In a normal pregnancy, decidual spiral arteries are transformed into wide diameter, non-vasoactive vessels capable of meeting the increased demands of the developing fetus for nutrients and oxygen. Disruption of this transformation is associated with PE and FGR. Very little is known of how these first trimester changes are regulated normally and even less is known about how they are compromised in complicated pregnancies. Interactions between maternal and placental cells are essential for pregnancy to progress and this review will summarise the challenges in investigating this area. We will discuss how first trimester studies of pregnancies with an increased risk of developing PE/FGR have started to provide valuable information about pregnancy at this most dynamic and crucial time. We will discuss where there is scope to progress these studies further by refining the ability to identify compromised pregnancies at an early stage, by integrating information from many cell types from the same pregnancy, and by improving our methods for modelling the maternal-fetal interface  •Pathology of PE/FGR begins in the first trimester.•Investigating pregnancies with increased risk of PE/FGR is giving valuable information.•This will improve further with advances in identifying compromised pregnancies. Trophoblast invasion and remodelling of the uterine vasculature occur in the first trimester of pregnancy and are tightly regulated in both a temporal and spatial manner. Information on the maternal-fetal interface in the first trimester can be gained from immunohistochemical studies however this does not give an indication of which dynamic cellular and molecular interactions are of functional importance in regulating these crucial events. In this review we will discuss some of the strategies taken to investigate the field, how they have informed what we know about the cell biology of normal pregnancies and those with placental complications and where the scope for future development lies.2Trophoblast invasion occurs in a tightly regulated manner, influenced by signals from the surrounding decidual environment. During the decidualisation process maternal immune cells are recruited to the uterus in significant numbers, with approximately 70% being decidual natural killer (dNK) cells, 20% macrophages and the remaining 10% T cells. During placentation, extravillous trophoblast (EVT) cells invade into the decidua and interact with this enriched environment of specialised immune cells. Cross-talk between the immune cells, stromal cells and the fetal EVT will contribute to regulating EVT invasion and the accompanying changes to the spiral artery structures required for successful pregnancy.Spiral artery remodelling involves the loss of vascular cells and matrix proteins and occurs in an orchestrated fashion. The initial steps involve activation and vacuolisation of endothelial cells (EC), hypertrophy and disorganisation of vascular smooth muscle cells (VSMC) and fibrinoid deposition EVT invasion can be either interstitial or endovascular with endovascular EVTs interacting directly with the EC while interstitial EVT interact first with the VSMCs. Invasion by either route will influence vascular structure via disruption of the heterotypic interactions between EC and VSMC known to be important for maintaining a healthy differentiated vessel There is increasing evidence that maternal immune cells in addition to the fetal EVT play important roles in the remodelling process. In humans all of the immune cell types are located around actively remodelling vessels The ability to investigate during the timeframe in which these changes are actively occurring is hindered by the difficulties inherent in studying human pregnancy. A wide-ranging evaluation of the cellular and molecular cross-talk at the maternal-fetal interface, at what is the most critical time in the first trimester, therefore remains to be performed. Being able to develop strategies to try and address this would advance our understanding of both normal human pregnancy as well as pregnancies complicated by PE and FGR.3Investigating vascular changes at a molecular or cellular level in early human pregnancy is restricted by ethical issues and while animals model some aspects of human pregnancy, they lack deep trophoblast invasion and comparable spiral artery transformation Access to human tissue is limited in ongoing pregnancies to that obtained during chorionic villous sampling (CVS) for genetic screening in the first to early second trimester, or that obtained following parturition. Some highly informative gene array studies have been carried out on tissue obtained from CVS suggesting that the decidual environment may be key in the establishment of placental pathology Placental tissue obtained at term comes from a pregnancy where it is known whether the woman developed PE or another placental complication and has the advantage that tissue is plentiful as the whole placenta can be studied. However this represents a time many months after active remodelling has occurred and any differences in the placentas of PE/FGR pregnancies may represent a consequence of the disorder rather than inform causative pathology. To investigate the decidua and myometrium, uterine biopsies can be taken at the time of delivery and histochemical studies carried out or cells and vessels isolated. This approach has proven useful in developing models of spiral artery remodelling where non-placental bed vessels are obtained and used in co-culture with EVT Tissue samples can also be obtained following termination of pregnancy in the first trimester. The approach taken by our group and others has been to focus on events occurring in the first trimester as this is the most informative time to study EVT invasion and vessel remodelling. Most studies using first trimester tissue have been done without any additional information to inform whether that pregnancy was developing normally. Herein lies the challenge as the clinical symptoms of conditions such as PE are not apparent until after 20 weeks gestation. How can we look at first trimester tissue and know whether it is from a normal or pathologic pregnancy? We have started to address this by using uterine artery resistance index (RI) measurements obtained by Doppler Ultrasound screening to identify women who would have had an increased risk of pregnancy complications had the pregnancy progressed, allowing us to divide the first trimester placental and decidual tissue into two study groups; that from pregnancies with a higher risk and a very low risk of developing PE/FGR. A disadvantage of this approach lies in the fact that many of the pregnancies designated higher risk in the first trimester would have ended up progressing normally despite the probable initial impairment. This will be addressed in the future studies section below. Even given this limitation we have reported fundamental differences in the behaviour of cells isolated from the fetal-maternal interface of high resistance index (RI) compared to normal RI pregnancies which will be described in the following section.4Studies of approximately 10,000 ongoing pregnancies showed that cases with a resistance index obtained from uterine artery Doppler scanning of >95th percentile (high RI) had a 5-fold increased risk of that pregnancy developing placental complications compared to those with a normal RI (<95th percentile) We have shown that primary trophoblast cells isolated from the hRI pregnancies are more sensitive to apoptotic cell death than those from nRI pregnancies, and this may be a contributing factor to impaired invasion Differences in how the maternal immune cells behave between these patient groups is also starting to become clearer with dNK cells from pregnancies with impaired remodelling showing abnormalities in secreted proteins and functional interactions with other decidual cells There is evidence for the involvement of dNK cells directly in spiral artery remodelling in vitro, has increased our knowledge of how placentation in the first trimester develops normally and pathologically. There is however scope for much development of these areas in the future, which will be addressed in the following section.It is clear that studying the uterine artery Doppler screened patient groups, combined with improved techniques for isolating pure cell types and modelling events 5Improvements in early diagnostic tools are proving valuable clinically, for example reliable serum or metabolic biomarkers that more accurately predict development of PE before the clinical symptoms become apparent in vitro culture systems are needed to look at dynamic multi-cellular interactions. Some of the general processes involved in spiral artery remodelling have been reported by a number of groups, including our own, using monolayer co-cultures in vivo allowed us to determine which genes were differentially expressed following stimulation by trophoblast and show VSMC de-differentiation The complexities of modelling cellular interactions in a more 3-dimensional (3D) environment also provide challenges and potential for development. Immunohistochemical studies can provide much information about early human pregnancy however Advances in isolation and culture methods for primary cells means that multiple cell types can be isolated from first trimester tissue from an individual pregnancy. We routinely isolate stromal cells, dNK cells and macrophages as well as endothelial cells  from decidual tissue of the uterine artery Doppler screened women. From the placenta we can isolate trophoblast, stromal, endothelial and macrophages. In the future the ability to look at multiple cell types across an individual pregnancy (with a known risk of developing complications) provides an opportunity for some complex profiling integrating information about genes, microRNAs, proteome and secretome with readouts from functional and biochemical cell based assays. This will allow us to start to get an overview of the maternal-fetal interface in an individual pregnancy. Determining whether this complex information can be integrated to model both normal and PE pregnancies will require strong collaborations with the bioinformatics and mathematical modelling fields. We will then be able to interrogate these models asking questions such as the importance of particular cellular or molecular interactions to successful placentation. The ultimate aim of developing robust models of the maternal-fetal interface would be to help in the identification of novel targets and the safe design of therapies.There is no conflict of interests.


This article contains data related to the research article entitled “A survey analysis of the wood pellet industry in Finland: Future perspectives"  [1]. The dataset include information about the importance of wood pellets on the global bioenergy development and role of wood pellets on the Finnish bioenergy development. Data leads to an expansion of knowledge and discoveries of new possibility for wood pellets industry analysis. Specifications TableValue of the data•The data show opportunities and challenges of Finnish wood pellets development.•It allows predicting the future wood pellets markets in Finland.•Data helps to make future actions and managements for improving the development of wood pellets within the country and outside.•Data leads to an expansion of knowledge and discoveries of new possibility for wood pellets industry analysis.•The data can be used to analyze the wood pellets markets for other countries, similar opportunities and challenges can exist in many other European countries.1The shared data describes the role of wood pellets in bioenergy development in Finland 2The data analysis of the Finnish wood pellet industry was done using a qualitative approach. It based on literature reviews combined with the results of a questionnaire, which is a typical qualitative research method


Sepsis is an umbrella syndrome created by clinicians to identify patients with an acute infection and a high risk of death. The Sepsis-3 definition group recognized new organ dysfunction as the key indicator determining whether a patient falls into the group with a high risk of death or not . The samIn a recent issue of the Annals of Intensive Care, Sacha et al.  reportedDue to the retrospective nature and the fact that the database contained only a limited set of variables, the authors could not report other hemodynamic parameters than MAP, catecholamine requirements and lactate levels. Given the striking difference in the response to AVP therapy, it is obvious that the two patient groups (AVP responders and AVP non-responders) relevantly differed in their hemodynamic status and hence their response to infusion of a strong vasoconstrictor drug such as AVP. This result underlines the common oversight of both intensivist and researchers that arterial hypotension and increased lactate levels in patients with sepsis would be signs of a uniform circulatory pathology. Basic physiology and recent research , 9 indicIndependent of these pathophysiologic speculations, the results of this study clearly underline that arterial hypotension alone is an inappropriate trigger for vasopressor or AVP therapy in critically ill patients (with sepsis). Instead of continuing our quest for a single therapeutic intervention miraculously capable of improving the mortality of a highly heterogeneous patient population, future clinical studies must elucidate the different and unique phenotypes hidden under the umbrella syndrome of sepsis and septic shock. Only with an improved understanding of the various pathophysiologic phenotypes presenting with arterial hypotension and elevated lactate levels in sepsis can adequate resuscitation strategies be developed and tested. Such resuscitation strategies must take these phenotypes with their specific time sensitivities to and indications for therapeutic interventions as well as appropriate resuscitation endpoints into account. In light of the missing answers to these fundamental questions of septic shock resuscitation, the current search for the ideal type of fluid, vasopressor, or inotropic agent appears of only minor relevance.


