An integrative model of prostate cancer interaction with the bone microenvironment.

Despite advanced efforts in early diagnosis, aggressive surgical treatment, and use of targeted chemotherapies, the prognosis for many cancers is still dismal. This emphasizes the necessity to develop new strategies for understanding tumor growth and metastasis. Here we use a systems approach that combines mathematical modeling and numerical simulation to develop a predictive computational model for prostate cancer and its subversion of the bone microenvironment. This model simulates metastatic prostate cancer evolution, progressing from normal bone and hormone levels to quantifiable diseased states. The simulations clearly demonstrate phenomena similar to those found clinically in prostate cancer patients. In addition, the major prediction of this model is the existence of low and high osteogenic states that are markedly different from one another. The existence and potential realization of these steady states appear to be mediated by the Wnt signaling pathway and by the effects of PSA on TGF-ß, which encourages the bone microenvironment to evolve. The model is used to explore several potential therapeutic strategies, with some potential drug targets showing more promise than others: in particular, completely blocking Wnt and greatly increasing DKK-1 had significant positive effects, while blocking RANKL did not improve the outcome.

Vitrectomy with fibrovascular membrane delamination for proliferative diabetic retinopathy with or without preoperative Avastin.

OBJECTIVE: To describe and compare 1. The changes in intraretinal microstructure using serial spectral domain optical coherence tomography (SD-OCT) preceding and following pars plana vitrectomy and delamination of fibrovascular membranes and 2. Intraoperative and postoperative complications in patients with proliferative diabetic retinopathy (PDR) who had preoperative Avastin (group A) or not (group B). SUBJECTS AND METHOD: This retrospective, interventional case series includes 113 eyes. Outcome measures included LogMAR distance best-corrected visual acuity (BCVA), SD-OCT integrity of photoreceptor inner and outer segments junction (IS/OS), and integrity of external limiting membrane (ELM), intraoperative and postoperative complications. RESULTS: Pre-operative central macular thickness (CMT) was significantly correlated with the final post-operative LogMAR BCVA in group A. Both groups were also categorised into three sub-groups based on post-operative IS/OS integrity (group 0: IS/OS intact; group 1: IS/OS irregular but not completely disrupted; group 2: IS/OS completely disrupted). Mean BCVA improved significantly and IS/OS integrity and ELM integrity postoperatively, were significantly and positively correlated with final BCVA in group A. Intraoperative complications such as iatrogenic tears and haemorrhage and postoperative such as vitreous haemorrhage and neovascular glaucoma were significantly less in group A compared to group B. CONCLUSION: Pre-operative Avastin reduces the risk of intraoperative and postoperative complications and results in better postoperative anatomic and functional outcomes in fibrovascular delamination surgery for patients with PDR.

Characteristics, socioeconomic status and ethnic variations of primary idiopathic macular hole repair in vitreoretinal centers in the United Kingdom.

OBJECTIVE: The purpose of this multicentre retrospective study was to investigate the characteristics and role of ethnicity and socioeconomic status amongst patients with idiopathic macular holes (IMH) and the surgical outcome. SUBJECTS AND METHOD: Consecutive patients undergoing primary IMH surgery at three vitreoretinal units in the UK (King's College Hospital, London, UK, Western Eye Hospital, London, UK, Sunderland Eye Infirmary, Sunderland, UK) between January 2007 and May 2017 were included. The main outcome measure was anatomical closure of IMH. RESULTS: Two hundred and thirty three primary IMH surgeries were included. All patients underwent pars plana vitrectomy, internal limiting membrane peeling, and gas tamponade. 69.10% of patients were European Caucasian, 6.44% were Asian, and 24.46% were Afro-Caribbean. The mean base macular hole diameter (BD) was 475.5mcm. Mean BD was 432.2mcm in European Caucasian patients, 481.3mcm in Asians (P=0.005), and 505.61mcm in Afro-Caribbeans (P=0.006). Regression analysis demonstrated that BD and Afro-Caribbean ethnicity were independent significant risk factors for surgical failure. Those who have longer duration of symptoms (Afro-Caribbeans) and leave in more deprived places (Afro-Caribbeans) in England where found to have lower success rate on macular hole closure. CONCLUSION: Asian and Afro-Caribbean patients present with larger IMH than European Caucasians. In addition to IMH base diameter, black origin and lower socioeconomic status are independent risk factors for surgical failure. This study presents a large population-based data analysis on ethnic variation in macular holes and may assist in the management and predicting the surgical outcome.

