Cerebral microdialysis in clinical studies of drugs: pharmacokinetic applications

The ability to deliver drug molecules effectively across the blood–brain barrier into the brain is important in the development of central nervous system (CNS) therapies. Cerebral microdialysis is the only existing technique for sampling molecules from the brain extracellular fluid (ECF; also termed interstitial fluid), the compartment to which the astrocytes and neurones are directly exposed. Plasma levels of drugs are often poor predictors of CNS activity. While cerebrospinal fluid (CSF) levels of drugs are often used as evidence of delivery of drug to brain, the CSF is a different compartment to the ECF. The continuous nature of microdialysis sampling of the ECF is ideal for pharmacokinetic (PK) studies, and can give valuable PK information of variations with time in drug concentrations of brain ECF versus plasma. The microdialysis technique needs careful calibration for relative recovery (extraction efficiency) of the drug if absolute quantification is required. Besides the drug, other molecules can be analysed in the microdialysates for information on downstream targets and/or energy metabolism in the brain. Cerebral microdialysis is an invasive technique, so is only useable in patients requiring neurocritical care, neurosurgery or brain biopsy. Application of results to wider patient populations, and to those with different pathologies or degrees of pathology, obviously demands caution. Nevertheless, microdialysis data can provide valuable guidelines for designing CNS therapies, and play an important role in small phase II clinical trials. In this review, we focus on the role of cerebral microdialysis in recent clinical studies of antimicrobial agents, drugs for tumour therapy, neuroprotective agents and anticonvulsants

Pyelolithotomy in a patient with Glanzmann thrombasthenia and antiglycoprotein IIb/IIIa antibodies: the shortest possible duration of treatment with recombinant activated factor VII and platelet transfusions

Transfusion of platelet concentrates remains the first-line therapy for Glanzmann thrombasthenia in case of bleeding or preparation for surgery. However, development of antibodies to platelet glycoprotein (Gp) IIb/IIIa complex or human leukocyte antigens (HLA) is frequent and the main cause of platelet refractoriness. Recombinant activated factor VII (rFVIIa) is a potent alternative for patients with Glanzmann thrombasthenia with anti-platelet antibodies

Prenatal Sonographic Diagnosis of Multicystic Congenital Mesoblastic Nephroma

The authors report an unusual presentation of congenital mesoblastic nephroma as a multilocular cystic renal lesion. Prenatal sonography revealed a unilateral, encapsulated, multilocular cytic mass with solid components measuring 5.7 x 5.4 x 4.3 cm in the left renal fossa. There was no increase in vascularity and no signs of hydrops fetalis. On the forth postnatal day left-sided radical nephrectomy was performed and histopathological examination revealed cellular type congenital mesoblastic nephroma. A multicystic appearance is rare as the vast majority of prenatally diagnosed congenital mesoblastic nephroma cases presented in the literature are of the classic type with solid homogenous or heterogenous appearence. (c) 2012 Wiley Periodicals, Inc. J Clin Ultrasound41:59-61, 201

Pseudoaneurysm of the bulbourethral branch of the internal pudendal artery presenting as a urethral pseudodiverticulum in a child

Pseudoaneurysm of the internal pudendal artery or its branches is a rare complication of pelvic trauma. It generally causes arteriocavernosal fistula leading to priapism. Connection between the urethra and the pseudoaneurysm has been documented in a few cases; however, pseudoaneurysm causing a urethral pseudodiverticulum has not been reported. We report a 7-year-old boy with a pseudoaneurysm of the bulbourethral branch of the left internal pudendal artery leading to a urethral pseudodiverticulum

Failed orchiopexy - Leading causes and surgical management

Introduction: Failure after orchiopexy or cryptorchidism after inguinal surgery are not so rarely encountered conditions. Reoperative orchiopexies are technically demanding procedures. In our study, we aimed to examine the causes of failures and outcomes of reorchiopexies. Patients and Methods: Between 1993 and 2003, a total of 28 children who underwent reoperative orchiopexy were included into the study. Undescended testes was detected as unilateral in 24 and bilateral in 4 cases. The mean age of patients at the time of second operation was 6.8 years. The mean period of time between the first and the second operations was 3.2 ( 1 - 13 years) years. Results: The first operations were orchiopexies in all patients. After the first operations, 15 testes were found to be localized at the high scrotal position, 8 at the level of the external ring and 9 within the inguinal canal. Overall, reorchiopexies were performed on 32 testes in 28 patients. During the second operation, patent processus vaginalis was detected in 11 (34.4%), and unsuccessful hernia repair in 9 (28.1%) cases. After reorchiopexies, two testes with preoperative inguinal location could only be brought to high scrotal position and in another case orchiectomy was performed to an atrophic testis. Overall, after a mean follow-up period of 3.8 ( 1 - 7 years) years following the second operations, 29 (93.5%) testes were scrotal without evidence of atrophy. Conclusion: In our series, inadequate repair of inguinal hernia or patent processus vaginalis, as noted in 62.5% of the cases, was determined as an important factor leading to failure after surgical treatment of undescended testis. Adequate dissection and correction of inguinal hernia increase the success rate after orchiopexies. Copyright (C) 2004 S. Karger AG, Basel