Great expectations? GPs' estimations of time required to deliver BMJ's '10 minute consultations'.

OBJECTIVES: To estimate the time required to undertake consultations according to BMJ's 10-minute consultation articles.To quantify the tasks recommended in 10-minute consultation articles.To determine if, and to what extent, the time required and the number of tasks recommended have increased over the past 22 years. DESIGN: Analysis of estimations made by four general practitioners (GPs) of the time required to undertake tasks recommended in BMJ's 10-minute consultation articles. SETTING: Primary care in the UK. PARTICIPANTS: Four doctors with a combined total of 79 years of experience in the UK National Health Service following qualification as GPs. MAIN OUTCOME MEASURES: Median minimum estimated consultation length (the estimated time required to complete tasks recommended for all patients) and median maximum estimated consultation length (the estimated time required to complete tasks recommended for all patients and the additional tasks recommended in specific circumstances). Minimum, maximum and median consultation lengths reported for each year and for each 5-year period. RESULTS: Data were extracted for 44 articles. The median minimum and median maximum estimated consultation durations were 15.7 minutes (IQR 12.6-20.9) and 28.4 minutes (IQR 22.4-33.8), respectively. A median of 17 tasks were included in each article. There was no change in durations required over the 22 years examined. CONCLUSIONS: The approximate times estimated by GPs to deliver care according to 10-minute consultations exceed the time available in routine appointments. '10 minute consultations' is a misleading title that sets inappropriate expectations for what GPs can realistically deliver in their routine consultations. While maintaining aspirations for high-quality care is appropriate, practice recommendations need to take greater account of the limited time doctors have to deliver routine care.

Understanding the patient's experience of coeliac disease diagnosis: a qualitative interview study.

BACKGROUND: Coeliac disease (CD) presents with non-specific symptoms, and delays to diagnosis are common. The traditional diagnostic pathway involves serological testing followed by endoscopic biopsy; however, the evidence is increasing about the effectiveness of a diagnosis without the need for a biopsy. AIM: To understand the patient's experience of being diagnosed with CD. DESIGN AND SETTING: A qualitative study was conducted, which involved semi-structured interviews with adults diagnosed with CD living in the UK. METHOD: Participants (n = 20) were purposefully sampled from 200 adults who had completed a diagnostic confidence survey. Interviews were conducted via video-conferencing software (Zoom), recorded, and transcribed verbatim. Data were analysed using reflexive thematic analysis. RESULTS: Interviewees faced pre-diagnostic uncertainty, presenting with non-specific symptoms that many experienced for several years and may have normalised. GPs often attributed their symptoms to alternative diagnoses, commonly, irritable bowel syndrome or anaemia. Investigations caused further uncertainty, with half of the interviewees unaware that their initial serology included a test for CD, and reporting long waits for endoscopy and challenges managing their diet around the procedure. Their uncertainty reduced once they received their biopsy results. Endoscopy was presented as the 'gold standard' for diagnosis and most interviewees believed that the procedure was necessary for diagnostic confidence and conviction in a lifelong gluten-free diet. CONCLUSION: Patients experience uncertainty on the pathway to a diagnosis of CD. GPs could improve their experiences by being mindful of the possibility of CD and sharing information about serological testing. Policy and guidance should address the time to endoscopy and diet during diagnosis. If diagnosis without biopsy is adopted, then consideration should be given to clinical pathway implementation and communication approaches to reduce patient uncertainty.

Newborn and child-like molecular signatures in older adults stem from TCR shifts across human lifespan.

CD8+ T cells provide robust antiviral immunity, but how epitope-specific T cells evolve across the human lifespan is unclear. Here we defined CD8+ T cell immunity directed at the prominent influenza epitope HLA-A*02:01-M158-66 (A2/M158) across four age groups at phenotypic, transcriptomic, clonal and functional levels. We identify a linear differentiation trajectory from newborns to children then adults, followed by divergence and a clonal reset in older adults. Gene profiles in older adults closely resemble those of newborns and children, despite being clonally distinct. Only child-derived and adult-derived A2/M158+CD8+ T cells had the potential to differentiate into highly cytotoxic epitope-specific CD8+ T cells, which was linked to highly functional public T cell receptor (TCR)αß signatures. Suboptimal TCRαß signatures in older adults led to less proliferation, polyfunctionality, avidity and recognition of peptide mutants, although displayed no signs of exhaustion. These data suggest that priming T cells at different stages of life might greatly affect CD8+ T cell responses toward viral infections.

