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Women's satisfaction with an intravaginal Lactobacillus capsule for the treatment of bacterial vaginosis.

OBJECTIVE: To assess women's satisfaction with a vaginal capsule containing human-derived, H(2)O(2)-producing Lactobacillus crispatus at completion of a randomized, placebo-controlled study for treatment of bacterial vaginosis (BV). METHODS: Women aged 14-35 years with BV were randomized to Lactobacillus or placebo intravaginal capsule twice daily for 3 days monthly for 3 months. Attitudes were assessed with a standardized scale at the final follow-up visit, and associations of satisfaction with clinical and gram stain cure of BV were determined. RESULTS: Four hundred twenty-four women were randomized at enrollment, and 232 (55%) provided data on satisfaction at the final visit. Overall, satisfaction with the capsule was high and was independent of subjects' race, age, and prior history of BV. Report of satisfaction with the capsule, belief that it contained healthy bacteria, and belief that its use improved vaginal health were directly related to clinical cure and to improved Nugent score. Except for women who had BV at the final follow-up visit, most subjects believed that the capsule contained healthy bacteria independent of any outcome reflecting cure. Willingness to use the capsule again was not significantly related to whether subjects experienced clinical cure or normalization of Nugent score at either visit. Adverse effects were rare and were largely related to a perceived difference in vaginal discharge. CONCLUSIONS: Satisfaction with an intravaginal capsule and positive beliefs about its use for BV treatment were prevalent, especially among women with a clinical and microbiological response to BV therapy. However, most women expressed willingness to use the product again regardless of clinical response. Acceptability of and interest in alternative BV treatments, such as L. crispatus intravaginal applications, are high.

Administration, Intravaginal↗

Comparative pharmacokinetics and pharmacodynamics of lansoprazole oral capsules and suspension in healthy subjects.

The pharmacokinetics and pharmacodynamics of lansoprazole suspension and lansoprazole capsules were studied. Thirty-six healthy males and females were randomized in a single-dose, open-label, two-period crossover study. Lansoprazole 30 mg was administered via a nasogastric tube as simplified lansoprazole suspension (in 8.4% sodium bicarbonate) or orally as the intact capsule after a minimum 12-hour fast and 5 hours before lunch. Ambulatory 24-hour intragastric pH was monitored at baseline and on day 1 of each treatment period to assess lansoprazole's pharmacodynamics. Blood samples were collected before drug administration and at predetermined intervals up to 24 hours after each dose to assess lansoprazole's pharmacokinetics. Both formulations effectively raised the mean 24-hour intragastric pH (mean 24-hour pH of 3.75 with suspension and 3.52 with intact capsule) and maintained it above threshold values of 3 and 4 for more than 40% of the 24-hour postdose period. The suspension was associated with a significantly shorter mean time to the maximum observed concentration (tmax) compared with the intact capsule. The mean maximum observed plasma concentration (Cmax) of the suspension was significantly higher and the mean area under the concentration-time curve from time zero to infinity (AUC infinity) was significantly lower than those of the intact capsule (879 versus 810 ng/mL and 1825 versus 2229 ng.hr/mL). The 90% confidence intervals obtained by two one-sided tests for both Cmax and AUC infinity were contained within the 0.80 to 1.25 range, confirming the bioequivalence of the two regimens. Simplified lansoprazole suspension effectively controls intragastric pH, is bioequivalent to the intact capsule, and represents an effective therapeutic option for patients who have difficulty swallowing or are unable to swallow lansoprazole capsules.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Diagnostic yield and clinical outcomes after capsule endoscopy in 100 consecutive patients with obscure gastrointestinal bleeding.

