Hip screw migration of peritrochanteric fracture fixation devices is a described complication in English literature. Medial migration occupies the majority of these cases whereas lateral migration is rare. We report the case of an 85-year-old woman whose intramedullary osteosynthesis of a trochanteric fracture was complicated by hip screw lateral migration. Mobilization was not influenced and no cut-out or non-union was detected. The migrated hip screw was easily removed and the discomfort vanished. The need for adequate surgical technique and radiographic examination after re-injuries even if the patient remains ambulatory is emphasised. Fractures of the trochanteric region of the femur are very common in the elderly. Many fixation devices have been developed for these fractures; the most widely used being the numerous versions of intramedullary nails which tend to replace the sliding nail plate systems. Intra-operative blood loss and operating time is much minimised, immediate load-bearing is ensured, and postoperative morbidity remains low . DespiteOne of the most common complications of intramedullary systems is lag screw migration combined with hardware cut-out or non-union ,5. HereiAn 85-year-old woman presented with a hip fracture after a fall. The radiographic control revealed a type 31-A.2.2, secondary to the AO classification, intertrochanteric fracture Figure  of the rPeritrochanteric fractures represent a significant risk in every age group. Moreover in the elderly they may represent a risk to life. Intramedullary nailing is widely used for fixation of such fractures ensuring less operating time, minimized wounds, immediate weight bearing, faster mobilization and thus less morbidity . NeverthThe most common and well-documented mechanical complication of these devices are: a) cut-out of the hip screw through the femoral head with varus collapse of the fracture ; b) fracLateral migration is more rare than medial. Up to our knowledge there are not any published cases of lateral migration, in a single use of a hip screw, without a new fracture or a cut-out accompanying the migration. Studies concerning the use of perhaps the most studied nail (Gamma nail - Howmedica) conclude that there have been no instances of implant failure without non-union or re-fracture .Hip screw migration is considered to be an evolutionary complication and the ability of the implant to resist migration under dynamic loading is of critical importance. Walking subjects the implant-bone interface to combined axial and torsional loading and may play a role in lag screw migration. In our case slight, painless lateral migration (of approximately 10 mm) was noticed 2.5 months post surgery and full lateral migration was noticed two weeks later after the occurrence of a new fall. The new injury caused great nail protrusion and haematoma of the hip accompanied with tenderness which gave away after the lag screw removal. We could not reach any profound explanation for the migration mechanism. The fact that the way of the lag screw into the femoral head was reamed and that the diameter of the non-threaded part of the lag screw was the same with that of the thread could provide some explanation for the behaviour of the screw and more particularly for the convenience of total migration once it was slightly detached from its original position. Moreover the osteoporotic bone of the patient did not offer an adequate grip to stabilize the sliding screw and prevent its loosening. Osteoporosis on the other hand did not seem to create any delay to bone union.One could suppose that this is the case of a semi-completed Z-effect since the lag screw migrated laterally as if the optional anti-rotational screw (which we did not use) was there to play the role of the medially migrated half. It should be reminded here that Werner-Tutschku et al  were the25 mm should rarely fail by cut-out [The age of the patient, the quality of the bone, the pattern of the fracture, the stability of the reduction, the angle of the implant, and the position of the lag screw within the femoral head have all been related to this mechanism of failure, but there has been no clear consensus as to the interrelationships or relative importance of each factor. Previous clinical studies suggest that lag screws placed with a tip-apex distance (TAD) of less than  cut-out ,15. In oIntramedullary nailing tends to become the treatment of choice for proximal femoral fractures and has a low implant failure rate. Although closed reduction and minimally invasive exposure minimise delayed union and non-union they are not enough for the avoidance of such complications. Caution is needed in the placement of the lag screw in manner that respects the limitations of Tip Apex Distance. A well centred lag screw contributes to better transmission of axial forces and inducts the earlier callus formation. Thus complications such the one described in this paper do not result in re-fractures, non-union or mal-union.AP: Anteroposterior; PFN: Proximal Femoral Nail; TAD: Tip Apex Distance; TFN: Trochanteric Fixation Nail; CCD: Caput Collumn Diaphysis.Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.The authors declare that they have no competing interests.NL collected the data and drafted the manuscript. GM involved in revising the manuscript for important intellectual content. IG was the consultant surgeon responsible for the patient. All authors read and approved the final manuscript.


Tumours of the vulva and vagina are rare and there are relatively few studies of circulating markers in these conditions. The urinary measurement of the core fragment of the beta-subunit of hCG has been proposed as a useful tumour marker in non-trophoblastic gynaecological malignancies. This study describe the measurement of urinary beta-core in 50 patients with vulvovaginal malignancy. In contrast to other studies corrections were made for both the effect of urine concentration and the age of the patient. Each patient was followed up for at least 24 months, and at this time their status was correlated with their initial level of urinary beta-core. The sensitivity of beta-core was only 38%, but of those patients with elevated levels 90% had died within 24 months, while only 32% of those with normal levels had died. For both patients at initial presentation and those with recurrent disease, there was a highly significant difference in the survival curve between those with elevated beta-core levels and those with normal levels. This is similar to findings in cervical carcinoma, and suggests that for lower genital tract cancer the measurement of urinary beta-core may be valuable as a prognostic indicator, allowing a more informed approach to treatment and follow-up.


Serum vitamin A concentration were measured in 26 newly diagnosed lung-cancer patients and found to be significantly lower than those of patients of similar age with either non-malignant lung or non-lung diseases. The levels of vitamin A in the lung-cancer patients, but not in the controls, were significantly correlated with serum concentrations of retinol-binding protein (RBP) and zinc. It is suggested that low levels of zinc might reduce the synthesis of RBP and thus reduce the mobilization of vitamin A from the liver.


As indicated in the sample size paragraph, study power was considered in terms of both the whole year group and the high-risk sub-group. The incorrect emphasis in the published study protocol paper on the high risk sub-group analysis was a legacy of the funding proposal protocol, in which the sub-group sample size calculations critically determined the number of schools required for the trial.In preparing the main results paper from this trial, we have noticed an important error in the study protocol paper. In the Some other changes to the paragraph are also required to contextualise the corrected status of the outcomes. The corrected version of the paragraph should read:The trial's primary outcome measure is smoking prevalence measured (i) among the high-risk group and (ii) among the entire year group. The high-risk group is defined as those students who, at baseline, had experimented with cigarettes, were ex-smokers, or were occasional (less than weekly) smokers. These students are a primary target group because they are at greatest risk of becoming regular smokers, and the feasibility study showed an effect amongst this group [18]. Smoking prevalence is defined as students smoking a cigarette in the previous seven days. These outcome measures are being validated by measurement of salivary cotinine (a metabolite of nicotine), as studies have found cotinine to be the most accurate biomarker of smoke exposure in the previous two to three days . Secondary outcome measures include perceptions of norms regarding adolescent smoking, and intention to quit.We apologise for any inconvenience caused in our oversight with regard to this important detail.The pre-publication history for this paper can be accessed here:


This paper describes a simple flow-injection (FI) manifold for the determination of a variety of species in industrial water. The chemical systems involved in the determination of ammonia (formation of Indophenol Blue), sulfate (precipitation with Ba(II)), and iron  were selected so that a common manifold could be used for the sequential determination of batches of each analyte. A microcolumn of a suitable ion exchange material was used for on-line preconcentration of each analyte prior to injection; linear ranges for the determination of the analytes at the ng/ml levels were obtained with good reproducibility. The manifold and methods are ready for full automation.


In 1996, investigation of a hantavirus pulmonary syndrome (HPS) outbreak in southern Argentina found evidence of person-to-person transmission of a hantavirus. The infection control ramifications of this finding led to this review of hantavirus epidemiology in the United States; the review suggests that Sin Nombre virus infection is rarely, if ever, transmitted from person to person and that existing guidelines for prevention of HPS remain appropriate for North America.


Multidrug-resistant strains of Mycobacterium tuberculosis seriously threaten tuberculosis (TB) control and prevention efforts. Molecular studies of the mechanism of action of antitubercular drugs have elucidated the genetic basis of drug resistance in M. tuberculosis. Drug resistance in M. tuberculosis is attributed primarily to the accumulation of mutations in the drug target genes; these mutations lead either to an altered target  or to a change in titration of the drug . Development of specific mechanism-based inhibitors and techniques to rapidly detect multidrug resistance will require further studies addressing the drug and drug-target interaction.


The 'deleted in colon carcinoma' (DCC) gene has been considered a candidate tumour-suppressor gene that encodes for a transmembrane protein with strong structural similarity to members of the superfamily of neural cell adhesion molecules. It has been mapped to the chromosomal region 18q21.1 and it is implicated in cellular differentiation and developmental processes. In human osteosarcoma allelic loss frequently occurs on the long arm of chromosome 18, suggesting a possible involvement of the DCC gene in the pathogenesis of this tumour entity. In the present study the mRNA and protein expression and rearrangements at the DNA level of the DCC gene were addressed in 25 osteosarcomas and several tumour cell lines, including osteosarcoma- and colon carcinoma-derived cell lines. Using an reverse transcriptase polymerase chain reach in (RT-PCR)-based approach DCC expression was found to be lost or substantially reduced in 14 of 19 high-grade osteosarcomas, in three of six lower grade osteosarcomas and most of the tumour cell lines, in contrast to normally differentiated osteoblasts. Immunohistochemical studies on DCC protein expression of 14 selected tumours correlated well with the RT-PCR-based results. In view of the putative tumour-suppressor characteristics of the DCC gene its loss or reduction of expression could be a specific event in the development or progression of many high-grade osteosarcomas.


