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Locally advanced small-bowel adenocarcinoma missed primarily by capsule endoscopy but diagnosed by push enteroscopy.

Wireless-capsule-endoscopy is a new painless method that is able both to visualize the entire small bowel and to detect even small lesions. We report here the case of a patient in whom a locally advanced small-bowel adenocarcinoma was initially missed on capsule endoscopy, but was diagnosed by subsequent push enteroscopy. Capsule endoscopy was carried out in a 47-year-old patient with a history of obscure gastrointestinal bleeding, iron-deficiency anemia, and a lack of symptoms suggestive of stenosis. The capsule imaging revealed angiodysplasias in the jejunum, but no other abnormalities. Push enteroscopy was carried out to allow argon plasma coagulation treatment of the angiodysplasias that had been detected; it revealed a polypoid tumor 20 mm in diameter at 150 cm from the incisors, with the capsule endoscope still located proximal to the tumor and with its optical dome turned towards the push enteroscope. Clinical staging and subsequent surgical resection showed a locally advanced adenocarcinoma (pT4, pN0 (0/7), pMx, G3).[nl]Small-bowel tumors within the reach of push enteroscopy may be missed by capsule endoscopy. Although wireless capsule endoscopy is a major advance in the investigation of the small bowel, well-designed clinical studies still need to define the precise algorithm for diagnostic work-up of suspected small-bowel diseases.

Adenocarcinoma↗

Diagnostic yield of wireless capsule enteroscopy in comparison with computed tomography enteroclysis.

BACKGROUND AND STUDY AIMS: It is still difficult to visualize changes in the small intestine. Wireless capsule enteroscopy is a new method that promises to provide new insights into the small intestine. In a prospective study, the diagnostic yield of wireless enteroscopy was therefore compared with computed tomography (CT) enteroclysis. PATIENTS AND METHODS: Twenty-two patients with suspected small-bowel pathology underwent CT enteroclysis and wireless capsule enteroscopy examinations, conducted by two independent blinded investigators. The results of the two investigations (diagnoses and the number, extent, and location of lesions detected) were compared by a third investigator. RESULTS: The patients included in the study had obscure gastrointestinal bleeding (n = 8), Crohn's disease (n = 8), unexplained diarrhea (n = 5), or suspected carcinoid tumor (n = 1). Pathological lesions were detected using capsule enteroscopy in 13 patients (59 %) and using CT enteroclysis in eight (36 %; P = 0.12). In seven patients (one case each of colonic Crohn's disease, diverticulitis, Meckel's diverticulum, carcinoid tumor, mesothelioma, colonic polyps, and irritable bowel syndrome), no pathological changes were found in the small intestine using either method. The diagnosis was established by wireless capsule enteroscopy in four patients with obscure bleeding, whereas CT enteroclysis was positive in only one patient ( P = 0.1). Crohn's disease was found in two patients with unexplained diarrhea. Small-bowel lesions were identified in six patients with known Crohn's disease using capsule enteroscopy or CT enteroclysis. The only side effect of wireless capsule enteroscopy observed was abdominal pain in one patient with Crohn's disease. There were no serious side effects with CT enteroclysis. CONCLUSIONS: Wireless capsule enteroscopy detects more small-bowel lesions than CT enteroclysis in patients with obscure gastrointestinal bleeding and Crohn's disease.

Adolescent↗

Effects of capsule endoscopy on cardiac pacemakers.

