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A simple method for preparing radioactive capsules in colon transit study.

Colon transit study is currently performed by delivering technetium-99m or indium-111 labelled activated charcoal to the colon in a methacrylate-coated capsule (coated capsule). However, the coating procedure is complicated and methacrylate has not been approved by the Food and Drug Administration. Therefore, a simpler method is needed for the clinical routine use of colon transit study. In this study, we used a commercial empty enteric capsule and a coated capsule for the measurement of colon transit time. We compared the in vitro stability and in vivo scintigraphy of 99mTc-labelled activated charcoal in the coated capsule and the enteric capsule to evaluate the possibility of clinical usage of the enteric capsule for colon transit time study. Activated charcoal powder was mixed with 49mTc-diethylene triamine pentaacetic acid (DTPA) and vaporized to dryness. The dry 99mTc-DTPA activated charcoal was loaded into the coated capsule and the enteric capsule. In vitro stability study was performed by immersing these capsules in a colourless buffer of variable pH which mimicked the conditions in the stomach and the small bowel. Capsule disruption was determined. Colon transit scintigraphy with 99mTc-DTPA charcoal was performed in five normal volunteers using these two capsules. The in vitro stability of these two types of capsule was similar and the colon transit scintigraphy findings were almost identical. Most capsules dissolved in the ascending colon and very few in the terminal ileum. It is concluded that enteric capsule is a suitable alternative to coated capsule for measurement of colon transit.

Capsules↗

Gamma scintigraphic evaluation of the fate of hydroxypropyl methylcellulose capsules in the human gastrointestinal tract.

The fate (movement and disintegration) of hard novel hydroxypropyl methylcellulose (HPMC) two-piece capsules in the human gastrointestinal tract was investigated using a gamma scintigraphic imaging method. Two different prolonged-release formulations without an active ingredient were used. The capsules contained different viscosity grades of HPMC powder (HPMC K100 and HPMC K4M). The aim was to determine the main reason why the pharmacokinetic profiles of model drugs change when the diluent was changed to a higher viscosity grade. The results were compared with our previous pharmacokinetic studies with corresponding capsules containing metoclopramide hydrochloride or ibuprofen as a model drug. The first observation was that the HPMC capsules had a tendency to attach to the oesophagus. Therefore, it is recommended that the HPMC capsules as well as gelatine capsules be taken with a sufficient amount of water (150-200 ml) in an upright position and maintaining the upright position for several minutes. The viscosity grade of the HPMC did not affect the transit times of the capsules in the GI tract. The major differences between the two formulations were the complete disintegration times of the capsules and the spreading of the capsules to the large intestine. Most of the HPMC K100-based capsules were completely disintegrated during the 8h study, whereas the HPMC K4M-based capsules still exhibited plug formations in the large intestine. Also the HPMC K100-based capsules spread better to the ascending colon than the HPMC K4M-based capsules. The faster disintegration of the HPMC K100-based capsules explains the differences in the pharmacokinetic profiles of the model drugs between the HPMC K100- and K4M-based capsules in our previous studies. The main absorption site of the drugs from the capsules studied here is probably the large intestine when taken in a fasting state.

Adult↗

Adhesive capsulitis of the shoulder: MR diagnosis.

OBJECTIVE: Adhesive capsulitis is a clinical syndrome of pain and severely decreased joint motion ("frozen shoulder") caused by thickening and contraction of the joint capsule and synovium. Although arthrographic criteria for the diagnosis have been described, to our knowledge, the MR characteristics have not been reported. Accordingly, we studied the MR findings in 10 patients with this syndrome. MATERIALS AND METHODS: MR images of 25 subjects were included in the study. Nine had adhesive capsulitis documented by arthrography, and one had adhesive capsulitis proved at surgery. The MR findings in these patients were compared with those of 15 asymptomatic volunteers. Images were assessed for thickness of the joint capsule and synovium, for thickness of the coracohumeral ligament, and for volume of articular fluid. Capsule and synovium thickness was measured adjacent to the axillary recess. The volume of intraarticular fluid was calculated from direct measurements of the axillary recess and biceps tendon sheath. The rotator cuff interval was qualitatively evaluated for the presence of abnormal tissue. RESULTS: Thickening of capsule and synovium on MR images was characteristic of adhesive capsulitis, with a significant difference between mean thickness in patients with adhesive capsulitis (5.2 mm) and in asymptomatic volunteers (2.9 mm) (p < .01). Capsule and synovium thickness greater than 4 mm was a specific (95%) and sensitive (70%) criterion for the diagnosis of adhesive capsulitis. There was no significant difference in volume of articular fluid or thickness of the coracohumeral ligament between patients with adhesive capsulitis and asymptomatic volunteers (p > .5). The rotator cuff interval was not useful for assessing changes of adhesive capsulitis. CONCLUSION: Joint capsule and synovium thickness greater than 4 mm is a useful MR criterion for the diagnosis of adhesive capsulitis. The volume of articular fluid seen on MR images is not significantly diminished in patients with adhesive capsulitis.