OBJECTIVES: The endoscopic capsule is a useful tool for visualizing the small bowel in patients with obscure gastrointestinal bleeding. In this study the authors evaluated the diagnostic aid provided by the endoscopic capsule, the factors predicting a significant finding and their impact on the patients' clinical evolution. METHODS: A total of 100 patients (52 men and 48 women, average age 64.4 years) underwent capsule endoscopy. Of this group, 52 patients presented with obscure-overt bleeding and 48 with obscure-occult bleeding. After an average follow-up time of 11.4 months, the clinical outcome was evaluated in 95 patients. RESULTS: The endoscopic capsule identified significant findings in 68% of patients. The most common diagnosis (33.8%) was angiodysplasias. The most important factor predicting significant findings was the previous need for transfusion in the overt bleeding group. As the result of the findings, a specific intervention was made in 75.8% of patients. At the end of follow-up, the clinical outcome was considered positive in 71.6% of patients. Capsule retention occurred in one patient, who required surgery. CONCLUSION: In patients with obscure gastrointestinal bleeding, capsule endoscopy provides a high degree of diagnostic aid. The best candidates for this procedure are patients with obscure-overt bleeding who have required blood transfusions. Capsule endoscopy has a positive influence on an important proportion of patients, whether oriented towards new diagnostic techniques or towards a definitive treatment.

Adolescent↗

Capsular opacification after cataract surgery and capsule.

The lens capsule, the keystone of modern cataract surgery, has been the subject of some important and interesting investigations over the past year. This review addresses 1) inhibition of posterior capsule opacification (surgical techniques, intraocular lens design, and pharmacologic methods); 2) treatment of posterior capsule opacification; and 3) characteristics of the capsule. Of special interest are techniques for inhibiting posterior capsule opacification in pediatric patients by optic capture through a posterior capsulorhexis, the concept that sharp optic edges markedly decrease posterior capsule opacification as compared with round-edged implants, and promising work demonstrating that an immunotoxin may be effective in prevention of posterior capsule opacification.

Adolescent↗

Feasibility and tolerability of transnasal/per-oral placement of the wireless pH capsule vs. traditional 24-h oesophageal pH monitoring--a randomized trial.

BACKGROUND: The wireless pH is a new technique to monitor oesophageal acid exposure. AIM: To compare the feasibility and tolerability of the wireless pH capsule vs. the traditional pH probe. METHODS: Consecutive patients referred for a pH test were enrolled into the study. Patients were randomized to traditional pH probe, or wireless pH capsule. Patients recorded their activities, food consumption, symptoms, satisfaction with the test and completed a quality of life questionnaire. RESULTS: Of the 50 patients recruited, 25 patients underwent placement of the traditional pH probe, and 25 the wireless pH capsule. Patients with the wireless pH capsule had less nose pain, runny nose, throat pain, throat discomfort and headache as compared with those with the traditional pH probe (P = 0.047, P = 0.001, P = 0.032, P = 0.001, P = 0.009, respectively). Patients in the wireless pH capsule group had more chest discomfort during the pH test (P = 0.037). Patients in the wireless pH capsule group perceived the test as interfering less with their overall daily activities, eating and sleep (P =0.001, P = 0.003, P = 0.025, respectively), and had overall satisfaction with the test (P = 0.023). CONCLUSIONS: Transnasal/per-oral placement of the wireless pH capsule is significantly better tolerated then the traditional pH probe.

Capsules↗

Meta-analysis: capsule enteroscopy vs. conventional modalities in diagnosis of small bowel diseases.

BACKGROUND: Prospective trials support the role of capsule enteroscopy as an improvement in diagnosing mucosal lesions in the small bowel. AIM: To determine the diagnostic yield and safety of capsule enteroscopy vs. alternative diagnostic modalities (such as push enteroscopy, small bowel follow-through or enteroclysis) in patients with small bowel diseases. METHODS: A search for prospective studies comparing capsule enteroscopy vs. other diagnostic tests in adults was performed between 1966 and 2005. Selected articles were included in a meta-analysis. Three analyses were run separately, all included studies and studies having occult gastrointestinal bleeding or Crohn's disease as main outcome. RESULTS: Seventeen studies (526 patients) met inclusion criteria. The rate difference (i.e. the absolute pooled difference in the rate of positive findings) between capsule enteroscopy and alternative modalities for small bowel disease was 41% (95% CI 35.6-45.9); 37% (95% CI 29.6-44.1) for occult gastrointestinal bleeding; and 45% (95% CI 30.9-58.0) for Crohn's disease. Failure to visualize the caecum occurred in 13%, significantly more often in occult bleeders (17%) than in patients with Crohn's disease (8%) (P < 0.006). Adverse events were recorded in 29 patients (6%). Capsule retention was more frequent in patients with Crohn's disease (3% vs. 1%, OR 4.37). CONCLUSIONS: Capsule enteroscopy proved significantly superior to push enteroscopy and small bowel radiology in the diagnosis of ileal diseases. Capsule enteroscopy is safe, though prior radiology is still necessary to rule out small bowel strictures in patients with known or suspected Crohn's disease.

