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BackgroundMajor depressive disorder with psychotic features (MDDPsy), compared to nonpsychotic MDD, involves an increased risk of suicide and failure to achieve treatment response. Symptom scales can be useful to assess patients with MDDPsy. The aim of the present study was to validate French versions of the Delusion Assessment Scale (DAS) and Psychotic Depression Assessment Scale (PDAS).MethodsOne hundred patients were included. The scales were filled out by psychiatrists. Data from participants who accepted a second interview were used for inter-judge reliability. The scalability and psychometric properties of both scales were assessed.ResultsData from 94 patients were used. Owing to low score variability between patients, the predefined threshold for scalability (≥0.40) was not reached for both scales. Factorial analysis of the DAS identified five factors, different from those of the original version. Five factors were also identified in the PDAS, of which two comprised items from the HDRS and the other three items from the BPRS. Floor and ceiling effects were observed in both scales, due in part to the construction of certain subscales. Unlike the PDAS, the DAS had good internal consistency. Multiple correlations were observed between the DAS dimensions but none between those of the PDAS. Both scales showed good inter-judge reliability. Convergent validity analyses showed correlations with HDRS, BPRS and CGI.LimitationsInter-judge reliability was calculated from a relatively small number of volunteers.ConclusionsThe good psychometric properties of the French versions of the DAS and PDAS could help in assessing MDDPsy, in particular its psychotic features, and hence improve response to treatment and prognosis.

Abstract Objective Walking groups are increasingly being set up but little is known about their efficacy in promoting physical activity. The present study aims to assess the efficacy of interventions to promote walking in groups to promoting physical activity within adults, and to explore potential moderators of this efficacy. Method Systematic literature review searches were conducted using multiple databases. A random effect model was used for the meta-analysis, with sensitivity analysis. Results The effect of the interventions (19 studies, 4 572 participants) on physical activity was of medium size (d = 0.52), statistically significant (95%CI 0.32 to 0.71, p Conclusion Interventions to promote walking in groups are efficacious at increasing physical activity. Despite low homogeneity of results, and limitations (e.g. small number of studies using objective measures of physical activity, publication bias), which might have influence the findings, the large fail-safe N suggests these findings are robust. Possible explanations for heterogeneity between studies are discussed, and the need for more investigation of this is highlighted.

Abstract Background Self-rated health is commonly employed in research studies that seek to assess the health status of older individuals. Perceptions of health are, however, influenced by individual and societal level factors that may differ within and between countries. This study investigates levels of self-rated health (SRH) and correlates of SRH among older adults in Australia, United States of America (USA), Japan and South Korea. Methods Cross-sectional data were drawn from large surveys of older respondents (≥ 65 years) in Australia (n = 7,355), USA (n = 10,358), Japan (n = 3,541) and South Korea (n = 3,971), collected between 2000 and 2006. Harmonized variables were developed to represent socioeconomic, lifestyle and health indicators. We then assessed whether these variables, and their potentially different impact in different countries, could account for cross-national differences in levels of SRH. Results SRH differed significantly between countries, with older Koreans reporting much poorer health than those in the other three nations. This was not the result of biases in response patterns (for example central versus extreme tendency). Health-related correlates of SRH were similar across countries; those with more medical conditions, functional limitations or poor mental health gave poorer ratings. After accounting for the differential impact of determinants in different national contexts, Australians reported better SRH than other nations. Conclusions We conclude that when examining correlates of SRH, the similarities are greater than the differences between countries. There are however differences in levels of SRH which are not fully accounted for by the health correlates. Broad generalizations about styles of responding are not helpful for understanding these differences, which appear to be country, and possibly cohort specific. When using SRH to characterize the health status of older people, it is important to consider earlier life experiences of cohorts as well as national and individual factors in later life. Further research is required to understand the complex societal influences on perceptions of health.