Adult↗

Fourier transform infrared spectroscopy studies of alginate-PLL capsules with varying compositions.

Microencapsulation of cells is a promising approach to prevention of rejection in the absence of immunosuppression. Clinical application, however, is hampered by insufficient insight into the factors that influence the biocompatibility of the capsules. Capsules prepared of alginates with a high guluronic (G) acid content proved to be more adequate for clinical application since they are more stable, but, unfortunately, they are less biocompatible than capsules prepared of intermediate-G alginate. In order to get some insight into the physicochemical factors that influence the biocompatibility of capsules for the encapsulation of living cells, the chemical compositions of alginate[bond]Ca beads and alginate[bond]PLL capsules were studied by Fourier transform infrared spectroscopy. We found that during the transition of the alginate[bond]Ca beads to alginate[bond]PLL capsules, Ca connecting the alginate molecules, disappeared at the surface of both high-G and intermediate-G alginate[bond]PLL capsules. At the same time, it turned out that high-G alginate[bond]PLL capsules contained more hydrogen bonding than did intermediate[bond]G alginate capsules. Thus the well-known higher stability of high-G alginate[bond]PLL compared to intermediate-G alginate[bond]PLL capsules is not caused by a higher degree of binding to Ca of the alginate molecules but rather by the presence of more hydrogen bonds. Another observation was that after the transition from bead to capsule, high-G alginate[bond]PLL capsules contained 20% more PLL than the intermediate-G alginate[bond]PLL capsules. Finally, we show that in both high-G and intermediate-G alginate[bond]PLL capsules, the PLL exists in the alpha-helix, in the antiparallel beta-sheet, and in the random coil conformation. This study shows that FT-IR allows for successful analyses of the chemical factors essential for understanding differences in the biocompatibility of alginate[bond]PLL capsules.

Alginates↗

Human and porcine anterior lens capsule as support for growing and grafting retinal pigment epithelium and iris pigment epithelium.

PURPOSE: To establish a method for transplantation of cultured monolayers of RPE and IPE into the subretinal space, anterior lens capsule was evaluated for its suitability to serve as growth support and carrier for transplantation procedures. MATERIALS AND METHODS: Twenty-four anterior lens capsules were obtained from porcine eyes. The same number of human lens capsules was obtained during cataract surgery. Six lens capsules of each species were stored at -80 degrees C. Subsequently, the capsules were transferred onto type-I collagen. A second set of six lens capsules was treated identically except for the cryo treatment. A third set of six capsules was initially exposed to 0.05% trypsin for 30 min. Suspended porcine RPE and IPE cells (5 x 10(4) cells/well) were seeded on the top of each capsule. The remaining six lens capsules served as controls and were incubated in uncoated 12-well dishes without undergoing experimental treatment. The cultures were maintained in a water-saturated atmosphere at 37 degrees C with 5% CO(2). Six days later, viability, morphology, and cell density were determined. The capsules covered by a confluent monolayer of cells were transferred into uncoated wells and cultivated for another 10 days. At the end of the experiment, light and phase-contrast microscopy was performed on all capsules. RESULTS: Storage at -80 degrees C and exposure to trypsin resulted in significant reduction of cellular contamination. The highest cell density was found after 5 days when capsules which had undergone cryopreservation or trypsin exposure served as support for RPE and IPE. The pigment cell layer was firmly attached to the capsules and permitted a transfer to other culture flasks without significant cell loss. The IPE cell layer remained confluent after transfer to uncoated culture flasks, while the RPE cell layer ceased to proliferate 10 days after transfer. CONCLUSIONS: Lens capsules may be suitable for growing and supporting monolayers of pigment epithelial cells. Especially IPE cells formed stable monolayers on anterior lens capsules which could be transferred to secondary culture flasks without inflicting damage on the cells.