Improving detection of undiagnosed HIV through routine screening in a central London emergency department.

HIV is a global public health issue. Routine testing for HIV should be performed on all 16-59 years old attending emergency departments (EDs) in high-prevalence areas in the UK.In August 2020, Charing Cross Hospital ED, situated in an 'extremely high-prevalence' area, had no formal guidelines on HIV testing. We aimed to increase HIV testing in 16-59 years old attending our ED to 25% by August 2021 through a quality improvement project, based on the Methodology for Improvement Model, performing six Plan-Do-Study-Act cycles over a 12-month period.An initial ED staff survey revealed 55% (n=22/40) of respondents were unsure of national HIV testing guidelines. Barriers to good testing practice included: lack of clarity on protocols for consent and indication, cost and perceived stigmatisation of patient groups. Interventions were employed at regular intervals, including employment of an HIV nurse advocate, inclusion of HIV tests in a blood test careset during ED triage, and updated trust guidelines that reflect national guidelines.Overall, we did achieve our original 12 month aim, with an average testing rate of 28% of our target group between September 2020 and August 2021. Extending the project to January 2022 has resulted in continued improvements in monthly testing rates, reaching 44% in December 2021. Further analysis revealed interventions led to a statistically significant and sustained increase in monthly testing rates on seven occasions.Valuable lessons were learnt in sustaining improvements in a busy department, changing long-held beliefs regarding consent for testing, and education around HIV care in the UK. Project write-up was formatted using the Revised Standards for Quality Improvement Reporting Excellence (SQUIRE) template.

Periprosthetic Capsule Formation and Contracture in a Rodent Model of Implant-Based Breast Reconstruction With Delayed Radiotherapy.

INTRODUCTION: Capsular contracture (CC) is the most common complication of breast implantation, with an incidence of nearly 50% in patients undergoing breast reconstruction with subsequent radiotherapy. Although the move toward submuscular (SM) device placement led to a decreased incidence of CC, subcutaneous (SQ) implantation has seen a resurgence. The purpose of this study was to use a rodent model of breast reconstruction with smooth silicone implants and delayed radiotherapy to assess the occurrence of CC in SQ versus SM implantation. METHODS: Custom 2 mL smooth round silicone implants were placed bilaterally into 12 female Sprague Dawley rats that were randomized into 4 groups of 3, with each group differing by implantation plane (SQ vs SM) and irradiation status (irradiated vs nonirradiated). Rats from the SQ group received implants bilaterally underlying the skin on the flank. Rats in the SM groups received implants bilaterally under the latissimus dorsi muscle. Irradiated rats received 20 Gy localized to each implant on postoperative day 10. One rat from each group was imaged with a micro-computed tomography scanner at baseline and at explant 3 months later, whereupon capsules from all rats were examined histologically. RESULTS: Rats in the SQ group showed evidence of contracture on gross examination and greater evidence of morphologic disruption per micro-computed tomography scan. There was no evidence of contracture or morphologic disruption in either SM group. Mean ± SD capsule thickness was 39.0 ± 9.0 µm in the SQ versus 37.6 ± 9.8 µm in the SM nonirradiated groups and 43.9 ± 14.9 µm in the SQ versus 34.3 ± 8.3 µm in the SM irradiated groups (all P > 0.05). CONCLUSIONS: In a rodent model of smooth silicone breast implantation and delayed radiotherapy, although there did not appear to be differences in capsule thickness regardless of device placement plane, SQ implants demonstrated gross evidence of CC. These data indicate that capsule thickness is only part of a larger pathogenetic picture, which should take into consideration the contribution from all peri-implant tissue.

Seeing New Opportunities to Help Smokers Quit: A UK National Survey of Optometrist-Delivered Smoking Cessation Behavioral Support Interventions.