Abstract Background The aim of the present research is to conduct a fully powered explanatory trial to evaluate the efficacy of a brief self-regulation intervention to increase walking. The intervention will be delivered in primary care by practice nurses (PNs) and Healthcare Assistants (HCAs) to patients for whom increasing physical activity is a particular priority. The intervention has previously demonstrated efficacy with a volunteer population, and subsequently went through an iterative process of refinement in primary care, to maximise acceptability to both providers and recipients. Methods/ Design This two arm cluster randomised controlled trial set in UK general practices will compare two strategies for increasing walking, assessed by pedometer, over six months. Patients attending practices randomised to the self-regulation intervention arm will receive an intervention consisting of behaviour change techniques designed to increase walking self-efficacy (confidence in ability to perform the behaviour), and to help people translate their "good" intentions into behaviour change by making plans. Patients attending practices randomised to the information provision arm will receive written materials promoting walking, and a short unstructured discussion about increasing their walking. The trial will recruit 20 PN/HCAs (10 per arm), who will be trained by the research team to deliver the self-regulation intervention or information provision control intervention, to 400 patients registered at their practices (20 patients per PN/HCA). This will provide 85% power to detect a mean difference of five minutes/day walking between the self-regulation intervention group and the information provision control group. Secondary outcomes include health services costs, and intervention effects in sub-groups defined by age, ethnicity, gender, socio-economic status, and clinical condition. A mediation analysis will investigate the extent to which changes in constructs specified by the Theory of Planned Behaviour lead to changes in objectively assessed walking behaviour. Discussion This trial addresses the current lack of evidence for interventions that are effective at increasing walking and that can be offered to patients in primary care. The intervention being evaluated has demonstrated efficacy, and has been through an extensive process of adaptation to ensure acceptability to both provider and recipient, thus optimising fidelity of intervention delivery and treatment receipt. It therefore provides a strong test of the hypothesis that a self-regulation intervention can help primary care patients increase their walking. Trial registration Current Controlled Trials ISRCTN95932902

Abstract Background Resistance and susceptibility to scrapie has been associated with single nucleotide polymorphisms located within codons 136, 154 and 171 of the ovine prion protein gene (PRNP). Dual-labelled HyBeacon probes were developed to analyse single and clustered polymorphisms within these and neighbouring codons. Methods Extracted DNAs and unpurified blood samples were genotyped with respect to polymorphisms in PRNP codons 136, 141, 154 and 171. PCR amplicons were investigated using a LightTyper instrument, measuring the stability of probe/target hybridisation through peak melting temperatures and determining the sequence of nucleotides at polymorphic sites. Results The performance of HyBeacon assays was evaluated in a validation study comparing genotypes with those obtained using a primer extension assay (Sequenom MassEXTEND) analysed on a MALDI-ToF mass spectrometer. Over 12,000 sheep samples were successfully genotyped, reliably detecting A136, V136, T136, T137, L141, F141 R154, H154, L168, R171, Q171, H171 and K171 sequence variants using only 4 HyBeacon probes. Conclusion HyBeacon assays provide an extremely robust and accurate method for the analysis of single and clustered PRNP polymorphisms in a high-throughput format. The flexibility of the diagnostic tests ensures that samples are correctly genotyped even in the presence of additional sequence variations that flank the polymorphisms of interest. Such sequence variations may also be neutralised using universal bases such as 5-nitroindole if required.

Abstract Background We do not yet know how to use blood glucose self-monitoring (BGSM) most effectively in the self-management of type 2 diabetes treated with oral medication. Training in monitoring may be most effective in improving glycaemic control and well being when results are linked to behavioural change. Methods/design DiGEM is a three arm randomised parallel group trial set in UK general practices. A total of 450 patients with type 2 diabetes managed with lifestyle or oral glucose lowering medication are included. The trial compares effectiveness of three strategies for monitoring glycaemic control over 12 months (1) a control group with three monthly HbA1c measurements; interpreted with nurse-practitioner; (2) A self-testing of blood glucose group; interpreted with nurse- practitioner to inform adjustment of medication in addition to 1; (3) A self-monitoring of blood glucose group with personal use of results to interpret results in relation to lifestyle changes in addition to 1 and 2. The trial has an 80% power at a 5% level of significance to detect a difference in change in the primary outcome, HbA1c of 0.5% between groups, allowing for an attrition rate of 10%. Secondary outcome measures include health service costs, well-being, and the intervention effect in sub-groups defined by duration of diabetes, current management, health status at baseline and co-morbidity. A mediation analysis will explore the extent to which changes in beliefs about self-management of diabetes between experimental groups leads to changes in outcomes in accordance with the Common Sense Model of illness. The study is open and has recruited more than half the target sample. The trial is expected to report in 2007. Discussion The DiGEM intervention and trial design address weaknesses of previous research by use of a sample size with power to detect a clinically significant change in HbA1c, recruitment from a well-characterised primary care population, definition of feasible monitoring and behaviour change strategies based on psychological theory and evidence, and measures along the hypothesised causal path from cognitions to behaviours and disease and well being related outcomes. The trial will provide evidence to support, focus or discourage use of specific BGSM strategies.