Animals↗

Randomized, open-label preference study of two cyclosporine capsule formulations (usp modified) in stable solid-organ transplant recipients.

BACKGROUND: Prior research has indicated patient dissatisfaction with the odor, size, and taste of cyclosporine capsules, as well as the halitosis and body odor the capsules can cause. OBJECTIVES: The purposes of this investigation were to (1) compare the overall cyclosporine capsule preference (Gengraf vs Neoral) in stable, solid-organ transplant recipients, (2) assess patient preference based on specific capsule attributes, and (3) determine the reliability of the Cyclosporine Capsule SatiSfaCtion Survey (original to this study). METHODS: In this multicenter, randomized, open-label, parallel-group, preference study, patients were recruited from 144 centers in North America with established transplant programs. Solid-organ transplant recipients who had taken stable doses of cyclosporine (Neoral) for >/=2 consecutive months were randomized in a 9:1 ratio to receive another cyclosporine formulation (Gengraf) or to remain on Neoral therapy. Patients completed the Cyclosporine Capsule Satisfaction Survey prior to randomization (baseline survey) and after taking the study drug for 4 weeks (final survey). The survey consisted of multiple attribute items with high face validity in assessing patients' perceptions and preferences with regard to their overall experience, as well as specific attributes of cyclosporine capsules known to affect patient acceptance. RESULTS: The intent-to-treat population included 1906 patients (1211 men, 693 women [sex unknown in 2 patients]; mean [SD] age, 50.2 [12.4] years). A total of 1708 patients were switched to Gengraf; 198 continued on Neoral. Based on their overall experience with both capsule formulations, the majority of patients switched to Gengraf (61.9%) responded that they preferred the Gengraf capsule, compared with 13.7% who preferred the Neoral capsule and 24.4% who indicated no preference (P < 0.001). A similar preference for Gengraf was observed based on capsule odor (66.3%), ease of swallowing (51.5%), taste (57.1%), and impact on breath odor (52.5%) and body odor (48.4%) (P < 0.001 for each test). The results of internal consistency and reproducibility calculations were high for the Cyclosporine Capsule Satisfaction Survey. Internal consistency ranged from alpha = 0.84 to 0.95 for the subscales and was alpha = 0.95 for the overall score. Ranges for reproducibility in the subscales were r = 0.75 to 0.79, with an overall reproducibility of r = 0.85. Guyatt's responsiveness statistics for the subscale and overall scores were moderately high to very high, indicating that the survey is capable of measuring change in response to treatment. CONCLUSIONS: Of the transplant recipients receiving Gengraf in this study, most preferred Gengraf to Neoral based on overall experience, capsule odor, difficulty swallowing, taste, breath odor, and body odor. Among all study patients, fewer patients receiving Gengraf were bothered by capsule odor, difficulty in swallowing, taste, or the impact on breath or body odor compared with patients who continued to receive Neoral. Internal consistency, reproducibility, and responsiveness results show that the Cyclosporine Capsule Satisfaction Survey is a psychometrically valid instrument that is appropriate for use in clinical trials.

Adolescent↗

Cloning and analysis of gene clusters for production of the Escherichia coli K10 and K54 antigens: identification of a new group of serA-linked capsule gene clusters.

