The effect of different collagen modifications for titanium and titanium nitrite surfaces on functions of gingival fibroblasts.

OBJECTIVES: Targeted modifications of the bulk implant surfaces using bioactive agents provide a promising tool for improvement of the long-term bony and soft tissue integration of dental implants. In this study, we assessed the cellular responses of primary human gingival fibroblasts (HGF) to different surface modifications of titanium (Ti) and titanium nitride (TiN) alloys with type I collagen or cyclic-RGDfK-peptide in order to define a modification improving long-term implants in dental medicine. MATERIALS AND METHODS: Employing Ti and TiN implants, we compared the performance of simple dip coating and anodic immobilization of type I collagen that provided collagen layers of two different thicknesses. HGF were seeded on the different coated implants, and adhesion, proliferation, and gene expression were analyzed. RESULTS: Although there were no strong differences in initial cell adhesion between the groups at 2 and 4 hours, we found that all surface modifications induced higher proliferation rates as compared to the unmodified controls. Consistently, gene expression levels of cell adhesion markers (focal adhesion kinase (FAK), integrin beta1, and vinculin), cell differentiation markers (FGFR1, TGFb-R1), extracellular protein markers (type I collagen, vimentin), and cytoskeletal protein marker aktinin-1 were consistently higher in all surface modification groups at two different time points of investigation as compared to the unmodified controls. CONCLUSION: Our results indicate that simple dip coating of Ti and TiN with collagen is sufficient to induce in vitro cellular responses that are comparable to those of more reliable coating methods like anodic adsorption, chemical cross-linking, or RGD coating. TiN alloys do not possess any positive or adverse effects on HGF. CLINICAL RELEVANCE: Our results demonstrate a simple, yet effective, method for collagen coating on titanium implants to improve the long term integration and stability of dental implants.

Chronic widespread pain, including fibromyalgia: a pathway for care developed by the British Pain Society.

Chronic widespread pain (CWP), including fibromyalgia, is a highly prevalent condition with a range of disabling symptoms, both physical and psychological. The British Pain Society (BPS) is supporting the treatment of this group of patients through a care pathway and this article describes the rationale and discussion points relevant to the CWP and fibromyalgia pathway. There are several aims in producing this pathway: to reduce variation in the standards of care, to reduce delays at all stages of care, and in particular, to enable clinicians to help patients accept a diagnosis of CWP. This diagnosis should be based on the presence and distribution of symptoms in the absence of another defined pathological process: the features in the history or clinical examination are generally more important than laboratory investigations. There is an emphasis on addressing all aspects of symptomatology (physical, psychological, social, and personal needs) without an overemphasis on any one treatment modality. The pathway has focused on the potential pitfalls in the use of long-term opioids and the rationale is provided why these are not recommended. Patients with CWP value explanation and education and although clinicians may be unfamiliar with the condition, the majority of clinicians have generic skills in managing long-term conditions which can be supplemented by the interventions and actions detailed in this pathway.

Pelvic pain: a pathway for care developed for both men and women by the British Pain Society.

This paper aims to explain the key points and highlight some of the controversies in the development of the British Pain Society's pelvic pain patient pathway map. Many clinicians lack experience and confidence with this group of patients, and this issue is highlighted. Additionally, the difficulties of classification and definitions in this area are discussed in detail. These are historical causes of disagreement among specialists which can lead to confused clinical care. This group of patients have multiple issues that cross many professional boundaries; they are best managed by the co-ordinated involvement of multiple teams. Patients suffer from significant distress and disability that often needs specialist assessment and intervention (interdisciplinary). This suggests that an integrated approach is required across the historic boundaries of primary and secondary care. A variety of interventions, including opioids and neuromodulation are recommended in the pathway and the controversies surrounding these inclusions are aired in detail.

Initial assessment and management of pain: a pathway for care developed by the British Pain Society.

There is wide variation in how pain is managed in the UK. Patients often find themselves caught in a sea of referrals while continuing to suffer with poorly relieved symptoms. The British Pain Society's (BPS) Initial Assessment and Management of Pain care pathway (one of the five new BPS care pathways published by the Map of Medicine(®)) sets out how best to initially manage persistent pain. Patient education and supported self-management is recommended from an early stage. This pathway focuses on the start of the journey of a patient with pain, where a full diagnostic work-up is not yet complete. The pathway covers diverse recommendations such as appropriate content of a pain consultation, the use of clinical decision management tools to aid stratification of care, and resources to support patients to make informed decisions. Recommendations for monitoring of therapeutic effect are also included. Early identification of people at high risk of chronic disability may allow more intensive management, better use of resources, and reduction in disability. Implementation poses significant challenges; more research is needed to determine the most effective interventions. This article highlights practice points for the non-specialist, discusses areas of controversy, and examines the challenges of implementation.