Anxiety disorders are among the most prevalent psychiatric disorders, causing significant suffering and disability. Relative to other psychiatric disorders, anxiety disorders tend to emerge early in life, supporting the importance of developmental mechanisms in their emergence and maintenance. Behavioral inhibition (BI) is a temperament that emerges early in life and, when stable and extreme, is linked to an increased risk for the later development of anxiety disorders and other stress-related psychopathology. Understanding the neural systems and molecular mechanisms underlying this dispositional risk could provide insight into treatment targets for anxiety disorders. Nonhuman primates (NHPs) have an anxiety-related temperament, called anxious temperament (AT), that is remarkably similar to BI in humans, facilitating the design of highly translational models for studying the early risk for stress-related psychopathology. Because of the recent evolutionary divergence between humans and NHPs, many of the anxiety-related brain regions that contribute to psychopathology are highly similar in terms of their structure and function, particularly with respect to the prefrontal cortex. The orbitofrontal cortex plays a critical role in the flexible encoding and regulation of threat responses, in part through connections with subcortical structures like the amygdala. Here, we explore individual differences in the transcriptional profile of cells within the region, using laser capture microdissection and single nuclear sequencing, providing insight into the molecules underlying individual differences in AT-related function of the pOFC, with a particular focus on previously implicated cellular systems, including neurotrophins and glucocorticoid signaling., Competing Interests: Competing interests statement:N.H.K. serves as a consultant to the Board of Scientific Advisors, Pritzker Neuropsychiatric Disorders Consortium; Skyland Trail National Advisory Board; CME Outfitters, LLC; Corcept Therapeutics Incorporated; and the Institute for Early Adversity Research External Scientific Advisory Board at the University of Texas-Austin. He is the current Editor-in-Chief of the American Journal of Psychiatry. No other authors have potential conflicts to declare.

Background: Children exhibiting extreme anxious temperament (AT) are at an increased risk for developing anxiety and depression. Our previous mechanistic and neuroimaging work in young rhesus monkeys linked the central nucleus of the amygdala to AT and its underlying neural circuit., Methods: Here, we used laser capture microscopy and RNA sequencing in 47 young rhesus monkeys to investigate AT's molecular underpinnings by focusing on neurons from the lateral division of the central nucleus of the amygdala (CeL). RNA sequencing identified numerous AT-related CeL transcripts, and we used immunofluorescence (n = 3) and tract-tracing (n = 2) methods in a different sample of monkeys to examine the expression, distribution, and projection pattern of neurons expressing one of these transcripts., Results: We found 555 AT-related transcripts, 14 of which were confirmed with high statistical confidence (false discovery rate < .10), including protein kinase C delta (PKCδ), a CeL microcircuit cell marker implicated in rodent threat processing. We characterized PKCδ neurons in the rhesus CeL, compared its distribution with that of the mouse, and demonstrated that a subset of these neurons project to the laterodorsal bed nucleus of the stria terminalis., Conclusions: These findings demonstrate that CeL PKCδ is associated with primate anxiety, provides evidence of a CeL to laterodorsal bed nucleus of the stria terminalis circuit that may be relevant to understanding human anxiety, and points to specific molecules within this circuit that could serve as potential treatment targets for anxiety disorders., (Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: An early-life anxious temperament (AT) is a risk factor for the development of anxiety, depression, and comorbid substance abuse. We validated a nonhuman primate model of early-life AT and identified the dorsal amygdala as a core component of AT's neural circuit. Here, we combine RNA sequencing, viral-vector gene manipulation, functional brain imaging, and behavioral phenotyping to uncover AT's molecular substrates., Methods: In response to potential threat, AT and brain metabolism were assessed in 46 young rhesus monkeys. We identified AT-related transcripts using RNA-sequencing data from dorsal amygdala tissue (including central nucleus of the amygdala [Ce] and dorsal regions of the basal nucleus). Based on the results, we overexpressed the neurotrophin-3 gene, NTF3, in the dorsal amygdala using intraoperative magnetic resonance imaging-guided surgery (n = 5 per group)., Results: This discovery-based approach identified AT-related alterations in the expression of well-established and novel genes, including an inverse association between NTRK3 expression and AT. NTRK3 is an interesting target because it is a relatively unexplored neurotrophic factor that modulates intracellular neuroplasticity pathways. Overexpression of the transcript for NTRK3's endogenous ligand, NTF3, in the dorsal amygdala resulted in reduced AT and altered function in AT's neural circuit., Conclusions: Together, these data implicate neurotrophin-3/NTRK3 signaling in the dorsal amygdala in mediating primate anxiety. More generally, this approach provides an important step toward understanding the molecular underpinnings of early-life AT and will be useful in guiding the development of treatments to prevent the development of stress-related psychopathology., (Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Alterations in central extended amygdala (EAc) function have been linked to anxiety, depression, and anxious temperament (AT), the early-life risk to develop these disorders. The EAc is composed of the central nucleus of the amygdala (Ce), the bed nucleus of the stria terminalis (BST), and the sublenticular extended amygdala (SLEA). Using a non-human primate model of AT and multimodal neuroimaging, the Ce and the BST were identified as key AT-related regions. Both areas are primarily comprised of GABAergic neurons and the lateral Ce (CeL) and lateral BST (BSTL) have among the highest expression of neuropeptides in the brain. Somatostatin (SST) is of particular interest because mouse studies demonstrate that SST neurons, along with corticotropin-releasing factor (CRF) neurons, contribute to a threat-relevant EAc microcircuit. Although the distribution of CeL and BSTL SST neurons has been explored in rodents, this system is not well described in non-human primates. In situ hybridization demonstrated an anterior-posterior gradient of SST mRNA in the CeL but not the BSTL of non-human primates. Triple-labeling immunofluorescence staining revealed that SST protein-expressing cell bodies are a small proportion of the total CeL and BSTL neurons and have considerable co-labeling with CRF. The SLEA exhibited strong SST mRNA and protein expression, suggesting a role for SST in mediating information transfer between the CeL and BSTL. These data provide the foundation for mechanistic non-human primate studies focused on understanding EAc function in neuropsychiatric disorders., (Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.)

