resulting from mutations in the F8 gene. Our objective was to identify the spectrum of mutations of the F8 gene in Lebanese patients, and to perform genotype/phenotype correlations. A group of 79 HA patients from 55 unrelated families was studied. Patients were screened for intron 22 and intron 1 inversion using PCR. In the absence of mutations in both introns, a dHPLC screening followed by a DNA sequencing of all coding regions was performed. When patients presented novel mutations, 150 control chromosomes were tested to exclude common polymorphisms. Large deletions were confirmed by MLPA technique. The mRNA was specifically studied whenever a splice site mutation was detected. In addition, studies of the putative biochemical function and FVIII 3D structures were conducted. Thirty‐four mutations were identified in this study of which 21 were novel: 11 missense, two nonsense, two splice sites, five small deletions and one large deletion. Inhibitor found in three over 75 patients correlated with large deletion, intron 22 inversion, and nonsense mutations. We were able to identify all causative mutations in those HA patients. This knowledge represents a huge step for genetic counselling.
Mutation analysis of haemophilia B in the Irish population: increased prevalence caused by founder effect
Authors: JENKINS P. V. , EGAN H. , KEENAN C. , O’SHEA E. , SMITH O. P. , NOLAN B. , WHITE B. , O’DONNELL J.
Published: May 2008

Summary.  Haemophilia B generally arises as a result of unique mutations within the F9 gene and occurs with a prevalence of approximately one case per 30 000 males worldwide. The population prevalence of haemophilia B in Ireland at one per 12 500 males is particularly high. To identify the mutations responsible for haemophilia B and to define the biological basis underlying the increased prevalence in the Irish population, we performed sequence analysis of the F9 gene in 51 apparently unrelated kindred. In 18 kindred with severe or moderate haemophilia B, we identified 14 different mutations; these occurred throughout the F9 gene and included small deletions, missense, non‐sense and splice‐site mutations and included four novel candidate mutations. In contrast to the variety of different causative mutations with moderate or severe haemophilia B, we found three common mutations accounted for 83% (24/29) of Irish kindred with mild haemophilia B. The mutation n‐6 G>A in the promoter region of F9 (which results in the characteristic haemophilia B Leyden phenotype) was found in 10 unrelated kindred. The mutation C>T 30933 in exon 8 (Ala271Val) was identified in a further 10 apparently unrelated kindred. Finally, 10430 G>A mutation (Gly60Ser) was observed in four different kindred. Haplotype analysis was performed on the index cases with the most common mutations and supported the hypothesis that the increased population prevalence of mild haemophilia B in the Irish population arose as a result of founder effect rather than an increased incidence of de‐novo F9 mutations.
Accidental swallowing of an endodontic file
Authors: Kuo S.‐C. , Chen Y.‐L.
Published: May 2008

Aim  To report the management of an iatrogenic incident in which an endodontic file was swallowed accidentally and passed into the gastrointestinal tract.

Summary  A 51‐year‐old male swallowed a 21 mm, size 30 endodontic file during root canal treatment without rubber dam. In the absence of clinical complications, the patient was reviewed with serial chest and abdominal radiographs, and stool tests for occult blood until the instrument was discharged at 3 days. This report discusses early differential diagnosis for locating foreign bodies and underlines the importance of serial radiographic evaluation for signs of foreign body migration.

Key learning points • The use of rubber dam is mandatory for patient safety during root canal treatment.

• Early location of an inhaled or ingested foreign body facilitates appropriate and timely treatment management and referral.

• When a foreign body passes into the gastrointestinal tract, clinical symptoms and signs should be monitored closely until it is excreted or removed.

• An endodontic file can pass through the gastrointestinal tract asymptomatically and apparently atraumatically within 3 days.
The efficacy of dynamic irrigation using a commercially available system (RinsEndo®) determined by removal of a collagen ‘bio‐molecular film’ from an ex vivo model
Authors: McGill S. , Gulabivala K. , Mordan N. , Ng Y.‐L.
Published: May 2008

Aim  To compare the efficacy of three irrigation protocols using an established ex vivo bio‐molecular film model.

Methodology  Thirty human teeth with single straight canals were randomly allocated to three groups [static, manual‐dynamic, automated‐dynamic (RinsEndo®)]; each with a sub‐group (n = 5) for needle position at 4 or 10 mm short of the working length (WL). The root canals were prepared to apical size 40, taper 0.08. The teeth were split longitudinally into two halves and a standard coat of stained‐collagen was applied to the canal surfaces. The re‐assembled teeth were irrigated using one of the protocols with the irrigation needle at one of two positions. Digital images of the canal surfaces, before and after irrigation with 18 mL of 2.5% NaOCl, were used to score surface coverage with stained‐collagen using image‐analyses (ipWin4®). The data were analysed using linear regression models.

