The increasing threat to European forests from the invasive foliar pine pathogen, Lecanosticta acicola.

European forests are threatened by increasing numbers of invasive pests and pathogens. Over the past century, Lecanosticta acicola, a foliar pathogen predominantly of Pinus spp., has expanded its range globally, and is increasing in impact. Lecanosticta acicola causes brown spot needle blight, resulting in premature defoliation, reduced growth, and mortality in some hosts. Originating from southern regions of North American, it devastated forests in the USA's southern states in the early twentieth century, and in 1942 was discovered in Spain. Derived from Euphresco project 'Brownspotrisk,' this study aimed to establish the current distribution of Lecanosticta species, and assess the risks of L. acicola to European forests. Pathogen reports from the literature, and new/ unpublished survey data were combined into an open-access geo-database (http://www.portalofforestpathology.com), and used to visualise the pathogen's range, infer its climatic tolerance, and update its host range. Lecanosticta species have now been recorded in 44 countries, mostly in the northern hemisphere. The type species, L. acicola, has increased its range in recent years, and is present in 24 out of the 26 European countries where data were available. Other species of Lecanosticta are largely restricted to Mexico and Central America, and recently Colombia. The geo-database records demonstrate that L. acicola tolerates a wide range of climates across the northern hemisphere, and indicate its potential to colonise Pinus spp. forests across large swathes of the Europe. Preliminary analyses suggest L. acicola could affect 62% of global Pinus species area by the end of this century, under climate change predictions. Although its host range appears slightly narrower than the similar Dothistroma species, Lecanosticta species were recorded on 70 host taxa, mostly Pinus spp., but including, Cedrus and Picea spp. Twenty-three, including species of critical ecological, environmental and economic significance in Europe, are highly susceptible to L. acicola, suffering heavy defoliation and sometimes mortality. Variation in apparent susceptibility between reports could reflect variation between regions in the hosts' genetic make-up, but could also reflect the significant variation in L. acicola populations and lineages found across Europe. This study served to highlight significant gaps in our understanding of the pathogen's behaviour. Lecanosticta acicola has recently been downgraded from an A1 quarantine pest to a regulated non quarantine pathogen, and is now widely distributed across Europe. With a need to consider disease management, this study also explored global BSNB strategies, and used Case Studies to summarise the tactics employed to date in Europe.

Effects of two types of energy restriction on methylation levels of adiponectin receptor 1 and leptin receptor overlapping transcript in a mouse mammary tumour virus-transforming growth factor-α breast cancer mouse model.

The role of adiponectin and leptin signalling pathways has been suggested to play important roles in the protective effects of energy restriction (ER) on mammary tumour (MT) development. To study the effects of ER on the methylation levels in adiponectin receptor 1 (AdipoR1) and leptin receptor overlapping transcript (Leprot) genes using the pyrosequencing method in mammary fat pad tissue, mouse mammary tumour virus-transforming growth factor-α (MMTV-TGF-α) female mice were randomly assigned to ad libitum (AL), chronic ER (CER, 15 % ER) or intermittent ER (3 weeks AL and 1 week 60 % ER in cyclic periods) groups at 10 weeks of age until 82 weeks of age. The methylation levels of AdipoR1 in the CER group were higher than those in the AL group at week 49/50 (P < 0·05), while the levels of methylation for AdipoR1 and Leprot genes were similar among the other groups. Also, the methylation levels at CpG2 and CpG3 regions of the promoter region of the AdipoR1 gene in the CER group were three times higher (P < 0·05), while CpG1 island of Leprot methylation was significantly lower compared with the other groups (P < 0·05). Adiponectin and leptin gene expression levels were consistent with the methylation levels. We also observed a change with ageing in methylation levels of these genes. These results indicate that different types of ER modify methylation levels of AdipoR1 and Leprot in different ways and CER had a more significant effect on methylation levels of both genes. Epigenetic regulation of these genes may play important roles in the preventive effects of ER against MT development and ageing processes.