Two simple models for the spread of heavy drinking among a network of individuals are re-introduced and analysed. We provide theorems on the spread of alcohol abuse for these models in cases involving simple connection schemes. Indicators for this spread that resemble the [Formula: see text] used in disease assessment are suggested and studied. We further provide computations with our models on general application networks and begin to study the reliability of the spread indicators.

Metallic, especially gold, nanostructures exhibit plasmonic behavior in the visible to near-infrared light range. In this study, we investigate optical enhancement and absorption of gold nanobars with different thicknesses for transverse and longitudinal polarizations using finite element method simulations. This study also reports on the discrepancy in the resonance wavelengths and optical enhancement of the sharp-corner and round-corner nanobars of constant length 100 nm and width 60 nm. The result shows that resonance amplitude and wavelength have strong dependences on the thickness of the nanostructure as well as the sharpness of the corners, which is significant since actual fabricated structure often have rounded corners. Primary resonance mode blue-shifts and broadens as the thickess increases due to decoupling of charge dipoles at the surface for both polarizations. The broadening effect is characterized by measuring the full width at half maximum of the spectra. We also present the surface charge distribution showing dipole mode oscillations at resonance frequency and multimode resonance indicating different oscillation directions of the surface charge based on the polarization direction of the field. Results of this work give insight for precisely tuning nanobar structures for sensing and other enhanced optical applications.

Background: In vertebrate olfactory receptor neurons, sensory cilia transduce odor stimuli into changes in neuronal membrane potential. The voltage changes are primarily caused by the sequential openings of two types of channel: a cyclic-nucleotide-gated (CNG) cationic channel and a calcium-gated chloride channel. In frog, the cilia are 25 to 200 µm in length, so the spatial distributions of the channels may be an important determinant of odor sensitivity., Principal Findings: To determine the spatial distribution of the chloride channels, we recorded from single cilia as calcium was allowed to diffuse down the length of the cilium and activate the channels. A computational model of this experiment allowed an estimate of the spatial distribution of the chloride channels. On average, the channels were concentrated in a narrow band centered at a distance of 29% of the ciliary length, measured from the base of the cilium. This matches the location of the CNG channels determined previously. This non-uniform distribution of transduction proteins is consistent with similar findings in other cilia., Conclusions: On average, the two types of olfactory transduction channel are concentrated in the same region of the cilium. This may contribute to the efficient detection of weak stimuli.

Identification of detailed features of neuronal systems is an important challenge in the biosciences today. Transduction of an odor into an electrical signal occurs in the membranes of the cilia. The Cl(Ca) channels that reside in the ciliary membrane are activated by calcium, allow a depolarizing efflux of Cl(-) and are thought to amplify the electrical signal to the brain.In this paper, a mathematical model consisting of partial differential equations is developed to study two different experiments; one involving the interaction of the cyclic-nucleotide-gated (CNG) and Cl(Ca) channels and the other, the diffusion of Ca(2+) into cilia. This work builds on an earlier study (Mathematical modeling of the Cl(Ca) ion channels in frog olfactory cilia. Ph.D. Thesis, University of Cincinnati, Cincinnati, OH, 2006; Math. Comput. Modelling 2006; 43:945-956; Biophys. J. 2006; 91:179-188), which suggested that the CNG channels are clustered at about 0.28 of the length of a cilium from its open end. Closed-form solutions are derived after certain reductions in the model are made. These special solutions provide estimates of the channel distributions. Scientific computation is also used. This preliminary study suggests that the Cl(Ca) ion channels are also clustered at about one-third of the length of a cilium from its open end.