Although the pathogenesis and clinical significance of cerebral white matter lesions remain controversial, it is well established that age and hypertension are the most important factors related to the presence of these lesions. Hypertension is known to be the most important factor for developing stroke and vascular dementia. In addition, the presence of cerebral white matter lesions is an important prognostic factor for the development of stroke, and also for cognitive impairment and dementia. The mechanisms underlying hypertension-related cognitive changes are complex and are not yet fully understood. Correlations between cerebral white matter lesions and elevated blood pressure provide indirect evidence that structural and functional changes in the brain over time may lead to lowered cognitive functioning when blood pressure control is poor or lacking.Some authors have suggested that the presence of white matter lesions in hypertensive patients could be considered an early marker of brain damage.


Schizophrenia and bipolar disorder are severe mental disorders with unknown etiology. Our research group has studied biomarkers in the cerebrospinal fluid (CSF) of twins with schizophrenia and bipolar disorder to be able to determine the genetic and environmental influences. In brain disorders, CSF is the most appropriate substrate to study as it may reflect the brain biochemistry better than blood. In this presentation I aim to give an overview of our findings and their relation to psychotic disorders. I intend to present our most recent preliminary finding and to discuss future prospects.We studied CSF-markers from a cohort of 50 monozygotic (MZ) and dizygotic (DZ) twins with schizophrenia or bipolar disorder. The twins have gone through diagnostic assessments and have been extensively phenotyped with questionnaires, symptom scales for psychiatric symptoms as well as neuropsychological testing. We have analyzed monoamines, microglia-, neurodegenerative-, kynurenine-, and inflammatory markers using immunoassays and high-performance liquid chromatography techniques. We have also studied microscopic structures with scanning electron microscopy.One of our main findings was that soluble cluster of differentiation 14 protein (sCD14) was higher in twins with schizophrenia or bipolar disorder compared to their not affected co-twins. A later analysis showed that the difference within the discordant twin-pairs was higher in the DZ twin pairs  compared with the MZ twin pairs  suggesting that genetic components along with unique environmental effects have an influence on the higher sCD14 levels in patients with schizophrenia and bipolar disorder. We also found that sCD14 was higher in those patients with more psychotic symptoms.In our study on microscopic structures in CSF we found that the structures were prevalent not only in the patients with schizophrenia and bipolar disorder but also in their not affected co-twins. The finding suggests that genetic factors may be partly involved in the formation of the structures.We have analyzed inflammatory and neurodegerative markers in the CSF of twins with psychotic disorders to be able to study genetic and environmental influences. Our results indicate that sCD14 may have an influence on microglia activation in psychosis. We have continued with analyses on the correlations between all the markers, the monoamine metabolites and associations with symptoms and cognitive ability and the preliminary results from these analyses will be presented.To conclude CSF analyses for biomarkers in twins may result in extended knowledge regarding the genetic and environmental relationships. Our unique twin data gives us the possibility to study CSF-markers in relation to psychiatric symptoms and cognitive measures. For future studies it would be of interest to assemble twin-samples from several research groups to be able to study research questions regarding gene and environment interactions.


Understanding exactly how disparity is processed from binocular views of the world is a long standing problem in vision. It has been hypothesised that an important first step in visual processing is to generate an energy efficient sparse coding of visual inputs. This reduces both noise and redundancy. Mathematical models of such codings have been found to produce components that resemble the responses of simple cells in V1. Similar results with binocular inputs suggest that these methods can be used to build hypothetical models of early binocular visual processing. In our study we have used Independent Components Analysis in the vein of work by Hyvärinen and colleagues to find components that form an efficient coding of binocular visual inputs. The distribution of these components was analysed. We found statistical evidence for a bimodal distribution of interocular differences in phase tuning, further strengthening the summation/difference channels theory of Li and Atick (1994). We have also found components tuned to detect mixtures of phase disparity and position disparity in each view similar to the physiological findings of Anzai et al. (1997). This is consistent with the arguments of Read and Cumming (2007) that both phase disparity and position disparity are necessary for stereopsis.


Laboratory mouse strains are known for their large phenotypic diversity and serve as a primary mammalian model in genotype-phenotype association studies. One possible attempt to understand the reason for this diversity could be addressed by careful investigation of the unique evolutionary history of their wild-derived founders and the consequence that it may have on the genetic makeup of the laboratory mouse strains during the history of human fancy breeding. This review will summarize recently published literature that endeavors to unravel the genetic background of laboratory mouse strains, as well as give new insights into novel evolutionary approaches. I will explain basic concepts of molecular evolution and the reason why it is important in order to infer function even among closely related wild and domesticated species. I will also discuss future frontiers in the field and how newly emerging sequencing technologies could help us to better understand the relationship between genotype and phenotype.


Many biomedical studies of the past seven years have failed in giving a sound picture of what hookah  smoke and smoking are. The reasons are many: from the widespread use of a confusing neologism (“waterpipe”) instead of the few clear and natural words used for centuries by indigenous and non-indigenous people in their real life, to the use of artificial smoking (machines) instead of relying on quantitative and qualitative analysis of toxicants directly performed on real hookah smokers.


The ideal size of intramedullary device to fix corrective osteotomy of proximal femur in abnormal bone in children and small patients may not be easily available. We report the successful use of Rush rod in combination with multiple Kirschner wires to fix the corrective osteotomy of coxa vara and shepherd crook deformity in two patients with osteogenesis imperfecta and fibrous dysplasia. The union was achieved on time, neck shaft angle and rotation were maintained. It is especially common in abnormal bone like fibrous dysplasia and osteogenesis imperfecta. Correction of these deformities will improve limb length discrepancy. It will also improve the hip abductor mechanism by correcting the working length of abductor muscle thus correcting Trendelenburg gait. Fixation for corrective osteotomy for coxa vara or shepherd’s crook deformity in abnormal bone like osteogenesis imperfecta and fibrous dysplasia in children and small patients is challenging due to difficulties to obtain appropriate size of intramedullary nail to fit a small bone. Plates and screws are not the preferred method due to stress points on both ends that may lead to fractures. We report the successful modification of the technique described by Fassier The first patient was a 14-year old boy with fibrous dysplasia who presented with limping due to worsening deformity of the left femur . The TreThe second patient was a 14-year old girl with osteogenesis imperfecta who presented with inability to ambulate without walking frame since sustaining a fracture of the proximal femur six years prior to presentation . She hadWe performed the procedure in both patients in the supine position with standard lateral exposure. Transverse osteotomy was carried out at the subtrochanteric level. The proximal segment was reamed retrograde from the osteotomy site using cannulated drill to ensure it started at the lateral most and exited at the greater trochanter. Next, a few Kirschner wires sized 1.6mm were inserted from the lateral femur at subtrochanteric level to the neck. These wires acted as joy-sticks during manipulation of the proximal femur to the required neck-shaft angle (NSA). The distal segment was also reamed using cannulated drill bit to ensure no penetration of the cortex. In the first patient, a Rush rod of selected length and diameter was inserted antegrade from the greater trochanter to the osteotomy site. The Rush rod was then passed through the osteotomy side to distal femur while the NSA was maintained by the Kirschner wires . In the An ideal implant for fixation of osteotomy for this deformity of abnormal bone would be an intramedullary nail with proximal locking screw to the neck to maintain the correction of NSA and distal locking screw to provide stability. Inability to obtain correct diameter and length of intramedullary locking nail at the time of the surgery prompted us to look for an alternative method.2. In 2003, Fassier improved this technique by combining Wagner’s method with Finidori’s technique which used telescopic rods to fix the subtrochanteric corrective osteotomy1. Fassier et al in 2008 showed satisfactory outcome with this technique in 18 hips with osteogenesis imperfecta and three hips with fibrous dysplasia 3. There was a complication rate of 12% which was largely implant related.One of the early methods in correcting coxa vara is the Wagner method that involves passing two Kirschner wires through the femoral neck and the external portion of the wires moulded and fixed to the femoral shaft by cerclage wireset al3, we modified the technique by using Rush rods as the intramedullary fixation device. Apart from its low cost, it is also a strong solid nail. The Rush rod can be cut according to the desired length as opposed to either intramedullary locking nail or Fassier-Duval nails. Furthermore, in proximal lesions, we were able to control the length of the rod so that it did not breach the distal femur growth plate, as seen in our first patient.Instead of using telescopic rods, as reported by Fassier 4. This modified method provides intramedullary load sharing fixation to the osteotomised bone for long term support. The Kirschner wires that are placed through the neck with the distal half bent and held to the side of the shaft by cerclage wire maintain the NSA as well as prevent rotation. Rotational instability is the limitation faced by the FassierDuval telescopic rod5. In order to achieve an acceptable NSA and rotational alignment, the position of cerclage wires must be distal to the osteotomy site. This method provides relative stability to facilitate union. When the nail is properly positioned with a snug fit in the proximal fragment, as seen in the second patient, two Kirschner wires are adequate to maintain NSA and rotation. In case of fibrous dysplasia, the implant may be removed once the lesion has completely healed. In the case of osteogenesis imperfecta, we propose not to remove the implants unless complications arise.Another difference from the original procedure described by Fassier, was that we did not penetrate the lateral cortex of distal of proximal fragment. Instead, we used cannulated drill bit to create canal in the lateral most part of the shaft. This is possible in an abnormal bone that has big lateral diameter in mal-united fibrous dysplasia bone (first patient) and oval shape osteogenesis imperfecta bone (second patient). If greater valgus correction is required, the penetration through lateral cortex should be chosen. The use of cannulated drill bit is an important step to avoid cortex penetration at unwanted locations especially in deformed and soft osteogenesis imperfecta bone. This method ensures the desired direction of canal to maintain the NSA and avoids the piriformis fossa which might cause injury to important retinacular vessel to the femoral head in immature patientsWe would also like to highlight that in the second patient with osteogenesis imperfecta, the Rush rod was inserted in a retrograde manner through the knee joint. A retrograde entrance from the knee allows protection of the whole femur from the intercondylar notch where the hook of the Rush rod sits firmly, through the shaft till proximal penetration in the piriformis fossa. We think that it is worth taking the risk of causing joint stiffness with the benefit of reducing the risk of recurrent fracture in osteogenesis imperfecta patients. This patient did not develop any limitation of knee motion. However, the patient should still be warned regarding the possibility of joint stiffness and long term complications.Based on the experiences gained from these two cases, we are of the opinion that our modified method can be an alternative when an appropriately sized interlocking nail is not available for correction of coxa vara or shepherd’s crook deformity in abnormal bone.