Results  The canal area covered with stained‐collagen was significantly (P < 0.001) less after dynamic irrigation (manual/automated) compared with static irrigation; but automated‐dynamic irrigation was significantly (P = 0.037) less effective than manual‐dynamic irrigation. The ‘orientation of needle port’, ‘corono‐apical level of canal’ and ‘apical extent of needle placement’ were significant (P < 0.001) factors influencing efficacy of irrigation. Residual collagen was most evident in the coronal third. Deeper penetration of the needle tip resulted in significantly (P < 0.001) more effective collagen removal.

Conclusions  Automated‐dynamic irrigation was significantly more effective (16%) than static irrigation but significantly less effective (5%) than manual‐dynamic irrigation. Irrigation was more effective (7%) when the needle was placed closer to WL.
Biofilm on the apical region of roots in primary teeth with vital and necrotic pulps with or without radiographically evident apical pathosis
Authors: Rocha C. T. , Rossi M. A. , Leonardo M. R. , Rocha L. B. , Nelson‐Filho P. , Silva L. A. B.
Published: May 2008

Aim To evaluate, by scanning electron microscopy (SEM), the presence of biofilms on the external surfaces of the apical third of roots of human primary teeth with vital or necrotic pulps with and without radiographically evident periradicular pathosis.

Methodology Eighteen teeth were selected: group I – normal pulp (n = 5), group II – pulp necrosis without radiographic evidence of periapical pathosis (n = 7) and group III – pulp necrosis with well‐defined radiographic periapical pathosis (n = 6). After extraction, the teeth were washed with saline and immersed in 0.03 g mL−1trypsin solution for 20 min. The teeth were then washed in sodium cacodilate buffer and stored in receptacles containing modified Karnovsky solution. The teeth were sectioned, dehydrated in an ethanol series, critical‐point dried with CO2, sputter coated with gold and the external root surface in the apical third examined by SEM.

Results In the teeth of groups I and II, the apical root surfaces were covered by collagen fibres, with no evidence of bacteria (100%). In the teeth of group III, the root apices had no collagen fibres but revealed resorptive areas containing microorganisms (cocci, bacilli, filaments and spirochetes) in all cases (100%).

Conclusion Microorganisms organized as biofilms on the external root surface (extraradicular infection) were detected in primary teeth with pulp necrosis and radiographically visible periapical pathosis.
Reliability of body temperature measurements in hospitalised older patients
Authors: Giantin Valter , Toffanello Elena D , Enzi Giuliano , Perissinotto Egle , Vangelista Stefania , Simonato Matteo , Ceccato Corrado , Manzato Enzo , Sergi Giuseppe
Published: May 2008

Aims and objectives.  To compare different body temperature assessment methods in older people and to assess the role of cognitive and functional characteristics in temperature recordings.

Background.  Axillary gallium‐in‐glass thermometers are commonly used. Their accuracy depends on the proper placement of the device and their permanence in place for eight minutes. With adequate instruction, well‐functioning patients can measure their axillary temperature by themselves, while in cognitively and functionally impaired older people, inadequate understanding of instructions and misplacement of the thermometer might determine significant recording errors. Electronic ear and axillary temperature measurements are faster, but their accuracy has not been demonstrated convincingly with older people.

Methods.  Patients (n = 107; aged 65–104 years) were recruited. Barthel Index and Short Portable Mental Status Questionnaire (SPMSQ) scores were obtained for each patient. Temperature readings were obtained using: the axillary gallium‐in‐glass thermometer, with (Tnurse) and without (Tself) the nurse's assistance; the electronic axillary thermometer (Tel) and the infrared tympanic thermometer (Ttymp). The Tnurse was considered as the reference method.

Results.  Mean difference and standard deviation (mean ± SD) in temperature recordings between the different techniques and Tnurse differed significantly from zero for Tself (−0·40 SD 0·42) and Ttymp (+0·19 SD 0·48). No significant differences in temperature recordings emerged between Tnurse and Tel. In simple linear regression models, the difference between Tself and Tnurse significantly correlated with age, gender, SPMSQ score and Barthel Index. Multiple linear regression analysis showed an underestimation of body temperature in older patients with cognitive impairments.