Ligand-bound CRP activates            complement and the protein reportedly binds various Fc receptors. Coincident            with a now decade-long resurgence in clinical interest in associations of CRP with            disease, our laboratory has been investigating the biology of CRP in vivo using            human CRP transgenic mice (CRPtg). At that time we confirmed that CRP affects            a host defense function mediated at least in part through the elimination of            pathogens. Less appreciated and not as well understood as CRP's ability to bind            antigen and aid in the elimination of microbes, is its known ability to bind            autoantigens and presumed capacity to promote clearance of apoptotic cells. These            latter properties of CRP have long been suspected to contribute to homeostasis and            to autoimmune disease. In this article we review and update the evidence            generated in CRPtg by our group and in vitro by others' that indicates CRP is more            than just an antimicrobial molecule and convenient marker of inflammation - rather,            it protects against autoimmunity. A mechanistic            hypothesis is presented to account for this cause-and-effect relationship.C-reactive protein (CRP) is a blood component comprised of five identical            subunits with a combined molecular mass of 110 kDa; in the presence of Ca


Dear Editor,I read the article 'Effectiveness of using teachers to screen eyes of school-going children in Satna district of Madhya Pradesh, India' with dueThe children not attending school can be covered comprehensively by promoting regular eye camps with the aid of the local Government and encouraging the people to attend the same by proper use of media. The high false-positive rate in the study, adding t


BMC Biology that the mechanisms responsible for maintaining the imprinted state in Drosophila may be evolutionarily conserved and that CTCF may also play a critical role in this process.The nuclear factor CTCF has been shown to be necessary for the maintenance of genetic imprinting at the mammalian H19/Igf2 locus. MacDonald and colleagues now report in http://www.biomedcentral.com/1741-7007/8/105See research article  Igf2) and the RNA gene H19. However, understanding of the mechanisms controlling imprinting in non-mammalian species has lagged behind and it is unclear whether imprinting in insects and mammals is a conserved biological process with the same underlying molecular mechanisms. In this issue of BMC Biology, Lloyd, Meller and colleagues [Drosophila CCCTC binding factor (dCTCF) protein in the maintenance of maternal imprinting and propose that dCTCF has an evolutionarily conserved role in the maintenance of the imprinted state.Genetic imprinting is an epigenetic phenomenon that results in the expression of certain genes in a parent-of-origin chromosome-specific manner. Although imprinting was originally discovered in insects  and has lleagues  examine Drosophila is associated with position-effect variegation, in which chromosomal rearrangements place genes with visible phenotypes close to heterochromatin. MacDonald et al. [Drosophila mini-chromosome in which most of the X chromosome is deleted and the garnet gene is placed next to the centromeric heterochromatin; the garnet protein resembles clathrin and nonclathrin adaptin proteins and is similar to the delta subunit of the mammalian AP-3 adaptin complex. The rearrangement causes a variegated expression of garnet, such that the eyes of the adult flies show sectors of expressing and non-expressing cells characteristic of heterochromatin-induced silencing. Interestingly, this variegated expression is imprinted and it is observed in individuals carrying the paternal mini-X-chromosome, whereas the maternally transmitted copy shows normal expression of the garnet gene [All but one case of imprinting described in d et al.  use a Drnet gene . This obgarnet gene expression in the maternal versus paternal chromosomes, the authors [garnet gene from the maternal mini-X-chromosome, leading to a variegated eye color similar to that seen from the paternally inherited chromosome. This observation suggests that dCTCF is required for the non-variegated expression of the garnet gene when it is maternally inherited.To study whether dCTCF is involved in the differential regulation of  authors  examinedgarnet phenotype: the transcription of the gene under the control of regulatory sequences and the spreading of heterochromatin silencing - these two components may not be easy to separate mechanistically. In the mammalian H19/Igf2 locus, direct transcriptional activation can be distinguished from indirect effects from the surrounding chromatin thanks to information obtained from the analysis of the function of CTCF in the spatial organization of the maternal locus. This organization functions to maintain the imprinted expression of H19 and the silencing of Igf2 on the maternal chromosome. If CTCF binding in the imprinting control region (ICR) is abolished, both Igf2 and H19 can be transcribed from the maternal allele because of the disruption in the CTCF-mediated maternal allele chromatin organization; this organization prevents the interaction between enhancers and the promoter of Igf2. These observations suggest that the role of CTCF in the maintenance of imprinting involves its ability to mediate interactions that result in a specific three-dimensional architecture of the locus. In fact, CTCF is not directly involved in the transcription activation of the mouse H19 and Igf2 genes [Two different processes affect the visually observed f2 genes -10.Drosophila, the primary effect of the maternal imprint is to inhibit the spread of heterochromatin-induced silencing . The finding that the garnet gene is poorly expressed from the paternally transmitted mini-X-chromosome and is not affected by reduced dCTCF expression [garnet gene in the maternally derived mini-X-chromosome could then be accomplished by the establishment of a distinct barrier to the spread of heterochromatin (Figure garnet transcription that indirectly antagonizes heterochromatin spreading (Figure garnet in the maternal germline would be the imprint that inhibits heterochromatin spreading in the somatic cells of the progeny.In pression  suggestsn Figure  or by a g Figure . In the et al. [H19/Igf2 locus. Given the functional conservation of CTCF as an insulator protein between flies and mammals, it is interesting to ask whether this is also the case in Drosophila. MacDonald et al. [garnet gene is not subject to heterochromatin-induced silencing in a mini-X-chromosome inherited from females heterozygous for mutations in the dCTCF gene. This observation suggests that dCTCF is not required for the establishment of the maternal imprint. However, the question remains as to whether further reduction in the levels of dCTCF in the maternal germline may actually show an effect on this process. For example, it is possible that dCTCF expression during oogenesis is much higher than in somatic cells, and that the small reduction in dCTCF levels in heterozygous mutant females is not sufficient to affect the establishment of the imprint. Alternatively, there may be other mechanisms that can prevent the spreading of heterochromatin during gametogenesis independent of dCTCF. Such a mechanism could use other insulator proteins or alternative processes to prevent heterochromatin spreading.After showing a role for dCTCF in the maintenance of the maternal imprint, MacDonald et al.  exploredd et al.  found thDrosophila, it is possible that the role of dCTCF in maintaining the imprinted state is related to the ability of this protein to mediate interactions that create a chromatin domain insulated from heterochromatin silencing (Figure et al. [Drosophila will shed new light not only on the understanding of the mechanisms controlling this process, but also on the understanding of the evolutionary conservation of CTCF function.CTCF has multiple roles in chromatin organization and gene regulation that derive from its ability to mediate intra- and inter-chromosome interactions . Given tg Figure . The fine et al.  agree wi


