The increasing use of complementary and alternative medicines in Australia has generated concern regarding the information on these products available to both healthcare providers and the public. The aim of this study was to examine the practice behaviours of naturopaths in relation to both the provision of and access to information on complementary and alternative medicines (CAM).A representative sample of 300 practicing naturopaths located nationally were sent a comprehensive survey which gathered data on self reported practice behaviour in relation to the provision of information on oral CAM to clients and the information needs of the practitioners themselvesA response rate of 35% was achieved. Most practitioners (98%) have a dispensary within their clinic and the majority of practitioners perform the dispensing themselves. Practitioners reported they provided information to clients, usually in the form of verbal information (96%), handwritten notes (83%) and printed information (75%). The majority of practitioners (over 75%) reported always giving information on the full name of the product, reason for prescribing, expected response, possible interactions and contraindications and actions of the product. Information resources most often used by practitioners included professional newsletters, seminars run by manufacturers, patient feedback and personal observation of patients. Most practitioners were positive about the information they could access but felt that more information was required in areas such as adverse reactions and safe use of CAM in children, pregnancy and breastfeeding. Most naturopaths (over 96%) were informed about adverse events through manufacturer or distributor newsletters. The barriers in the provision of information to clients were misleading or incorrect information in the media, time constraints, information overload and complex language used in printed information. The main barrier to the practitioner in information access was seen as the perceived division between orthodox and complementary medicine practitioners.Our data suggest most naturopaths were concerned about possible interaction between pharmaceuticals and CAM, and explore this area with their patients. There is scope to improve practitioners' access to information of adverse events including an increased awareness of sources of information such as the Australian Therapeutic Goods Administration (TGA) website. The use of complementary medicines in Australia has become commonplace. In 2002 it was estimated that 52% of the Australian population had used at least one non-physician-prescribed complementary medicine in the previous year. These mThe Expert Committee on Complementary Medicines in the Health System in Australia was convened in 2003 and asked to consider the regulatory, health system and industry structures necessary to ensure that the objectives of the National Medicines Policy (NMP) and in particular that of the National Strategy for Quality Use of Medicines (QUM), were met in relation to complementary medicines. The report from the Expert Committee raised a number of concerns surrounding the information available to healthcare providers and consumers regarding complementary medicines, and one of the recommendations of the committee was the commissioning of a study to determine the needs of healthcare professionals and consumers on complementary medicines and the options available for conveying this information[Previous research has surveyed the naturopathic and Western herbalists workforce, providiResearch in the USA has also examined practice patterns of naturopathic physicians. The demIn Australia the profession of naturopathy is essentially unregulated. A level of self-regulation is exerted by the professional associations in the form of minimum qualification levels and monitoring of annual requirements such as Continuing Professional Education, however there are a large number of these associations and entry requirements vary between the groups. Several Australian States are currently exploring options for the regulation of naturopaths and other complementary medicine practitioners .The current agreed minimum qualification level enforced by the main professional associations is Advanced Diploma in Naturopathy. This qualification is contained within the Health Training Package HLT02 and represents a consistent base level of training within the industry. The Advanced Diploma courses are taught at privately-owned Vocational Education and Training Colleges which are registered through the various State Education Authorities. Some of these colleges are also registered to deliver degree courses, and several universities also deliver courses in naturopathy.The purpose of this study was to examine the practice behaviours of naturopaths in relation to the provision of and access to information on oral complementary medicines. In particular we were interested to know what are their counseling and advice-giving behaviors and are these behaviors adequate to ensure safe and judicious use of oral complementary medicines. The study had two aims:1. to explore the information provided by naturopaths to clients on these medicines, circumstances under which information would not be provided to a client, and the types of questions clients ask in respect to oral complementary medicines, and2. to examine the skill base of naturopaths with accessing information, how practitioners find out about adverse events and changes in regulation to complementary medicines and their confidence in respect to answering client questions about these medicines.We designed a short self completion questionnaire with the aim of collecting data from naturopaths describing their practice behaviors, education and training, information gathered during a consultation with a client, experience with accessing information and knowledge about complementary and alternative therapies and socio demographic characteristics. The questionnaire adopted and adapted questionnaires that had been used to assess practice behaviors and practitioner knowledge around CAM and the use of other over the counter medicines -9. A totThe sampling frame was based on a population of 3,000 naturopaths from three States in Australia. The sample size was estimated at 300, based on an estimate that 90% of naturopaths would actively prescribe herbs, with a 95% confidence interval, this allows for a 5% error and a 50% response rate. A stratified sample was dawn from three States in Australia.Data were collected from a national survey of practicing naturopaths in Australia. A representative sample of 300 naturopaths was undertaken from a listing of naturopaths held by the Medical Benefits Fund (MBF), a large national health insurance fund in Australia. It was decided to sample from a database held by a health fund because of the absence of a central database of naturopaths held by any professional association. MBF did not release the list of practitioners but undertook the sampling procedure under direction of the research team and provided the administrative support to mail out the questionnaires. The Fund generated a list of active naturopaths defined as those who have had a claim paid in the previous 12 months. Subjects were assigned a random number selected by a researcher independent from the study team.Naturopaths were sent a questionnaire with a covering letter explaining the purpose of the study and a reply paid envelope. Two reminders were sent out to facilitate the return of questionnaires. Statistical analysis was performed using SPSS version 11.5 . FrequenIn total 300 questionnaires were sent out, and 110 were returned. However, five of these were non practicing practitioners giving a response rate of 35%. The majority identified themselves as Caucasian and female and were in the 45–54 age category. A diploma was the standard qualification  reported having a dispensary in their clinic, with 101 (97%) naturopaths performing the dispensing themselves, and a small number (7%) using unqualified staff. Seventy-eight percent of naturopaths always advised their patients to purchase their products from their clinic, with the remainder advising their patients to purchase their products from the pharmacy or health food shop.Twenty eight (27% of the sample) never dispensed a repeat medication before undertaking a follow up consultation, while 74 (71%) practitioners often or sometimes did so. Generally, there was a reluctance to dispense medications without a consultation. Practitioners reported never dispensing a product without full consultation: (1) if the patient was presenting with a different condition (45% of practitioners), (2) if the patient had consulted with another naturopath (49%), and (3) if the patient requested it (58%).The majority of naturopaths (96%) gave verbal information to their patients on complementary medicines. Most also provided written information which included practitioner handwritten notes (83%), printed information (75%) and less often printed information from journal articles (26%), text books (25%) or manufacturer information (35%).The content of information presented to patients varied between practitioners Table . InformaThe approach in counselling on appropriate use of naturopathic products will be influenced by the practitioner's training and their skills in life long learning. Ninety one (83%) naturopaths reported their formal training met their needs when performing the day to day practice of naturopathy.often by practitioners to obtain information on CAM included articles in professional newsletters (91%), reference textbooks (72%), continuing professional education (CPE) seminars run by manufacturers (70%), patient feedback (66%), personal observation of patient response (58%), and CPE activity run by other industry bodies (55%). Use of the scientific literature or discussion with other health professionals was reported less often. For example the resources used sometimes included discussion with naturopathic colleagues (49%), journal articles describing a case study (43%), journal articles describing randomised clinical trials (41%), information from course notes (43%), popular health magazines (44%) and reference web sites (37%). Information sources used rarely by practitioners included interaction with pharmacists (46% of naturopaths), medical doctors (44% of naturopaths) or other health care practitioner (40% of naturopaths).There are a number of information resources available to practitioners and we asked naturopaths to indicate the frequency with which they used a particular resource. The resources used most Naturopaths' views on the adequacy of information resources they can draw on to help answer questions relating to CAM are reported in Table A number of factors were expressed as being very important in influencing practitioner confidence with providing information to their patients. This included: knowledge of these products (95%), access to scientific or clinical information (85%), belief in the effectiveness of these products (84%), belief in the quality of the products (84%) and belief in the safety of the products (81%).A safety concern relating to the use of CAM are adverse events associated with herbal medicines. Over 96% of naturopaths reported they were notified about adverse events through manufacturer or distributor newsletters. Other sources of notification were from professional associations (88%) and professional association journals, website or email discussion lists (86%), CPE (69%) and informal discussion with colleagues (60%). Less than 30% of the naturopaths used the Therapeutic Goods Administration (TGA)  website as a source of notification of adverse events.Practitioners were asked how their knowledge of adverse events could be improved. Fifty percent of practitioners identified formal education as a need and 58% identified improved access to CPE activities and other relevant information sources were needed. Formal training or improved skills to assess quality scientific or clinical evidence was viewed positively by 30% of naturopaths.Practitioners were asked open ended questions regarding whether the information they were able to access about CAMs was adequate, what they considered the barriers to the provision of information about CAMs to patients were, and what suggestions they had for ways of overcoming these barriers.The majority of practitioners were very positive about the information they could access although there were common themes in these answers regarding the time taken to access quality information. A number of practitioners mentioned the need for unbiased information and expressed concerns regarding the objectivity of the information that was supplied by the manufacturers of those products.In general, practitioners expressed strong opinions about what they perceived to be the barriers to their own access to information. The perceived division between orthodox and complementary medicine practitioners was the strongest theme presented. Themes identified less frequently were perceived Government bias against complementary medicines, the cost of accessing information and the lack of research. Other comments related to the need for professional registration of naturopaths and a need for orthodox medical practitioners to have a greater awareness of and training in complementary medicines.With regard to the information provision to patients, the barriers were seen as misleading or incorrect information in the media, time constraints within the consultation, information overload on the part of the client, information supplied with the product in language too complex for the client, and self-prescribing of CAMs through over-the-counter sales of these products. When suggesting ways to overcome these barriers, practitioners sought greater recognition and status of the naturopathic profession and increased integration and communication with the orthodox health community. Many practitioners also felt that restricting CAM products from over-the-counter sales and allowing them to be supplied by complementary practitioners only would assist with information provision to the client. There were also calls for manufacturers to include more information on their products and for greater balance in media reporting of CAM-related issues.Self reported data from this study reported on the practice behaviour of naturopaths in relation to providing information on complementary medicines. Our data suggest most naturopaths are concerned about safety in relation to possible interaction between orthodox Western medicine and CAM and this is an area naturopaths explore with their patients during the consultation. There is scope to improve the practice behaviour of some naturopaths to ensure greater safety by giving consideration to reducing the number of practitioners who would dispense a product without consultation (on solely the patient's request), and not using unqualified staff to dispense a product.We found both consistencies and inconsistencies between practitioners where information on the product was presented. Most practitioners reported providing information on the dose, the full name, reason for prescribing the product, possible interactions, expected response, contra-indications, expected response and the action of the product. However, information was not provided by 40% or more of practitioners on possible adverse effects, interaction with other substances, and the names and ingredients of the herbal product. A bias resulting from the self report of behaviour can not be excluded.With an increasing profile of safe use of complementary medicines, improved labelling by the naturopath has the potential to reduce public health concerns and increase the judicious use of herbal medicines. Although the majority of prescribing took place in the clinic, 22% of practitioners advised their patients to purchase product from the pharmacy or health food store. Patients who are sent to these outlets may or may not be given a written directive with the item to be purchased. Patients may be sold product which is different to that recommended by the naturopath, be given conflicting advice regarding dosage or may simply forget the instructions given to them, particularly when those instructions differ from that printed on the label.Initial naturopathic training met the needs of naturopaths with performing the day to day practice of naturopathy. We have identified a number of deficiencies that will need to be addressed to ensure naturopaths can remain up to date with increasing quality information on CAM and continue to provide high standards of counselling. Naturopaths identified that information resources relating to the safety of CAM use in children, use during pregnancy and breastfeeding, the adverse effects of CAM, the safety of using CAM as related to certain medical conditions and interactions of CAM and other medicines as not very adequate. Given the insufficient research base describing any adverse effects in some of these patient groups, providing evidence based practice in these areas will remain inadequate and naturopaths will need to continue practising with caution.Naturopaths use a wide variety of information sources to obtain information on CAM, although conventional health care practitioners and practitioners from another CAM discipline were not widely used as a resource to access information. This is similar to the findings from the workforce survey where practitioners reported that they felt well prepared for practice within their clinical training with the exception of the area of inter-professional communications. Our finComplementary Medicines in the Australian Health System (2003) identified a need to improve access to information about adverse reports[The naturopathic and Western herbal medicine workforce survey reported that adverse events were relatively common, and calculated that naturopaths would on an average encounter 1.2 adverse events in their patients per year of full time practice, or one e reports. Our stuA limitation of this study is the low response rate which may limit the generalisations we can make relating to the national population of naturopaths. The demographic characteristics of our study population allow limited comparison with published data from national surveys from Australia and the United States,3. Data The findings from this study are timely in relation to the Australian Government's recognition of the need to identify the information and skills needed by health care professionals to assess the quality of evidence concerning the use of complementary medicines. This study provides baseline data for describing the practice behaviors in naturopaths in relation to counseling and advice-giving behaviors and their skills in accessing information on CAM adverse events. It will facilitate the evaluation of practice behaviour over time. The majority of naturopaths in Australia report behaviours that suggest they provide appropriate and judicious use of oral CAMs for their patients but the practitioners identify the need for further training to ensure safe and judicious practice continues in the future.The author(s) declare that they have no competing interests.CS conceptualised the research, analysed the data and took the lead with writing the paper.KM participated in conceptualising the research, study design, analysed the data and contributed to the preparation of the manuscript.EH participated in the study design and reviewed the manuscript.SS participated in the study design and reviewed the manuscript.GB participated in the study design and reviewed the manuscript.DR participated in the study design and reviewed the manuscript.The pre-publication history for this paper can be accessed here:


