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Background: Quality indicators can be used within healthcare to measure and benchmark performance. Variations in the access and quality of healthcare for musculoskeletal conditions highlights the need for a nationally agreed set of indicators., Objectives: The study's primary aim was to develop a set of care quality themes and indicators for musculoskeletal community care., Methods: An online Delphi process was used, that included clinicians, managers, researchers, and patients. In round one, participants rated 79 indicators, across six care quality themes, for their importance to quality community musculoskeletal care. Following this, participants discussed the results of the first round in an online panel and then re-rated indicators in a second-round survey. The panel discussion focused on a) the importance rating of indicators, and b) the wording of care quality themes. Consensus for high importance was set at ≥60% in both rounds of the study., Results/findings: Forty-six individuals participated in the first round of the study, with 21 participating in the second round. After the second round, six care quality themes emerged: 1) Optimising patient access and assessment, 2) Optimising patient education, self-management, and rehabilitation, 3) Optimising personalised care, 4) Optimising diagnosis, imaging, investigation, and referrals, 5) Optimising patient experience and outcomes, and 6) Population health relevant to musculoskeletal conditions. Within the six themes, 59 indicators were ranked as highly important., Conclusions: This study has developed a set of care quality themes and indicators for community musculoskeletal care. In the next stage of indicator development, real-world data will be used to validate the indicators across several constructs., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The OPTimisE intervention was developed to address uncertainty regarding the most effective physiotherapy treatment strategy for people with Lateral Elbow Tendinopathy (LET)., Objectives: To assess the feasibility of conducting a fully-powered randomised controlled trial (RCT) evaluating whether the OPTimisE intervention is superior to usual physiotherapy treatment for adults with LET., Design: A mixed-methods multi-centred, parallel pilot and feasibility RCT, conducted in three outpatient physiotherapy departments in the UK., Method: Patients were independently randomised 1:1 in mixed blocks, stratified by site, to the OPTimisE intervention or usual care. Outcomes were assessed using pre-defined feasibility progression criteria., Results: 50 patients were randomised (22 Female, 28 Male), mean age 48 years (range 27-75). Consent rate was 71% (50/70), fidelity to intervention 89% (16/18), attendance rate in the OPTimisE group 82% (55/67) vs 85% (56/66) in usual care, outcome measure completion 81% (39/48) at six-month follow-up. There were no related adverse events. Patients and physiotherapists reported that the OPTimisE intervention was acceptable but suggested improvements to the trial design. 49 patients were recruited from physiotherapy referrals vs one from primary care records. Outcome measure return rates were higher when completed online (74%) compared to postal questionnaire (50%). Exploratory analysis showed improvements in both groups over time., Conclusions: It is methodologically feasible to conduct a fully powered RCT comparing the clinical and cost-effectiveness of the OPTimisE intervention versus usual physiotherapy treatment. Considering the similar improvements observed in both groups, careful consideration is needed regarding the priority research question to be addressed in future research., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare. This paper presents independent research funded by the National Institute for Health and Care Research (NIHR) and Chartered Society of Physiotherapy Charitable Trust. The views expressed are those of the author(s) and not necessarily those of Chartered Society of Physiotherapy Charitable Trust, the NHS, the NIHR or the Department of Health and Social Care., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Benchmarking musculoskeletal (MSK) services is limited by the need to adjust for differences in patient characteristics/case-mix. Without this providers and services cannot be usefully compared. This paper investigates the predictive ability of case-mix adjustment models in a primary/community care cohort., Objectives: To investigate the predictive ability of two existing MSK case-mix adjustment models and compare to the predictive ability of an evidence informed and statistically informed model., Method: A secondary analysis of the 'Subgrouping for Targeted Treatment in Musculoskeletal Conditions' cluster randomised controlled trial data (n = 1211). Stepwise linear regression models were built and compared using available baseline variables. The MSK-HQ was used as the primary functional status outcome., Results: Two existing models were compared (UK National PROMs Model, US FOTO Model) using available variables. Of these models the modified US FOTO model showed the best predictive ability in this cohort predicting 44% of the variation in MSK-HQ outcome, the modified UK National PROMs model predicted 41%. A newly developed evidence informed model (Keele Model 1) performed no better than the existing models, and a statistically informed model (Keele Model 2) gave only an additional 2% increase in model power compared to the modified US FOTO model., Conclusion: All models showed strong predictive ability. The modified US FOTO model looks to be best suited to the UK primary/community care cohort of the existing models. This model performed so well that we recommend that this model is used in a UK setting moving forwards rather than development of an alternative UK model., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: At present there is no core outcome set (COS) for use in community and primary care Musculoskeletal (MSK) services across the UK. Services are therefore collecting different MSK outcomes and metrics in different ways and at different times. Standardising MSK data collection is essential in order for fair and impactful benchmarking to improve the quality of care delivered to the millions of patients presenting each year with MSK disorders., Objective: To gain consensus on a proposed set of metrics that could be used to develop a COS for use in routine practice in community and primary care MSK services in the UK and to make recommendations to inform a future national MSK audit., Methods: A consensus process involving researchers, healthcare professionals and patients. Previous research generated an initial list of proposed metrics. This proposal was then taken to wider stakeholder consensus via an online survey designed for both healthcare professionals and MSK service users., Results: 199 respondents completed the survey, 166 healthcare professionals and 33 service users (25/33 eligible to answer all items within the survey). Metrics that reached strong consensus were; age, pain site, comorbidities, duration of symptoms, work status, work absence, work absence duration. No Patient Reported Outcome Measures (PROMs) met strong consensus and all Patient Reported Experience Measures (PREMs) other than timeliness/convenience met strong consensus criteria., Conclusion: 7 baseline factors and 9 PREM domains reached strong consensus. The MSK-HQ PROM was the highest rated outcome measure so was also recommended for inclusion in an MSK COS., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The STarT Back Tool (Subgrouping for Targeted Treatment; SBT) was developed and validated in the United Kingdom for adults with non-specific low back pain (LBP) to provide risk stratification groups. An Arabic version has not yet been developed. Consequently, our objectives were: First, to cross-culturally adapt the SBT for use in Arabic speaking adults (SBT-Ar) with LBP. Second, to assess the face, content and construct validity of SBT-Ar against relevant reference standards., Methods: This was a prospective, cross-sectional study carried out in the outpatient department in a tertiary care hospital. A total of 59 participants (aged 18-60) with LBP able to read Arabic completed the questionnaire. SBT cross-cultural adaptation was performed according to published guidelines. Face and content validity were explored by individual interviews. Construct validity was assessed using pre-hypothesized correlations with relevant reference standards., Results: Following 48 individual interviews the SBT final version was reached and demonstrated face and content validity. The SBT-Ar total score and psychosocial sub-scale had acceptable internal consistency and no redundancy (Cronbach α = 0.7). Moderate Spearman's correlations were found between the SBT-Ar total score and reference standards (Arabic Pain Numeric Rating Scale NRS-Ar r = 0.50 and Arabic Oswestry Disability Index ODI-ar r = 0.51). As expected the SBT-Ar psychosocial subscale had medium to high correlations with the psychosocial reference measures (Arabic Fear-Avoidance Beliefs Questionnaire Physical Activity FABQPA-Ar r = 0.41, Arabic Hospital Anxiety and Depression Scale-Anxiety HADSA-Ar r = 0.58, Arabic Hospital Anxiety and Depression Scale-Depression HADSD-Ar r = 0.45 and Arabic Pain Catastrophizing Scale PCSAr r = 0.69).The SBT-Ar showed no significant floor or ceiling effects., Conclusion: This study culturally adapted and preliminary validated SBT into Arabic., Study Design: Prospective, Cross-sectional., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

