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Sublingual (s.l.) vaccination is an efficient way to induce elevated levels of systemic and mucosal immune responses. To mediate mucosal uptake, ovalbumin (OVA) was genetically fused to adenovirus 2 fiber protein (OVA-Ad2F) to assess whether s.l. immunization was as effective as an alternative route of vaccination. Ad2F-delivered vaccines were efficiently taken up by dendritic cells and migrated mostly to submaxillary gland lymph nodes, which could readily stimulate OVA-specific CD4(+) T cells. OVA-Ad2F + cholera toxin (CT)-immunized mice elicited significantly higher OVA-specific serum IgG, IgA and mucosal IgA antibodies among the tested immunization groups. These were supported by elevated OVA-specific IgG and IgA antibody-forming cells. A mixed T(h)-cell response was induced as evident by the enhanced IL-4, IL-10, IFN-γ and TNF-α-specific cytokine-forming cells. To assess whether this approach can stimulate neutralizing antibodies, immunizations were performed with the protein encumbering the β-trefoil domain of C-terminus heavy chain (Hcβtre) from botulinum neurotoxin A (BoNT/A) as well as when fused to Ad2F. Hcβtre-Ad2F + CT-dosed mice showed the greatest serum IgG, IgA and mucosal IgA titers among the immunization groups. Hcβtre-Ad2F alone also induced elevated antibody production in contrast to Hcβtre alone. Plasma from Hcβtre + CT- and Hcβtre-Ad2F + CT-immunized groups neutralized BoNT/A and protected mice from BoNT/A intoxication. Most importantly, Hcβtre-Ad2F + CT-immunized mice were protected from BoNT/A intoxication relative to Hcβtre + CT-immunized mice, which only showed ∼60% protection. This study shows that s.l. immunization with Ad2F-based vaccines is effective in conferring protective immunity.

Zoonotic transmission of brucellosis often results from exposure to Brucella-infected livestock, feral animals, or wildlife or frequently via consumption of unpasteurized milk products or raw meat. Since natural infection of humans often occurs by the oral route, mucosal vaccination may offer a means to confer protection for both mucosal and systemic tissues. Significant efforts have focused on developing a live brucellosis vaccine, and deletion of the znuA gene involved in zinc transport has been found to attenuate Brucella abortus. A similar mutation has been adapted for Brucella melitensis and tested to determine whether oral administration of ΔznuA B. melitensis can confer protection against nasal B. melitensis challenge. A single oral vaccination with ΔznuA B. melitensis rapidly cleared from mice within 2 weeks and effectively protected mice upon nasal challenge with wild-type B. melitensis 16M. In 83% of the vaccinated mice, no detectable brucellae were found in their spleens, unlike with phosphate-buffered saline (PBS)-dosed mice, and vaccination also enhanced the clearance of brucellae from the lungs. Moreover, vaccinated gamma interferon-deficient (IFN-γ(-/-)) mice also showed protection in both spleens and lungs, albeit protection that was not as effective as in immunocompetent mice. Although IFN-γ, interleukin 17 (IL-17), and IL-22 were stimulated by these live vaccines, only RB51-mediated protection was codependent upon IL-17 in BALB/c mice. These data suggest that oral immunization with the live, attenuated ΔznuA B. melitensis vaccine provides an attractive strategy to protect against inhalational infection with virulent B. melitensis.

Brucella abortus remains a threat to the health and well-being of livestock in states bordering the Greater Yellowstone Area. During the past several years, cohabitation of infected wildlife with cattle has jeopardized the brucellosis-free status of Idaho, USA; Wyoming, USA; and Montana, USA. Current livestock B. abortus vaccines have not proven to be efficacious in bison (Bison bison) or elk (Cervus elaphus nelsoni). One problem with the lack of vaccine efficacy may stem from the failure to understand wildlife immune responses to vaccines. In an attempt to understand their immune responses, bison were vaccinated with eukaryotic DNA expression vectors encoding the Brucella periplasmic protein, bp26, and the chaperone protein, trigger factor (TF). These DNA vaccines have previously been shown to be protective against Brucella infection in mice. Bison were immunized intramuscularly at weeks 0, 2, and 4 with bp26 and TF DNA vaccines plus CpG adjuvant or empty vector (control) plus CpG. Blood samples were collected before vaccination and at 8, 10, and 12 wk after primary vaccination. The results showed that bison immunized with bp26 and TF DNA vaccines developed enhanced antibody, proliferative T cell, and interferon-gamma (IFN-γ) responses upon in vitro restimulation with purified recombinant bp26 or TF antigens, unlike bison immunized with empty vector. Flow cytometric analysis revealed that the percentages of CD4(+) and CD8(+) T lymphocytes from the DNA-vaccinated groups were significantly greater than they were for those bison given empty vector. These data suggest that DNA vaccination of bison may elicit strong cellular immune responses and serve as an alternative for vaccination of bison for brucellosis.

