On the design of low modulus Ti-Nb-Au alloys for biomedical applications.

Developing new low modulus structures is important for reducing the risk of aseptic loosening during loading of implant materials. However, an alloy that may also confer some advantage at preventing septic loosening could dramatically improve the outcomes for patients. Nevertheless, the predictive power of current models remains limited to common alloying additions. As such, this study considers the mechanical properties of a range of Ti-Nb-Au superelastic alloys to elucidate the composition range for which low modulus structures can be achieved. These modulus values are compared to other critical design parameters such as strain recovery and strength. It was found that Au additions are effective at suppressing the formation of the ω phase and allow alloys with lower moduli to be achieved. It was also shown that low ß phase stability is critical for achieving the lowest modulus, and that this susceptibility to transform to a martensite may enable higher strengths to be achieved. However, this low ß phase stability also limits the strain recovery that may be achieved meaning these two properties are not necessarily independently tuneable. These data provide important context for the design of new systems containing unusual alloying additions such as Au.

Factor VIII activity of BAY 94-9027 is accurately measured with most commonly used assays: Results from an international laboratory study.

INTRODUCTION: Discrepancies in the measurement of modified factor VIII (FVIII) products have been recognized, highlighting the need for adjustments in clinical laboratory practices to ensure effective monitoring of patients treated with these products, particularly using the one-stage (activated partial thromboplastin time [aPTT]) assay. AIM: To assess the ability of clinical laboratories to measure the activity of BAY 94-9027, a PEGylated extended half-life FVIII product, using routine (predominantly one-stage) assays in clinical laboratories METHODS: Blinded samples of FVIII-deficient plasma spiked with defined levels of BAY 94-9027 and a recombinant FVIII product comparator were provided to 52 clinical laboratories that routinely conduct FVIII testing. Samples were provided at 3 concentrations (low, medium and high), and laboratories analysed the samples using routine in-house one-stage and, when available, chromogenic assays. Acceptable spiked recovery (accuracy) of the local laboratory methods to measure BAY 94-9027 was the primary endpoint of the study. RESULTS: Accurate FVIII measurements were obtained at all concentrations for both products using the chromogenic assay and most of the commonly used one-stage reagents, both ellagic acid and silica based. Two specific silica-based reagents, APTT-SP and PTT-A, underestimated BAY 94-9027 levels at all concentrations, consistent with previous findings. CONCLUSIONS: FVIII activity of BAY 94-9027 was accurately measured with most commonly used one-stage assays used in routine clinical practice. The chromogenic assay was also accurate. It is recommended that clinical laboratories identify and avoid specific inappropriate reagents, such as the APTT-SP and PTT-A, in their one-stage assays for FVIII monitoring.

Long-term hypovitaminosis D and secondary hyperparathyroidism outcomes of the Roux-en-Y gastric bypass: a systematic review.

INTRODUCTION: Pre-operative Vitamin D deficiency is markedly prevalent in prospective bariatric surgery patients. While bariatric surgery leads to significant weight loss, it can exacerbate or prolong Vitamin D deficiency. We systematically reviewed the literature to assess whether secondary hyperparathyroidism is maintained in the medium to long term in patients following the Roux-en-Y gastric bypass. METHODS: A comprehensive literature search was conducted through Medline, Embase, Scopus, Web of Science, Dare, Cochrane library and HTA database. The search terms used were bariatric surgery, gastric bypass and hyperparathyroidism. RESULTS: Fourteen studies were included (n = 2688 subjects). Parathyroid hormone levels rose gradually from a mean pre-operative level of 5.69 ± 1.2 pmol/L to 6.36 ± 0.77 pmol/L, 7.59 ± 0.73 pmol/L and 8.29 ± 1.41 pmol/L at 2 years, between 2 and 5 years, and beyond 5 years, respectively. Vitamin D levels slowly fell to a mean of 20.50 ± 4.37 ng/mL and 20.76 ± 3.80 ng/mL between follow-up intervals 2-5 years and beyond 5, respectively. CONCLUSION: It appears that hyperparathyroidism persists at 5-year follow-up after gastric bypass, despite most patients being supplemented with calcium and Vitamin D.

Inhibitors in haemophilia A: a perspective on clotting factor products as a potential contributing factor.