In this paper, a mathematical model of the diffusion of cAMP into olfactory cilia and the resulting electrical activity is presented. The model, which consists of two nonlinear differential equations, is studied using perturbation techniques. The unknowns in the problem are the concentration of cAMP, the membrane potential, and the quantity of most interest in this work: the distribution of CNG channels along the length of a cilium. Experimental measurements of the total current during this diffusion process provide an extra boundary condition which helps determine the unknown distribution function. A simple perturbation approximation is derived and used to solve this inverse problem and thus obtain estimates of the spatial distribution of CNG ion channels along the length of a cilium. A one-dimensional computer minimization and a special delay iteration are used with the perturbation formulas to obtain approximate channel distributions in the cases of simulated and experimental data.

It has been suggested that spontaneous synchronous neuronal activity is an essential step in the formation of functional networks in the central nervous system. The key features of this type of activity consist of bursts of action potentials with associated spikes of elevated cytoplasmic calcium. These features are also observed in networks of rat cortical neurons that have been formed in culture. Experimental studies of these cultured networks have led to several hypotheses for the mechanisms underlying the observed synchronized oscillations. In this paper, bursting integrate-and-fire type mathematical models for regular spiking (RS) and intrinsic bursting (IB) neurons are introduced and incorporated through a small-world connection scheme into a two-dimensional excitatory network similar to those in the cultured network. This computer model exhibits spontaneous synchronous activity through mechanisms similar to those hypothesized for the cultured experimental networks. Traces of the membrane potential and cytoplasmic calcium from the model closely match those obtained from experiments. We also consider the impact on network behavior of the IB neurons, the geometry and the small world connection scheme.

Olfactory cilia contain the known components of olfactory signal transduction, including a high density of cyclic-nucleotide-gated (CNG) channels. CNG channels play an important role in mediating odor detection. The channels are activated by cAMP, which is formed by a G-protein-coupled transduction cascade. Frog olfactory cilia are 25-200 microm in length, so the spatial distribution of CNG channels along the length should be important in determining the sensitivity of odor detection. We have recorded from excised cilia and modeled diffusion of cAMP into a cilium to determine the spatial distribution of the CNG channels along the ciliary length. The proximal segment, which in frog is the first 20% of the cilium, appears to express a small fraction of the CNG channels, whereas the distal segment contains the majority, mostly clustered in one region.

Identification of detailed features of neuronal systems is an important challenge in the biosciences today. Cilia are long thin structures that extend from the olfactory receptor neurons into the nasal mucus. Transduction of an odor into an electrical signal occurs in the membranes of the cilia. The cyclic-nucleotide-gated (CNG) channels which reside in the ciliary membrane and are activated by adenosine 3',5'-cyclic monophosphate (cAMP) allow a depolarizing influx of Ca(2+) and Na(+) and are thought to initiate the electrical signal.In this paper, a mathematical model consisting of two nonlinear differential equations and a constrained Fredholm integral equation of the first kind is developed to model experiments involving the diffusion of cAMP into cilia and the resulting electrical activity. The unknowns in the problem are the concentration of cAMP, the membrane potential and, the quantity of most interest in this work, the distribution of CNG channels along the length of a cilium. A simple numerical method is derived that can be used to obtain estimates of the spatial distribution of CNG ion channels along the length of a cilium. Certain computations indicate that this mathematical problem is ill-conditioned.

Virus-induced secretion of proinflammatory chemokines (e.g., regulated on activation, normal T cells expressed and secreted [RANTES], interleukin [IL]-8) by airway epithelial cells helps to initiate antiviral responses and airway inflammation by enhancing inflammatory cell recruitment. To define mechanisms for virus-induced chemokine secretion, monolayers of nontransformed bronchial epithelial cells were transfected or incubated with polydeoxyinosinic-deoxycytidylic acid (synthetic double-stranded [ds] RNA), rhinovirus dsRNA, or single-stranded RNA (ssRNA), and the secretion of selected chemokines was determined. Transfection or incubation with dsRNA, but not ssRNA, significantly enhanced secretion of RANTES and IL-8, but not eotaxin or macrophage inflammatory protein-1alpha. Mechanistically, dsRNA induced and activated dsRNA-dependent protein kinase (PKR), and activated nuclear factor-kappaB and p38 mitogen-activated protein kinase. Furthermore, the PKR inhibitor 2-aminopurine significantly blocked dsRNA-induced RANTES and IL-8 secretion, whereas the p38 mitogen-activated protein kinase inhibitor SB203580 suppressed dsRNA-induced IL-8, but not RANTES. These findings indicate that dsRNA selectively induce the secretion of chemokines such as IL-8 and RANTES, and implicate dsRNA-sensitive signaling proteins in this process. Moreover, these data suggest that this may be an important mechanism for the selective secretion of chemokines by viruses (e.g., rhinovirus, respiratory syncytial virus, influenza) that synthesize dsRNA during replication.