The design and validation of an optical coherence tomography-based classification system for focal vitreomacular traction.

PURPOSE: To develop and validate a classification system for focal vitreomacular traction (VMT) with and without macular hole based on spectral domain optical coherence tomography (SD-OCT), intended to aid in decision-making and prognostication. METHODS: A panel of retinal specialists convened to develop this system. A literature review followed by discussion on a wide range of cases formed the basis for the proposed classification. Key features on OCT were identified and analysed for their utility in clinical practice. A final classification was devised based on two sequential, independent validation exercises to improve interobserver variability. RESULTS: This classification tool pertains to idiopathic focal VMT assessed by a horizontal line scan using SD-OCT. The system uses width (W), interface features (I), foveal shape (S), retinal pigment epithelial changes (P), elevation of vitreous attachment (E), and inner and outer retinal changes (R) to give the acronym WISPERR. Each category is scored hierarchically. Results from the second independent validation exercise indicated a high level of agreement between graders: intraclass correlation ranged from 0.84 to 0.99 for continuous variables and Fleiss' kappa values ranged from 0.76 to 0.95 for categorical variables. CONCLUSIONS: We present an OCT-based classification system for focal VMT that allows anatomical detail to be scrutinised and scored qualitatively and quantitatively using a simple, pragmatic algorithm, which may be of value in clinical practice as well as in future research studies.

Third-order thermo-mechanical properties for packs of Platonic solids using statistical micromechanics.

Obtaining an accurate higher order statistical description of heterogeneous materials and using this information to predict effective material behaviour with high fidelity has remained an outstanding problem for many years. In a recent letter, Gillman & Matous (2014 Phys. Lett. A 378, 3070-3073. ()) accurately evaluated the three-point microstructural parameter that arises in third-order theories and predicted with high accuracy the effective thermal conductivity of highly packed material systems. Expanding this work here, we predict for the first time effective thermo-mechanical properties of granular Platonic solid packs using third-order statistical micromechanics. Systems of impenetrable and penetrable spheres are considered to verify adaptive methods for computing n-point probability functions directly from three-dimensional microstructures, and excellent agreement is shown with simulation. Moreover, a significant shape effect is discovered for the effective thermal conductivity of highly packed composites, whereas a moderate shape effect is exhibited for the elastic constants.

United Kingdom National Ophthalmology Database Study of Vitreoretinal Surgery: report 1; case mix, complications, and cataract.

AIM: To report the vitreoretinal (VR) surgical case mix in the United Kingdom, the intraoperative complication rate of pars plana vitrectomy (PPV), and the incidence of post-vitrectomy cataract extraction. METHODS: Participating hospitals prospectively collected ophthalmic data using a single electronic medical record system, with automatic extraction of anonymised data to a national database. This study included the subset of 11618 VR operations undertaken on 9619 eyes, of 8741 patients, over 8 years, from 27 sites. Surgical data included the indication for surgery, all procedure elements, and whether or not an intraoperative complication occurred. Post-vitrectomy cataract data were also analysed. The main outcome measures were a description of the indications for surgery, intraoperative PPV complication rate, and percentage of eyes undergoing post-vitrectomy cataract surgery (PVCS). RESULTS: The most common indications for VR intervention were retinal breaks and rhegmatogenous retinal detachment (48.5%), macular hole (9.8%), epiretinal membrane (9.6%), and diabetic eye disease (7.3%). Overall, 7.8% of PPVs had at least one intraoperative complication-the most common were iatrogenic retinal breaks (3.2%), and lens touch (1.2-1.6% of phakic eyes). PVCS occurred in 50.2, 68.7, and 74.0% of eyes at 1, 2, and 3 years, respectively. CONCLUSION: VR surgery is undertaken for a wide range of conditions, but a small number of diagnoses encompass the majority of cases. Intraoperative PPV complications are not uncommon, and post-vitrectomy cataract is to be expected in most phakic eyes.

Visual and anatomical outcomes following vitrectomy for complications of diabetic retinopathy: the DRIVE UK study.