BACKGROUND: Smoking is a risk factor for various eye conditions. Brief smoking cessation interventions have demonstrated effectiveness when delivered by a range of health care professionals. Optometrists are well placed in the community to advise otherwise healthy smokers to quit, yet remain relatively neglected in smoking cessation research and policy. In a national survey, this study investigated self-reported practices of UK optometrists for delivering brief tobacco smoking cessation interventions to patients. METHODS: A randomly selected sample of 1200 optometrists out of the 9000 optometrists registered on the UK College of Optometrists database were invited to complete a 40-item, web-based survey assessing: training related to smoking cessation, current practice (ie, the proportion of patients to which components of very brief advice [Ask, Advise, Assist] and other evidence-based smoking cessation behavior change techniques were delivered), and barriers/enablers to intervention delivery. RESULTS: In total, 408 (34%) responses were received. Most (83%) optometrists received no training in practical skills for delivering smoking cessation support. A third (34%) routinely assessed smoking status. Fewer self-reported advising smokers to quit (22%), offering assistance (via referral to dedicated services) (3%), or advice on smoking cessation medications (2%). Perceived barriers included insufficient knowledge/training (81%) and time (65%). Optometrists were more likely to assess and advise on smoking cessation if they practiced in Scotland, χ2(2) = 32.95, p < .001; an independent optometry practice, χ2(1) = 4.27, p = .39; or had received smoking cessation training, χ2(1) = 13.1, p < .001. CONCLUSIONS: Substantial gaps exist in UK optometrists' current smoking cessation training and practice. Evidence-based training resources are needed to support the implementation of smoking cessation interventions into routine optometry practice. IMPLICATIONS: Optometrists are well placed in the community to deliver brief advice interventions to a large population of smokers. This survey provides a comprehensive description of current UK optometry practice related to the provision of evidence-based brief tobacco smoking cessation interventions to patients. Although optometrists perceive advising on smoking cessation as part of their role, numerous substantial gaps in current practice and training remain, which need to be addressed through targeted interventions to increase implementation.

Effect of sex on vaccination outcomes: important but frequently overlooked.

It is well established that vaccination does not affect males and females equally. For example, females generally mount greater antibody responses to vaccination than males, but also suffer more adverse events following vaccination, probably as a result of more robust immunity. Despite this, most researchers in the field of vaccinology do not take biological sex into account when conducting their studies. This omission is likely to lead to a loss of important information in terms of both reactogenicity and immunogenicity following vaccination as well as those suffering adverse events. It also suggests that the vaccine dose in males and females may need to be different in order to achieve the same outcome of protective immunity while minimising reactogenicity.

Tissue Engineering Auricular Cartilage Using Late Passage Human Auricular Chondrocytes.

PURPOSE: The significant shortcomings associated with current autologous reconstructive options for auricular deformities have inspired great interest in a tissue engineering solution. A major obstacle in the engineering of human auricular cartilage is the availability of sufficient autologous human chondrocytes. A clinically obtainable amount of auricular cartilage tissue (ie, 1 g) only yields approximately 10 million cells, where 25 times this amount is needed for the fabrication of a full-scale pediatric ear. It is thought that repeated passaging of chondrocytes leads to dedifferentiation and loss of the chondrogenic potential. However, little to no data exist regarding the ideal number of times that human auricular chondrocytes (HAuCs) can be passaged in a manner that maximizes the cellular expansion while minimizing dedifferentiation. METHODS: Human auricular chondrocytes were isolated from discarded otoplasty specimens. The HAuCs were then expanded, and cells from passages 3, 4, and 5 were encapsulated into discs 8 mm in diameter made from type I collagen hydrogels with a cell density of 25 million cells/mL. The constructs were implanted subcutaneously in the dorsa of nude mice and harvested after 1 and 3 months for analysis. RESULTS: Constructs containing passages 3, 4, and 5 chondrocytes all maintained their original cylindrical geometry. After 3 months in vivo, the diameters of the P3, P4, and P5 discs were 69 ± 9%, 67 ± 10%, and 73 ± 15% of their initial diameter, respectively. Regardless of the passage number, all constructs developed a glossy white cartilaginous appearance, similar to native auricular cartilage. Histologic analysis demonstrated development of an organized perichondrium composed of collagen, a rich proteoglycan matrix, cellular lacunae, and a dense elastin fibrin network by Safranin-O and Verhoeff stain. Biochemical analysis confirmed similar amounts of proteoglycan and hydroxyproline content in late passage constructs when compared with native auricular cartilage. CONCLUSIONS: These data indicate that late passage HAuCs (up to passage 5) form elastic cartilage that is histologically, biochemically, and biomechanically similar to native human elastic cartilage and have the potential to be used for auricular cartilage engineering.