Low back and radicular pain: a pathway for care developed by the British Pain Society.

These consensus guidelines aim to provide an overview of best practice for managing chronic spinal pain reflecting the heterogeneity of low back pain. Most guidelines have covered only one aspect of spinal care and thus have been divisive and potentially worsened the quality of care. Additionally, some of the evidence base is subjective and of poor quality. The British Pain Society low back pain pathway has reached across all disciplines and involved input from patients. It is recognized, however, that there is an urgent need for further good-quality clinical research in this area to underpin future guidelines. Considerable work is still needed to clarify the evidence; however, foundations have been laid with this pathway. Key features include: risk stratification; clarification of intensity of psychological interventions; a logical progression for the management of sciatica; and decision points for considering structural interventions such as spinal injections and surgery.

Neuropathic pain: a pathway for care developed by the British Pain Society.

Neuropathic pain is a common chronic pain condition that can be challenging to treat, particularly for non-specialists. The development of the Map of Medicine care pathway for the management of neuropathic pain was led by the British Pain Society. Focusing on treatment by non-specialists, this pathway is based on new evidence, consensus, and the interests of service users. This paper presents the care pathway and accompanying evidence base, highlighting its salient features, and discussing important treatment points. After initial assessment, the pathway progresses through first-, second-, and third-line drug treatment, includes advice on topical treatment and opioids (in specific circumstances), and describes non-pharmacological approaches. Importantly, timely review of patients and referral to specialist secondary or tertiary care must be considered as vital components of the pathway. Although the emphasis was not on specialist treatment, advice is given on existing interventions, including neural stimulation and multi-disciplinary care. These, and other steps on the pathway, will be subject to further review as more evidence becomes available. In the meantime, the pathway represents a straightforward, valuable and accessible approach for healthcare professionals managing the distress and impact of neuropathic pain.

[Bronchial carcinoma and knee pain. Secondary hypertrophic osteoarthropathy]. / Bronchialkarzinom bei Knieschmerzen. Die sekundäre hypertrophe Osteoarthropathie.

Secondary hypertrophic osteoarthropathy (HOA), also known as Marie-Bamberger syndrome, is a rare neoplastic syndrome featuring clubbing of the tips of the digits, periosteal proliferation and synovial effusion of adjacent joints. We report a case where a patient without any other known medical condition developed persistent arthralgia and mobility restriction after bruising the left knee. As the initial X-ray examination of the knee showed a distinct periosteal proliferation of the left femoral bone, extended diagnostics were initiated during which a bronchial carcinoma was identified. After surgical removal of the primary tumor the symptoms of irritation in the knee joint recovered totally.

The effect of multigenerational diet containing genetically modified triticale on immune system in mice.

The safety assessment of genetically modified (GM) food and feed is performed to identify the possible effects upon animal and human health, also the long-term, multigenerational influence upon functioning of different organs and systems, such as the immune system. In this study C57BL/6J mice were fed for five consecutive generations with pellets containing 20% of conventional triticale grain (control) vs. pellets containing 20% of the transgenic triticale grain resistant to BASTA herbicide (experimental). The F5 experimental animals showed enlarged inguinal and axillary lymph nodes, but not spleens, and increased WBC counts in blood (but within the norm for Mus musculus). Immunophenotyped cell suspensions derived from spleens, inguinal and axillaris lymph nodes and PBMCs from blood showed the significant decrease in the percentage of T cells in spleen and lymph nodes and the B cells in lymph nodes and blood of the F5 experimental mice in comparison to the control F5 mice. Immunoblotting analysis of IL-2, IL-4, IL-10, IL-12, IL- 6, IFN-gamma levels in serum showed significantly increased IL-2 levels and decreased IL-6 levels in the F5-experimental mice sera. No significant changes in the levels of IgE in sera in both mice groups were observed. The obtained results indicate that multigenerational use of feeds for rodents containing the GM-triticale leads to expansion of the B cell compartment in the secondary lymphoid organs, but it is not caused by malignant processes or the allergic response.

