Transplantation of an obesity-associated human gut microbiota to mice induces vascular dysfunction and glucose intolerance.

Recent preclinical data suggest that alterations in the gut microbiota may be an important factor linking obesity to vascular dysfunction, an early sign of cardiovascular disease. The purpose of this study was to begin translation of these preclinical data by examining whether vascular phenotypes in humans are transmissible through the gut microbiota. We hypothesized that germ-free mice colonized with gut microbiota from obese individuals would display diminished vascular function compared to germ-free mice receiving microbiota from lean individuals.We transplanted fecal material from obese and lean age-and sex-matched participants with disparate vascular function to germ-free mice. Using Principle Component Analysis, the microbiota of colonized mice separated by donor group along the first principle component, accounting for between 70-93% of the total variability in the dataset. The microbiota of mice receiving transplants from lean individuals was also characterized by increased alpha diversity, as well as increased relative abundance of potentially beneficial bacteria, including Bifidobacterium, Lactobacillus, and Bacteroides ovatis. Endothelium-dependent dilation, aortic pulse wave velocity and glucose tolerance were significantly altered in mice receiving microbiota from the obese donor relative to those receiving microbiota from the lean donor or those remaining germ-free.These data indicate that the obesity-associated human gut microbiota is sufficient to alter the vascular phenotype in germ-free mice in the absence of differences in body weight or dietary manipulation, and provide justification for future clinical trials to test the efficacy of microbiota-targeted therapies in the prevention or treatment of cardiovascular disease.

Evaluation of an AI system for the detection of diabetic retinopathy from images captured with a handheld portable fundus camera: the MAILOR AI study.

OBJECTIVES: To evaluate the performance of an artificial intelligence (AI) system (Pegasus, Visulytix Ltd., UK*) at the detection of diabetic retinopathy (DR) from images captured by a handheld portable fundus camera. METHODS: A cohort of 6404 patients (~80% with diabetes mellitus) was screened for retinal diseases using a handheld portable fundus camera (Pictor Plus, Volk Optical Inc., USA) at the Mexican Advanced Imaging Laboratory for Ocular Research. The images were graded for DR by specialists according to the Scottish DR grading scheme. The performance of the AI system was evaluated, retrospectively, in assessing referable DR (RDR) and proliferative DR (PDR) and compared with the performance on a publicly available desktop camera benchmark dataset. RESULTS: For RDR detection, Pegasus performed with an 89.4% (95% CI: 88.0-90.7) area under the receiver operating characteristic (AUROC) curve for the MAILOR cohort, compared with an AUROC of 98.5% (95% CI: 97.8-99.2) on the benchmark dataset. This difference was statistically significant. Moreover, no statistically significant difference was found in performance for PDR detection with Pegasus achieving an AUROC of 94.3% (95% CI: 91.0-96.9) on the MAILOR cohort and 92.2% (95% CI: 89.4-94.8) on the benchmark dataset. CONCLUSIONS: Pegasus showed good transferability for the detection of PDR from a curated desktop fundus camera dataset to real-world clinical practice with a handheld portable fundus camera. However, there was a substantial, and statistically significant, decrease in the diagnostic performance for RDR when using the handheld device.

Diet and cancer risk reduction: The role of diet-microbiota interactions and microbial metabolites.

According to recent estimates, over one third of the human population will be diagnosed with cancer at some point in their lifetime. While genetic factors play a large part in cancer risk, as much as 50 % of cancers may be preventable through various lifestyle modifications. Nutrition is a major modifiable risk factor, both through its impacts on obesity as well as through dietary chemical exposures that can either increase or decrease cancer risk. However, specific associations and mechanistic links between diet and cancer risk are either inconsistent or elusive. New insights regarding the reciprocal interactions between diet and the gut microbiota, the trillions of organisms that reside in our intestines, may help clarify how diet impacts cancer. The gut microbiota is largely shaped by an individual's diet and has far-reaching effects on metabolism, the immune system, and inflammation- important factors in the development and progression of various cancers. Likewise, the microbiota modifies dietary components, and consequently, exposure to metabolites that can influence cancer. This review explores some of these diet-microbiota interactions in the context of their potential impacts on cancer prevention.

Microbial metabolite indole-3-propionic acid supplementation does not protect mice from the cardiometabolic consequences of a Western diet.

