Extended administration of the association of zidovudine plus ritonavir during rat pregnancy: maternal and fetal effects

The purpose of the study was to evaluate at term, the effects of the association of zidovudine/ritonavir administered during the entire period of rat pregnancy. Forty pregnant EPM-1 Wistar rats were divided randomly into four groups: one control (drug vehicle control, n=10) and three experimental treated with an oral solution of zidovudine/ritonavir (Exp 1 = 10/20 mg/kg bw, n = 10; Exp 2 = 30/60 mg/kg bw, n=10; Exp 3 = 90/180 mg/kg bw, n=10) from day 0 up to day 20 of pregnancy. Maternal body weights were recorded at the start of the experiment and at the 7th, 14th and the 20th day thereafter. At term (20th day) the rats were anesthetized and, upon laparotomy and hysterotomy, the number of implantations, resorptions, living fetuses, placentae and intrauterine deaths were recorded. The collected fetuses and placentae were weighed, and the concepts were examined under a stereoscopic microscope for external malformations. The maternal body gain and the mean fetal weight at term were both significantly lower (p < 0.01 and p < 0.0001, respectively) in the experimental groups compared to the control. The recorded resorptions were higher in Exp 2 and Exp 3 groups than in the control group. The other parameters were not affected. The exposure of pregnant rats at term to a 1:2 association of zidovudine plus ritonavir resulted in a significant reduction in maternal body weight gain and increased rate of fetal resorption.     

Morphological and biochemical appraisal of the liver and renal effects of indinavir on rat pregnancy

Since indinavir is currently used in combination with other antiretroviral agents, there is a scarcity of studies in the literature on its single-drug perinatal safety. Thus, we decided to examine the gross maternal and fetal effects of indinavir administered alone during the entire period of rat pregnancy. Forty pregnant animals were assigned at random to four groups (C = control) treated with the drug vehicle (distilled water); the experimental groups were treated with indinavir as follows: E1 = 40 mg/kg; E2 = 120 mg/kg; E3 = 360 mg/kg from "zero" up to the 20th day of gestation. Drug or vehicle were administered daily by gavage. Each group consisted of ten animals. At term-pregnancy, the rats were deeply anesthetized and blood samples were collected for alanine aminotransferase (ALT) and aspartate aminotransferase (AST), creatinine and urea determinations. Fragments of maternal and fetal livers and kidneys were taken and routinely processed for histopathological study. Serum ALT activity in the E2 group was significantly higher (p < 0.01) than that of the other groups. The concentration of creatinine in blood was lower in the E2 and E3 groups than in group E1 (p < 0.01), whereas blood urea in group E3 was significantly lower than in the other groups (p < 0.01). Morphological (light microscopy) studies revealed that no significant effects of the drug could be detected regarding either maternal or fetal organs of the E1 and E2 groups. However, the maternal hepatocytes in the E3 group showed heterochromatic nuclei. In addition, there was some fatty infiltration, congested sinusoids and portal dilation. Maternal kidneys in the E2 and E3 groups revealed vascular dilation around the convoluted tubules. Regarding the biochemical determinations, the alterations observed were mild, without biological relevance, thus indicating that the treatment with indinavir during the entire gestation was essentially devoid of hepatic or renal effects which could result in altered metabolic parameters. It is concluded that indinavir was well tolerated in therapeutic and even in 9-fold higher doses. Notwithstanding, discrete morphological alterations occurred in the maternal compartment, but with no functional expression that could indicate deleterious effects on mothers and/or fetuses.     

Primary chemotherapy with sequential docetaxel followed by docetaxel and epirubicin in large operable breast cancer

Primary chemotherapy is increasingly used in patients with large operable breast cancer. Docetaxel and epirubicin are the most active agents in breast cancer treatment. PURPOSE: To evaluate clinical response rate, breast conserving surgery and pathological response rate in patients with large operable breast cancer treated with docetaxel followed by docetaxel and epirubicin as primary chemotherapy. PATIENTS AND METHODS: Patients with operable breast cancer more than 3 cm in the longest diameter with T2N0, T2N1 and T3N0 disease were enrolled. Patients were treated with three cycles of docetaxel 100 mg/m2 followed by three cycles of docetaxel 75 mg/m2 and epirubicin 90 mg/m2 prior to surgery. RESULTS: Sixty-five patients were enrolled between 09/2002 and 12/2005. The median age was 48.9 years and 72.3% were premenopausal. Median tumour size was 4.26 cm, 10.8% were T3 tumours and 38.5% had clinical positive lymph nodes. Of the tumours 58.5% were grade 1/2, 33.9% ER positive and 21.5% c-erb negative. All six cycles were administered to 62 patients; six cycles were delayed and five had dose reductions. Complete clinical response occurred in 41.5% of patients and partial response in 49.2%. Breast conserving surgery was performed in 30% of patients however it was feasible in 57%. Complete pathological response occurred in both primary tumour and nodes in 28%, and in 34% just in the primary tumour. Nine percent of cases had neutropenia and 7.7% febrile neutropenia, and two cases had a hypersensitivity reaction to docetaxel. One associated treatment death occurred. CONCLUSION: Docetaxel followed by epirubicin and docetaxel as primary chemotherapy results in a high clinical and pathological response rate. The majority of adverse events were predictable and manageable.     

Primary peritoneal borderline tumour: report of an unusual case

Primary peritoneal borderline tumour is a rare lesion, histologically indistinguishable from non-invasive peritoneal implants found in association with ovarian tumours of borderline malignancy. We report a case of a primary peritoneal borderline tumour diagnosed in a 30-year-old patient with pelvic pain, infertility and elevated serum CA-125.     

Prenatal sonographic diagnosis of a rare Cantrell's pentalogy variant with associated open neural tube defect - a case report

Cantrell's pentalogy is a very rare congenital anomaly. The hallmark of this condition is the presence of ectopia cordis and an abdominal wall defect. Its association with craniorachischisis is even more infrequent with just a few cases reported in the literature. The authors describe a case of a prenatal ultrasound diagnosis of Cantrell's pentalogy with posterior encephalocele and spinal dysraphism associated.