Mixtures of drugs from different chemical families have been proposed as a valid strategy to delay the development of anthelmintic resistance. The current work summarizes the outcome of the evaluation of the plasma disposition kinetics of albendazole (ABZ) and ivermectin (IVM) administered either alone or co-administered to lambs infected with gastrointestinal (GI) nematodes resistant to both anthelmintic molecules. Thirty six (36) Corriedale lambs naturally infected with multiple resistant GI nematodes were allocated into six treatment groups: (a) ABZ intravenous (ABZ(IV)); (b) IVM(IV); (c) ABZ(IV) + IVM(IV); (d) ABZ intraruminal (IR); (e) IVM subcutaneous (SC) and (f) ABZ(IR) + IVM(SC). Plasma samples were collected over 15 days post-treatment and analysed by HPLC. The estimated pharmacokinetic (PK) parameters were statistically compared using parametric and non-parametric statistical tests. The presence of IVM did not affect the plasma disposition kinetics of ABZ and its metabolites after the i.v. administration. However, the ABZ sulphoxide (ABZSO) area under the concentration vs. time curve (AUC) was significantly lower (P < 0.01) after the intraruminal (i.r.) administration of ABZ alone compared to that obtained for the combined treatment with IVM [subcutaneous (s.c.) injection]. The IVM plasma AUC obtained after its i.v. co-administration with ABZ was 88% higher (P < 0.05) compared to the treatment with IVM alone. Any marked difference on IVM PK parameters was observed between the treatments ABZ + IVM and IVM alone injected subcutaneously. The data obtained here indicate that the co-administration of ABZ and IVM does not induce an adverse kinetic interaction. This type of pharmacology-based evaluation of drug interactions is becoming highly relevant as drug combinations are now widely used as an alternative to control resistant helminth parasites in livestock.
Background The superiority of laparoscopic transperitoneal (TP) versus retroperitoneal (RP) adrenalectomy is an ongoing debate. Methods Data from 163 patients (TP: n = 135; RP: n = 28) undergoing minimally invasive adrenalectomy were analyzed. Both operative [intraoperative blood loss, previous abdominal surgery, conversion rate, operative time and tumor size] and perioperative [BMI (body mass index), ASA (American Society of Anesthesiologists) score, time of hospitalization, time of oral intake, histology and postoperative complications] parameters were compared. Both the learning curve (LC) and tumor size were analyzed. Results We found significant differences in the mean operative time (p = 0.019) and rate of previous abdominal surgery (p = 0.038) in favor of TP. Significantly larger tumors were removed with TP (p = 0.018). Conversion rates showed no significant difference (p = 0.257). Also, no significant differences were noted for time of hospitalization, intraoperative blood loss and postoperative complications. In terms of the LC, we saw significant differences in previous abdominal surgery (p = 0.015), conversion rate (p = 0.011) and operative time (p = 0.023) in favor of TP. Large (LT) and extra-large tumors (ELT) were involved in 47 lesions (LT: 40 vs. ELT: 7), with a mean tumor size of 71.85 and 141.57 mm, respectively. Mean intraoperative blood loss was 64.47 ml vs. 71.85 ml, time of hospitalization was 5.10 vs. 4.57 days and mean operative time was 76.52 vs. 79.28 min for LT and ELT, respectively. Conclusion A shorter operative time and lower conversion rate in favor of TP were noted during the learning curve. TP proved to be more effective in the removal of large-, extra-large and malignant lesions. The RP approach was feasible for smaller, benign lesions, with a more prolonged learning curve.
Benign metastasizing leiomyoma (BML) is a rare disease in women undergoing surgery for uterine leiomyoma. About 100 cases have been reported in the literature, none of which describe the biological behavior of lesions. The authors present the case of a 36-year-old, asymptomatic woman who had undergone uterus extirpation seven years earlier for leiomyoma of the uterus. Routine chest radiography revealed multiple nodules in both lungs. Biopsy verified metastases from the original uterine leiomyoma. of the seven metastasectomies was 95% (range: 40-150%). Pathological examination of the nodules proved that, despite continuous oncological treatment, there were no signs of necrosis, thrombosis, or fibrosis. The number of mitoses within the nodules did not change. According to our surgical results and the fact that oncological treatment did not have a significant effect on the course of the disease, we conclude that in the management of multiple BML lesions, surgically removing as many lesions as possible is advised.
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