Emerging evidence suggests that intestinal microbes regulate host physiology and cardiometabolic health, although the mechanism(s) by which they do so is unclear. Indoles are a group of compounds produced from bacterial metabolism of the amino acid tryptophan. In light of recent data suggesting broad physiological effects of indoles on host physiology, we examined whether indole-3-propionic acid (IPA) would protect mice from the cardiometabolic consequences of a Western diet. Male C57BL/6J mice were fed either a standard diet (SD) or Western diet (WD) for 5 mo and received normal autoclaved drinking water or water supplemented with IPA (0.1 mg/mL; SD + IPA and WD + IPA). WD feeding led to increased liver triglycerides and makers of inflammation, with no effect of IPA. At 5 mo, arterial stiffness was significantly higher in WD and WD + IPA compared with SD (WD: 485.7 ± 6.7 and WD + IPA: 492.8 ± 8.6 vs. SD: 436.9 ± 7.0 cm/s, P < 0.05) but not SD + IPA (SD + IPA: 468.1 ± 6.6 vs. WD groups, P > 0.05). Supplementation with IPA in the SD + IPA group significantly increased glucose AUC compared with SD mice (SD + IPA: 1,763.3 ± 92.0 vs. SD: 1,397.6 ± 64.0, P < 0.05), and no significant differences were observed among either the WD or WD + IPA groups (WD: 1,623.5 ± 77.3 and WD + IPA: 1,658.4 ± 88.4, P > 0.05). Gut microbiota changes were driven by WD feeding, whereas IPA supplementation drove differences in SD-fed mice. In conclusion, supplementation with IPA did not improve cardiometabolic outcomes in WD-fed mice and may have worsened some parameters in SD-fed mice, suggesting that IPA is not a critical signal mediating WD-induced cardiometabolic dysfunction downstream of the gut microbiota.NEW & NOTEWORTHY The gut microbiota has been shown to mediate host health. Emerging data implicate gut microbial metabolites of tryptophan metabolism as potential important mediators. We examined the effects of indole-3-propionic acid in Western diet-fed mice and found no beneficial cardiometabolic effects. Our data do not support the supposition that indole-3-propionic acid (IPA) mediates beneficial metabolic effects downstream of the gut microbiota and may be potentially deleterious in higher circulating levels.

Sodium Glucose Co-Transporter 2 Inhibition Does Not Favorably Modify the Physiological Responses to Dietary Counselling in Diabetes-Free, Sedentary Overweight and Obese Adult Humans.

Sedentary obesity is associated with increased risk of many cardio-metabolic diseases, including type 2 diabetes. Weight loss is therefore a desirable goal for sedentary adults with obesity. Weight loss is also a well-documented side effect of sodium glucose co-transporter 2 (SGLT2) inhibition, a pharmaceutical strategy for diabetes treatment. We hypothesized that, compared with placebo, SGLT2 inhibition as an adjunct to out-patient dietary counselling for weight loss would lead to more favorable modification of body mass and composition, and greater improvement in glucose regulation and lipid profile. Using a randomized, double-blind, repeated measures parallel design, 50 sedentary men and women (body mass index: 33.4 ± 4.7 kg/m2; mean ± SD) were assigned to 12 weeks of dietary counselling, supplemented with daily ingestion of either a placebo or SGLT2 inhibitor (dapagliflozin: up to 10 mg/day). Dietary counselling favorably modified body mass, body fat, glucose regulation, and fasting concentrations of triglyceride and very low-density lipoprotein cholesterol (main effects of counselling: p < 0.05); SGLT2 inhibition did not influence any of these adaptations (counselling × medication interactions: p > 0.05). However, SGLT2 inhibition when combined with dietary counselling led to greater loss of fat-free mass (counselling × medication interaction: p = 0.047) and attenuated the rise in high-density lipoprotein cholesterol (counselling × medication interaction: p = 0.028). In light of these data and the health implications of decreased fat-free mass, we recommend careful consideration before implementing SGLT2 inhibition as an adjunct to dietary counselling for weight loss in sedentary adults with obesity.

Intermittent low dose carbon monoxide inhalation does not influence glucose regulation in overweight adults: a randomized controlled crossover trial.

