Anticancer activity of new 3-amino-pyrrolidinedione-nitrogen mustard derivatives on murine sarcoma 180

A 2,5-pyrrolidinedione linked nitrogen mustard derivative, (R,S)3-[N,N-bis(2-chloroethyl)]-amino-1-(2'-methoxyphenyl)pyrrolidine- 2,5-dione hydrochloride (I) showed a marked antiproliferative effect on mouse Sarcoma 180. Since (I) is also active against L1210 and P388 leukaemias, its toxicity in mice was evaluated. A study of acute toxicity revealed focal liver cell necrosis. Another derivative, (R,S)3-[N,N-bis-(2-chloroethyl)]amino-1-(4'-n-butoxyphenyl)pyrrolidine- 2,5-dione dihydrate (II), which also possessed significant anticancer effect on P388 and L1210 leukaemias, was inactive against Sarcoma 180.     

Modulating effect of alpha-[N,N-[bis(2-hydroxyethyl)]-amino-N- (o-methoxyphenyl)-pyrrolidin-2,5-dione on the chemotherapy of murine tumours

alpha-[N,N-[bis(2-hydroxyethyl)]-amino]-N- (o-methoxyphenyl)pyrrolidin-2,5-dione (I), an intermediate in the synthesis of pyrrolidinedione-N-mustards, did not exhibit antitumour activity against P388 lymphocytic leukemia, Sarcoma 180 (ascites) and Ehrlich (ascites) carcinoma tumours. The effect of co-administration of (I) with established anticancer drugs was studied against these murine tumours. The activity of 5-fluorouracil against Sarcoma 180 (ascites) and Ehrlich (ascites) carcinoma was significantly enhanced by co-administration with (I). Other anticancer drugs, when co-administered with (I), did not show any enhancing effect.     

Adult testicular granulosa cell tumor: a review of the literature for clinicopathologic predictors of malignancy

Adult testicular granulosa cell tumors are rare sex cord-stromal tumors of which only 28 have been previously reported. As compared with their ovarian counterparts, these tumors may follow a more aggressive course because the proportion of malignant cases is higher. To date, there are no clinical or pathologic features that definitively predict malignancy. We reviewed all prior case reports for features that may predict their malignant potential. Tumor size greater than 5.0 cm is the only feature statistically associated with malignancy. Mitotic count, tumor necrosis, patient age, and the presence of gynecomastia do not, at present, predict benign versus malignant behavior.     

Comparison of agar dilution, broth microdilution, disk diffusion, E-test, and BACTEC radiometric methods for antimicrobial susceptibility testing of clinical isolates of the Nocardia asteroides complex.

An evaluation was undertaken to determine the optimal method for the in vitro susceptibility testing of 26 Nocardia asteroides complex isolates to the following antimicrobial agents: amikacin, ampicillin, amoxicillin-clavulanate, ceftriaxone, ciprofloxacin, erythromycin, imipenem, minocycline, and trimethoprim-sulfamethoxazole. Five testing methods were studied including the agar dilution, broth microdilution, and disk diffusion methods, the epsilometer test (E-test), and the BACTEC radiometric method. Results for each antimicrobial agent and each testing method were interpreted as indicating susceptibility, intermediate susceptibility, or resistance according to current guidelines of the National Committee for Clinical Laboratory Standards (NCCLS) for bacteria that grow aerobically and were then compared to a "gold standard" susceptibility test result. The gold standard result for each Nocardia isolate was established by a consensus of the results of the majority of testing methods used in the study. When the results were combined for all antimicrobial agents tested against all Nocardia isolates by all methods, the BACTEC radiometric method produced the highest level of agreement (97.9%) with the consensus results and had the fewest very major (n = 1), major (n = 2), and minor (n = 2) errors. In contrast, the results of the agar dilution method were in least agreement (93.2%) with the consensus results, and this method also produced the most very major (n = 8), major (n = 4), and, along with the disk diffusion method, minor (n = 6) errors. For all test methods, interpretive errors were most frequent when testing ampicillin or amoxicillin-clavulanate. Moreover, for all Nocardia nova isolates tested, ampicillin susceptibility results by any of the testing methods were not in agreement with the results of testing for beta-lactamase by the nitrocefin (Cefinase) disk method. We conclude that among the methods evaluated, the BACTEC radiometric method appeared to be the best for determining the in vitro susceptibilities of members of the N. asteroides complex to a panel of nine antimicrobial agents. However, none of the test methods, including the BACTEC method, accurately predicted the ampicillin resistance of the N. nova isolates tested, all of which produced beta-lactamase. Presuming that this beta-lactamase hydrolyzes ampicillin, this disparity may relate to the NCCLS breakpoints that were used, which may require modification for this antimicrobial agent when tested against N. nova isolates.     