Proteinuria is common in diabetic patients and usually reflects the presence of diabetic glomerulosclerosis. This paper reviews the differential diagnosis of proteinuria in diabetic patients and discusses the role of renal biopsy examination in identification and management of minimal change disease in this cohort. Identification of nondiabetic glomerular disease requires careful correlation of clinical history and renal biopsy findings and may have important implications for prognosis and therapy.


Ion mobility spectrometry was first introduced to the analytical community in 1970 as an ultratrace organic technique under the name of plasma chromatography. Using highly sensitive ionization methods commonly employed in electron capture detectors coupled with an atmospheric pressure drift region to separate ions produced, it had the potential for widespread application in the separation and detection of trace quantities of organics.As researchers began to investigate the method, a number of serious problems rapidly became evident: Competitive ion-molecule reactions which occurred in the ionization region of the detector limited its use as a quantitative instrument when complex mixtures were introduced into the spectrometer. Long residence times (sometimes measured in hours) in the spectrometer prevented practical application to a large number of samples. Often spectra for a single component were found to contain multiple ion peaks, hopelessly complicating true multicomponent interpretation.We designed and constructed an ion mobility spectrometer that was specifically suited for the detection of trace organics after separation by high resolution gas chromatography . Using aMore recently, our work has led to investigation of the mobility of ions produced from organic compounds with molecular weights higher than those that can be conveniently eluted from a gas chromatograph. One approach to achieve this goal has been to use supercritical fluid chromatography as the introduction method for IMS ,9. BesidNow that interfaces and operational modes for the ion mobility detector have been developed for both gas and supercritical fluid chromatography, the methodology is being investigated for application to real samples. The real challenge for ion mobility spectrometry as a chromatographic detector, however, lies in the detection of compounds separated by liquid chromatography. A significant step toward achieving this goal is the recent development of an electrospray ion source for IMS. By introducing the effluent from a liquid stream into the spectrometer via an electrically charged capillary, we have been able to capture ion mobility spectra from nonvolatile compounds dissolved in the mobile phase. The practical utility of this method of ionization is currently under investigation.


There is debate over the mechanisms that govern the orienting of attention. Some argue that the enhanced performance observed at a cued location is the result of increased perceptual sensitivity or preferential access to decision-making processes. It has also been suggested that these effects may be the result of trades in speed for accuracy on the part of the observers. In the present study, observers performed either an exogenous or an endogenous orienting of attention task under both normal instructions (respond as quickly and as accurately as possible) and speeded instructions that used a deadline procedure to limit the amount of time observers had to complete a choice reaction time (CRT) task. An examination of the speed-accuracy operating characteristics (SAOCs) yielded evidence against the notion that CRT precuing effects are due primarily to a tradeoff of accuracy for speed.


Severe corneal complications associated with the use of anti inflammatory drugs (NSAID) eye drops are known. We report the case of a patient of 57 years treated for rheumatoid arthritis with a central corneal perforation of the right eye following the use of indomethacin eye drops in the postoperative period following cataract surgery. The image shows a paracentral corneal perforation with iris prolaps. The course was favorable with improvement in visual acuity and complete healing of the corneal perforation after stoping indometacin and using of bandage contact lens. The anti inflammatory drugs should be avoided in cases of rheumatoid arthritis because they increase the risk of perforation. Indomethacin, like other molecules in the same therapeutic class should be used with caution in patients with general risk factors of suffering from ocular surface.


Human hantavirus disease cases, caused by Puumala virus (PUUV), are mainly recorded in western and southern areas of Germany. This bank vole reservoir survey confirmed PUUV presence in these regions but its absence in northern and eastern regions. PUUV occurrence is associated with the presence of the Western bank vole phylogroup. Myodes glareolus  causes most hantavirus disease cases in Central and Western Europe and is the only human pathogenic hantavirus in Fennoscandia  revealed 79 positive and 361 negative samples  Table. AIncluding results of previously published studies  Table. Acytochrome b PCR was performed and used for determination of the bank vole evolutionary lineages as described previously  according to manufacturer’s guidelines. The cytochromeb–based typing revealed the presence of the bank vole Western, Eastern, and Carpathian evolutionary lineages  is preferentially associated with the presence of the Western evolutionary lineage of the bank vole, but the virus was also detected in sympatric animals of the Eastern or Carpathian lineage. Future studies will have to determine if the current distribution of PUUV can be explained by the postglacial colonization of Germany by bank voles of the Western evolutionary lineage from western refugia through southern Germany (The observed limited geographic distribution of PUUV in bank voles has important implications for public health measures and development of early warning modules for hantavirus outbreaks. These public health measures of monitoring local bank voles for PUUV strains (Serologic and molecular Puumala virus detection in bank voles from Germany and bank vole evolutionary lineage, and Puumala virus phylogenetic tree reconstructed with novel and published partial small segment sequences.


Chemokines are a family of polypeptides that direct the migration of leukocytestoward a site of infection. They play a major role in autoimmune disease and chemokine receptors have recently been found to mediate HIV-1 fusion. In this short review we examine the role of chemokines in host defence and in the pathophysiology of autoimmune diseases. We conclude by discussing various therapeutic approaches that target chemokine receptors and that could be beneficial in disease.


To the editor,We read with interest the recent case of an unusual intravesical foreign body reported by Bansal et al. . A case The authors allude to the array of intravesical bodies that have been reported and mention the psychological reasons for self insertion . It shouThe important role of radiology in determining the luceny, location and size of foreign bodies is discussed and the preference for endoscopic management is mentioned . The incThe authors conclude by discussing urogenital fistulae as a consequence of foreign body insertion. Recent reports have highlighted the additional acute complication of urethral avulsion following polyembolokoilamania necessitating emergency urethroplasty .Finally, it should be acknowledged that not all cases of self embedding behaviour require intervention as some patients deliberately request no intervention  and repo


A retrospective detailed study of 272 cases of breast carcinoma treated by radical mastectomy was published by Hamlin (1968). An extended analysis of the material for 258 of these cases is now reported.Data for 21 prognostic factors from 258 patients have been subjected to multiple regression analysis to determine the independent effect and thus the relative importance of each factor. The findings confirm previous single factor analyses and demonstrate that nine of the factors are independently associated with survival.Mathematical manipulation of the information obtained in this analysis allowed a risk score to be allotted to each patient. Grouping of patients by the prediction scores is found in this series to be more closely related to survival than is clinical staging of the same patients.


A bioluminescence technique involving single photon imaging was used to quantify the spatial distribution of the metabolites ATP, glucose and lactate in cryosections of various solid tumours and normal tissue. Each section was covered with an enzyme cocktail linking the metabolite in question to luciferase with light emission proportional to the metabolite concentration. The photons emitted are imaged directly through a microscope and an imaging photon counting system. In some cases, good agreement was observed between the distribution of relatively high concentrations of ATP and glucose in viable cell regions of the periphery, while the reverse was seen in more necrotic tumour centres with comparatively high lactate levels. In general, lactate was distributed more diffusely over the sections while ATP was more highly localised and glucose assumed an intermediate pattern. In contrast to the large degree of heterogeneity seen in tumours, distribution patterns of metabolites were much more homogeneous in normal tissue, such as heart muscle. Mean values for metabolite levels in cryosections using bioluminescence are in good agreement with those obtained from the same tumour by conventional methods.