The polysaccharide capsules of Escherichia coli have been classified into three groups: I, II, and I/II. The third group, I/II, has been poorly studied and possesses characteristics of both group I and group II capsules. In this report, we describe the cloning of the K10 and K54 capsule gene clusters, two representatives of group I/II capsules. Probes taken from DNA flanking regions 1 and 3 of the group II capsule clusters hybridized to these group I/II clones, confirming that the group I/II capsule genes are flanked by the same DNA and are therefore located in the same serA-linked region of the chromosome as group II capsule gene clusters. Southern blotting showed that homologous sequences were present in both the K10 and K54 capsule gene clusters and in other group I/II strains. No homology was detected between these sequences and the chromosomal DNA of either a group I or a group II strain. Likewise, no homology was detected to the chromosomal DNA of either a K11 or K19 strain, both of which had previously been classified as group I/II strains. In the K10 and K54 capsule gene clusters, these conserved sequences flanked a serotype-specific region in a manner analogous to group II capsule gene organization. Complementation of mutations in the kpsE, kpsD, and kpsC genes in region 1 of the K5 capsule gene cluster by subclones of the K10 and K54 capsule gene clusters indicated that certain stages in the export of group II and I/II capsules may be conserved. In the light of the findings presented here, we suggest that the group I/II capsule gene clusters are sufficiently different from group II capsule gene clusters to justify their renaming as group III.

Antigens, Bacterial↗

Immunolocalization of prolyl 4-hydroxylase subunits, alpha-smooth muscle actin, and extracellular matrix components in human lens capsules with lens implants.

Lens capsules become fibrotic after the extraction of a cataract. To understand this phenomenon, we evaluated the immunolocalization of prolyl 4-hydroxylase (an enzyme involved in procollagen hydroxylation), and extracellular matrix components and cytoskeletal components in a normal human lens capsule and in others with intraocular lenses. Lens capsules containing intraocular lenses were removed from a patient with proliferative vitreoretinopathy and three with proliferative diabetic retinopathy during vitreous surgery. Two circular sections of the anterior capsules with lens epithelial cells were obtained by anterior capsulotomy during cataract surgery. In addition, a lens capsular bag was obtained immediately after phacoemulsification. The lens capsules were processed for light microscopic immunohistochemical detection of the alpha and beta subunits of prolyl 4-hydroxylase, extracellular matrix components (including collagen types, laminin and cellular fibronectin) or cytoskeletal components (such as cytokeratin, vimentin and alpha-smooth muscle actin). Monolayer lens epithelial cells were seen on the inner surface of the normal anterior capsules. Each intraocular lens was found to be fixed in the capsular bag. Light microscopic immunohistochemistry showed that these proliferating cells expressed vimentin and alpha-smooth muscle actin; in contrast, quiescent lens epithelial cells did not stain for alpha-smooth muscle actin. Marked immunostaining for subunits of prolyl 4-hydroxylase was detected in lens epithelial cells proliferating on the capsules, while no or only faint prolyl 4-hydroxylase immunoreactivity was detected in quiescent lens epithelial cells immediately after phacoemulsification. Collagen types I, III and VI and cellular fibronectin were observed diffusely in accumulated connective tissue on a capsule with an intraocular lens. Type IV collagen immunoreactivity was seen both in the capsules and in the connective tissue accumulation on the capsules. Collagen V and laminin were detected in association with cellular proliferation. Collagen VII and VIII and laminin 5 were not seen. We concluded that during wound healing of the lens capsule after cataract extraction, the lens epithelial cells that proliferate on the inner surface of the capsule transform it into a myofibroblastic phenotype, expressing prolyl 4-hydroxylase and alpha-smooth muscle actin. These proliferating cells are involved in the production of collagen on the lens capsule. This results in a postoperative fibrotic process and contraction of the lens capsule.

Actins↗

Optical coherence tomography assessment of capsule closure after cataract surgery.