BACKGROUND AND STUDY AIMS: Capsule endoscopy is a new, noninvasive diagnostic technique which enables visualization of the mucosa of the small intestine in physiological conditions and without the need to subject the patient to external radiation. Wireless capsule video endoscopy is contraindicated in patients with a cardiac pacemaker. However, on the basis of the characteristics of the radiofrequency band used by the endoscopic capsule, together with a series of other factors, it is possible that the patient's use of a pacemaker should not be a contraindication to capsule endoscopy. PATIENTS AND METHODS: This work had two phases: an in vitro study, using an interference detector, and an in vivo study involving 20 patients with cardiac pacemakers who showed symptoms or signs that justified a capsule endoscopy investigation. RESULTS: No interference was observed during the first, in vitro, phase of the study. In the second phase, patients wore a Holter recorder for a mean time of 10 hours, during which the average number of recorded QRS complexes exceeded 30,000. All the pacemakers functioned normally. Interference due only to myopotentials was detected in a single patient in whom modification of the pacemaker programming was necessary. In the other 19 patients, neither sensing nor stimulation failures were observed. CONCLUSIONS: No interference between the pacemaker and the endoscopic capsule was observed. All the pacemakers functioned normally, and no increased incidence of adverse effects was observed. Neither was any pacemaker-induced interference observed on the capsule endoscopy images.

Aged↗

Esophageal capsule endoscopy versus esophagogastroduodenoscopy for evaluating portal hypertension: a prospective comparative study of performance and tolerance.

BACKGROUND AND STUDY AIMS: Esophagogastroduodenoscopy (EGD) is the most effective method for examining the upper gastrointestinal tract, and particularly for evaluating portal hypertension in cirrhotic patients, especially for screening purposes. The aim of this study was to assess the feasibility, safety, accuracy, and tolerance of PillCam ESO capsule endoscopy for this indication. PATIENTS AND METHODS: In this prospective study, unsedated EGD and capsule endoscopy examinations were conducted on the same day in cirrhotic patients at the time of diagnosis. The patients quantified the tolerability (relative to pain, nausea, choking sensations, etc.) of the two procedures using a 100-mm visual analogue scale. The time required for the recording and for diagnosis with the capsule examination were documented, as were the patients' preferences in comparison with EGD. Two independent endoscopists blinded to the EGD diagnoses assessed the diagnostic accuracy of the images obtained. RESULTS: Twenty-one patients were included in the study (mean age 62, mean Model for End-Stage Liver Disease score 10.5, mean Child-Pugh score 7.3). The procedure was safe. One patient was unable to swallow the capsule. The mean recording time was 213 s (range 6 - 1200 s); the procedure accurately assessed the presence or absence of esophageal varices in 16 of 19 patients (84.2 %); and it correctly indicated a need for primary prophylaxis (esophageal varices of grade 2 or more and/or red signs) in 100 % of cases. The tolerability of the capsule endoscopy examination was significantly better, and all of the patients preferred capsule endoscopy to EGD (which was transnasal in 11 patients). CONCLUSIONS: Capsule endoscopy was feasible, safe, accurate, highly acceptable, and preferred by cirrhotic patients undergoing screening for portal hypertension. This new technique requires further and more extensive evaluation, as well as assessment of its cost-effectiveness.

Aged↗

Diffusion exchange NMR spectroscopic study of dextran exchange through polyelectrolyte multilayer capsules.

Diffusion exchange of dextran with molecular weights 4.4 and 77 kDa through polyelectrolyte multilayer (PEM) hollow capsules consisting of four bilayers of polystyrene sulfonate/polydiallyldimethylammonium chloride has been investigated using two-dimensional nuclear-magnetic-resonance methods: diffusion-diffusion exchange spectroscopy (DEXSY) and diffusion-relaxation correlation spectroscopy (DRCOSY). Results obtained in DRCOSY experiments show that the diffusion process of dextran 77 kDa exhibits an observation time dependence suggesting a diffusion behavior restricted by confinement. We find evidence for both single capsule and capsule aggregate states, with a partitioning of the 77-kDa dextran between the free and capsule states much larger than that suggested by volume fraction alone. Results from DEXSY experiments show that dextran 77 kDa is in diffusive exchange through the capsules with an exchange time of around 1 s. In contrast, the capsules have no detectable influence on the diffusion process of the dextran 4.4 kDa. This quantitative information may be used in designing PEM capsules as drug carriers.

Journal Article↗

Demonstration of the sustained anthelmintic efficacy of a controlled-release capsule formulation of ivermectin in weaner lambs under field conditions in New Zealand.