It has been well documented that the pineal hormone, melatonin, which plays a major role in the control of reproduction in mammals, also plays a role in the incidence and growth of breast and mammary cancer. The curative effect of melatonin on the growth of dimethylbenz [a]anthracene-induced (DMBA-induced) mammary adenocarcinoma (ADK) has been previously well documented in the female Sprague–Dawley rat. However, the preventive effect of melatonin in limiting the frequency of cancer initiation has not been well documented.The aim of this study was to compare the potency of melatonin to limit the frequency of mammary cancer initiation with its potency to inhibit tumor progression once initiation, at 55 days of age, was achieved. The present study compared the effect of preventive treatment with melatonin (10 mg/kg daily) administered for only 15 days before the administration of DMBA with the effect of long-term (6-month) curative treatment with the same dose of melatonin starting the day after DMBA administration. The rats were followed up for a year after the administration of the DMBA.The results clearly showed almost identical preventive and curative effects of melatonin on the growth of DMBA-induced mammary ADK. Many hypotheses have been proposed to explain the inhibitory effects of melatonin. However, the mechanisms responsible for its strong preventive effect are still a matter of debate. At least, it can be envisaged that the artificial amplification of the intensity of the circadian rhythm of melatonin could markedly reduce the DNA damage provoked by DMBA and therefore the frequency of cancer initiation.In view of the present results, obtained in the female Sprague–Dawley rat, it can be envisaged that the long-term inhibition of mammary ADK promotion by a brief, preventive treatment with melatonin could also reduce the risk of breast cancer induced in women by unidentified environmental factors. MBYDJC equally carried out the experimental studies. MHP made a contribution to the acquisition of data. AM performed the histological analysis. RS participated in the design of the study and performed the statistical analysis. BK conceived the study and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.


First, scientists from the Moscow Kurchatov Institute presented physical evidence that the dominant sources of energy released by the exploding reactor were not the officially assumed thermal explosions  but rath131I  mortality and teratogenic effects were observed in Germany, Poland, and the former Soviet Union shortly after the Chernobyl explosion . Excess In the absence of scientifically convincing evidence rebutting such challenges to official assessments of the physical events and long-term human consequences of the Chernobyl catastrophe, the Precautionary Principle in public health issues  requires


Peripheral sensory diabetic neuropathy is characterized by morphological, electrophysiological and neurochemical changes to a subpopulation of primary afferent neurons. Here, we utilized a transgenic mouse model of diabetes (OVE26) and age-matched controls to histologically examine the effect of chronic hyperglycemia on the activity or abundance of the enzymes acid phosphatase, cytochrome oxidase and NADPH-diaphorase in primary sensory neuron perikarya and the dorsal horn of the spinal cord. Quantitative densitometric characterization of enzyme reaction product revealed significant differences between diabetic, compared to control, animals for all three enzymes. Levels of acid phosphatase reaction product were found to be significantly reduced in both small diameter primary sensory somata and the dorsal horn. Cytochrome oxidase activity was found to be significantly lower in small primary sensory somata while NADPH-diaphorase labeling was found to be significantly higher in small primary sensory somata and significantly lower in the dorsal horn. In addition to these observed biochemical changes, ratiometric analysis of the number of small versus large diameter primary sensory perikarya in diabetic and control animals demonstrated a quantifiable decrease in the number of small diameter cells in the spinal ganglia of diabetic mice. These results suggest that the OVE26 model of diabetes mellitus produces an identifiable disturbance in specific metabolic pathways of select cells in the sensory nervous system and that this dysfunction may reflect the progression of a demonstrated cell loss. Diabetic sensory neuropathies are a common, clinically observed sequelae of hyperglycemia and are characterized by a progressive degradation of primary afferent function ,2. FunctThe OVE26 transgenic mouse line  used in this study displays a well-characterized chronic hyperglycemia and hypoinsulinemia within days after birth. ,6. Ten  were conducted using SigmaStat (Jandel). Controls for densitometric analysis consisted of: 1) simultaneous sectioning and mounting of diabetic and control tissue on the same slide to ensure identical histological processing; 2) statistical analysis to verify consistency of staining between animals within control and experimental groups; 3) correction for small fluctuations in tissue opacity/thickness by subtractive illumination whereby the density value of white matter was subtracted from the immediately adjacent ventral horn; and 4) manual adjustment and calibration of the video camera parameters and microscope illumination and acquisition of all images using identical settings. All experiments were conducted in accordance with the guidelines of our institutions and the National Institutes of Health regarding the care and use of animals for experimental procedures.Quantitative analysis of CO, AP and NADPH-d staining was undertaken on both the dorsal horn of the L5 segment of the spinal cord and the large and small cells of L5 sensory ganglion using previously described densitometric analysis ,12. The 2 area) to large (500 and 1950 μm2 area) primary sensory somata in the fifth lumbar spinal ganglia revealed a significant decrease in the proportion of small to large cells in diabetic  compared to control  mice . Quantitative densitometric analysis of the abundance and distribution of enzyme histochemical reaction product in dorsal root ganglia (DRG) revealed substantive differences between diabetic and control mice . Small somata from the ganglia of diabetic mice exhibited lower levels of AP  and CO  reaction product and an increase in the density of the reaction product for NADPH-d  in comparison to control animals. No differences were observed in large diameter neurons from diabetic as compared to control animals.Prior to fixative perfusion, the phenotypic status of OVE26 diabetic mice were confirmed by their characteristic small eyes caused by the GR19 gene in their transgenic construct . All aduP = 0.026; 27 sections quantified) and NADPH-d  reaction product in lamina I and II of the dorsal horn of control and diabetic mice  declare that they have no competing interests.RZ completed this work as part of his doctoral dissertation and was involved in the writing of this manuscript and contributed both intellectually and practically to the content. PE created, characterized and supplied the transgenic mice and was also involved in the writing of this manuscript and contributed both intellectually and practically to the content. PC provided the lab, supervision, and support for this work, exclusive of that associated with generation and characterization of the mouse model. PC was also involved in the design and coordination of this study and participated in the writing of this manuscript and contributed both intellectually and practically to the content. All authors read and approved the final manuscript.