Adult↗

Antipyrine absorption after delayed oesophageal capsule transit.

Twenty fasted patients were given hard gelatin capsules containing antipyrine and barium, and in ten patients the capsule arrested and disintegrated in the oesophagus. Plasma antipyrine was assayed at 10 min intervals for 1 h, then 30 min intervals for a further 3 h. The plasma concentration-time curves for the patients in whom the capsule entered the stomach rapidly, and for those in whom the capsule lodged in the oesophagus, were compared. The absorption in the first hour was calculated from the area under the plasma concentration-time curve and found to be significantly lower if the capsule disintegrated in the oesophagus (P less than 0.0005). The time to peak plasma concentration was delayed by an average of 46 min (P less than 0.01) and the peak plasma concentration was significantly lower (P less than 0.05) if delayed capsule transit occurred. Delayed capsule transit through the oesophagus significantly changed the pharmacokinetic profile of antipyrine.

Absorption↗

True exfoliation of the lens capsule. A clinicopathological report.

A case of true senile exfoliation of the lens capsule is reported. Electron microscopic examination of the capsule confirmed capsular delamination. The proteins in the remaining sample of exfoliated capsule and in normal capsules were analysed by polyacrylamide gel electrophoresis in the presence of the dissociating agent, sodium dodecyl sulphate, and under reducing conditions (SDS--PAGE). Densitometric scans of electrophoretograms indicated the virtual absence of a 58 kilodalton (kDa) component and approximately half the level of a 74 kDa component in the exfoliated capsule relative to normal capsule. The remaining protein components detected were of identical molecular weight and abundance compared with the normal lens capsule.

Aged↗

The capsule biosynthetic locus of Pasteurella multocida A:1.

Pasteurella multocida is the aetiological agent of fowl cholera, bovine haemorrhagic septicaemia and atrophic rhinitis in pigs. Many strains of P. multocida express a capsule on their surface. However, nothing is known about the capsule biosynthetic locus in P. multocida although the capsule has been implicated as a virulence factor. The entire capsule locus of P. multocida A:1 was cloned and sequenced. The locus is divided into three regions. Region 1 comprises four ORFs which are involved in the transport of the capsule polysaccharide to the surface. Region 2 comprises five ORFs whose postulated protein products are involved in the biosynthesis of the polysaccharide capsule. Region 3 comprises two ORFs whose postulated products show similarity to proteins that are involved in the phospholipid substitution of the polysaccharide capsule.

Amino Acid Sequence↗

Modified ventilated capsule for the measurement of sweating rate in the exercising horse.

Modification of a ventilated capsule technique for the measurement of sweating rate (SR) is described for application in an exercising horse. The plastic capsule was sealed against the coat of the horse. Dry air was blown through the capsule over the skin and the change in absolute humidity (g/m3) between air entering and leaving the capsule was used to calculate SR. The effect of flow rate on the response characteristics of the system was investigated and measured over a range of sweating rates in a group of horses completing a short exercise test. Repeatability of SR measurements made at 2 sites, one 10 cm distal to the tuber sacrale (SRS) and the other approximately overlying C4 in the neck (SRN), were compared. To encourage the rapid and complete evaporation of moisture from the area of coat enclosed by the SR capsule, it was demonstrated that the degree of saturation of the air leaving the capsule should be maintained below 15% relative humidity (RH). This was best achieved at flow rates exceeding 35 l/min. No significant difference was found between the 2 repeated tests separated by 3 days, with respect to right atrial temperature (TRA) and SR. The modified system for the measurement of SR in the exercising horse used in this study was shown to be fast responding and capable of measuring a wide range of sweating rates. A good seal was maintained throughout and the capsule was removed without causing damage to the coat.