Contemporary theory of spiking neuronal networks is based on the linear response of the integrate-and-fire neuron model derived in the diffusion limit. We find that for non-zero synaptic weights, the response to transient inputs differs qualitatively from this approximation. The response is instantaneous rather than exhibiting low-pass characteristics, non-linearly dependent on the input amplitude, asymmetric for excitation and inhibition, and is promoted by a characteristic level of synaptic background noise. We show that at threshold the probability density of the potential drops to zero within the range of one synaptic weight and explain how this shapes the response. The novel mechanism is exhibited on the network level and is a generic property of pulse-coupled networks of threshold units. Our work demonstrates a fast-firing response of nerve cells that remained unconsidered in network analysis, because it is inaccessible by the otherwise successful linear response theory. For the sake of analytic tractability, this theory assumes infinitesimally weak synaptic coupling. However, realistic synaptic impulses cause a measurable deflection of the membrane potential. Here we quantify the effect of this pulse-coupling on the firing rate and the membrane-potential distribution. We demonstrate how the postsynaptic potentials give rise to a fast, non-linear rate transient present for excitatory, but not for inhibitory, inputs. It is particularly pronounced in the presence of a characteristic level of synaptic background noise. We show that feed-forward inhibition enhances the fast response on the network level. This enables a mode of information processing based on short-lived activity transients. Moreover, the non-linear neural response appears on a time scale that critically interacts with spike-timing dependent synaptic plasticity rules. Our results are derived for biologically realistic synaptic amplitudes, but also extend earlier work based on Gaussian white noise. The novel theoretical framework is generically applicable to any threshold unit governed by a stochastic differential equation driven by finite jumps. Therefore, our results are relevant for a wide range of biological, physical, and technical systems. Understanding the dynamics of single neurons, recurrent networks of neurons, and spike-timing dependent synaptic plasticity requires the quantification of how a single neuron transfers synaptic input into outgoing spiking activity. If the incoming activity has a slowly varying or constant rate, the membrane potential distribution of the neuron is quasi stationary and its steady state properties characterize how the input is mapped to the output rate. For fast transients in the input, time-dependent neural dynamics gains importance. The integrate-and-fire neuron model The analytical treatment of the threshold process is hampered by the pulsed nature of the input. A frequently applied approximation treats synaptic inputs in the diffusion limit, in which postsynaptic potentials are vanishingly small while their rate of arrival is high. In this limit, the summed input can be replaced by a Gaussian white noise current, which enables the application of Fokker-Planck theory The spike threshold renders the model an extremely non-linear unit. However, if the synaptic input signal under consideration is small compared to the total synaptic barrage, a linear approximation captures the main characteristics of the evoked response. In this scenario all remaining inputs to the neuron are treated as background noise see . CalculaLinear response theory enables the characterization of the recurrent dynamics in random networks by a phase diagram In simulations of neuron models with realistic amplitudes for the postsynaptic potentials, we observed a systematic deviation of the output spike rate and the membrane potential distribution from the predictions by the Fokker-Planck theory modeling synaptic currents by Gaussian white noise. We excluded any artifacts of the numerics by employing a dedicated high accuracy integration algorithm Our theory applied to the integrate-and-fire model with small but finite synaptic amplitudes Consider a leaky integrate-and-fire model The membrane potential of the model neuron follows a first order stochastic differential equation. Therefore, in this section we consider a general first order stochastic differential equation driven by point events. In order to distinguish the dimensionless quantities in this section from their counterparts in the leaky integrate-and-fire model, we denote the rates of the two incoming Poisson processes by In the presence of an absorbing boundary at First we consider the diffusion limit, in which the rate of incoming events diverges, while the amplitude of jumps goes to zero, such that mean Now we return to the problem of finite jumps. We proceed along the same lines as in the diffusion limit, seeking the stationary solution of the Fokker-Planck equation (2). We keep the boundary conditions at If The general solution of the stationary Fokker-Planck equation (3) is a sum of a homogeneous solution The normalization condition determines the as yet unknown constant probability flux We now apply the theory developed in the previous section to the leaky integrate-and-fire neuron with finite postsynaptic potentials. Due to synaptic impulses, the membrane potential drifts towards t region  the apprt region  our analts , see , the dene noise  . The insWe now proceed to obtain the response of the firing rate plitudes .The instantaneous response of the firing rate to an impulse-like perturbation can be quantified without further approximation. The perturbation shifts the probability density by response  which foThe increasing and convex dependence of the response probability on the amplitude of the perturbation is a generic feature of neurons with subthreshold mean input that also persists in the case of finite synaptic rise time. In this regime, the membrane potential distribution has a mono-modal shape centered around the mean input, which is inherited from the underlying superposition of a large number of small synaptic impulses. The decay of the density towards the threshold is further enhanced by the probability flux over the threshold: a positive synaptic fluctuation easily leads to the emission of a spike and therefore to the absorption of the state at the threshold, depleting the density there. Consequently, the response probability The integral response (15) as well as the instantaneous response (5) both exhibit stochastic resonance; an optimal level of synaptic background noise Due to the convex nature of the instantaneous response  its relaAn example network in which the linear non-instantaneous response cancels completely and the instantaneous response becomes dominant is shown in hoot at  . Figure shown in . The pooIn this work we investigate the effect of small, but non-zero synaptic impulses on the steady state and response properties of the integrate-and-fire neuron model. We obtain a more accurate description of the firing rate and the membrane potential distribution in the steady state than provided by the classical approximation of Gaussian white noise input currents The instantaneous non-linear response is potentially a relevant mechanism for processing of transient signals by neurons. In auditory cortex, the irregular firing of neurons has been shown to be driven by simultaneous coactivation of several of their synaptic afferents Our finding of an immediate non-linear response has an implication on the intensely debated question how common input affects the correlation of the spiking activity of pairs of neurons Synapses with spike timing dependent plasticity (STDP) Postsynaptic potentials exhibit a finite rise time, whereas the membrane potential of the integrate-and-fire neuron model jumps at each incoming synaptic event. Although this is a simplification, the model reproduces experimental spike trains surprisingly well Previous work has shown that the spike generation mechanism influences the transient properties of neurons The hybrid approach combining a diffusion approximation with an explicit treatment of finite jumps near the boundary allowed us to uncover hitherto unknown properties of the integrate-and-fire model by analytical means. The diffusion approximation, however, still limits our approach: for synaptic amplitudes


Advance health care directives and informed consent remain the cornerstones of patients' right to self-determination regarding medical care and preferences at the end-of-life. However, the effectiveness and clinical applicability of advance health care directives to decision-making on the use of life support systems at the end-of-life is questionable. The Uniform Anatomical Gift Act (UAGA) has been revised in 2006 to permit the use of life support systems at or near death for the purpose of maximizing procurement opportunities of organs medically suitable for transplantation. Some states have enacted the Revised UAGA (2006) and a few of those have included amendments while attempting to preserve the uniformity of the revised Act. Other states have introduced the Revised UAGA (2006) for legislation and remaining states are likely to follow soon.presumption of donation intent and the use of life support systems to ensure medical suitability of organs for transplantation. The default choice trumps the expressed intent in an individual's advance health care directive to withhold and/or withdraw life support systems at the end-of-life. The Revised UAGA (2006) overrides advance directives on utilitarian grounds, which is a serious ethical challenge to society. The subtle progression of the Revised UAGA (2006) towards the presumption about how to dispose of one's organs at death can pave the way for an affirmative "duty to donate". There are at least two steps required to resolve these challenges. First, physicians and hospitals must fulfill their responsibilities to educate patients on the new legislations and document their preferences about the use of life support systems for organ donation at the end-of-life. Second, a broad based societal discussion must be initiated to decide if the Revised UAGA (2006) infringes on the PSDA and the individual's right of autonomy. The discussion should also address other ethical concerns raised by the Revised UAGA (2006), including the moral stance on 1) the interpretation of the refusal of life support systems as not applicable to organ donation and 2) the disregarding of the diversity of cultural beliefs about end-of-life in a pluralistic society.The Revised UAGA (2006) poses challenges to the Patient Self Determination Act (PSDA) embodied in advance health care directives and individual expression about the use of life support systems at the end-of-life. The challenges are predicated on the UAGA revising the default choice to  In 1990, the U.S. Congress passed the Patient Self-Determination Act (PSDA) reinforcing individuals' rights to determine their final health care. The PSDA became effective in 1991 so that patients can make decisions about their medical care and specify whether they want to accept or refuse specific medical care [The PSDA requires Medicare and Medicaid providers, including hospitals, to give adult individuals, at the time of inpatient admission, certain information about their rights under state laws governing advance health care directives, including: (1) the right to participate in and direct their own health care decisions; 2) the right to accept or refuse medical or surgical treatment; (3) the right to prepare advance health care directives and (4) information on the provider's policies governing the utilization of these rights [ the righAlmost 16 years later, advance health care directives and power-of-attorney for health care still play a limited, yet important, role in assisting with health care decisions about the use of life support systems and medical technologies at the end-of-life . About 2Criticisms have been rightfully expressed concerning the current deficiencies of construction, documentation, accessibility and applicability of advance health care directives . The maiConsidering the above shortfalls, this commentary highlights additional and unique challenges posed by the Revised Uniform Anatomical Gift Act (UAGA) 2006 on advance health care planning and directives about the use of life support systems at the end-of-life . Some stIn 2006, the publication of two influential reports from the Institute of Medicine and National Conference on Donation After Cardiac Death opened a new era for deceased organ donation ,10. TradThe National Conference of Commissioners on Uniform State Laws (NCCUSL) promulgated the Revised UAGA (2006) with the substantial and active participation of the major stakeholders representing donors, recipients, physicians, procurement organizations, regulatory agencies and the US Department of Health & Human Services. The stakeholders represented a broad spectrum of organizations with special interest or advocacy for the practice of organ transplantation. The primary intent of revising the UAGA in 2006 was to solve the critical organ shortage by maximizing the likelihood of organ donation. To accomplish this objective, the Revised UAGA (2006) increases opportunities of organ procurement after cardiac death for transplantation . The anaThe Revised UAGA (2006) reaffirms that if a donor has a document of gift, there is no reason to seek consent from the donor's family as they have no right to give it legally . If an iThe Revised UAGA (2006) section 14 was drafted in accordance with the controlling federal law requiring hospitals to notify an organ procurement organization (OPO) of any individual whose death is imminent or who has died in-hospital to increase opportunities of organ procurement for transplantation . In casenot to have life prolonged by the administration of life support systems should not be construed as an expression of a contrary intent for the use of life support systems for donation purpose [is a prospective donor.The Revised UAGA (2006), section 14, emphasizes the general direction in an advance health care directive or power-of-attorney for health care that the patient's wish  purpose . In effecontrary intent to prevent the use of life support systems for organ donation purposes in either a declaration or advance health care directives.If determined to be a prospective donor, the Revised UAGA (2006), section 21, creates a default rule requiring that measures necessary to ensure the medical suitability of an organ for transplantation may not be withheld or withdrawn. The initiation and/or continuation of life support systems is the default rule and overrides a prospective donor's expression in an advance health care directive not to have life prolonged by life support systems. To resolve the tension between the presumed intent to donate organs and the expressed intent not to have life support systems administered merely to prolong life, section 21 presumes that for a prospective donor the desire to save lives by making an anatomical gift trumps the desire to have life support systems withheld or withdrawn. The Revised UAGA (2006) requires a prospective donor to expressly provide In 2007, an amendment was introduced to the Revised UAGA (2006), section 21, to recognize the conflict between initiation and/or continuation of life support systems based on becoming a prospective donor and the expressed wishes of appropriate end-of-life care in advance health care directives. Section 21(b) (2007) requires the attending physician to resolve the conflict with the prospective donor or surrogate decision maker for clarification of intent and any contraindications for appropriate end-of-life care.With the new UAGA legislation, advance health care planning should include education on the new requirement of the Revised UAGA (2006) about the use of life support systems for organ donation at the end-of-life. These changes are predicated on the UAGA revising the default choice to presumption of donation intent and, therefore, the requirement for life support systems to ensure medical suitability of organs for transplantation. Figure Patients with documents of gift are considered donors irrespective of advance health care directives and they are required to comply with organ procurement protocols figure . In the The laxity of criteria of medical suitability for donation is most disturbing to patients who become prospective donors without documents of gift and who have unequivocal advance health care directives expressing intent for withholding and/or withdrawal of life support systems at the end-of-life figure . Under sIn the endeavor to solve the critical organ shortage, the Revised UAGA 2006) has transformed the traditional 'altruistic' to a disturbing 'utilitarian' approach towards organ procurement for transplantation. National palliative and hospice care organizations ,17 promo06 has trThe Revised UAGA (2006) has not adopted presumed consent for organ procurement. Nevertheless, the most disturbing consequence of the Act is that patients will be forced to have life support systems initiated or continued while awaiting the assessment of their organs for donation. In an epidemiologic study of the use of intensive care at the end-of-life in the US, one in five Americans die using intensive care services . It is lThe application of life support systems for the purpose of organ donation without explicit consent is contraindicated at end-of-life and inconsistent with recommended practice guidelines for quality palliative care ,22. LifeThe Revised UAGA (2006) requirement of life support systems for patients with clearly contrary end-of-life wishes represents a radical departure from the PSDA (1991) and original intent of advance health care directives. In fact, it can be argued that the Revised UAGA (2006) intrudes into patients' autonomy and infringes on their rights to self-determination of medical care at the end-of-life.Some states have already enacted the Revised UAGA 2006) and a few of those have included amendments while attempting to preserve the uniformity of the revised Act (Figure 006 and aPSDA = Patient Self Determination ActOPO = Organ procurement organizationUAGA = Uniform Anatomical Gift ActUS = United StatesSee table There are no affiliations or financial involvement with any organization or entity with a direct financial interest in the subject matter or materials discussed in the manuscript. The authors declare that they have no competing interests.The JLV, MYR and JLM attest they have made substantial contributions in drafting the manuscript and revising it critically for important intellectual content; that they have given final approval of the version to be published; and that they have participated sufficiently in the work to take public responsibility for appropriate portions of the content. JLV, MYR and JLM read and approved the final manuscript