Equine practitioners are frequently called to attend to soft tissue injuries. The majority of these cases are routine and straightforward; however, a certain percentage may present as a life-threatening situation with potentially serious complications. Client communication, adequate preparation, patient stabilization, accurate injury assessment and appropriate wound preparation are key factors to expedite recovery and achieve a favorable outcome. Understanding the limitations of field therapy and deciding when to transport the case to a clinic or referral center plays an important role in the successful management of these cases.

A collagen-coated Vicryl mesh bioprosthesis was used to repair a 4 x 4 cm full-thickness abdominal wall defect, created in experimental rats. The tensile strength of the repair at 6 months reached 70% of the original abdominal wall. Implant collagen could not be differentiated from host collagen after 2 weeks. The increase in collagen content of the repair was responsible for the increasing tensile strength of the wound with time. All histological sections showed good tolerance of the implant. These results support the use of collagen Vicryl membrane to repair large abdominal wall defects. Clinical trials are indicated.

No ideal dural grafting material is currently available. Many materials have been evaluated in this role, and for many neurosurgeons cadaveric human lyophilized dura has been popular. Recently this material has been putatively associated with Creutzfeldt-Jakob disease. In this study we compared three degradable materials, collagen vicryl (Bovine collagen coated vicryl mesh), Zenoderm (Porcine dermis) and Lyodura (Lyophilized human cadaveric dura) as dural substitutes. In an experimental model using the New Zealand White Rabbit the materials were implanted into dural defects of dimensions 1.7 cm by 1 cm. In the control group the dura was not repaired. In total 47 animals were used and sacrificed at time intervals of 2, 4, 8, 12, and 24 weeks. On gross examination the collagen vicryl produced few adhesions to the cerebral cortex and was replaced by a neomembrane which showed good union with the host dura. In the control group no new layer was formed and there were severe cortical adhesions. Zenoderm and Lyodura remained undegraded and produced more adherence to the cerebral cortex than the collagen vicryl implant. The histological examination showed collagen vicryl to support ingrowth of fibroblasts and the production of a new collagen layer which by 3 months resembled the original host dura. The inflammatory response to the implant did not persist after 3 months. The other substitutes were revitalized by host cells but remained undegraded at 6 months with ingrowth of woven bone and persistence of inflammatory and foreign body response. The results show collagen vicryl to be a suitable dural substitute with potential advantages over other currently used degradable materials, and should be evaluated more fully, both in laboratory studies and clinically.

This experimental study assessed the use of a collagen-coated vicryl mesh tube to reconstruct the esophagus in growing piglets. Initial experiments, in which a segment of thoracic esophagus was excised and replaced by this prosthetic tube, resulted in all the animals succumbing to mediastinitis within the first 3-4 days. This was shown, at post-mortem, to be due to leakage of the prosthesis, secondary to acid reflux, resulting in dissolution of the prosthesis. The collagen-coated vicryl mesh was thereafter treated with glutaraldehyde and in-vitro studies showed that the glutaraldehyde-treated material exhibited a higher resistance to 0.01 M HCl at pH 2.0, when compared with untreated material. In addition, the glutaraldehyde-treated material also showed an increased resistance to digestion by bacterial collagenase. Further experiments to reconstruct the cervical esophagus in growing piglets were performed using the revised glutaraldehyde cross-linked collagen coated vicryl mesh tube. All the animals survived the procedure and the prosthesis were leakproof immediately post-operatively. The animals, however, developed severe stenosis at a mean of 11 days post-operatively. Attempts at neo-epithelialization of the graft were seen histologically. There was considerable granulation tissue and scar tissue formation on the mediastinal aspect of the graft. It is suggested that collagen coated vicryl mesh tube may find applications in the treatment of esophageal atresia only if the problem of stenosis of the prosthesis can be solved.

A retrospective study was conducted on 35 equine patients with lower leg wounds that were managed utilizing skin graft procedures. Two pinch graft, five punch graft, seven tunnel graft, eight split-thickness mesh graft and thirteen full-thickness mesh expansion graft procedures were performed in the initial treatment. The average wound size was 188 cm(2). Twentyfour cases had pregrafting complications: 10 wounds developed sequestra; three wounds were grossly contaminated and infected; and 11 cases developed granulation tissue complications prior to grafting. Graft failure following the initial procedure was seen in 12 cases and occurred with all techniques except pinch grafting. Graft failure was often attributable to poor quality of granulation tissue as well as anatomic site, especially the dorsal surface of the tarsus. An average of two additional grafting procedures was required to successfully treat initial failures. Pinch grafts took the longest time to epithelialize (70 days), followed by punch grafts (47 days). Both were similar in terms of being the least durable and least cosmetically acceptable of all techniques used. Split-thickness and full-thickness mesh expansion grafts were technically the most difficult, but showed the most rapid epithelialization (28 days), greatest durability, and the best cosmetic appearance. Tunnel grafts provided a practical technique for grafting cases which were either not suited for, or which had failed with, mesh expansion grafts.