A single treatment of adult animals with the potent carcinogen NMU was known to induce tumours in a wide variety of organs, with the notable exception of liver. Administration of NMU after partial hepatectomy gave rise to the first liver cell adenomata ever observed in rats due to this carcinogen. The tumours were induced when NMU was given during the period of increased DNA synthesis but not when given early in the pre-replicative period. Although tumours were induced in other organs, the incidence of these did not correlate with the timing of NMU administration. It is suggested that replication of damaged DNA may be a relevant event in carcinogenesis.


Distress associated with attendance at a radiotherapy department was assessed in 80 consecutive patients. All patients were interviewed within 24 h of their first fraction of radiotherapy; 31 patients were also interviewed at the end of treatment. The problem identified at first interview as causing the most distress was worry about the effects of disease and its treatment upon the patient's family. At second interview the dominant complaint was of not being allowed to wash. Psychological problems, including anxiety and sleep disturbances, caused more overall distress than did physical symptoms. The method used in this study for eliciting information on the side-effects of therapy is straightforward and has yielded data that are provocative and suggest interesting avenues for further investigation.


A novel tumour system has been used to study the effect of natural killer cells on tumour growth by using agents which modify natural killer cell activity. The tumour cells are hybridoma cells which secrete antibody specific for red blood cells so that tumour growth can be quantitated by a haemolytic plaque assay. Spleen-seeking variants have been derived from original hybrids which are sensitive to natural killer cells. Treatment of mice with polyinosinic-polycytidylic acid substantially enhanced natural killer cell activity and correlated closely with a reduction in the growth of the hybridoma tumour cells in the spleen and life extension. Conversely, a single injection of anti-asialo GM, antibody resulted in a substantial increase in the number of plaque forming splenic tumour cells and virtual elimination of natural killer cell activity. These data demonstrate the important role of natural killer cells in constraining the growth of a tumour of B cell origin and establishes the usefulness of this tumour model in studying the biology of effects on tumour growth.


An audit was carried out of 51 oncology patients referred to a clinical psychology service to identify the characteristics of patients selected for referral and to assess change following psychological intervention. A survey was conducted of an unselected sample of oncology patients representative of the workload of the oncology department from which the referrals came, to determine the prevalence of comparable psychosocial problems among patients who were not referred for help and to assess whether doctors were aware of the problems patients reported. Data were collected using the Hospital Anxiety and Depression (HAD) and Mental Adjustment to Cancer (MAC) scales and a problem checklist devised for this study. Referred patients were significantly more anxious and depressed (P < 0.001) and showed poorer adjustment on MAC scales than the surveyed sample, but 30% of the latter group warranted assessment for anxiety and 23% for depression. The number of psychosocial problems of their severity. Intervention was clinically significant mood disorder irrespective of the specific problems of their severity. Intervention was associated with a significant improvement in distress and problems for referred patients by the time of discharge. Psychosocial problems were often undetected by staff even in referred patients. The checklist is a feasible screening method for potentially remediable problems which are cumulatively a significant contributor to cancer patients' distress.


Across the pharmaceutical industry, there are a variety of approaches to laboratory automation for high throughput screening. At Sphinx Pharmaceuticals, the principles of industrial engineering have been applied to systematically identify and develop those automated solutions that provide the greatest value to the scientists engaged in lead generation.


Drosophila species Dobzhansky and Sturtevant provided the first view of the molecular basis of species identity in their 1938 seminal study classifying the chromosome rearrangements that distinguish two PLoS Genetics, Lucia Carbone et al. Nomascus leucogenys leucogenys) to address a fascinating problem in evolutionary biology: why are some groups of organisms characterized by a high frequency of chromosome change while others are karyotypically stable?The view that has emerged over the last decade, with a sharp acceleration since the publication of the human genome sequence, is of a fluid genomic landscape that is dotted with evidence of both large- and fine-scale chromosome rearrangements. What has remained a mystery are the mechanisms responsible for chromosome rearrangements that karyotypically define species. In this issue of Gibbons are members of the Hominoidea superfamily, which includes humans and great apes, but they are unique among Hominoidea, and indeed rare among mammals, in having experienced an extraordinarily high rate of karyotypic change Building on their previous work defining the synteny map for the northern white-cheeked gibbon with respect to its human cousin, these authors used a comparative genomics approach to analyze sequences spanning breaks of synteny for repeat distribution and genomic signatures that would lend some insight into the mechanism of interchromosomal rearrangement. Corroborating data from other studies on a smaller set of gibbon breakpoints Rather than simply quantifying the repeat classes at the gibbon-specific breaks of synteny, Carbone et al. took this study one step further by asking whether the epigenetic signatures of specific repeat classes may be an important distinguishing feature in highly divergent genomes. Previous work has shown that gibbon Alu elements are more active than their human counterparts The epigenetic alteration of genomic sequences by DNA methylation is appreciated as a major regulatory force in the evolution of genome structure and expression, and is known as a potent regulator of mobile DNA activity. Through bisulfite sequence analysis, the authors show that the gibbon Alus are undermethylated compared to their human orthologues. The authors suggest these epigenetic differences between human and gibbon as a possible mechanism to account for the disparity in the number of chromosome rearrangements between the gibbons and old world primates.The proposal that mobile DNA itself participates in DNA rearrangement is not new to biology. Mobile elements, such as transposons and retrotransposons, were first implicated in DNA rearrangements in studies of maize by McClintock The novelty in this study is that there is hypomethylation of the gibbon Alus at evolutionary breakpoints, and thus the epigenetic architecture of these regions may have facilitated the rearrangements in the gibbon karyotype. The lower levels of methylation in these repeats may lead to an open chromatin configuration that increases the opportunity for double-strand breakage and repair mechanisms such as intrachromosomal non-allelic homologous recombination and non-homologous end joining . HoweverMcClintock first implicated transposable elements in the speciation process when she stated that “species crosses are…a potent source of genomic modification” and that “major restructuring of chromosome components may arise in a hybrid” Exciting advances in sequencing technology will now afford full genome-scale methylation studies  that can offer insight into the diversity of elements that may be differentially methylated between gibbons and humans, and whether Alus are the sole target. Additionally, testing for a similar association between mobile DNA and methylation state at breaks of synteny in other species groups that have experienced rapid karyotypic change  are exciting areas of future work that may finally shed light on the mechanisms responsible for the chromosome diversity observed in a broad range of species.


Corresponding dose-effect curves obtained for growth of the primary tumour (Pr) and its metastases in unirradiated tissues showed that local irradiation of Pr caused an exponential decrease in growth of metastases due to any dissemination occurring after irradiation, but was also responsible for stimulating growth of metastases already established before treatment in lymph nodes and in lungs. This stimulating effect was most marked when Pr was larger at the time of treatment and when high doses were given to eradicate Pr. This effect is attributed to the liberation of growth stimulating substances (GSS) from a pool of GSS produced in the irradiated Pr by sterilized, but metabolically active and growing tumour cells (HR cells). This effect of HR cells on tumour growth and metastases was also demonstrated when rats were inoculated with viable tumour cells and subsequently treated by injecting large doses of HR cells prepared The systemic effects of GSS on metastases were most clearly seen after immunosuppression of recipient hosts by sublethal whole body irradiation, since immunosurveillance in unirradiated rats resulting from a rapidly developing allogenic tumour-host incompatibility caused marked reductions in clonogenicity of the tumour which tended to overshadow the GSS effect. The latter was also masked in immunosuppressed hosts when excessively high rates of dissemination were due to growth of large Pr inocula for sufficiently long to “saturate” the capacity for growth of metastatic tumour in lymph nodes and lungs.The relevance of these findings to clinical radiotherapy is discussed.


Immunofluorescent tracing by rabbit antiserum with specific reactivity against intestinal mucosa revealed cross-reaction with human ovarian mucinous cystadenoma epithelium and not with epithelium of any of several other human mucous epithelia. The mucinous cystadenoma epithelium apparently contains at least one but not all of the specific intestinal mucosal antigens. The findings support the view that such tumours are histogenetically of intestinal type, as might occur for example by unilateral intestinal development of a teratoma.


