The role of B- and T-cell immunity in toltrazuril-treated C57BL/6 WT, µMT and nude mice experimentally infected with<Emphasis Type="Italic"> Neospora caninum</Emphasis>

Neospora caninum is a protozoan parasite predominantly known for causing abortion in cattle and neuromuscular disease in dogs. So far, no efficient metaphylactic chemotherapy has been developed. In preliminary studies, toltrazuril had been successfully used against experimental neosporosis in mice and calves. In the present study, we used immunocompetent and immunodeficient mouse strains to address the role of immunity in supporting the chemotherapy of experimental N. caninum infection. WT, µMT and athymic nude mice were intraperitoneally inoculated with 1×10⁶ Nc-1 tachyzoites. The drug was administered in the drinking water for 6 consecutive days so as to obtain a daily dose of approximately 20 mg toltrazuril/kg body weight. The course of infection was monitored by clinical, histological and immunohistochemical means, as well as by the search for parasite DNA using PCR-analyses of various organs. In immunocompetent WT mice, treatment proved to be of high efficacy by abrogation of any lesion formation or PCR-positivity in medicated C57BL/6 mice and a significant reduction of lesion formation or PCR-positivity in BALB/c animals. Similarly, treated µMT mice exhibited a significant reduction in cerebral lesion formation as well as in parasite DNA detectability by PCR when compared to untreated animals. Athymic nude mice, however, did not respond to treatment in that only a delay of the parasite dissemination was achieved, and nude mice still showed the neosporosis disease symptoms, although later than untreated animals. We conclude that treatment with toltrazuril appears to act parasitostatically rather than parasitocidically. This is supported by the fact that: (1) although the lack of B-cells did not impair the effect of toltrazuril, (2) the lack of T-cells did not allow for a full efficacy of treatment. Therefore, chemotherapy with toltrazuril against experimental infections with N. caninum requires the support of T-cell immunity in order to be successful.An erratum to this article can be found at     

Colonoscopically placed hemoclips as treatment for massive appendiceal stump bleeding

Massive bleeding from an appendiceal stump is a rare but occasionally seen severe complication. The bleeding may drain into the abdominal cavity, the retroperitoneum, or the digestive tract. Gastrointestinal hemorrhage may occur early or even years after appendectomy. The typical management includes ligation of the bleeding vessel or cecal resection done by either emergency laparotomy or laparoscopy. An alternative treatment option would be an angiographic embolization of the bleeding vessel. We report on a 33-year-old woman with severe lower gastrointestinal hemorrhage 1 day after an apparently uncomplicated appendectomy for acute phlegmonous appendicitis with ligation and invagination of the appendiceal stump. Hemoglobin level dropped to 6.3 g/dl and made blood transfusion necessary. The cause of bleeding was a small intramural branch of the appendiceal artery at the appendiceal stump, which was diagnosed by emergency colonoscopy. The hemorrhage could be controlled endoscopically by placing hemoclips on the distinct vessel in combination with a biological tissue adhesive. The patient recovered thereafter without further intervention. Endoscopic clipping for the treatment of appendiceal stump bleeding is a novel, effective, and safe procedure. Thereby, conventional emergency laparotomy or laparoscopy or angiographic embolization can be avoided.     

Impact of neoadjuvant chemoradiation on anal sphincter function in patients with carcinoma of the midrectum and low rectum

HYPOTHESIS: Preoperative chemoradiation for patients with stage II and III midrectal and low rectal cancer may improve survival and decrease local recurrence rate. We evaluated the long-term impact of neoadjuvant chemoradiation on anal sphincter function. DESIGN: Prospective analysis. SETTING: Tertiary referral center. PATIENTS: From March 1, 1996, to January 31, 2002, 50 patients with midrectal and low rectal cancer who underwent total mesorectal excision were prospectively enrolled. INTERVENTIONS: Patients received either surgical therapy alone (group 1, n = 22) or preoperative, combined chemoradiation (group 2, n = 28). Group 2 was divided into patients with midrectal (group 2A, n = 14) and low rectal (group 2B, n = 14) cancer. Anorectal manometry was performed preoperatively and a median of 384 days postoperatively. MAIN OUTCOME MEASURES: Anal resting pressure, squeeze pressure, anal sphincter vector volumes, length of the high-pressure zone, sensory threshold of the pouch, and rectal capacity. RESULTS: Preoperative manometric values were comparable between the groups. No statistically significant manometric differences occurred in group 1 postoperatively. Mean resting pressure (preoperative and postoperative, respectively: 89 +/- 35 mm Hg, 53 +/- 17 mm Hg), resting vector volume (605 +/- 324 cm( 3), 142 +/- 88 cm(3)), and maximal tolerable volume (144 +/- 29 mL, 82 +/- 44 mL) decreased significantly in chemoradiated patients postoperatively (P<.05). Manometric values of group 2B patients remained stable postoperatively, while mean resting pressure (73 +/- 22 mm Hg vs 52 +/- 14 mm Hg) and resting vector volume (631 +/- 288 cm(3) vs 145 +/- 78 cm(3)) decreased significantly in group 2A patients (P<.001). CONCLUSIONS: Total mesorectal excision does not influence anal sphincter function during long-term follow-up. Neoadjuvant chemoradiation results in disordered anal sphincter function in patients with midrectal cancer. Low and rectoanal anastomosis seems to obtain better anal sphincter function than higher anastomosis in chemoradiated patients.     

