Molecular dissection of TNFR-TNFα bidirectional signaling reveals both cooperative and antagonistic interactions with p75 neurotrophic factor receptor in axon patterning.

During neural development, complex organisms rely on progressive and regressive events whereby axons, synapses, and neurons are overproduced followed by selective elimination of a portion of these components. Tumor necrosis factor α (TNFα) together with its cognate receptor (Tumor necrosis factor receptor 1; TNFR1) have been shown to play both regressive (i.e. forward signaling from the receptor) and progressive (i.e. reverse signaling from the ligand) roles in sympathetic neuron development. In contrast, a paralog of TNFR1, p75 neurotrophic factor receptor (p75NTR) promotes mainly regressive developmental events in sympathetic neurons. Here we examine the interplay between these paralogous receptors in the regulation of axon branch elimination and arborization. We confirm previous reports that these TNFR1 family members are individually capable of promoting ligand-dependent suppression of axon growth and branching. Remarkably, p75NTR and TNFR1 physically interact and p75NTR requires TNFR1 for ligand-dependent axon suppression of axon branching but not vice versa. We also find that p75NTR forward signaling and TNFα reverse signaling are functionally antagonistic. Finally, we find that TNFα reverse signaling is necessary for nerve growth factor (NGF) dependent axon growth. Taken together these findings demonstrate several levels of synergistic and antagonistic interactions using very few signaling pathways and that the balance of these synergizing and opposing signals act to ensure proper axon growth and patterning.

Of the necessary interplay of therapy and pedagogy in psychiatric hospitals for children with intellectual disability.

BACKGROUND: Mentally ill children with intellectual disabilities do not always receive the services they need for effective change at psychiatric hospitals, as their verbal limitations render standard procedures in diagnostics and therapy difficult or impossible, as their ability to transfer insights acquired in one setting to another is impaired and as their families and caretakers are often overwhelmed by their needs. This is why an integral vision for children with intellectual disabilities is presented. Drawing on three case reports, it is highlighted how an interdisciplinary approach, a changed hospital set-up and constant interplay between therapy and pedagogy, between services to the child and to its caregivers can help overcome these difficulties. METHOD: Case reports. CONCLUSIONS: Some children risk being mistakenly treated as intellectually disabled. If testing reveals, for example, autism with a mild learning disability, psychoeducation and the pedagogical training for (special school) personnel can help prevent underachievement and bring about a setting that can help the child flourish. Both sensitive care and pedagogical intervention that fit the developmental age of severely intellectually disabled children can prevent their receiving sedatives to treat aggressive behaviour. Substantial and lasting shifts in mood, even happiness can result if parents and caregivers get the pedagogical training and the assistance they need to take care of their children. Reliable and well-structured pedagogical training and environments can enhance and often substitute for unavailable therapeutic interventions for this specific group. With some profound intellectually and multiply disabled children, beginning medical treatment at home may not be safe. The (in)effectiveness of specific psychiatric medications needs to be monitored by observations however. For reliable results with intellectually disabled children, a clinical setting that resembles their everyday life is needed.

[Bone substitute materials as local drug carriers : Current status of substitutes of various origins]. / Knochenersatzwerkstoffe als lokale Wirkstoffträger : Aktueller Stand bei Ersatzstoffen verschiedenen Ursprungs.