Exploration of Mental Health Issues of Students among University Health Science Academics in Japan.

Academic educators in universities are well positioned to detect early signs and symptoms of unexplained behaviour change in students that could be the beginning of mental health issues. The purpose of this research was to explore the attitudes, beliefs, knowledge and practices of university academics in Japan towards health science students with psychological/mental health issues. This study used a qualitative descriptive design. Three focus groups using a semi-structured interview guide were conducted with 15 academics teaching health science students. Data were collected between March to October 2019. Themes revealed three areas of interest: 1) Reflection on mental health issues in Japan with sub-themes "family issues"; "society expectations and changes", and "stigma"; 2) Reflection on students' mental health issues with sub-themes "student behaviors", "staff involvement", "barriers encountered"; and, 3) Potential supports with sub-themes "university assistance", "communication and connection", and "interventions and prevention." The findings provide insight and can benefit student populations across diverse cultural university settings. Further research to investigate academic staff support with early recognition of mental ill-health and ability to provide information and advice to students is warranted. Recommendations include mental health education for academics and for students to encourage healthy university campuses and well-being within the community.

Ten years of enzyme replacement therapy in paediatric onset mucopolysaccharidosis II in England.

The outcome of 110 patients with paediatric onset mucopolysaccharidosis II (MPS II) since the commercial introduction of enzyme replacement therapy (ERT) in England in 2007 is reported. Median length of follow up was 10 years 3 months (range = 1 y 2 m to 18 years 6 month). 78 patients were treated with ERT, 18 had no ERT or disease modifying treatment 7 had haematopoietic stem cell transplant, 4 experimental intrathecal therapy and 3 were lost to follow up. There is clear evidence of improved survival (median age of death of ERT treated (n = 16) = 15.13 years (range = 9.53 to 20.58 y), and untreated (n = 17) = 11.43 y (0.5 to 19.13 y) p = .0005). Early introduction of ERT improved respiratory outcome at 16 years, the median FVC (% predicted) of those in whom ERT initiated <8 years = 69% (range = 34-86%) and 48% (25-108) (p = .045) in those started >8 years. However, ERT appears to have minimal impact on hearing, carpal tunnel syndrome or progression of cardiac valvular disease. Cardiac valvular disease occurred in 18/46 (40%), with progression occurring most frequently in the aortic valve 13/46 (28%). The lack of requirement for neurosurgical intervention in the first 8 years of life suggests that targeted imaging based on clinical symptomology would be safe in this age group after baseline assessments. There is also emerging evidence that the neurological phenotype is more nuanced than the previously recognized dichotomy of severe and attenuated phenotypes in patients presenting in early childhood.

YouTube provides poor information regarding anterior cruciate ligament injury and reconstruction.

PURPOSE: YouTube is a global medium used predominantly by young adults (aged 18-49 years). This study examined the quality of YouTube information regarding ACL injury and reconstruction. METHODS: YouTube was searched on the 13th of June 2015 for "ACL" and "anterior cruciate ligament" with/without associated terms of "injury", "reconstruction", and "surgery". Videos were evaluated by two independent reviewers [EF (Reviewer 1), (Reviewer 2)] using two recognized information scoring systems (Modified DISCERN (MD) 0-5 and JAMA Benchmark 0-4) and an adaptation of a score designed for written ACL information [ACL Specific Score (ASS) 0-25]. The ASS categorized scores as very good (21-25), good (16-20), moderate (11-15), poor (6-10), and very poor (0-5). Number of views/likes/dislikes, animation, and continent of origin and source (e.g., corporate/educational) were recorded. Correlation of video characteristics with number of views was examined using the analysis of variance (ANOVA) model. Agreement between reviewers was assessed by Interclass Correlation Co-efficient (ICC). RESULTS: Following a filtering process of the 964,770 identified videos, 39 videos were retained. The mean MD score was 2.3 (standard deviation (SD) ±0.9) for Reviewer 1 and 2.2 (SD ±0.9) for Reviewer 2 (ICC = 0.7). The mean JAMA score was 2.5(SD ±0.7) for Reviewer 1 and 2.3 (SD ±0.7) for Reviewer 2 (ICC = 0.8). The mean ASS was 6.3 (SD ±3.5) for Reviewer 1 and 4.6 (SD ±2.9) for Reviewer 2 (ICC = 0.9). Five videos achieved moderate score (13%), while 15 (38%) and 19 (49%) scored as poor and very poor, respectively. There was no correlation between number of views and video quality/video source for any scoring system. CONCLUSION: The majority of videos viewed on YouTube regarding ACL injury and treatment are of low quality.