Background: The use of tranexamic acid (TXA) in total hip replacement (THR) typically reduces blood loss by approximately 400 mL, and typical total blood loss is still approximately 1 L. A barrier to harnessing the full potential of TXA is disagreement on the optimum timing of administration. To address this, we aimed to identify the period of greatest blood loss., Methods: We analyzed the perioperative data of 870 patients who had undergone THR, total knee replacement, or unicompartmental knee replacement just before the introduction of TXA to our unit. Total blood loss was calculated on postoperative day (POD) 1 and POD2 using an equation based on change in hematocrit., Results: Average total blood loss at POD2 was 1505, 1322, and 611 mL for THR, total knee replacement, and unicompartmental knee replacement, respectively. Between 86% and 96% of this blood loss occurred in the period between skin closure and POD1. Intraoperative loss did not correlate with total loss at POD2. Blood transfusion was more likely if the patient was female (odds ratio [OR], 6.8) or if they had preoperative anemia (OR, 8.3) than if there was a high-volume blood loss (OR, 1.6)., Conclusions: Approximately 90% of blood loss occurs between skin closure and the first postoperative 24 hours. "Intraoperative blood loss" and "transfusion rate" are not reliable markers of total blood loss. The full potential of TXA could be harnessed by using it during the period of greatest blood loss, that is, during the first postoperative 24 hours.