Conclusion.  Unassisted gallium‐in‐glass axillary temperature assessment is inadequate, in older patients. The differences between Tself and Tnurse are significantly influenced by age and mental decline. Tel provides adequate accuracy.

Relevance to clinical practice.  In geriatric settings, the electronic axillary thermometer is a safe and accurate alternative to the more traditional gallium‐in‐glass thermometer, with the advantage of saving time (five seconds in recording vs. eight minutes).
Towards understanding gender differences in disordered eating among adolescents
Authors: Hautala Lea Anneli , Junnila Jouni , Helenius Hans , Väänänen Aija‐Mari , Liuksila Pirjo‐Riitta , Räihä Hannele , Välimäki Maritta , Saarijärvi Simo
Published: May 2008

Aims and objectives.  The aim of the study was to enhance the detection of disordered eating in adolescents. The objectives were to examine gender differences in the prevalence of eating disorder symptoms, in occurrence of health‐risk factors and susceptibility to these and to investigate associations between health‐risk factors and eating disorder symptoms.

Background.  Disordered eating has a strong female preponderance. Reasons for the gender discrepancy are not well known. However, to develop effective strategies for eating disorder prevention, we need to understand gender differences in disordered eating and the related factors.

Design.  This is a school‐based, cross‐sectional cohort study with a natural design.

Methods.  The SCOFF and the R‐BDI questionnaires were administered to students (14–15 years old) attending the eighth grade of secondary school. Information about health‐risk factors was obtained from the adolescents’ school health‐care records.

Results.  The results were based on data from 1036 (71% of the sample) students. Self‐reported eating disorder symptoms were prevalent in 24% of the girls and 16% of the boys. Girls reported many of the health‐risk factors studied at a higher rate than boys. However, there were no gender differences in susceptibility to these factors. Dissatisfaction with appearance or weight, use of tobacco, lack of regular meals and poor communication with parents increased the likelihood of eating disorder symptoms in both genders.

Conclusions.  Gender differences in disordered eating are relatively small in adolescence. To enhance the detection of eating disorder symptoms, both girls and boys should be screened for these problems in secondary school.

Relevance to clinical practice.  The results can help nurses to use the information obtained from adolescents’ health‐care records, their annual health examinations and their responses to the SCOFF questionnaire to identify those who need further intervention, including adolescent boys.
Stroke: coping strategies and depression among Chinese caregivers of survivors during hospitalisation
Authors: Qiu Yanru , Li Sijian
Published: May 2008

Aims and objectives. The main aim of this study was to identify the coping strategies of stroke caregivers, to identify the factors associated with caregivers’ depression and to identify predictors of caregivers’ depression.

Background. Stroke has a high incidence in China. Most stroke survivors are accompanied by family caregivers during hospitalisation. However, little is known about these informal caregivers’ coping strategies to the consequences brought on by stroke and their depressive symptoms.

Method. A correlation and cross‐sectional design was used and a purposive sample of 92 stroke survivors and their caregivers completed the questionnaires, which were used to describe the demographic of both the caregiver and stroke survivor, coping strategies (the Brief COPE Inventory) and depression of caregivers (the Center for Epidemiologic Studies Depression Scale). Spearman's correlation and multiple stepwise regression analysis were used in data analyses.

Results. Several coping strategies (planning, positive reframing, acceptance, active coping, use of instrumental support and humour) were most commonly used by stroke caregivers. The length of hospital stay, stroke survivor's cognitive status and functional status, family income and coping strategies such as (i) denial, (ii) self‐blame, (iii) planning and (iv) religion had significant correlations with caregiver's depression. The best predictors of caregiver's depression were denial, planning and stroke survivor's functional status.

Conclusions. This study contributes to our knowledge about the coping strategies and depression level of stroke caregivers on the Chinese mainland. The depression rate is very high during hospitalisation, although these caregivers often had positive coping responses to the stroke event. Many factors were associated with caregivers’ depression.

Relevance to clinical practice. Nurses should not only pay attention to stroke survivors but also to their caregivers. To help them adjust well from the stroke consequences and avoid depression, nurses should implement effective interventions.
Incidence and risk factors of breast cancer lymphoedema
Authors: Park Jin Hee , Lee Won Hee , Chung Hae Soo
Published: May 2008

Aim.  The purpose of this study was to examine the incidence of lymphoedema and to identify risk factors of lymphoedema in patients with breast cancer undergoing mastectomy in Korea.