BACKGROUND: Autologous bone grafts (autografts) are used in surgery for defect filling and impaction grafting during hip socket and femur reconstruction. Because of their superior osteoinductive capacity, autografts are considered the "gold standard" for these treatments. However, because of a better cost-benefit ratio, allografts are also often used. In the case of limited donor availability for autologous or allogenic bone grafts, bone substitute materials (BSMs) are a reasonable alternative or supplement. BSM are based on or combine different substances. Growth factors of the bone morphogenetic protein family BMP are recombinant proteins that specifically induce the growth of bone and cartilage tissue. CHARACTERISTICS: One advantage of BSM is the option to combine them with several anti-infective agents. The choice of the anti-infective substance should not only be based on the antimicrobial efficacy, but should also take into account possible dose-dependent cellular and pharmacological side effects at the implantation site. Thus, microbiologists, pharmacists and surgeons should decide together which combination is the most appropriate. COMBINATION PRODUCTS: BSM with active agent additives are considered combination products that are characterized by a main effect (bone replacement function) and a secondary effect (prophylaxis of bacterial recolonization of BSM). Both functions must be thoroughly (clinically) evidenced in the course of the registration process as a class III medical device. Drug authorities evaluate the active agents, their function and corresponding indication. Currently, only a few combination products are available on the market. As a consequence of the only limited availability of such commercial combination products, surgeons in clinical practice often manually add the active agent to BSM in the theatre prior to implantation. However, such a customized addition of antibiotics places the surgeon in a situation of a manufacturer where he assumes liability for the product.

[Potential of allogeneic bone grafts as antibiotic carriers : Effect of different preparation processes on efficacy]. / Allogene spongiöse Knochenpräparate als Antibiotikaträger : Einfluss verschiedener Aufbereitungsverfahren auf die Wirksamkeit.

BACKGROUND: The rising number of primary joint replacements worldwide is causing an increase of endoprosthetic revision surgery due bacterial infection. Revision surgery using non-cemented implants seems beneficial for the long-term outcome, and the use of antibiotic-impregnated bone grafts might control the infection and provide a good support for the implant. In this study, we evaluated the release of antibiotics from fresh-frozen and lyophilized allogeneic bone grafts. METHODS: Heat-treated, lyophilized and fresh frozen cryopreserved bone chips were impregnated with gentamicin sulphate, gentamicin palmitate and vancomycin, and calcium carbonate/calcium sulphate treated with antibiotics. The efficacy of each preparation was measured by drug release tests and bacterial susceptibility using B. subtilis, S. aureus and methicillin-resistant Staphylococcus aureus. RESULTS: The release of gentamicin from lyophilized bone was similar to the release rate from fresh frozen bone during the entire experiment. This might be related to the similar porosity and microstructure of the bone chips. The release of gentamicin from lyophilized and fresh frozen bone was high on the first and second days, then decreased and stayed at a low rate until the end of the second week. CONCLUSION: Depending on the surgical strategy, either polymethylmethacrylate or allogeneic bone are able to deliver sufficient concentrations of gentamicin to achieve bacterial inhibition within 2 weeks after surgery. In the case of uncemented revision of joint replacements, allogeneic bone can deliver therapeutic doses of gentamicin and peak levels immediately and a fortnight after implantation.

Scattering of the Halo Nucleus

Angular distributions of the elastic, inelastic, and breakup cross sections of the halo nucleus ^{11}Be on ^{197}Au were measured at energies below (E_{lab}=31.9 MeV) and around (39.6 MeV) the Coulomb barrier. These three channels were unambiguously separated for the first time for reactions of ^{11}Be on a high-Z target at low energies. The experiment was performed at TRIUMF (Vancouver, Canada). The differential cross sections were compared with three different calculations: semiclassical, inert-core continuum-coupled-channels and continuum-coupled-channels ones with including core deformation. These results show conclusively that the elastic and inelastic differential cross sections can only be accounted for if core-excited admixtures are taken into account. The cross sections for these channels strongly depend on the B(E1) distribution in ^{11}Be, and the reaction mechanism is sensitive to the entanglement of core and halo degrees of freedom in ^{11}Be.

Epidemiological and serological investigation of a waterborne Campylobacter jejuni outbreak in a Danish town.