Attentional bias toward and distractibility by sexual cues: A meta-analytic integration.

From an evolutionary perspective, sexual stimuli are highly salient and are assumed to be processed with high priority. Hence, attentional processing of sexual cues is expected to not only bias attention but to also distract from other cognitive (foreground) tasks. It is, however, unclear to what extent these stimuli capture attention and whether there are differences between men and women. This meta-analysis combined the results of 32 studies employing experiments of attentional bias toward and distraction by sexual stimuli. From these, 13 studies provided data to examine gender differences. Overall, attentional bias and distractibility was lower than anticipated (gz = 0.43, p < .001) and there was support for the assumption of higher attention bias/interference in men (gs = 0.29, p = .031). Importantly, there was evidence for the presence of publication bias. With this in mind, findings are discussed in the context of stimulus features, the impact of provoked sexual arousal and motivational state, and gender-specific and -nonspecific neural processing of sexual stimuli which influence attention toward them.

Severe unexplained loin pain (loin pain haematuria syndrome): management and long-term outcome.

BACKGROUND: The intractable and unexplained loin pain of severe 'loin pain haematuria syndrome' (LPHS) causes great psychosocial distress and disability. AIM: To examine the psychological factors in LPHS patients who had failed to respond to non-opiate analgesia, and explore the feasibility of conservative management. DESIGN: Retrospective review of case notes, medical and GP records, with follow up. METHODS: We studied 21 consecutive patients referred from specialist renal centres to a regional pain clinic. All records were reviewed, and patients received a comprehensive psychiatric and social assessment. Medication with pain-coping strategies was emphasized, and surgical solutions were discouraged. RESULTS: Patients' median age was 43 years (range 21-64) and duration of symptoms 11 (1-34) years. Sixteen were receiving opiates, and none had enduring benefit from surgery. Patients were divisible into three groups: twelve (57%) gave a history of recurrent, unexplained symptoms involving other parts of the body (somatoform disorder); seven had chronic loin pain; dissimulation was suspected in two. At follow-up (median 42 months), eight (38%) rated their pain absent or improved. Of the 11 whose pain was the same or worse, all were on opiates and seven had a somatoform disorder. A further two patients had developed 'other' medical problems. Despite our advice, three patients underwent major surgery for pain. DISCUSSION: We recommend that patients be managed in a regional pain clinic, where a multidisciplinary approach promotes self-management of pain. Patients who were able to accept conservative treatment, and taper or withdraw opiate analgesia, had a better prognosis.

Connective tissue responses to oxysterols.

We studied the effect of sterols and oxidized sterols on promoting tissue inflammation and necrosis, and on causing cell death in tissue culture. The cells studied were mouse fibroblasts and macrophages, and pig vascular smooth muscle. The lipid preparations were dibromide-purified cholesterol, air-oxidized cholesterol, 25-hydroxycholesterol, cholesterol-5alpha, 6 beta-epoxide and cholestane 3 beta, 5 alpha, 6 beta-triol. Of these, the triol was most active in its cytopathic effect on cells in culture, in size of granuloma formation and in producing necrosis. The epoxide, 25-hydroxycholesterol and air-oxidized cholesterol produced rather less effect on tissues and cultures than the triol, but more than purified cholesterol and the control. The results are considered in relation to the presence of oxysterols in stored foodstuffs and their possible presence over the surface of cholesterol crystals in the tissues.

Substance P in cutaneous primary sensory neurons--a comparison of models of nerve injury that allow varying degrees of regeneration.