To be useful, clinical practice guidelines need to be evidence based; otherwise they will not achieve the validity, reliability and credibility required for implementation.This paper compares the methods used in gathering, analysing and linking of evidence to guideline recommendations in ten current hypertension guidelines.It found several guidelines had failed to implement methods of searching for the relevant literature, critical analysis and linking to recommendations that minimise the risk of bias in the interpretation of research evidence. The more rigorous guidelines showed discrepancies in recommendations and grading that reflected different approaches to the use of evidence in guideline development.Clinical practice guidelines as a methodology are clearly still an evolving health care technology. Clinical practice guidelines can provide building blocks for changing and improving health care  and are Like many other conditions hypertension has been the subject of many different international guidelines. The World Health Organisation (WHO) have described hypertension – defined as a blood pressure of greater than 140/90 mmHg – as one of the ten leading risk factors influencing the global burden of disease . ReducinThe aim of this study was to review how well 10 guidelines for hypertension addressed validity in terms of their methods and their use of published evidence.We reviewed the methods used in development and the key recommendations of ten current guidelines  meetWe evaluated the methods used to develop each guideline with particular reference to three dimensions that relate to the use of research evidence, as found in the full published report of each guideline:• the construction of the guideline development group and its component stakeholders.• the use of published literature and the strategy used in screening for the primary evidence; in particular, the use of existing systematic reviews or the performance of a new systematic review explicitly to answer questions posed by the guideline.• the grading of evidence and recommendations: in particular, an explicit link between recommendations and supporting evidence.We compared recommendations on four areas that were common to all the guidelines: diagnosis of hypertension, lifestyle modification, criteria for initiation of antihypertensive drug therapies and initial recommended drug therapy. We also explored links between recommendation grades and citations and looked at how these differed in recommendations for drug therapy and salt intake.The measures used to assess the guideline development process are summarised in table Only three guidelines were constructed by multidisciplinary groups where the members' affiliations and conflicts of interest were described; these three guideline groups included patient representatives as well as key professional stakeholders. A further six guidelines provided only a list of names and institutional affiliations of members of the guideline development group. One further guideline gave no details of the guideline development group  per day for women and from 24 to 30 g (ethanol) per day for men. Differences in the daily limits for alcohol consumption may reflect the variations on guidance for sensible drinking in different countries. Most guidelines recommended a diet rich in fruit and vegetables with reduced saturated and total fats. Guidelines typically recommended 30–45 minutes of aerobic exercise three to five times per week. Although their recommendations were similar, guidelines lacked consistency in the estimations of the effect of lifestyle changes on blood pressure, possibly reflecting the different data sources used. Guidelines varied in the additional areas that they addressed: potassium, magnesium and calcium supplementation, management of stress and caffeine consumption were considered by some of the guidelines. This demonstrates one of the challenges facing guideline developers. Each clinical care pathway involving assessment, diagnosis, treatment and follow-up requires multiple complex decisions. A clinical guideline will be unable to offer guidance on every consideration that must be made by caregivers and patients. Guidelines will reflect this complexity and are likely to vary in their scope and coverage of the decisions involved in the care pathway.All of the guidelines addressed lifestyle modification as an integral part of the management of hypertension and as a first line treatment in mild hypertension, and made similar recommendations for weight loss, limiting alcohol and sodium intake, regular exercise and smoking cessation  relied upon a similar and extensive body of work, either directly using the original data in a systematic review or indirectly sourcing the study via a previously published systematic review  feature transparent and fully reported: guideline group methods and participation; involvement of stakeholders and sponsors; reporting and use of evidence and linking of recommendation to evidence; understanding of health care delivery, the policy context and narratives of patient experience.ACE angiotensin converting enzymeARB angiotensin receptor blockerBMI body mass indexg gramkg kilogramm metremmHg millimetres of mercurymins minutesThe authors contributed to the development of one of the guidelines reviewed .FC, HOD and JMM wrote the manuscript.ME critically revised the manuscript.FC, JC, FRB, HOD and JMM performed data abstraction.FC and FRB performed literature searches.JMM designed the study.The pre-publication history for this paper can be accessed here:


A number of growth factors have been implicated in the control of the proliferation of breast cancer cells and some have been reported to mediate the proliferative effects of oestradiol. MCF-7 cells were treated with growth factors in the presence and absence of oestradiol. Oestradiol increased the response of cells to the proliferative effects of epidermal growth factor (EGF), transforming growth factor alpha  and basic fibroblast growth factor (bFGF). Platelet derived growth factor (PDGF) and cathepsin D had no effect in the presence or absence of oestradiol while TGF-beta slightly reduced the stimulation by oestradiol. In the absence of oestradiol, there was little effect of combinations of growth factors although the effects of bFGF and IGF-I were additive. In the presence of oestradiol, the effects of bFGF and TGF-alpha were additive whereas bFGF acted as an IGF-I antagonist. Overall, bFGF had the greatest effect on cell proliferation although this was less marked than the previously described effect of the IGFs and insulin. The effects of oestradiol on the sensitivity of cells to the proliferative effects of bFGF did not appear to result from regulation of bFGF receptor expression.


The normal growth, development and function of an organism requires precise and co-ordinated control of gene expression. A major part of this control is exerted by regulating messenger RNA (mRNA) production and involves complex interactions between an array of transcriptionally active proteins and specific regulatory DNA sequences. The combination of such proteins and DNA sequences is specific for given gene or group of genes in a particular cell type and the proteins regulating the same gene may vary between cell types. In addition the expression or activity of these regulatory proteins may be modified depending on the state of differentiation of a cell or in response to an external stimulus. Thus, the differentiation of embryonic cells into diverse tissues is achieved and the mature structure and function of the organism is maintained. This review focusses on the role of perturbations of these transcriptional controls in neoplasia. Deregulation of transcription may result in the failure to express genes responsible for cellular differentiation, or alternatively, in the transcription of genes involved in cell division, through the inappropriate expression or activation of positively acting transcription factors and nuclear oncogenes. Whether the biochemical abnormalities that lead to the disordered growth and differentiation of a malignant tumour affect cell surface receptors, membrane or cytoplasmic signalling proteins or nuclear transcription factors, the end result is the inappropriate expression of some genes and failure to express others. Current research is starting to elucidate which of the elements of this complicated system are important in neoplasia.


Human epithelial ovarian tumours were successfully established as xenografts in nude mice in 54% of cases. An evaluation of the biological characteristics of tumours propagated in nude mice was carried out and the functions investigated included morphology, growth kinetics, cellular DNA content, cell surface antigen expression and sensitivity to chemotherapy. To allow a more detailed study of the influence of ploidy on biological behaviour, xenografted tumour with varying degrees of aneuploidy and tumours with a common ancestry but different ploidies were also established. Although this is a highly selective model system favouring the growth of biologically aggressive tumours the xenografts, in general, reflect many of the characteristics of the tumours from which they were derived and are likely to provide a useful model for investigating the biology of ovarian cancer.


To investigate the influence of hormones on the process of cellular differentiation the growth and differentiation of a transplantable tumour, induced by inoculation of pluripotent mouse embryonal carcinoma (EC) cells have been studied in athymic nude mice and, normal and hypopituitary Snell dwarf mice. All athymic nude mice developed tumours independent of the numbers of cells inoculated. In contrast, the tumour percentage in normal Snell mice was lower, showing a dose-dependent increase of takes. In dwarfs tumour percentage was comparable with that observed in normal Snell mice. The morphological differentiation of teratocarcinomas grown in athymic nude mice, normal and dwarfed Snell mice shows derivatives of all three germ layers next to undifferentiated embryonal carcinoma cells. This suggests that the pituitary hormonal deficiencies of the dwarfs  did not influence the tumour induction nor the development of the different tissues present in this type of tumour.