NEW FINDINGS: What is the central question of this study? Low dose carbon monoxide (CO) inhalation plays a role in regulating proteins involved in glucose metabolism; does low dose CO improve glucose and insulin responses to an oral glucose tolerance test in overweight adults? What is the main finding and its importance? Five days of intermittent CO inhalation does not alter the glucose or insulin responses to ingestion of a glucose bolus in overweight adults. Low dose CO is utilized in various physiological assessment procedures; these findings allow researchers and clinicians to utilize these procedures without concern of altering glucose metabolism. ABSTRACT: Low dose carbon monoxide (CO) inhalation upregulates several proteins important for glucose metabolism. Such changes could be clinically significant and may be relevant to those who use CO as a research tool. We hypothesized that low dose CO inhalation would improve glucose and insulin responses to an oral glucose bolus in overweight humans. Eleven young adults (5 men, 6 women; body mass index: 25-35 kg m-2 ) were included in this randomized, placebo-controlled, single-blinded crossover study. Following screening, participants completed two 7-day protocols with a 4-week washout. Twenty-four hours prior to and following five consecutive days of either once daily CO (men: 1.2 ml (kg body mass)-1 ; women: 1.0 ml (kg body mass)-1 ) or placebo (room air) inhalation, participants underwent oral glucose tolerance tests (OGTT). For key outcome variables, there were no significant main effects or interactions across condition or time point (mean ± SD), including fasting glucose (mg dl-1 : pre-placebo: 85.2 ± 10.1; post-placebo: 82.9 ± 10.6; pre-CO: 83.6 ± 7.7; post-CO: 84.0 ± 9.0), 2 h post glucose (mg dl-1 : pre-placebo: 100.9 ± 20.0; post-placebo: 98.7 ± 13.1; pre-CO: 94.2 ± 23.2; post-CO: 94.4 ± 14.9), or the Matsuda index (pre-placebo: 16.1 ± 11.5; post-placebo: 20.3 ± 24.7; pre-CO: 15.6 ± 15.3; post-CO: 17.5 ± 16.8). In conclusion, 5 days of low dose CO administration did not influence glucose and insulin responses to an OGTT in overweight adults. Low dose CO inhalation is utilized in a variety of physiological assessment procedures; these findings allow researchers to utilize these procedures without concern of altering glucose metabolism.

Influence of Sodium Glucose Cotransporter 2 Inhibition on Physiological Adaptation to Endurance Exercise Training.

CONTEXT: The combination of two beneficial antidiabetes interventions, regular exercise and pharmaceuticals, is intuitively appealing. However, metformin, the most commonly prescribed diabetes medication, attenuates the favorable physiological adaptations to exercise; in turn, exercise may impede the action of metformin. OBJECTIVE: We sought to determine the influence of an alternative diabetes treatment, sodium glucose cotransporter 2 (SGLT2) inhibition, on the response to endurance exercise training. DESIGN, PARTICIPANTS, AND INTERVENTION: In a randomized, double-blind, repeated measures parallel design, 30 sedentary overweight and obese men and women were assigned to 12 weeks of supervised endurance exercise training, with daily ingestion of either a placebo or SGLT2 inhibitor (dapagliflozin: ≤10 mg/day). OUTCOME MEASUREMENTS AND RESULTS: Endurance exercise training favorably modified body mass, body composition (dual-energy x-ray absorptiometry), peak oxygen uptake (graded exercise with indirect calorimetry), responses to standardized submaximal exercise (indirect calorimetry, heart rate, and blood lactate), and skeletal muscle (vastus lateralis) citrate synthase activity (main effects of exercise training, all P < 0.05); SGLT2 inhibition did not influence any of these physiological adaptations (exercise training × treatment interaction, all P > 0.05). However, after endurance exercise training, fasting blood glucose was greater with SGLT2 inhibition, and increased insulin sensitivity (oral glucose tolerance test/Matsuda index) was abrogated with SGLT2 inhibition (exercise training × treatment interaction, P < 0.01). CONCLUSION: The efficacy of combining two beneficial antidiabetes interventions, regular endurance exercise and SGLT2 inhibition, was not supported. SGLT2 inhibition blunted endurance exercise training-induced improvements in insulin sensitivity, independent of effects on aerobic fitness or body composition.

Visual outcomes in patients with zonular dialysis following cataract surgery.