Papillary carcinoma of the breast in a male patient with a treated prostatic carcinoma diagnosed by fine-needle aspiration biopsy: a case report and review of the literature

Papillary carcinoma of the male breast is very rare. In this case report, we describe the cytologic, histologic, immunohistochemical, and radiological findings of a papillary carcinoma of male breast. A 67-yr-old man, who had a previous history of prostatic adenocarcinoma, presented with a retroareolar painless mass. There was no known history of breast cancer in his family. A fine-needle aspiration biopsy (FNAB) was performed. Cytological examination revealed a cellular aspirate with three-dimensional papillary clusters. A diagnosis of papillary lesion favoring papillary carcinoma was rendered. Immunohistochemical staining of the cell-block of the FNAB revealed the presence of mammaglobin, and the absence of prostatic specific antigen. The patient underwent lumpectomy, which showed a moderately differentiated infiltrating papillary carcinoma with adjacent areas of ductal carcinoma in situ. FNAB is a useful technique in identifying male breast carcinoma. In conjunction with ancillary studies, this procedure can effectively differentiate between a primary versus metastatic lesion.     

Anti-tumor effect of 3-amino-N-substituted-pyrrolidine-2,5-dione-N-mustard hydrochloride.

The anti-tumor effect of 3-amino-N-substituted pyrrolidine-2,5-dione-N-mustard hydrochloride (PNM.HCl) against Ehrlich (ascites) carcinoma (EAC) was studied. A substantial increase in the survival of mice bearing EAC tumor was achieved following daily administration of PNM.HCl at subtoxic dosages. The therapeutic efficacy of PNM.HCl was maintained with changes in dosages and the schedules of administration. The effect of PNM.HCl when administered with conventional anti-cancer drugs at different time schedules against EAC was also studied. The results demonstrated an augmentation of anti-tumor activity in the case of certain anti-cancer drugs against EAC tumor, thereby suggesting a potential usefulness of PNM.HCl in multi-drug therapy.     

Knowledge and attitudes towards antiretroviral therapy among factory workers participating in a cohort on HIV and AIDS, Addis Ababa, Ethiopia

This study investigates barriers that may pose a threat to a successful implementation of an antiretroviral treatment (ART) program in Ethiopia. As prelude to the provision of ART among factory workers participating in a cohort study on HIV and AIDS in Ethiopia, we measured knowledge and attitudes towards several aspects of ART and provided an educational intervention. The proportion of participants having good knowledge on issues concerning adherence was found reasonably good (67.7%), concerning the benefit of ART was intermediate (37.7%) and concerning eligibility was very low (16.8%). Knowledge concerning eligibility improved somewhat after the provision of the educational intervention. Only one third of HIV infected persons discloses their HIV status to their partner. Several aspects that could impact adherence to ART will be discussed, such as ART knowledge, social support, willingness to take ART, and disclosure of serostatus, taking the cohort study site into account. Results indicate a tremendous need to educate cohort participants before and during introduction of ART. Efforts to increase knowledge of ART, and especially knowledge of eligibility criteria to start ART, seem warranted, as well as encouragement to identify social support and disclose HIV serostatus, as these factors directly impact the success of an ART program.