INTRODUCTION: End-stage diabetic eye disease is an important cause of severe visual impairment in the working-age group. With the increasing availability of refined surgical techniques as well as the early diagnosis of disease because of screening, one would predict that the prevalence of this condition is decreasing and the visual outcome is improving. AIM: To study the prevalence and visual outcome following vitrectomy for complications of diabetic retinopathy. MATERIALS AND METHODS: This study identified the patients who underwent vitrectomy from January 2007 to December 2009 because of diabetes-related complications in South East London. Data collected included baseline demographics, best-corrected visual acuity, indication for the vitrectomy, complication, outcome, and duration of follow-up. RESULTS: The prevalence of people requiring vitrectomy who are registered in the diabetes register of this region was 2 per 1000 people with diabetes. Vitrectomy was required in 185 eyes of 158 patients during this period. These included 83 Caucasians, 51 Afro-Caribbeans, 17 South Asians, and 7 from other ethnic groups. There were 58 patients with type I diabetes and 100 with type II, with a mean duration of diabetes of 23 and 16.5 years, respectively. The reason for vitrectomy included tractional retinal detachment (TRD) in 109 eyes, non-clearing vitreous haemorrhage (NCVH) in 68 eyes, and other causes in 8 eyes. In all, 50% of the eyes with TRD and NCVH, and 87% of the eyes with NCVH improved by at least three ETDRS lines at 12 months. Poor predictors of visual success included longer duration of diabetes (OR: 0.69), use of insulin (OR: 0.04), presence of ischaemic heart disease (OR: 0.04), delay in surgery (OR: 0.59), and the failure to attend clinic appointments (OR: 0.58). Preoperative use of intravitreal bevacizumab in eyes with TRD undergoing vitrectomy showed a marginal beneficial effect on co-existent maculopathy (P=0.08) and required less laser intervention post procedure, but did not affect the number of episodes of late-onset vitreous haemorrhage post vitrectomy (P=0.81). CONCLUSION: Visual outcome has improved significantly in eyes with complications due to diabetic retinopathy compared with the previously reported Diabetic Vitrectomy Study.

Cost analysis comparing adjuvant epimacular brachytherapy with anti-VEGF monotherapy for the management of neovascular age-related macular degeneration.

AIMS: To consider the cost implication of adopting epimacular brachytherapy (EMB) for the treatment of neovascular (wet) age-related macular degeneration (wAMD), compared with ranibizumab or bevacizumab monotherapy. METHODS: This analysis compared the cumulative 3-year costs of anti-VEGF (vascular endothelial growth factor) monotherapy to EMB combined with anti-VEGF therapy. Two patient groups were considered: newly diagnosed (treatment-naïve) patients; and patients already receiving chronic anti-VEGF therapy. RESULTS: In the treatment-naïve patients, the highest cumulative treatment costs were associated with ranibizumab monotherapy (£25,658), followed by bevacizumab monotherapy (£16,177), EMB with ranibizumab (£14,002), then EMB with bevacizumab (£10,289). In previously treated patients, the highest treatment costs were ranibizumab monotherapy (£18,355), followed by EMB with ranibizumab (£17,428), bevacizumab monotherapy (£16,177), then EMB with bevacizumab (£12,129). CONCLUSION: EMB combined with anti-VEGF treatment has the potential to yield considerable cost savings, compared with anti-VEGF monotherapy. If the ongoing large studies of EMB confirm the published feasibility data, then adjuvant EMB may represent a cost-effective alternative to anti-VEGF monotherapy.

The ATAC adjuvant breast-cancer trial: six-year results of the endometrial subprotocol.

Postmenopausal women with localised, early breast cancer (n = 285) were enrolled in a prospective subprotocol of the 'arimidex, tamoxifen, alone or in combination' (ATAC) trial to assess gynaecological abnormalities arising during treatment with anastrozole (1 mg/day) or tamoxifen (20 mg/day). After 6 years' follow-up, there appeared to be non-significantly fewer endometrial abnormalities with anastrozole than with tamoxifen (12.4% vs 20.2%, odds ratio 0.52; 95% confidence intervals 0.20, 1.32; p = 0.17). The time to first endometrial abnormality was non-significantly longer for patients receiving anastrozole compared with tamoxifen (hazard ratio 0.57; 95% confidence intervals 0.26, 1.22; p = 0.15), with most abnormalities occurring within the first year of treatment. Fewer patients treated with anastrozole appeared to require medical intervention for endometrial abnormalities, compared with patients on tamoxifen. This study showed that there was no significant difference in endometrial pathology between anastrozole and tamoxifen treatment groups.

Vital staining with indocyanine green: a review of the clinical and experimental studies relating to safety.