Following an unusually heavy rainfall in June 2009, a community-wide outbreak of Campylobacter gastroenteritis occurred in a small Danish town. The outbreak investigation consisted of (1) a cohort study using an e-questionnaire of disease determinants, (2) microbiological study of stool samples, (3) serological study of blood samples from cases and asymptomatic members of case households, and (4) environmental analyses of the water distribution system. The questionnaire study identified 163 cases (respondent attack rate 16%). Results showed a significant dose-response relationship between consumption of tap water and risk of gastroenteritis. Campylobacter jejuni belonging to two related flaA types were isolated from stool samples. Serum antibody levels against Campylobacter were significantly higher in cases than in asymptomatic persons. Water samples were positive for coliform bacteria, and the likely mode of contamination was found to be surface water leaking into the drinking-water system. This geographically constrained outbreak presented an ideal opportunity to study the serological response in persons involved in a Campylobacter outbreak. The serology indicated that asymptomatic persons from the same household may have been exposed, during the outbreak period, to Campylobacter at doses that did not elicit symptoms or alternatively had been exposed to Campylobacter at a time prior to the outbreak, resulting in residual immunity and thus absence of clinical signs.

[Peppermint oil in the acute treatment of tension-type headache]. / Oleum menthae piperitae (Pfefferminzöl) in der Akuttherapie des Kopfschmerzes vom Spannungstyp.

Tension-type headache is the most frequent form of headache. The local topical treatment with peppermint oil (oleum menthae piperitae) has proven to be significantly more effective than placebo in controlled studies. Peppermint oil targets headache pathophysiology in multiple ways. The efficacy is comparable to that of acetylsalicylic acid or paracetamol. Solutions of 10 % peppermint oil in ethanol are licensed for the treatment of tension-type headache in adults and children above 6 years. It is included in treatment recommendations and guidelines by the respective professional societies and is regarded as a standard treatment for the acute therapy of tension-type headaches.

In vitro evaluation of novel antimicrobial coatings for surgical sutures using octenidine.

BACKGROUND: Sutures colonized by bacteria represent a challenge in surgery due to their potential to cause surgical site infections. In order to reduce these type of infections antimicrobially coated surgical sutures are currently under development. In this study, we investigated the antimicrobial drug octenidine as a coating agent for surgical sutures. To achieve high antimicrobial efficacy and required biocompatibility for medical devices, we focused on optimizing octenidine coatings based on fatty acids. For this purpose, antimicrobial sutures were prepared with either octenidine-laurate or octenidine-palmitate at 11, 22, and 33 µg/cm drug concentration normalized per length of sutures. Octenidine containing sutures were compared to the commercial triclosan-coated suture Vicryl® Plus. The release of octenidine into aqueous solution was analyzed and long-term antimicrobial efficacy was assessed via agar diffusion tests using Staphylococcus aureus. For determining biocompatibility, cytotoxicity assays (WST-1) were performed using L-929 mouse fibroblasts. RESULTS: In a 7 days elution experiment, octenidine-palmitate coated sutures demonstrated much slower drug release (11 µg/cm: 7%; 22 µg/cm: 5%; 33 µg/cm: 33%) than octenidine-laurate sutures (11 µg/cm: 82%; 22 µg/cm: 88%; 33 µg/cm: 87%). Furthermore sutures at 11 µg/cm drug content were associated with acceptable cytotoxicity according to ISO 10993-5 standard and showed, similar to Vicryl® Plus, relevant efficacy to inhibit surrounding bacterial growth for up to 9 days. CONCLUSIONS: Octenidine coated sutures with a concentration of 11 µg/cm revealed high antimicrobial efficacy and biocompatibility. Due to their delayed release, palmitate carriers should be preferred. Such coatings are candidates for clinical testing in regard to their safety and efficacy.

Separate norovirus outbreaks linked to one source of imported frozen raspberries by molecular analysis, Denmark, 2010-2011.