Ten field trials were conducted in the North and South Islands of New Zealand to evaluate the anthelmintic efficacy and production responses attributable to treatment of weaner lambs with an intra-ruminal controlled-release capsule formulation of ivermectin. A total of 800 Coopworth, Perendale and Romney lambs weighing on average 20.8-34.8 kg were used. Lambs were either untreated or treated shortly after weaning with an ivermectin controlled-release capsule which delivers ivermectin at 0.8 mg per day for 100 days (minimum dose rate 20 microg/kg/day). Bodyweights, faecal nematode egg counts and dag scores (assessment of faecal soiling in the breech area) were determined before treatment and at about 4,8, 12, 14 and 16 weeks after treatment. Sheep treated with the Ivermectin capsule gained significantly more weight (11.6 kg) over the 16 weeks of the trials compared to untreated sheep (7.3 kg) (p < 0.01). Before treatment, faecal strongylid and Nematodirus spp. egg counts were equivalent (p > 0.10) but, at each time point thereafter, egg counts in ivermectin capsule-treated sheep were significantly lower (p < 0.01 or p < 0.05). Dag scores were not different at the start of the trial (p > 0.10), but at the end of the trial control sheep had significantly greater dags (p < 0.05) than sheep treated with the ivermectin capsule. These findings indicate that treated animals contributed significantly fewer nematode eggs to the contamination of pasture and therefore pasture contamination should be significantly reduced for at least 112 days. The productivity of the ivermectin capsule-treated sheep over the I6 weeks of the trials was also significantly increased compared to salvage-treated controls. Furthermore, the presence of dags, which predispose sheep to blowfly strike in the breech area and result in production losses due to the costs of dagging and downgrading of breech wool, were also significantly (p < 0.05) reduced in the ivermectin capsule-treated sheep.

Journal Article↗

Ruffini mechanoreceptors in isolated joint capsule: responses correlated with strain energy density.

Mechanoreceptive afferents innervating the posterior capsule of the cat knee joint were recorded in a preparation of isolated capsule. The purpose of the experiments was to identify mechanical states in the capsule that were associated with afferent discharge. The capsule was excised from the knee with its bone attachments intact, so that the geometry of the capsule could be reproduced in vitro. The capsule was deformed, and measurements were made of stresses and strains in the plane of the capsule. Afferent discharge was correlated with each of the components of plane stress, plane strain, and strain energy density (SED). SED, the stored elastic energy at the receptor location, was the only mechanical variable that was consistently positively correlated with afferent discharge. A model of the Ruffini-type receptor is presented that accounts for the sensitivity to SED.

Afferent Pathways↗

Simultaneous production of two capsular polysaccharides by pneumococcus. II. The genetic and biochemical bases of binary capsulation.

Study of the capsular genome of pneumococcus has shown that it controls a multiplicity of biochemical reactions essential to the synthesis of capsular polysaccharide. Mutation affecting any one of several biochemical reactions concerned with capsular synthesis may result in loss of capsulation without alteration of other biochemical functions similarly concerned. Mutations affecting the synthesis of uronic acids are an important cause of loss of capsulation and of virulence by strains of pneumococcus Type I and Type III. The capsular genome appears to have a specific location in the total genome of the cell, this locus being occupied by the capsular genome of whatever capsular type is expressed by the cell. Transformation of capsulated or of non-capsulated pneumococci to heterologous capsular type results probably from a genetic exchange followed by the development of a new biosynthetic pathway in the transformed cell. The new capsular genome is transferred to the transformed cell as a single particle of DNA. Binary capsulation results from the simultaneous presence within the pneumococcal cell of two capsular genomes, one mutated, the other normal. Interaction between the biochemical pathways controlled by the two capsular genomes leads to augmentation of the phenotypic expression of the product controlled by one and to partial suppression of the product determined by the other. Knowledge of the biochemical basis of binary capsulation can be used to indicate the presence of uronic acid in the capsular polysaccharide of a pneurnococcal type the composition of the capsule of which is unknown.