Objective: FloSeal is a thrombin-gelatin hemostatic matrix that is used to obtain hemostasis. There have been isolated case reports of FloSeal causing bowel obstructions, requiring surgical intervention. We report 3 cases of what we believe were FloSeal-induced small bowel obstructions (SBO)., Methods: We present a series of small bowel obstructions after FloSeal use. Our series includes urology, gynecologic oncology, and general surgery cases at the same institution where the product was appropriately used and resulted in the same complication., Results: FloSeal was used for hemostasis in all patients. In each instance, a small bowel obstruction developed in 7 days to 9 days. All patients were reexplored laparoscopically and found to have an intense inflammatory reaction at the site of the FloSeal. The adhesions were lysed and the obstructions resolved., Conclusions: Although further study is needed, the common factor in all these SBOs was a hemostatic agent. In our and others' series, the time to SBO was 7 days to 9 days. If an early postoperative SBO occurs after FloSeal is used, prompt reexploration should be considered.

Background: Immunization with recombinant carboxyl-terminal domain of the heavy chain (Hc domain) of botulinum neurotoxin (BoNT) stimulates protective immunity against native BoNT challenge. Most studies developing a botulism vaccine have focused on the whole Hc; however, since the principal protective epitopes are located within beta-trefoil domain (Hcbetatre), we hypothesize that immunization with the Hcbetatre domain is sufficient to confer protective immunity. In addition, enhancing its uptake subsequent to nasal delivery prompted development of an alternative vaccine strategy, and we hypothesize that the addition of targeting moiety adenovirus 2 fiber protein (Ad2F) may enhance such uptake during vaccination., Results: The Hcbetatre serotype B immunogen was genetically fused to Ad2F (Hcbetatre/B-Ad2F), and its immunogenicity was tested in mice. In combination with the mucosal adjuvant, cholera toxin (CT), enhanced mucosal IgA and serum IgG Ab titers were induced by nasal Hcbetatre-Ad2F relative to Hcbetatre alone; however, similar Ab titers were obtained upon intramuscular immunization. These BoNT/B-specific Abs induced by nasal immunization were generally supported in large part by Th2 cells, as opposed to Hcbetatre-immunized mice that showed more mixed Th1 and Th2 cells. Using a mouse neutralization assay, sera from animals immunized with Hcbetatre and Hcbetatre-Ad2F protected mice against 2.0 LD50., Conclusion: These results demonstrate that Hcbetatre-based immunogens are highly immunogenic, especially when genetically fused to Ad2F, and Ad2F can be exploited as a vaccine delivery platform to the mucosa.

Background and Objectives: As bariatric surgery becomes more widespread, atypical complications will be seen with more frequency. In this case series, we report on 3 cases of superior mesenteric artery syndrome after gastric bypass and the laparoscopic treatment., Methods: This is a case series of 3 patients who presented with the persistent postprandial symptoms of pain and nausea after gastric bypass, and through an extensive workup were eventually diagnosed with superior mesenteric artery syndrome. All 3 patients had dramatic weight loss after laparoscopic Roux-en-y gastric bypasses. Gastric remnant distention was not a consistent finding, but persistent postprandial nausea, epigastric pain, and computed tomographic findings of a narrowed angle between the superior mesenteric artery and the aorta were consistently found. Two patients were treated with a laparoscopic gastroduodenal jejunostomy anastomosis, and one patient had a duodenojejunostomy, all with resolution of their symptoms., Results: A laparoscopic gastroduodenal (or duodeno-) jejunal bypass was performed in each case, which resolved the obstruction caused by the superior mesenteric artery syndrome., Conclusions: Superior mesenteric artery syndrome can be caused by the dramatic weight loss induced by a gastric bypass. This post weight loss surgery phenomenon may be far more prevalent and underdiagnosed than reported, and should be considered in all patients with greater than average weight loss at one year and who have persistent postprandial nausea and epigastric pain. This can be successfully treated by bypassing the obstruction, while maintaining the weight loss induced by the Roux-en-y gastric bypass.