We have studied changes in neuropeptide expression in four different models of nerve injury in adult rats. The models involved the cutaneous sural and saphenous nerves, and were associated with different degrees of regrowth and peripheral target reinnervation. These were: simple crush of the nerve, complete cut and self-anastomosis; cut and ligation, and cut and anastomosis of the nerve to an isolated stump of peripheral nerve. Thus, in the first two models a partial or complete reinnervation of peripheral targets was possible, while in the third and fourth it was not. The last model allowed regenerating fibres to come into contact with Schwann cells in the distal stump. We measured substance P-like immunoreactivity in the manipulated nerves (by radioimmunoassay) and the number of manipulated afferents expressing the peptide in dorsal root ganglion cells (by combined immunohistochemistry and retrograde labelling), at time points up to 12 weeks after the nerve manipulations. The retrograde labelling also allowed estimates of cell death. Two weeks after the nerve injuries, when no cell death had occurred, the nerves subjected to a cut lesion (last three models) all showed very low levels of substance P-like immunoreactivity, both in the amounts in peripheral nerve, and in the number of manipulated cell staining positively (P < 0.01). In contrast, the crush model showed no significant change in substance P levels in the nerve (P > 0.05), but a significant increase in the number of immunopositive cells (P < 0.01). Twelve weeks after the nerve manipulations, a variable degree of cell death was seen. Only 9% of afferents in the crush model were lost (P > 0.05 compared with normal) but a 39 and 45% loss was seen in tie and resuture models, respectively, (P < 0.05) for both, compared with normal), and a 63% loss in the stump model (P < 0.01 compared to normal, and P < 0.05 compared to tie and resuture models). An analysis of cell size distributions indicated that cell death affected both large and small cells. At 12 weeks, the levels of substance P in the first two models (associated with peripheral reinnervation) had returned towards, but did not reach, normal (P < 0.01), whilst the stump model showed no significant recovery and the tie model was intermediate. Proportionately more manipulated cells were found to express substance P immunoreactivity in the stump model than expected after allowing for cell death.(ABSTRACT TRUNCATED AT 400 WORDS)

Comparison of a needle-free high-pressure injection system with needle-tipped injection of intracavernosal alprostadil for erectile dysfunction.

Patients identified from hospital records as using alprostadil injections for erectile dysfunction were invited to take part in this open crossover study. On alternate weeks eight patients were given intracavernosal needle injections and transdermal needle-free injection of alprostadil in a randomized order. Efficacy of injection and associated pain were assessed and compared for the two methods. Pain produced during injection was significantly greater with the needle-free system than with the needle-tipped injection whilst efficacy was significantly less. Bruising was reported in all except one patient following needle-free injection only. Patient ratings of the needle-free injector were significantly lower than ratings for needle-tipped alprostadil delivery and when asked to express a preference, every patient chose the needle-tipped injection over the needle-free device.

Characterization of secondary hyperalgesia produced by topical capsaicin jelly--a new experimental tool for pain research.

Peripheral administration of the nociceptive agent capsaicin is used as an experimental tool to study neurophysiological and pharmacological aspects of the generation and control of pain. When investigating secondary hyperalgesia phenomena, current topical and intradermal capsaicin delivery methods have two key limitations. Intradermal injection can evoke severe chemogenic pain and both delivery methods produce an unstable area of dynamic mechanical allodynia. We present validity studies of a new preparation for capsaicin delivery that overcomes these limitations. The novel capsaicin formulation consists of a water-based semisolid jelly preparation containing 1% capsaicin which is applied topically under adhesive-free occlusion to a small area of the skin. We demonstrate that in healthy human subjects this model evokes areas of flare, punctate hyperalgesia and mechanical allodynia which are equivalent to established models and that these areas are stable over time and reproducible on repeat experiments. The jelly formulation evokes only minimal chemogenic pain and, as the preparation remains in situ throughout the study providing constant capsaicin exposure, a stable area of dynamic mechanical allodynia is produced. These validation studies show that this novel capsaicin administration method is a practical, reliable and viable tool for investigating experimental secondary hyperalgesia.

Sensory threshold changes without initial pain or alterations in cutaneous blood flow, in the area of secondary hyperalgesia caused by topical application of capsaicin in humans.

Changes in von Frey hair perception, pricking pain, and vibration thresholds were examined in six healthy human adults, in the zone of secondary hyperalgesia, 45 min following the topical application of capsaicin at concentrations of 0.05 and 0.1 mg/ml. In two of these subjects, cutaneous blood flow was monitored at 10-min intervals, before, during and after capsaicin application, using laser Doppler perfusion imaging. Thresholds for all three parameters were significantly reduced after capsaicin treatment, in a dose-dependent manner. However, there was no visible skin flare, and no change in cutaneous blood flow at these doses of capsaicin. The effects on von Frey perception threshold and vibration threshold have not been demonstrated previously, and may be indicative of central changes, initiated by afferent fibres (presumably C fibres) that are not vasoactive.

Retrograde labelling of dorsal root ganglion cells in the rat: a quantitative and morphological comparison of Fluoro-Gold with horseradish peroxidase labelling.