PURPOSE: To develop a technique for documenting and quantifying capsule bend formation in pseudophakic eyes, evaluate when the anterior and posterior lens capsules become completely apposed to the optic, and determine how soon a capsule bend is created at the optic edge of an intraocular lens (IOL) after cataract surgery. SETTING: Medical University of Vienna, Department of Ophthalmology, Vienna, Austria. METHODS: This prospective study comprised 33 eyes of 33 patients with age-related cataract who were scheduled to have cataract surgery. All eyes had phacoemulsification with implantation of 1 of 3 types of open-loop IOLs: 1-piece acrylic (SA60AT, Alcon), 3-piece acrylic (AcrySof MA60BM, Alcon), or 3-piece silicone (911A, AMO). Each group included 11 eyes. One and 3 days and 1, 2, 3, and 4 weeks after surgery, contact between the lens capsule and IOL optic as well as capsule bend formation were evaluated using optical coherence tomography (OCT). The postoperative times at which the capsule came into contact with the IOL optic and when the capsule bend formed were determined. RESULTS: One day postoperatively, the mean distance between the anterior capsule and the IOL was 197 microm in the 1-piece acrylic IOL group, 161 microm in the 3-piece acrylic IOL group, and 220 microm in the 3-piece silicone IOL group. The posterior capsule was in contact with the IOL on the same day or earlier than the anterior capsule in 28 patients (85%). Postoperatively, the capsule bend formed at a mean of 10 days in the 1-piece acrylic group, 13 days in the 3-piece acrylic group, and 15 days in the 3-piece silicone group. The short-term reproducibility of the OCT technique was excellent (r = 0.99). CONCLUSIONS: Optical coherence tomography produced cross-sectional tomograms of capsule-IOL contact in the early postoperative period. There was no significant difference in the time to capsule bend formation between the 3 IOLs. However, capsule bend formation at the optic edge occurred earlier with the 1-piece acrylic IOL than with the 3-piece silicone IOL.

Acrylic Resins↗

Stability of the distal radioulnar joint contributed by the joint capsule.

PURPOSE: The distal radioulnar joint (DRUJ) capsule is assumed to be an important stabilizer of the DRUJ. There are few published data regarding the capsule and its specific contribution to stability of the DRUJ. METHODS: We analyzed the contribution of the joint capsule to DRUJ stability in a biomechanical study consisting of collection of force/displacement data from 16 adult human cadaveric upper extremities. Each specimen was subjected to anteroposterior translation testing of the radius relative to the ulna in 3 positions of forearm rotation (neutral, 60 degrees pronation, 60 degrees supination) by serial sectioning of the DRUJ capsule. The experimental conditions tested included intact capsule, sectioned dorsal capsule, sectioned volar capsule, and repaired capsule. RESULTS: Isolated dorsal capsule sectioning resulted in volar instability of the radius to the ulna primarily in the maximum pronated position. Significant dorsal instability of the radius was observed after isolated volar capsule sectioning in the maximum supinated position. The restabilizing effect of capsule shortening was observed near the maximums of forearm rotation. The additional stability owing to capsule shortening surpassed that of the distal radioulnar ligament at these positions. CONCLUSIONS: We showed the effect of capsular injury on DRUJ joint stability and the restabilizing effect of capsule shortening. The importance of the capsule to DRUJ stability should be considered when planning surgical procedures to restore the unstable DRUJ.

Humans↗

Microcapsules of alginate-chitosan. II. A study of capsule stability and permeability.

The stability of alginate-chitosan capsules was shown to depend strongly on the amount of chitosan bound to the capsules. When the capsules were made by dropping a solution of sodium alginate into a chitosan solution (one-stage procedure), all the chitosan was located in a thin alginate-chitosan membrane on the surface. These capsules were much weaker than the capsules made by reacting calcium alginate beads in an aqueous solution of chitosan and calcium chloride (two-stage procedure). Capsules with high mechanical strength were obtained after shorter reaction times when the number-average molecular weight of the chitosan was reduced to around 15,000, when the capsules were made more homogeneous and when the capsule diameter was reduced to around 300 microm. When these capsules were treated with calcium sequestrant such as citrate under conditions where calcium alginate gels normally dissolve, they still had a gel core indicating the presence of chitosan throughout the capsule matrix. The permeability of the two-stage capsules was reduced when the chitosan molecular weight was increased and the degree of acetylation was increased, and when the capsules were made more inhomogeneous. The addition of another several layers of alginate and chitosan resulted in capsules virtually impermeable to IgG, suggesting an average capsule pore diameter less than 90 A.

Alginates↗

The polysaccharide capsule of the pathogenic fungus Cryptococcus neoformans enlarges by distal growth and is rearranged during budding.

