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Pro-kinetic medications as aids in imaging the small bowel by video-capsule.

The m2a wireless video-capsule (Given Imaging Ltd., Israel) is a miniature ingestible camera utilized for the color imaging of the small intestine walls. Despite its diagnostic yield superiority over all other diagnostic modalities, a substantial part of the pathologies are not spotted. Considering the transmitted pictures high quality a resolution problem is ruled out, but rather it is assumed that parts of the intestinal wall surface are missed in the imaging process. Another important problem is the difficulty encountered by the capsule in crossing the antro-duodenal junction, probably due to pyloric hypomotility. Pro-kinetic drugs are capable of increasing the small intestine peristaltic wave velocity and contractile amplitude, thus assisting the video-capsule movements and widening the camera photo arc. The arc width is directly proportional to the surface imaging capacity. A specific dose range (cisapride 25-30 mg, metoclopramide 30 mg approximately) is calculated and an analysis is made of the use of these pro-kinetic drugs to increase the device diagnostic yield. It should be emphasized that: (1) despite a potential risk for complications, such as bleeding from small intestine lesions, radiological studies underline the high safety profile of metoclopramide; (2) increased capsule speed of progress is not expected to cause a loss of imaged area; (3) an oral dose below 15 mg (metoclopramide or cisapride) may not suffice to accelerate the capsule transit through the antro-duodenal junction. The concept is patent protected.

Antiemetics↗

Wireless pH testing as an adjunct to unsedated transnasal esophagoscopy: the safety and efficacy of transnasal telemetry capsule placement.

OBJECTIVES: The introduction of 48-hour wireless pH testing offers clinicians a new alternative for the objective documentation of reflux. The success of transnasal wireless pH capsule placement has not been previously described. The purpose of this investigation was to describe our experience with transnasal wireless pH capsule placement. METHODOLOGY: All patients undergoing unsedated transnasal esophagoscopy and wireless pH capsule placement between January 1, 2003 and July 31, 2003 were prospectively evaluated. Data concerning patient tolerance, success of capsule placement and function, complications, and pH recordings were collected. RESULTS: During this time, 46 persons were evaluated. The mean age of the cohort was 52 years. Of the patients, 50% were male. The indications for the procedure were chronic cough (18/46), gastroesophageal reflux disease (18/46), and larygopharyngeal reflux (10). Of the procedures performed, 85% (39/46) were successful. Complications included epistaxis (2/46), laryngospasm (2/46), and vasovagal reaction (1/46). CONCLUSIONS: The transnasal placement of a wireless pH capsule is a safe and effective diagnostic adjunct to unsedated transnasal esophagoscopy.

Capsules↗

Reduced anterior internal capsule and thalamic volumes in first-episode psychosis.

BACKGROUND: The thalamus is the gateway for sensory and motor information en route to the cortex. Information is processed via thalamocortical and corticothalamic pathways coursing through the internal capsules. In this study, we investigated the relationship between the anterior limb of the internal capsule, posterior limb of the internal capsule, and thalamus in first-episode psychosis (FEP). METHODS: Twenty-nine FEP subjects (26 DSM-IV schizophrenia, 2 schizoaffective disorder, 1 psychosis not otherwise specified) and 22 healthy volunteers participated in this study. Anterior limb of the internal capsule (AIC), posterior limb of the internal capsule (PIC), and the thalamus volumes were manually determined from MRI scans. RESULTS: FEP subjects had reduced AIC volumes (F(1,45)=6.18, p=0.017) and thalamic volumes (F(1,45)=8.00, p=0.007) compared to healthy volunteers. PIC volumes did not differ. Significant correlations between AIC volumes and thalamic volumes were observed in subjects with FEP, but not in healthy volunteers. Negative relationships between thalamic volumes and symptom severity were also observed. CONCLUSIONS: The AIC and thalamic volumes were reduced in subjects with FEP compared to healthy volunteers. Abnormalities in thalamocortical and orticothalamic pathways may contribute to functional disruption of neural circuits in psychosis.