Mutation↗

Collagen coatings reduce the incidence of capsule contracture around soft silicone rubber implants in animals.

Silicone rubber miniprostheses known to be associated with a high rate of experimental capsule contracture were implanted subcutaneously in rats. Prostheses were coated either with 2 layers of collagen cross-linked with formaldehyde or with 1 layer of collagen cross-linked with glutaraldehyde. Noncoated prostheses were implanted as controls. Contracture was defined as grossly observable distortion of the implant mounds from round to avoid. Capsules were examined histologically at explant at 255 days. In the control group with no coating present capsules formed very early in 100% of the implants. The group with a 2-layer, formaldehyde-treated collagen coat demonstrated the greatest total surface area covered with coating, the least degree of capsule formation, the lowest rate of contracture (7%), and the longest onset. The group with a single layer of collagen treated with glutaraldehyde showed an intermediate coverage of coating, an intermediate degree of capsule formation, an intermediate contracture rate (50%), and an intermediate time of onset. These observations confirm earlier results by showing a correlation between intact collagen coating and absence of capsule formation, and also further demonstrate a significant reduction in the rate of capsule contracture for collagen-coated implants.

Animals↗

The effects of radiation therapy on the tissue capsule of soft tissue implants.

A prosthesis has been developed for cosmesis after lumpectomy surgery for breast carcinoma. The device is saline filled and percutaneously adjustable in volume to permit an optimal cosmetic result after surgical wound healing. A series of 24 studies of 18 weeks' duration using the adult rabbit animal model were first used to study tissue capsule formation around textured versus smooth surface control implants and to evaluate the effects of volume adjustments on the tissue capsule. Single or multiple adjustments of implant volume had no effect on tissue capsule thickness or morphology. Because lumpectomy surgery is invariably followed by radiation therapy, a series of six studies was then conducted to determine the effects of a typical course of radiation therapy on tissue capsule formation. One week after device implantation, a 4 x 4 cm field including the implant was irradiated with 5,000 rad (200 rad/day x 5 days/week x 5 weeks). The animals were maintained for a 6 week period after radiation treatment. After sacrifice, the implants were removed, and the tissue capsules studied using conventional histologic techniques, including scanning and transmission electron microscopy. There was no statistically significant difference in tissue capsule thickness compared to nonirradiated controls. Tissue capsule morphology, however, differed markedly. Radiation therapy decreased angiogenesis, cellularity, and the inflammatory cell response to the implants. Qualitatively, radiation treatment seemingly improved rather than compromised the connective tissue response to the implants.

Animals↗

Computed tomography of the hip joint capsule.

In 95% of cases, computed tomography (CT) enables the articular capsule of the hip joint to be directly visualized. Articular effusion in the hip joint can also be recognized in the CT image. In inflammatory arthritis and active osteoarthrosis of the hip joint, thickening of the articular capsule or articular effusion appears in the CT image. In addition, "undulation" of the articular capsule sometimes occurs. However, we have also observed this wavy configuration of the hip joint capsule in discrete latent osteoarthrosis of the hip joint. It is, therefore, unequivocally indicative of disease only when seen in association with articular effusion or thickening of the capsule. Focal fatty accumulation of the capsule distinguished from articular capsule tissue by its low density.

Arthritis↗

Nifedipine-retard versus nifedipine-capsules for the therapy of hypertensive crisis in black patients.