Animals↗

Poly-gamma-glutamate capsule-degrading enzyme treatment enhances phagocytosis and killing of encapsulated Bacillus anthracis.

The poly-gamma-d-glutamic acid capsule confers antiphagocytic properties on Bacillus anthracis and is essential for virulence. In this study, we showed that CapD, a gamma-polyglutamic acid depolymerase encoded on the B. anthracis capsule plasmid, degraded purified capsule and removed the capsule from the surface of anthrax bacilli. Treatment with CapD induced macrophage phagocytosis of encapsulated B. anthracis and enabled human neutrophils to kill encapsulated organisms. A second glutamylase, PghP, a gamma-polyglutamic acid hydrolase encoded by Bacillus subtilis bacteriophage PhiNIT1, had minimal activity in degrading B. anthracis capsule, no effect on macrophage phagocytosis, and only minimal enhancement of neutrophil killing. Thus, the levels of both phagocytosis and killing corresponded to the degree of enzyme-mediated capsule degradation. The use of enzymes to degrade the capsule and enable phagocytic killing of B. anthracis offers a new approach to the therapy of anthrax.

Animals↗

The capsule is a virulence determinant in the pathogenesis of Pasteurella multocida M1404 (B:2).

Capsules from a range of pathogenic bacteria are key virulence determinants, and the capsule has been implicated in virulence in Pasteurella multocida. We have previously identified and determined the nucleotide sequence of the P. multocida M1404 (B:2) capsule biosynthetic locus (J. D. Boyce, J. Y. Chung, and B. Adler, Vet. Microbiol. 72:121-134, 2000). The cap locus consists of 15 genes, which can be grouped into three functional regions. Regions 1 and 3 contain genes proposed to encode proteins involved in capsule export, and region 2 contains genes proposed to encode proteins involved in polysaccharide biosynthesis. In order to construct a mutant impaired in capsule export, the final gene of region 1, cexA, was disrupted by insertion of a tetracycline resistance cassette by allelic replacement. The genotype of the tet(M) OmegacexA mutant was confirmed by Southern hybridization and PCR. The acapsular phenotype was confirmed by immunofluorescence, and the strain could be complemented and returned to capsule production by the presence of a cloned uninterrupted copy of cexA. Wild-type, mutant, and complemented strains were tested for virulence by intraperitoneal challenge of mice; the presence of the capsule was shown to be a crucial virulence determinant. Following intraperitoneal challenge of mice, the acapsular bacteria were removed efficiently from the blood, spleen, and liver, while wild-type bacteria multiplied rapidly. Acapsular bacteria were readily taken up by murine peritoneal macrophages, but wild-type bacteria were significantly resistant to phagocytosis. Both wild-type and acapsular bacteria were resistant to complement in bovine and murine serum.

Animals↗

Upper and lower respiratory tract infection by Streptococcus pneumoniae is affected by pneumolysin deficiency and differences in capsule type.

Pneumococci frequently colonize the upper respiratory tract, and these pneumococci are believed to act as a reservoir for infection of the lower respiratory tract and bacteremia. We investigated how the pneumococcal toxin pneumolysin affects the capacity of pneumococci to infect the upper and lower respiratory tract of the mouse. Wild-type Streptococcus pneumoniae serotype 2 and 3 strains, a serotype 2 pneumolysin-deficient mutant, and a serotype 2 mutant with the pneumolysin gene reinserted were used to study differences in colonization and disease. In addition, we also examined a pneumococcal chimeric mutant (capsule type switched from serotype 2 to serotype 3) to gain further insight into the role that capsule plays in nasopharyngeal infection. Absence of pneumolysin was found to be associated with significantly lower numbers of pneumococci in the nasopharynx, trachea, and lungs. Differences in pneumococcal capsule type were found to have significant effects on pneumococcal infection of the nasopharynx, trachea, and lungs. However, it was the combination of capsule type and genetic background that was important, and the influence of this combination varied with the site of infection. For example, in the nasopharynx the wild-type serotype 3 strain and the capsule-switched mutant behaved similarly, whereas in the lungs the mutant that was switched to serotype 3 survived less well than the wild-type serotype 3 strain. The combination of capsule type and genetic background also determined virulence. Thus, the wild-type serotype 3 strain was virulent, whereas the capsule-switched mutant was avirulent.