Considerations on accuracy, pattern and possible underlying factors of brain microbleed progression in older adults with absence or mild presence of vascular pathology.

Objective To analyse brain microbleed (BMB) progression, its possible underlying factors, and the influence of inter-observer differences, in older individuals with none or mild vascular pathology. Methods This study analysed magnetic resonance images, cognitive, demographic and laboratory data from all individuals from the Alzheimer's Disease (AD) Neuroimaging Initiative database who had the required sequences for identifying BMBs over three consecutive years at the time the database was accessed (January 2016). BMBs were assessed independently by two observers with similar levels of experience. Results A total of 291 patients were included in the study. The number of individuals with BMBs and the number of BMBs per individual slightly and nonsignificantly increased across three consecutive years (Y1: 55/291 [19%]; Y2: 61/291 [21%]; Y3: 66/291 [23%]) with 1-2 BMBs and (Y1: 11/291 [4%]; Y2: 12/291 [4%]; Y3: 14/291 [5%]) with ≥ 3 BMBs. Both observers identified a similar pattern of BMB prevalence and progression in each cognitive group (normal < early/late mild cognitive impairment (MCI) > AD patients) despite inter-observer differences (1.5 BMBs, 95% confidence interval -3.7, 6.2], κ=0.543), which were mainly in the cortex. Serum cholesterol was the main predictor of change in BMB count between time-points but did not predict overall progression. Conclusions Inter-observer differences are always present and it is difficult to ascertain their influence in the analysis of BMB progression, which was observed in cognitively normal and MCI individuals, but not in AD patients. This should be confirmed in further studies.

Optimizing cell sourcing for clinical translation of tissue engineered ears.

Background . Currently, the major impediment to clinical translation of our previously described platform for the fabrication of high fidelity, patient-specific tissue engineered ears is the development of a clinically optimal cell sourcing strategy. A limited autologous auricular chondrocyte (AuC) supply in conjunction with rapid chondrocyte de-differentiation during in vitro expansion currently makes clinical translation more challenging. Mesenchymal stem cells (MSCs) offer significant promise due to their inherent chondrogenic potential, and large availability through minimally invasive procedures. Herein, we demonstrate the promise of AuC/MSC co-culture to fabricate elastic cartilage using 50% fewer AuC than standard approaches. METHODS: Bovine auricular chondrocytes (bAuC) and bovine MSC (bMSC) were encapsulated within 10 mg ml-1 type I collagen hydrogels in ratios of bAuC:bMSC 100:0, 50:50, and 0:100 at a density of 25 million cells ml-1 hydrogel. One mm thick collagen sheet gels were fabricated, and thereafter, 8 mm diameter discs were extracted using a biopsy punch. Discs were implanted subcutaneously in the dorsa of nude mice (NU/NU) and harvested after 1 and 3 months. RESULTS: Gross analysis of explanted discs revealed bAuC:bMSC co-culture discs maintained their size and shape, and exhibited native auricular cartilage-like elasticity after 1 and 3 months of implantation. Co-culture discs developed into auricular cartilage, with viable chondrocytes within lacunae, copious proteoglycan and elastic fiber deposition, and a distinct perichondrial layer. Biochemical analysis confirmed that co-culture discs deposited critical cartilage molecular components more readily than did both bAuC and bMSC discs after 1 and 3 months, and proteoglycan content significantly increased between 1 and 3 months. CONCLUSION: We have successfully demonstrated an innovative cell sourcing strategy that facilitates our efforts to achieve clinical translation of our high fidelity, patient-specific ears for auricular reconstruction utilizing only half of the requisite auricular chondrocytes to fabricate mature elastic cartilage.