Two types of mouse tumour have been used to study the radiomodifying actions of Misonidazole (MISO) and WR-2721 when used alone and in combination with each other. Single dose studies were performed in both of the tumours and fractionated studies were performed on the anaplastic carcinoma, CA MT. Radioprotection with WR-2721 was seen in both tumours, being most marked at low X-ray doses. The protection was more obvious and the sensitization by MISO less in the fractionated experiment. The combination of MISO and WR-2721 gave an intermediate response compared with either drug used alone, resulting in some sensitization with single doses and an overall protection with repeated small doses. An interactive toxicity of the 2 drugs was also observed, suggesting an additive effect when assessed in terms of lethality. These studies indicate that the effects of both MISO and WR-2721 are dependent upon the oxygen status of the cells in the tumour, and that MISO can act in an oxygen-mimetic manner to modify the radioprotection observed with WR-2721.


An animal model was used to study the effects of oral treatment with a small molecular selective inhibitor of cysteine proteinases, Z-Phe-Arg-fluoromethylketone (Z-Phe-Arg-FMK) on primary tumour development. Poorly differentiated rapidly growing and moderately differentiated slowly growing human pancreatic tumours were implanted in the neck of nude mice that were orally treated or not with the inhibitor. Growth rates of the tumours were determined during 38 days after implantation. The poorly differentiated tumours were not affected by treatment with the inhibitor. Development of the moderately differentiated tumours was inhibited significantly by Z-Phe-Arg-FMK treatment. Moreover, the amount of stroma was increased and the volume of cancer cells was reduced in the moderately differentiated tumours that had grown in the treated animals. Reduction in size of the tumours was not achieved by reduction in growth rate but in a delay of the onset of growth. It is concluded that cysteine proteinases play a transient role at the start of tumour development only when cancer cells are surrounded by stroma as was the case in the moderately differentiated but not in the poorly differentiated pancreatic tumours. However, this role of cysteine proteinases can easily be taken over by other proteinases. © 2000 Cancer Research Campaign


There was a spelling error in the name of a member of the UNAIDS/WHO/SACEMA Expert Group on Modelling the Impact and Cost of Male Circumcision for HIV Prevention. The correct name is Laith Abu-Raddad.


When assessing the value of a particular treatment, it is important to consider the impact it may have on the quality of life of those being treated. This is particularly so for cancer patients, whose life expectancy may be short. Patients with advanced colorectal cancer who participated in two international comparative studies of raltitrexed ('Tomudex') vs standard 5-fluorouracil (5-FU) plus leucovorin (LV) completed previously validated quality-of-life questionnaires  at various times during the studies. Early statistically significant advantages of raltitrexed vs 5-FU plus LV on quality of life were observed at week 2 in five of eight of the EuroQol and three of four of the Rotterdam Symptom Check List dimensions. Such advantages were not observed using the EORTC questionnaire, which was not completed until week 12. The necessary dose delays and different dose schedules made it difficult in these studies to compare the impact on quality of life of the two treatments. It may be that performance status, effect on disease-related symptoms and the incidence of toxicity are the most important indications of a patient's quality of life.


Our studies of the metastatic behaviour of FSA1231 and FSA1233 show that the role of selection processes of metastatic variants at the secondary sites is minimal in the spontaneous metastasis of these systems. In contrast, tumour-cell release efficiency (number of blood-borne clonogenic tumour-cells) correlates well with the difference in spontaneous lung metastasis efficiencies of the cell clones FSA1231 and FSA1233. Also, the different tumour-cell release efficiencies could explain the discrepancy between artificial and spontaneous metastasis of these cell clones.


The experimental results of the study show that inorganic tin and methyltin substancesinduce slight inhibition of the catalytic activity of horse liver alcohol dehydrogenase (HLADH), unable to beimproved during pre-incubation with the enzyme. The conditions for carrying out the kinetic investigation ofthe mentioned phenomenon were optimized and as it turned out the mechanism of methyltin trichlorideaction, as the most effective methyltin inhibitor, is more complex than the proposed interaction of the metalatom with SH-groups of the enzyme protein. It was demonstrated that the tin compounds act in the samemanner as methylmercury compounds and might serve as oxidative agents towards the co-enzyme NADH.Kinetic data on MeSnCl3 were calculated. Data acquired on NAD-dependent ADH from horse liver and thoseregarding NAD-dependent LDH from sturgeon liver were compared.The study of inorganic tin (SnCl


The treatment of breast cancer patients has changed rapidly in the past decade, but empirical data at local and national level are scarce. Predicting the consequences of screening for primary treatment is consequently difficult. The aim of this analysis of records on admissions to hospital of women with breast cancer and/or for breast surgery (1975-90) together with a survey of all Dutch radiotherapy departments (1986-88) is to show the change in breast-conserving therapy and other primary treatment before the start of breast cancer screening in The Netherlands. There was a modest increase in breast-conserving therapy after 1981, coinciding with the first publication on its trial, followed by a sharp increase between 1985 and 1990, after the second publication. At the end of that 5 year period, 36% of all women with newly diagnosed invasive breast cancer underwent this type of surgery. Breast-conserving surgery is always followed by radiotherapy, but there has been a clear reduction in post-operative radiation after mastectomy. The percentage of breast-conserving therapy is at present higher in The Netherlands than in the USA. Implementing the Dutch screening programme will result in a maximum increase in breast-conserving therapy at national level of 34%, which stabilises at +21%, or a 50% maximum increase at local level. The number of women treated by mastectomy will ultimately decrease by 9%. Given the rapidity of change towards the use of breast-conserving surgery, which is enhanced by screening, recent information will be needed in predicting capacity and assessing whether screen-detected women are treated adequately.


The level of expression of keratinocyte growth factor (KGF) mRNA has been measured in human breast cell lines, purified populations of epithelial cells, myoepithelial cells and fibroblasts from reduction mammoplasty tissue and a panel of 42 breast cancers and 30 non-malignant human breast tissues using a semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) procedure. We found similar levels of KGF mRNA in malignant and non-malignant breast tissues. The study of the amount of KGF mRNA in breast cell lines and purified populations of cells revealed that fibroblasts are the predominant source of KGF with malignant and non-malignant epithelial cells containing very low levels of KGF mRNA. We have examined the distribution of fibroblast growth factor receptor (FGFR)-2-IIIb, which is a high-affinity receptor for KGF and find that it is present on malignant and non-malignant epithelial cells. The level of FGFR-2-IIIb present on breast cancer cell lines was sufficient for KGF stimulation of breast cancer cell proliferation. Other members of the fibroblast growth factor family have been either not expressed in the human breast  or have been found at much reduced levels in breast cancer  and this is the first member of the family to potentially influence the progression of breast cancer through stimulation of cell division.


A case-control study of occupational and recreational sun exposure, Mediterranean and other sun-exposed holidays, tanning history and history of isolated episodes of severe sunburn has been carried out on 113 patients with cutaneous malignant melanoma and 113 age- and sex-matched controls. Social class and skin type were also considered in the analysis of the data which involved the use of conditional multiple logistic regression. A highly significant increase in the history of severe sunburn was recorded in melanoma patients of both sexes in the 5-year period preceding presentation with their tumour. Higher social class and negative history of recreational sun exposure were also significantly increased in patients by comparison with controls. In the male group severe sunburn, lack of occupational sun exposure and higher social class were significant factors while in the female group only severe sunburn was significantly increased in the melanoma patients. This study thus provides evidence to suggest that short intense episodes of UV exposure resulting in burning may be one of the aetiological factors involved in subsequent development of melanoma.


Cancer of the oesophagus was a rare disease in the South African black population until the last few decades. Increases in incidence have occurred and at present it is the commonest cancer in black men in many parts of South Africa. A case-control study of 200 oesophageal cancer patients and 391 hospital controls has been carried out in order to determine the risk factors in the urban black population of Soweto. The results indicate that the cancer patients were long-term urban residents from a very low socio-economic group. The association between smoking pipe tobacco and oesophageal cancer previously noted in South Africa is confirmed. In addition, consumption of traditional beer was found to be a major risk factor.