A prospective autopsy study of deaths of women who had been diagnosed previously as having cancer of the breast was performed between October 1986 and December 1990. During the study period 28 deaths occurred and nine of these (32%) were attributable directly to breast cancer; a figure similar to that found in our earlier retrospective study. In this study the autopsy findings in both the breast cancer and non-breast cancer deaths were recorded and five cases underwent post-mortem radiological skeletal survey to detect metastases. The findings confirm the role of the post mortem in modern medicine as a method of auditing clinical practice. Of particular importance, is the finding that the clinical presumption of disseminated breast cancer as a cause of 'terminal' illness in some patients may be misleading and dangerous, possibly denying some patients treatment of potentially remedial conditions by the institution of inappropriate terminal care.


The fluorometric microculture cytotoxicity assay (FMCA) was employed for analysing the effect of different chemotherapeutic drug combinations and their single constituents in 44 cases of acute myelocytic leukaemia (AML). A large heterogeneity with respect to cell kill was observed for all combinations tested, the interactions ranging from antagonistic to synergistic in terms of the multiplicative concept for drug interactions. However, an 'additive' model provided a significantly better fit of the data compared to the effect of the most active single agent of the combination (Dmax) for several common antileukaemic drug combinations. When the two interaction models were related to treatment outcome 38% of the non-responders showed preference for the additive model whereas the corresponding figure for responders was 80%. Overall, in 248 of 290 (85%) tests performed with drug combinations, there was an agreement between the effect of the combination and that of the most active single component. Direct comparison of Dmax and the combination for correlation with clinical outcome demonstrated only minor differences in the ability to predict drug resistance. The results show that FMCA appear to report drug interactions in samples from patients with AML in accordance with clinical experience. Furthermore, testing single agents as a substitute for drug combinations may be adequate for detection of clinical drug resistance to combination therapy in AML.


The FAMMM syndrome consists of the familial occurrence of cutaneous malignant melanoma and atypical nevi (dysplastic nevi), and is inherited as an autosomal dominant trait. Conflicting results have been reported on the question of whether the syndrome includes increased susceptibility to non-melanoma cancers. We have studied cancer of all anatomic sites and histologies in nine FAMMM families which were ascertained in a pigmented lesions clinic in the Netherlands. We evaluated two hypotheses: that the number of systemic cancers observed in the families was excessive, compared to expected incidence, based on Dutch incidence data, and that there was variation (or heterogeneity) among families in the frequency of systemic cancer. A significant excess of systemic cancer  was observed. Significant heterogeneity was also found among the families; three of the nine families had marked excess in numbers of systemic cancers, and the remaining families had normal numbers of cancers among the known FAMMM gene carriers and their first degree relatives. Thus, we provide evidence of increased susceptibility to systemic cancer occurring in conjunction with the FAMMM syndrome in a subset of this resource.


The common failure of health systems to ensure adequate and sufficient supplies of injection devices may have a negative impact on injection safety. We conducted an assessment in April 2001 to determine to which extent an increase in safe injection practices between 1995 and 2000 was related to the increased access to injection devices because of a new essential medicine policy in Burkina Faso.We reviewed outcomes of the new medicine policy implemented in1995. In April 2001, a retrospective programme review assessed the situation between 1995 and 2000. We visited 52 health care facilities where injections had been observed during a 2000 injection safety assessment and their adjacent operational public pharmaceutical depots. Data collection included structured observations of available injection devices and an estimation of the proportion of prescriptions including at least one injection. We interviewed wholesaler managers at national and regional levels on supply of injection devices to public health facilities.Fifty of 52 (96%) health care facilities were equipped with a pharmaceutical depot selling syringes and needles, 37 (74%) of which had been established between 1995 and 2000. Of 50 pharmaceutical depots, 96% had single-use 5 ml syringes available. At all facilities, patients were buying syringes and needles out of the depot for their injections prescribed at the dispensary. While injection devices were available in greater quantities, the proportion of prescriptions including at least one injection remained stable between 1995 (26.5 %) and 2000 (23.8 %).The implementation of pharmaceutical depots next to public health care facilities increased geographical access to essential medicines and basic supplies, among which syringes and needles, contributing substantially to safer injection practices in the absence of increased use of therapeutic injections. Injections are one of the most common medical procedures, with an estimated 16 thousand million injections administered each year in developing and transitional countries, most of which are for therapeutic purposes . To prevThe common failure of health systems to ensure adequate and sufficient supplies of injection devices may have a negative impact on injection safety. The WHO model list of essential medicines made no mention of the need to supply injection devices in quantities that matched supplies of essential injectable medicines although 44% of active ingredients were mentioned in injectable form . In a syBurkina Faso is a good setting to examine how access to injection devices impacts on injection safety. In 1995, an injection safety assessment indicated that (1) sterile injection devices were used for each injection in 80% of the urban health care facilities, 60% of provincial facilities and 11% of the rural facilities and (2) up to 48% of health care facilities visited reported insufficient quantities of injection devices available . In 96% We conducted a cross-sectional survey in 2001 to assess retrospectively the situation between 1995  and 2000  structured observations of injection devices available in the health facility, (2) reviews of the registers to estimate the proportion of prescriptions including at least one injection during the months of June between 1995 and 2000, (3) interviews of health care workers using standardized questionnaires, (4) interviews of operational public pharmaceutical depots managers using standardized questionnaires, (5) structured observations of 5 ml syringes with needle and 15 basic essential medicines available in the depot (chosen as sentinel indicators of availability and good stock management) and (6) structured interviews of district wholesalers managers. We recorded the origin and brand name of injection devices observed and the sale prices of syringes and needles in the pharmaceutical depots. Seven teams of two investigators collected the information. All teams standardized their data collection procedure before the fieldwork through training and a field visit.We interviewed the manager of the national wholesaler who provided figures estimating the number of injection devices sold annually in the public health care sector and fixed retail prices. We converted the retail prices of syringes and needles in the public sector set by the Ministry of Health in US$ according to the exchange rate in use in May 2001 (1 US$ for 750 Francs CFA). We used the standard set of medicines and basic consumables given to open a pharmaceutical depot in Burkina Faso by Nongovernmental Organizations (NGOs) with the Ministry of Health approval to estimate the proportion of the essential medicines expenditure used to procure injection devices. This standard package was representative of a typical consumption of a depot and covered the need of a population of 10 000 persons for three to six months in Burkina Faso. Finally, we reviewed the major changes in the new national essential medicines policy, particularly related to access to medicines and basic supplies, including the number of operational pharmaceutical depots set up throughout the country annually and the regulation of medicine retailed prices in the public sector.We entered and analysed data using the version 1.2d of the Sphinx plus software . Proportions were calculated using the number of health care facilities visited (52), the number of pharmaceutical depots or the number of health care workers interviewed as denominator, as appropriate.The Ministry of Health approved the protocol and provided an introduction letter for the visit of health care facilities. We met each regional director prior to field visits in each area. However, there was no communication with the health care facilities prior to the arrival of the field workers. We informed participants about the purpose of the assessment and about their right to refuse. Participation was voluntary for all interviewed. When injections were about to occur with non-sterile devices, field workers were asked to interrupt tactfully the procedure. All information was collected confidentially using codes.Geographical access to injection devices improved substantially between 1995 and 2000. Of the 52 health care facilities visited in April 2001, 50 (96%) were equipped with a public sector pharmaceutical depot selling syringes and needles directly to patients. Of these, 37 (74%) had been established between 1995 and 2000  of the essential medicines expenditure . In the While single-use injection devices should be made available in every health care facilities, they should also be made available in a way that ensures equity. In Burkina Faso, the poorest part of the population may not be able to assume the financial burden of single-use injection devices according to the Bamako Initiative. The use of cost recovery scheme could decrease service utilization by the general population and subsequently expose the poorest to unsafe injection practices and reuse of single-use injection devices . The lowThe generalized use of single-use injection devices in preventive and curative services has not led to major side effects in Burkina Faso. Excessive availability of injectable medicines can increase irrational use of injections and restricted access to injectable medications is associated with a reduction of injection overuse . HoweverIncreased access to injection devices is not the only explanation that may account for the improvement of injection practices in Burkina Faso. Increased awareness regarding risks of transmission of pathogens, including HIV, through unsafe injections among the population may have played a role ,17,18. IThis programme review suffers from three main limitations. First, the 1995 and 2000 assessments used different methodologies and the 1995 assessment did not use standard WHO methods  However,One element of the strategy to ensure injection safety is a continuous availability of sufficient quantities of injection devices in health-care facilities . WHO, UNIn Burkina Faso, establishing pharmaceutical depots next to health care facilities through the national policy of essential medicines increased access to safe injection devices and contributed substantially to safer injection practices along with other factors, including an increased consumer demand for safe injection devices. The better access to single use injection devices was not parallelled by an increase in injection prescriptions. However, health care waste management policies need to address the increased amount of sharps waste generated.The author(s) declare that they have no competing interests.SL who was the principle investigator and writer of the article has shared with JT, the conception of the protocol and study design. PS participated in the formulation of the assessment tool, provided comments on the assessment tool and the writing of the study. YH wrote the initial terms of reference of the study, participated in the analysis of the data and in the writing of the paper. KH supervised all aspects of the investigations and of the writing.The pre-publication history for this paper can be accessed here:


Some earlier studies based on relatively small data sets have suggested that the month of diagnosis affects survival of breast cancer patients. This phenomenon has been suggested to be attributable to daylight-related hormonal factors. Factors related to the holidays of both the medical personnel and the women themselves might also provide the explanation. In this study we assessed the effect of the month of diagnosis on the survival of 32,807 female breast cancer patients diagnosed in Finland in 1956-1985. Our results indicate that the month of diagnosis is a significant prognostic factor after adjusting for age at diagnosis, period of diagnosis, and stage at diagnosis. The adjusted relative excess risk of death was highest among those diagnosed in July and August, and lowest in March and November, the difference between the lowest and highest risk being 18%. Since colorectal cancer should not have any daylight-related hormone dependent risk determinants, a control cohort of 12,950 women with a diagnosis of colorectal cancer in the same calendar period was studied in a similar way. The survival pattern by month of diagnosis among the colorectal cancer patients was similar to that among breast cancer patients, indicating that general factors associated with the health behaviour of women and the health services (such as holidays) rather than biological factors may cause seasonal variations in survival of cancer patients.