Norovirus outbreaks occur frequently in Denmark and it can be difficult to establish whether apparently independent outbreaks have the same origin. Here we report on six outbreaks linked to frozen raspberries, investigated separately over a period of 3 months. Norovirus from stools were sequence-typed; including extended sequencing of 1138 bp encompassing the hypervariable P2 region of the capsid gene. Norovirus was detected in 27 stool samples. Genotyping showed genotype GI.Pb_GI.6 (polymerase/capsid) with 100% identical sequences. Samples from five outbreaks were furthermore identical over the variable capsid P2 region. In one outbreak at a hospital canteen, frozen raspberries was associated with illness by cohort investigation (relative risk 6·1, 95% confidence interval 3·2-11). Bags of raspberries suspected to be the source were positive for genogroup I and II noroviruses, one typable virus was genotype GI.6 (capsid). These molecular investigations showed that the apparently independent outbreaks were the result of one contamination event of frozen raspberries. The contaminated raspberries originated from a single producer in Serbia and were originally not considered to belong to the same batch. The outbreaks led to consultations and mutual visits between producers, investigators and authorities. Further, Danish legislation was changed to make heat-treatment of frozen raspberries compulsory in professional catering establishments.

[Augmentation with PMMA cement]. / Augmentation mit PMMA-Zement.

Cements based on polymethyl methacrylate (PMMA) can be used without any problem in a variety of clinical augmentations. Cement-related complications in surgical procedures involving PMMA cements, such as embolism, thermal necrosis, toxicity and hypersensitivity, are often due to other causes. Knowledge about the properties of the cement helps the user to safely employ PMMA cements in augmentations. High radio-opacity is required in vertebral body augmentations and this is provided in particular by zirconium dioxide. In vertebral body augmentations, a low benzoyl peroxide (BPO) content can considerably prolong the liquid dough phase. In augmentations with cement fillings in the region of a tumor, a high BPO content can specifically increase the peak temperature of the PMMA cement. In osteosynthetic augmentations with PMMA, necrosis is rare because heat development in the presence of metallic implants is low due to heat conduction via the implant. Larger cement fillings where there is no heat conduction via metal implants can exhibit substantially higher peak temperatures. The flow properties of PMMA cements are of particular importance for the user to allow optimum handling of PMMA cements. In patients with hypersensitivity to antibiotics, there is no need to avoid the use of PMMA as there are sufficient PMMA-based alternatives. The PMMA cements are local drug delivery systems and antibiotics, antiseptics, antimycotics and also cytostatics can be mixed with the cement. Attention must be paid to antagonistic and synergistic effects.

[Overweight in primary school-age children. Prevalence and risk factors]. / Gewichtsentwicklung im frühen Grundschulalter. Prävalenz, Inzidenz und Risikofaktoren für Übergewicht und Adipositas.

BACKGROUND: Various studies show that pre-school age is a sensitive period for the development of overweight and obesity. During a longitudinal study between 2010 and 2013, the municipal health authority (city of Frankfurt) in cooperation with the university children's hospital investigated the development of weight in children aged 5 to 8. MATERIALS AND METHODS: The weight and height of a collective of 5720 children were measured (2010/11). In addition, nutritional and exercise habits, as well as media consumption was documented for 4758 children through a questionnaire during the school enrolment procedure. The weight and height of 3481 children were measured again in the second grade (2012/13). RESULTS: Over a period of 24 months, the percentage of overweight (not obese) children increased from 7.5 to 9.4 % and that of obese children from 4.5 to 5.0 %. 164 of 2818 children with a normal initial weight (5.8 %) changed to percentile class overweight or obese. 79 of 260 children who were initially overweight, not obese (30 %), changed to the group of normal weight, but only 4 out of 156 obese children (3 %). Increased TV consumption (> 1 h per day), availability of their own television, lack of physical activity, and consumption of high-calorie drinks were risk factors for the development of overweight during the primary school age. 72 % of parents of overweight children and 22 % of obese children falsely classified their children as normal weight. CONCLUSIONS: Targeted education about the risk of obesity in the primary school age and offers for early intervention should be established in the healthcare services concerned.

Aerobic microbial Fe acquisition from ferrihydrite nanoparticles: effects of crystalline order, siderophores, and alginate.