Background.  Lymphoedema is a serious problem for many breast cancer survivors. Although the potential impact of lymphoedema is extensive, it is largely unrecognised.

Methods.  Women with breast cancer (n = 450) receiving mastectomy were recruited from outpatient breast cancer clinics of two university hospitals in Seoul, Korea from October 2004 to May 2005. Lymphoedema was defined by circumferential measurement. This study examined the risk factors associated with lymphoedema through the literature review. A descriptive design was used for this study and data were collected using structured questionnaire. Data were analysed by chi‐square test and multiple logistic regression.

Results.  Among the 450 cases of breast cancer, 24·9% had developed lymphoedema. There were significantly increased risks of lymphoedema if women were with higher staging, had modified radical mastectomy, had axillary lymph node dissection, received axillary radiotherapy and were with body mass index greater than 25 kg/m2. A significantly decreased risk of lymphoedema was found in women who exercised regularly, received pretreatment education of lymphoedema and had performed preventive self‐care activities.

Conclusions.  Lymphoedema is recognised as an unpleasant and uncomfortable consequence of breast cancer‐related treatment. Patients should be advised of the risk of lymphoedema and educated to detect its symptoms.

Relevance to clinical practice.  It is of importance to recognise breast cancer patients at risk for lymphoedema. Nurses should inform patients with breast cancer about their risk for lymphoedema and guidelines to reduce the risk and to emphasise self‐care activities for prevention.
Use of sibutramine to assist obese women with weight loss can be successful in dietitian‐led clinics: another tool in the dietitian’s toolbox
Authors: Barratt R. , Frost G. , O’Boyle A. , Millward J. , Truby H.
Published: May 2008

Background  This study investigated differences in weight loss outcomes in obese women with Type 2 diabetes (T2D) compared to those without T2D attending a 6‐month dietetic led ‘Lifestyle’ intervention. In those who had failed to reach weight loss goals using the ‘Lifestyle’ approach, the study further examined the effect on weight loss with the addition of sibutramine (Reductil®, Abbott Laboratories, USA) over a 6‐month period.

Methods  The study comprised a case–control analysis of data from 38 obese female patients (18 with T2D) from the ‘Lifestyle’ and ‘Pharmacotherapy’ clinics attending a tertiary hospital in the UK.

Results  In the ‘Lifestyle’ treatment groups, those with T2D lost significantly less body weight than those without T2D [5.26 kg (4.54%) versus 9.89 kg (9.55%), respectively]. For subjects who had failed to lose weight via the ‘Lifestyle’ intervention, the addition of sibutramine resulted in a similar weight loss compared to their pair‐matched ‘Lifestyle’ only ‘successful’ counterparts (9.66% versus 9.55%).

Conclusions  Not all obese women, and those with T2D in particular, will derive benefit from ‘Lifestyle’ advice and those who are resistant to this treatment approach may be assisted by pharmacotherapy. Dietitians can play a role in identifying those individuals who may benefit from the use of pharmacotherapy.
The Interleukin‐23 / Interleukin‐17 axis in intestinal inflammation
Authors: Maloy Kevin J.
Published: May 2008

Although the precise aetiology of inflammatory bowel disease (IBD) remains unclear, recent discoveries have led to an improved understanding of disease pathogenesis. Whilst these findings have underscored the central role of innate and adaptive immune responses in intestinal inflammation, they have also precipitated a paradigm shift in the key cytokine pathways that drive disease. The prevailing dogma that IBD was mediated by interleukin (IL)‐12‐driven T‐helper (Th)1 CD4 T cell responses towards the bacterial flora has been largely dispelled by findings that the closely related cytokine IL‐23 appears to be the key mediator of intestinal inflammation. IL‐23 is associated with a novel subset of IL‐17‐secreting CD4 T cells termed Th17 cells and rodent studies have implicated the IL‐23/IL‐17 axis in autoimmune inflammation. Genome‐wide association studies in IBD patients have confirmed the predominant role of the IL‐23 pathway, indicating that this could represent an important future therapeutic target.
A gut feeling of the PXR, PPAR and NF‐κB connection
Authors: Wahli W.
Published: May 2008