Indocyanine green (ICG) is extremely effective when used as a vital stain during macular hole surgery. By staining the internal limiting membrane, ICG facilitates removal of this delicate and sometimes hard to visualize structure. There is, however, considerable debate regarding its safety. This review considers the clinical and experimental studies of ICG and a related agent, infracyanine green. Some clinical papers show visual field defects, reduced visual acuity, and persistence of ICG at the macula and optic nerve. Other clinical studies fail to demonstrate toxicity. The experimental studies are also conflicting, but there are emerging trends. These suggest that surgeons who continue to use ICG should use concentrations not greater than 0.05 mg/ml, in fluid-filled eyes, with short exposure times, iso-osmolar solutions, and avoid proximal or prolonged endoillumination of stained tissue. A smaller number of studies suggest that infracyanine green produces similar staining to ICG, and may possibly be safer, but there are too few well-designed studies to reach a conclusion. Although the use of ICG continues, on the balance of evidence, this review suggests that it is has the potential to produce subtle visual damage.

Nature of packs used in propellant modeling.

In recent years we have constructed closely packed spheres using the Lubachevsky-Stillinger algorithm to generate morphological models of heterogeneous solid propellants. Improvements to the algorithm now allow us to create large polydisperse packs on a laptop computer, and to create monodisperse packs with packing fractions greater than 70% which display significant crystal order. The use of these models in the physical context motivates efforts to examine in some detail the nature of the packs, including certain statistical properties. We compare packing fractions for binary packs with long-known experimental data. Also, we discuss the near-neighbor number and the radial distribution function (RDF) for monodisperse packs and make comparisons with experimental data. We also briefly discuss the RDF for bidisperse packs. We also consider bounded monodisperse packs, and pay particular attention to the near-wall structure where we identify significant order.

Klebsiella pneumoniae flocculation dynamics.

The bacterial pathogen Klebsiella pneumoniae is a cause of community- and hospital-acquired lung, urinary tract and blood stream infections. It is a common contaminant of indwelling catheters and it is theorized in that context that systemic infection follows shedding of aggregates off of surface-adherent biofilm colonies. In an effort to better understand bacterial proliferation in the host bloodstream, we develop a PDE model for the flocculation dynamics of Klebsiella pneumoniae in suspension. Existence and uniqueness results are provided, as well as a brief description of the numerical approximation scheme. We generate artificial data and illustrate the requirements to accurately identify proliferation, aggregation, and fragmentation of flocs in the experimental domain of interest.

Differential summer water use by Pinus edulis and Juniperus osteosperma reflects contrasting hydraulic characteristics.

Previous studies of pinyon-juniper woodlands show that Pinus edulis Engelm. makes better use of soil water from summer precipitation pulses than does co-occurring Juniperus osteosperma (Torr.) Little. To investigate the basis of this difference, we examined seasonal variation in cavitation and hydraulic conductance. Pinus edulis remained isohydric over the growing season. Minimum water potentials never fell below -2.3 MPa, and the extent of xylem cavitation remained near constant during the dry season. In contrast, J. osteosperma was anisohydric, reaching water potentials as low as -6.9 MPa, and experiencing progressively greater xylem cavitation as the dry season progressed despite having more cavitation-resistant xylem than P. edulis. We conducted an irrigation experiment to observe the responses of the study species to a summer pulse of water. Although sap flow increased in both species in response to the 25-mm irrigation pulse, only J. osteosperma responded to the 10-mm pulse. This was inconsistent with the response of P. edulis to light rain events and may have been due to a difference in the distribution of irrigation water and rain water between the under- and between-canopy areas. Whole-plant conductance increased following the 25-mm irrigation in P. edulis but remained constant in J. osteosperma. We hypothesized that this difference was caused, in part, by differential refilling of embolized xylem. Area specific hydraulic conductivity was 66% higher in roots of irrigated P. edulis trees relative to roots of control trees 3 days after the 25-mm irrigation (t = 2.14, P = 0.02, df = 16). There was no change in hydraulic conductivity of the roots of J. osteosperma or in the stems of either species. Our results indicate that the response to an irrigation pulse in P. edulis depended on cavitation avoidance in stems and the reversal of cavitation in roots, resulting in increased whole-plant conductance and water uptake. In contrast, J. osteosperma failed to exploit light summer rain events but was able to extract deep soil water at low water potentials.