PurposeTo evaluate the visual outcomes of patients with zonular dialysis following cataract surgery.Patients and methodsMedical records of all patients with documented zonular dialysis, either pre- or peri-operatively, undergoing cataract surgery between 2004-2010 at Queen Alexandra Hospital, Portsmouth, were retrospectively reviewed. Baseline demographics and biometry were analysed, and ocular co-morbidities documented. Intraoperative complications and the use of a capsular tension ring (CTR) were identified. Early and late best-corrected visual acuity (BCVA) post surgery were determined using LogMar values. Univariate and multivariate linear regression analysis was performed to determine associations with BCVA post surgery, and further subgroup analysis performed in groups determined by CTR use.ResultsThe records of 22 312 consecutive eyes undergoing cataract surgery were reviewed. The incidence of zonular dialysis was 0.50% (111 eyes). A CTR was inserted in 46 eyes. Using a multivariate linear regression model, better initial pre-operative BCVA (P=0.019), the use of a CTR (P=0.014), and the absence of vitreous loss during surgery (P=0.008, ß 0.45) were associated with improved early postoperative BCVA (mean follow-up 6.6 weeks). Better medium-term postoperative BCVA was significantly associated with preoperative BCVA (P=0.002) and the use of a CTR during surgery (P=0.004, ß -0.41).ConclusionsThe overall incidence of zonular dialysis is low. CTR use intra-operatively suggests improved early and medium-term BCVA and should be considered in all cases of zonular dialysis.

Long-term outcomes of Fine Needle Diathermy for established corneal neovascularisation.

BACKGROUND/AIMS: Corneal neovascularisation (CoNV) can lead to significant ocular comorbidity with reduction in vision and cosmesis. A number of techniques have been described to reduce CoNV, but these can be expensive. Our study aimed to determine the safety, efficacy and long-term outcomes of fine needle diathermy (FND) for CoNV. METHODS: A 5-year retrospective study identified all cases of FND. Indications, intraoperative complications, and postoperative visual acuity, after treatment and retreatments, were documented, along with the procedure time. Evidence of regression and number of retreatments were identified. RESULTS: 56 eyes from 52 patients underwent FND for CoNV. The main indications included herpes simplex keratitis (HSK) (53%, n=25) and microbial keratitis/peripheral ulcerative keratitis (13%, n=6). Pretreatment acuity was significantly correlated with extent of CoNV (p=0.044). One complication was noted during the procedure-an intrastromal and subconjunctival haemorrhage (rate 2%). 68.1% of patients demonstrated regression at first follow-up (mean 6.9 weeks), and 89.3% (n=42) showed regression with two or less treatments. Mean post-FND acuity was 0.72 (range -0.2-3.0) vs 0.82 (-0.2-3.0) preprocedure (p=0.08). VA improved in the HSK subgroup (p=0.012). Mean follow-up was 18.9 months (range 1-56 months). CONCLUSIONS: In the largest case series reported, FND appears to be a safe and effective technique in the long term to induce regression of CoNV, with significant improvement in the VA of patients with HSK.

The journey to femtosecond laser-assisted cataract surgery: new beginnings or a false dawn?

Femtosecond laser-assisted cataract surgery (FLACS) represents a potential paradigm shift in cataract surgery, but it is not without controversy. Advocates of the technology herald FLACS as a revolution that promises superior outcomes and an improved safety profile for patients. Conversely, detractors point to the large financial costs involved and claim that similar results are achievable with conventional small-incision phacoemulsification. This review provides a balanced and comprehensive account of the development of FLACS since its inception. It explains the physiology and mechanics underlying the technology, and critically reviews the outcomes and implications of initial studies. The benefits and limitations of using femtosecond laser accuracy to create corneal incisions, anterior capsulotomy, and lens fragmentation are explored, with reference to the main platforms, which currently offer FLACS. Economic considerations are discussed, in addition to the practicalities associated with the implementation of FLACS in a healthcare setting. The influence on surgical training and skills is considered and possible future applications of the technology introduced. While in its infancy, FLACS sets out the exciting possibility of a new level of precision in cataract surgery. However, further work in the form of large scale, phase 3 randomised controlled trials are required to demonstrate whether its theoretical benefits are significant in practice and worthy of the necessary huge financial investment and system overhaul. Whether it gains widespread acceptance is likely to be influenced by a complex interplay of scientific and socio-economic factors in years to come.

The Portsmouth-based glaucoma refinement scheme: a role for virtual clinics in the future?