Many existing tools have poor user interfacesand limited real-time performance when applied to realistically large datasets; muchof the user's cognitive capacity is therefore focused on controlling the tool ratherthan on performing the research. The UTOPIA project is addressing some of theseissues by building reusable software components that can be combined to makeuseful applications in the field of bioinformatics. Expertise in the fields of humancomputer interaction, high-performance rendering, and distributed systems is beingguided by bioinformaticians and end-user biologists to create a toolkit that is botharchitecturally sound from a computing point of view, and directly addresses end-userand application-developer requirements.Bioinformaticians routinely analyse vast amounts of information held both in largeremote databases and in flat data files hosted on local machines. The contemporarytoolkit available for this purpose consists of an


Results are presented which show that mesothelial cells (MC) from ovarian cancer patients can both stimulate and inhibit the clonogenic growth of ovarian tumour cells (TC) in a dose-dependent fashion. TC lines from both non-ovarian and ovarian tumours were variable in their response to MC. Colony formation was rarely induced when the TC population was non-clonogenic and a bladder cell line showed inhibition of colony formation in the presence of MC. Primary tumour cultures from ovarian cancer patients also showed a variable response to MC. Fibroblasts from malignant, benign and non-neoplastic sources were significantly less effective in stimulating the clonogenic growth of responsive cell lines. Conditioned medium was a poor substitute for the presence of intact viable cells, and distance between feeder cell and TC was an important factor in determining the magnitude of response. A significant relationship between the feeder effect of MC and their proliferation in soft agar was observed when epidermal growth factor was used in the medium. The relevance of the findings in the context of the pattern of spread of ovarian cancer is discussed.


The effects of X-radiation on the Nembutal-induced redistribution of the cardiac output in two types of transplanted mouse tumours and some normal mouse tissues have been investigated, using rubidium-86 and 125I-human serum albumin. Irradiation causes an increase in 86Rb uptake (relative blood perfusion) by the tumours of anaesthetized mice, but has little or no effect in non-anaesthetized mice. The increase is dose- and time-dependent. Tumour plasma space is not significantly affected by radiation and Nembutal. Muscle blood perfusion is severely decreased in anaesthetized mice and is not affected by radiation, at least within the time limits of the experiments. This means that radiation-induced functional vascular changes in normal and neoplastic tissues follow different time courses. On the basis of the present results, and of the results of other authors, it is argued that irradiation damages the vasculature of tumours in such a way that it becomes more sensitive to changes in systemic blood pressure.


The new trends in immunochemistry related to the replacement ofradioisotopic labels with non-radioactive labels are presented. Immunoenzymatic, fluorescent and chemiluminescent techniques are described in terms of their basic principles and their most common applications. The advantages of computer-controlled calibration are also discussed.


Recently, eight allelic variants of the pertactin gene (prn1-8) have been characterized in Bordetella pertussis strains isolated in Europe and the United States. It has been suggested that the divergence of the pertactin types of clinical isolates from those of the B. pertussis vaccine strains is a result of vaccine-driven evolution. Sequencing of the prn, which is relatively time-consuming, has so far been the only method for the differentiation of prn types. We have developed a rapid real-time polymerase chain reaction assay suitable for large-scale screening of the prn type of the circulating strains. This method correctly identified the prn type of all tested 41 clinical isolates and two Finnish vaccine strains. The method is simple and reliable and provides an alternative for sequencing in pertussis research.


Saccharomyces cerevisiae and the nematode Caenorhabditis elegans.The availability of complete genome sequences necessitates the development of standardized functional assays to analyse the tens of thousands of predicted gene products in high-throughput experimental settings. Such approaches are collectively referred to as ‘functional genomics’. One approach to investigate the properties of a proteome of interest is by systematic analysis of protein–protein interactions. So far, the yeast two-hybrid system is the most commonly used method for large-scale, high-throughput identification of potential protein–protein interactions. Here, we discuss several technical features of variants of the two-hybrid systems in light of data recently obtained from different protein interaction mapping projects for the budding yeast


A study of Burkitt's lymphoma (BL) in Papua New Guinea for the years 1958-87 revealed four instances of familial BL. Incident cases occurred within 1 year of each other in the four families. Personal follow-up was possible for three of these families whose pedigrees showed that two or more siblings were affected. There was no significant variation of the incidence of BL by year of diagnosis or month of onset. There was significant variation in annual average incidence of BL between the three provinces studied, with the highest incidence in the Nuku and Lumi census districts (of the West Sepik Province). This is the first report of familial BL outside Africa.


The anti-tumour action of methylene dimethane sulphonate (MDMS) has been further investigated in relation to its immunosuppressive properties. Following a dose of 10 mg/kg, the proportion of permanent regressions of Yoshida lymphosarcoma transplants is lower in animals treated during the first 5 days of tumour growth. Re-implants on day 28 to those animals in which regression of the tumour had occurred indicated that the immune response to the tumour increases during the first 7 days of tumour growth.Studies of the effect of MDMS on the primary antibody-forming cell response of mice to sheep red cell antigens showed this drug to be an immunosuppressant comparable in strength to x-radiation. MDMS given to rats prior to tumour transplantation also acted as an immunosuppressant in this system resulting in an increased rate of tumour growth. For both responses the maximum immunosuppressive effect was obtained when the interval between drug administration and antigenic challenge was minimal.


A mortality study of French Polynesia in the period 1984-92, although limited by the small population living close to the test sites and the high proportion of deaths attributed to ill-defined causes, found no excess of cancer that could confidently be attributed to the 41 atmospheric test explosions in 1966-74. A study of cancer incidence is planned.


Objective: To test whether special training of general practitioners alters the care of dementia patients through their systematic recommendation of caregiver counseling and support groups.More than 90% of dementia patients are cared for by their general practitioners, who are decisively involved in the diagnosis, therapy and recommendation of support services. 129 general practitioners enrolled 390 dementia patients and their informal caregivers in a prospective, three-arm cluster-randomized 2-year study. Arm A constituted usual care, in Arm B and C support groups and caregiver counseling  were recommended by the general practitioners. The general practitioners received arm-specific training. Diagnostic and therapeutic behavior of physicians was recorded at baseline. Informal caregivers were questioned in follow-up after 2 years about the utilization of support services.The diagnostic behavior of the general practitioners conforms to relevant guidelines. The procedure in newly-diagnosed patients does not differ from previously diagnosed patients with the exception of the rate of referral to a specialist. About one-third of the newly-diagnosed dementia patients are given an anti-dementia drug. The utilization of support groups and counseling increased five- and fourfold, respectively. Utilization of other support services remained low (< 10%), with the exception of home nursing and institutional short-term nursing.Trained general practitioners usually act in conformity with guidelines with respect to diagnosing dementia, and partly in conformity with the guidelines with respect to recommended drug therapy. Recommendations of support services for informal caregivers by the general practitioner are successful. They result in a marked increase in the utilization rate for the recommended services compared to offers which are not recommended by the general practitioner.ISRCTN68329593 Medical care of elderly people in Germany is given by general practitioners in the majority of cases. This applies also to dementia patients: more than 90% are diagnosed and cared for by the general practitioner . He is rVarious studies have thus far investigated the diagnostic behavior of general practitioners toward dementia patients ,7-9. StoIn the literature, a guideline-supported care rate of patients with Alzheimer's disease (AD) with evidence-based anti-dementia drugs of 26% ,16 or evFor diagnostics, the International Guideline of the National Institutes for Health and Clinical Excellence (NICE) recommend thorough exploration, including the medical history, a physical-clinical examination, and performance of a cognitive screening. Moreover, a laboratory series  should be part of the basic screening. Other procedures  should only be performed after careful consideration. Imaging procedures are recommended for diagnostics of dementia subtypes . The diaFor the treatment of AD patients, the German "Dementia" Guideline for general practitioners recommends drug therapy  and non-drug therapy , whereby the use of anti-dementia drugs is subject to critical discussion . The criIn addition to treating dementia patients, the aim is to support informal caregivers with appropriate support and respite services which have been found to be effective -28, suchInitiative Demenzversorgung in der Allgemeinmedizin: Dementia Care Initiative in Primary Practice) presented here, the care of dementia patients living at home and their informal caregivers was to be optimized with respect to diagnostics, therapy and support services. This took place on the basis of training of general practitioners and systematic recommendation of support groups in the form of peer groups and actively approaching caregiver counseling of informal caregivers.In the German IDA-Study  be increased by recommendation of the general prac-titioner?What effect does the utilization of family caregiver counseling have on the utilization of other available support services?This was a three-armed cluster-randomized controlled longitudinal study of patients with dementia living at home with at least one care-giving informal caregiver. Patients in the study region of Middle Franconia, Bavaria, Germany, were included if they had mild or moderate dementia (MMSE 10-24) according to the diagnosis criteria of DSM-IV  respectiGeneral practitioners in all study groups participated in a training course on dementia diagnosis. In the two intervention groups B and C, they additionally received training on evidence based dementia treatment. They also recommended support groups and actively approaching family counselling to caregivers beginning either at baseline (study Arm C) or after the 1-year follow-up (study Arm B).http://www.controlled-trials.com/. A detailed description of the study design has already been published elsewhere , par, par29]]General practitioners behave largely in conformity with guidelines in their diagnostic procedures in dementia patients. The therapeutic behavior with respect to prescription of anti-dementia drugs was in the majority less in accordance with guideline recommendations. However, there are some hints that behavior in conformity with guidelines could be promoted by means of training. Utilization of support services by informal caregivers remains low, as long as the informal caregivers are not intensively motivated to use such services. The role of the general practitioners as a motivator for informal caregivers is very significant, since the mediation of support services through the general practitioner led to a clear increase in utilization. For research, it is important to investigate the efficacy of further concepts in overcoming barriers to utilization among the informal caregivers of dementia patients.The sponsors have commissioned two academic research institutions with the scientific evaluation of the IDA project by giving unconditional research funds. A contract between the sponsors and academic researchers ensures that the latter have the full scientific responsibility and have the right to publish the results. Members of the sponsoring organizations closely cooperate in design and conduct of the project, but only the academic researchers have full access to all of the data in this study and take complete responsibility for the integrity of the data and the accuracy of the data analysis. CD, EG, MGS, RH and PMe are independent scientists who have received funding for this study as described above. CD received an honorarium for presentation of the IDA-study results at a public symposium from Eisai GmbH. Sponsoring organizations: SW is employee of the AOK Bavaria - Health insurer, JL is employee of the Federal Association of the AOK, HM is employee of Eisai GmbH, PMa is Head of Market Access of Pfizer Germany and SR is a former employee of Pfizer Germany. The IDA project was initiated and financed by the four partners with equal rights in conception, development and implementation: the AOK Bavaria - Health insurer and the Federal Association of the AOK - one of the largest statutory health insurances in Germany - and the research-based pharmaceutical companies Eisai and Pfizer. The aim of this public-private-partnership is to improve the care of dementia patients and the support of their informal care-givers.CD carried out the statistical procedures, interpretation of the data and wrote the manuscript. RH is principal statistical investigator, participated in the design of the study and gave advice concerning data analysis. EG is principal clinical investigator, participated in the design of the study and helped to draft the manuscript. PMe contributed to the data analysis by calculating cluster-effect adjusted measures. MGS carried out the data management and quality assurance of the data. JL planned and supervised the project and gave advice concerning structuring the manuscript. HM, PMa, SR planned and accompanied the research project and revised the manuscript. SW was the head of the local project team and revised the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6963/10/314/prepub