Since PLA2 carry out their catalytic function at membrane surfaces, the kinetics of these enzymes depends on what the enzyme ‘sees’ at the interface, and thus the observed rate is profoundly influenced by the organization and dynamics of the lipidwater interface . In this review we elaborate the advantages of monitoring interfacial catalysis in the scooting mode, that is, under the conditions where the enzyme remains bound to vesicles for several thousand catalytic turnover cycles. Such a highly processive catalytic turnover in the scooting mode is useful for a rigorous and quantitative characterization of the kinetics of interfacial catalysis. This analysis is now extended to provide insights into designing strategy for PLA2 assays and screens for their inhibitors.Several cellular processes are regulated by interfacial catalysis on biomembrane surfaces. Phospholipases A


This is my third year working for the Kuru Research Project and I have been assigned to take charge of the fieldwork. Our fieldwork is based in Waisa village and we have nine field patrol officers who make five teams for kuru surveillance right around the four corners of Okapa District. There are two technical officers based in the field transcribing interview tapes recorded by Jerome Whitfield, Sena Anua and myself.five suspected kuru patients have ‘recovered’ and are well;five suspected kuru patients are still sick with no change of symptoms and are diagnosed as not having kuru; andfour suspected kuru patients have died from other disease.One patient, a man aged 62 years, died of kuru in March 2005. There were 14 suspected cases of kuru from January 2005 to September 2007:Arrange field patrols for kuru surveillance of villages in remote parts of the kuru-affected region every quarter and prepare a report.Assist Jerome Whitfield in conducting interviews on the cultural and mortuary practices of the Atigina and Pamusagina people.Diagnose and film suspected kuru patients and compile reports for Jerome and Michael Alpers.Check and regularly report on the sickness status of suspected kuru patients.Transcribe recorded tapes from the Fore language into English.The other responsibilities in the field are:


In comparison with normal controls the number of colony forming cells (CFC) is moderately increased (about three-fold) in the bone marrow and enormously increased in the peripheral blood of untreated patients. In the peripheral blood their number in general is related to the total leucocyte count. In patients whose blood counts have been restored to normal by the use of cytotoxic drugs the number of CFC in the peripheral blood is very greatly reduced. In the marrow of treated patients CFC are present in approximately normal numbers. When used as feeder layer sto support the culture of normal bone marrow cells, the peripheral blood leucocytes of untreated patients are a uniformly poor source of colony stimulating factor (CSF) and fractionation experiments suggest that this is not due merely to a relative scarcity of monocytes. After treatment the peripheral blood has normal CSF activity and this is associated with the monocytic cell component. The last data may be explained in either of two ways: it is possible that restoration of the blood of patients with CGL to normal values removes a homeostatic factor suppressing the formation of CSF by functionally normal monocytes, or alternatively treatment with cytotoxic drugs leads to the replacement of defective monocytes by a population of relatively normal CSF producing cells.We have used the technique of human haemopoietic cell culture in agar to study the peripheral blood and bone marrow colony forming capacity of 23 patients with Ph


The VX2 carcinoma has been used extensively as an experimental model for different aspects of tumour behaviour and is usually maintained by serial intramuscular injections of tumour cells. The tumour grows rapidly, infiltrating between muscle bundles into the fibrous tissue replacing ischaemic muscle and into the vascular tree. The most interesting method of spread occurs within the sarcolemma and this may be responsible for the rounded cell nests described in this tumour.


Sir,Intravenous drug therapy is the corner stone of patient management in today’s hospital practice and the discipline of pediatrics is no exception. The drug dosage in pediatrics is usually calculated according to the body weight or surface area leading to less cumulative dose when compared to adults. Unfortunately there are no separate pediatric drug dose formulations for most of the commonly used drugs. It is a Intravenous drug dosage for pediatric use is often limited by the strength of the drugs available commercially, especially in developing countries. Most druSince in developing countries like India where sepsis is the leading cause of mortality necessitating the use of antibiotics, it is high time the medical fraternity realizes this potential lacuna in treating pediatric patients. We feel that the pharmaceutical majors should realize the urgent need to introduce commonly used drugs, especially life-saving medicines in doses suitable for pediatric use so that the basic right of every child to receive safe medication is not jeopardized.


We show that, from the earliest morphologically recognisable stages of development, mouse skin papillomas induced by a chemical initiation-promotion regime are polyclonal. We have demonstrated polyclonality directly by immunohistochemical staining of the mosaic cell populations in embryo aggregation chimaeras, a method which removes some of the uncertainties of previous conclusions based on analysis using electrophoretic polymorphisms. The findings may imply that initiation within a single cell and promotion of its clonal descendents is not a sufficient explanation for the origin of these tumours and that interaction between cells of more than one clone is involved.


Current data from in vitro and in vivo animal models indicate that fibronectin-binding integrin receptors expressed by colon cancer cells may regulate tumour growth. While individual members of the beta 1 subfamily of integrins have now been clearly identified in colorectal cancer, little information exists with respect to the alpha V subfamily. In the present study we show that alpha V can associate with multiple and different beta subunits capable of binding fibronectin in this tumour type. This is likely to have functional implications for growth and spread of colorectal cancer.


Adrenocortical activity has been assessed in patients with inoperable carcinoma of the bronchus or with disseminated malignant disease of other organs. The mean basal plasma cortisol level was higher in the former than in the latter and both were higher than the controls. Each had abnormally high midnight levels, particularly those with oat cell carcinoma of the bronchus. After the administration of a single dose of dexamethasone both groups suppressed poorly compared with the controls. Failure to suppress was associated with a poor prognosis.


The method of measuring changes in the structuredness of cytoplasmic matrix (SCM) in single cells is described. Data on SCM distributions and fractions of human lymphocyte populations which respond to stimulations with PHA and CaBP in healthy donors and patients with malignant disorders are presented.


It has been shown that lymphocytes isolated from the peripheral blood of patients with chronic lymphocytic leukaemia do not modify the mustard group of chlorambucil, as has been demonstrated previously in Yoshida ascites cells. However, lymphocytes from patients with an unsatisfactory clinical course or poor response to treatment were able to modify the aromatic region of the drug molecule; little change occurred in the aromatic absorption of intracellular chlorambucil in patients who responded to treatment. This simple test may provide a rapid assessment of a patient's potential response to chemotherapy.


The liver is morphologically and functionally modulated by sex hormones. Long-term use of oralcontraceptives and androgenic steroids can induce benign and malignant hepatocellular tumors.Hepatocellular carcinoma (HCC) is more prevalent in men than in women. The role of sex hormonesand their receptors in the development of HCC was reviewed. Some HCCs may be androgen dependentbut others may be estrogen or even both dependent. Further studies are mandatory in order to utilizesuch characteristics of HCC for an effective prophylaxis and therapy of this tumor.


We investigated cases of shigellosis in San Francisco and Alameda Counties identified during 1996 by active laboratory surveillance to assess the role of HIV infection as a risk factor for shigellosis. Dramatically elevated rates of shigellosis in HIV-infected persons implicate HIV infection as an important risk factor for shigellosis in San Francisco.