This research compared the bioavailability of Fe associated with two forms of the hydrous Fe oxyhydroxide nanomineral ferrihydrite (Fh)--the smaller (1-3 nm), less ordered 2-line (2L) phase and the slightly larger, (2-6 nm) more ordered 6-line (6L) phase--to the common aerobic soil bacterium Pseudomonas mendocina ymp. P. mendocina can acquire Fe from minerals using high-affinity Fe(III) binding ligands known as siderophores and a cell-associated metalloreductase that requires direct cell-mineral contact. Wild-type (WT) P. mendocina and a siderophore(-) mutant were used to monitor siderophore -related and -independent Fe acquisition from 2L and 6L Fh. Both WT and mutant strains acquired Fe from Fh, although Fe acquisition and growth were substantially greater on the 2L phase than on the 6L phase. In the absence of bacteria, copious quantities of the biofilm exopolysaccharide alginate slightly promoted dissolution of 2L and 6L Fh. In biotic experiments, added alginate slightly enhanced growth and Fe acquisition from 6L Fh but not from 2L Fh. Recent research has led to an emerging understanding that Fe-oxide nanoparticle structure, stability, and reactivity are highly sensitive to size at the nanoscale; this research emphasizes how subtle differences in nanoparticle size-related properties can also affect bioavailability.

[Classification and therapy of medication-overuse headache: impact of the third edition of the International Classification of Headache Disorders]. / Klassifikation und Therapie des Medikamenten-Übergebrauch-Kopfschmerzes (MÜK) : Auswirkungen der 3. Auflage der internationalen Kopfschmerzklassifikation auf die Praxis.

The diagnosis of medication-overuse headache (MOH) is of central importance because this secondary headache disorder can be treated very effectively and patients do not usually respond to headache prophylaxis as long as MOH persists. The article describes important changes in the diagnostic criteria of different MOH subtypes after publication of the International Classification of Headache Disorders (ICHD-3beta) in 2013. The new classification has a crucial and direct impact on prevention and treatment of MOH. In addition interactions exist with the new criteria of chronic migraine. With a controlled medication intake scheme according to the 10-20 rule and using a medication break, MOH usually remits in most patients. If patient education and advice does not lead to remission of MOH, a specialized managed medication break or withdrawal treatment becomes necessary. This can be done on an outpatient, day clinic or inpatient basis. In uncomplicated cases, the results of these three treatment settings do not differ. From a cost-effectiveness standpoint, the outpatient treatment should be given priority. In complicated cases, a fully inpatient withdrawal treatment using a multimodal treatment concept is significantly superior.

[The significance of depot medication in the long-term-treatment of schizophrenia]. / Stellenwert von Depotformulierungen in der Langzeittherapie der Schizophrenie.

Relapse prevention in schizophrenia is a key aim in therapy. However, it is estimated that approximately 75% of patients with schizophrenia relapse within five years. Each relapse might worsen the disease and increase the risk of psychosocial and work-related disadvantages. A continuous long-term therapy is able to reduce this risk, but medical non-adherence, which is influenced by numerous factors, is a limitation. Naturalistic studies show that depot-antipsychotics compared with oral antipsychotics lead consistently to a better outcome, for example by reducing relapse rates or hospitalisation. Numerous meta-analyses of randomised controlled trials comparing oral versus depot-antipsychotics also show this advantages. However these results are not consistent in all meta-analyses. Results of controlled studies do not appropriately reflect the reality of daily practice. The advantages of depot-antipsychotics are shown more distinctly in naturalistic studies. The following review reflects the current therapy of schizophrenia and discusses adequately a broad application of depot-antipsychotics based on existing data. In addition, concerns and prejudices of physicians and patients against antipsychotic long-term therapy and depot-formulation are discussed and a recommendation is provided.

A long-lasting outbreak of Salmonella Typhimurium U323 associated with several pork products, Denmark, 2010.