Bowel diseases reveal the complex interplay of sensing and signalling pathways in maintaining healthy homeostasis of the intestine. Recent studies of the xenobiotic nuclear receptor, pregnane X receptor and the inflammatory mediator nuclear transcription factor kappaB (NF‐κB) reveal a functional link between xenobiotic neutralization and inflammation and explain how certain xenobiotics can affect the immune response. Furthermore, another nuclear receptor, peroxisome proliferator‐activated receptor γ (PPARγ) has been shown to produce beneficial effects in experimental inflammatory bowel diseases by repression of NF‐κB thereby reducing inflammation, whilst its close relative PPARβ/δ appears at a central position in signalling pathways involved in the progression of colon cancer. Recently accumulated knowledge on the action of these nuclear receptors and NF‐κB in intestinal homeostasis may provide the rationale for the development of innovative treatment strategies with selective receptor modulators.
Neuro‐glial crosstalk in inflammatory bowel disease
Authors: Neunlist M. , Van Landeghem L. , Bourreille A. , Savidge T.
Published: May 2008

Inflammatory bowel disease (IBD) is a multifactorial disease in which environmental, immune and genetic factors are involved in the pathogenesis. Although biological therapies (antibodies anti‐tumour necrosis factor‐α or anti‐integrin) have considerably improved the symptoms and quality of life of IBD patients, some drawbacks have emerged limiting their long‐term use. In addition, prevention of relapses and treatment of resistant ulcers remains a clinical challenge. In this context, a better understanding of the pathophysiology of IBD and the development of novel therapeutic intervention would benefit from further basic and preclinical research into the role of the cellular microenvironment and the interaction between its cellular constituents. In this context, the role of the enteric nervous system (ENS) in the regulation of the intestinal epithelial barrier (IEB) and the gut immune response has fuelled an increased interest in the last few years. Recent advances, summarized in this review, have highlighted the ENS as playing a key role in the control of IEB functions and gut immune homeostasis, and that alterations of the ENS could be directly associated in the development of IBD and its associated symptoms.
CHROMATOLYSIS AND AXONAL DYSTROPHY IN THE AUTONOMIC NERVOUS SYSTEM IN GRASS SICKNESS OF EQUIDAE
Authors: GILMOUR J. S.
Published: May 2008

Light and electron microscopic examinations of autonomic ganglia from cases of grass sickness have been carried out. The main alterations are pyknosis, cytoplasmic vacuolation originating from granular endoplasmic reticulum, and axonal dystrophy. The cell body changes bear some resemblance to chromatolysis.
THE PATHOLOGY OF ULNAR NERVE COMPRESSION IN MAN
Authors: NEARY D. , EAMES ROSEMARY A.
Published: May 2008

Three ulnar nerves at the elbow were obtained at necropsy on two patients with unrelated terminal illnesses and were examined by light and electron microscopy. In one case clinical evidence of ulnar neuropathy had been present. A neuromatous swelling was found on one nerve immediately proximal to the tendinous arch of the flexor carpi ulnaris muscle. At this level abnormalities in single teased fibres were found in all three nerves, including segmental demyelination and remyelination, and the presence of paranodal bulbous swellings and demyelination. Transverse sections showed a gradation of changes proximally and distally, the greatest abnormalities being present at the level of the tendinous arch. Perineurial thickening and endo‐neurial oedema were seen, the latter producing a reduction in fibre density which returned to normal on either side of the lesion. Percentage frequency histograms showed a marked reduction in the proportion of large diameter fibres at the level of the lesion. Numerous clusters of regenerated and remyelinated fibres (regeneration clusters) were present; these were significantly increased in number in those areas in which abnormalities were present in single teased fibres. The significance of the changes has been discussed. It is suggested that the presence of many regeneration clusters in otherwise apparently normal transverse sections of nerves taken from sites where entrapment may occur indicates that underlying abnormalities will be seen in single teased nerve fibres and early compression neuropathy is present.
UNMYELINATED FIBRES IN NORMAL AND COMPRESSED PERIPHERAL NERVES OF THE BABOON: A QUANTITATIVE ELECTRON MICROSCOPIC STUDY
Authors: FOWLER T. J. , OCHOA J.
Published: May 2008

The calibre spectrum of unmyelinated axons in normal medial popliteal nerves of baboons, fixed by perfusion with glutaraldehyde and measured by electron microscopy, is consistently unimodal. Following acute compression with a pneumatic tourniquet sufficient to cause a local conduction block, unmyelinated fibres are usually undamaged. This offers an anatomical basis for the selective sensory sparing (particularly pain) in a neurapraxia. Following local compression severe enough to cause Wallerian degeneration in a proportion of the myelinated fibres, a new population of axonal profiles eventually grows within the unmyelinated fibres. The features of these profiles are those of axonal sprouts and their presence results in a bimodal calibre spectrum of unmyelinated axons. This suggests that in these cases the period of prolonged compression has resulted in damage to the unmyelinated fibres.
HISTOCHEMICAL AND ULTRASTRUCTURAL STUDIES OF PRIMARY SENSORY NEURONS IN MICE WITH DYSTONIA MUSCULORUM. I. ACETYLCHOLINESTERASE AND LYSOSOMAL HYDROLASES
Authors: HANKER J. S. , PEACH R.
Published: May 2008