Native collagen, acetylated collagen, collagen/10% chondroitin sulphate, collagen/2.5% hyaluronic acid and collagen/20% hyaluronic acid were implanted both as film and as sponge into rat lumbar muscle for 7 and 14 d. After 7 d implantation, all materials elicited an acute inflammatory cell response characterized by numerous polymorphs and histocytes. The cell population after 14 d was principally mononuclear, i.e. leucocytes, neutrophils, macrophages, lymphocytes and fibroblasts. Both films and sponges followed a similar pattern. Native collagen elicited a subacute inflammatory response after 7 d. However, 14 d after implantation, a marked infiltration by neutrophils was apparent with subsequent degradation of existing collagen material. Acetylated collagen film evoked a much greater inflammatory cell response than native collagen. Both collagen/hyaluronic acid composites elicited a similar response. The collagen/10% chondroitin sulphate composite elicited the least inflammatory cell response at 7 d, whereas infiltration by host fibroblasts after 14 d implantation was clearly seen.

Collagen films were prepared by three different methods involving acid homogenization at pH 3.0 of a collagen suspension for 1.5 min (film A) and 15 min (film B) and alkaline homogenization at pH 10 for 15 min (film C), after which the resulting slurries were degassed and dried over sterile air. Subsequent examination by scanning electron microscope (SEM) revealed that all samples showed a distinctly layered structure which was much finer in the acid films. Implantation into the lumbar muscle of rats followed by histology and SEM studies revealed that film B was completely resorbed at 14 d whereas remnants of film A could still be seen at this period. The slowest rate of resorption was observed with film C, traces of which could still be found at 70 d. Invading inflammatory cells moved into the collagen films between the layers from the edges only causing the whole structure to 'ribbon out'. The surfaces of all three films appeared to be impenetrable to cells. Incubation of the three films with bacterial collagenase revealed similar relative rates of degradation to those observed in vivo.

A composite membrane produced from collagen and vicryl mesh has been used to cover the kidney surface following partial nephrectomy in rabbits. The membrane readily held sutures, gave satisfactory haemostasis, and prevented leakage of urine. The experiments showed that the prosthesis biodegraded in less than twenty weeks. The only observed long-term effect of the material was thickening of the renal capsule. The results indicate that this membrane may be a suitable reparative material for use in traumatised kidneys in humans.

Collagen-coated Vicryl mesh was assessed as a prosthetic repair material in the oesophagus of growing piglets. In a group of six piglets (group A), a full thickness defect was created in the oesophagus without fully transecting the organ. The removed tissue was subsequently replaced with a patch of collagen-coated Vicryl mesh. Animals were killed at 4 weeks and in the five surviving piglets the prosthesis had been replaced by host scar tissue with a normal epithelial lining. Two further groups of six piglets (groups B and C) were used as controls. In group B the oesophagus was either partly transected (four animals) or completely transected (two animals) and an anastomosis was performed, whereas in group C a 2.5-cm length of oesophagus was removed so that the anastomosis was performed under tension. In group B, all six piglets survived, whereas in group C, where the anastomosis was performed under tension, only two piglets survived. Microscopic and macroscopic examination of all groups showed that the collagen-coated Vicryl prosthesis was replaced by scar tissue; moderate stenosis was observed in only one animal in group A. Collagen-coated Vicryl mesh may be used either to reinforce an anastomosis performed under tension or may find use in tubular form to bridge the gap between the two ends of the oesophagus to be joined. It is envisaged that such a material may find applications in the treatment of oesophageal atresia.

The assimilation characteristics of absorbable bovine fibrin implants in an experimental situation are described, and the effect of delaying absorption with formaldehyde treatment is demonstrated. Essentially, in vivo in the rat, Biethium fibrin implants are absorbed in approximately four to eight weeks because of the polymorphonuclear leukocyte digestion. An indication of the clinical uses in stress incontinence and hemorrhage of the liver are given, together with a look at the future of some of the other areas in which this absorbable, biologic plastic may fit into the surgeon's armamentarium to replace deficient or destroyed tissue.

The evolution of a collagen/vicryl composite membrane designed as a prosthetic material for use in urinary tract surgery is described. The early experiments in which collagen film alone was used to repair experimental ureterotomies are reviewed together with our first experiments with the collagen/vicryl prosthesis in the repair of partial nephrectomies and of full thickness defects created in the urinary bladder of experimental rabbits. These early results led to the preparation of a composite using a more highly purified collagen and employing a method of sterilisation (gamma irradiation) which would be acceptable for regular use in medical products. The results of a further series of partial nephrectomy and full thickness bladder repairs show that irradiation does not compromise the efficacy of the collagen/vicryl composite in vivo.