Background: Bicuspid aortic valve (BAV) is associated with asymmetric dilatation of the proximal ascending aorta. We previously demonstrated increased susceptibility of smooth muscle cells to oxidative stress in the BAV-aneurysmal aorta and hypothesized that antioxidant expression is regionally defined and influenced by the BAV morphotype., Methods: BAV valve morphology was defined according to number of raphes: type 0 (0 raphes), type 1 (1 raphe), or type 2 (2 raphes) and by the raphe location among the left (L), right (R) or non (N) coronary cusps. Ascending aortic specimens were partitioned into three regions corresponding to the sinuses of Valsalva, denoted R, N (greater curve), and L (lesser curve). Transcripts 1, 2, and 3 from the gene expressing superoxide dismutase (Sod) were quantified in all three regions. Results were compared with aneurysmal and nonaneurysmal aortic specimens from patients with a tricuspid aortic valve., Results: Region-specific Sod1 upregulation and Sod2 downregulation were dependent on the BAV morphotype. Sod3 was uniformly downregulated in all regions in a morphotype-independent manner. Sod1 upregulation was noted in the R region of the nonaneurysmal type 1 L/R morphotype. Aortic valve regurgitation, but not stenosis, affected the expression of Sod isoforms in specimens of degenerative aneurysms., Conclusions: Region-specific transcription profiles of Sod on the basis of BAV morphotype deepen our understanding of its associated aortopathy and provide biological insight on the asymmetric dilatation pattern. This work indicates regional differences exist in the oxidative stress biology of the proximal aortic wall, and this may lead to newer diagnostic techniques to adjudicate aortic catastrophe risk., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Endothelial nitric oxide (NO) synthase (eNOS) has been implicated in the development of bicuspid aortic valve (BAV) and with differential expression in the ascending aorta of BAV patients. However, little is known about functional disruptions in the eNOS pathway and the effect on BAV-associated aortic dilatation. We tested the hypothesis that eNOS function is regionally diminished in ascending thoracic aortic aneurysms associated with BAV., Methods: Thoracic aortic aneurysms specimens were collected from patients with BAV (n = 21) or tricuspid aortic valve (n = 12). Tissue samples were harvested from three circumferential regions corresponding to locations above the right, left, and noncoronary sinuses. Adventitial-stripped specimens containing media and intima only were analyzed for NO synthase 3 gene expression and total eNOS protein. Indicators of eNOS activity (pSer1177-eNOS) and NO bioavailability (phosphorylation of vasodilator-stimulated phosphoprotein at Ser239) were also measured., Results: NO synthase 3 and eNOS protein were elevated in the right aortic region of BAV specimens compared with tricuspid aortic valve specimens. Activation of eNOS, as indicated by pSer1177-eNOS, was higher in BAV specimens across all regions. Despite increases in eNOS and pSer1177-eNOS, BAV specimens displayed no change in pSer239-vasodilator-stimulated phosphoprotein compared with tricuspid aortic valve specimens., Conclusions: BAV is associated with regional disruptions in the eNOS pathway, most markedly in the right aortic region. The discrepancy between increased eNOS activity and the absence of increased NO bioavailability in this region provides insight into physiologic mechanisms potentially underlying the asymmetric dilatation pattern observed in BAV., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Stratified care for back pain involves targeting treatment to subgroups of patients based on their key characteristics such as prognostic factors, likely response to treatment and underlying mechanisms. It aims to tailor therapeutic decisions in ways that maximise treatment benefit, reduce harm and increase health-care efficiency by offering the right treatment to the right patient at the right time. From being called the 'Holy Grail' of back pain research over a decade ago, stratified care is becoming the zeitgeist in research and clinical practice. In this chapter, we introduce and evaluate the quality and underpinning evidence for three examples of stratified care for back pain to highlight their general principles, research design issues and clinical practice implications. We include consideration of their merits for implementation in practice. We conclude with a set of remaining, key research questions., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Studies have shown that the shape and size of the placenta at birth predict blood pressure in later life. The influences that determine placental morphology are largely unknown. We have examined the role of mother's body size., Methods: We studied 522 neonates who were born in a maternity hospital in Mysore, South India. The weight of the placenta and the length and breadth of its