Design,synthesis, structure-activity relationships,and molecular modeling studies of 2,3-diaryl-1,3-thiazolidin-4-ones as potent anti-HIV agents

Starting from 1H,3H-thiazolo[3,4-a]benzimidazoles (TBZs), we performed the design, synthesis, and the structure-activity relationship studies of a series of 2,3-diaryl-1,3-thiazolidin-4-ones. Some derivatives proved to be highly effective in inhibiting HIV-1 replication at nanomolar concentrations with minimal cytotoxicity, thereby acting as nonnucleoside HIV-1 RT inhibitors (NNRTIs). Computational studies were used to delineate the ligand-RT interactions and to probe the binding of the ligands to HIV-1 RT.     

Arthritis as a rare extra-intestinal manifestation of acute sigmoid diverticulitis.

BACKGROUND: A causal association between acute diverticulitis of the sigmoid colon and arthritis has rarely been reported. CASE REPORT: We report the case of a 60-year-old patient who developed migrating arthritis of the knee and ankle during the recurring episode of acute diverticulitis of the sigmoid colon. Treatment with NSAIDs and antibiotics had little effect on joint disease, but medical treatment was successful in reducing the diverticulitis-related symptoms. Arthritis promptly improved after surgical resection of the sigmoid colon, and 30 months later the patient is free of symptoms in the previously affected joints. CONCLUSIONS: Five cases of diverticulitis-associated arthritis have been reported. The similar case reported here reconfirms that joint disease has a limited response to medical approaches. Colon resection is recommended for patients with diverticulitis-associated arthritis which does not respond promptly to antibiotic therapy.     

Event-related brain potentials during a continuous performance test (CPT) task in normal children

BACKGROUND: Continuous Performance Test (CPT) is a commonly used paradigm to assess attention disorders that could involve working memory processes. METHODS: Event-related potentials (ERPs) during a CPT (X-AX) test were obtained in 16 healthy male students, with ages ranging from 9 to 11 years (X = 10.3). In grouped averaged ERPs, an endogenous slow positive potential was recorded in the first task (infrequent letter detection); maximum was at 460 msec with a slight lateralization tendency toward left parietal area. In the second task (target detection with an A as warning signal), an early (maximum at 330 msec) and more acute peak was detected without evidence of any lateralization. RESULTS: Reaction times were significantly shorter for the second task. Electrophysiologic differences between both target conditions showed an early, remarkable, and statistically significant component located at the parietal area at 340 msec. CONCLUSIONS: These ERPs findings could be interpreted as correlates with working memory processes in children.     

Gemcitabine in combination with doxorubicin in advanced breast cancer: final results of a phase II pharmacokinetic trial.

PURPOSE: Gemcitabine has promising single-agent activity in advanced breast disease. The aim of this phase II study was to determine the efficacy, toxicity, and pharmacokinetic profile of gemcitabine administered with doxorubicin as first-line treatment in patients with metastatic breast cancer. PATIENTS AND METHODS: Of the 42 women with metastatic breast cancer (age 33 to 74 years; mean age, 55 years), 13 were chemotherapy-naive and 29 had received adjuvant chemotherapy. Gemcitabine (800 or 1,000 mg/m(2)) and doxorubicin (25 mg/m(2)) were administered intravenously on days 1, 8, and 15 of each 28-day cycle. Blood samples were drawn on day 8 of cycles 1, 2, and 3 and of subsequent odd cycles for gemcitabine pharmacokinetic determinations and before and after the first dose of cycle 1 or 2 for doxorubicin determinations. RESULTS: There were three complete and 20 partial responses, for an overall response rate of 55% (95% confidence interval [CI], 40% to 70%) and a complete response rate of 7%. The median survival time for all 42 patients was 27 months (95% CI, 13.4 to 30.0 months) and the 1-year survival rate was 80%. Toxicity was mainly hematologic. The disposition of both drugs was unchanged when they were administered on the same day compared with when they were given singly. CONCLUSION: The combination of gemcitabine (800 mg/m(2)) and doxorubicin (25 mg/m(2)) can be safely administered using a weekly schedule. The disposition of both drugs is unchanged when they are administered on the same day. This combination shows promising activity with acceptable toxicity compared with other combination therapies.     

Role of x-ray computed tomography in the preoperative evaluation of aneurysm of the abdominal aorta

The authors have studied the files of 50 consecutive patients (1987-89) operated for abdominal aortic aneurysm (AAA) and examined with CT. The criteria for inclusion were surgical features. CT can be made more accurate for the study of AAA: Thus the location of the neck of the aneurysm relative to the renal arteries was defined in 94% of all cases. In addition, CT yields information about the wall of the aneurysm, whether it be thickened (3 inflammatory aneurysms were properly diagnosed) or, mor importantly, weakened (solution of continuity in the wall in the "prior-to-rupture" appearance). Owing to the quality of its performances and to its noninvasive character, the authors regard CT with contrast injection as an essential technique for the preoperative assessment of abdominal aortic aneurysm in most cases. The examination must be carried out strictly, especially for the contiguous sections of the renal arteries and their extension to the crural arch. As it demonstrates weakened areas more easily, a more accurate study of the aneurysmal wall with CT might increase the surgical indications for some smaller aneurysms, the potential evolution of which does not seem to be associated with their diameter only.     

Long-term results of a prospective study on the treatment of medulloblastoma in adults

BACKGROUND: Because medulloblastoma (MB) is rare in adults, the few studies on this condition have been retrospective, and the follow-up has tended to be short. Furthermore, the different therapeutic strategies used in these patients has made it difficult to assess survival rates and prognostic factors. METHODS: In 1989, a prospective Phase II trial was initiated to evaluate the efficacy of treatment for adults with MB. Patients were staged completely with a neuroradiologic examination of the brain and neuroaxis and by cerebrospinal fluid cytology, according to Chang's staging system. Low-risk patients received radiotherapy alone, whereas high-risk patients received 2 cycles of upfront chemotherapy followed by radiotherapy and adjuvant chemotherapy. The current article reports on the long-term results from that trial. RESULTS: After a median follow up of 7.6 years, among a total of 36 adults with MB, the overall progression-free survival (PFS) and overall survival (OS) rates at 5 years were 72% and 75%, respectively. In low-risk patients, the 5-year PFS rate was 80%, and the 5-year OS rate was 80%; in high-risk patients, the 5-year PFS rate was 69%, and the 5-year OS rate was 73%. CONCLUSIONS: In adult patients with MB, long-term follow-up was essential for evaluating the real impact of treatments. Low-risk and high-risk patients did not differ significantly in terms of PFS or OS.     

Methimazole embryopathy: a contribution to defining the phenotype

It has been suggested that children prenatally exposed to methimazole may present some features in common but the phenotype remains to be defined. The reported facial features include upward slanted palpebral fissures, arched flared eyebrows and small nose with a broad bridge. Choanal atresia and other anomalies like esophageal atresia and aplasia cutis were also described with this embryopathy. Additionally, developmental delay was reported in some patients along with one of these major malformation. We present a patient with the mentioned facial features, developmental delay and radio-ulnar synostosis whose mother has been exposed to methimazole during pregnancy and any other ethiological cause could be recognize.