In a randomized parallel-group placebo-controlled study, we compared the short-term hypotensive efficacy and the safety of a single administration of nifedipine-retard (20-mg tablets) with that of two administrations 6 h apart of nifedipine capsules (10 mg) in 10 and 11 black patients, respectively, with acute severe hypertension. Both groups had similar pretreatment blood-pressure (BP) values. Blood pressure was recorded at 10-min intervals for 12 h by using an automated device. In the first 3 h of treatment, nifedipine capsules induced a faster and greater hypotensive effect than nifedipine retard, which was associated with an increase in heart rate. At 2 h after treatment, nifedipine capsules decreased BP to levels (159 +/- 5/105 +/- 3 mm Hg) that were significantly lower than those reached by nifedipine-retard (175 +/- 4/118 +/- 4 mm Hg; p < 0.05). Both preparations induced a similar maximal BP decrease of approximately 30% of the placebo values, but the peak decrease of BP occurred significantly later with nifedipine-retard (283 +/- 31 min after administration) than with nifedipine capsules (100 +/- 14 min; p < 0.01). Four hours after administration, the hypotensive effect of nifedipine capsules was blunted, and a second administration was necessary, whereas nifedipine-retard reduced BP slowly and continuously for < or =12 h and more smoothly. Flush and headache were more frequently found with nifedipine capsules. We conclude that in black patients with hypertensive crisis, nifedipine capsules produce an abrupt decrease in BP that may be potentially harmful. Thus for patients suitable for treatment with nifedipine, nifedipine-retard is preferable because it effectively reduces BP for > or =12 h while achieving a rapid enough effect without critical short-term decreases in BP.

Administration, Oral↗

The influence of time on human breast capsule histology: smooth and textured silicone-surfaced implants.

Although the histology of capsular tissue is well described in the literature, most studies in humans do not correlate histologic findings with implant age (number of years an implant was in place before sampling). As such, questions regarding the long-term histology in humans remain. The microanatomy of 93 human periprosthetic capsular tissues surrounding 22 textured and 71 smooth silicone-surfaced prostheses was studied. The implants were divided into two groups according to the time between implantation and capsulectomy: between 0 and 5 years or more than 5 years. Hematoxylin and eosin and Masson trichrome-stained sections were analyzed by light microscopy, with and without polarization. Eighteen of the textured implants contained silicone gel and four contained saline. Sixty of the smooth implants contained silicone gel, eight contained saline, and in three, the filler type was not known. For the majority of patients, surgery was performed for augmentation mammaplasty, and the implants were removed because of capsular contracture. The following histologic features were assessed: synovial-like metaplasia, villous hyperplasia, density of the collagenous capsule, alignment of collagen fibers within the capsule, and the presence of foreign material and of a foreign body reaction. The following trends were observed. In smooth implants, increasing implant duration was associated with a decrease in the presence of synovial-like metaplasia (p = 0.003) and villous hyperplasia; there was no significant difference in the presence of a dense collagenous capsule, the orientation of collagen fibers, or the presence of a foreign body reaction. An increase was observed in the presence of foreign material (p = 0.01). In textured implants, increasing implant duration was associated with a decrease in the presence of synovial-like metaplasia, villous hyperplasia (p = 0.003), dense collagenous architecture, and parallel orientation of collagen fibers (p = 0.017). An increase in the presence of a foreign body type reaction and foreign material (p = 0.024) was observed. In comparing textured and smooth-surfaced implants, synovial-like metaplasia was observed more often in the textured group, both at 0 to 5 years (p = 0.01) and at greater than 5 years (p < 0.01). Textured implants more often had villous hyperplasia at 0 to 5 years (p = 0.03) but not beyond 5 years. Smooth implants more often had a dense collagenous capsule than textured implants after 5 years. No significant difference was seen in the orientation of collagen fibers in capsules around smooth and textured implants at 0 to 5 years. After 5 years, the incidence of capsules with collagen fibers arranged parallel to the implant surface was significantly greater in the smooth group than in the textured group (p = 0.01). The presence of a foreign body type reaction was seen more often in the textured group between 0 and 5 years (p = 0.01) and at greater than 5 years (p < 0.01), and the presence of foreign material was more often seen in the textured group between 0 and 5 years (p = 0.06) and at greater than 5 years (p < 0.01). In summary, the cytologic changes around implants seem to be dynamic in nature, and implantation duration and shell type play a significant role. Synovial-like metaplasia, villous hyperplasia, and foreign material were more often observed in the textured group within the 0 to 5 year interval. Beyond 5 years, synovial-like metaplasia, a foreign body type reaction, and foreign material were more often observed in the textured group. Differences in the density of collagenous capsules were not significant at any time point, and collagen fibers oriented parallel to the implant surface were more often observed in the smooth group after 5 years. The significance of these findings awaits further investigation.