Histochemical and ultrastructural studies of primary sensory neurons in mice with dystonia musculorum. I. Acetylcholinesterase and lysosomal hydrolases

Enzyme histochemical and fine structural studies were performed on mice with a hereditary sensory neuropathy (dystonia musculorum). The dystonic mice were compared with normal litter mates. Acetylcholinesterase activity was studied in trigeminal and spinal ganglia and sensory receptors as well as in sympathetic ganglia. Lysosomal hydrolases and ultrastructural features were studied in the trigeminal and spinal ganglia. Striking changes in the amount and distribution of enzymic activity were observed in the perikarya of sensory ganglion neurons in dystonic mice. Perikaryal involvement was indicated by displacement of the nucleus, enlargement of the perikaryon, peripheral location of Nissl substance, loss of enzymic activity and an increase in the number of neurofilaments–features similar to those that follow physical interruption of the axon. The focal axonal swellings that occurred along sensory nerve fibers contained concentrations of lysosomal hydrolases and sometimes acetylcholinesterase activity. They were generally more numerous in the nerve fibers located distal to the ganglion rather than proximal to it. At the ultrastructural level these swellings contained lysosomal bodies and remnants of organelles. Some abnormalities in the myelin and the size of paranodal gaps were also observed. These results are discussed in relation to interruptions in axoplasmic flow and experimental neuropathies including those of the ‘dying‐back’ type.
CELL DEATH AND THE CELL‐CYCLE IN THE SUBEPENDYMAL LAYER OF NEONATE RATS AFTER THE ADMINISTRATION OF ETHYL NITROSOUREA
Authors: KNOWLES J. F.
Published: May 2008

Cell proliferation and cell death in the subependymal layer of neonate rats have been investigated during the 28 hour period following the subcutaneous injection of ethyl nitrosourea (ENU) and a labelling dose of (3H) thymidine. The ENU caused two waves of cell death which affected unlabelled cells and, to a lesser extent, labelled cells. Feulgen microdensitometry showed that almost all degenerate cells contained a diploid amount of DNA and thus were postmitotic. The percentage‐labelled mitoses in test animals showed two peaks that occurred at similar times in the controls, but the first peak was greatly decreased and the second peak increased when compared with the controls. The labelling index was reduced compared with control animals. The mitotic index was also reduced and remained relatively constant throughout the experimental period.
EFFECTS OF TRAUMA ON CELL PRODUCTION IN THE SUBEPENDYMAL LAYER OF THE RAT NEOCORTEX
Authors: WILLIS P. , BERRY M. , RICHES A. C.
Published: May 2008

The response of the subependymal layer (SEL) of the adult rat neocortex was studied after direct trauma, using X‐rays, and indirect trauma, after placing a stab wound in the hemisphere close by, but without injuring, the SEL. The SEL in the injured hemisphere underwent marked hypertrophy and hyperplasia by ten days after injury, but the contralateral SEL was unaffected. It is proposed that hyperplasia of the SEL was brought about by the production of immature glial cells in response to the presence of a mitotic stimulant which had diffused into the SEL from the site of injury. X‐irradiation caused 98% reduction in the numbers of dark subependymal cells within 24 hours but their numbers recovered within 10 days. In the experiment involving a combination of direct and indirect trauma, the recovery of dark cell number after irradiation was significantly enhanced in the injured, when compared to the uninjured hemisphere. This result supports the hypothesis that stimulation of mitosis by an anti‐chalone‐like substance, released after knife wounding, had occurred. This substance is likely to be a constituent of plasma, rather than a breakdown product of damaged brain parenchyma. Endogenous division and/or cellular importation may account for the recovery of the SEL observed in these experiments.
DEVELOPMENT OF POLYPLOID GLIAL CLASSES IN THE HUMAN CEREBELLUM AND THEIR RELATIONSHIP TO PURKINJE CELLS
Authors: MANN D. M. A. , YATES P. O. , BARTON C. M.
Published: May 2008