Rheumatoid arthritis (RA) is a chronic and disabling polyarthritic disease, which affects mainly women in middle and old age.            Proteus mirabilis microbes and RA. We propose that sub-clinical Proteus urinary tract infections are the main triggering factors and that the presence of molecular mimicry and cross-reactivity between these bacteria and RA-targeted tissue antigens assists in the perpetuation of the disease process through production of cytopathic auto-antibodies.Extensive evidence based on the results of various microbial, immunological and molecular studies from different parts of the world, shows that a strong link exists between             Proteus anti-bacterial measures involving the use of antibiotics, vegetarian diets and high intake of water and fruit juices such as cranberry juice in addition to the currently employed treatments.Patients with RA especially during the early stages of the disease could benefit from


In this report from the 1st European Conference of the European Science Foundation Programme on Functional Genomics, we provide coverage of the high-profile plenarytalks and a cross-section of the many presentations in the disease analysis symposiaand functional genomics technologies workshops.


Successful anterior cruciate ligament reconstruction with a tendon graft necessitates solid healing of the tendon graft in the bone tunnel. Improvement of graft healing to bone is crucial for facilitating an early and aggressive rehabilitation and ensuring rapid return to pre-injury levels activity. Tendon graft healing in a bone tunnel requires bone ingrowth into the tendon. Indirect Sharpey fiber formation and direct fibrocartilage fixation confer different anchorage strength and interface properties at the tendon-bone interface. For enhancing tendon graft-to-bone healing, we introduce a strategy that includes the use of periosteum, hydrogel supplemented with periosteal progenitor cells and bone morphogenetic protein-2, and a periosteal progenitor cell sheet. Future studies include the use of cytokines, gene therapy, stem cells, platelet-rich plasma, and mechanical stress for tendon-to-bone healing. These strategies are currently under investigation, and will be applied in the clinical setting in the near future. One of the most challenging and important problems physicians are facing is the failure of anterior cruciate ligament (ACL) reconstruction after injury and primary surgical repair -4. It isACL reconstruction using semitendinosus and gracilis tendons has become popular in recent years. Tendon-to-bone incorporation of the tendon graft within a bone tunnel is a main concern when using a tendon graft for ligament reconstruction. Successful ACL reconstruction with a tendon graft requires solid healing of the tendon graft in the bone tunnel as soon as possible after surgery. Enhancing the healing of the tendon graft to the bone is crucial to facilitate an early and aggressive rehabilitation and a rapid return to full activity. The basic biology of the tendon graft-bone tunnel healing remains incompletely understood. Distinct variability occurred in the morphological characteristics of the healing at the site of attachment of the tendon and the bone. The tendon-to-bone healing in a bone tunnel occurs by bone ingrowth into the fibrovascular interface tissue that initially forms between the tendon and the bone. First, progressive mineralization of the interface tissue occurs. Subsequently, the bone grows into the outer tendon and the tendon graft becomes incorporated into the surrounding bone. Progressive re-establishment of the continuity of collagen fibers between the tendon and the bone results in restoration of a tendon-bone junction -16.The primary site of weakness during the early postoperative period is the tendon-bone interface, particularly while the tendon attaches to the bone within the intraarticular environment. The osteointegration of the tendon grafts used for the replacement of an ACL may still be unsatisfactory and may be associated with postoperative anterior-posterior laxity. The firm attachment of the tendon graft to the bone allows earlier and more aggressive rehabilitation and a quicker return to full activity.To improve the healing of the ACL graft, new strategies to promote the intra-articular and intraosseous healing are evolving. Although these strategies are currently under investigation, they are expected to be clinically applied in the near future. The strategies to improve the tendon-to-bone tunnel healing focus on providing appropriate molecular signaling thereby allowing cell differentiation which result in an effective healing response between the tendon and the bone. A sufficient population of stem cells is required for optimal tissue regeneration. The mesenchymal stem cell-treated grafts have cartilage at the tendon-bone interface -20. BoneThese various methods demonstrate the challenge of achieving a secure biologic fixation of the tendon graft in a bone tunnel with the current ACL reconstruction techniques.Our strategy to enhance the tendon-to-bone healing is to use the periosteum, hydrogel with periosteal progenitor cells (PPCs) and BMP-2 and PPC sheets.The periosteum consists of multipotent mesodermal cells. In addition, it contains chondroprogenitor and osteoprogenitor cells, which can form both cartilage and bone under appropriate conditions -37. The In the bone tunnel model, cross sections of the bone tunnel showed that the periosteal tissue formed a fibrovascular interface between the tendon and the bone. Due to the new bone formation, the cancellous bone in the bone tunnel interdigitated with the fibrous interface tissue four weeks after operation. There was progressive mineralization and maturation of the new bone that grew into the interface fibrous layer. There appeared to be excellent integration between the fibrous interface layer and the bone and between the tendon and the interface layer at eight weeks after operation. Progressive collagen fiber-bone anchoring, maturation and organization between the tendon and the bone lining cells occurred. In addition, fibrocartilage formed between the tendon and the bone .In the ACL reconstruction model, radiographs showed bone resorption as well as the formation of new bone around the femoral and tibial bone tunnel in the periosteum-treated tendon graft. There was further matrix deposition at the tendon-to-bone interface. Eight weeks after operation, the periosteum-enveloping specimens demonstrated cartilage and bone formation around the tendon graft in the femoral and tibial tunnel. There was extensive formation of new bone trabeculae and cartilage at the tendon-to-bone interface with new bone direct apposition to the tendon .The periosteum-treated tendon graft was used for ACL reconstruction to enhance the healing of the tendon graft in the bone tunnel. The graft was composed of double loops of semitendinosus and gracilis tendons. A periosteal flap was harvested from the anterior tibial cortex and divided into two flaps. The periosteum was wrapped with the cambium layer, placed outside to face the tunnel wall and then sutured on the tendon at both sides where the tendon graft approaches the tunnel opening Fig. 1)..1). In tPPCs have the potential to differentiate into osteogenitor and chondrogenitor cells in an adequate microenvironment. PPCs are used to enhance the tendon-to-bone healing process by forming a fibrocartilage interface. A novel injectable hydrogel supplemented with PPCs and BMP-2 was developed for an easier delivery into the bone tunnel.Photopolymerization allows for an impressive degree of spatial and temporal control with implications for diverse, minimally invasive applications for tissue regeneration. -50 PPCs Hyaluronic acid (HA) is applied for biomaterial fabrication and application to transduce intrinsic signals within a structure and to enhance tissue formation. In addition, it plays a crucial role in promoting cell differentiation and cell growth ,57. In oIn the bone tunnel model, we tested the feasibility of HA tethered to BMP-2 to stimulate PPCs to direct the fibrocartilagenous attachment and new bone formation in an extra-articular tendon-to-bone healing model. The PPC-BMP-2 hydrogel was injected and photogelated in the bone tunnel after placing the tendon graft into the bone tunnel. The histological analysis showed that interface fibrocartilage and new bone formed within six weeks. The healing of the tendon-to-bone interface underwent a gradual remodeling process. The biomechanical testing revealed a higher maximum pull-out strength and stiffness with a statistically significant difference. It appears that photoencapsulation of BMP-2 and PPCs has a powerful inductive ability for the healing between tendon and bone .In the ACL reconstruction model, the PPC-BMP-2 hydrogel was injected and photogelated in the femoral and tibial tunnel after ACL reconstruction with a flexor digitorum longus tendon in rabbits. Histological analysis of the tendon-to-bone interface in the femoral and tibial tunnel showed that an interface layer was formed by the hydrogel. After eight weeks, there was further matrix deposition with fibrocartilage formation at the tendon-to-bone junction. After 12 weeks, large areas of fibrocartilage at the tendon-to-bone junction formed an interface. The use of the PEGDA-based hydrogel provided an adequate matrix for the encapsulation of cells and signal factors. In addition, it was an effective local delivery method to reach the bone tunnel through injection. After the hydrogel is injected, it can be solidified via a photoinitiated polymerization process which ensures encapsulation of the stem cells and growth factors  Fig. 3)3).A scaffold-free method using polymerized fibrin-coated dishes to generate functional PPC sheets that can be used as periosteum-like tissue transplants was developed. Polymerized fibrin-coated polyethylene dishes were fabricated with fibrinogen monomers which were mixed with thrombin. PPCs derived from the periosteum of the tibia of rabbits were cultivated on a fibrin-coated surface. The laminated cell sheets were detached from the polymerized fibrin layer by proteases secreted from the cells. The PPC sheets were seeded onto the small intestinal submucosa (SIS) layer. The PPC sheets could be harvested non-invasively as intact, transplantable sheets by using an