The antigenic phenotype, ultrastructure and bone resorbing ability of mononuclear and multinucleated giant cells of four giant cell tumour of tendon sheath (GCTTS) lesions was assessed. Both the giant cells and the mononuclear cells exhibited the antigenic phenotype of cells of the monocyte/macrophage lineage. The giant cells, unlike osteoclasts, did not respond morphologically to calcitonin and showed ultrastructural and immunophenotypic features of macrophage polykaryons. However, like osteoclasts, the giant cells showed direct evidence of resorption pit formation on bone slices. This indicates that the GCTTS is composed of cells of histiocytic differentiation with the giant and mononuclear cell components expressing a similar antigenic phenotype. Bone resorption by macrophage polykaryons shows that this is not a unique defining characteristic of osteoclasts. Qualitative differences in the degree and pattern of bone resorption by macrophage polykaryons distinguish it from that of osteoclasts and may underlie the clinical behaviour of osteolytic lesions.


We describe a modified access technique for the proximal (open) part of single stage hybrid exclusion of aneurysm of the aortic arch.3 patients had a bifurcated Dacron graft for the innominate and left subclavian arteries and an additional end-to-side anastomosis of the left common carotid artery on the limb to the left subclavian artery. With our modification, access to the left subclavian artery is by left subclavicular incision and creation of an anterior tunnel via the left thoracic outlet from the origin of the left subclavian artery along its anatomical course to the subclavicular plane.Advantages and disadvantages of this technique in relation to anatomy and pathology. A number of techniques and variations thereof are currently employed in surgery for the aortic arch.The two –  and singPreoperative imaging with contrast thorax computed tomography is required to visualize adequately the degree of calcification of the ascending aorta and the vascular anatomy of the arch, with particular attention to the degree of calcification around the origins of head and neck vessels.The standard preparation and draping of the patients for aortic arch surgery has been previously well described.Our approach Figure  specificOnce proximal and distal control is achieved on the ascending aorta and the three arch vessels with colour-coded silastic slings, 5,000 international units of heparin are given intravenously. The proximal anastomosis  is fashioned following application of side-biting clamp and continuous 4.0 Polypropylene sutures were used reinforced with Teflon felt. The innominate artery (IA) anastomosis  follows with 5.0 polypropylene suture and partial clamping of the vessel. Subsequently, whilst flow in the IA resumes, the LSC anastomosis (primary left top end) is similarly constructed after feeding the 10 mm left limb of the graft by way of a Roberts clamp and vascular tape through a tunnel leading from the sternotomy, anterior to the origin of the LSC by the thoracic outlet to the left subclavicular incision. Care is taken for the graft not to be compressed or otherwise distorted through the tunnel with temporary approximation of the sternal edges whilst fashioning the anastomosis, while important neighbouring structures  are safeguarded. The proximal part of LCC is ligated with heavy silk, a vascular clamp is applied in the distal part and the LCC is divided. The last distal anastomosis (secondary left top end) is that of the distal LCC on the antero-medial aspect of the 10 mm left limb of the graft to the LSC with same suture technique and tapering.The other two proximal parts of arch vessels  are ligated with heavy silk ties to avoid endo-leak and the proximal anastomosis is marked by heavy radio-opaque clips to orientate the deployment of the endoaortic graft that is next inserted by the vascular surgeon and interventional radiologist in order to obliterate the distal part of the aneurysm. The endovascular part of the operation has also been previously well described.With small differences in the minutiae of the operation, we have applied this technique in three patients, avoiding these with Marfan syndrome (see conclusion). The outcome was favourable in each occasion.Previously described advantages of hybrid technique for exclusion of aortic aneurysm are avoidance or reduction in global cerebral ischemia time, avoidance of cerebral perfusion or cerebroplegia and limitation of primary aorto-graft anastomosis to one proximal and two distal .Concerns in relation to the endovascular stent exclusion have been expressed for endoleak and long-term aortic arch stability.In the technique presented in this article two further advantages may be ascribed:-facile access to the LSC in obese patients of short stature or barrel chest (or both) where the artery lies deep and posterior in the thoracic inlet where its approach through the sternotomy is problematic including risks of uncontrollable bleeding and injury to the left recurrent laryngeal nerve. This particular patient somatotype is where we recommend this technique.-Optimisation of distal anastomoses when significant discrepancies exist in diameter between the limbs of Dacron grafts and head and neck vessels.Potential disadvantages of our technique include: morbidity from the additional incision and, perhaps most importantly, compromise of the left limb of the graft by distortion in the' tunnel'. Similarly, the longer length of the left limb of the graft increases the possibility of kinking or distortion. Translocation of the LCA and injury from the side-biting clamp on the innominate are other potential risks.We do not intend to apply this technique to patients with Marfan's somatotype to whom traction on the arch exposes adequately the proximal LSC through the sternotomy. For them, warm arch surgery with cerebral perfusion is an established alternative.Lastly, we note the need for multidisciplinary collaboration between vascular surgeons, cardiothoracic surgeons and interventional radiologists.The author(s) declare that they have no competing interests.AP drafted the manuscript, CR and AC assisted in writing and creating the figures, NC and TA developed the technique and co-authored the manuscript.


We appreciate the letter from Alessio and Lucchini concerning the number and variety of toxicants able to affect serum prolactin levels. Reflecting on the wide variability of the currently available data, we would like to make two additional points.The first point concerns the usefulness of serum prolactin as a potential indicator of neurotoxicity for populations at risk. This biomarker indeed appears to be influenced by a large number of both organic and inorganic chemicals, which have seemingly little in common in terms of mechanistic action . Moreover, one chemical—cadmium, for example—can have a biphasic dose-dependent effect on serum prolactin , an effeB1 knock-out mice  [as demonstrated by the hyperprolactinemia developed by GABAout mice ], glycinout mice . In viewAnother important issue to keep in mind concerns the biological significance of all of the modifications we observed in our study . DespiteAlthough the lack of specificity of prolactin reduces the immediate usefulness of these dopaminergic biomarkers, the question of the potential clinical impact of the small but significant changes in terms of neurotoxicity  certainl