The capsule of Cryptococcus neoformans can undergo dramatic enlargement, a phenomenon associated with virulence. A prior study that used Ab to the capsule as a marker for older capsular material concluded that capsule growth involved the intermixing of new and old capsular material with displacement of older capsular polysaccharide towards the surface. Here we have revisited that question using complement (C), which binds to capsular polysaccharide covalently, and cannot redistribute by dissociation and binding at different sites. The experimental approach involved binding of C to cells with small capsules, inducing capsule growth, and following the location of C relative to the cell wall as the capsule enlarged. C remained close to the cell wall during capsule growth, indicating that capsule enlargement occurred by addition of new polysaccharide near the capsule edge. This conclusion was confirmed by an independent method that employed radioactive metabolic labelling of newly synthesized capsule with 3H-mannose followed by gradual capsular stripping with gamma-radiation. Capsule growth proceeded to a certain size, which was a function of cell size, and was not degraded when the cells were transferred to a non-inducing medium. During budding, an opening appeared in the capsule of the mother cell that permitted the nascent bud to separate. Scanning EM suggested that a physical separation formed between the capsules of the mother and daughter cells during budding, which may avoid mixture between both capsules. Our results indicate that C. neoformans capsular enlargement also occurs by apical growth and that budding results in capsular rearrangements.

Animals↗

Mechanical properties of the human posterior lens capsule.

PURPOSE: To investigate mechanical properties of the human posterior lens capsule. METHODS: Twenty-five human donor eyes were obtained from an eye bank. The age of the donors ranged from 1 to 94 years. Test specimens were prepared as tissue rings from posterior lens capsules by means of excimer laser. Capsular thickness was measured microscopically as the difference in focus between microspherules placed on the outer and inner surfaces of the capsule. The capsular rings were slipped over two pins connected to a motorized micropositioner and a force transducer and stretched at a constant rate with continuous recording of load and deformation. Data for the posterior lens capsule were compared with previously published data for the anterior lens capsule. RESULTS: The thickness of the posterior lens capsule ranged from 4 to 9 micro m and showed no significant changes with age. Ultimate mechanical strength of the posterior lens capsule decreased significantly with age. Ultimate strain ranged from 101% to 34%, ultimate load ranged from 15.9 to 1.1 mN, ultimate stress ranged from 16.1 to 1.1 N/mm(2), ultimate elastic stiffness ranged from 52.1 to 5.7 mN, and ultimate elastic modulus ranged from 27.4 to 3.3 N/mm(2). The load-strain and the stress-strain relationships in the posterior lens capsule were nonlinear, and therefore elastic stiffness and elastic modulus varied as a function of strain. In the low-strain region (0%-10% strain), elastic stiffness and elastic modulus ranged between 0.3 to 2.4 mN and 0.3 to 2.3 N/mm(2), respectively, and seemed to increase during the first part of life until middle age. CONCLUSIONS: Mechanical strength of the posterior lens capsule was found to decrease markedly with age. The age-related loss of mechanical strength seemed to begin earlier in the posterior lens capsule than in the anterior lens capsule. In accommodative function range (low strains), the mechanical quality of the posterior lens capsule was similar to the anterior lens capsule, which indicates that the mechanical effectiveness of the lens capsule in situ varies proportionally with capsular thickness.

Adolescent↗

The shell dissolution of various empty hard capsules.

The shell dissolution properties of gelatine, gelatine/polyethylene glycol (PEG) and hydroxypropyl methylcellulose (HPMC) capsules were studied as a function of temperature, dissolution medium, and after different storage conditions. In any dissolution medium with a pH below or equal to 5.8, HPMC capsule shells dissolved rapidly, and there was no difference in the time in which dissolution occurred in the tested temperature interval of 10 to 55 degrees C. Gelatine and gelatine/PEG capsule shells, generally, did not dissolve at temperatures below 30 degrees C. The shell dissolution time of all capsules tested was prolonged and more variable in mixed phosphate buffer pH = 6.8. The addition of enzymes (pepsin, pancreatin) to any dissolution medium was found not to enhance the differences between the different types of capsules investigated. In practical terms, the results indicated that capsule formulations should not be taken with drinks from the carbonated Cola-type. Gelatine containing capsules should preferably be administered with a warm drink, whereas HPMC capsules could be given with cold or warm drinks. The latter type of capsules should also be preferred for preparations to be taken in the fasted state. A short storage of gelatine containing capsules under hot humid tropical conditions appeared not to alter the dissolution properties of the shells, and changes in disintegration times and dissolution times of formulations filled in such capsules might be a reflection of changes of the powders incorporated rather than of the capsule shells. However, a short storage of HPMC capsules under such conditions appeared to influence the capsule shell matrix.