INTRODUCTION: The occurrence of a neutralizing antibody in previously untreated patients (PUPs) with haemophilia A appears to be the result of an intricate interplay of both genetic and environmental factors. Recently, the type of factor VIII (FVIII) product used in the PUPs population has been implicated as a risk factor for inhibitor development. AIM: The aim of this review was to explore in a systematic manner potential hypotheses for the product-related findings in these studies (i.e. differences in the expression system of the cell lines used to produce recombinant FVIII [rFVIII], differences in the administered antigen load or changes in clinical practice over time). RESULTS: Review of the available clinical studies illustrates the high degree of variability for the risk of inhibitor development for the same products across different studies. Differences in cell lines or antigen load were not found to provide a reasonable explanation. CONCLUSION: The possibility of changes in clinical practice over time and patient selection bias (i.e. the preferential use of one product over another in patients at higher risk for inhibitors) offers a potential explanation and should be carefully considered when evaluating the studies.

IgG4-related disease: a novel, important but easily missed condition.

Immunoglobulin G4-related disease (IgG4-RD) is a multisystem, fibroinflammatory condition unrecognised in medical science until the last decade. It is characterised by progressive scarring and dysfunction of affected organs and tissues including the pancreas, hepatobiliary tree, kidneys, salivary glands, retroperitoneum and lungs. The diagnosis is made with the presence of numerous IgG4 positive plasma cells within a histologically-distinct chronic inflammatory process; most patients also have elevated serum IgG4. Though early cases were all identified in Japan, subsequent reports clearly demonstrate that IgG4-RD exists worldwide. There are no data confirming the prevalence of IgG4-RD in the West but it is thought to be very rare. Limited awareness of the condition and its heterogeneous presentation frequently results in misdiagnosis. Prompt and correct diagnosis is critical, as a rapid reversal of even advanced disease is often seen with corticosteroid therapy. We present three cases that illustrate some of the typical features of this condition.

Extrapancreatic manifestations in autoimmune pancreatitis.

It is increasingly recognized that organs beyond the pancreas may be clinically involved in patients with autoimmune pancreatitis (AIP). Other gastrointestinal sites (such as the extrapancreatic biliary tree, liver, and ampulla) appear particularly affected, but involvement of many other organs (including kidneys, lungs, retroperitoneum, and brain) is increasingly reported. A similar histological lesion, characterized by an IgG4-positive lymphoplasmacytic infiltrate, affects both the pancreas and extrapancreatic tissues, strongly suggesting an aetiopathogenic link. In this review we discuss the clinical presentation and disease course, diagnostic features, and management of extrapancreatic involvement in AIP.

Does systematic 2-field lymphadenectomy for esophageal malignancy offer a survival advantage? Results from 178 consecutive patients.

More extensive resection for esophageal cancer has been reported to improve survival in several series. We compared results from an unselected consecutive cohort of patients undergoing radical esophagectomy, including removal of all periesophageal tissue with a 2-field abdominal and mediastinal lymphadenectomy for esophageal and gastroesophageal malignancy. A prospective electronic database was reviewed for patients with esophageal malignancy undergoing an open esophagectomy between 1991 and 2004. Data were analyzed on an SPSS file (version 12.0, Chicago, IL, USA) using chi(2) or Fisher's exact test; odds ratio and 95% confidence interval; and the Kaplan-Meier method, log-rank test and Cox's proportional hazards regression for survival analysis. There were 178 patients with a median age of 65 years and a 70/30 male to female ratio. Median follow-up was 20.4 months. Pathology comprised adenocarcinoma in 64% of patients, squamous cell carcinoma 30%, and other malignancies 6%. Seventeen patients had neoadjuvant therapy. Hospital mortality was 3.3%. Complete resection was achieved in 87%. Local recurrence occurred at a median of 13 months in 6.7% of patients. Overall 5-year survival was 42%. For patients with invasive squamous cell carcinoma and adenocarcinoma the 5-year survival was 47% and 40.3%, respectively, and for patients without nodal involvement it was 71.5%, with one to four nodes involved, 23.5% and with >4 nodes, 5% (P < 0.001). Survival decreased with increasing direct tumor spread (P < 0.001) and pathological stage (P < 0.001). Esophageal resection with systematic 2-field lymphadenectomy can be performed with acceptable operative mortality and favorable survival.

Manipulation of food intake and weight dynamics using retrograde neural gastric electrical stimulation in a chronic canine model.