In Northern Ghana, a combination of torrential rains coupled with the spilling of the Bagre dam in neighboring Burkina Faso in the past few years has resulted in perennial flooding of communities. This has often led to the National Disaster Management Organization (NADMAO) the main disaster responder agency in Ghana, being called upon to act. However affected communities have never had the opportunity to evaluate the activities of the agency. The aim of this study is therefore to assess the performance of the main responder agency by affected community members to improve on future disaster management.A mixed qualitative design employing a modified form of the community score card methodology and focus group discussions was conducted in the 4 most affected communities during the last floods of 2012 in the Kasena-Nankana West district of the Upper East Region of Northern Ghana. Community members comprising of chiefs, elders, assembly members, women groups, physically challenged persons, farmers, traders and youth groups formed a group in each of the four communities. Generation and scoring of evaluative indicators was subsequently performed by each group through the facilitation of trained research assistants. Four Focus group discussions (FGDs) were also conducted with the group members in each community to get an in-depth understanding of how the responder agency performed in handling disasters.A total of four community score cards and four focus group discussions were conducted involving 48 community representatives. All four communities identified NADMO as the main responder agency during the last disaster. Indicators such as education/awareness, selection process of beneficiaries, networking/collaboration, timing, quantity of relief items, appropriateness, mode of distribution of relief items, investigation and overall performance of NADMO were generated and scored. The timing of response, quantity and appropriateness of relief items were evaluated as being poor whereas the overall performance of the responder agency was above average.NADMO was identified as the main responder agency during the last disasters with community members identifying education/awareness, selection process of beneficiaries, networking/collaboration, timing of response, quantity of relief items, appropriateness of relief items, mode of distribution of relief items, investigation and overall performance as the main evaluative indicators. The overall performance of NADMO was rated to be satisfactory.Kasena-Nankana West district, NADMO, community score card, Rural Northern Ghana According to the UN Office for the Coordination of Humanitarian Affairs, the 2007 floods alone killed 22 people, destroyed or completely damaged 11,239 homes, washed away 12,220 hectares of farmland and affected 275,000 people.5As the reported number of people affected by disasters has risen over the past decades, so has the expectations placed on responding agencies by donors, the public and affected populations also increased.7The Kasena Nankana west district was one of the hardest hit in all the previous disastrous events resulting in widespread humanitarian effort by government; non-governmental organizations (NGOs) such as the International Federation of the Red Cross and the Inter-NGO Consortium; and individuals. All the humanitarian aid was channeled through the National Disaster Management Organization (NADMO) the main disaster responder agency in Ghana established by act 517 of 1996 to manage disasters and similar emergencies in the country.There is currently scarcity of knowledge concerning the performance of the main disaster responder agency by community members in Northern Ghana especially after the disastrous floods of 2007, 2010 and 2012. We therefore conducted this study to assess the performance of the main responder agency at the grass root level in Northern Ghana and to set the platform for an interactive feedback between responder agency and community members for future disaster management.Study area and DesignThis study was conducted from May to June 2014 in the four most affected communities  of the last floods of 2012 in the Kasena-Nankana West district of the Upper East Region of Northern Ghana. The Kassena-Nankana West District is one of the thirteen districts in the Upper East Region of Ghana. Its population according to the 2010 Population and Housing Census is 70,667 representing 6.8 percent of the region’s total population. Males constitute 50.8 percent and females represent 49.2 percent. Seventy nine percent of the population is rural. The population is engaged in various economic and social activities including; subsistence farming, business/trade, rearing domestic animals among others.9 The map of the Kassena-Nankana West District showing the study communities is shown in Due to the growing interest and importance in the use of qualitative, especially participatory techniques in evaluating relief programsThe Community Score Card methodology,11,12The community score card (CSC) process is a community-based monitoring tool that is a hybrid of the techniques of social audits and citizen report cards. The CSC is an instrument to exact social and public accountability and responsiveness from service providers. By linking service providers to the community, citizens are empowered to provide immediate feedback to service providers. The CSC process uses the “community” as its unit of analysis, and is focused on monitoring at the local/facility level. It can therefore facilitate the monitoring and performance evaluation of services, projects and even government administrative units by the community themselves. Since it is a grassroots process, it is also more likely to be of use in a rural setting. CSC process involves basically four components: input tracking scorecard, community generated performance scorecard, self-evaluation scorecard by service providers and an interface meeting between users and providers to provide respective feedback and generate a mutually agreed reform agenda.10For the purpose of this study, we employed only the component of community generated performance scorecard as this involves the generation of evaluative indicators by community members themselves.Selection of study participantsAt the community level, members comprising of chiefs, elders, assembly members, women groups, physically challenged persons, farmers, traders and youth groups formed a group in each of the four communities. This target population was those actually chosen by community members to represent them in the communities’ dealings with the responder agency during the disasters. Each group was considered to be heterogeneous since the members were from different backgrounds, ages and genders. All participants were however aged 18 years and above.Data collection process and analysisTwo experienced research assistants were trained on the community score card approach, the study protocol and procedures to assist the investigators in data collection.In all, four community visits where made to each community by the research team. The first visit was to explain the purpose of the study to the chiefs, elders and opinion leaders of the communities. During the second community visit, a community meeting was held where the purpose of the study and scorecard methodology (with much emphasis on indicator generation) was explained to community members after which each community chose its own group members. On the third visit, the field research team facilitated an indicator-generation process where groups generated and defined a set of indicators. The definitions of indicators were given entirely by group members themselves after which group representatives from each group met to consolidate and harmonize these definitions under the guidance of the research team. In the final community visit, group members met to score each indicator where a circle was drawn on the ground and divided into different sections by one of the participants in each group. Items like sticks, sandals and stones were used to denote an indicator in each of the divided sections of the circle. Participants cast a small stone each in the divisions of the circle (figure 2) to represent their individual grading/score of an indicator as arrived at by consensus. The groups further settled on a collective scoring measure or rating of 1-100 to score some indicators. These scoring processes in the form of a scoring matrix were then summarized into a score card and presented in the form of tables.Focus group discussions (FGDs) were also conducted with the group members in each community during the third community visit to get an in-depth understanding of how the responder agency performed in handling disasters. FGDs were recorded with an audio tape and later transcribed verbatim from the local language (kassem) into English in a text form for analysis. The investigators read through all the transcripts exhaustively to check for inconsistencies after which coding and categorization was done manually using the conventional analysis approach as outlined by Hsiu-Fang and Sarah.Ethical considerationsEthical approval was given by the Navrongo Health Research Centre Institutional Review Board (ID: NHRCIRB 183) and Kasena-Nankana West district assembly and district NADMO office. Permission to carry out this survey at the community level was verbally sought from the chiefs and elders of the respective communities first, after which a verbal informed consent was also gotten from individual members of the participating groups. The consent procedure was reviewed by and approved by the ethics committee.In total four community score cards and four focus group discussions were conducted involving 48 community representatives. Males accounted for 56% (27) of the population with the remaining 44% (21) being females. The average age of participants was 52 years. An average of 12 members formed a group in each of the communities.Findings of both the community score card and focus group discussions are presented together.Community Score CardsAll four communities identified NADMO as the main responder agency during the last and previous disasters. Community generated indicators included: Education/awareness, Selection process of beneficiaries, Networking/Collaboration, Timing of response, Quantity of relief items, Appropriateness of relief items, Mode of distribution of relief items, Investigation and Overall performance of NADMO.The consolidated and harmonized definitions of the indicators is presented in Focus Group DiscussionsEducation/awarenessTwo of the communities (Nyangania and Nakong) said they did not receive enough education and sensitization on the flooding situation resulting in community members being hit hard by the floods. This they said also affected their resilience level adversely.“The local FM station did a good job by constantly announcing and reminding us of when they were going to open the dam from neighboring Burkina Faso. This helped members of the community to prepare adequately and so we were able to adapt to the floods quite well with the help of NADMO” (Group member of Navio community-FGD)“Our community did not receive information or education from any organization. So when the flood came we were not prepared at all and this led to loss of lives and properties of community members” (Group member of Nakong community-FGD)Section process of beneficiariesMembers of three communities  identified this as an indicator with only one of these communities (Nakong) rating this indicator high.