Variability of Spleen and Mesenteric Lymph Node in Control Cynomolgus Monkeys ( Macaca fascicularis) from Nonclinical Safety Studies: A Retrospective Assessment.

We assessed the variability of spleen and mesenteric lymph node (MLN) microscopic observations and the correlations of these observations with other study data from 478 control cynomolgus monkeys from 53 routine nonclinical safety studies. Spleen weight parameters (absolute and relative to body or brain weights) were highly variable both within a control group on an individual study (up to 5.11-fold) and among animals with the same light microscopic observation. Grades for microscopic observations were also highly variable. The most frequent microscopic observations for spleen were changes in the size and number of germinal centers (58%), acidophilic (hyaline) material in lymphoid follicles (52%), and compound lymphoid follicles (20%). The most frequent microscopic observations in the MLN were eosinophil infiltrates (90%), changes in size and number of germinal centers (42%), and brown pigment (21%). The only meaningful relationships ( r2 > 0.3) were positive correlations between reticuloendothelial hyperplasia and malarial pigment in the spleen and between each of these observations and spleen weight parameters. We conclude that determination of test article-related effects on the immune system in routine monkey toxicology studies requires careful consideration and a weight-of-evidence approach due to the low numbers of animals/group, the inherent variability in spleen and MLN parameters, and the infrequent correlation among immune system-related end points.

Maturity-related Variability of the Thymus in Cynomolgus Monkeys (Macaca fascicularis).

Terminal body weights (TBWs), thymus weight parameters, and thymus morphology were retrospectively evaluated in 453 cynomolgus monkeys assigned to control groups on nonclinical toxicity studies. Morphology of bone, ovary, and testis/epididymis were used to determine maturity status of individual animals. There was no correlation between TBW and thymus weight (absolute and/or relative to TBW or brain weight). Thymus weight parameters and grades of decreased lymphocytes in the thymus were highly variable in immature animals compared to mature animals. There was also high (up to 11-fold) variability of thymus weight parameters within a given control group on the same study (generally 3 or 4 animals per sex). Several parameters evaluated had more pronounced age-related changes in males when compared to females. Our results demonstrate the inherent variability of thymus weight parameters and morphologic observations for cynomolgus monkeys on toxicology studies. Changes in thymus parameters in cynomolgus monkeys are unreliable indicators of immunomodulation or immunotoxicity in the absence of other relevant findings. Therefore, the thymus parameters commonly evaluated in preclinical safety assessments should not be the primary data set used to determine the presence of a direct test article-related effect on the immune system.

Volumetric MRI of the limbic system: anatomic determinants.

The limbic system comprises the hippocampal formation, fornix, mamillary bodies, thalamus, and other integrated structures. It is involved in complex functions including memory and emotion and in diseases such as temporal lobe epilepsy. Volume measurements of the amygdala and hippocampus have been used reliably to study patients with temporal lobe epilepsy but have not extended to other limbic structures. We performed volume measurements of hippocampus, amygdala, fornix and mamillary bodies in healthy individuals. Measurements of the amygdala, hippocampus, fornix and mamillary bodies revealed significant differences in volume between right and left sides (P < 0.001). The intraclass coefficient of variation for measurements was high for all structures except the mamillary bodies. Qualitative image assessment of the same structures revealed no asymmetries between the hemispheres. This technique can be applied to the study of disorders affecting the limbic system.

Predictive value of induction of psychogenic seizures by suggestion.

Induction by suggestion has previously been reported to be effective in the diagnosis of psychogenic seizures (PS). However, the sensitivity and specificity of this procedure has not previously been studied. Results of induction of PS by suggestion were analyzed in 93 patients with purely PS. The diagnosis of PS was based on the recording of a clinical event on video-electroencephalography, the absence of clinical or electroencephalography the absence of clinical or electroencephalographic evidence of epilepsy, and the subsequent followup and withdrawal of anticonvulsants supporting the diagnosis of PS. A control-group was composed of 20 patients with epilepsy in which induction was tried. Both groups were comparable for age, sex, and educational level. Induction was performed following a standardized protocol. The test was carried out placing a colored patch on the neck. The test was considered positive when the induced clinical events were typical, according to a witness familiar with the patient's seizures. Induction was positive in 72 of 93 cases with PS and in none with epilepsy. Sensitivity of this test for the diagnosis of PS was 77.4%, specificity 100%, positive predictive value 100%, and negative predictive value 48.7%.

Planned delayed nephrectomy after ethanol embolization of renal carcinoma.

Planned delayed nephrectomy after preoperative ethanol infarction was done in 6 patients with renal carcinoma. Three patients had intracaval extension of tumor, 2 had renal vein but no vena caval extension and 1 had no renal vein or vena caval involvement. Nephrectomy was delayed 22 to 44 days after embolization. In the patients with inferior vena caval extension shrinkage of tumor thrombus after embolization allowed for easier surgical resection. Furthermore, delay of nephrectomy after preoperative infarction was of value in improving the clinical status of high risk patients.

Lesions of the posterior compartment of the elbow.

This article examines the diagnosis and treatment of lesions of the posterior compartment of the elbow, along with the anatomy and biomechanics of the elbow of the throwing athlete. An indepth evaluation of specific lesions and a detailed description of elbow arthroscopy are also presented.

Percutaneous removal of a Gianturco coil from the pulmonary artery with use of flexible intravascular forceps.

Inadvertent migration of a stainless steel coil to the right lower lobe pulmonary artery occurred during a varicocele embolization procedure. A percutaneous technique and flexible intravascular forceps were used to retrieve and remove the coil.