Administration, Oral↗

Immunolocalization of cytokines and their receptors in adhesive capsulitis of the shoulder.

The purpose of this study was to test the hypothesis that specific cytokines are involved in the initiation and evolution of the fibrotic process in adhesive capsulitis of the shoulder. After approval from the Institutional Review Board, biopsies of shoulder capsule and synovium were collected during shoulder arthroscopy from 19 patients with adhesive capsulitis, 14 patients with nonspecific synovitis and no fibrosis or clinical evidence of adhesive capsulitis, and seven patients undergoing surgery for another pathology who had a normal capsule and synovium. Immunohistochemical localization with monoclonal antibodies to transforming growth factor-beta and its receptor, platelet-derived growth factor and its receptor, basic fibroblast growth factor, interleukin-1 beta, tumor necrosis factor-alpha, and hepatocyte growth factor was performed using standard immunoperoxidase techniques. The frequency of cytokine staining was correlated with the clinical diagnosis. Synovial cells, fibroblasts, T-cells, and B-cells were identified with specific antibodies, and newly synthesized matrix was examined for type-I and type-III collagen by immunohistochemical staining. The predominant cell types present were synovial cells and fibroblasts. Staining for type-III collagen in adhesive capsulitis tissues indicated new deposition of collagen in the capsule. There was staining for transforming growth factor-beta and its receptor, platelet-derived growth factor and its receptor, interleukin-1 beta, and tumor necrosis factor-alpha in adhesive capsulitis and nonspecific synovitis tissues, compared with minimal staining in normal capsule. Staining was more frequent in synovial cells than in capsular cells. The frequency of cell and matrix staining for transforming growth factor-beta, platelet-derived growth factor, and hepatocyte growth factor was greater in adhesive capsulitis tissues than in those from patients with nonspecific synovitis. No difference in the frequency of staining between primary (idiopathic) and secondary adhesive capsulitis was found. The results of this study indicate that adhesive capsulitis involves both synovial hyperplasia and capsular fibrosis. Cytokines such as transforming growth factor-beta and platelet-derived growth factor may be involved in the inflammatory and fibrotic processes in adhesive capsulitis. Matrix-bound transforming growth factor-beta may act as a persistent stimulus, resulting in capsular fibrosis. Understanding the basic pathophysiology of adhesive capsulitis is an important step in the development of clinically useful antifibrotic agents that may serve as novel treatments for patients with this conditions.

Adult↗

Safety of capsule endoscopy in patients with pacemakers.

BACKGROUND: Capsule endoscopy, a new technology, allows visualization of the entire small intestinal mucosa. The main indication for capsule endoscopy at present is the evaluation of GI bleeding of obscure origin. Studies to date suggest that capsule endoscopy is safe and is associated with few adverse events. One concern, which has not been studied, is the potential effect of the capsule on cardiac pacemakers and other electromedical devices. The primary aims of this study were to evaluate the safety of capsule endoscopy in patients with cardiac pacemakers who are being evaluated for GI bleeding of obscure origin and to determine whether pacemakers have any effect on the images captured by the capsule endoscope. METHODS: Patients with cardiac pacemakers referred for evaluation of GI bleeding of obscure origin were entered into the study. Before the procedure, an electrocardiogram was obtained, and pacemaker functions were checked. Capsule endoscopy was performed in a hospital setting to allow closer monitoring, instead of the outpatient clinic, which is our routine. Cardiac rhythm was assessed simultaneously during capsule endoscopy with a Holter monitor. Post-procedure pacemaker function was again checked for any disturbance. When the capsule endoscopy studies were reviewed, observations were made with particular reference to technical difficulty or interference with imaging. OBSERVATIONS: Five consecutive patients (4 men, 1 woman; mean age, 73 years, range 56-92 years) with cardiac pacemakers were studied. In all patients, the indication for capsule endoscopy was GI bleeding of obscure origin. A cardiologist and pacemaker nurse specialist reviewed the Holter monitor recordings and evaluated pacemaker function after the procedure for each patient. No arrhythmia or other adverse cardiac event was noted during capsule transmission. No pacemaker-induced interference on the capsule endoscopy images was observed. CONCLUSIONS: Capsule endoscopy appears to be safe in patients with cardiac pacemakers and does not appear to be associated with any significant adverse cardiac event. Pacemakers do not interfere with capsule imaging.