“In fact we were really very satisfied with how NADMO selected those who were to benefit from the relief items they brought to us” (Group member of Nakong community-FGD)“The way NADMO selected those who were to benefit from the relief items was poor. For example some of the affected people who wrote done their names did not receive any item whiles some people who didn’t write their names at all were given relief items” (Group member of Kajelo community-FGD)NetworkingThis indicator was identified by only one community with members of the group identifying the existence of networking and collaboration between NADMO officials and other stakeholders in the management of the last disasters.“NADMO officials, leaders of some political parties and other organizations who donated relief items to us worked together in deciding those who got those items” (Group member of Navio community-FGD)Timing of responseWhereas three of the communities  got some response from the responder agency, the response rather arrived very late with the fourth community (Nyangania) not receiving any response at all during the last floods in 2012.“Although we eventually got some items such as cups, mattresses, blankets and buckets from NADMO, these items arrived very late. We hope next time there is a disaster such as this, NADMO and any organization which has items to donate, will do that as quick as possible to help the community recover more quickly” (Group member of Kajelo community-FGD)“For the last floods that we experienced here, NADMO visited us to write the names of those who were affected through the community elders. However they never came back again and so no single person received any relief item in this community” (Group member of Nyangania community-FGD)Quantity of relief itemsMajority of respondents from communities were the responder agency responded opined that the quantity of relief items were generally inadequate.“The quantity of relief items we received was not enough at all. Imagine after writing down the names of so many affected people only 8 mattresses were distributed to the worst affected areas of Kajelo through the elders of the community” (Group member of Kajelo community-FGD)Appropriateness of relief itemsThose communities that got a response from NADMO rated the appropriateness of this response to be inadequate. All the 3 communities that got some help from NADMO said the relief items they received were exactly what they needed to cope and recover from the floods.“Though officials of NADMO came to write our names and the items we actually needed, what they eventually brought to us was different and this did not help us that much especially on how we coped and recovered from the floods” (Group member of Navio community-FGD)Mode of distribution of relief itemsOnly one (Nakong) community evaluated the responder agency using this as an indicator with group members stating that the mode of distributing relief items was unsatisfactory.“The unfair manner with which the relief items were distributed to affected members of the community rather brought about some disagreements and conflicts amongst the beneficiary since some people thought they were most affected and therefore deserved more items. Some members of this community have also come to complain to me that the relief items were distributed along partisan lines and not based on merit” (Group member of Nakong community-FGD)InvestigationGroup members in only one (Kajelo) community identified community needs assessment by the responder agency as an evaluative indicator with 50% of the members saying that this was poorly done and the other 50% saying this was not carried out at all.“Although NADMO came around to assess the extent of damage by the floods before writing the names of those to benefit from any relief item in my area, this was poorly done as some of the people who were seriously affected didn’t get the right quantity of items to help them deal with the situation” (Group member of Kajelo community-FGD)“NADMO never did any investigation or assessment of the level of damage by the floods in my locality before writing down the names of those affected. And so some of those who were not seriously affected got the same items as those who were seriously hit by the floods” (Group member of Kajelo community-FGD)Overall performanceAll four communities evaluated NADMO using this as an indicator. Apart from one (Kajelo) community that rated the overall performance of NADMO to be unsatisfactory, the rest of the communities thought that NADMO performed creditably well in its handling of the recent disasters.“I will say that overall, NADMO performed quite well when you look at how they handled the entire disaster situation” (Group member of Navio community-FGD)“Even though NADMO did not respond to our needs this time round, judging by what they did during the previous floods I will say that their performance was satisfactory” (Group member of Nyangania community-FGD)“I wasn’t happy with the performance of NADMO at all. They were not fair with the way they responded to this particular disaster. Those who really needed the items never got them and for those who eventually received their items got them very late. So how can you say that NADMO did well?” (Group member of Navio community-FGD)The methodology employed in this study can be said to be one of the new emerging participatory techniques used in evaluating relief programs and agencies especially against the background that the CSC is being used for the first time for this purpose.The Hyogo World Conference on Disaster Reduction in 2005 stressed on the importance of information management and exchange which is meant to provide easy understanding of information on disaster risks and protection options, especially to citizens in high-risk areas, so as to encourage and enable people to take action to reduce risks and build resilience.Selection of beneficiaries during and after disasters can be a very daunting task. In this particular disaster, majority of the community members labeled a number of allegations against the responder agency. Similarly in a qualitative study to evaluate post-flood disaster response strategies in southern Ghana, some male participants in a focus group discussion also accused the same disaster responder agency as being discriminatory and actually decided not to violently contest the seeming discrimination they felt so as to sustain the unity in their community.16,Post-disaster governmental manipulations of response processes has been identified to exacerbate existing inequalities within affected communities which has often tend to provoke angry protest and demonstration against the institutions in charge.17,,,In non-disaster situations, many of the agencies involved in disaster management operate independently of each other. At the community level in a disaster situation however, this is often not the case as complexity arises from a variety of elements, systems, processes and actors in a complex network of many interactions between these agencies at various levels necessary for achieving mutual adjustment and a collective goal.,16It is a usual practice for NADMO to register victims of disasters before resources are mobilized and sent to the community.In one of the study communities, the need to conduct a needs assessment during and after disasters was identified as evaluative indicator as community members thought this was crucial especially concerning the distribution of relief items by the responder agency. This point has also been emphasized by Oaks in an Overview of the Damage Assessment Process: as he suggests that, after disasters, the damage assessment process is fundamental to relief and reconstruction as it triggers the beginning of formalized disaster relief and recovery aid.26Majority of group members in the affected communities in the Kasena Nankana west district of northern Ghana rated the overall performance of the responder agency to be above average. Although some group members rated certain specific generated indicators low, they thought that in the whole, the responder agency performed creditably well. This finding only emphasis the fact that community members tend to assess performance when certain specific needs are met and not just an overall scoring scale of evaluative indicators as is usually found in quantitative studies. However contrary to the findings of our study, an earlier qualitative study involving the same responder agency found the overall performance of the agency to be poor after the catastrophic 2010 flooding situation in southern Ghana.27 The observed differences in the results across the four communities can be attributed to the fact the these communities are often affected differently by the perennial floods with the response from the responder agency being different depending on the level of preparedness by NADMO at the local level and availability of support from all stakeholders.LimitationsNotwithstanding the strong qualitative methodological approach adapted by this study, the study had some limitations. We conducted the study in only four communities and about two years after the disaster occurred and therefore the accuracy and precision of the information provided could have been affected especially that some of the community leaders would have relocated, died or forgotten certain vital events that occurred.Although the composition of the groups was heterogeneous, group members were only elders and representatives of the communities and therefore their opinions might not necessarily be the views of the ordinary members of the communities who were hit hardest by the floods.This study used a combined qualitative methodological approach of focus group discussions and the community score card in four communities in Northern Ghana to evaluate the performance of the main disaster responder agency. All four communities identified NADMO as the main responder agency during the last disasters with community members identifying education/awareness, selection process of beneficiaries, networking/collaboration, timing of response, quantity of relief items, appropriateness of relief items, mode of distribution of relief items, investigation and overall performance as the main evaluative indicators. Although the indicators were rated differently by each community; the timing of response, quantity and appropriateness of relief items were generally poor whereas the overall performance of the responder agency was generally satisfactory.Since these communities are often prone and vulnerable to the perennial floods, we recommend that the main responder agency responds more timely and fast whiles engaging the other stake holders in disaster management to ensure that communities get enough of the most appropriate relief items. We also encourage that after each disaster, all the stake holders in disaster management great that platform were the disaster responder agency will be evaluated by the affected communities as a feedback to improve on future disaster managementThe authors have declared that no competing interests exist.This study was made possible by the generous support of the Global Disaster Preparedness Center and Response 2 Resilience. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The views presented in this paper are solely those of the researchers and are completely independent of the funder.All relevant data are within this manuscript.Stephen ApangaEmail: apangastephen@hotmail.comUniversity for Development Studies, Department of Community Health and Family Medicine School of Medicine and Health Sciences