Breast Implantation↗

Evaluation of a modified piezoresistive technique and a water-capsule technique for direct and continuous measurement of intra-abdominal pressure in a porcine model.

OBJECTIVE: Intravesical pressure measurement is considered to be the gold standard for the assessment of intra-abdominal pressure. However, this method is indirect and depends on a physiologic bladder function. We evaluated a modified piezoresistive technique and a water-capsule technique for direct and continuous intra-abdominal pressure measurement. DESIGN: Experimental study. SETTING: Animal research laboratory. SUBJECTS: Eleven male domestic pigs. INTERVENTIONS: In anesthetized and mechanically ventilated animals, CO2 was insufflated to stepwise increase the intra-abdominal pressure to 30 mm Hg. Pressure was then held constant for 9 hrs followed by decompression. Piezoresistive measurement and water-capsule measurement probes were placed intra-abdominally. MEASUREMENTS AND MAIN RESULTS: Readings of intravesical pressure measurement, piezoresistive measurement, and water-capsule measurement were taken hourly. Mean difference to insufflator readings, confidence intervals, and limits of agreement were calculated. Differences between applied pressure and intra-abdominal pressure readings were assessed using a two-factor analysis of variance. No significant differences between methods could be observed. During stepwise pressure increase, limits of agreements were -3.6 to 3.6 mm Hg. Confidence intervals were -3.4 to 3.5 (intravesical pressure measurement), -1.6 to 1.5 (piezoresistive measurement), and 0.5 to 2.9 mm Hg (water-capsule measurement). In the presence of constantly elevated intra-abdominal pressure, limits of agreement ranged from -8.2 to +8.2 mm Hg. Confidence intervals were -0.4 to 6.2 (intravesical pressure measurement), -0.2 to 2.7 (piezoresistive measurement), and 1.1 to 5.1 mm Hg (water-capsule measurement). CONCLUSIONS: Both piezoresistive measurement and water-capsule measurement had smaller confidence intervals than intravesical pressure measurement, indicating higher precision, whereas water-capsule measurement had a significant offset. Piezoresistive measurement could be the most suitable device for continuous direct intra-abdominal pressure monitoring in specific patients.

Abdomen↗

Influence of patient selection on the outcome of capsule endoscopy in patients with chronic gastrointestinal bleeding.

BACKGROUND: In chronic gastrointestinal bleeding, success rates in the range of 48% to 76% have been reported for diagnosing clear bleeding sources using capsule endoscopy. The influence of patient selection on the numbers of positive findings yielded by capsule endoscopy is as yet unclear. METHODS: From April 2001 to June 2003, capsule endoscopy was carried out in 74 of a total of 127 patients (58%) who presented for capsule endoscopy with a high suspicion of gastrointestinal bleeding in the small-bowel region. Seventy of the 74 patients were included in the analysis. This group of patients was divided into a study group (32 patients) and a post-study group (38 patients), and the two groups were compared. RESULTS: Stricter patient selection was carried out in the study group than in the post-study group: 49% of those in the study group underwent capsule endoscopy, compared with 65% of those in the post-study group. The overall success rate for detecting relevant bleeding sources was 54%; in the study group, the rate was 66%; whereas in the post-study group, it was only 45%. Significant differences observed between the two groups of patients included the lowest hemoglobin value (5.9+/-1.4 g/dL in the study group, compared with 7.7+/-2.1 g/dL in the post-study group) and transfusion requirements (a median of 10 units in the study group, vs. 2 units in the post-study group). None of the patients who had a minimum hemoglobin value >or=10 g/dL had a positive capsule result. CONCLUSIONS: Patient selection has a considerable influence on the success rate of capsule endoscopy. In patients with chronic gastrointestinal bleeding, the minimum hemoglobin value and transfusion requirements appear to be the decisive parameters.