surface, were measured after delivery., Results: Higher maternal fat mass predicted a larger placental surface (p = 0.02), while larger maternal head circumference predicted a more oval placental surface (p = 0.03). Higher maternal fat mass and larger maternal head circumference were associated with greater placental efficiency, indicated by lower ratios of the length (p = 0.0003 and p = 0.0001 respectively) and breadth (p = 0.0002 and p < 0.0001) of the surface to birthweight. In a sub-sample of 51 mothers whose own birthweight was available, higher maternal birthweight was related to lower ratios of the length and breadth of the surface to birthweight (p = 0.01 and 0.002). Maternal height was unrelated to placental size or shape., Conclusions: Higher maternal fat mass, reflecting the mother's current nutritional state, and larger maternal head circumference, reflecting the mother's fetal/infant growth, are associated with changes in the shape and size of the placental surface and greater placental efficiency. We suggest that these associations reflect effects of the mother's nutrition at different stages of her lifecourse on the development of the placenta and on materno-placento-fetal transfer of nutrients., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Back pain remains a challenge for primary care internationally. One model that has not been tested is stratification of the management according to the patient's prognosis (low, medium, or high risk). We compared the clinical effectiveness and cost-effectiveness of stratified primary care (intervention) with non-stratified current best practice (control)., Methods: 1573 adults (aged ≥18 years) with back pain (with or without radiculopathy) consultations at ten general practices in England responded to invitations to attend an assessment clinic. Eligible participants were randomly assigned by use of computer-generated stratified blocks with a 2:1 ratio to intervention or control group. Primary outcome was the effect of treatment on the Roland Morris Disability Questionnaire (RMDQ) score at 12 months. In the economic evaluation, we focused on estimating incremental quality-adjusted life years (QALYs) and health-care costs related to back pain. Analysis was by intention to treat. This study is registered, number ISRCTN37113406., Findings: 851 patients were assigned to the intervention (n=568) and control groups (n=283). Overall, adjusted mean changes in RMDQ scores were significantly higher in the intervention group than in the control group at 4 months (4·7 [SD 5·9] vs 3·0 [5·9], between-group difference 1·81 [95% CI 1·06-2·57]) and at 12 months (4·3 [6·4] vs 3·3 [6·2], 1·06 [0·25-1·86]), equating to effect sizes of 0·32 (0·19-0·45) and 0·19 (0·04-0·33), respectively. At 12 months, stratified care was associated with a mean increase in generic health benefit (0·039 additional QALYs) and cost savings (£240·01 vs £274·40) compared with the control group., Interpretation: The results show that a stratified approach, by use of prognostic screening with matched pathways, will have important implications for the future management of back pain in primary care., Funding: Arthritis Research UK., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Metabolic consequences of vitamin D deficiency have become a recent research focus. Maternal vitamin D status is thought to influence musculoskeletal health in children, but its relation with offspring metabolic risk is not known., Objective: We aimed to examine the association between maternal vitamin D status and anthropometric variables, body composition, and cardiovascular risk markers in Indian children., Design: Serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured at 28-32 wk gestation in 568 women who delivered at Holdsworth Memorial Hospital, Mysore, India. Anthropometric variables, glucose and insulin concentrations, blood pressure, and fasting lipid concentrations were measured in the offspring at 5 and 9.5 y of age. Muscle-grip strength was measured by using a hand-held dynamometer at age 9.5 y. Arm-muscle area was calculated as a measure of muscle mass. Fasting insulin resistance was calculated by using the homeostasis model assessment equation., Results: Sixty-seven percent of women had vitamin D deficiency [serum 25(OH)D concentration <50 nmol/L]. At ages 5 and 9.5 y, children born to vitamin D-deficient mothers had smaller arm-muscle area in comparison with children born to mothers without deficiency (P < 0.05). There was no difference in grip strength between offspring of women with and without vitamin D deficiency. At 9.5 y, children of vitamin D-deficient mothers had higher fasting insulin resistance than did children of nondeficient women (P = 0.04). There were no associations between maternal vitamin D status and other offspring risk factors at either age., Conclusion: Intrauterine exposure to low 25(OH)D concentrations is associated with less muscle mass and higher insulin resistance in children.