Neural gastric electrical stimulation (NGES) could be a new technique for treating obesity. However, chronic animal experimentation exploring the efficacy of this therapy is lacking. In this study we investigated the utility of retrograde NGES in a chronic canine model. Nine mongrel dogs (26.8 +/- 5.2 kg) underwent laparoscopic implantation of 2-channel neurostimulator leads in the distal antrum. Five dogs formed a control group and four dogs underwent stimulation. Food intake and weight dynamics were regularly monitored during two separate research protocols, each comprising 2-week baseline, stimulation and washout periods. The stimulation voltage was constant in the first protocol and was ramped in the second. In the first protocol three out of the four stimulated dogs demonstrated significant decrease in food intake (P < 0.05). However, this materialized in a significant weight reduction in one dog only. In the second protocol, all stimulated dogs exhibited significant food intake and weight reduction (P < 0.05) compared to controls. Necropsies and histopathological analysis did not reveal any abnormalities in the stomach, the adjacent organs or around the implant. NGES could be a safe new technique for reducing food intake and weight and, therefore, it might be helpful for treating obesity.

Gastric pouch adenocarcinoma and tubular adenoma of the pylorus: a field effect of dysplasia following bariatric surgery.

There are reports of gastric carcinoma following bariatric surgery, but it is unclear if these procedures predispose to malignancy. We present a case of a 60-year-old man who, 15 years after vertical banded gastroplasty (VBG), had a massive upper GI bleed. Endoscopy revealed a large tumor of the gastric pouch. Histology confirmed an intestinal type of gastric adenocarcinoma arising in a background of H. pylori-negative gastritis with atrophy, foveolar hyperplasia and intestinal metaplasia. An incidental tubular adenoma at the pylorus was also identified. The pathogenesis of gastric pouch carcinoma is discussed. The present example of neoplastic change in both the pouch and pylorus may indicate that a field effect for dysplasia develops subsequent to VBG.

A retrospective analysis of the efficacy and safety of infliximab as rescue therapy in acute severe ulcerative colitis.

BACKGROUND: Forty per cent of patients with acute severe ulcerative colitis will not respond to intravenous corticosteroids and require second-line medical therapy or colectomy. A recent controlled trial has suggested that infliximab may be effective as rescue therapy. AIM: To assess the value of infliximab as rescue therapy for acute severe colitis in a retrospective cohort of ulcerative colitis patients in Scotland. METHODS: All patients satisfied Truelove and Witts criteria on admission, failed to respond to intravenous corticosteroids and received infliximab (5 mg/kg) as rescue therapy. Response was defined as need for colectomy at hospital discharge and by 90 days. RESULTS: A total of 39 patients (median age 31.7 years) were treated. 26/39 (66%) responded, avoiding colectomy during the acute admission, and were followed up for a median of 203 days (Interquartile range = 135.5-328.5). Hypoalbuminaemia was a consistent predictor of non-response on univariate and multivariate analysis. At day 3 of intravenous steroids, 9/18 (50.0%) with serum albumin <34 g/L had urgent colectomy vs. 1/13 (7.7%) >or=34 g/L (P = 0.02, OR = 12.0, C.I. 1.28-112.7). Two serious adverse events occurred - one death due to Pseudomonas pneumonia, and one post-operative fungal septicaemia. CONCLUSIONS: Infliximab represents a moderately effective rescue therapy for patients with acute severe ulcerative colitis. Serious adverse events, including death, do occur and should be discussed with patients prior to therapy.

A randomized trial comparing heater probe plus thrombin with heater probe plus placebo for bleeding peptic ulcer.

BACKGROUND & AIMS: This multicenter, double-blind, controlled trial compared the efficacy of combined endoscopic hemostatic treatment using the heater probe plus thrombin injection with that of the heater probe plus placebo injection as treatment for peptic ulcers with active bleeding or nonbleeding visible vessels. Efficacy was defined in terms of primary hemostasis, prevention of rebleeding, and need for urgent surgery. METHODS: Two hundred forty-seven patients presenting with major peptic ulcer bleeding were randomized to heater probe plus thrombin or to heater probe plus placebo. The groups were well matched for all risk categories including age, endoscopic stigmata, shock, and severity of comorbid diseases. Endoscopic therapy was applied using the heater probe followed by injection of thrombin or placebo. RESULTS: Successful primary hemostasis was achieved in 97% of patients. Rebleeding developed in 19 (15%) of thrombin plus heater probe patients and 17 (15%) of placebo plus heater probe patients. Emergency surgery was necessary in 16 and 13 patients, respectively. Eight patients in the thrombin group had adverse events compared with 4 in the placebo group. Eight (6%) of thrombin plus heater probe patients and 14 (12%) of placebo plus heater probe patients died (P = 0.21). CONCLUSIONS: The combination of thrombin and the heater probe does not confer an additional benefit over heater probe and placebo as endoscopic treatment for bleeding peptic ulcer. Our trial does not support the use of this combination of hemostatic therapy.