This study was completed as part of a project for the Quality Assurance Agency on the enhancement theme of 'Research teaching linkages: enhancing graduate attributes' in the disciplines of Medicine, Dentistry and Veterinary Medicine. The aims of this investigation were to elucidate a list of desirable research related graduate attributes for the disciplines of Medicine, Dentistry and Veterinary Medicine and provide evidence as to how they could be covered within such curricula.Semi structured interviews, symposium breakout sessions and conference workshops were used to define and rank attributes suggested by curricula design experts from the three disciplines. Students graduating from a BSc Medical Science degree program were surveyed to determine how well they felt the curriculum and associated final year project equipped them with the identified attributes.A list of seven high level attributes which were desirable in graduates wishing to pursue either a professional or research career were identified. 105 students reported that a final year project was particularly effective at developing an understanding of the need to have an inquiring mind and critical appraisal skills whilst other components of their degree course covered team working skills, core knowledge and an understanding of ethics and governance.This study identified desirable attributes from graduates from medical, dental and veterinary degree programs and provides evidence to support the case for student projects helping to achieve both clinical and research related graduate attributes in medical undergraduates. The project also provides a focus for debate amongst those involved in curriculum design as to whether the attributes identified are those desirable in their graduates and to examine their current curriculum to determine coverage. The study reported here was part of a project funded by the Quality Assurance Agency (QAA) Scotland Enhancement theme programme investigating 'Research teaching linkages: enhancing graduate attributes' in the disciplines of Medicine, Dentistry and Veterinary Medicine . One comThere has been debate regarding the shortfall in graduates from professional degrees who opt to include research in their career plans. The Selborne Report raised concerns over the future of Veterinary Medicine research , whilst Professional attributes should already be covered within the curriculum as required by the governing bodies the General Medical Council (GMC) , the GenAlso of interest is the opinion of students graduating from such professional/vocational programs as to whether the courses do cover the attributes discovered. The BSc in Medical Sciences at St Andrews is a three year Honours degree program, after which graduates move on to their clinical years at other Medical Schools. The program itself is designed to provide 'an excellent scientific foundation for clinical practice'  and therThe first aim of this study was to identify what research related graduate attributes were desirable in graduates from Medical, Dental or Veterinary degrees. A secondary aim was to determine whether such research related attributes can be covered in a curriculum whose content is governed by regulating bodies. The third and final aim was to investigate student opinion as to whether a course designed to provide a scientific foundation in Medicine would equip graduates with the identified attributes.Semi structured interviews were carried out with key staff members responsible for curriculum design from all Medicine, Dentistry and Veterinary Medicine schools in Scotland. Interviewees were purposively selected as being involved with curriculum design within their school. Further interviews were carried out with selected staff from English schools. These schools  were selected to provide a wide range of views from different teaching and learning environments. The interview was structured around the Quality Assurance Agency enhancement theme 'Research-Teaching Linkages: enhancing graduate attributes' aims, and was piloted with two participants from different Medical schools, after which minor revisions were made.A total of 24 interviews were completed, either in person or over the telephone. Sampling was concluded once all Scottish schools and the selected English school representatives were interviewed. Interviews were recorded and transcribed. Of interest to this study was the question: 'Can you name 10 key research attributes that graduates from your course should have?'Qualitative analysis of the transcripts was carried out using a grounded theory approach . Two of Quote 1: 'Asking questions, as in a method of learning an enquiring mind'Quote 2: 'Encouraging aspects of the personal and professional behaviour such as being interested in a problem enough to try and find out more about it'Delegates (n = 58) at the symposium 'Research Teaching Linkages in the disciplines of Medicine, Dentistry and Veterinary Medicine',  discussed the list of attributes during small group breakout sessions. Group composition was balanced to ensure they contained representatives from each discipline. Using a variation of nominal group technique, participants were asked to discuss and define the predefined list of attributes and rank them in order of preference from a professional standpoint and then again from a research standpoint. Groups were invited to discard any attributes they thought were not vital. During collation of the results from all groups, attributes ranked by less than three out of the five groups at the symposium were discarded. Attributes that were deemed vital by three or more groups at the symposium had their average ranks calculated. This provided a final list of attributes, the definitions of which were provided by the groups. The definitions were further refined at a QAA Enhancement Themes conference  workshop aimed at the three disciplines.Final year students (n = 104) of the BSc Medical Sciences degree program at the University of St Andrews were asked to complete a questionnaire to evaluate the course as part of the curriculum review process. The part of the questionnaire relevant to this study focussed on how well equipped they felt with the graduate attributes defined previously in the study. For example questions asked whether completion of either the degree program or the final year project module had given them 'an understanding of the evidence base for practice', or 'has made you aware of the need for an inquiring mind' (1 = agree - 5 = disagree).The data was investigated for normality and statistical analysis was carried out using appropriate tests in SPSS v 14.Ethical approval was granted by the Bute Medical School Ethics Committee.Interviews with 24 staff members from Medical, Dental and Veterinary schools yielded 122 graduate attributes, an average of five per interviewee. There were no differences between the three disciplines in terms of the attributes suggested by faculty members. Qualitative analysis (described above) of the interview transcripts resulted in 16 higher level attributes.Discussion at the Research Teaching Linkages symposium breakout sessions resulted in nine attributes being thought to be vital for a professional career and 10 for a research career. Table As can be seen from Table Response rate of the student questionnaire was 100%. Table Degree program average scores for all attributes were significantly higher than 2, which would be a 'neutral' response . The final year project was also thought to equip students well with all attributes, apart from team working where the average score was lower than neutral .It can be seen from Table Interviews with faculty members with responsibility for curriculum design from all three disciplines and ranking by further experts in the area resulted in two lists of attributes, one desirable in a graduate pursuing a professional career, the second in a graduate pursuing a research career. The definitions agreed in the study Table  provide Interestingly the top seven attributes in both lists were the same, although not ranked in exactly the same order of preference. This suggests that such graduate attributes are high level skills which would be applicable to both research and professional situations. This finding has implications for curricula design in Medical, Dental and Veterinary degree programs. Curricula in all three disciplines are prescribed by guidelines issued by the governing bodies, the GMC , GDC 5]5] and RCA BSc program in Medical Sciences may not have precisely the same aims as the standard five year MBChB and this is one limitation of this study, as graduates may have a slightly different focus in their careers. The course at the University of St Andrews provides the basis for entrance to the third year of an MBChB course, but also attempts to deliver an understanding of the scientific basis of Medicine and therefore should be equipping its graduates with the research related attributes determined in the previous part of the study. The results show that the final year students considered that the degree program as a whole, did provide them with the opportunity to develop all of the top seven attributes identified in this project as being common to both professional and research careers. The final year project component of the course was viewed as being particularly effective at equipping students with the ability to understand the importance of having an inquiring mind and developing their critical appraisal skills. Similar outcomes for research projects were shown in a qualitative study in science undergraduates and their faculty advisors by Seymour et al . They noOther limitations of this study include the sample of interviewees, which included individuals from all Scottish Medical, Dental and Veterinary schools and a selected sample from English schools. The English schools were selected for participation on the basis of achieving representatives from a wide range of curriculum types although it is not an exhaustive sample. We acknowledge that this may have impacted on the views that were obtained.Data analysis employed both qualitative and quantitative methods. The development of the list of refined attributes from the interview suggestions utilised NVivo software which may have affected coding and clustering of data and therefore the emerging themes. The process was however carried out by two authors (AL and JS) who achieved consensus.This study is timely as the Higher education sector becomes ever more globalised. Many Veterinary schools in the UK comply with European Association of Establishments for Veterinary Education curriculum guidelines . The TunCurriculum designers in Medicine, Dentistry and Veterinary Medicine can utilise the seven graduate attributes identified in this study as a means of ensuring that they produce graduates who are equally well equipped for either a professional or research career. By mapping these core attributes to current learning activities they can ensure that there are opportunities within their curriculum for students to develop and practice these skills. The definitions of these attributes will allow a focus for discussion on the opportunities available within the different curricula.Results of the student study confirmed the belief that involving students in a research project was an excellent way to equip them with many of the identified attributes. Students completing a BSc Medical Sciences reported that the final year project was particularly effective in developing an inquiring mind and the skills of critical appraisal.The authors declare that they have no competing interests.AL was a member of the original project team, carried out interviews, facilitated symposium breakout sessions and drafted this article. SG derived the initial QAA project proposal and recently presented some of the results of the project at the AMEE conference, Prague. JS was project director of the original QAA project, carried out interviews, facilitated symposium breakout sessions and commented on drafts of this article. All authors read and approved the manuscript.The pre-publication history for this paper can be accessed here:


An expert working group of the European Association for Palliative Care has revised and updated its guidelines on the use of morphine in the management of cancer pain. The revised recommendations presented here give guidance on the use of morphine and the alternative strong opioid analgesics which have been introduced in many parts of the world in recent years. Practical strategies for dealing with difficult situations are described presenting a consensus view where supporting evidence is lacking. The strength of the evidence on which each recommendation is based is indicated. © 2001 Cancer Research Campaign


To determine diagnostic value of magnetic resonance urography in cases of duplex renal system.Twenty cases between five month to nine years with suspected or known duplex renal system were evaluated by ultrasound (USG), micturating cystourethrography (MCU), intravenous urography (IVU) and magnetic resonance urography (MRU). The findings of these diagnostic imaging studies were then compared with each other and against the results of final diagnosis established at surgery.Duplex renal system could be identified in two of these cases on USG, was diagnosed in four in IVU and could be diagnosed in all cases with MRU.MRU is superior and far accurate than IVU, MCU and USG in diagnosing duplex renal system. Conventional radiological investigations are commonly being used for the diagnosis of duplex renal system. However, each of them has limitations and hence multimodality workup is required in their evaluation.It may be possible to avoid it with its associated cost, if similar information were available from a single imaging modality which will reduce the time and will give better diagnosis using magnetic resonance urography (MRU) for its diagnosis. This article describes our initial experience using MRU for the diagnosis of duplex renal system and comparing its findings with other conventional radiological investigations.et al.[The concept of MRU has been introduced since 1986 by Henning et al. and is bThe purpose of the study was to confirm the efficacy of MRU and comparing its findings with other radiological investigations.This was a prospective study done over a period of one year from 2006 to 2007. At the outset of the study the patients with diagnosed or suspected duplex renal anomalies on routine radiological investigations or those not picked on conventional investigations as intravenous urography (IVU), micturating cystourethrography (MCU), ultrasound (USG) and nuclear scintigraphy and having persitant urogical symptoms underwent MRU using gadolinium contrast after obtaining proper consent for the procedure. IVU, MCU were performed using standard protocols of the procedure and USG was done in all the cases. Nuclear scintigraphy study was done using technetium T99 labeled diethylenetriaminopentaacetic acid (DTPA) and dimercaptosuccinic acid (DMSA) with lasix at 10 min of study.MRU was done using heavily T2-weighted images, contrast enhanced T1-weighted MR sequences and maximum intensity projection (MIP) after proper hydration in 1.5T MR scanner imaging.Very young and uncooperative patients were given oral sedation. These patients were given as per body weight to maintain proper hydration. Intravenous gadolinium contrast was used for the study for image acquisition using abdominal or body coil, with patient in supine position and coil positioned over upper abdomen and centered on kidneys. After initial localizing images were obtained in the following sequences:T2 HASTE single sliceT2 HASTE multislice3D GRE T1TRUFI 2DFL2D 80TSE FS T2Post contrast images in T1 sequences were obtained.Total twenty cases were subjected for MRU after they were either diagnosed to have duplex on conventional radiological investigations or were suspected to be having duplex renal system and routine radiological investigations failed to pick the condition.USG was suspicious in two cases and IVU showed four cases to be having duplex renal system including these two cases. MRU successfully picked up duplex moiety in either of the side in all of these patients. Fourteen were female patients and rests were male. Three patients had bilateral duplex renal system. Ten patients underwent upper pole heminephrectomy for nonfunctioning upper moiety. One patient had both the moieties functioning and hence underwent upper pole ureteric reimplantation for the refluxing moiety. Two patients had pathological single unit on one side and normally functioning duplex unit on the other side and underwent nephrectomty of the pathological single unit of the opposite side. Two patients are under regular follow up and are asymptomatic and on chemoprophylaxis and doing well and two patients did not turn up for further follow up. One patient had unilateral duplex with ureterocele of the upper mioty which was normally functioning and incision of uereterocele was done. We compared the sensitivity and specificity of the IVU and MRU in the diagnosis of the duplex system and compared it with operative findings. MRU showed the sensitivity and specificity of 100% as compared to only forty percent sensitivity of the IVU. But specificity of IVU was 100% here.Duplication is the most common congenital anomaly in the urinary tract, a 0.7% incidence in one series. During iMCU can diagnose associated refluxing unit in cases of duplex moity and ureterocele however as a single investigation cannot diagnose duplex system.IVU which is considered as a standard investigation for morphological assessment of renal parenchyma fails to identify nonfunctioning upper moieties of duplex system.Abnormal alignment of upper pole calices of lower moity because of pressure effect of dysplastic upper moity can be seen on IVU which may give clue to the diagnosis.Renal scintigraphy is necessary to know the differential functional status of the duplex moieties which influences the treatment. It however gives poor anatomical delineation.et al. described the concept of computed tomographic urography (CTU) as a diagnostic method in renal diseases. Multislice computed tomography (CT) with contrast and 3D reconstruction also gives excellent anatomical details but has high radiation exposure and risk of allergy to the contrast.[In 1996, Pearlman We found that, MR urography as a single investigation gives excellent anatomical description of the duplex renal moieties even when they are nonfunctioning. MRU is a noninvasive examination method that does not entail ionizing radiations and does not require iodinated contrast as in IVU or CTU and safer in children. It is excellent in identifying nonfunctioning or poorly functioning duplex system.The heavily weighted T2 images best pick up the dilated non functioning moieties using static fluid as hyperintence images . This teBut there are studies where this is calculated and found to be almost 99% sensitive and more than ninety five percent specific for the diagnosis of the duplex renal system.6We attribute the reasons for failure of IVU to diagnose the duplex system where operative intervention was not required to presence of ectopic moity superimposed on the bony structures and could not be seen in IVU in three cases, borderline functioning in these same cases, poor patient preparation in another two cases and where the pressure from the dilated lower moity was obstructing the drainage as well as compromising the perfusion of the duplex moity and hence was appearing like non functioning moity on IVU. In one case, the anatomical arrangement of the calyses was so close to each other that on IVU they resembled as calyses of the single unit and misinterpreted by the radiologist and only MRU could detect the duplex in this.It is obvious that conventional radiology cannot singly pick up duplex renal anomaly and hence there is no single gold standard conventional investigation for its diagnosis and here the role of MRU appears to be superior to all conventional investigations and also gives better anatomical and functional accuracy in diagnosing duplex system which surpasses its disadvantages of cost, time, and need of sedation for the procedure.591059Moreover, the time of examination for MRU is lesser than for scintigraphy done for quantification of function.In our cases, MRU successfully picked up duplex renal system and in the cases where operative intervention was required, also helped in deciding the plan of management which was not possible by conventional investigations.In our initial experience, MRU may become the single investigative modality compared to other conventional radiological investigations in cases of duplex renal system.–14