Low back pain is a common, disabling condition with high personal and economic costs. Despite clinical guidelines, there have not been tangible reductions in the population prevalence of back pain or its serious long-term consequences. One reason for this might be that the 'one-size fits all approach' advocated by many guidelines fails to target treatments at patients who might benefit the most, thus diluting their potential benefits. Identifying subgroups of patients for whom different treatments are superior has been referred to as the 'Holy Grail' of low back pain research. Maximising the potential for targeted interventions is predicated on better understanding of the prognostic factors that are causally related to clinical outcome and identifying which are a) most predictive of outcome and b) most likely to be modifiable. Systematic identification of key obstacles to recovery in primary care back pain patients from high quality epidemiological studies can inform the development of early, targeted interventions. Only then can closer matching of treatments to patient characteristics be a clinical reality. This paper critically reviews progress in subgrouping for targeted treatment for patients with low back pain, identifies the key arguments for and against subgrouping and highlights the attributes of robust approaches in this field., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

A 58-year-old woman presented with a lump on the left side of the neck. Investigations by ultrasound-guided fine needle aspiration, magnetic resonance imaging, and positron emission tomography were all indicative of a diagnosis of a solitary malignant mass with no primary lesion identified. The patient underwent a level I-V leftside selective neck dissection. The histology results reported the mass as a carotid body paraganglioma. These are highly vascular lesions. Paragangliomas have characteristic features on the different imaging modalities; in this case they were atypical. This article reviews the main imaging modalities of paragangliomas and cytologic findings of the fine needle aspiration, which is not often performed for these cases owing to their high vascularity., (Crown Copyright 2010. Published by Mosby, Inc. All rights reserved.)

Between 2004 and 2008 the Forensic Isotope Ratio Mass Spectrometry (FIRMS) network organised four Inter-Laboratory Camparison excercises with the aim of harmonising and validating isotopic measurements to be used for forensic applications. The samples distributed comprised materials of potential forensic interest such as packaging and pharmaceuticals to be analysed for delta2H, delta13C, delta15N and delta18O composition. As many as 30 international laboratories participated in these comparisons. Results have shown overall improvements for both within- and inter-laboratory reproducibility with respect to delta13C and delta15N measurements. Only a small number of laboratories returned results for delta2H and delta18O analysis and these results highlighted a need for improvement in the reproducibility of these measurements and a need to address the exchange of hydrogen between samples and ambient moisture. Results also highlighted the importance of sample preparation procedures and the need to standardise both these procedures and calibration against Standard Reference Materials. Future Inter-laboratory Comparison exercises will assess the suitability of laboratories to submit data to national and international databases similar to those currently operated for fingerprints, DNA etc.

A number of two-way radios, similar to those which have been employed to initiate Improvised Explosive Devices (IEDs), were acquired from a commercial supplier and grouped into four pairs. Samples of plastic material were collected from five distinct regions of each radio and analysed by Infrared and Raman spectroscopy to identify the nature of the material. One radio of each pair was then subjected to detonation with a commercially available plastic explosive. The combination of radio and explosive was considered to be representative of the components of an IED. Following detonation, fragments were recovered and, where possible, identified as specific sampling points of the radio. A combination of delta2H and delta13C stable isotopic analysis of material from each of the five sampling points was found to provide a pattern which was characteristic of a given radio and provided a means to associate pairs of radios. When few fragments were recovered, no positive association could be made between the fragments and the paired, undamaged radio. This was attributed, in part, to manufacturing variation in the radios. However, when three or more post-blast fragments were recovered it was possible to associate these with the paired, undamaged radio with a high degree of certainty.

A method was developed for the isolation of 3,4-methylenedioxymethylamphetamine (MDMA) and other active ingredients from illicit ecstasy tablets. The method employed supported liquid extraction (SLE) with cartridges containing a modified form of diatomaceous earth. The method developed was simple and robust and the extract could be analysed directly, by GC-MS, to identify ingredients and reduced in volume for isotope ratio MS analysis of both delta(13)C and delta(15)N. The technique was shown to be highly reproducible, independent of the tablet matrix and considerably faster than existing liquid-liquid extraction methods. Crucially, no significant isotopic fractionation was observed as a result of the extraction process.

The versatility of isotope ratio mass spectrometry is demonstrated by reference to diverse case studies. Variations in the natural isotopic composition of non-biological, organic materials are compared as a means by which samples may be associated or discriminated. These techniques may be used to augment or compliment conventional forensic methodologies. delta13C analysis was used to demonstrate that different masking tape had been recovered in two, apparently similar cases, involving the smuggling of money. Visually similar ecstasy tablets were compared by consideration of the delta13C and delta15N composition of MDMA extracted from the tablets. Although only a limited number of tablets were analysed, the isotopic similarity between two different seizures was sufficient to induce a guilty plea from a person suspected of possessing both. A combination of delta2H, delta13C, delta15N and delta18O together with GC-MS analyses were applied to small samples of seized heroin. Although GC-MS analysis indicated differences between the chemical composition of two of the heroin samples, isotopic analysis suggested similarities, which were confirmed by further delta2H, delta13C and delta18O isotopic analysis of the clingfilm in which the samples were wrapped.