We have compared retrograde labelling of rat primary sensory neurons using Fluoro-Gold (FG) and horseradish peroxide conjugated with wheat germ agglutinin (HRP-WGA). Fluoro-Gold 2.5% after 48 h transit time and FG 5% after 24 and 48 h retrogradely labelled similar numbers of cell profiles as HRP-WGA (P greater than 0.1% Student's t-test). The calculated cell size distribution for the above FG groups were similar to those for the HRP-WGA. However, FG 2.5% after a 24 h transit time labelled significantly fewer cells (P less than 0.001 Student's t-test). FG retrograde transport may be used to identify the same population of DRG cells as HRP-WGA.

The consequence of delayed versus immediate nerve repair on the properties of regenerating sensory nerve fibres in the adult rat.

Transected saphenous neurones were allowed to regenerate for 3 months via distal stumps of sural nerve following an immediate or a 3 month delayed repair. The number of DRG neurons surviving following the 3 months regeneration period were approximately 60% of normal after both immediate and delayed repair. The percentage of DRG cell bodies identified by the application of Fluro-gold proximal to the repair site and immunopositive for SP, CGRP and galanin was increased following both early and delayed repair compared to baseline values. These values were not significantly different for early repair compared to late repair. Similarly, peripheral measurements of SP in the proximal stump of saphenous nerve (by radioimmunoassay) were not significantly different between models with primary repair compared to delayed repair. These results suggest that the intrinsic regeneration properties of primary sensory neurones are not impaired when repair is delayed.

A trial of intravenous lidocaine on the pain and allodynia of postherpetic neuralgia.

This study investigated the effect of intravenous lidocaine at two doses (1 mg/kg and 5 mg/kg over 2 hours) and an intravenous saline placebo on the pain and allodynia of postherpetic neuralgia (PHN). Twenty-four patients were studied using a randomized, double-blind, within-patient crossover design. Each patient received normal saline, lidocaine 0.5 mg/kg/h, and lidocaine 2.5 mg/kg/h for a 2-h period. The McGill Pain Questionnaire Short Form, visual analogue scores (VAS), and area of allodynia were measured at intervals during the infusions. Free plasma lidocaine levels were also measured. The results were statistically analyzed using Student's t-test for paired data. The VAS for ongoing pain showed a significant reduction after all the infusions (P < 0.05). For dynamic pressure-provoked pain, the VAS was unaffected by placebo but showed a reduction at an equal level of significance with both lidocaine infusions (P < 0.05). The area of allodynia of PHN, as mapped by brush stroke, declined in association with intravenous lidocaine (0.5 mg/kg/h = P < 0.05; 2.5 mg/kg/h = P < 0.001). Placebo had no significant effect on the area of allodynia. These findings demonstrate a positive effect on pain and allodynia following a brief intravenous infusion of lidocaine. The higher dose infusion may produce plasma levels in the toxic range, with no significant clinical increase in response.

The twelfth rib syndrome.

The twelfth rib syndrome appears to be a fairly common and underdiagnosed chronic pain syndrome. It is more common in women than men (3:1) and is usually described as a constant dull ache or sharp stabbing pain that may last from several hours to many weeks. Lateral flexion, rotation of the trunk, and rising from a sitting position classically aggravate the pain. Manipulation of the affected rib and its costal cartilage reproduces it exactly. The diagnosis of this syndrome is clinical, requires exclusion of specific etiologies, and should only be made when the patient's symptoms can be exactly reproduced by manipulation of the affected rib. If symptomatology is complicated, it may be necessary to use an image intensifier for accurate location of the pain locus. Patients with this syndrome can be overinvestigated and have even undergone surgical procedures when this diagnosis has been overlooked. To describe the varied presentation of this syndrome, we describe the clinical manifestations in six patients.

Ultrastructure of the secondary yolk sac in pig's embryo.

During the investigated period of development the pig embryo secondary yolk sac consists of two parallel epithelia (endodermal and mesodermal) separated by a layer of vascularized mesenchyme. Endoderm cells and blood vessels undergo morphological changes connected with the embryo age. The development of the blood vessels is at the vasculogenesis stage. Blood stem cells, erythroblasts, megakaryocytes and platelets were observed in the lumen of vessels. A comparison our results with the development of the pig embryo liver shows that the transferring the haemopoetic function from the yolk sac to the liver begins on about 27 dpc. Until 51 day of embryo development the yolk sac does not show any signs of involution. Possibly yolk sac supports the liver in its haemopoetic function until the time when that organ becomes a fully efficient haemopoetic organ.