BACKGROUND: Glaucoma referrals continue to impart a significant burden on Hospital Eye Services (HES), with a large proportion of these false positives. AIMS: To evaluate the Portsmouth glaucoma scheme, utilising virtual clinics, digital technology, and community optometrists to streamline glaucoma referrals. METHOD: The stages of the patient trail were mapped and, at each step of the process, 100 consecutive patient decisions were identified. The diagnostic outcomes of 50 consecutive patients referred from the refinement scheme to the HES were identified. RESULTS: A total of 76% of 'glaucoma' referrals were suitable for the refinement scheme. Overall, 94% of disc images were gradeable in the virtual clinic. In all, 11% of patients 'attending' the virtual clinic were accepted into HES, with 89% being discharged for community follow-up. Of referrals accepted into HES, the positive predictive value (glaucoma/ocular hypertension/suspect) was 0.78 vs 0.37 in the predating 'unrefined' scheme (95% CI 0.65-0.87). The scheme has released 1400 clinic slots/year for HES, and has produced a £244 200/year cost saving for Portsmouth Hospitals' Trust. CONCLUSION: The refinement scheme is streamlining referrals and increasing the positive predictive rate in the diagnosis of glaucoma, glaucoma suspect or ocular hypertension. This consultant-led practice-based commissioning scheme, if adopted widely, is likely to incur a significant cost saving while maintaining high quality of care within the NHS.

Management challenges arising from a traumatic 360 degree cyclodialysis cleft.

We describe the case of a 28-year-old naval officer who attended the ophthalmology service following blunt ocular trauma to the left eye. Clinical examination revealed a shallow anterior chamber, hypotony, and a 360° cyclodialysis cleft. We discuss the management options in this case, with an overview of the current literature.

Anterior keratouveitis secondary to Hydroa vaccineforme: a role for ophthalmic slit-lamp examination in this condition?

The authors report the case of an 8-year-old girl of Caucasian origin who attended the Emergency Eye Clinic with a 3-week history of a red, light sensitive left eye during the month of April. Her Snellen visual acuities were 6/5 right and 6/9 left. Examination revealed perilimbal injection and anterior chamber inflammation in the left eye consistent with an anterior uveitis. Inferior stromal haze and fine keratic precipitates were noted in the left cornea. Intraocular pressures were normal, with no vitritis and healthy looking discs, maculae and peripheral retina. Systemic examination revealed a papular rash over the face consistent with previously diagnosed Hydroa vaccineforme. With intensive topical steroids the inflammation gradually resolved.

Avulsion of the proximal hamstring origin. Surgical technique.

BACKGROUND: The torn hamstring is a common athletic injury. The purpose of the present study was to review the clinical presentation of this injury, the diagnostic imaging findings, the surgical technique of reattachment, and the likely clinical outcome of surgery for the treatment of avulsion of the proximal hamstring origin. METHODS: Seventy-two consecutive reconstructions in seventy-one patients with avulsion of the proximal hamstring origin were performed at a single center. The mean age at the time of the operation was 40.2 years. The mean duration of follow-up was twenty-four months, and all patients with a minimum duration of follow-up of six months were included. There were no exclusions. Patients were independently reviewed, and the mean postoperative isotonic hamstring strength was compared with that on the uninjured side. RESULTS: Waterskiing was the most frequent cause of injury (twenty-one cases). The mean time between the injury and the operation was twelve months. The most common pathological finding was a complete avulsion of the proximal hamstring origin (sixty-three cases; 87.5%), with a mean retraction of 7 cm (range, 0 to 20 cm). The mean postoperative isotonic hamstring strength measured 84% (range, 43% to 122%) and the mean postoperative hamstring endurance measured 89% (range, 26% to 161%) when compared with the values on the contralateral side. CONCLUSIONS: It is important to distinguish proximal hamstring origin avulsions (for which we recommend early surgical repair) from the majority of hamstring muscle injuries (which respond well to nonoperative treatment). The present study suggests that, in cases of complete avulsion with hamstring retraction, a delay in surgical repair renders the repair more technically challenging, may increase the likelihood of sciatic nerve involvement, increases the need for postoperative bracing, and reduces postoperative outcome in terms of hamstring strength and endurance. Once the nature of the injury has been established, the surgical treatment of hamstring origin avulsions has predictable and satisfactory results.

Avulsion of the proximal hamstring origin.