A survey of UK optometry trainees' smoking cessation training.

BACKGROUND: Smoking is a risk factor for a number of eye conditions, including age-related macular degeneration, cataracts and thyroid eye disease. Smoking cessation interventions have been shown to be highly cost-effective when delivered by a range of healthcare professionals. Optometrists are well placed to deliver smoking cessation advice to a wide population of otherwise healthy smokers. Yet optometrists remain a relatively neglected healthcare professional group in smoking cessation research and policy. Surveys of UK medical/nursing schools and of optometrists' training internationally demonstrate significant deficits in current curricular coverage regarding smoking cessation. This study aimed to identify the extent of smoking cessation training in UK optometry trainees' undergraduate and pre-registration training. METHODS: All undergraduate optometry schools in the UK (n = 9) were invited to participate in a web-based survey of their curricular coverage and assessment related to smoking cessation, and of perceived barriers to delivering smoking cessation training. A content analysis of the College of Optometrists Scheme for Registration Trainee Handbook 2014 was conducted to identify competence indicators related to smoking cessation. RESULTS: Nine undergraduate optometry schools (100%) responded to the survey. The majority reported dedicating limited hours (0-3) to teaching smoking cessation, and predominantly focused on teaching the harmful effects of smoking (89%). Only one school provides practical skills training for delivering evidence-based smoking cessation interventions, including very brief advice. The majority of schools (78%) reported that they did not formally examine students on their knowledge or skills for supporting smoking cessation, and rated confidence in their graduates' abilities to deliver smoking cessation interventions as 'poor' (78%). Lack of knowledge amongst staff was identified as the key barrier to teaching about smoking cessation support. The pre-registration competency framework does not include any competence indicators related to providing support for quitting smoking. CONCLUSIONS: There are substantial gaps in the current curricula of UK optometry training, particularly regarding practical skills for supporting smoking cessation. Increased curricular coverage of these issues is essential to ensure trainee optometrists are adequately trained and competent in supporting patients to quit smoking.

Fabrication and in vivo microanastomosis of vascularized tissue-engineered constructs.

Tissue engineering endeavors to create replacement tissues and restore function that may be lost through infection, trauma, and cancer. However, wide clinical application of engineered scaffolds has yet to come to fruition due to inadequate vascularization. Here, we fabricate hydrogel constructs using Pluronic(®) F127 as a sacrificial microfiber, creating microchannels within biocompatible, biodegradable type I collagen matrices. Microchannels were seeded with human umbilical vein endothelial cells (HUVEC) or HUVEC and human aortic smooth muscle cells (HASMC) in co-culture, generating constructs with an internal endothelialized microchannel. Histological analysis demonstrated HASMC/HUVEC-seeded constructs with a confluent lining after 7 days with preservation and further maturation of the lining after 14 days. Immunohistochemical staining demonstrated von Willebrand factor and CD31(+) endothelial cells along the luminal surface (neointima) and alpha-smooth muscle actin expressing smooth muscle cells in the subendothelial plane (neomedia). Additionally, the deposition of extracellular matrix (ECM) components, heparan sulfate and basal lamina collagen IV were detected after 14 days of culture. HUVEC-only- and HASMC/HUVEC-seeded microchannel-containing constructs were microsurgically anastomosed to rat femoral artery and vein and perfused, in vivo. Both HUVEC only and HUVEC/HAMSC-seeded constructs withstood physiologic perfusion pressures while their channels maintained their internal infrastructure. In conclusion, we have synthesized and performed microvascular anastomosis of tissue-engineered hydrogel constructs. This represents a significant advancement toward the generation of vascularized tissues and brings us closer to the fabrication of more complex tissues and solid organs for clinical application.

Development of an acellular bioengineered matrix with a dominant vascular pedicle.