Treatments for people living with schizophrenia in Sub-Saharan Africa: an adapted realist review.

AIM: To identify the treatments and interventions available and their impact on people living with schizophrenia in Sub-Saharan Africa. BACKGROUND: Help-seeking behaviour and the choice of treatment are largely influenced by socio-cultural factors and beliefs about the causes of mental illness. This review addresses the gap in knowledge regarding the treatment options available to people living with schizophrenia in Sub-Saharan Africa. DESIGN: Adapted realist literature review. DATA SOURCES: Electronic databases searched in June 2016 included PubMed, EMBASE, PsycINFO, ProQuest and CINAHL. REVIEW METHODS: The adapted realist review approach used to synthesize the published research involved identifying the review aim, searching and selecting relevant studies, extracting, iteratively analysing and synthesizing relevant data and reporting results. RESULTS: Forty studies from eight countries were reviewed. Most people were treated by both faith/traditional healers and modern psychiatry. Common treatments included antipsychotics, electroconvulsive therapy and psychosocial interventions. Few treatment options were available outside major centres, there was poor adherence to medication and families reported a high level of burden associated with caring for a relative. LIMITATIONS: Major limitations of this review were the lack of studies, variable quality and low level of evidence available from most countries from Sub-Saharan Africa and lack of generalizability. CONCLUSION: People living with schizophrenia in Sub-Saharan Africa were treated by faith, traditional healers and modern psychiatry, if at all. Further research is needed to better understand the local situation and the implications for caring for people from this region. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Mental health services in Sub-Saharan Africa are limited by fiscal shortages, lack of mental health services and qualified mental health professionals. This review provides evidence to inform nursing and healthcare policy, including recruiting and training mental health professionals and ensuring access to evidence-based, person-centred and culturally relevant mental health services within the primary care context.

Prevalence of Mental Disorders among Older People in Nepal: A Systematic Review.

Background There has been limited research into the prevalence of mental disorders amongst older adults in developing countries. Developing countries such as Nepal are undergoing significant demographic changes with an increasing number and proportion of older persons. Objective This systematic review reports the prevalence of mental health disorders amongst the elderly in Nepal. Method Databases searched were PubMed, CINAHL, Scopus and PsycINFO. A hand search for relevant articles appearing in reference lists and previously identified research was also undertaken. Result Of the 26 studies (32 articles) included most were community and aged-care home -based studies measuring depression. The prevalence of depressive symptom cases ranged from 25.5% to 60.6% in the community, 17.3% to 89.1% in aged-care facilities and 53.2% to 57.1% in hospital settings. The prevalence of depressive disorders in similar settings varied between 4.4% (in community) to 53.2% (in hospital). The prevalence of anxiety symptom cases ranged from 21.7% to 32.3%. Psychosis, alcohol dependence and dementia were other identified disorders amongst the elderly. Disordered symptom cases are more prevalent in aged-care facilities than in community settings and mental disorders are higher for hospital-based studies compared to community settings. Conclusion This review identified a higher prevalence of depression amongst the elderly in Nepal compared to studies conducted in developed countries. The high rates of reported prevalence among the elderly warrant the need to develop more effective public health and welfare approaches to prevent, treat and manage the mental disorders among this vulnerable population.

Expression of CD105 on expanded mesenchymal stem cells does not predict their chondrogenic potential.