BACKGROUND: The torn hamstring is a common athletic injury. The purpose of the present study was to review the clinical presentation of this injury, the diagnostic imaging findings, the surgical technique of reattachment, and the likely clinical outcome of surgery for the treatment of avulsion of the proximal hamstring origin. METHODS: Seventy-two consecutive reconstructions in seventy-one patients with avulsion of the proximal hamstring origin were performed at a single center. The mean age at the time of the operation was 40.2 years. The mean duration of follow-up was twenty-four months, and all patients with a minimum duration of follow-up of six months were included. There were no exclusions. Patients were independently reviewed, and the mean postoperative isotonic hamstring strength was compared with that on the uninjured side. RESULTS: Waterskiing was the most frequent cause of injury (twenty-one cases). The mean time between the injury and the operation was twelve months. The most common pathological finding was a complete avulsion of the proximal hamstring origin (sixty-three cases; 87.5%), with a mean retraction of 7 cm (range, 0 to 20 cm). The mean postoperative isotonic hamstring strength measured 84% (range, 43% to 122%) and the mean postoperative hamstring endurance measured 89% (range, 26% to 161%) when compared with the values on the contralateral side. CONCLUSIONS: It is important to distinguish proximal hamstring origin avulsions (for which we recommend early surgical repair) from the majority of hamstring muscle injuries (which respond well to nonoperative treatment). The present study suggests that, in cases of complete avulsion with hamstring retraction, a delay in surgical repair renders the repair more technically challenging, may increase the likelihood of sciatic nerve involvement, increases the need for postoperative bracing, and reduces postoperative outcome in terms of hamstring strength and endurance. Once the nature of the injury has been established, the surgical treatment of hamstring origin avulsions has predictable and satisfactory results.

Delayed reconstruction of a quadriceps tendon.

Rupture of the quadriceps tendon is an uncommon injury and rapid diagnosis is important because delay in surgical repair generally is believed to adversely affect outcome. One study of 20 patients suggests repair should be done during the first 48 to 72 hours postinjury to achieve a successful outcome and late repair led to unsatisfactory recovery. Cases of delayed tendon repair have been reported, the longest to our knowledge being 11 months before surgical intervention. We present a case of successful outcome of a quadriceps tendon rupture reconstructed at least 8 years after occurrence and a review of the literature of delayed reconstructions. We show that successful restoration of extensor mechanism function can be achieved several years after tendon rupture.

Hydroxyapatite-ceramic-coated femoral stems in revision hip surgery.

We describe the clinical and radiological results of 120 consecutive revision hip replacements in 107 patients, using the JRI Furlong hydroxyapatite-ceramic-coated femoral component. The mean age of the patients at operation was 71 years (36 to 92) and the mean length of follow-up 8.0 years (5.0 to 12.4). We included patients on whom previous revision hip surgery had taken place. The patients were independently reviewed and scored using the Harris hip score, the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) and the Charnley modification of the Merle d'Aubigné and Postel score. Radiographs were assessed by three reviewers for the formation of new bone, osteolysis, osseointegration and radiolucent lines in each Gruen zone. The mean Harris hip score was 85.8 (42 to 100) at the latest post-operative review. The mean WOMAC and Merle d'Aubigné and Postel scores were 34.5 and 14.8, respectively. The mean visual analogue score for pain (possible range 0 to 10) was 1.2 overall, but 0.5 specifically for mid-thigh pain. There were no revisions of the femoral component for aseptic loosening. There were four re-revisions, three for infection and one for recurrent dislocation. Radiological review of all the femoral components, including the four re-revisions showed stable bony ingrowth and no new radiolucent lines in any zone. Using revision or impending revision for aseptic loosening as an end-point, the cumulative survival of the femoral component at ten years was 100% (95% confidence interval 94 to 100). We present excellent medium- to long-term clinical, radiological and survivorship results with the fully hydroxyapatite-ceramic-coated femoral component in revision hip surgery.

Hydroxyapatite ceramic-coated femoral stems in young patients. A prospective ten-year study.

We describe the clinical and radiological results of 38 total hip replacements (THR) using the JRI Furlong hydroxyapatite-ceramic (HAC)-coated femoral component in patients younger than 50 years. The mean age at the time of operation was 42 years (22 to 49) and the mean length of follow-up was ten years (63 to 170 months). All patients receiving a Furlong HAC THR were entered into the study regardless of the primary pathology including patients who had undergone previous hip surgery. The mean Harris hip score improved from 44 before operation to 92 at the last post-operative review. After 12 years the cumulative surivival for the stem was 100% (95% confidence interval 89 to 100). No femoral component was revised. Our results show that the Furlong HAC implant gives excellent long-term results in young patients with high demands.