Exploring structure-activity relationships around the phosphomannose isomerase inhibitor AF14049 via combinatorial synthesis

Phosphomannose Isomerase (PMI) has been shown by genetic methods to be an essential enzyme in fungal cell wall biosynthesis. The PMI inhibitor AF14049 was discovered as an unanticipated side product from high-throughput library screening against the enzyme from C, albicans. Solid-phase synthetic methods were developed and a series of libraries and discrete analogs synthesized to explore SAR around AF14049.     

Three-dimensional respiratory-gated MR angiography of coronary arteries: comparison with conventional coronary angiography

OBJECTIVE: MR coronary angiography is most often performed using two-dimensional techniques. Although three-dimensional (3D) acquisitions do have important advantages, they take too long for a single breath-hold and are thus susceptible to respiratory motion artifacts. The purpose of this study was to investigate the accuracy of a unique respiratory-gated 3D MR angiographic technique in identifying the proximal coronary arteries in patients suspected of having coronary artery disease. In addition, we investigated the capability of this technique to detect proximal stenoses. SUBJECTS AND METHODS: We performed a prospective blinded study in 20 patients who were referred for conventional coronary angiography. A cardiac-gated 3D gradient-echo sequence with fat suppression was used. Retrospective respiratory gating was performed using navigator echoes of the diaphragm position. Using multiplanar reformatting, two independent readers blindly analyzed the data sets for visualization of major coronary arteries, lengths of imaged segments, and detection of significant stenoses (> 50% occlusion of the luminal diameter by conventional angiography). RESULTS: Seventy-seven of 80 (96%) coronary arteries were positively identified. In one patient, an anomalous coronary anatomy was readily identified and confirmed by conventional angiography. The average lengths of the imaged segments of the right, left main, left anterior descending, and left circumflex coronary arteries were 58 +/- 13 mm, 9 +/- 5 mm, 59 +/- 16 mm, and 24 +/- 10 mm, respectively. Overall sensitivity for the detection of stenoses was low (38%), with a specificity of 95%. Interobserver agreement was 0.92, with a kappa value of 0.65. CONCLUSION: Respiratory-gated 3D MR angiography allows accurate identification of proximal coronary arteries and may be valuable for 3D imaging of coronary anomalies. Further technical improvements are required to enhance the value of the technique in detecting stenoses.     

Wasp and bee venom allergy

To diagnose insect venom allergy a good patient history is important. Allergological tests (skin test, specific IgE titre) confirm the diagnosis. Patients are advised on preventive measures (e.g. with respect to clothing and use of perfume). They are also instructed on medical treatment (antihistaminics, epinephrine) in case they are stung again. In patients having had a serious systemic reaction immunotherapy should be considered. Immunotherapy leads to complete protection in more than 98% of patients with wasp (yellow jacket) venom allergy and in 75-80% of patients with bee venom allergy. Serious adverse reactions to immunotherapy are rare. Immunotherapy lasts at least 3 to 5 years. After cessation of immunotherapy the frequency of systemic reactions to the sting of a wasp or bee is in the range of 5-15%. There are insufficient data on the long-term effect of immunotherapy.     

Synthesis and pharmacological evaluation of new flosulide analogues, synthesized from natural safrole

OBJECTIVE: To study the effect of adjuvant chemotherapy after curative hepatic resection in patients with hepatocellular carcinoma. DESIGN: A randomized controlled trial. SETTING: A tertiary referral center. PATIENTS: During a 54-month period, 142 patients with hepatocellular carcinoma underwent hepatic resection at 1 institution. Sixty-six patients who survived the operation and had no demonstrable evidence of residual disease on ultrasonographic examination and hepatic angiographic testing at 1 month after surgery agreed to participate in the study. The median follow-up time was 28.3 months. INTERVENTION: Thirty patients received a combination of intravenous epirubicin hydrochloride (8 doses of 40 mg/m2 each at 6-week intervals) and transarterial chemotherapy using an emulsion of iodized oil and cisplatin (3 courses with a maximum dose of 20 mL each at 2-month intervals). Thirty-six patients had no adjuvant treatment. MAIN OUTCOME MEASURES: Recurrence rate and disease-free survival. RESULTS: A total of 138 courses of intravenous epirubicin was given to the 30 patients. Sixty-one courses of transarterial chemotherapy were given to only 29 of the 30 patients assigned to the treatment group, because the hepatic artery in 1 patient was thrombosed. Six patients (20%) had chemotherapy-related complications with no mortality. Twenty-three of 30 patients in the treatment group and 17 of 36 patients in the control group had recurrences (P=.01). Patients who received adjuvant chemotherapy had a higher incidence of extrahepatic metastases (11 patients vs 5 patients; P=.03). The respective disease-free survival rates at 1, 2, and 3 years were 50%,36%, and 18% for the treatment group and 69%, 53%, and 48% for the control group (P=.04). CONCLUSION: In a group of patients who underwent curative resection of hepatocellular carcinoma, postoperative adjuvant chemotherapy using the present regimen was associated with more frequent extrahepatic recurrences and a worse outcome.     

Cellulitis--an unreported complication of long-term SCI patients

Teaching portfolios are stimulating much discussion as more comprehensive approaches to evaluating teaching are sought. Portfolios can be used effectively for both formative and summative evaluative purposes. The content of a portfolio may vary greatly, but commonly includes material that reflects student learning, evaluative materials, and a personal statement on the faculty's philosophy of education. Professional growth often accompanies developing a personal teaching portfolio.