This paper shows that control of foodborne disease outbreaks may be challenging even after establishing the source of infection. An outbreak of Salmonella Typhimurium U323 infections occurred in Denmark from March to September 2010, involving 172 cases. Before the detection of human cases, several positive isolates of the outbreak strain had been found in a particular pig slaughterhouse and thus early traceback, investigation and control measures were possible. Several batches of pork and pork products were recalled and the slaughterhouse was closed twice for disinfection. No single common food item was identified as the outbreak source, but repeated isolation of the outbreak strain from the slaughterhouse environment and in pork and products as well as patient interviews strongly suggested different pork products as the source of infection. Furthermore, a matched case-control study identified a specific ready-to-eat spreadable pork sausage (teewurst) as the source of a sub-outbreak (matched odds ratio 17, 95% confidence interval 2·1-130).

[Integrated headache care network. Kiel Migraine and Headache Center and German National Headache Treatment Network]. / Sektorenübergreifende schmerzmedizinische Versorgung. Schmerzklinik Kiel und bundesweites Kopfschmerzbehandlungsnetz.

Migraine and other headaches affect 54 million people in Germany. They rank among the ten most severely disabling complaints and the three most expensive neurological disorders. Nevertheless, they are not adequately recognized in the healthcare system with sketchy diagnoses and inadequate treatment. This inadequate care is not primarily due to a lack of medical and scientific knowledge on the development and treatment of headaches but is predominantly due to organizational deficits in the healthcare system and in the implementation of current knowledge. To overcome the organizational barriers the national headache treatment network was initiated in Germany. For the first time it allows national cross-sectoral and multidisciplinary links between inpatient and outpatient care. A hand in hand treatment programme, better education, better information exchange between all partners and combined efforts using clearly defined treatment pathways and goals are the basis for state of the art and efficient treatment results. The treatment network is geared towards the specialized treatment of severely affected patients with chronic headache disorders. A national network of outpatient and inpatient pain therapists in both practices and hospitals works hand in hand to optimally alleviate pain in a comprehensive cross-sectoral and multidisciplinary manner. For therapy refractive disorders, a high-intensive supraregional fully inpatient treatment can be arranged. This concept offers for the first time a nationwide coordinated treatment without limitation by specialization and bureaucratic remuneration sectors.

Repair of a canine patellar ligament rupture using the ComPact UniLock 2.4/3.0 mm System.

An 11-year old, female, Mix Breed dog was presented after being hit by a car with a rupture of the left patellar ligament. Due to a suspected wound infection close to the stifle joint, surgical repair was delayed for 10 days. The ruptured ligament was sutured and augmented with fascia lata. Additionally, two ComPact UniLock 2.4/3.0 mm plates connected with 1.0 mm orthopaedic wire were used to protect the primary repair. No immobilization of the stifle joint was needed. The implants were removed after 7 weeks, because of suspected infection and loosening. The successful utilization of an alternative surgical technique for the repair of the patellar ligament rupture in the dog has also been documented by pre- and post-operative temporal-spatial gait analysis (GaitFour®).

Palmitic acid coating of allogeneic cancellous bone for local antibiotic treatment: A porcine impaction bone grafting model.