Background: A revised Goldman Cardiac Risk Index has been suggested to identify patients at higher risk for cardiac complications in patients who undergo major noncardiac surgery. The aim of this study was to test the usefulness of this model in an independent series of patients who underwent abdominal aortic surgery and to compare the index with the multiple gated acquisition (MUGA) scan in the prediction of cardiac complications., Methods: We studied 77 patients who underwent MUGA scan before elective abdominal aortic reconstruction. The revised index was calculated for each patient after recording the following five risk factors: history of ischemic heart disease, congestive heart failure, cerebrovascular disease, insulin-dependent diabetes, and creatinine level more than 2 mg/dL. Technetium-99m MUGA scan provided information about the resting left ventricular ejection fraction (LVEF) and the presence of regional wall motion abnormalities., Results: Fourteen patients (18%) had cardiac complications develop. The index proved to be a satisfactory predictor of postoperative cardiac events (P =.008), and an abnormal LVEF failed to do so (P =.1). The presence of wall abnormalities, with or without an abnormal LVEF, predicted cardiac complications (P =.004 and P =.006). Patients with a higher index score showed a tendency to have a lower LVEF (Spearman rank correlation, r = -0.43; P <.001). Wall abnormalities, with or without an abnormal LVEF, were more frequent in patients with higher scores (P =.03 and P =.009). Combining the index with the LVEF or the wall abnormalities or both could further stratify the cardiac risk (P =.004, P =.0003 and P =.0006, with chi(2) test for trend)., Conclusion: For those patients who undergo elective abdominal aortic surgery, the revised Goldman Cardiac Risk Index is a simple method of evaluating cardiac risk with minimum resource implications. MUGA scan can offer additional stratification in patients judged with the index to be at high risk.

Objective: To evaluate the results on malignant melanomas of the eyelid and palpebral conjunctiva treated with iodine-125 (125I) brachytherapy with shielding of the eye., Design: Noncomparative case series., Participants: Fourteen patients treated with 125I brachytherapy at an ocular oncology referral center from 1974 through 1996, all of whom had had previous debulking, incomplete resection, or recurrence after surgery., Intervention: A stainless steel pericorneal ring eyeshield was attached to the extraocular muscles, over which a lid was fitted to protect the cornea without touching it. Iodine-125 seeds in polythene tubes were inserted into the eyelid and attached to the lid margin for a single plane implant. In five cases additional seeds were glued on to the shield as well for a volume implant. A median dose of 37 Gy (range, 17.3-67.6 Gy) was given over the course of 113 hours (range, 47-190 hours) to the outer surface of target volume., Main Outcome Measures: Local control is regarded as freedom from recurrence in those without measurable disease and complete clinical regression in those with measurable disease. Morbidity is assessed in terms of function and cosmesis. Survival is given from the time of the implant., Results: There was local control in 13 patients maintained from 11 to 227 months (median, 39 months). There were two recurrences at 8 and 13 months in the first patient who received 17.3 Gy. Late complications consisted of mild eyelid telangiectasia, mild eyelid atrophy, and loss of eyelashes in most patients. Five patients, four of whom had upper eyelid tumors, experienced a dry eye, which was managed with tear supplements, and one of these patients developed a cataract. A corneal ulcer developed in one eye, which later perforated after treatment of a subsequent bulbar melanoma and was exenterated. Another eye was enucleated after treatment for a subsequent melanoma in the fornix. Cosmesis was acceptable to patient and doctor in the other 12 patients. Vision was maintained in seven patients, reduced in two, and not recorded in the remaining three patients. Three patients died of hematogenous metastases at 44, 62, and 79 months after implant, one of bronchial carcinoma at 46 months and one of an astrocytoma at 39 months. All patients were clear of local disease. The remainder survived for a median of 45 months (range, 18-227 months)., Conclusions: Iodine-125 brachytherapy can be used as an alternative to wide excision or exenteration of these tumors. There was good local control, reasonable maintenance of vision, and good cosmesis.