OBJECTIVE: Total bone marrow-derived mesenchymal stem cell (BMSC) populations differ in their potential to undergo chondrogenesis, with individual BMSCs differing in their chondrogenic capacity. The aim of this study was to explore the use of CD105 as a marker to isolate a chondrogenic subpopulation of BMSCs from the total, heterogeneous population. DESIGN: BMSCs were isolated from patients undergoing total hip replacement and following expansion (Passage 1-Passage 5), CD105 expression was investigated by FACS analysis. FACS was also used to sort BMSCs based on the presence of CD105 (CD105(+)/CD105(-)) or their amount of CD105 expression (CD105(Bright)/CD105(Dim)). After 3 or 5 weeks of differentiation, chondrogenic potential was determined by thionine staining for glycosaminoglycan (GAG) content and by detection of collagen type II using immunohistochemistry. RESULTS: Expanded total BMSC populations were composed almost exclusively of CD105(+) cells, the percentage of which did not correlate to subsequent chondrogenic potential; chondrogenic potential was observed to diminish with culture although CD105 expression remained stable. Similarly, differences in chondrogenic potential were observed between donors despite similar levels of CD105(+) BMSCs. Comparison of CD105(Bright) and CD105(Dim) BMSCs did not reveal a subpopulation with superior chondrogenic potential. CONCLUSIONS: Chondrogenic potential of BMSCs is often linked to CD105 expression. This study demonstrates that CD105 expression on culture expanded BMSC populations does not associate with a chondroprogenitor phenotype and CD105 should not be pursued as a marker to obtain a chondroprogenitor population from BMSCs.

Response of 33 UK patients with infantile-onset Pompe disease to enzyme replacement therapy.

BACKGROUND: Enzyme replacement therapy (ERT) for infantile-onset Pompe disease has been commercially available for almost 10 years. We report the experience of its use in a cohort treated at three specialist lysosomal treatment centres in the UK. METHODS: A retrospective case-note review was performed, with additional data being gathered from two national audits on all such patients treated with ERT. The impact on the outcome of various characteristics, measured just prior to the initiation of ERT (baseline), was evaluated using logistic regression. RESULTS: Thirty-three patients were identified; 13/29 (45%) were cross-reactive immunological material (CRIM) negative, and nine were immunomodulated. At baseline assessment, 79% were in heart failure, 66% had failure to thrive and 70% had radiological signs of focal pulmonary collapse. The overall survival rate was 60%, ventilation-free survival was 40% and 30% of patients were ambulatory. Median follow-up of survivors was 4 years, 1.5 months (range 6 months to 13.5 years). As with previous studies, the CRIM status impacted on all outcome measures. However, in this cohort, baseline failure to thrive was related to death and lack of ambulation, and left ventricular dilatation was a risk factor for non-ventilator-free survival. CONCLUSION: The outcome of treated patients remains heterogeneous despite attempts at immunomodulation. Failure to thrive at baseline and left ventricular dilation appear to be associated with poorer outcomes.

The challenges of managing coexistent disorders with phenylketonuria: 30 cases.

INTRODUCTION: The few published case reports of co-existent disease with phenylketonuria (PKU) are mainly genetic and familial conditions from consanguineous marriages. The clinical and demographic features of 30 subjects with PKU and co-existent conditions were described in this multi-centre, retrospective cohort study. METHODS: Diagnostic age of PKU and co-existent condition, treatment regimen, and impact of co-existent condition on blood phenylalanine (Phe) control and PKU management were reported. RESULTS: 30 patients (11 males and 19 females), with PKU and a co-existent condition, current median age of 14 years (range 0.4 to 40 years) from 13 treatment centres from Europe and Turkey were described. There were 21 co-existent conditions with PKU; 9 were autoimmune; 6 gastrointestinal, 3 chromosomal abnormalities, and 3 inherited conditions. There were only 5 cases of parental consanguinity. Some patients required conflicting diet therapy (n=5), nutritional support (n=7) and 5 children had feeding problems. There was delayed diagnosis of co-existent conditions (n=3); delayed treatment of PKU (n=1) and amenorrhea associated with Grave's disease that masked a PKU pregnancy for 12 weeks. Co-existent conditions adversely affected blood Phe control in 47% (n=14) of patients. Some co-existent conditions increased the complexity of disease management and increased management burden for patients and caregivers. CONCLUSIONS: Occurrence of co-existent disease is not uncommon in patients with PKU and so investigation for co-existent disorders when the clinical history is not completely consistent with PKU is essential. Integrating care of a second condition with PKU management is challenging.