BACKGROUND: This study assessed the feasibility of creating a tissue engineering platform by decellularization of fasciocutaneous tissue. MATERIALS AND METHODS: A fasciocutaneous flap based upon the superficial inferior epigastric artery was harvested from the abdominal wall of 8-wk-old male Sprague-Dawley rats. All cellular components were removed by sequential treatment with sodium azide, DNAse, and sodium deoxycholate. The degree of decellularization was qualitatively assessed by histology and quantitatively assessed by spectrophotometry. Persistence of relevant extracellular matrix proteins was shown following staining with orcein and hematoxylin. The duration of circuit patency was determined by continuous perfusion with a peristaltic perfusion pump. RESULTS: Gross and histologic examination demonstrated removal of cellular constituents with preservation of tissue matrix architecture, including macrochannels and microchannels. This was confirmed by the application of spectrophotometry to DNA isolates, which showed that the decellularized flap retained 4.04 ng/µL DNA, compared with the non-processed control, which retained 37.03 ng/µL DNA, and the acellular control, which was read as having 0.65 ng/µL DNA. The extracellular matrix of vessel walls was shown to remain intact. Peristaltic perfusion of the cannulated pedicle inflow channel with phosphate buffered saline at a rate of 200 µL/min confirmed circuit patency for 6 h. CONCLUSION: Fasciocutaneous flaps harvested with an intact vascular pedicle and associated tissue vascular network can be successfully decellularized and perfused ex vivo. This methodology, which is scalable to human size tissues, provides promise as a technique for the production of customizable engineered tissues.

Electrochemical glucose sensors--developments using electrostatic assembly and carbon nanotubes for biosensor construction.

In 1962, Clark and Lyons proposed incorporating the enzyme glucose oxidase in the construction of an electrochemical sensor for glucose in blood plasma. In their application, Clark and Lyons describe an electrode in which a membrane permeable to glucose traps a small volume of solution containing the enzyme adjacent to a pH electrode, and the presence of glucose is detected by the change in the electrode potential that occurs when glucose reacts with the enzyme in this volume of solution. Although described nearly 50 years ago, this seminal development provides the general structure for constructing electrochemical glucose sensors that is still used today. Despite the maturity of the field, new developments that explore solutions to the fundamental limitations of electrochemical glucose sensors continue to emerge. Here we discuss two developments of the last 15 years; confining the enzyme and a redox mediator to a very thin molecular films at electrode surfaces by electrostatic assembly, and the use of electrodes modified by carbon nanotubes (CNTs) to leverage the electrocatalytic effect of the CNTs to reduce the oxidation overpotential of the electrode reaction or for the direct electron transport to the enzyme.

Effective expansion of alloantigen-specific Foxp3+ CD25+ CD4+ regulatory T cells by dendritic cells during the mixed leukocyte reaction.

Thymic-derived CD25+ CD4+ T regulatory cells (Tregs) suppress immune responses, including transplantation. Here we evaluated the ability of dendritic cells (DCs) to expand alloantigen-specific Tregs in the mixed leukocyte reaction (MLR) that develops from polyclonal populations of T cells. The allogeneic DCs, when supplemented with IL-2 in the cultures, were much more effective than bulk spleen cells in expanding the numbers of Tregs. Likewise, DCs and not spleen cells were effective in sustaining expression of the transcription factor Foxp3 in Tregs, but neither IL-2 nor CD80/86 was required for this effect in the cultures. On a per-cell basis, the DC-expanded, but not unexpanded, Tregs were more potent suppressors of a fresh MLR by CD25- CD4+ T cells. Suppression was 3- to 10-fold more active for MLRs induced by the original alloantigens than for third-party stimulators. When DC-expanded Tregs were introduced into sublethally irradiated hosts, the T cells suppressed graft-versus-host-disease induced by CD25- CD4+ T cells. Again, suppression was more active against the same mouse strain that provided the DCs to expand the Tregs. Therefore, alloantigen-selected Tregs are more effective suppressors of responses to major transplantation antigens, and these Tregs can be expanded from a polyclonal repertoire by DCs.

COX-2 up-regulation in idiopathic carpal tunnel syndrome.