Adolescent↗

Responses of diencephalic nociceptive neurones to orofacial stimuli and effects of internal capsule stimulation in the rat.

The effect of conditioning stimulation of the internal capsule on nociceptive neurones in the rat diencephalon was investigated. The animals were anaesthetised with N(2)O/O(2) (2:1) and 0.5% halothane, and immobilised with pancuronium bromide. Nociceptive neurones responding to noxious stimulation of the face and oral structures were recorded in the ventral posteromedial nucleus, posterior group and zona incerta. These neurones were classified into wide dynamic range and nociceptive-specific types. Functional segregation of these nociceptive neurones was not apparent within the nucleus or between nuclei. A test stimulus with a single rectangular pulse (5-70 V) was applied to the centre of the receptive field; the nociceptive neurones exhibited short- and/or long-latency responses. Both responses in about 45% of the nociceptive neurones were inhibited by conditioning stimuli to the contralateral internal capsule with trains of 33 pulses (300 microA) at 330 Hz. The percent inhibitory effects on the nociceptive neurones of each area were 68.0+/-14.8% (n = 6) in the ventral posteromedial nucleus, 72.8+/-12.4% (n = 4) in the posterior group and 61.5+/-7.5% (n = 4) in the zona incerta. Effective sites for conditioning stimulation were concentrated in the lateral side of the internal capsule, through which the corticofugal fibres from the somatosensory cortex pass. These findings suggest that the transmission of nociceptive information to the diencephalon is modulated by stimulation of the internal capsule at the level of the trigeminal sensory complex in the brainstem. They might provide a novel way to elucidate the neurophysiological basis for antinociception by stimulation of the internal capsule observed in clinical studies.

Animals↗

Bowel preparation increases the diagnostic yield of capsule endoscopy: a prospective, randomized, controlled study.

BACKGROUND: The aim of this study was to determine the value of small-bowel preparation for patients undergoing capsule endoscopy. METHODS: The study design was prospective, randomized, and controlled. Eighty patients referred for capsule endoscopy were randomized into two equal groups. Patients in Group A (mean age 54.40 [15.65] years) ingested 2 L of a polyethylene glycol/electrolyte solution 16 hours before the test, whereas patients in Group B (mean age 59.85 [14.58] years) prepared for the procedure by taking only clear liquids during the prior day. The primary outcome evaluated was the effect of bowel preparation on the quality of capsule images, as assessed with an objective scoring system in which cleansing was graded as "adequate" or "inadequate" by blinded examiners. A secondary outcome was the effect of bowel preparation on diagnostic yield. For this purpose, the results of capsule endoscopy were classified as positive findings, findings of uncertain significance, and no findings. RESULTS: Cleansing of the small intestine was considered "adequate" in 36 patients in Group A (90%) vs. 24 patients of Group B (60%) (p = 0.004). A diagnosis was established in 26 patients in Group A (65%) compared with 12 patients in Group B (30%) (p = 0.003). CONCLUSIONS: Bowel preparation before capsule endoscopy improves visualization of the small intestine, which may lead to an improvement in diagnostic yield.

Adolescent↗

[Effectiveness of endoscopic capsule for the detection of small-bowel bleeding of unknown origin and for the diagnosis of Crohn's disease].

The objective of this study is to assess the effectiveness of the endoscopic capsule for the diagnosis of bleeding of the small bowel and of Crohn's disease. A systematic review was performed. Studies with more than 10 patients, using the capsule and some other procedure for diagnostic purposes, and published in peer reviewed journals, were included. In order to evaluate the papers, a quality scale was created. The diagnostic yield of the capsule for small-bowel bleeding was approximately 55-75%. With other procedures, the diagnostic yield was around 30%. For Crohn's disease, the diagnostic yield of the capsule was between 43-70% while it was 0-50% with other procedures. The reviewed studies have methodological limitations, yet they seem to point to the fact that the capsule may have a better diagnostic yield than other diagnostic procedures for small-bowel bleeding and Crohn's disease.