Animals↗

Genetic basis for biosynthesis of the (alpha 1-->4)-linked N-acetyl-D-glucosamine 1-phosphate capsule of Neisseria meningitidis serogroup X.

The genetic basis for biosynthesis of the (alpha1-->4)-linked N-acetyl-D-glucosamine 1-phosphate capsule of Neisseria meningitidis serogroup X was defined. The biosynthesis gene cassette was a approximately 4.2-kb region located between ctrA of the capsule transport operon and galE, which encodes the UDP-glucose-4-epimerase. This location was identical to the locations of the biosynthesis cassettes in other meningococcal serogroups. Three open reading frames unique to meningococcus serogroup X were identified. Deletion-insertion mutation and colony immunoblotting confirmed that these three genes were essential for serogroup X capsule expression, and the genes were designated xcbA, xcbB, and xcbC (serogroup X capsule biosynthesis). Reverse transcriptase PCR indicated that the xcbABC genes form an operon and are cotranscribed divergently from ctrA. XcbA exhibited 52% amino acid similarity to SacB, the putative capsule polymerase of meningococcus serogroup A, suggesting that it plays a role as the serogroup X capsule polymerase. An IS1016 element was found within the intergenic region separating ctrA and xcbA in multiple strains, and this element did not interfere with capsule expression.

Acetylglucosamine↗

Salmonella produces an O-antigen capsule regulated by AgfD and important for environmental persistence.

In this study, we show that Salmonella produces an O-antigen capsule coregulated with the fimbria- and cellulose-associated extracellular matrix. Structural analysis of purified Salmonella extracellular polysaccharides yielded predominantly a repeating oligosaccharide unit similar to that of Salmonella enterica serovar Enteritidis lipopolysaccharide O antigen with some modifications. Putative carbohydrate transport and regulatory operons important for capsule assembly and translocation, designated yihU-yshA and yihVW, were identified by screening a random transposon library with immune serum generated to the capsule. The absence of capsule was confirmed by generating various isogenic Deltayih mutants, where yihQ and yihO were shown to be important in capsule assembly and translocation. Luciferase-based expression studies showed that AgfD regulates the yih operons in coordination with extracellular matrix genes coding for thin aggregative fimbriae and cellulose. Although the capsule did not appear to be important for multicellular behavior, we demonstrate that it was important for survival during desiccation stress. Since the yih genes are conserved in salmonellae and the O-antigen capsule was important for environmental persistence, the formation of this surface structure may represent a conserved survival strategy.

Bacterial Capsules↗

Streptococcus iniae capsule impairs phagocytic clearance and contributes to virulence in fish.

Surface capsular polysaccharides play a critical role in protecting several pathogenic microbes against innate host defenses during infection. Little is known about virulence mechanisms of the fish pathogen Streptococcus iniae, though indirect evidence suggests that capsule could represent an important factor. The putative S. iniae capsule operon contains a homologue of the cpsD gene, which is required for capsule polymerization and export in group B Streptococcus and Streptococcus pneumoniae. To elucidate the role of capsule in the S. iniae infectious process, we deleted cpsD from the genomes of two virulent S. iniae strains by allelic exchange mutagenesis to generate the isogenic capsule-deficient DeltacpsD strains. Compared to wild-type S. iniae, the DeltacpsD mutants had a predicted reduction in buoyancy and cell surface negative charge. Transmission electron microscopy confirmed a decrease in the abundance of extracellular capsular polysaccharide. Gas-liquid chromatography-mass spectrometry analysis of the S. iniae extracellular polysaccharides showed the presence of l-fucose, d-mannose, d-galactose, d-glucose, d-glucuronic acid, N-acetyl-d-galactosamine, and N-acetyl-d-glucosamine, and all except mannose were reduced in concentration in the isogenic mutant. The DeltacpsD mutants were highly attenuated in vivo in a hybrid striped bass infection challenge despite being more adherent and invasive to fish epithelial cells and more resistant to cationic antimicrobial peptides than wild-type S. iniae. Increased susceptibility of the S. iniae DeltacpsD mutants to phagocytic killing in whole fish blood and by a fish macrophage cell line confirmed the role of capsule in virulence and highlighted its antiphagocytic function. In summary, we report a genetically defined study on the role of capsule in S. iniae virulence and provide preliminary analysis of S. iniae capsular polysaccharide sugar components.