We determined the human leucocyte antigen (HLA)-A, -B and -DR allele frequencies in recipients and donors of 115 cornea transplants, for recipients who developed graft rejection and those who did not. No difference in HLA allele frequencies of the recipients was found. The frequencies of the HLA-A26, -B35 and -B44 alleles in cornea donors were increased in recipients who developed graft failure. The detrimental effect on corneal graft survival of these alleles was significant (p < 0.001). No such effect was observed in renal transplantation. Corneal graft survival was similar when one or two A26, B35 or B44 alleles were present on the donor cornea. The negative effect was similar in magnitude to the previously reported negative effect of an HLA-B locus match between donor and recipient. When both a B-locus match and an A26, B35 or B44 allele were present, the negative effect on graft survival was twice as strong, indicating that different immune mechanisms are responsible for these phenomena.

Several 5,5'-substituted-2,4-imidazolidinedithiones, synthesized from aldehydes or ketones, have been purified by HPLC using poly(styrene-divinylbenzene) packings. Purified 5,5'-substituted-2,4-imidazolidinedithiones have been identified in column effluent by UV absorbance and corroborated by mass spectrometry. Several silica-based, polymeric, and poly(styrene-divinylbenzene)-based packings were evaluated as matrices for resolution of a mixture of purified 5,5'-substituted-2,4-imidazolidinedithiones.

Background: In high-risk keratoplasty, the failure rate from rejection is high, especially in the early postoperative period. If rejection could be prevented during this period, then ultimately a degree of immunologic privilege may be re-established, resulting in long-term graft survival. Cyclosporine (CSA) given systemically prevents graft rejection, but because of the potential side effects and cost, the duration of treatment is an important factor. The author examines the effectiveness of short- and long-term CSA regimens in preventing irreversible graft rejection., Methods: Forty-three patients with high-risk corneas (vascularization in 3 or 4 quadrants and > 16 stromal vessels) received corneal grafts and systemic CSA. Fourteen patients received the drug for 12 months and 29 for a shorter period of 4 to 6 months. A similar high-risk group of 37 patients received no systemic medication., Results: In the control group, 23 grafts (62.2%) irreversibly rejected, compared with 9 (31.0%) and 1 (7.1%) in the short- and long-term CSA groups, respectively. The grafts of patients receiving CSA had a significantly better survival rate (P = 0.0005) than those in the control group. If time of CSA treatment also was considered, significance increased (P = 0.00008)., Conclusions: Systemic CSA significantly reduces failure from irreversible rejection in high-risk keratoplasty, but for maximal effect, a 12-month period of treatment is necessary.

Two chemical assays have been developed for identifying and quantifying peptides which either could be biologically active by virtue of their alpha-carboxamidation or could be substrates for peptidylglycine alpha-amidating mono-oxygenase. The first assay is specific for the alpha-carboxamide of peptides. Using bis[trifluoroacetoxy]iodobenzene, the alpha-carboxamide was converted via a Hoffman reaction into a primary amine, which was then quantified by ninhydrin. The second assay is specific for glycine at the carboxy-terminus of a peptide. Glycine at the carboxy-terminus was derivatized to form 2-thiohydantoin, which was then separated and quantified by reverse phase HPLC. These assays were used to detect peptides in HPLC-separated extracts of bovine hypothalamus, bovine anterior lobe pituitary and porcine heart which may be of biological interest.

A peptide of novel structure was isolated from accessory glands of the female house fly, Musca domestica by molecular-weight limit centrifugal ultrafiltration and reversed-phase HPLC. After amino acid and protein sequence analyses, the structure of this peptide was confirmed by chemical synthesis and plasma desorption mass spectral analysis to be Leu-Leu-Asn-Ala-Leu-Pro-Leu-Asp-Ala-Leu-Ser-Ser-Leu-Thr-Gly-NH2. The accessory gland peptide stimulated contraction of the house fly oviduct at concentrations of 10(-7) M and above.

Forty-eight patients with corneal grafts with severe endothelial rejection were randomly assigned to two treatment groups. One group of 24 patients received prednisolone acetate 1% drops hourly and a single intravenous pulse of 500 mg methylprednisolone. The other group of 24 patients received the same topical therapy plus oral prednisone 60 to 80 mg daily. Nineteen (79.2%) grafts survived in the group that received pulse therapy compared with 15 (62.5%) grafts in the oral group; the difference was not significant (P = 0.17). However, in patients who sought treatment early (less than or equal to 8 days) survival rates were 92.3% and 54.5%, respectively, which indicated a significant advantage for pulse therapy (P less than 0.05). Pulse therapy also appeared beneficial in preventing subsequent rejection episodes. Five (26.3%) of the 19 surviving grafts in the group that received pulse therapy had a further rejection episode compared with 10 (66.7%) of the surviving 15 grafts in the oral group; the difference is significant (P less than 0.025).