Adolescent↗

The accuracy of an endoscopy nurse in interpreting capsule endoscopy.

OBJECTIVE: The average physician time required to view a wireless capsule endoscopy study at our institution is 50 min. It is unknown whether a nurse could preview the capsule endoscopy video and accurately detect all significant lesions. If so, it may allow the physician to review only the predetected abnormalities and thereby greatly reduce physician reading time. Our aim was to evaluate whether a nurse can accurately detect lesions on capsule endoscopy. METHODS: An endoscopy nurse who was trained to read capsule endoscopy reviewed 20 consecutive capsule endoscopy studies and recorded all findings. The same studies were viewed independently by a gastroenterologist. The two sets of recorded findings were reviewed, and a comparison of the accuracy in detecting landmarks and clinically significant lesions was made. RESULTS: The nurse missed two of 27 significant lesions seen by the gastroenterologist (93% sensitivity, 95% CI = 74-99%), and the gastroenterologist missed three seen by the nurse. The nurse accurately recorded gastric emptying time and time of passage through the ileocecal valve to within 1 min of the times recorded by the gastroenterologist in 18 of 20 patients (90% agreement, 95% CI = 67-98%). CONCLUSIONS: In this study, the endoscopy nurse detected 93% of the clinically significant lesions seen by the gastroenterologist. The clinical implication of this is that a physician extender could preread capsule endoscopies, allowing the gastroenterologist to view only the demarcated abnormalities. This could improve the cost effectiveness of capsule endoscopy and lead to wider physician acceptance of the test.

Clinical Competence↗

Influence of oxidation state on iron binding by Bacillus licheniformis capsule.

We examined ferric (Fe3+) and ferrous (Fe2+) iron binding by the anionic gamma-glutamyl capsule polymer of Bacillus licheniformis ATCC 9945. The addition of FeCl3 to B. licheniformis capsule under aerobic conditions resulted in flocculation due to the capsule-induced formation of amorphous, rust-colored ferrihydrite. Significant binding of iron, which could be attributed to binding by both the anionic capsule and the ferrihydrite precipitate, occurred. In contrast, the addition of FeCl2 to B. licheniformis capsule under anaerobic conditions resulted in significantly less iron being bound and no color change or flocculation occurring. Capsule-bound ferric iron could be partially released upon addition of several reducing agents. From these observations, it can be concluded that the oxidation state of iron significantly influences its tendency to be bound by anionic bacterial polymers such as capsules.

Bacillus↗

Participation of complement in host defense against capsule-deficient Haemophilus influenzae.

To investigate the role of complement in immunity to capsule-deficient Haemophilus influenzae, rats were depleted of C3 with cobra venom factor and challenged with three different strains of capsule-deficient H. influenzae. Two of them (Rd and U1) did not elaborate type b capsular antigen, whereas the other (S2) elaborated 0.16% of the amount made by its type b parent strain. Depletion of C3 significantly enhanced early intravascular bacterial survival after intravenous inoculation and strikingly increased the susceptibility of rats to infection with capsule-deficient H. influenzae. After intraperitoneal inoculation with strain Rd or U1, C3-depleted rats developed bacteremia, whereas control rats did not; challenge with strain S2 resulted in transient bacteremia in normal rats and in death in C3-depleted animals. To determine whether the greater virulence of strain S2, as compared with strain Rd or U1, was accounted for by the small amounts of capsular antigen it elaborated, we also compared its relative virulence to that of three genetically closely related capsule-deficient variants elaborating either small amounts of type b capsule or producing no detectable b antigen. No difference in virulence was observed among these four variants; all C3-depleted rats inoculated developed bacteremia of similar magnitude followed by similar mortality rates. These studies demonstrate a significant role for complement in host defense mechanisms against capsule-deficient H. influenzae and suggest that interstrain differences of virulence are not attributable to residual elaboration of small amounts of type b capsule.

Animals↗