Capsules↗

Promotion of oral insulin absorption in diabetic rabbits using pH-dependent coated capsules containing sodium cholate.

The hypoglycemic effect of oral insulin (40 U) capsules coated with a pH-dependent soluble polymer (Eudragit S100) and containing various doses of sodium cholate (20, 50, 100 mg) was studied in alloxan-hyperglycemic rabbits and compared with that of s.c. insulin injection (20 U). Sodium cholate (20 and 50 mg/capsule) produced a dose-related enhancement of an insulin-induced decrease in the blood glucose level. Insulin capsules containing sodium cholate (50 mg/capsule) produced a steady reduction of the blood glucose level reaching 69% of the initial values (P < 0.01) by 3 h and 48% (P < 0.001) by 5 h after administration. This capsule produced an AUC0-5 h of 125 +/- 14.8 mg.h/dl with relative hypoglycemia (R.H.) of 25.8% compared with insulin s.c. The capsules containing sodium cholate (100 mg), however, did not significantly (P > 0.05) improve the hypoglycemic effect of insulin more than the smaller dose (50 mg/capsule) producing an AUC and R.H. of 135 +/- 12.3 mg.h/dl and 27.9%, respectively. The capsule coated with Eudragit S100 and containing insulin mixed with sodium cholate seems to be a promising formulation to overcome the unavailability of oral insulin.

Administration, Oral↗

Macronutrient selection through postingestive signals in sea bass fed on gelatine capsules.

The role of the food orosensory properties on protein (P), fat (F) and carbohydrate (CH) self-selection was investigated in fish fed gelatine capsules containing pure macronutrients. A total of 40 sea bass (39.6+/-6.2 g initial body weight) distributed in eight 75-l tanks were used. In a sequence of experimental phases, sea bass were fed a pelleted complete diet, an encapsulated complete diet or a combination of separately encapsulated pure macronutrients. In order to induce associative learning, capsules containing a given macronutrient were paired with a particular colour. Our results demonstrate that fish are able to regulate food intake, so as to balance their energy intake, when they are fed a complete encapsulated diet and, therefore, without using the orosensory properties of the diet. Moreover, sea bass learn to discriminate and select among colour-coded, pure macronutrient capsules to compose a complete and balanced diet using colour as the only external cue. The composition of selected diet was 55% P, 23% CH and 22% F in terms of macronutrient percentage. The diet orosensory properties do not seem to be necessary to regulate macronutrient intake either, suggesting that an associative learning between capsule colour and content can be established through monitoring of macronutrient intake by postingestive and/or postabsorptive mechanisms. These results provide the first insight into energy and macronutrient self-selection by fish fed on gelatine capsules containing separate macronutrients.

Animals↗

Bioavailability of lansoprazole granules administered in juice or soft food compared with the intact capsule formulation.

BACKGROUND: The ability to administer the contents of an encapsulated-dose formulation in liquids or soft foods without compromising drug bioavailability is highly desirable for patients who are unable to swallow or have difficulty swallowing. OBJECTIVE: The purpose of this study was to compare the bioavailability of lansoprazole granules administered in 2 types of juice and a soft food with that of the intact capsule administered with water. METHODS: Healthy adult volunteers were eligible for this single-center, Phase I, single-dose, randomized, open-label, 4-period crossover study. Subjects received the enteric-coated granular contents of a 30-mg lansoprazole capsule in 3 test regimens (in 180 mL of orange juice, 180 mL of tomato juice, or 1 tablespoon of strained pears, each followed by 180 mL of water) and 1 reference regimen (the 30-mg intact capsule with 180 mL of water). The regimens were rotated at > or = 6-day intervals so that each subject received all 4 regimens. Blood samples for pharmacokinetic analyses were obtained during the 12 hours after each regimen. RESULTS: Twenty healthy adult volunteers (10 men, 10 women; mean age, 36 years [range, 19-53 years]) completed this study. Bioavailability of the 3 test regimens was assessed using the two 1-sided tests procedure for mean maximum plasma concentration and area under the plasma concentration-time curve (AUC) from time 0 through the last measurable concentration and AUC from time 0 to infinity. These results were compared with that of the intact capsule. This comparison indicated that the 90% CIs for all 3 test regimens were within the acceptable bioequivalence range of 0.80 to 1.25. Lansoprazole was well tolerated, with most of the adverse events being mild. Headache was the most frequently reported adverse event. CONCLUSION: The results of this study indicate that the bioavailability of lansoprazole granules, when administered in orange juice, tomato juice, or a small amount of strained pears, was similar to that of the intact capsule in these healthy adult volunteers.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Lansoprazole: administration of the contents of a capsule dosage formulation through a nasogastric tube.