Inborn Error of Metabolism (IEM) screening in Singapore by electrospray ionization-tandem mass spectrometry (ESI/MS/MS): An 8 year journey from pilot to current program.

IEM screening by ESI/MS/MS was introduced in Singapore in 2006. There were two phases; a pilot study followed by implementation of the current program. The pilot study was over a 4 year period. During the pilot study, a total of 61,313 newborns were screened, and 20 cases of IEM were diagnosed (detection rate of 1:3065; positive predictive value (PPV) of 11%). Regular self-review, participation in external quality assessment and the Region 4 Genetic collaborative programs (http://www.region4genetics.org/) had led to the robust development of our current NBS MS/MS program. Overall, from July 2006 to April 2014, we screened a total of 177,267 newborns. The mean age at the time of sampling was 47.9h. Transportation of samples to the testing laboratory averaged 0.92 day. Upon receipt of sample, the NBS result was available within 1.64 days and within 3.8 days if a second tier test was required. Using absolute cut-off values in place of the initial 99th percentile reference range for the analyte markers and the introduction of two 2nd tier tests (MMA and Succinylacetone) had significantly reduced the high recall rate from an initial 1.5% during the period 2006-07 to 0.12% in 2013. The NBS MS/MS program was supported by a centralized confirmatory/diagnostic testing laboratory and a rapid response team of metabolic specialists. The detection rate was 1: 3165 (1:2727 if maternal conditions were also included). There were 23 newborns affected with organic acidemias (incidence: 1:6565), 23 with fatty acid oxidation disorders (incidence: 1:6565), and 10 with amino acidopathies (incidence 1:17,726). The performance metrics for the screening test were acceptable (sensitivity: 95.59%, specificity: 99.85%, PPV: 20%, FPR: 0.15). Participation in the NBS MS/MS program by hospitals was voluntary, and in 2013, the uptake rate was 71% of the annual births. We hope that newborn screening by MS/MS will become a standard of care for all babies in Singapore.

Benchmarking non-attendance patterns in paediatric medical imaging: A retrospective cohort study spotlighting First Nations children.

INTRODUCTION: Non-attendance at Medical Imaging (MI) appointments can result in inefficiencies in healthcare resource allocation, increased financial burdens, and lead to potential barriers to effective healthcare delivery. We evaluated factors associated with non-attendance of MI appointments for children including variables: gender; age groups; residential postcodes; Indigenous status; appointment dates; appointment reminders and socio-economic status. METHOD: Retrospective cohort study of children with scheduled MI appointments at a Tertiary paediatric hospital in Australia, between January and December 2022. Data were extracted from the Radiology Information System and integrated with socio-economic census data through linking with postcode. Chi-squared, and logistic regression analysis were performed to identify significant predictors of non-attendance. RESULTS: Out of 17,962 scheduled outpatient appointments, 6.2 % did not attend. Males were less likely to attend than females (7.3 % vs. 5.8 %; p < 0.001). Older children had the highest frequency of non-attendance (p < 0.001). First Nations identified children had a higher likelihood of non-attendance at 14.5 % compared to non-First Nations at 5.8 %, and the odds ratio (OR) of First Nation children not attending was 2.54 (CI 2.13-3.03; p < 0.001) higher than non-First Nations children. Children from areas of disadvantage were less likely to attend (p < 0.001). Bone mineral densitometry had the highest odds of non-attendance (19.4 % of bookings) compared to other imaging modalities (p < 0.001). CONCLUSION: The following characteristics were associated with non-attendance: older male gender, residing in areas of socio-economic disadvantage, or identifying as First Nations Australians. By reviewing these findings with the cultural and professional experience of our Indigenous co-author, we have identified some strategies for improving attendance amongst First Nations children. IMPLICATIONS FOR PRACTICE: Factors associated with non-attendance, or "missed opportunities for care", provide opportunities for intervention to improve attendance for vulnerable groups of children who require medical imaging.