The objective of this study was to determine whether cyclooxygenase-2 (COX-2) is up-regulated in the synovium of patients with carpal tunnel syndrome. Twenty patients were enrolled: 16 consecutive patients with carpal tunnel syndrome and four control patients (exploration for non-carpal tunnel syndrome-related wrist or forearm pathology). Clinical data (demographics, pertinent history, symptomatology) were obtained preoperatively. Flexor tenosynovial tissue was isolated from all patients and clinically graded as thin, intermediate, or thick. Histologic evaluation was conducted to rule out the presence of inflammatory cells. Immunohistochemical staining for COX-2 was performed. The immunohistochemical data were confirmed by reverse transcriptase-polymerase chain reaction analysis of COX-2 mRNA. Results showed that the majority of carpal tunnel syndrome specimens (88 percent) showed synovial hypertrophy compared with 0 percent of the controls (p < 0.05). Also, 69 percent of carpal tunnel syndrome specimens (11 of 16) versus 0 percent of controls (zero of four) stained positively for COX-2 (p < 0.05). Of the carpal tunnel syndrome patients, 91 percent of thick specimens versus 33 percent of intermediate specimens versus 0 percent of thin specimens showed COX-2 staining. The authors conclude that synovial hypertrophy is a prominent finding in carpal tunnel syndrome. COX-2 is up-regulated in the tenosynovium of patients with carpal tunnel syndrome, and this upregulation may correlate with the clinical grade of the tenosynovium. The role of COX-2 in carpal tunnel syndrome may be to mediate remodeling of pathologic tissue. To this end, it may be a potential therapeutic target for specific inhibition.

Expression of cyclooxygenase-2 in the periprosthetic capsule surrounding a silicone shell implant in the rat.

Prosthetic breast implants are used frequently for both aesthetic and reconstructive purposes. Histologically, the normal tissue response to silicone implants typically involves an inflammatory infiltrate that consists initially of macrophages, and later consists of fibroblasts, myofibroblasts, and lymphocytes. To characterize further the nature of the inflammatory response to silicone breast implants, the authors evaluated the expression of the enzyme cyclooxygenase-2 (COX-2) by the tissues and cells of the breast capsule after silicone augmentation in an animal model. COX-2 is an inducible enzyme that is expressed primarily in response to inflammatory stimuli and mediates the production of prostaglandins that support the inflammatory process. Fifty-nine animals at five time points were evaluated. Specifically, on days 4, 7, 14, 28, and 80 the authors identified cytoplasmic COX-2 expression in each of the three cell types of interest, including endothelial cells, macrophages, and fibroblasts. Selective COX-2 inhibiting agents may be an appropriate pharmacological intervention for modulating the formation of periprosthetic capsules.

Intelligent Instrumentation.

Feasibility studies on the application of multivariate statistical and mathematical algorithms to chemical problems have proliferated over the past 15 years. In contrast to this, most commercially available computerized analytical instruments have used in the data systems only those algorithms which acquire, display, or massage raw data. These techniques would fall into the "preprocessing stage" of sophisticated data analysis studies. An exception to this is, of course, are the efforts of instrumental manufacturers in the area of spectral library search. Recent firsthand experiences with several groups designing instruments and analytical procedures for which rudimentary statistical techniques were inadequate have focused efforts on the question of multivariate data systems for instrumentation. That a sophisticated and versatile mathematical data system must also be intelligent (not just a number cruncher) is an overriding consideration in our current development. For example, consider a system set up to perform pattern recognition. Either all users need to understand the interaction of data structures with algorithm type and assumptions or the data system must possess such an understanding. It would seem, in such cases, that the algorithm driver should include an expert systems specifically geared to mimic a chemometrician as well as one to aid interpretation in terms of the chemistry of a result. Three areas of modem analysts will be discussed: 1) developments in the area of preprocessing and pattern recognition systems for pyrolysis gas chromatography and pyrolysis mass spectrometry; 2) methods projected for the cross interpretation of several analysis techniques such as several spectroscopies on single samples; and 3) the advantages of having well defined chemical problems for expert systems/pattern recognition automation.