A single-dose, open-label, randomized, crossover bioavailability study was conducted in 24 healthy adult male volunteers to assess an alternative method of administration of lansoprazole capsules. The results of 22 subjects were analyzed. Subjects received regimen A (granules from a 30-mg capsule mixed with apple juice and administered through a nasogastric tube) or regimen B (an intact 30-mg capsule) during the first study period. The regimens were reversed during the second period 1 week later. Blood samples were obtained over 12 hours and pharmacokinetic variables were determined. No statistically significant differences in mean time elapsed to peak concentration, mean peak concentration, area under the curve (AUC)0-t, and AUC0-infinity were detected between regimens by using analysis of variance. Bioavailability was assessed by the 90% confidence interval of the two one-sided tests on the natural logarithm of AUC. The 90% confidence interval for the AUCzero-infinity ratio was 0.955 to 1.140 for regimens A to B. These results indicate similar bioavailabilities between the two regimens and demonstrate that lansoprazole capsules may be administered by mixing the capsule contents with apple juice for administration through a nasogastric tube.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Mechanical detachment of the anterior hyaloid membrane from the posterior lens capsule.

OBJECTIVE: To investigate the incidence of spontaneous detachment of the anterior hyaloid membrane from the posterior lens capsule and to explore the possibility of surgical separation of the anterior hyaloid membrane. DESIGN: Prospective nonrandomized interventional comparative trial and comparative human tissue study. PARTICIPANTS: Thirty-eight eyes of 32 patients undergoing primary pars plana vitrectomy combined with cataract extraction and intraocular lens implantation and 3 eye bank eyes for histopathologic examination. METHODS: The anterior hyaloid membrane and posterior lens capsule were observed with a fiberoptic endoscope. Surgical separation of the anterior hyaloid membrane was attempted by either the hydrodissection method before cataract extraction (18 eyes) or the direct suction method after cataract extraction (20 eyes). In eye bank eyes, histopathologic examination was performed with (one eye) and without (two eyes) surgical separation of the anterior hyaloid membrane. MAIN OUTCOME MEASURES: Incidence of spontaneous detachment and success rate of surgical detachment of the anterior hyaloid membrane. RESULTS: No eye displayed spontaneous detachment of the anterior hyaloid membrane. Using the hydrodissection method, complete detachment of the anterior hyaloid membrane was achieved in 10 eyes (55.6%), partial detachment was attained in 2 eyes (11.1%), and detachment was not induced at all in 6 eyes (33.3%). With the direct suction method, the anterior hyaloid membrane was completely separated from the posterior lens capsule in 10 eyes (50%), partially detached in 10 eyes (50%), and not detached at all in any eye. The direct suction method had a significantly higher success rate than the hydrodissection method (P < 0.001, chi-square test). In eye bank eyes, the surgical manipulation induced complete separation of the anterior hyaloid membrane from the lens capsule. CONCLUSIONS: Spontaneous detachment of the anterior hyaloid membrane from the posterior lens capsule is very rare. Under endoscopic observation, surgical detachment of the anterior hyaloid membrane was possible in half of the patients.

Adult↗

Pasteurella multocida capsule: composition, function and genetics.