The possibilities of clustering between those electoral wards which display higher than expected incidences of cases of the lymphomas occurring between 1978 and 1982 are examined. Clusters are defined as being those wards with cases in excess (at a probability of less than 10%) which are geographically adjacent to each other. A separate analysis extends the definition of cluster to include high incidence wards that are adjacent or separated by one other ward. The results indicate that many high incidence lymphoma wards do occur close together and when computer simulations are used to compute expected results, many of the observed results are shown to be highly improbable both in the overall number of clustering wards and in the largest number of wards comprising a 'cluster'.


Sir,The only study to assess prevalence of dementia in elderly in Sri Lanka has reported a prevalence of 3.98% in a semi urban population. There isWe conducted a preliminary study to assess cognitive impairment and depression in a sample of geriatric patients presenting to the University Medical Unit of the National Hospital of Sri Lanka . This prospective study included all patients over 65 years, who were admitted over four weeks. The Mini Mental State Examination  and the geriatric depression scale (GDS) were used to screen for cognitive impairment and depression respectively.P>0.05).. The percentages of gender and ethnicity did not differ significantly from the population average (P>0.05).We also assessed the impact of educational level and social support on cognitive impairment with a statistical model. It was hypothesized that better education and family support will protect against cognitive impairment. However (holding age and gender constant), the cognitive impairment did not correlate with either factor, alone or in combination  and cognitive impairment (>50%) was very highThe assumption that better education and family support leads to less cognitive impairment could not be validatedThe symptoms of depression may be due to illness itself. Yet it underscores the lack of psychiatric input in medical wards as none of these patients were referred to a psychiatrist. The second observation may be due to:Errors in variables that defined family support (frequency of visits by relations and living with family), which may not indicate coherent family functioningPathology of dementiaDepressive pseudo dementiaSampling errorsThe findings of this preliminary study are significant and indicate theImportance of improving mental health among geriatric patientsNeed for coordinating psychiatric and medical care to reduce disease burdenNeed for routine screening of elderly patients for cognitive impairmentNeed for a large multi center hospital-based study to assess the interaction of socioeconomic factors, depression, dementia and disease burden


The evolution and structure of adenomatous polyps and adenocarcinomata of the colon in NMRI mice induced by dimethylhydrazine are described. Severe toxic reactions in the liver and other organs are produced by dimethylhydrazine (DMH), but tumours are induced only in the colon and around the anus. The 100% incidence and growth characteristics of the tumours make it potentially a good model system, but investigators should take into account the widespread nonspecific cellular injury induced by this carcinogen.


The weights of mouse sarcoma 180 differed according to the varieties of mouse. In two varieties in which both sexes were studied the tumour weights were lower in females. In three varieties the tumours weighed less at lower environmental temperatures than at higher ones. At three environmental temperatures in the physiological range the surfaces were cooler than the adjacent skin, and the tissues of tumours were cooler than the surrounding subcutaneous tissues. These differences were greater in cooler than in warmer environments and increased as tumours grew larger. There were no histological changes to account for the different tumour weights at different environmental temperatures and it seems probable that tumours are unable to maintain their temperature and their metabolism in cool environments. In mice of the same breed kept at room temperature the smallest animals had the largest tumours in a weight range of 18-28 g.


This study has examined cells from naturally-occurring murine mammary tumours to ascertain whether cell surface glycoproteins play a significant role in colonisation of the lungs after intravenous inoculation. It was found that gel electrophoretic analysis of membrane extracts and lectin adsorption studies did not reveal any consistent differences in glycoprotein composition of cells from tumours which can heavily colonise the lungs relative to ones from tumours which cannot do so or to cells from pulmonary metastases. Also, alteration of structural and functional properties of surface glycoproteins by treatment with succinylated lectins or with drugs such as tunicamycin and swainsonine, which inhibit glycosylation of membrane proteins, had no specific effects on metastatic colonisation of the lungs. Tunicamycin apparently decreased capability to form experimental metastases but also diminished tumourigenicity on subcutaneous inoculation, although it did not affect tumour cell viability in vitro. This information supports earlier studies from this laboratory involving enzymic digestion of the surface of living tumour cells before inoculation and demonstrates that the pulmonary colonisation capability of these mammary tumour cells can withstand global disorganisation of membrane glycoprotein structure and composition. This implies that either the surface glycoproteins are not important in the colonisation process, or that these tumour cells have great capability for rapid repair of their surfaces. It is concluded that a clear answer to whether surface glycoprotein composition has a decisive role in pulmonary colonisation by these mammary tumour cells requires introduction of stable heritable traits into tumour cell populations by genetic manipulation.


High throughput screening has significantly contributed to advances in drug discovery. The great increase in the number of samples screened has been accompanied by increases in costs and in the data required for the investigated compounds. High throughput profiling addresses the issues of compound selectivity and specificity. It combines conventional screening with data mining technologies to give a full set of data, enabling development candidates to be more fully compared.


The discovery of effective cancer treatments is a key goal for pharmaceutical companies. However, the current costs of bringing a cancer drug to the market in the USA is now estimated at $1 billion per FDA approved drug, with many months of research at the bench and costly clinical trials. A growing number of papers highlight the use of data mining tools to determine associations between drugs, genes or protein targets, and possible mechanism of actions or therapeutic efficacy which could be harnessed to provide information that can refine or direct new clinical cancer studies and lower costs. This report reviews the paper by R.J. Epstein, which illustrates the potential of text mining using Boolean parameters in cancer drug discovery, and other studies which use alternative data mining approaches to aid cancer research. The discovery of effective treatments for cancer represents a key goal for pharmaceutical companies who wish to identify drugs that can prolong survival time and even reverse cancers, while having an acceptable toxicity profile. However, the average cost of bringing a drug to the commercial market in the USA is now estimated at $1 billion per FDA approved drug, and many factors have compounded the expense of these developments such that cancer drug discovery is now both extremely slow and costly even for a potential blockbuster. Among the many factors contributing to the cost are the high price of clinical trial organisation and the bench research hours required to validate the efficacies and toxicities associated with a drug despite the use of time saving technologies such as high throughput screening to determine efficacies and genomic analyses of drug effects. A growing number of papers highlight the use of data mining tools to determine associations between drugs, genes or protein targets, and possible mechanism of actions or therapeutic efficacy which could be harnessed to provide information that can refine or direct new clinical cancer studies.One common method of data mining is referred to as text mining. Richard EpsteinEpstein also provides examples of how text mining can determine associations between types of cancers and a particular gene for example, AKT.5However, there are a few known limitations to text mining. Associations are based on the use of constant terminology for a drug or gene, whereas this may not be the case for example, where drug names are changed by companies. Also there is restricted access to full text journals and also restriction to abstract publications and some chemical and physical science journals in databases such as pubmed so that data associations need to be retrieved from a more limited source of overall citations. Text mining may therefore be better utilized by combining it with other data mining tools such as microarray database mining. This uses microarray gene data from experiments which have analysed genomes or sets of genes of particular cells or tissues.The power of data mining has now been harnessed by a growing industry specialising in the production of databases which can utilise text or gene or protein data. A selection of databases with direct application to cancer drug or target molecule discovery are presented in The tools that these databases provide for both the drug industry and academia can maximise the mining process compared to manual mining techniques. Whereas data mining has not yet resulted in blockbuster discovery on its own merit, the use of this technology harnessed with the power of dedicated databases and bench top research, has already contributed to deciphering mechanisms of action of genes and drugs and should allow a much more rapid progress toward discovery of effective cancer therapies in the future.