Animals↗

Wireless capsule endoscopy: a comparison with push enteroscopy in patients with gastroscopy and colonoscopy negative gastrointestinal bleeding.

BACKGROUND: The development of wireless capsule endoscopy allows painless imaging of the small intestine. Its clinical use is not yet defined. The aim of this study was to compare the clinical efficacy and technical performance of capsule endoscopy and push enteroscopy in a series of 50 patients with colonoscopy and gastroscopy negative gastrointestinal bleeding. METHODS: A wireless capsule endoscope was used containing a CMOS colour video imager, transmitter, and batteries. Approximately 50,000 transmitted images are received by eight abdominal aerials and stored on a portable solid state recorder, which is carried on a belt. Push enteroscopy was performed using a 240 cm Olympus video enteroscope. RESULTS: Studies in 14 healthy volunteers gave information on normal anatomical appearances and preparation. In 50 patients with gastrointestinal bleeding and negative colonoscopy and gastroscopy, push enteroscopy was compared with capsule endoscopy. A bleeding source was discovered in the small intestine in 34 of 50 patients (68%). These included angiodysplasia (16), focal fresh bleeding (eight), apthous ulceration suggestive of Crohn's disease (three), tumour (two), Meckel's diverticulum (two), ileal ulcer (one), jejunitis (one), and ulcer due to intussusception (one). One additional intestinal diagnosis was made by enteroscopy. The yield of push enteroscopy in evaluating obscure bleeding was 32% (16/50). The capsule identified significantly more small intestinal bleeding sources than push enteroscopy (p<0.05). Patients preferred capsule endoscopy to push enteroscopy (p<0.001). CONCLUSIONS: In this study capsule endoscopy was superior to push enteroscopy in the diagnosis of recurrent bleeding in patients who had a negative gastroscopy and colonoscopy. It was safe and well tolerated.

Adolescent↗

Mechanical states encoded by stretch-sensitive neurons in feline joint capsule.

1. The sensitivity of group II joint afferents innervating cat knee joint capsule to in-plane stretch was studied in vitro. Single afferents were recorded from teased filaments of the posterior articular nerve. The capsule was stretched by applying forces through tabs along the edges of the capsule (3 tabs/edge) with the use of an apparatus that allowed for independent control of each load. The relationships between the neural responses of these afferents and the local continuum mechanical state of the joint capsule have been investigated. By appropriately loading the tissue margins, it was possible to establish states of uniaxial and biaxial tension, including shear. 2. Plane stress was calculated from the loads along the tissue margins. Stress at the location of the mechanoreceptor ending was estimated by interpolation. Strain was calculated from deformations of the capsule measured by tracking markers on its surface. Full characterization of tissue stress and strain made it possible to determine strain energy density and the magnitudes of other coordinate invariant mechanical quantities. 3. Individual afferents (n = 15) exhibited pronounced selectivity to the direction of applied stress and strain. There was no overall preferred orientation across neurons, and simple correlation of individual stress or strain components with the neuronal response revealed no consistent relationship between neuronal response and any single tensor component. However, linear multiple regression of the combined stress and strain components with the neuronal response revealed high correlation (mean R = 0.91), indicating that the measured mechanical states strongly determine the neuronal response. There was a much stronger relationship between neuronal response and stress variables than with strain variables. Simple correlation of the first invariant of the stress tensor with neuronal response had the highest mean correlation of the tensor quantities (R = 0.51). On average, strain energy density was only modestly correlated with the neural response (R = 0.28). 4. These findings indicate that capsule mechanoreceptors are encoding the local continuum mechanical state in the joint capsule. The neural response of these mechanoreceptors is more strongly correlated to local stress than to local strain.

Adaptation, Physiological↗