Ulcers and nonvariceal bleeding.

Peptic ulcer remains the commonest and most significant cause of nonvariceal upper gastrointestinal bleeding. The incidence of peptic ulcer bleeding is rising in elderly patients, particularly for duodenal ulcer. Patients presenting with upper gastrointestinal bleeding who have low Rockall scores are at low risk of rebleeding and death. These patients currently utilize considerable health-care resources, but could safely be managed at home. The Rockall score can be used to predict the risk of rebleeding and death following variceal bleeding, but for patients with ulcer bleeding, its ability to predict death is questioned. Acid suppression is effective in preventing rebleeding from peptic ulcer. Standard doses of intravenous omeprazole may be as effective as high-dose regimens. Oral omeprazole also reduces rebleeding following endoscopic therapy for peptic ulcer. Mallory-Weiss tears result in significant bleeding in 23 % of cases. Endoscopic therapy may only be required in cases in which active bleeding is present. Endoscopic therapy is effective and safe in patients with major peptic ulcer bleeding who are over 80 years old. For peptic ulcer, injection of larger volumes of epinephrine (adrenaline; mean 16.5 ml) are more effective than small volumes (mean 8 ml). Injection of normal saline alone is less effective than bipolar electrocoagulation. The addition of fibrin glue to epinephrine injection does not confer an additional benefit over epinephrine alone. Argon plasma coagulation can be used to treat a range of lesions in the gastrointestinal tract. It is also effective for treatment of bleeding ulcer, but is no better than established methods. Haemoclips may be useful in bleeding Mallory-Weiss tears, but their use is difficult in patients bleeding from peptic ulcer. The presence of a large ulcer and active bleeding at the time of endoscopy are independent predictors of failure of endoscopic therapy.

Relevance of the Rockall score in patients undergoing endoscopic therapy for peptic ulcer haemorrhage.

OBJECTIVE: To assess the ability of the Rockall score to predict outcome in patients who undergo endoscopic therapy for peptic ulcer haemorrhage. DESIGN: Retrospective data analysis. SETTING: Patients admitted to the three major acute hospitals in Lothian, UK. PARTICIPANTS: Details of 211 patients involved in two randomized trials of endoscopic therapy between 1995 and 1999 were accessed, and Rockall scores calculated. All patients had ulcers with active bleeding or non-bleeding visible vessels requiring endoscopic therapy. The patients were followed up for 6 months and end points included rebleeding and death. MAIN OUTCOME MEASURES: A comparison of mean Rockall scores for those patients who did not rebleed, those who re-bled and those who died. Identification of those patients at greatest risk of rebleeding or death after endoscopic therapy. RESULTS: One hundred and seventy-six patients did not rebleed, with mean score 6.17 (SD = 1.61). Rebleeding occurred in 35 patients whose mean score was 6.97 (SD = 1.52). There were 29 deaths with mean score 7.34 (SD = 1.40). The differences between the three groups were significant by one-way ANOVA (P < 0.001). Fifty-six patients had a Rockall score of 8 or over and, of these, 16 (29%) re-bled and 14 (25%) died. Of the 155 patients with scores of 7 or less, 19 (12%) re-bled and 15 (10%) died. The difference between these groups was significant with chi2 = 7.912 (P = 0.005) for rebleeding and chi2 = 8.147 (P = 0.004) for death. CONCLUSIONS: The Rockall score can be used to predict poor outcome in patients who undergo therapeutic endoscopy for major peptic ulcer bleeding.

Salmeterol plus theophylline combination therapy in the treatment of COPD.