Objective: The purpose of this study was to evaluate the possible association between Lewis phenotype status in pregnant women and preterm labor (PTL) or preterm rupture of the membranes (PROM).Methods: Red blood cell (RBC) Lewis phenotype was determined in 113 pregnant women admitted for PTL or PROM and in 121 controls. The results were controlled for the influence of race on Lewis phenotype.Results: Pregnancy was associated with a higher frequency in women with the a–b– phenotype. There was no association between RBC Lewis phenotype and the occurrence of PTL or PROM.Conclusions: A susceptibility to PTL or PROM is not due to a lack of Lewis antigen expression onthe plasma membrane of the vaginal mucosa.


Two cases are described, one with proven lymphosarcoma and doubtful autoimmune disease, and the second with the reverse situation, in which circulating abnormal mononuclear cells showed PHA responsiveness and an abnormal chromosomal constitution . These findings are discussed in the light of previous cytogenetic studies of lymphoreticular neoplasia and autoimmune disease and the relationship between these two conditions.


The system could be adapted to the clinical determination of oestrogen receptor content in biopsy material from mammary and endometrial tumours and would be of value in predicting hormone dependency.A thin-layer gel filtration system for the assay of oestrogen receptors in target organ tissue samples as small as 50 mg is presented and compared with the sucrose gradient centrifugation method. Only specific high-affinity binding of [


The exact cause of liver failure occurring after long standing biliary obstruction is not known.Impairment of hepatic mitochondrial respiration was postulated in some studies. Sodiumthiosulphate (STS) is known to have a protective effect on liver function during administration ofhepatotoxic chemotherapy. In the present experimental study the effect of treatment with STS inthe presence of obstructive jaundice was studied by determination of the survival rate of ratssubjected to biliary obstruction and by polarographic determination of the hepatic mitochondrialfunction. Treatment with STS was found to result in a significant improvement in rats'survival rate (p < 0.05). Polarography demonstrated significant preservation of mitochondrialrespiratory capacity after treatment with STS. The results of the present study show that thedeterioration in liver function in the presence of biliary obstruction is probably caused byimpairment of mitochondrial respiration. This may be preserved by treatment with STS. Theexact explanation of its effect is not yet clear.


Sir,One cannot but agree with the pitch for substantial changes in the current pharmacology curriculum. TraditioCurrent medical graduates learn their first lessons in rational and appropriate prescribing in busy out patient departments during their internship. Their knowledge about practical drug dosing and modifications to be made in various clinical scenarios leaves much more to be desired. The new guidelines for teaching pharmacology must be radical in scraping what is useless and in recommending a practical patient-based learning. This will bring the interest of medical students back into pharmacology classes.


Vaccination against influenza is currently recommended for patients with rheumatoid arthritis (RA). The safety and efficacy of vaccination in patients suffering from rheumatic diseases is still a matter of debate. This review summarizes the studies performed on the safety and immunogenicity of influenza vaccination in patients with RA as well as the rheumatic complications of the vaccine in otherwise healthy persons. Several trials have shown that the vaccine induces an adequate humoral response and does not induce clinical exacerbation of RA. Rheumatic complications (mainly vasculitis) following influenza vaccination in the general population are scarce.


The activities of certain enzymes in the tissus of mice infected with Friend virus have been studied. Progressive increases in LDH, G6PDH and 6PGDH have been observed in the spleen and liver concomitant with malignant transformation. Plasma LDH activity was also observed to increase over the period of study, but changes in the isoenzyme distribution probably resulted from contamination of the Friend virus preparation with lactic dehydrogenase virus. The tissue enzyme changes are similar to those observed in human malignancies.


Research on biological data integration has traditionally focused on the development ofsystems for the maintenance and interconnection of databases. In the next few years,public and private biotechnology organisations will expand their actions to promote thecreation of a post-genome semantic web. It has commonly been accepted that artificialintelligence and data mining techniques may support the interpretation of huge amounts ofintegrated data. But at the same time, these research disciplines are contributing to thecreation of content markup languages and sophisticated programs able to exploit theconstraints and preferences of user domains. This paper discusses a number of issues onintelligent systems for the integration of bioinformatic resources.


Experiments are described in which dose-response data have been obtained for EMT6 mouse tumour cells growing in vivo and exposed to various cytotoxic agents. A comparison has been made of the response of solid tumours in the flank and of rapidly growing lung nodules. The results are discussed with regard to their cell kinetic implications and compared with our results for the chemosensitivity of EMT6 cells in exponential and plateau phase growth in vitro.


The role of the vagus nerve in liver regeneration after partial hepatectomy was studied by comparing theeffects of hepatic branch vagotomy with those of hepatic branch sympathectomy in rats. The liver weight as a percentage of body weight decreased significantly 7 days after vagotomy compared with the controls and this was associated with a reduction in food intake. There was no difference in the liver weights between the control rats and the pair-fed vagotomized rats. Hepatic sympathectomy had no significant effect on the liver weight. The serum scores indicating hepatic function showed no difference between the control and the vagotomized rats except alkaline phosphatase. The concentration of insulin was unchanged. The number of mitotic hepatocytes remained high at 7 days after vagotomy: Theseobservations led us to conclude that the vagus nerve stimulates liver regeneration, and its effect depends on vagal factors directly and specifically.


Because two authors were added to the author byline, the funding statement should also include the following: SF was supported by a studentship from the French Ministry of Research. JYG was supported by Programme Amazonie du CNRS and ANR through Projet MIRETTE.


A survey of all hospital pharmacies in the former North Western Regional Health Authority has revealed that hospital personnel continue to prepare cytotoxic drugs in suboptimal conditions, despite the widespread introduction of pharmacy cytotoxic reconstitution services. Other concerns include the lack of formal training for medical staff in the administration of these agents and the frequent absence of written procedures for dealing with extravasation and chemotherapy errors.


However the existence of chronic inflammatory conditions that do not have an established infective cause and are associated with the development of tumours strongly suggests that the inflammatory process itself provides the prerequisite environment for the development of malignancy. This environment includes upregulation of mediators of the inflammatory response such as cyclo-oxygenase (COX)-2 leading to the production of inflammatory cytokines and prostaglandins which themselves may suppress cell mediated immune responses and promote angiogenesis. These factors may also impact on cell growth and survival signalling pathways resulting in induction of cell proliferation and inhibition of apoptosis. Furthermore, chronic inflammation may lead to the production of reactive oxygen species and metabolites such as malondialdehyde within the affected cells that may in turn induce DNA damage and mutations and, as a result, be carcinogenic. Here it is proposed that the conditions provided by a chronic inflammatory environment are so essential for the progression of the neoplastic process that therapeutic intervention aimed at inhibiting inflammation, reducing angiogenesis and stimulating cell mediated immune responses may have a major role in reducing the incidence of common cancers. © 2001 Cancer Research Campaign


DNA samples obtained from 29 testicular germ cell tumours have been screened for instability at nine different microsatellite sequences consisting of dinucleotide, trinucleotide and tetranucleotide loci. Overall, in tumours from six (21%) patients we found abnormalities in at least one of the loci examined. Mutation was most frequently found in tetranucleotide and trinucleotide repeats with only a low proportion of alterations in dinucleotide repeats. This pattern of instability is distinct from that reported in colorectal cancer and other cancers that have a high level of alterations in dinucleotide repeats.


Leucocytes containing a high proportion of blast cells were obtained from 11 patients with acute myeloid leukaemia, and leucocytes were also obtained from 2 normal subjects. Ferritin was partially purified from leucocyte extracts and subjected to anion-exchange chromatography and isoelectric focusing. The Fe content of leucocyte ferritin was low, and in all but one case the preparations contained isoferritins corresponding to those found in normal tissues or serum. Only some of the preparations contained the relatively acidic isoferritins which have been described as "carcinofoetal", but which are also present in normal heart and kidney. Ferritin from one patient contained isoferritins of lower isoelectric point than heart ferritin. These results show that there does not appear to be any specific isoelectric focusing pattern for leukaemic cells, and that assays for acidic isoferritins are unlikely to be of use in the diagnosis of leukaemia and in monitoring treatment. However, the very acidic protein found in one preparation suggests that the search for abnormal subunits of ferritin may be fruitful in acute leukaemia.


The cumulative radiation effect (CRE) is one of several empirical scalar descriptions of biological effect which enable corrections to be made for gaps in radiotherapy treatment. Predictions of this theory were tested using mouse crypt regeneration and mouse skin as biological models. These experimental results are discussed in terms of the dependence of tissue regeneration potential during a gap on the biological effect achieved before the gap, and on gap length. A hypothesis is proposed to reconcile the apparent conflict between the two experiments. While the simple exponential gap formulation of the CRE is seen to be inadequate, insufficient data are available at present to modify it.