Association of SET domain and myotubularin-related proteins modulates growth control.

Several proteins that contribute to epigenetic mechanisms of gene regulation contain a characteristic motif of unknown function called the SET (Suvar3-9, Enhancer-of-zeste, Trithorax) domain. We have demonstrated that SET domains mediate highly conserved interactions with a specific family of proteins that display similarity with dual-specificity phosphatases (dsPTPases). These include myotubularin, the gene of which is mutated in a subset of patients with X-linked myotubular myopathy, and Sbf1, a newly isolated homologue of myotubularin. In contrast with myotubularin, Sbf1 lacks a functional catalytic domain which dephosphorylates phospho-tyrosine and serine-containing peptides in vitro. Competitive interference of endogenous SET domain-dsPTPase interactions by forced expression of Sbf1 induced oncogenic transformation of NIH 3T3 fibroblasts and impaired the in vitro differentiation of C2 myoblast cells. We conclude that myotubularin-type phosphatases link SET-domain containing components of the epigenetic regulatory machinery with signalling pathways involved in growth and differentiation.

Disruption of an imprinted gene cluster by a targeted chromosomal translocation in mice.

Genomic imprinting is an epigenetic process in which the activity of a gene is determined by its parent of origin. Mechanisms governing genomic imprinting are just beginning to be understood. However, the tendency of imprinted genes to exist in chromosomal clusters suggests a sharing of regulatory elements. To better understand imprinted gene clustering, we disrupted a cluster of imprinted genes on mouse distal chromosome 7 using the Cre/loxP recombination system. In mice carrying a site-specific translocation separating Cdkn1c and Kcnq1, imprinting of the genes retained on chromosome 7, including Kcnq1, Kcnq1ot1, Ascl2, H19 and Igf2, is unaffected, demonstrating that these genes are not regulated by elements near or telomeric to Cdkn1c. In contrast, expression and imprinting of the translocated Cdkn1c, Slc22a1l and Tssc3 on chromosome 11 are affected, consistent with the hypothesis that elements regulating both expression and imprinting of these genes lie within or proximal to Kcnq1. These data support the proposal that chromosomal abnormalities, including translocations, within KCNQ1 that are associated with the human disease Beckwith-Wiedemann syndrome (BWS) may disrupt CDKN1C expression. These results underscore the importance of gene clustering for the proper regulation of imprinted genes.

RNAi-mediated germline knockdown of FABP4 increases body weight but does not improve the deranged nutrient metabolism of diet-induced obese mice.

OBJECTIVE: To investigate the impact of reduced adipocyte fatty acid-binding protein 4 (FABP4) in control of body weight, glucose and lipid homeostasis in diet-induced obese (DIO) mice. METHODS: We applied RNA interference (RNAi) technology to generate FABP4 germline knockdown mice to investigate their metabolic phenotype. RESULTS: RNAi-mediated knockdown reduced FABP4 mRNA expression and protein levels by almost 90% in adipocytes of standard chow-fed mice. In adipocytes of DIO mice, RNAi reduced FABP4 expression and protein levels by 70 and 80%, respectively. There was no increase in adipocyte FABP5 expression in FABP4 knockdown mice. The knockdown of FABP4 significantly increased body weight and fat mass in DIO mice. However, FABP4 knockdown did not affect plasma glucose and lipid homeostasis in DIO mice; nor did it improve their insulin sensitivity. CONCLUSION: Our data indicate that robust knockdown of FABP4 increases body weight and fat mass without improving glucose and lipid homeostasis in DIO mice.