Maturation of human Purkinje cells has been shown to commence at about 37 weeks gestation and is not fully completed until 18 months of post‐natal life. It is characterized by the synchronous expansion of the nucleus and nucleolus coupled with an increase in cytoplasmic RNA. Immature cells have a diploid DNA content, which, in contrast to some previous reports, remains constant throughout the perinatal period, and subsequent adult cell life. Although the diploid glial cell population is established shortly after birth, development of a tetraploid glial class is described which does not start until birth and is not complete before 18 months of age. Different roles for each glial class are therefore suggested. Diploid glia are thought to assist during Purkinje cell maturation and subsequent maintenance of physiology. Tetraploid glia may have a role in the establishment of learned patterns of coordinated movement and constitute the basis of cerebellar memory.
CEREBRAL AMYLOIDOSIS IN SCRAPIE IN THE MOUSE: EFFECT OF AGENT STRAIN AND MOUSE GENOTYPE
Authors: BRUCE MOIRA E. , DICKINSON A. G. , FRASER H.
Published: May 2008

Cerebral amyloid deposits, predominantly in the form of discrete plaques are common in mice infected with certain scrapie isolates. In this paper the incidences of cerebral amyloidois occurring with different combinations of agent strain and mouse genotype are investigated. Seven different agents from four primary sources were studied in three mouse genotypes (C57BL, VM and their F1 cross). It is shown that the degree of amyloidosis is a passageable characteristic of the agent depending also on host genotype. However, the amyloid incidence is not influenced by the agent and mouse genotype independently but depends on a specific interaction between the two. For two scrapie agents, 22A and ME7 there is a correlation between incubation period and the incidence of cerebral amyloid in the three mouse genotypes. The degree of cerebral amyloid for ME7 remains unaffected by passage through the two genotypes of mouse, C57BL and VM, and through another species, a Cheviot sheep.
OSMOTIC OPENING OF PERINEURIAL DIFFUSION BARRIER IN PERIPHERAL NERVE
Authors: KRISTENSSON K. , OLSSON Y.
Published: May 2008

The effects of hyperosmolar solutions (sodium chloride and urea) on the perineurial diffusion barrier were tested in experiments using adult mouse sciatic nerves. The solutions were either injected around the nerves in living mice or applied to nerves from killed animals. Thereafter horseradish peroxidase (HRP) was injected around the nerves in order to detect any changes in permeability. HRP was visualized in frozen sections by an enzyme histochemical technique. Hypertonic solutions both in vivo and in vitro caused a pronounced increased permeability of the perineurial diffusion barrier, which persisted for at least one month after injection of 20% NaCl in living mice. In other experiments a hypertonic solution (20% NaCl) was injected one day prior to intradermal inoculation of herpes simplex virus into one hind limb. This treatment dramatically increased the susceptibility of the mice to the infection. This virus has the capacity to spread along nerves to the central nervous system from the site of injection, and is probably taken up at the periphery and then transported centrally inside axons to the cell bodies. The hypothesis is put forward that an important factor for this increased susceptibility is that virions may have an easier access to available surfaces of the nerve fibres due to osmotic opening of the perineurium.
INVASION OF SCHWANN CELLS INTO THE SPINAL CORD OF THE RAT FOLLOWING LOCAL INJECTIONS OF LYSOLECITHIN
Authors: BLAKEMORE W. F.
Published: May 2008

NVASION OF SCHWANN CELLS INTO THE SPINAL CORD OF THE RAT FOLLOWING LOCAL INJECTIONS OF LYSOLECITHIN

Focal areas of primary demyelination were induced in the spinal cord of rats by local injection of lysolecithin. In addition to loss of myelin there was also loss of astrocytes and oligodendrocytes in some parts of the demyelinated area. All demyelinated axons were subsequently remyelinated either by oligodendrocytes or by Schwann cells. Schwann cells remyelinated axons in the centre of the lesion and beneath the pia; the remaining axons were remyelinated by oligodendrocytes. By three months after the lesion the two types of remyelinated fibres were always separated from each other by astrocytes covered by basement membrane. It was concluded that the glial limiting membrane (basement membrane‐covered astrocytes) normally inhibits Schwann cell entry into the spinal cord. When this is destroyed they can enter, but when it becomes re‐established their free migration into the neuropil is once again inhibited.
BOVINE GENERALIZED GLYCOGENOSIS
Authors: RICHARDS R. B. , EDWARDS J. R. , COOK R. D. , WHITE R. R.
Published: May 2008