Pasteurella multocida is an important animal pathogen and many strains express a polysaccharide capsule. The antigenicity of the capsule can be used to identify five serogroups A, B, D, E and F. Disease predilection is generally related to serogroup, with haemorrhagic septicaemia strains belonging to serogroups B or E and fowl cholera strains to serogroup A. The importance of the capsule in virulence has been implicated in a number of studies but these studies have been hampered by a lack of isogenic strains and an understanding of capsule biosynthesis at the molecular level. Recently, the nucleotide sequences and genetic organisation of the capsule biosynthetic loci have been determined for strains of P. multocida serogroups A and B.

Bacterial Capsules↗

Permeability and stability of chitosan-based capsules: effect of preparation.

Capsules were obtained by interpolymer complexation between chitosan (polycation) and sodium hexametaphosphate (oligoanion). The effect of preparation variables such as the pH, ionic strength as well as the reagent and porogen concentration on the capsule characteristics was evaluated. By decreasing the chitosan/SMP ratio, adding mannitol up to 1% or maintaining the salt concentrations below 0.15 w/v%, the diffusion characteristics can be modulated without disturbing the capsule mechanical stability. Higher concentrations of the cross-linking agent (2.25 w/v%) produced stable capsules only in the absence of electrolyte and low polyol amounts. Furthermore, by increasing the ionic strength, or the pH of the initial chitosan solution, the membrane exclusion limit shifted to higher values concomitant with a significant loss in the membrane compression resistance. The results obtained showed that the capsule characteristics could be independently controlled by manipulating the coacervation conditions.

Capsules↗

Spectroscopic identification of an amorphous-to-crystalline drug transition in a solid dispersion SCH 48461 capsule formulation.

Changes in the dissolution of a solid dispersion capsule formulation composed of amorphous SCH 48461 in a polyethylene glycol 8000 matrix were investigated. SCH 48461 [(3R,4S)-1,4-bis(4-methoxyphenyl)-3-(3-phenylpropyl)-2-azetidinone] is a potent cholesterol absorption inhibitor with low water solubility and low melting point. Several capsule lots placed under controlled storage conditions exhibited a slowing of dissolution as a function of time with large inter-lot and intra-lot dissolution variations. Capsule contents were analyzed by attenuated total reflectance infrared (ATR-IR) microspectroscopy and solid-state cross-polarization, magic angle spinning (CPMAS) 13C-nuclear magnetic resonance (NMR) spectrometry. ATR-IR microspectroscopic analysis showed large IR spectral differences between the lots including the presence of a crystalline drug fraction in lots which exhibited incomplete dissolution. Solid-state CPMAS 13C-NMR analysis confirmed the presence of a crystalline drug fraction in the problematic capsule lots. Both ATR-IR and CPMAS 13C-NMR spectral results produced a rank ordering of the crystalline drug fraction present in the capsule lots that correspond to the dissolution results.

Anticholesteremic Agents↗

Regional material properties of the human hip joint capsule ligaments.

The hip joint capsule functions to constrain translation between the femur and acetabulum while allowing rotational and planar movements. Despite the crucial role it plays in the pathogenesis of hip instability, little is known about its biomechanical properties. The goal of this study was to determine the regional material properties of the iliofemoral and ischiofemoral ligaments of the capsule. Ten human cadaveric specimens of each ligament were tested to failure in tension. The stress at failure, strain at failure, strain energy density at failure, toe- and linear-region elastic moduli, and the Poisson's ratio were measured for each ligament. The strain to failure was greatest in the ischiofemoral ligament, while no significant difference was noted in failure stress by region or ligament. The Young's moduli of elasticity ranged from 76.1 to 285.8 MPa among the different ligaments, and were generally consistent with properties previously reported for the shoulder capsule. The elastic moduli and strain energy density at failure differed by region. No significant differences in Poisson's ratio were found by region or ligament. The average Poisson's ratio was approximately 1.4, consistent with anisotropic behavior of ligamentous tissues. Understanding the material properties of the hip capsule may help the orthopaedic surgeon better understand normal ligament function, and thereby choose a surgical approach or strategy of repair. Furthermore, knowledge of the normal mechanical function of the hip capsule ligaments could assist in the evaluation of the success of a repair.