Endothelial progenitor cells are a population of bone marrow-derived mononuclear cells thought to engage in endothelial repair and hence are considered potential therapeutic agents in many pathological conditions. The mechanism of their exit from the bone marrow to the circulation and damaged tissues, termed mobilization, has not been fully elucidated. Despite this, several pharmacological interventions have been shown to influence mobilization of these specialized cells. Here we review the current understanding of their mobilization.

Nonpowder (ball-bearing and pellet) weapons derive their source of energy from compressed air or carbon dioxide. Such weapons are dangerous toys that cause serious injuries and even death to children and adolescents. A retrospective chart review study was undertaken to describe nonpowder gun injuries at a southwestern US urban level I adult and pediatric trauma center. Specific emphasis was placed on intracranial injuries. Over the past 6 years, a total of 29 pediatric and 7 adult patients were identified as having nonpowder firearm injuries. The patient population was overwhelmingly male (89.7%; mean age, 11 years). Overall, 17 out of 29 pediatric patients (56.8%) sustained serious injury. Nine patients (30.0%) required operation, 6 (20.7%) sustained significant morbidity, and there were 2 deaths (6.9%). Injuries to the brain, eye, head, and neck were the most common sites of injury (65.6%). Specific intracranial injuries in 3 pediatric patients are described that resulted in the death of 2 children. We suggest that age warning should be adjusted to 18 years or older for unsupervised use to be considered safe of these potentially lethal weapons., (Copyright 2009 S. Karger AG, Basel.)

Introduction: Peutz-Jeghers is a rare autosomal dominant disorder characterized by hamartomatous polyps and discoloration of mucosal membranes. The polyps can occur anywhere in the gastrointestinal tract and can grow large enough to cause bowel obstructions., Case Report: A 16-year-old male presented to the emergency department with signs and symptoms of an acute bowel obstruction. He had 2 days of abdominal pain, obstipation, and vomiting. He had a previous history of a colonoscopy with polypectomy at age 4, and hyperpigmentation of his mucous membranes., Results: Computed tomographic (CT) scan revealed an intussusception of the small intestine. An exploratory laparoscopy found an intussusception of the mid jejunum. A laparoscopic-assisted small bowel resection was performed. Pathology showed a 5-cm polyp that acted as a lead point for the intussusception. Colonoscopy and upper endoscopy revealed 5 more polyps in the stomach and colon that were removed., Conclusion: Small bowel obstructions can be managed successfully with minimally invasive approaches. The treatment of obstruction in these patients is to remove the offending hamartomatous polyp(s). The rest of the intestine needs to be examined and those polyps found should be removed. This can be done intraoperatively with laparoscopic-assisted enteroscopy and colonoscopy.

Peripheral systolic blood pressure is amplified above central aortic systolic pressure, but the late systolic shoulder of the peripheral pulse may approximate central systolic pressure. Because late systolic pressure also determines the peripheral augmentation index, a measure of pressure wave reflection within the systemic circulation, this implies a direct relationship between amplification and augmentation. We compared the late systolic shoulder of the peripheral pressure waveform with estimates of central systolic pressure obtained using a transfer function in 391 subjects undergoing diagnostic coronary angiography and/or elective angioplasty (30% with insignificant coronary artery disease). In a subset (n=12) we compared the late systolic shoulder of the peripheral pulse with central pressure obtained with a catheter placed in the aortic root. Measurements were made at baseline, during atrial pacing, and during administration of nitroglycerin. Late systolic shoulder pressure closely approximated transfer function estimates of central pressure (R=0.96; P<0.0001; mean difference+/-SD: 0.5+/-5.2 mm Hg). Despite changes in waveform morphology induced by pacing and nitroglycerin (reducing mean values+/-SE of the augmentation index from 76+/-3.8% to 66+/-4.6% and 60+/-3.3%, respectively), there was close agreement between the late systolic shoulder of the peripheral pulse and measured values of central pressure (R=0.96; P<0.001; mean difference: 1.7+/-4.8 mm Hg). In conclusion, the late systolic shoulder of the peripheral pulse closely approximates central systolic pressure and peripheral augmentation index, the ratio of central:peripheral pulse pressure. Interventions to lower augmentation index and peripheral vascular resistance will have multiplicative effects in lowering central blood pressure.

