Synthesis, conformational analysis, and cytotoxicity of new analogues of the natural cyclodepsipeptide jaspamide

Three analogues of the natural bioactive cyclodepsipeptide jaspamide (3-5) were efficiently synthesized using a combination of solid and solution phase techniques. The preliminary design of the molecules has involved the rational substitution and/or simplification of the most critical structural features of the lead compound. The synthetic products were subjected to pharmacological assays, and the conformational properties were investigated by MM (molecular mechanics) and MD (molecular dynamics) calculations, to describe the potential pharmacophoric core responsible for the observed activities.     

Naphthalimido derivatives as antifolate thymidylate synthase inhibitors

A new series of N-(substituted)benzyl-1,8-naphthalimides 4, structurally related to the previously reported thymidylate synthase (TS) inhibitor naphthaleins 3, were synthesized and compounds tested for their inhibition of several species of TS. Moreover, their in vitro cytotoxicity together with antimycotic and antibacterial properties were assayed. While no activity was detected in the antibacterial tests, the m-nitro (4ae) and the p-nitro (4af) derivatives were found able to partially inhibit TS at low micromolar concentrations. Introduction of nitro or (substituted)-amino groups in position 4 of the naphthalic ring always led to less active compounds.     

Self-limiting extravasation in the unused urinary bladder

Patients being evaluated as potential renal transplant recipients routinely undergo voiding cystourethrography. Eight patients were encountered in whom extraperitoneal extravasation was noted from the region of the ureterovesical junction during voiding (seven patients) or during filling (one patient). Extravasation was bilateral in six patients and unilateral in two. The patients neither experienced symptoms related to the extravasation, required treatment, nor had sequelae. Five of the eight patients have subsequently received renal transplants and their bladders were observed to be normal at surgery. Cystoscopy was also performed in two of these five patients and was unremarkable. After transplantation, these patients' bladders functioned normally and gave rise to no symptoms.     

Changes in body temperature and urinary cortisol after routine immunization in babies with intrauterine growth retardation

Aim : To investigate whether infants with intrauterine growth retardation (IUGR) experience different changes in temperature and cortisol excretion after routine immunization compared with normal healthy infants. Methods : Overnight deep body temperature and urinary cortisol to creatinine ratios were measured on the night after immunization and a control night in normal and IUGR infants. Results : In 60 normal infants, first vaccination at about 10 wk of age led to a significant increase in minumum overnight temperature compared to the control night, mean rise 0.25°C (95% CI, 0.12 to 0.38). In 35 IUGR infants the mean rise in temperature between immunization night and control night was 0.35°C (95% CI, 0.15 to 0.55). The increases in minimum temperature did not differ significantly between the normal and IUGR infants ( p = 0.11). Cortisol to creatinine ratios measured from overnight urine samples showed that 23 IUGR infants had consistently higher levels than 39 normal infants; control night medians 34 and 15 ( p = 0.01) and immunization night medians 56 and 26 ( p= 0.02), respectively. However, the percentage increase did not differ significantly between the IUGR infants and the normal infants. A smaller number of second immunizations were studied, but no significant differences were found.

Conclusion : These results suggest that although the impact of immunization is the same for IUGR and normal infants, because IUGR infants are less mature and at greater stress before immunization, the absolute levels that they experience after immunization are higher than those for normal infants.     

Pulmonary embolism after hip or knee replacement: postoperative changes on pulmonary scintigrams in asymptomatic patients

Serial pulmonary imaging has proved to be effective in the evaluation of patients undergoing total joint arthroplasty. A clinical dilemma arises in asymptomatic patients whose postoperative pulmonary images differ from the preoperative images. The authors prospectively evaluated 403 patients with serial imaging to determine the significance of changed postoperative images in asymptomatic patients undergoing total hip or knee arthroplasty. Twenty-two (5.5%) patients had significant changes on postoperative images. Seventeen were asymptomatic; all but one underwent pulmonary angiography. Documented pulmonary emboli were demonstrated in 100% of patients whose postoperative images changed to indicate a high probability of pulmonary embolism, 71% whose images changed to a moderate probability, and 0% whose images changed to indeterminate probability. Overall, pulmonary emboli occurred in 76% of all asymptomatic patients with significantly change postoperative images. Asymptomatic pulmonary embolism is a significant occurrence after total hip or knee repair, and a changed lung scan with appropriate clinical evaluation is an accurate indicator of pulmonary emboli in asymptomatic postarthroplasty patients.     

Demographic characteristics and prevalence of serologic markers among donors who use the confidential unit exclusion process: the Retrovirus Epidemiology Donor Study

BACKGROUND: Most blood centers utilize a confidential unit exclusion (CUE) process, intended to reduce the risk of transfusion-associated infectious diseases by allowing high-risk donors confidentially to exclude their blood from use for transfusion. The effectiveness of this method remains controversial. STUDY DESIGN AND METHODS: Confirmatory or supplemental test results for antibodies to human immunodeficiency virus, human T-lymphotropic virus type I, and hepatitis C virus, as well as hepatitis B surface antigen and syphilis and screening test results for antibodies to hepatitis B core (antigen) and alanine aminotransferase levels were obtained for approximately 1.8 million units donated during 1991 and 1992 at five blood centers within the United States. The prevalences of these infectious disease markers in units that the donors confidentially excluded (CUE+) and units that the donors did not exclude (CUE-) were calculated and examined within demographic subgroups. RESULTS: Units that were CUE+ were 8 to 41 times more likely to be seropositive for antibodies to human immunodeficiency virus and hepatitis C virus, hepatitis B surface antigen, and syphilis and three to four times more likely to react for antibody to hepatitis B core (antigen) or to have elevated alanine aminotransferase levels than units that were CUE- (p < 0.001). The positive predictive value of CUE (the percentage of CUE+ units that were confirmed seropositive for any marker) was 3.5 percent, and the sensitivity of CUE (the percentage of confirmed-seropositive units that were CUE+) was 2.3 percent. CONCLUSION: The current CUE process has low sensitivity and apparently low positive predictive value, and in many cases, it appeared that donors misunderstood it. Yet, CUE was not a “random process,” as CUE+ units were more likely to be seropositive for any infectious disease marker than CUE- units. This suggests that efforts to improve the CUE system may be warranted. As risk factors for transfusion-transmitted infection become more difficult to identify by history-based screening, however, such efforts may have limited effect.     

Development of the Manchester framework for the evaluation of emergency department pharmacy services

International Journal of Clinical Pharmacy - Many countries, including the United Kingdom, have established Emergency Department (ED) pharmacy services where some ED pharmacists now work as...