Aged↗

Posterior capsule folds and removal of ophthalmic viscosurgical devices.

PURPOSE: To evaluate the relationship between posterior capsule folds and an ophthalmic viscosurgical device (OVD) during cataract surgery. SETTING: Parkland Memorial Hospital, Dallas, Texas, USA. METHODS: A prospective observational study of 91 consecutive uneventful cataract extractions by phacoemulsification was performed. The presence or absence of posterior capsule folds was noted immediately after intraocular lens (IOL) implantation and after OVD removal. RESULTS: Posterior capsule folds were present in 21 of 49 cases (43%) with an MA60BM lens (Alcon Laboratories) and in 1 of 42 cases (2%) with an SA30AL lens. In the MA60BM group with folds, the folds were noted before OVD removal in 14 cases and after OVD removal in 16 cases. There was no significant difference in age, sex, axial length, horizontal corneal diameter, or IOL power between groups with and without posterior capsule folds. CONCLUSIONS: The presence of posterior capsule folds does not reliably signify the complete removal of OVDs.

Aged↗

Mathematical modeling of the forces between an intraocular lens and the capsule.

PURPOSE: To model the pressure relationship between an intraocular lens (IOL) and the capsular bag. SETTING: Department of Physics, Kings' College, London University, London, United Kingdom. METHODS: A mathematical model was made of the forces between the capsule and IOL showing that the pressure related to the local radius of curvature of the IOL at any given point. The local radius of curvature for round-edged and square-edged IOLs was measured from electron micrographs of the IOL profiles, and the corresponding pressure profiles were calculated and compared. RESULTS: The pressure between an IOL and the capsular bag was proportional to the quotient of the tension in the capsule divided by the local radius of curvature of the IOL, with a constant of proportionality that depended on the coefficient of friction between the capsule and IOL. Measuring the local radius of curvature of the 2 IOL types suggested a pressure increase of at least 69% +/- 6% at the optic edge with the square-edged IOL. CONCLUSIONS: The mathematical model predicted that IOLs with square-edged optic profiles exerts higher pressure on the posterior capsule than IOLs with round-edged optic profiles. The higher pressure may form a physical barrier to lens epithelial cell migration onto the posterior capsule.

Humans↗

Predicting posterior capsule opacification: value of early retroillumination imaging.

PURPOSE: To investigate the value of early retroillumination imaging of the posterior capsule in predicting the eventual development of posterior capsule opacification (PCO). SETTING: Ophthalmology Department, St. Thomas' Hospital, and Department of Physics, King's College, London, United Kingdom. METHODS: All patients with retroillumination images of the posterior capsule taken 6 months and 2 years after uneventful phacoemulsification with in-the-bag intraocular lens (IOL) implantation were selected. The images were taken using the same hardware and analyzed with the same software to calculate the percentage area of the posterior capsule covered by lens epithelial cells. The percentage area of PCO with all IOL types 6 months postoperatively was correlated with that at 2 years. RESULTS: One hundred forty patients had analyzable images at 6 months and 2 years. Of these, 63 had a poly(methyl methacrylate) (PMMA) IOL (Pharmacia 812A or Storz P497UV), 33 an acrylic (Alcon AcrySof MA30 or SA30), 22 a silicone (Allergan SI-30), and 22 a hydrophilic acrylic (Bausch & Lomb Hydroview H60). The correlation of the percentage area of PCO at 6 months with that at 2 years resulted in an r value of 0.71 (P <.0001) in the entire group. The r value was 0.48 in the PMMA group and 0.86 in the foldable IOL group (P <.0001) (r value: AcrySof, 0.66; silicone, 0.82; Hydroview, 0.75). CONCLUSIONS: Retroillumination imaging of the posterior capsule 6 months after cataract surgery predicted the PCO outcome at 2 years in eyes with foldable IOLs.

Acrylic Resins↗