Introduction: The worldwide rising number of joint replacements results in increasing revision surgery including a relevant portion of septic loosening accompanied by bone deficiencies. Loading of allogeneic bone with antibiotics provides high local antibiotic concentrations and might eradicate bacteria which appear resistant to systemic antibiotic application. Hydrophobic palmitic acid was shown to be a suitable carrier for antibiotics and prevents biofilm. Methods: Cancellous bone derived from 6 to 7 months old piglets was used for a standardized in vitro impaction bone grafting model according to previous studies. The specimens were either thermodisinfected or remained native and palmitic acid with one third and two third partial weight were added and compared with control. Shear force at the interface prosthesis to cement and between cement and bone was measured. The relative micromovements were measured with 6 inductive sensors with a resolution of 0.1 µm at three different measuring heights up to a maximum movement of 150 µm between cement and bone. Taking into account the corresponding applied torque the measured values were normalized in µm/Nm. Statistical analysis was done with SPSS Statistics® Version 26.0 IBM. Results: Smallest movement was measured for thermodisinfected cancellous bone and a not significant decrease of shear force resistance with addition of palmitic acid was found since supplementing native cancellous bone reduced shear force resistance significantly depending on the weight percentage of palmitic acid. Conclusion: Supplementation of porcine cancellous bone with palmitic acid did not significantly reduce shear force resistance of thermodisinfected bone since adding palmitic acid to native bone decreased it significantly depending on the volume added. Palmitic acid seems to be a suitable coating for allogeneic cancellous bone to deliver high local antibiotic concentrations and thermodisinfected cancellous bone might be able to store larger volumes of palmitic acid than native bone without relevant influence on shear force resistance.

Acute toxicity study of antibacterial organophilic bentonite incorporated with geranyl acetate in mice and geranyl acetate liberation in simulated gastric fluid.

In the present study, the antibacterial property of the organophilic bentonite (Bent-ODA) and organophilic bentonite incorporated with geranyl acetate ester (Bent-ODA-GA) was evaluated against bacteria Staphylococcus aureus, Escherichia coli and Salmonella typhimurium. Oral acute toxicity of Bent-ODA-GA was evaluated in mice, by a single oral dose of 300 and 2000 mg kg-1. Animals were observed for any toxicity clinical signs or mortality for 15 days according to OECD 423 guidelines. The release assay of GA presents in Bent-ODA in simulated gastric fluid, pH 3.5 and pH 6.5 was also performed. Bent-ODA-GA composite presented antibacterial activity against S. aureus and S. typhimurium bacteria with 10.7 ± 0.6 mm and 2.2 ± 0.1 mm inhibition halo, respectively, which make it possible to associate the composite antimicrobial feature due to the ester presence. The composite did not reveal any toxicity signs or mortality in any animal for acute toxicity treatment during the 15 days observation period. The LD50 of Bent-ODA-DA was estimated to be greater than 2000 mg kg-1. It was also observed that geranyl acetate is released from Bent-ODA in concentrations lower than 0.03 mg kg-1 for pH 3.5 and 0.004 mg kg-1 for pH 6.5, which are lower than those that could cause some toxic effects in animals.

Comparison and combination of blood-based inflammatory markers with faecal occult blood tests for non-invasive colorectal cancer screening.

BACKGROUND: Faecal occult blood tests (FOBTs) are widely used for colorectal cancer (CRC) screening. Blood-based inflammatory markers have been suggested as alternative or supplementary non-invasive CRC screening tests. METHODS: Among 179 CRC patients, 193 people with advanced adenoma and 225 people free of neoplasm, C-reactive protein (CRP), serum CD26 (sCD26), complement C3a anaphylatoxin and tissue inhibitor of metalloproteinases 1 (TIMP-1) levels in blood were measured by ELISA tests, and an immunochemical FOBT (iFOBT) and a guaiac-based FOBT were performed. Receiver operating characteristic curves were constructed and the areas under the curves (AUCs) were compared. RESULTS: The blood levels of CRP, sCD26 and TIMP-1 showed statistically significant differences between CRC patients and neoplasm-free participants, and levels of TIMP-1 were furthermore significantly elevated in advanced adenoma patients. For the four inflammatory markers, AUCs ranged from 0.52 to 0.62 for CRC detection and from 0.50 to 0.58 for advanced adenomas detection, compared with AUCs of 0.90 and 0.68 for the iFOBT. At 97% specificity, blood markers showed much lower sensitivities than FOBTs. Combining inflammatory markers with the iFOBT increased the AUC for advanced adenomas. CONCLUSION: These blood-based markers do not seem to be an alternative to FOBT-based CRC screening. The potential use of these and other blood-based tests in combination with iFOBT might deserve further attention.