Interleukin-4 acts at the locus of the antigen-presenting dendritic cell to counter-regulate cytotoxic CD8+ T-cell responses.

The mechanism underlying suppression of immune responses by interleukin-4 (IL-4) has remained unexplained. Here we show that the antigen-presenting dendritic cell is central to counter-regulation of autoimmune disease by IL-4. IL-4 acts at the locus of the dendritic cell to decrease the cytolytic T-cell response, preventing autoimmunity. Stimulation of cytotoxic precursors by antigen pulsed dendritic cells induces their differentiation but the process is blocked by IL-4. IL-4-influenced DC produce distinct effects on CD8+ T cells depending on their state of activation. The molecular basis for this regulation is the alteration of the expression ratio of the costimulatory ligands B7.1/B7.2 on dendritic cells. Our findings demonstrate that B7.2 induces expansion of CD8+ T cells and B7.1 governs their acquisition of cytolytic activity. IL-4 influences the dendritic cell to elicit qualitative differences in T-cell responses, providing the basis for counter-regulation mediated by IL-4.

The flow patterns of caudal epidural in upper lumbar spinal pathology.

Epidural steroid injections are an important therapeutic modality employed by spinal surgeons in the treatment of patients with chronic low back pain with or without lumbar radiculopathy. The caudal epidural is a commonly used and well-established technique; however, little is known about the segmental level of pathology that may be addressed by this intervention. This prospective study of over 50 patients aimed to examine the spreading pattern of this technique using epidurography. The effect of variation in Trendelenburg tilt and the eradication of lumbar lordosis on the cephalic distribution of the injectate were investigated. 52 patients with low back pain and radiculopathy underwent caudal epidural. All had 20 ml volume injected, comprised of 5 ml contrast (Ultravist™ Schering) 2 ml Triamcinolone (Adcortyl™ Squibb) and 13 ml local anaesthetic (1% lignocaine). Patients were randomised to either 0° or 30° of Trendelenburg tilt, as referenced from the lumbar spine. Patients were further randomised to presence or absence of lumbar lordosis, which was eradicated using a flexion device placed beneath the prone patient. A lateral image of each sacrum was obtained, to identify variations in sacral geometry particularly resistant to cephalic spread of injectate. The highest segment reached on fluoroscopy was recorded post injection. Fifty-two patients with a mean age of 50 years underwent caudal epidural. Thirty-one were in 0° head tilt, with 21 in 30° of head tilt. In each of these groups, 50% had their lumbar lordosis flattened prior to caudal injection. The median segmental level reached was L3, with a range from T9 to L5. Eradication of lumbar lordosis did not significantly alter cephalic spread of injectate. There was a trend for 30° tilt to extend the upper level reached by caudal injection (p=0.08). There were no adverse events in this series. Caudal epidural is a reliable and relatively safe procedure for the treatment of low back pain. Pathology at L3/4 and L4/5 and L5/S1 can be approached by this technique. Although in selected cases thoracic and high lumbar levels can be reached, this is variable. If pathology at levels above L3 needs to be addressed, we propose a 30° head tilt may improve cephalic drug delivery. The caudal route is best reserved for pathology below L3.

Detection of a second t(14;18) breakpoint cluster region in human follicular lymphomas.

Our results indicate that there are two major breakpoint cluster regions in chromosome 18 DNA for t(14;18) translocations in follicular lymphomas. The absence of a pFL-1 homologous transcript in a cell line containing a pFL-2-detectable translocation suggests that there may be two different pathogenetic consequences of t(14;18) translocations. One possibility is that, despite the distances between them (greater than 20 kb), breakpoints in the two cluster regions in some way affect transcription of the same gene product, which has not yet been identified. Alternatively, two separate transcriptional units may be involved. The availability of DNA probes for each of the two t(14;18) breakpoint cluster regions will allow further studies regarding the biologic significance of these two genetically distinct classes of t(14;18) translocations.