The ATAC ('Arimidex', Tamoxifen, Alone or in Combination) adjuvant breast cancer trial: first results of the endometrial sub-protocol following 2 years of treatment.

BACKGROUND: Tamoxifen treatment results in a doubling of the risk of endometrial cancer after 1-2 years of treatment and a quadrupling after 5 years. Anastrozole, a third-generation aromatase inhibitor, with superior efficacy to tamoxifen, may also offer tolerability benefits in terms of effects on the endometrium. METHODS AND RESULTS: A sub-protocol of the ATAC trial compared the incidence/type of intrauterine changes following treatment with these agents in a subgroup of patients (n = 285) from the main trial. After 2 years anastrozole treatment, endometrial thickness remained

The ATAC ('Arimidex', Tamoxifen, Alone or in Combination) adjuvant breast cancer trial: baseline endometrial sub-protocol data on the effectiveness of transvaginal ultrasonography and diagnostic hysteroscopy.

BACKGROUND: The 'Arimidex', Tamoxifen, Alone or in Combination (ATAC) trial is a randomized, double-blind trial comparing anastrozole ('Arimidex'), alone or in combination with tamoxifen, relative to tamoxifen alone as 5 year adjuvant treatment for post-menopausal women with early breast cancer. Since tamoxifen is associated with endometrial pathology, the ATAC endometrial sub-protocol was initiated to establish the background prevalence of intrauterine pathology, and to assess prospectively the incidence and nature of intrauterine changes following endocrine therapy. Another aim was to provide data from which advice could be generated on the best endometrium screening method for patients receiving tamoxifen. METHODS: Patients underwent endometrial assessments at entry to the sub-protocol. The baseline investigations comprised transvaginal ultrasound scanning (TVUS), a hysteroscopy and an endometrial biopsy. RESULTS: A total of 285 gynaecologically asymptomatic women from 31 centres in 10 countries entered the endometrial sub-protocol. The mean uterine volume was 47.7 cm3. The median endometrial thickness overall was 3 mm. Twenty-four histologically confirmed, pathological changes were observed. Twenty-three pathologies were confirmed by TVUS, and 21 were identified by hysteroscopy and confirmed by histopathology. Women with or without intrauterine pathology had median endometrial thickness of 5 and 3 mm respectively. CONCLUSIONS: The presence of pathology was associated with increased endometrial thickness. The relative sensitivity and specificity of hysteroscopy and endometrial thickness for the diagnosis of endometrial pathology was comparable to other studies. If screening of the endometrium prior to treatment is appropriate, this study supports the use of an endometrial thickness of 3 mm, as assessed by TVUS, as a threshold for needing further investigation. This study demonstrates that if the endometrial thickness is >3 mm, hysteroscopy and biopsy is the optimal method of detecting intrauterine pathology in women with breast cancer who are about to commence endocrine treatment.

The ATAC adjuvant breast cancer trial in postmenopausal women: baseline endometrial subprotocol data.

OBJECTIVE: The ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial is a randomised, double-blind trial comparing 'Arimidex' (anastrozole), alone or in combination with tamoxifen, relative to tamoxifen alone as a five year adjuvant treatment for postmenopausal women with early breast cancer. Because tamoxifen is associated with endometrial pathology, the ATAC endometrial subprotocol was initiated to establish the background prevalence of pathology, and to assess prospectively the incidence and nature of intrauterine changes before and following endocrine therapy. SETTING: International. POPULATION AND STUDY DESIGN: Two hundred and eighty-five women entered the subprotocol: the mean age was 60 years (range 44-80 years); 113 women (40%) had taken hormone replacement therapy prior to randomisation, and 238 women were parous (84%). The age at onset of the menopause was 32-58 years, with the majority becoming menopausal between 46 and 55 years of age. Two hundred and seventy-two women had a hysteroscopy before they commenced trial medication. Hysteroscopy was performed successfully in 265 women. In six women, failure of hysteroscopy at baseline led to withdrawal from the study. Three of the women who withdrew had a pipelle biopsy taken. Therefore, the total number of endometrial biopsies at baseline was 268. MAIN OUTCOME MEASURES: To assess the demographic characteristics of women entering the endometrial subprotocol and their hysteroscopic and histological findings before commencing trial medication. RESULTS: At hysteroscopy, there was a diagnosis of endometrial polyps in 34 women (13%), fibroids in 16 women (6%) and one case of suspicious endometrium, which was confirmed as a polyp on histology. Only 21 of the 34 polyps seen hysteroscopically were proven histologically (62% accuracy of hysteroscopy). Final histology found the prevalence of endometrial diagnostic categories as follows: 123 inactive endometrium (46%), 20 benign polyps (7%), 17 secretory endometrium (6%), 7 proliferative endometrium (3%), 3 atypical hyperplasia (2 in a polyp), 1 simple hyperplasia (in a polyp) and 1 fibroid. The remaining women had pipelle samples with insufficient tissue obtained, indicating a normal endometrial cavity. CONCLUSION: This is the first study of such size in gynaecologically asymptomatic breast cancer patients. This paper describes the findings in individual patients before any trial treatment was given. In this baseline group, 82% (219/268) of women had a normal endometrial cavity; 18% (49/268) had endometrial activity (proliferative or secretory endometrium in 9%) or an intracavity abnormality (hyperplasia, polyps and a fibroid in 9%). In total, 36% of biopsies had insufficient tissue for diagnosis, which in combination with a normal hysteroscopy was classed as normal. The appearance of a polyp hysteroscopically in this group was not proven histologically in approximately 40% of cases. The development of uterine pathology over time in the ATAC study will subsequently be assessed against the findings of this baseline paper.