Diagnostic ultrasonography was used during surgery to assist in the removal of a piece of wire from the retropharyngeal region. A 3-year-old Quarter Horse mare was referred with dysphagia of 2 days' duration. Radiography revealed a 9-cm piece of wire located caudodorsal to the larynx. A ventral surgical approach was performed, dissecting along the right side of the larynx and trachea. The surgical field was filled with 0.85% sterile physiologic saline solution. A 5 MHz-mm sector scanner probe immersed in the fluid was able to locate the wire and facilitate the direction and depth of dissection to where the wire was identified and removed.

Arthroscopic surgery was performed on 12 horses (2-4 years of age) to create a 7 x 14 mm full-thickness cartilage defect in one radial carpal bone and in the contralateral third carpal bone. Six horses remained confined to a small paddock and six horses underwent a program of increasing exercise consisting of walking, trotting, and cantering for 13 weeks. All lesions showed evidence of healing at week 6 that progressed to more complete healing at week 13. There was no difference in the amount of repair tissue covering the defect. Histologically, the lesions healed with a combination of fibrous tissue and fibrocartilage. The repair tissue was significantly thicker in the exercised horses but there was no difference in repair quality. It was concluded that radial carpal and third carpal lesions have an equal ability to heal and that early postoperative exercise is not detrimental to the repair tissue within these carpal cartilage defects.

Collagen/vicryl (Polyglactin) composite membrane has been used to repair full-thickness defects in the urinary bladder of rabbits. The material has been shown to be biodegradable, prevent leakage of urine, and is readily replaced by collagenous scar tissue lined with a urothelium. Regeneration of smooth muscle has been observed in the repair area of some animals. The results suggest that such a material may well be of use to urologists wishing to augment contracted bladders or in the repair of bladder fistulae in human subjects, thereby avoiding the use of bowel or other material e.g. omentum.

This investigation assessed a biodegradable collagen membrane which can be sutured around the ureter to prevent urine leakage, thus permitting healing to proceed more rapidly while the membrane itself is resorbed. Following an early in vitro investigation in which collagen was assessed, a more comprehensive survey has now been carried out. Tissue compatibility and biodegradation were assessed by implanting the film into the lumbar muscles of rats; it was then used to cover experimental ureterotomies in New Zealand White rabbits. The data obtained from the rabbits confirmed that a collagen membrane can prevent leakage of urine from the ureter during healing while it itself is biodegraded, indicating that a collagen membrane could be used to repair the injured urinary tract.

The regeneration of smooth muscle appears to take place within the fibrous tissue characteristically found when a biodegradable collagen/Vicryl prosthesis is used to repair full thickness defects in the rabbit urinary bladder. The question of whether the central smooth muscle was the result of myoblastic differentiation in the fibrous tissue or arose from healthy pre-existing detrusor muscle was resolved by serial sectioning and specific staining. Only in situ transmutation, or differentiation, explains the morphology, and the results therefore strongly suggest that this central smooth muscle regenerated from within the repair area.

This study was carried out to evaluate the use of 'Zenoderm' (enzyme treated procine dermis) as a patch for the repair of tracheal defects in rats, with particular reference to its application in the treatment of some cases of tracheal stenosis. Fifty-three rats were included in the study. Using microsurgical techniques, a defect was created in the cervical trachea and repaired using a suitable patch of 'Zenoderm' (two groups with different sized defects). In a further group of rats, healing of the trachea was studied after excision of a segment and end to end anastomosis. A set number of rats were sacrificed after intervals of 14, 28, 91 and 182 days when the trachea was excised and evaluated. Healing of the tracheae following end to end anastomosis was satisfactory in all cases with no evidence of stenosis. The two groups of tracheae with Zenoderm patches showed progressive stenosis at the area of the repair but there was no evidence of respiratory obstruction or distress. The Zenoderm patch and the regenerating epithelium were both evaluated by light microscopy and scanning electromicroscopy. The Zenoderm patch showed gradual absorption and was replaced by host collagen. There was gradual regeneration of epithelium which showed slow maturation from flat non-ciliated epithelium to partially cuboidal and columnar epithelium with some cilia showing early differentiation to respiratory epithelium. In conclusion, this experimental study confirmed the biocompatibility of 'Zenoderm' in rats. It provided a suitable surface for regeneration of tracheal epithelium. Replacement of the patch by the host collagen is promising but requires further study to assess its rigidity and ability to withstand pressure changes in the trachea.