Aged↗

Intragastric behavior and absorption kinetics of a normal and "floating" modified-release capsule of isradipine under fasted and fed conditions.

From measurements of drug levels in both gastric juice and plasma, we investigated whether or not a prolonged gastric residence time (GRT) is responsible for the slow absorption kinetics of a "floating" modified-release (MR) capsule of isradipine [isopropyl methyl (+/-)-4-(4-benzofurazanyl)-1,4-dihydro-2,6-dimethyl-3,5- pyridinedicarboxylate], a lipophilic dihydropyridine calcium channel blocker. The effects of a "high-fat" breakfast on the intragastric behavior and absorption kinetics were also assessed. In an open crossover design, five healthy subjects ingested either a normal or MR capsule of isradipine under fasted conditions. Serial samples of gastric juice (obtained via an indwelling nasogastric tube) and plasma were collected up to 24 h after drug intake, and were analyzed for isradipine by GC and RIA methods, respectively. The pH and titratable acid, protein, and pepsin concentrations of the gastric juice samples were also determined. Four additional subjects were similarly studied after ingesting the capsules following a high-fat breakfast. Under fasted conditions, gastric juice drug levels of the normal and MR capsules indicated a median GRT of less than 1.5 h in both cases. Plasma levels indicated a rapid absorption for the normal capsule (less than 2 h), but a remarkably slow absorption for the MR capsule, lasting 24 h or more. Under fed conditions, gastric juice and plasma profiles of the normal capsule were similar to those for the fasted case. In contrast, the MR capsule had an increased GRT (approximately 2.4 to 4.8 h) that was associated with a delayed and more extensive intragastric drug release. The corresponding plasma profiles showed a rapid absorption phase which correlated closely with the intragastric release kinetics. The influence of a high-fat meal on the release kinetics of the MR capsule did not appear related to the intragastric pH, or acid, protein, or pepsin concentrations. From these results we conclude that: (1) a prolonged GRT is not responsible for the slow absorption achieved with a "floating" MR capsule; (2) the presence or absence of food, rather than buoyancy, is the principal determinant of the GRT of the MR capsule; (3) the release and absorption of a lipophilic drug from a "floating" MR capsule may be affected by intragastric interaction with the lipid phase of meal; and (4) the major portion of drug release from the MR capsule takes place in the colon, rather than in the stomach.

Adult↗

Growth, synthesis and regional specialization of the embryonic chicken lens capsule.

The growth, synthesis and regional specialization of the lens capsule has been studied in chicken embryos and compared to adult chickens and mammals. During the final 15 days of embryonic development the surface area of the capsule increased 11-fold. This represents the minimum estimate of capsule growth, since it also increased in thickness during this period. Autoradiographic examination of [3H]proline- or 35SO4-labeled, detergent-cleaned, flat-mounted capsules suggested that all lens cells participated in capsule synthesis. This was supported by the observation that both lens epithelial and fiber cells incorporated [35S]-methionine into collagenase-sensitive proteins with molecular weights similar to type IV collagen. Histochemical staining of detergent-cleaned capsule explants (DCCEs) revealed regional differences in the carbohydrate composition of the capsule. Differences in collagenous proteins were also seen between the anterior and posterior regions of the capsule of the embryonic lenses. Following SDS-PAGE and silver staining a total of six collagenase-sensitive proteins were seen with molecular weights between 150 and 180 K. Three of these polypeptides were common to both anterior and posterior capsules, one was found only in the anterior capsule and the other two were found predominantly in the posterior capsule. No regional differences were seen in the collagenous proteins of capsules from adult chickens, rats or hamsters. The possibility is discussed that the unique pattern of collagenous polypeptides seen in embryonic capsules is related to the rapid growth of the embryonic lens.

Animals↗