Transurethral prostatic tissue ablation via a single needle delivery system: initial experience with radio-frequency energy and ethanol.

We report an initial clinical experience to evaluate the safety and efficacy of outpatient prostatic ablation for the treatment of symptomatic benign prostatic hyperplasia (BPH) using local anesthesia (OPAL) with radio-frequency energy and intraprostatic absolute ethanol injection (EI). Twenty-three patients were treated with OPAL and five patients were treated with EI. Pre-operative data for all patients included international prostate symptom score (IPSS), quality of life score (QL), maximum flow rate (Q(max)), and post void residual determination. Prostate specific antigen (PSA) and transrectal ultrasound prostate volume determination were also done for EI patients. Needle deployment into the prostate was carried out at the 2, 4, 8 and 10 o'clock positions for lateral lobe hyperplasia and the 6 o'clock position for middle lobe hyperplasia. IPSS, QL, Q(max) and post void residual data were collected at 1, 3, 6 and 12 months post procedure. Both procedures resulted in statistically significant reductions of IPSS and QL. Trends towards improvement were seen both for Q(max) and post void residual, with Q(max) significantly improved after OPAL. Among EI patients, the prostate volume was reduced at 6 months post treatment to 37.2+/-17.9 g from 53.0+/-19.0 g (P=0.03) preoperatively. OPAL was safe but suffered from a high re-treatment rate. EI demonstrated encouraging results with regards to safety, symptom improvement and prostate volume reduction.

Protein release profiles and morphology of biodegradable microcapsules containing an oily core.

The protein release profiles and the morphology of poly(D,L-lactide-co-glycolide) (PLG) and poly(epsilon-caprolactone) (PCL) microcapsules were investigated. The microcapsules were prepared by the (oil(1)-in-oil2)-in-water emulsion solvent evaporation method using bovine serum albumin (BSA) as a model protein. The internal and external morphologies of the microcapsules were examined using a light microscope, scanning electron microscope and a laser scanning confocal microscope. A Coulter counter was used to determine particle size and particle size distribution. Protein quantitation and molecular integrity were performed by the bicinchoninic acid protein assay micro-method and SDS-PAGE, respectively. Microcapsules with a polymeric wall surrounding an oily core containing the protein were formed. The encapsulation efficiency (39-96%) for PLG and (13-90%) for PCL increased with polymer molecular weight and particle volume mean diameter (Vmd). Vmd ranged from 87-128 to 42-157 microm for PLG and PCL, respectively. The protein release profile for PLG microcapsules was either continuous or irregularly pulsatile depending on particle morphology and was completed after cavity breakdown. However, that of PCL microcapsules was essentially irregularly pulsatile and was completed after a longer period of time without cavity breakdown but with significant swelling. There was no detectable cleavage of the protein during 6 months storage of PLG and PCL microcapsules at 4 degrees C. Furthermore, insignificant degradation of protein occurred during in vitro release from PCL microcapsules. In contrast, significant degradation occurred in PLG microcapsules. This approach to microencapsulation of a protein may be promising for the controlled delivery of protein vaccines, and the oil core may enhance the immunogenicity of some weak subunit vaccine candidates.