The clinical, pathological, and biochemical features of a glycogen storage disease in beef cattle are described. The light and electron microscope changes in skeletal muscle, heart and the central nervous system were similar to the lesions that have been described in glycogenosis Type II, or Pompe's disease, in man. The stored intracytoplasmic material was shown histochemically and electron microscopically to be glycogen. Biochemical assay of liver, skeletal muscle, and heart demonstrated a deficiency of the lysosomal enzyme α‐1, 4‐glucosidase.
MYOPATHY WITH MINICORES IN SIBLINGS
Authors: LAKE B. D. , CAVANAGH N. , WILSON J.
Published: May 2008

Myopathy with minicores in siblings

A muscle biopsy from a 5 year old boy with a myopathic disorder showed a wide range of fibre diameters, Type 1 fibre predominance and focal loss of ‘ATPase’ activity in some fibres. Electron microscopy showed, in about 10% of fibres, localized distortions and loss of Z‐lines within compactly grouped myofibrils with preservation of glycogen and mitochondria. His younger sibling, aged 1 year, who was only mildly hypotonic, showed similar but less marked abnormalities on muscle biopsy. These changes are those described in ‘multicore disease’, but it is suggested that the term ‘minicore’ might be more appropriate to avoid confusion with central core disease in which multiple cores are often found. Because of the preservation of mitochondria and glycogen, and the slightly atypical staining of Type 1 fibres it is suggested that the disorder might be caused by an abnormality of myosin or actin.
MYELINATION OF THE OVINE CNS WITH SPECIAL REFERENCE TO BORDER DISEASE. I. QUALITATIVE ASPECTS*
Authors: BARLOW R. M. , STOREY I. JANICE
Published: May 2008

Myelination of the ovine CNS with special reference to Border disease. I. qualitative aspects

A detailed qualitative study of the process of myelination in the dorsal funiculus of a series of ovine fetuses of known gestational age has been made and compared with age‐matched fetuses affected with experimental Border disease (hypomyelino‐genesis congenita). The fetuses, obtained by hysterectomy, were perfused with glutaraldehyde and examined by light and electron microscopy. It was found that the process of myelination in the normal fetal sheep is similar to that in other mammalian species. In Border disease the irregularities of axon profile which occur briefly during their normal premyelination enlargement tend not to resolve. This change is associated with slow and inadequate myelination and a large increase in and persistence of Type III glial cells. These cells contain hydrophilic lipids, butshow little evidence of phagocytosis.
A NEW METHOD FOR MEASURING CRANIAL CAVITY VOLUME AND ITS APPLICATION TO THE ASSESSMENT OF CEREBRAL ATROPHY AT AUTOPSY
Authors: DAVIS P. J. M. , WRIGHT E. A.
Published: May 2008

A new method for measuring cranial cavity volume and its application to the assessment of cerebral atrophy at autopsy

Cranial cavity volume has been measured at autopsy by occupying the cranial cavity completely with a lubricated balloon filled with water while the calvarium was held in place by a rigid metal coronet. The pressure in the balloon was raised to 150 mm Hg and the water‐filled balloon removed and weighed. Brain volume has been measured by an accurate displacement method. Repeat measurements showed a difference of no more than 8 ml and usually less than 5 ml. The ratio between the brain volume and the cranial cavity volume has been found to be constant in young adults 20–55 years old (92.2±SEM 1.6%). Cerebral atrophy has been measured by observing the deviation from this relationship. We have found a striking decrease in brain volume in normal old people. This is not due to water loss as brain density change with age was found to be slight.
MULTIPLE SCLEROSIS AND EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS: SPECIFIC DEMYELINATION OF CNS IN CULTURE
Authors: BORNSTEIN M. B. , RAINE C. S.
Published: May 2008

Multiple sclerosis and experimental allergic encephalomyelitis: specific demyelination of CNS in culture

Cultures of mouse spinal cord tissue coupled to dorsal root ganglia, in which both CNS and PNS myelin develop, have been exposed for various periods of time to sera from patients with multiple sclerosis (MS) and animals with experimental allergic encephalomyelitis (EAE) induced by inoculation with whole CNS tissue in complete Freund's adjuvant. In both instances (MS and EAE), there was a selective depletion of CNS myelin with no adverse effect visible on PNS myelin in the same cultures. Prolonged exposure to demyelinating sera led to a sclerotic appearance in the CNS portion of cultures while PNS myelination progressed unimpeded. The results lend weight to the hypothesis that MS results from an immunological mechanism directed specifically against the CNS.