BACKGROUND: Patients with COPD often require multiple therapies to improve lung function and decrease symptoms and exacerbations. Salmeterol and theophylline are indicated for the treatment of COPD, but the use of these agents in combination has not been extensively studied. OBJECTIVES: To compare the efficacy and safety of salmeterol plus theophylline vs either agent alone in COPD. METHODS: Randomized, double-blind, double-dummy, parallel-group trial in 943 patients with COPD. After an open-label theophylline titration period (serum levels, 10 to 20 microg/mL), patients were randomly assigned to receive salmeterol (42 microg bid) plus theophylline, salmeterol (42 microg bid), or theophylline for 12 weeks. Serial pulmonary function tests were completed on day 1 and treatment week 12. Patients kept diary cards and noted their peak flow rates, symptom scores, and albuterol use, and periodically completed quality-of-life and dyspnea questionnaires. RESULTS: All three groups significantly improved compared with baseline. Combination treatment with salmeterol plus theophylline provided significantly (p < or = 0.045) greater improvements in pulmonary function; significantly (p < or = 0.048) greater decreases in symptoms, dyspnea, and albuterol use; and significantly fewer COPD exacerbations (p = 0.023 vs theophylline). In general, treatment with salmeterol provided greater improvement in lung function and satisfaction with treatment compared with theophylline. Salmeterol treatment was also associated with significantly fewer drug-related adverse events (p < or = 0.042) than either treatment that included theophylline. The safety profile (adverse events, vital signs, and ECG findings) of the two treatments that included theophylline were similar. CONCLUSION: Patients with COPD may benefit from combination treatment with salmeterol plus theophylline, without a resulting increase in adverse events or other adverse sequelae.

Fluticasone propionate/salmeterol combination provides more effective asthma control than low-dose inhaled corticosteroid plus montelukast.

BACKGROUND: Asthma is a disease of chronic inflammation and bronchoconstriction. Inhaled corticosteroids (ICSs) provide important anti-inflammatory treatment but may not provide optimal control of asthma when taken alone. Two therapeutic alternatives for enhanced asthma control are to substitute the combination of fluticasone propionate (FP) and salmeterol (FP/Salm Combo) through the Diskus inhaler or to add montelukast to existing ICS therapy. OBJECTIVE: We compared the efficacy and safety of FP/Salm Combo through the Diskus inhaler versus montelukast added to FP (FP + montelukast) in patients whose symptoms were suboptimally controlled with ICS therapy. METHODS: We performed a multicenter, double-blind, double-dummy, parallel-group, 12-week study in 447 patients with asthma who were symptomatic at baseline while receiving low-dose FP. Patients were treated for 12 weeks with one of the following: (1) combination of FP 100 microg plus salmeterol 50 microg twice daily through the Diskus inhaler, or (2) FP 100 microg twice daily through the Diskus inhaler plus oral montelukast 10 mg once daily. RESULTS: FP/Salm Combo treatment provided better overall asthma control than FP + montelukast with significantly greater improvements in morning peak expiratory flow (+24.9 L/min vs +13.0 L/min, P <.001), evening peak expiratory flow (+18.9 L/min vs +9.6 L/min, P <.001), and forced expiratory volume in 1 second (+0.34 L vs +0.20 L, P <.001), as well as a change in the percentage of days with no albuterol use (+26.3% vs +19.1%, P =.032) and the shortness of breath symptom score (-0.56 vs -0.40, P =.017). The groups had comparable improvements in chest tightness, wheeze, and overall symptom scores. Asthma exacerbation rates were significantly lower (P =.031) in the FP/Salm Combo group (4 patients, 2%) than in the FP + montelukast group (13 patients, 6%). Adverse event profiles were comparable. CONCLUSION: Symptomatic patients on low-dose ICS therapy had significantly greater improvement in asthma control when switched to the FP/Salm Combo than when montelukast was added to ICS therapy.

Injection therapy for endoscopic haemostasis.

Endoscopic injection is widely used for the arrest of active ulcer bleeding and for prevention of re-bleeding from ulcers with visible vessels. Although of proven value in clinical trials, mechanisms of action are unclear; tamponade, vasoconstriction, endarteritis and a direct effect upon the clotting process at the site of the arterial defect have been proposed. Clinical trials show that dilute adrenaline is an effective agent and that the addition of sclerosants or alcohol confirms no extra benefit, yet risks serious side-effects. The best results are associated with injection of fibrin glue or thrombin which stimulate formation of a stable blood clot. The efficacy of injection, thermal modalities such as the heater probe and electrocoagulation using BICAP are comparable. In general, there is an advantage in combining injection with a thermal modality, although this may have merit in patients with severe, active ulcer bleeding. Patients who re-bleed following successful primary haemostatic injection treatment can be considered for further endoscopic intervention, but the decision to undertake a surgical operation or repeat endoscopic therapy is a matter of clinical judgement.