Multidetector computed tomographic angiography (MDCTA) is the new gold standard for diagnostic evaluation of the abdominal and/or mesenteric arteries. It is not invasive and provides a 2D and 3D global cartography of all abdominal arteries and that with only a limited amount of contrast media.MDCTA allows the optimal diagnosis of single or multiple arterial stenosis and easily analyses sometimes very complex collateral pathways. It constitutes a major advance to plan the arterial visceral safety of major commonly performed abdominal surgical procedures such as aorto-iliac surgery, endovascular aneurysm repair (EVAR), but also complex pancreatic and gastrointestinal or colonic surgery. It also allows to plan the most optimal strategy for revascularization of the mesenteric system through percutaneous angioplasty, stent placement or surgical bypass.This extensive pictorial review illustrates a large variety of situations which may be found during clinical practise. Single compression or stenosis of each digestive artery, combined and/or complex associations of stenosis and/or compressions of several arteries, secondary complications like aneurysms and classical but also sometimes unusual patterns of collateralization are richly illustrated. Specific syndromes comprising the median arcuate ligament syndrome (MALS) and the Leriche’s syndrome are also discussed. Today the panel of imaging techniques available to investigate abdominal vessels is varied comprising of duplex and color flow Doppler sonography, angio-CT, angio-MRI and conventional angiography (CA). The choice of one technique over another depends on its availability, the clinical circumstances, the degree of emergency but also on the patient’s physical characteristics, age and renal function.Multidetector computed tomographic angiography (MDCTA) today represents the best choice when the purpose of the examination is to quickly and easily obtain optimal global and non-invasive analysis and/or cartography of the abdominal and visceral vessels with all their interconnections. In this context MDCTA represents the new gold standard and outperforms CA. MDCTA has major advantages on CA. First, it is a very fast and non-invasive technique which only requires a limited amount of intravenous contrast media to provide high quality 2D and 3D anatomic images. Then a global cartography of all arteries may be obtained simultaneously, an opportunity that cannot be meet during CA. Multiple successive selective or semi-selective invasive catheterizations would be necessary to obtain such a global analysis of all abdominal vessels during CA. MDCTA has only several limitations. The detection threshold of the tiny arteries is lower than with CA and the opacification is static when compared to the dynamic aspect of CA which can better detect the direction of blood flow particularly in the collateral pathways. The fact that all arteries are opacified simultaneously can make spatial analysis difficult. Fortunately, secondary high quality selective reconstructions are able to dissociate and analyse the complexity of arterial superposition anatomic overlays. This nevertheless requires a good skill in the use of 3D post-processing programs.MDCTA offers the opportunity to quickly diagnose or rule out mesenteric stenosis or compression in patients presenting with suggestive abdominal pain or angina. It also constitutes a primordial advance progress to plan the arterial safety of many major abdominal surgical procedures comprising classical aorto-iliac surgery, endovascular aneurysm repair (EVAR), complex pancreatic and gastrointestinal or colonic surgery but also to optimally plan revascularization of the mesenteric system through percutaneous angioplasty (PTA), stent placement or surgical bypass .During embryogenesis, most segmental arteries regress and only three dominant major mesenteric visceral arteries persist: the celiac trunk (CTK), the superior mesenteric artery (SMA) and the inferior mesenteric artery (IMA) . FortunaPrevious studies have suggested that a significant stenosis of at least two of the three main digestive arteries must occur and/or that a complete occlusion of the CTK must precede the occlusion of the rest of the mesenteric arteries before the occurrence of clinical symptoms of mesenteric angina . Therefo1This extensive pictorial review illustrates a large variety of situations which may be found during clinical practise. Single compression or stenosis of each digestive artery, combined and/or complex associations of stenosis and/or compressions of several arteries, secondary complications like aneurysms and classical but also sometimes unusual patterns of collateralizations are richly illustrated. Specific syndromes such as the median arcuate ligament syndrome (MALS) and the Leriche’s syndrome that are also discussed.The incidence of hemodynamically significant CTK stenosis in an asymptomatic population has been evaluated to 7.3% and the most important etiology is extrinsic compression by the median arcuate ligament (MAL) of the diaphragm. Atherosclerosis remains only a rather minor cause of stenosis of the CTK . The MALThe Dunbar syndrome induced by the celiac trunk compression syndrome (CTCS) also called the median arcuate ligament syndrome (MALS) is a potential clinical entity characterized by a triad comprising epigastric pain, weight loss and postprandial pain with nausea and vomiting 678910. T678967911Atypical manifestations of the MALS are extremely variable ranging from exercise related pain and diarrhea in elite athletes to dramatic rupture of a secondary pancreaticoduodenal artery aneurysm (PDAA) developing on collaterals 8. Nevert6The physiopathology of MALS is also controversial: are the symptoms really caused by ischemia of the gut itself or by neurogenic compression or ischemia of the celiac ganglion ?During MDCTA the MALS exhibits a characteristic hooked appearance of the focal narrowing of the CTK and the deformation increases during expiration Figures  and 2. TIt is our opinion that the presence of these collaterals is crucial for the diagnosis of a significant or high degree of compression of the CTK even if the deformation of the CTK is moderate. Indeed, most of the abdominal MDCT are performed in deep inspiration which classically reduces and thus underestimates the compression syndrome. The presence of collaterals helps to diagnose this underestimation. The principle should be: no collateralisation, no MALS except if an additional stenosis on the SMA is present compromising the development of collaterals. Nevertheless, the presence of these collaterals proves that the compression is significant but also demonstrates a good substitution.As confirmed by several studies the CTCS of MALS is better appreciated during expiration Figure  especial791112Due to the permanent mechanical extrinsic compression experienced by the CTK in high-grade MALS only a short relief of symptoms followed by early restenosis is classically found after percutaneous angioplasty (PTA) with stenting. The traumatic effects of PTA on the intima and media may weaken the vessel which may become more susceptible to collapse. In addition, stent deployment may be compromised by slippage, mechanical fatigue or crushing secondary to permanent external compression Figure . TherefoFor the same reasons of chronic mechanical compression and major cyclic variation of flow during breathing the potential role of MAL in the development of CTK aneurysm and/or CTK dissection has also been reported Figure  515].15.515].Occasionally, in addition to the CTK the constricting effect of MAL may also manifest on the SMA and rarely on the renal arteries (RAs) 910. If t9Nevertheless, this type of double compression has only been infrequently reported. Only four of the 51 patients with MAL syndrome reported by Reilly had both CTK and SMA compressions . Other i121718CCMT is a very uncommon variant Figures  and 12 a131920A patient with a CCMT is potentially deprived of some of the protective benefits of dual origin vessels with multiple mutually supporting anastomoses. Occlusion or proximal stenosis affecting a common CCMT can have serious ischemic consequences to the intestine because the classical redundancy between the CA and SMA circulation is absent. Moreover, any disorder involving the common CCMT  or an extensive surgery (for example a Wipple’s procedure on the pancreas) may have dramatic consequences on the major abdominal viscera 22.Stenosis, occlusion and compression of the CTK by the MAL is known to be one of the main factors for increased collateral circulation and secondarily also to the formation of about 50 to 60% of all pancreatico artery aneurysms (PDAAs) 52425.24When compression occurs on the CTK compressed by MAL during expiration the CTK territory becomes abruptly supplied by reverse flow from the SMA through the PDAs causing acute hemodynamic stress in these arteries and promoting aneurysmal formation Figures  and 13 2526. The25232526The IMA is the smallest of the three main mesenteric arteries and supplies the distal transverse, descending and sigmoid colonic segments as well as the rectum . It rece29The two classical most critical area of watershed of the arterial supply of the left colon are the Griffith’s point in the area of the splenic flexure of the colon were the left branch of the middle colonic artery (branch of the SMA) joins with the ascending branch of the left colonic artery (branch of the IMA) and the Sudeck’s point where collateral communication is found between the last sigmoidal artery and the superior rectal artery, both branches of the IMA.The collateral pathway between the SMA and the AMI is not always clearly designed. There is a real lack of consensus in the terminology used in the literature causing much confusion. Many denominations are used comprising the arch of Riolan (AR) (considered as a vague historic term to discard) Figures  and 17, 29A pragmatic description consists to delineate three concentric different pathways running from the central mesenteric root to its periphery along the colon and comprising:Centrally, the inconstant arch of Riolan (AR), joining the middle and left colonic artery and running very close to the inferior mesenteric vein.In an intermediate location, the mesentery, the pathway observed in cases of severe stenosis or occlusion of the SMA and known as the Meandering Artery (MeA) Figures  and 18.Finally, in the extreme periphery of the mesentery, the marginal arcade of Drummond (MAD), which is classically not tortuous and runs along the left descending colon  Figures and 17.Many authors consider that the anatomic AR and the MeA of Moskowitz are the same entity, the MeA being the term classically describing the tortuous hypertrophic expansion of the AR in the presence of stenosis or obstruction of the SMA or of the IMA. The expansion of the MeA is greater in presence of stenosis or occlusion of the SMA or in the presence of combined stenosis of SMA and CTK than in isolated stenosis of the IMA because the blood flow load is greater for the SMA than for the IMA .In the presence of a large MeA it is thus recommended to surgeons to abandon or to seriously reconsider their plan for a major resection of the left colon . SecondaAIOD is most frequently a progressive chronic disease resulting of massive deposition of atheromatosis at the level of the aortic bifurcation and on the segment of aorta proximal from this bifurcation. Infrequent causes of AIOD are acute occlusion due to embolus or occlusion related to vasculitis . NeverthThe clinical Leriche’s syndrome (LS) includes the typical triad of symptoms of claudication, impotence and decreased peripheral pulses . In thesAIOD has different types of collateral pathways which can be classified as visceral-systemic (VS), systemic-systemic (SS) and visceral-visceral (VV) .The VV pathways  is provided by the CTK, SMA and IMA. This collateral pathway in which the digestives arteries are implicated becomes more prevalent in cases of AIOD extending more proximally along the aorta and thus approaching the level of the emergence of the RAs 34.The SS collateral pathway  comprise subcostal, intercostal and lumbar arteries representing the afferent vessels Figures  and 18. Another SS collateral system is provided by the sacral plexus where the lateral sacral arteries coming from the IIA and the median sacral artery coming from the aorta just above the aortic bifurcation develop collaterals .The internal thoracic artery (ITA) , and the superior and inferior epigastric arteries (EA) also constitute another SS collateral pathway of primordial importance for the lower limbs Figures  and 18. 34Finally, the VV pathway is also constituted by a cross pelvic collateral system constituted by communication between the superior, middle and inferior rectal arteries (ReAs) on both sides Figures  and 18.In each patient presenting with AIOD, the final collateral pattern is individually constituted by a mix of all these above described pathways. It essentially depends of the level of the occlusion: above the IMA, at the level of the IMA or below the IMA. The most proximally the aorta is occluded – from the iliac bifurcation (or under) to just under the level of emergence of the renal arteries – the most important is the recruitment of the digestive arteries and collateralization successively implicates the IMA, the SMA and finally the CTK itself . An optiThe FA is a branch of the hepatic artery (HA) that develops anastomoses with the vertical pathway constituted by the EA and the ITA. The FA may thus constitute a VS collateral pathway (in case of Leriche syndrome – LS) or a SV collateral pathway (in case of stenosis of the digestive arteries).The FA is essentially known by interventional radiologists who perform selective hepatic angiography . They arTo our knowledge, there are no studies reporting the prevalence of the FA detection during dynamic CT studies in healthy patients. Nevertheless, our opinion, based on our personal experience with 64-row multidetector CT is that this prevalence remains extremely low .In a previous report, we reported two cases in which it was likely that the FA was visualized because it was enlarged by a compensatory phenomenon related to the critical state of digestive arteries of the patients. One had a CCMT and the other had severe compression of the CTK and of the SMA by the MAL . AdditioLeft and right inferior phrenic arteries (IPAs) are other rare arteries being able of collateralization with the HA or with the CTK Figure . As for In our experience, we also recently found two cases of atheromatous stenosis of the splenic artery (SA) fortuitously diagnosed through the presence of unusual collateralisation. The first case was collateralized by a tortuous gastroepiploic artery (GEA) a situation which has only exceptionally been described in rare cases of absence or occlusion of the SA  Figure . The othThrough this extensive pictorial review, we have illustrated a large diversity of complex abdominal situations implicating the digestive arteries and/or the systemic abdominal arteries, the two arterial systems being frequently interconnected. These situations are not uncommon in clinical practise. We confirm and demonstrate that multidetector computed tomographic angiography (MDCTA) can be very effective not only to diagnose a single arterial stenosis or compression but also to dissect combined and/or complex associations of multiple stenosis and/or compressions of several arteries. MDCTA also appears uncompetitive unavoidable to map sometimes very complex networks of collateralization.MDCTA is confirmed being the gold standard for the diagnostic evaluation of abdominal and/or mesenteric arterial diseases. It represents a primordial advance to plan the safety of the digestive vascularisation before many major abdominal surgical procedures and to plan revascularization of the mesenteric arterial system itself.