Pneumococcal polysaccharide immunization in infants and children.

By using indirect hemagglutination, the antibody responses of normal infants and children to an octavalent pneumococcal vaccine that contained pneumococcal polysaccharide types 1, 3, 6, 7, 14, 18, 19, and 23 were evaluated. By 2 years of age, there was a significant rise in hemagglutination titers to all the polysaccharide types, except type 19. By 6 to 8 months of age, five of the eight types of pneumococcal polysaccharides tested resulted in up to 60% responders and, by 2 years, a significant number responded to all pneumococcal polysaccharide types in the vaccine. Pneumococcal polysaccharide type 3 resulted in a significant antibody response as early as 3 months of age, whereas type 19 never resulted in a significant antibody response. Except for type 3, it seemed that when the other pneumococcal polysaccharides tested produced an antibody response, the degree of resonse did not subsequently change significantly with increasing age. The relationship of antibody response to age for pneumococcal polysaccharides is similar to that found for other polysaccharide vaccines. Based on the results of our study, we would recommend immunization with pneumococcal vaccine at 6 months of age with repeat immunization at 2 years of age, especially in high-risk children.     

Comparison of three colon cleansing methods: evaluation of a randomized clinical trial with 300 ambulatory patients

In a prospective randomized clinical trial, three colon cleansing methods for colonoscopy were compared with regard to a) side effects, b) patient acceptance, c) residual liquid and stool during colonoscopy, and d) quality of the examination. The patients were randomly assigned to one of the following three groups for colon preparation: Group 1 (n = 100) 4 liters of Golytely, group 2 (n = 102) 2 liters of Golytely combined with Cascara-Salax, and group 3 (n = 98) X-Prep (a Senna preparation) combined with an enema. X-Prep (group 3) caused significantly more abdominal cramps than 4 liters of Golytely (group 1) or 2 liters of Golytely with Cascara-Salax (group 2) (p less than 0.001). Vomiting was most frequent in group 1 (p less than 0.05 vs. group 3). The patients therefore preferred X-Prep to 4 liters of Golytely (p less than 0.01). The cleanest colon was obtained with 4 liters of Golytely, while 2 liters of Golytely with Cascara-Salax was least efficacious. The quality of the examination was equal in groups 1 and 3, and clearly better than in group 2 (p less than 0.01). We thus conclude that while 4 liters of Golytely and X-Prep plus enema have equivalent cleansing efficacy for colonoscopy, patients judged X-Prep to be less unpleasant.     

Isolated fractures of the capitate: use of nuclear medicine as an aid to diagnosis

Fractures of the capitate are considered to be uncommon injuries of the wrist, however, delay in diagnosis may result in prolonged disability and avascular necrosis. Two cases are reported in which an isolated fracture of the capitate was diagnosed with a 99mTc-MDP nuclear medicine bone scan and confirmed with CT scan or repeated conventional x-rays. These two cases illustrate that an isolated fracture of the capitate should be considered in an individual presenting with persistent wrist pain of traumatic origin, even when conventional x-ray views are negative. The nuclear medicine bone scan can be a useful investigative tool and serve to guide further radiological investigations.     

Comparative diagnostic value of the calcium-pentagastrin test versus the tolbutamide test in a patient with a somatostatinoma

We describe a patient with a small somatostatinoma of the papilla of Vater without clinical evidence for diabetes mellitus, diarrhea, steatorrhea, or cholelithiasis, showing normal plasma basal levels for somatostatinlike immunoreactivity. The diagnosis was based on histologic and immunohistochemical analysis of tumor tissue and hypersomatostatinemia induced by the calcium-pentagastrin test. Before removal of the tumor both diagnostic tests recommended for the detection of a somatostatinoma, a tolbutamide test and a calcium-pentagastrin test, were performed. Whereas the calcium-pentagastrin test provoked a markedly elevated plasma somatostatin level in association with a depressed plasma neurotensin level, the tolbutamide test surprisingly did not. After removal of the tumor the calcium-pentagastrin test no longer induced hypersomatostatinemia. Further studies are needed to determine whether the calcium-pentagastrin test is a more reliable diagnostic test than the tolbutamide test in somatostatinomas with normal plasma basal levels.