Salmeterol added to inhaled corticosteroid therapy is superior to doubling the dose of inhaled corticosteroids: a randomized clinical trial.

This randomized, double-blind, double-dummy, parallel group clinical trial compared the efficacy and safety of adding salmeterol xinafoate to concurrent inhaled beclomethasone dipropionate therapy with doubling the dose of beclomethasone dipropionate in patients experiencing symptoms on low-dose beclomethasone. Salmeterol added to low-dose beclomethasone was superior (p < or = 0.05) to doubling the dose of beclomethasone in improving peak expiratory flow (PEF) and forced expiratory volume in 1 sec (FEV1), and in reducing symptoms of asthma, sleep loss, nighttime awakenings, and use of albuterol. Both treatment regimens had comparable safety profiles. In asthma patients inadequately controlled despite the use of low-dose inhaled corticosteroids (i.e., less than 400 microg per day), the addition of salmeterol may be a more effective treatment option than doubling the dose of inhaled corticosteroids.

Concurrent use of salmeterol with inhaled corticosteroids is more effective than inhaled corticosteroid dose increases.

This randomized, double-blind, parallel, multi-center study was designed to determine whether the addition of salmeterol to existing inhaled corticosteroid therapy provides greater therapeutic benefit than doubling the dose of inhaled corticosteroids in symptomatic patients with asthma. A total of 514 adults were randomized to either beclomethasone 168 micrograms plus salmeterol 42 micrograms twice daily or beclomethasone 336 micrograms twice daily for 24 weeks. Both treatments resulted in significantly improved symptom control and increased pulmonary function. However, beclomethasone plus salmeterol provided greater improvements than doubling the dose of beclomethasone (p < or = 0.05) in FEV1 and in daily-recorded measurements of morning (38 L/minute versus 20 L/minute after treatment with higher dose beclomethasone) and evening peak expiratory flow, asthma symptom scores, symptom-free days, supplemental albuterol use, and days and nights not requiring albuterol. There were no significant differences between treatment groups in the number of patients with abnormal response to corticotropin stimulation at Treatment Week 24. No treatment differences in asthma exacerbation and adverse event frequency rates were seen. Beclomethasone 168 micrograms plus salmeterol 42 micrograms administered twice daily was superior to beclomethasone 336 micrograms taken twice daily in patients symptomatic on beclomethasone 168 micrograms, with no added safety risks.

Activity of doxorubicin covalently bound to a novel human serum albumin microcapsule.

UNLABELLED: Doxorubicin is widely used in the treatment of human malignancies, however is associated with significant cardiac, bone marrow and gastro-intestinal toxicity. Delivery systems may ameliorate this toxicity and increase treatment specificity by increasing the proportion of drug delivered to sites of disease. We have developed a novel preparation of doxorubicin (Dox) covalently linked to a heat stabilised human serum albumin microparticle (HSAM) carrier (median particle diameter of 4 microm) and assessed its activity in 4 malignant cell lines. MATERIALS AND METHODS: Doxorubicin microcapsules were compared with free doxorubicin in the rat carcinoma cell line, WRC256, and the human lines, OVCAR3, MCF7 and the Dox resistant MCF7/Dox, using a cell counting technique. IC50 were calculated from regression analysis of the resulting survival curves. Endocytosis of the microcapsules by cells in culture was observed. The rate of microcapsule uptake was assessed using dual wavelength filtered fluorescence microscopy and flow cytometry. RESULTS: The mean IC50 following incubation with the Dox microcapsules was around 5 times greater than Dox for WRC256 (p < 0.001), MCF7 (p < 0.01) and for OVCAR3 (p < 0.01). MCF7/Dox was significantly more sensitive to Dox microcapsules than free Dox (p = 0.034). A negative correlation between the rate of microcapsule uptake and the IC50 values for each cell line in culture exists (r = -0.96, p = 0.04). CONCLUSIONS: We conclude that: 1) Doxorubicin microcapsules retain activity in vitro and appear to overcome p-glycoprotein mediated Dox resistance. 2) The observed activity of Dox microcapsules correlates with the rate of particle uptake. Further studies in animal tumour models are in progress.