intrinsic protease. The PPC sheets were wrapped around the tendon grafts which were then used for ACL reconstruction in rabbits. There was further matrix deposition with formation of fibrocartilage at the tendon-to-bone junction after eight weeks. The bioengineered PPC sheets and SIS co-layer cell sheet act as artificial periosteum which offers a novel therapeutic strategy to augment the healing at the tendon-to-bone junction Fig. .Current techniques of ACL graft reconstruction require healing of a tendon graft in a bone tunnel. The attachment site of the graft to the bone differs from the human anatomy where ligaments attach to the surface of bone. There are no sites in the body where a tendon is surrounded by bone such as in a bone tunnel. A common cause for an unsatisfactory ACL reconstruction is a failure of the graft-to-bone healing. Three fundamental factors may be responsible for the lack of cell signaling and differentiation resulting in an ineffective healing response between the tendon and the bone. These factors include the presence of inflammation in the postnatal organism, tendon-to-bone interface motion and an insufficient number of undifferentiated cells at the healing tendon-to-bone interface.The successful ACL reconstruction with a tendon graft necessitates effective healing of the tendon graft in the femoral and tibial bone tunnel. The tendon-to-bone healing progresses via an interzone of vascular, highly cellular fibrous tissue, which undergoes a maturation process that lasts until its matrix consists of oriented collagen fibers and the fibrous interface becomes indistinctable. ,60 The tWhen a bone-patellar tendon-bone (BPTB) graft is used for ACL reconstruction, the fixation of the graft depends on the bone-to-bone healing. However, the length of the patella tendon portion of most BPTB grafts is greater than the intra-articular length of the ACL, resulting in tendon-to-bone healing  rather than bone-to-bone healing. It is believed that the graft fixation strength is lower and the healing is poorer in the tendon graft compared with the bone plug healing in the tunnel. In the tendon graft, the weakest site was the graft-wall interface at three weeks and the intraosseous tendon graft at six weeks .Spatial and temporal differences in the tendon-to-bone healing exist in the different regions of the bone tunnel. The healing of the tendon-to-bone interface tissue shows a wide chondroid matrix at the intra-articular aperture, in contrast to a narrow, fibrous matrix at the intra-osseous portion. The collagen continuity between the tendon graft and the bone tunnel increased over time, with a more parallel orientation and increased collagen fiber continuity between the tendon and the bone. Significant differences in the healing between the tendon graft and the bone exist throughout the length of bone tunnel. The etiology of these differences includes a variable biological and biomechanical environment at different sites of the tunnel.  AdequateOn the basis of a normal ACL structure and the known function of the insertion site, the ideal tendon graft would attach broadly to the surface of the bone at the site of the femur and tibia by an intermediate zone of fibrocartilage.The periosteum contains multipotent mesodermal cells. It has been shown that the environment has an influence on the differentiation of cells in free periosteal grafts . The perThe cambium layer serves as a fibrous layer between tendon and bone when the periosteum is sutured on the surface of the tendon and transplanted into a bone tunnel. The bone ingrowth into the cambium layer as well as the interdigitation between the periosteal tissue and tendon can be observed after four weeks. The interface of the fibrous layer, which originates from the wrapped periosteum, becomes progressively incorporated. The organization of the interface develops over time. There is an extensive formation of fibrocartilage at the tendon-bone interface. The periosteum has the powerful inductive ability to enhance the healing between the tendon and the bone tunnel. The periosteum can induce the differentiation of mononuclear cells into chondroblastic and osteoblastic cells. Subsequently, it directs the production of fibrocartilage or osteoid followed by mineralization and progressive remodeling which occurs during the healing process . The perThe expansion of the tunnel is significantly greater following ACL reconstruction using hamstring tendon autografts. This is because of the greater distance between the normal insertion site and the biomechanical point of action of the ACL. The greater distance creates a potentially larger force moment during graft cycling which may lead to the greater expansion of the bone tunnel . AdequatIn order to enhance the tendon-to-bone tunnel healing, our laboratory intended to develop an injectable hydrogel to fill the tendon-bone tunnel interface in a tissue-engineering approach. Tissue-engineering therapies for biomimetic material rely on the stimulation of signaling growth factors to induce cellular chemotaxis, proliferation, differentiation and a notable formation of new tissue at the required site. Recent studies have shown that various growth factors play important roles in tissue repair both in vivo and in vitro ,61,67-72Based on the finding that the tendon-to-bone healing progresses by bone ingrowth into the fibrous tissue interzone, exogenous osteoinductive agents should be used to augment this process. We demonstrated improved healing by applying injectable photopolymerizable hydrogel at the tendon-to-bone interface ,74. Our Cell therapy for tissue regeneration together with tissue engineering technology develops rapidly. Functional cell sheets for transplants are formed by cells. Biomaterials serve as cell carrier. The cell sheets can be easily detached and maintain the complete connective matrix in cells, cell phenotype, proliferation and differentiation. In our study, periosteum-like cell sheets were formed for orthopedic tissue regeneration. The PPCs and chondrocytes were used to produce periosteum-like cell sheets. The PPC carriers were prepared by polymerization of fibrinogen monomers mixed with thrombin. Natural acellular SIS was used as delivery vehicle for the cell sheets. The PPC sheets were placed onto a SIS layer thereby forming an artificial periosteal bilayer. The PPC sheets were wrapped around the tendon graft and placed into the bone tunnel. Histology showed higher matrix deposition with fibrocartilage formation at the tendon-bone junction after four weeks. Our results suggest that well-organized and functional PPC sheets maintain their differentiated capacity and keep their ex vivo osteochondral potential. The PPC sheets could act as periosteum to offer a novel approach to enhance the healing at the tendon-bone junction.Successful ACL reconstruction with a tendon graft requires solid healing of the tendon graft in the bone tunnel. Recent improvements in ACL reconstruction techniques have highlighted the importance of new biologic strategies to promote the intraarticular and intraosseous healing. Future techniques to improve the tendon-to-bone healing may include the use of cytokines, which will provide important signals for tissue formation and differentiation, gene therapy techniques, which will ensure the prolonged presence of molecules important for the healing process, stem cells, which will help produce a population of undifferentiated cells, and transcription factors, which will help direct nuclear gene expression. In addition, platelet-rich plasma or platelet gel from autologous blood facilitates delivery of serum-derived cytokines. Several techniques are being developed to inhibit the expression of molecules that might prohibit successful healing. Furthermore, modulation of the biomechanical environment may have profound effects on the cellular and molecular events at the healing tendon-bone interface . These bThe author declares that they have no competing interests.CHC prepared all the manuscript.


The optimal radical non-surgical management of carcinoma of the oesophagus has yet to be determined. The combination of high-dose radiotherapy with chemotherapy is being explored, particularly in North America. The MRC Upper GI Working Party has debated the areas where there is scientific uncertainty and which clinical trials may be appropriate to undertake in the UK.


We have studied the radiomodifying action in mouse skin of WR-2721 and misonidazole (MISO) when used alone or in combination. The radioprotection with WR-2721 was drug-dose dependent and highly influenced by the O2 concentration at the time of irradiation. Significant sensitizaton was observed with MISO, especially in air-breathing mice. The combination of WR-2721 and MISO produced a radiation response intermediate between the resistant and sensitive responses to either drug alone. The precise degree of sensitivity was dependent on the relative doses of protector and sensitizer. We have also studied the interaction of both drugs in terms of drug-induced lethality, which showed a clear toxic interaction. The WR-2721 LD50 was reduced by a factor of 1.4 with only 200 mg/kg of MISO. We conclude that the combination of WR-2721 and MISO shows an interaction in terms of drug toxicity and radiation response, such that the radioprotection of skin is reduced or even abolished with low doses of MISO.


Leukaemia cells from the peripheral blood and bone marrow of patients with acute myeloblastic leukaemia were labelled in vitro with [125I]5-iodo-2'-deoxy-uridine (IUdR). The myeloblasts were then injected into groups of mice and the survival of these cells estimated by measuring isotope loss, using whole-body counting. The isotope excretion from mice treated with various doses of cytosine arabinoside (Ara-C) and those not treated with drugs were compared. This comparison showed that the sensitivity of myeloblasts to the drug varies from patient to patient, and in one case was different for myeloblasts from bone marrow and from blood from the same patient. We compare the clinical responses of myeloblasts to Ara-C in 6 patients, who had high peripheral blood myeloblast counts, with the sensitivities of their myeloblasts to Ara-C in mice. This comparison indicates that the assay might be a useful way of predicting the response of leukaemic cells in patients to cytotoxic agents.