Background and Objectives: The purpose of this study was to determine patient recall and comprehension after laparoscopic appendectomy in an underserved population. Laparoscopic surgery can lead to diagnostic uncertainty secondary to poor recall and variable port placement., Methods: After institutional review board approval, we identified a cohort of patients who underwent laparoscopic appendectomy from 2000 to 2004 at a single institution. We then attempted to contact the patients to conduct a 10-question telephone survey, which determined whether the patient spoke English or Spanish as a primary language, ethnicity, educational level, and questions about recall of perioperative events and diagnoses. If we could not reach the patient, we tried to call back on 2 different occasions., Results: Between 2000 and 2004, 186 patients underwent laparoscopic appendectomy. Of these, 65% were Hispanic. We found that only 17% of these patients returned for a postoperative visit. Only 19.3% could be contacted by phone. Forty-seven percent of the patients contacted by phone spoke Spanish exclusively. Overall 92% of patients contacted knew what operation they had, and gave their correct diagnosis., Conclusions: The low percentage of patients available to follow-up makes this study statistically insignificant. However, we believe that fact in itself is important. In Southwestern states, we see a large migrant population. This highlights the need to communicate effectively with the patients at the time of surgery, which we speculate we did based on the percentage of patients that knew their diagnosis.

Objective: Antiphospholipid antibodies are associated with increased risk of thrombosis, particularly as in antiphospholipid syndrome. This study aims to determine the acute effects of anticardiolipin antibodies on nitric oxide production and vascular function., Methods: Ex vivo aortic rings from male Sprague Dawley rats were incubated with IgG monoclonal anticardiolipin antibody (IS4) or a non-specific IgG control. In organ baths, response to phenylephrine and acetlycholine was determined alone and with nitro-L-arginine methyl ester (L-NAME), 1,400 W, D-arginine, L-arginine, sodium nitroprusside and cardiolipin. In vivo antibodies were injected into anaesthetised, spontaneously breathing male Sprague Dawley rats. Haemodynamic variables and serum nitric oxide were measured. Immunohistochemistry for iNOS and eNOS was performed in kidney vessels., Results: Phenylepherine contraction was decreased in the IS4 group compared to controls (p < 0.001). L-NAME, 1,400 W and cardiolipin, abolished this effect. L-Arginine caused significant relaxation in the IS4 group (p = 0.005). Mean arterial pressure in rats injected with IS4 was reduced compared to IgG and saline controls (p < 0.001). NO in plasma increased significantly after IS4 administration (p < 0.001). Immunohistochemistry showed increased iNOS expression in kidney arteries in the IS4 group, with no change in eNOS., Conclusion: Anticardiolipin antibodies induce NO production acutely via increased expression of iNOS in both ex vivo and in vivo models.

Five hundred fifty-three patients undergoing hip and knee reconstructive procedures in one institution that used a patient management system were compared with a retrospective group of 340 patients undergoing similar procedures in the same institution. All procedures were performed by one surgeon and the same patient management team. Measures of length of stay, discharge disposition, and hospital charges were recorded for all patients in each subgroup of total hip arthroplasty, revision total hip arthroplasty, total knee arthroplasty, revision total knee arthroplasty, unicompartmental knee arthroplasty, and bilateral procedures. The length of stay and hospital charges were reduced significantly in all groups, whereas the percentage of patients discharged to home was unchanged. There was no significant difference in complication rates between the two groups.

The management of a young woman with congenital kyphoscoliosis, who developed symptomatic nocturnal hypoventilation during the third trimester of pregnancy, is described. Nasal intermittent positive pressure ventilation (NIPPV) was safely and effectively used to correct nocturnal hypoxaemia and hypercapnia from the 30th-36th week of gestation, when a healthy boy was delivered by Caesarean section. Following delivery, the mother no longer required NIPPV and returned to her prepregnancy level of activity.

Growing chicks offered diets containing either surfeit or inadequate protein in the day but adequate protein at night adopted a pattern of nocturnal feeding but did not eliminate diurnal meals. Their weight gain surpassed that of corresponding dietary controls who received continuous access to surfeit or inadequate protein but was less than that of chicks with continuous access to a standard diet. Chicks receiving the standard diet at night with no food available in the light phase also grew but did so at a slower rate than the diurnally feeding control group. The shift in feeding patterns was not accompanied by a shift in body temperature, nor was nocturnal antipredator behavior, characterized by sustained motoric inhibition, disrupted by nocturnal feeding. These data demonstrate that feeding specializations which have been selected over a species' evolutionary history are not rigidly fixed but can be modified by the economic relations in the current habitat.