Safety and dose relationship of recombinant human activated protein C for coagulopathy in severe sepsis.

OBJECTIVES: To assess the safety and effect on coagulopathy of a range of doses of recombinant human activated protein C (rhAPC). To determine an effective dose and duration of rhAPC for use in future clinical trials. DESIGN: Double-blind, randomized, placebo-controlled, multicenter, dose-ranging (sequential), phase II clinical trial. SETTING: Forty community or academic medical institutions in United States and Canada. PATIENTS: One hundred thirty-one adult patients with severe sepsis. INTERVENTIONS: Intravenous infusion of rhAPC (12, 18, 24, or 30 microg/kg/hr) or placebo for 48 or 96 hrs. MEASUREMENTS AND MAIN RESULTS: No significant differences in incidence of serious bleeding events (4% rhAPC, 5% placebo, p >.999) or incidence of serious adverse events (39% rhAPC, 46% placebo, p = 0.422) between rhAPC- and placebo-treated patients were observed. One of 53 rhAPC-treated patients with suitable immunogenicity samples had a low level, transient, non-neutralizing anti-APC antibody response not associated with any clinical adverse event. Significant dose-dependent decreases in both D-dimer (p <0.001) and end of infusion interleukin 6 levels (p =.021) were demonstrated. No statistically significant effects on fibrinogen or platelet counts were observed. A nonstatistically significant 15% relative risk reduction in 28-day all-cause mortality was observed between rhAPC- and placebo-treated patients. CONCLUSIONS: rhAPC was safe and well-tolerated and demonstrated a dose-dependent reduction in D-dimer and interleukin 6 levels relative to placebo. The dose of 24 microg/kg/hr for 96 hrs was selected for use in future clinical studies.

The great imitator: miliary peritoneal tuberculosis mimicking stage III ovarian carcinoma.

PURPOSE: To report a case of peritoneal tuberculosis initially mistaken at the time of surgery for metastatic ovarian carcinoma. CASE REPORT: A 31-year-old Filipino female was found to have increasing abdominal pain, ascites, early satiety, increasing abdominal girth and bilateral complex masses. Diagnostic laparoscopy revealed the presence of > 4 liters of ascites, a frozen pelvis secondary to what appeared to be bilateral ovarian carcinomas, along with miliary seeding of the entire anterior abdominal wall, omentum, small bowel and small bowel mesentery, right and left diaphragmatic surfaces, and hepatic surface. Frozen section, at the time of laparotomy, revealed necrotizing granulomas most consistent with disseminated tuberculosis that was confirmed at the time of final pathologic review and culture. CONCLUSION: Peritoneal tuberculosis can be mistaken for widely metastatic ovarian carcinoma at time of surgery.

Right pulmonary artery occlusion secondary to a dissecting aortic aneurysm.

This report describes a case of right pulmonary artery obstruction caused by a dissecting aneurysm of the thoracic aorta. Initial ventilation-perfusion (V/Q) scan revealed no perfusion to the right lung. Lack of right lung perfusion plus other clinical abnormalities led to an initial diagnosis of massive embolism in the right lung. Bilateral pulmonary arteriography of the thoracic and abdominal aorta revealed extrinsic compression of the right pulmonary artery near its origin and the suggestion of an ascending aortic dissection. Subsequent ascending aortography and computed tomography (CT) confirmed a dissection of the ascending aorta. Aortography in the true lumen of the aorta revealed trivial aortic insufficiency. These diagnostic procedures confirmed the presence of an acute dissecting aneurysm of the ascending aorta that caused compression of the right pulmonary artery. The finding of a massive unilateral segmental defect with normal ventilation upon lung scanning does not always ensure a diagnosis of acute pulmonary embolus. Patient presentation with massive unilateral perfusion defect merits further evaluation with pulmonary arteriography.

Effect of supplemental oxygen on cardiopulmonary changes during gastrointestinal endoscopy.

This prospective study evaluated supplemental oxygen as an effective means of preventing hypoxemia and electrocardiographic changes in sedated patients undergoing endoscopic procedures. Ninety-five patients with documented ischemic heart disease and 106 patients without heart or lung disease were studied. Patients within each group received either supplemental oxygen (2 L/minute) via nasal cannula or room air. Hypoxemia (oxygen saturation below 90%) and ST-segment deviations occurred in cardiac and control groups. The combination of midazolam and meperidine significantly increased the risk for hypoxemia as compared to midazolam alone (44% versus 8%). Supplemental oxygen significantly decreased, but did not entirely prevent, hypoxemia in cardiac and control groups. The incidence of ST-segment deviation in cardiac patients who were hypoxic was significantly lower in the group receiving oxygen (p = .0015). Supplemental oxygen did not affect the incidence of arrhythmias. Prophylactic supplemental oxygen should be administered to patients with ischemic heart disease who undergo conscious sedation for upper and lower gastrointestinal endoscopic procedures.

Association of recurrent chlamydial infection with gonorrhea.

To determine whether concurrent gonorrhea reactivates latent chlamydial infection, we studied 74 recurrent chlamydial infections and the effect of concurrent gonorrhea at the recurrent episode on the chlamydial serovar identified. Serotyping of 74 recurrent pairs of chlamydial isolates from patients attending a sexually transmitted diseases clinic indicated that 47.1% (16 of 34) with gonorrhea at the time of recurrence harbored chlamydiae of the same serovar as at the initial infection, while only 22.5% (9 of 40) without gonorrhea had the same serovar (P = .03). The proportion of recurrences by the same serovar in the group without gonorrhea did not differ from the proportion predicted by a random exposure model (22.2% vs. 18.4%, P = .46), while the proportion in the gonorrhea group did (47.1% vs. 19.8%, P less than .0001). The possibility of reinfection did not appear more likely in the group with gonorrhea than in the group without. These observations support the hypothesis that concurrent gonorrhea can reactivate latent chlamydial infection.

Pinworm infestation of the genital tract.

Extraintestinal enterobiasis has been reported in the vagina, endometrium, myometrium, ovary, fallopian tube and pelvic peritoneum. Gravid female pinworms may migrate from the perianal area to the vagina, ascend through the genital tract and exit through the fallopian tube to the peritoneum. Ectopic enterobiasis seldom causes clinical symptoms, but chronic granuloma formation may simulate other mass lesions in the pelvis.

Chlamydial infections.

Chlamydia trachomatis infection is the most prevalent sexually transmitted disease in developed countries today. It produces a number of oculogenital syndromes in adults as well as conjunctivitis and pneumonitis in infants. However, the most important sequelae are infertility, ectopic pregnancy, and chronic pelvic pain in women. Available diagnostic tests including culture are less than 100% sensitive but may be of considerable value in detecting asymptomatically infected individuals. Antichlamydial therapy is usually effective and should be given empirically to individuals whose presentation places them at high risk for infection.