Stroke-specific outcome measures and descriptive measures of health-related quality of life (HRQoL) are unsuitable for informing decision-makers of the broader consequences of increasing or decreasing funding for stroke interventions. The quality-adjusted life year (QALY) provides a common metric for comparing interventions over multiple dimensions of HRQoL and mortality differentials. There are, however, many circumstances when – because of timing, lack of foresight or cost considerations – only stroke-specific or descriptive measures of health status are available and some indirect means of obtaining QALY-weights becomes necessary. In such circumstances, the use of regression-based transformations or mappings can circumvent the failure to elicit QALY-weights by allowing predicted weights to proxy for observed weights. This regression-based approach has been dubbed 'Transfer to Utility' (TTU) regression. The purpose of the present study is to demonstrate the feasibility and value of TTU regression in stroke by deriving transformations or mappings from stroke-specific and generic but descriptive measures of health status to a generic preference-based measure of HRQoL in a sample of Australians with a diagnosis of acute stroke. Findings will quantify the additional error associated with the use of condition-specific to generic transformations in stroke.We used TTU regression to derive empirical transformations from three commonly used descriptive measures of health status for stroke  to a preference-based measure (AQoL) suitable for attaching QALY-weights to stroke disease states; based on 2570 observations drawn from a sample of 859 patients with stroke.Transformations from the SF-36 to the AQoL explained up to 71.5% of variation in observed AQoL scores. Differences between mean predicted and mean observed AQoL scores from the 'severity-specific' item- and subscale-based SF-36 algorithms and from the 'moderate to severe' index- and item-based Barthel algorithm were neither clinically nor statistically significant when 'low severity' SF-36 transformations were used to predict AQoL scores for patients in the NIHSS = 0 and NIHSS = 1–5 subgroups and when 'moderate to severe severity' transformations were used to predict AQoL scores for patients in the NIHSS ≥ 6 subgroup. In contrast, the difference between mean predicted and mean observed AQoL scores from the NIHSS algorithms and from the 'low severity' Barthel algorithms reached levels that could mask minimally important differences on the AQoL scale.While our NIHSS to AQoL transformations proved unsuitable for most applications, our findings demonstrate that stroke-relevant outcome measures such as the SF-36 and Barthel Index can be adequately transformed to preference-based measures for the purposes of economic evaluation. The economic evaluation of health programs is often and increasingly a prerequisite in obtaining funding from third-party payers seeking to get the best value from a limited health budget. Where treatment is expected to impact on health-related quality of life (HRQoL), selecting an appropriate outcome measure frequently entails a trade-off between the sensitivity of available instruments for the disease or condition under study and the comparability (and therefore policy-relevance) of study results. Leaving aside the question of whether disease-specific outcome measures really are more sensitive than more generic measures, a number of difficulties arise in selecting a comparable outcome measure for use in economic evaluation.While the minimal clinically significant improvement on a descriptive measure such as the SF-36, NIHSS or Barthel could be used to partition the trial population into responders and non-responders before expressing findings in terms of cost per additional responder, such an approach would not achieve comparability of findings even in the event that every other evaluation was also to express results in terms of responders. Because descriptive measures lack weak interval properties, there is no guarantee that a 10 point improvement at the upper end of the scale is equivalent to a 10 point improvement at the lower end of the scale. The weak interval property simply requires that a given numerical change along a scale should have the same meaning regardless of the direction and location of that change  put it, and relevant dimensions of HRQoL. Richardson .We identify the 'correct' specification within each class of algorithm using standard diagnostic tests. Following Harvey , the 'coWith regards to (i), the higher the strength of association, the better the algorithm is able to predict variation along the scale. Note, however, that "two measures can be perfectly correlated but have poor agreement" . at the group level is all that is required. For the purposes of evaluating precision at the group level in the present study, we split the study sample into three sub-groups defined by stroke severity on the NIHSS . While (iii) is the most relevant test of predictive validity in measuring group-level treatment effects and health-state utilities, we report findings on all three criteria to provide a more complete evaluation of the strengths and weaknesses of our transformations. We conducted the analyses reported here using SPSS 15.0 for Windows ; in children with stroke.Finally, it should be emphasised that the models estimated in the present study are not intended for application in non-stroke populations. The weight attached to each item, subscale or scale entering each of our conversion algorithms reflects the covariance in our data between AQoL health states and Barthel, NIHSS or SF-36 health states. Because this covariance is likely to be quite different in stroke than in other disease-areas or the general population, our conversion algorithms may not be applicable to non-stroke populations. More generally, our findings are contingent upon the characteristics of our study population and on the coverage and sensitivity of the descriptive and preference-based measures used to generate our conversion algorithms. Note, for example, that our findings regarding the feasibility and value of TTU regression in stroke-specific outcome measures might not be generalisable to all condition-specific measures in all disease-areas. Likewise, where transformations have been derived and validated in a sample of stroke-patients with mean age exceeding 70 years, those transformations cannot be assumed valid for the purposes of predicting QALY-weights Despite these limitations, the conversion algorithms reported here represent an improvement on the regression-based conversion algorithms that have previously been validated for use in stroke ,28. MoreOur findings suggest that TTU regression can provide a useful second-best approach for deriving QALY-weights associated with stroke disease-states. While the NIHSS to AQoL transformations proved unsuitable for most applications, transformations from the SF-36 and Barthel to the AQoL provided sufficient predictive power to suggest that stroke-relevant outcomes can be transformed to preference-based measures for the purposes of economic evaluation. While a number of generic to generic transformations from the SF-36 to preference-based outcome measures are now available, the SF-36 to AQoL transformations reported here are the only published transformations to have been derived and validated in a sample of stroke patients . MoreoveThe implications for practice are two-fold. First, it is anticipated that our transformations will prove to be a valuable tool for analysts and should allow the best use to be made of the available data; improving the quality and policy-relevance of economic evaluations for stroke interventions. Second, improvements in the economic evaluation of stroke interventions should allow clinicians and policy-makers to make better decisions; potentially saving money and improving patient outcomes. Our findings also have a number of implications for research. First, researchers may wish to take account of the feasibility of TTU regression in certain condition-specific measures (but not in others) when selecting descriptive outcome measures for inclusion in clinical trials. Such considerations will be particularly important where resource constraints or patient burden preclude the direct observation of preference-based measures in the trial population. Second, researchers attempting to derive their own regression-based transformations for other descriptive measures should take particular note of the improvements in predictive validity that we were able to obtain by deriving separate transformations for clinically distinct subgroups of patients. Finally, our findings suggest that validity in predicting group-wise differences will not always translate to validity in predicting health state utilities or change scores for individual patients. Researchers responsible for the derivation of regression-based transformations might therefore wish to provide guidelines for end-users to ensure use consistent with validation data.The authors declare that they have no competing interestsDM participated in the design of the study, data analysis and interpretation of results, and drafted the manuscript. LS participated in the design of the study and interpretation of results, and suggested edits and revisions to the manuscript. JS contributed to the acquisition and interpretation of the data, participated in the interpretation of results, and suggested edits and revisions to the manuscript. All authors read and approved the final manuscript.


Chinese hamster ovary cells have been treated in vitro with the platinum coordination complexes cis-PAD or CHIP and with radiation, either alone or in combination with different doses and time intervals. The isobologram method has been used to make a graphic comparison of these combined-modality data in terms of additivity and enhancement. The data showed enhancement of the radiation effect by these platinum complexes in many combinations, and a truly synergistic effect in one case. This method of analysis points to the limited usefulness of the parameter dose-modifying effect (DMF) since the most synergistic combination did not have the highest DMF.


We have measured mitotic indices and 3H-thymidine-labelling indices for the colonic epithelial tumours induced in rats by the administration of dimethyl-hydrazine (DMH). The fraction-of-labelled-mitoses (FLM) technique has been used to estimate the duration of the cell-cycle phases. In general, mitotic and labelling indices in the tumours are similar to those in the proliferation zone of the normal crypt epithelium; lesions considered to be least well differentiated on histological grounds appear to have the lowest mean labelling index. Benign tumours and the different types of malignant tumours have mean cell-cycle times about half those of the normal mucosa.


Recent studies have suggested a correlation between the rate and incidence of apoptosis and the radiation response of particular cell lines. However, we found that increasing the rate of induction of apoptosis in the fibroblast line 208F, by transfecting it with human c-myc, did not lead to a change in its clonogenic survival dose-response for either gamma-irradiation or 125I-induced DNA damage. It was also found that expression of mutant (T24) Ha-ras in the 208F line appeared to decrease the level of apoptosis per mitosis after irradiation and inhibited the formation of nucleosomal ladders, but did not affect either the onset of the morphological features of apoptosis or the clonogenic survival dose-response of the cells to either gamma-irradiation or 125I-induced DNA damage. Our findings suggest that it may be incorrect to make predictions about the radiosensitivity of cells based only on knowledge of their mode of death.


PG hydrolyses thehomogalacturonan of the plant cell wall and is considered an important pathogenicityfactor of many fungi. PGIP is a specific inhibitor of fungal PGs and is thought to beinvolved in plant defence against phytopathogenic fungi. SPR was used either to study theeffect of the PG glycosylation on the formation of the complex with PGIP, and as asensitive affinity capture of an interacting peptide from a mixture of PG fragmentsobtained by limited proteolysis. Mass spectrometry allowed to characterise the interactingpeptide eluted from the sensor surface.A combination of surface plasmon resonance (SPR) and matrix-assisted laser-desorptionionization-time-of-flight mass spectrometry (MALDI-TOF-MS) was used to study theinteraction between


We would like to report on our experience of illustrating our operation notes with pre-, per- and post-operative digitalimages.