Carotid surgery without preoperative arteriography was performed in 101 consecutive patients with an average age of 68.5 years and almost equal sex distribution. This prospective study analyzed risk factors, operative approach, bruits, indications for surgery, and outcome. All patients were studied by real-time B-mode ultrasound and spectral analysis and none were referred for arteriogram. The majority of patients had a standard carotid endarterectomy, and the findings at surgery correlated with noninvasive imaging. No mortality was recorded in this series of patients; a 1% rate of neurologic morbidity was noted. These results suggest that one can safely operate on the basis of a duplex scan. A preoperative arteriogram is not always necessary for carotid evaluation.

In most cases the tracings of lacrimal pump pressure patterns may be interpreted, but, should only be used in conjunction with the patient's history and physical examination. A Schirmer and a distraction test should be included. The distraction test is important in order to indicate the magnitude of the lid tension and thereby the integrity of one of the components of the lacrimal pump. A variety of clinical entities were presented and correlation between these entities and their lacrimal pump pressure recordings were made. These pressure patterns evolved from 75 monitored lacrimal drainage problem cases. In rare circumstances the silicone tube could not be inserted where no pathology existed. Stenotic puncta or closed systems cause sharp spikes indicative of high pressure and poor flow. Tightening of the lower lid can significantly increase pressure patterns and increase tear transportation. Tightening of the levator palpebrae superioris may increase pressures in the nasolacrimal system. Monitoring of canalicular and lacrimal pressures is an effective means of determining the patency of a DCR and conjunctival DCR. Nasolacrimal system monitoring is a safe, painless and effective method of evaluating disorders within that system.

Three groups of New Zealand male while rabbits were given either 2.5 mg/kg of 25-hydroxycholesterol, cholestane-3 beta, 5 alpha, 6 beta-triol or vehicle only, intravenously. 24 h after treatment, the luminal surfaces of aortae of rabbits receiving 25-hydroxycholesterol were examined by scanning electron microscopy (SEM) and showed numerous balloon-like protrusions and crater-like defects as well as circulating, formed elements adhering on the luminal surface. The luminal surface of aortae of rabbits given cholestane-3 beta, 5 alpha, 6 beta-triol had similar but more frequent lesions when compared with those of the 25-hydroxycholesterol group. Microthrombi were occasionally found. The aortae of the control group had significantly fewer lesions. Transmission electron-microscopic studies showed intracytoplasmic vacuoles and diffuse subendothelial edema in the aortae of the two groups receiving the oxidation derivatives of cholesterol. The balloon-like protrusions and crater-like defects observed by SEM appeared to represent the initial sterol-induced endothelial cell injury. Repeated episodes of arterial injury followed by thrombus formation could eventually lead to atherosclerosis.

Several cholesterol autoxidation derivatives known to be cytotoxic to arterial smooth muscle cells both in vivo and in vitro were shown to inhibit hexose transport in these cells in culture. Cholestane-3 beta, 5 alpha, 6 beta-triol was the most potent inhibitory sterol. The rapid onset of inhibition (15 min) and the reversibility of the effect upon removal of the sterol from the tissue culture medium suggests that the effect may be due to incorporation of the sterol into the plasma membrane. 25-Hydroxycholesterol, a potent inhibitor of sterol biosynthesis in cultured arterial smooth muscle cells, did not affect hexose transport up to 8 hr of incubation. The cytotoxic effect of 25-hydroxycholesterol, therefore, may be a consequence of the reduced sterol biosynthesis caused by this sterol.

We injected Silastic RTV S-5392 to increase the obrital volume in 25 enophthalmic patients with enophthalmus. Once the technique had been perfected, the complication rate was nil. Seven patients examined 12-14 years later had no later complications and uniformly satisfactory results.

This work was carried out to determine the changes in conformity and in physiological movements of the eyelids with advancing age. Some conceptions fostered in the literature are false and should be discarded. Others have been corroborated. We conclude that the whole lateral canthus becomes lax and drifts medially with age. Therefore, surgical correction should aim at restoring the fixation of the lateral canthus to its youthful position.