Acute hyperthermia following stereotactic radiosurgery for pituitary adenoma

A 71-year-old male presented with a large pituitary adenoma with superior extension into the optic chiasm and suprasellar cistern. He was treated with stereotactic radiosurgery to a dose of 16 Gy. Approximately 1 h after radiosurgery he developed fever; his temperature peaked at 105.1 degrees F and normalized about 20 h later. This case demonstrates that acute hyperthermia is a potential complication following high dose stereotactic radiosurgery for large pituitary tumours.     

Volume fast spin-echo imaging of the cervical spine

RATIONALE AND OBJECTIVES: The authors prospectively evaluated a T2-weighted, three-dimensional (3D) volume, fast spin-echo (SE) pulse sequence in assessment of the cervical spine and compared it with standard imaging protocol. MATERIALS AND METHODS: Eighteen patients with neck pain underwent magnetic resonance (MR) imaging at 1.5 T with two-dimensional (2D) fast SE and axial 3D gradient-echo (GRE) protocols and with an additional sagittal T2-weighted volume fast SE protocol. The spinal cord and canal, neural foramina, and intervertebral disks were assessed by two neuroradiologists, and the results were compared with reports from the standard protocol. The quality of the partition (direct sagittal) and reconstructed images were evaluated. RESULTS: No differences existed in the assessment of spinal cord disease or disk herniation with 2D fast SE and volume fast SE imaging. Some mild variation occurred in assessment of the neural foramina. Partition images demonstrated a high level of resolution and contrast, while reconstructed images had consistently lower quality. However, this did not impede detection and grading of disk or spinal abnormalities, which were adequately shown on volume fast SE sagittal images. Neural foramina were well demonstrated on axial reconstructions from volume fast SE imaging. CONCLUSION: Volume fast SE imaging provides information about the spinal cord, canal, disks, and neural foramina that is comparable to the information provided by routine imaging. Its thinner sections and multiplanar reconstruction capability are advantages over 2D imaging. Its greater tissue contrast with better visualization of the cervical cord, greater signal-to-noise ratio, and less susceptibility artifact are advantages over 3D GRE imaging.     

Interactions of Phosphodiester and Phosphorothioate Oligonucleotides with Intestinal Epithelial Caco-2 Cells

Purpose. Oral bioavailability for antisense oligonucleotides has recently been reported but the mechanistic details are not known. The proposed oral delivery of nucleic acids will, therefore, require an understanding of the membrane binding interactions, cell uptake and transport of oligonucleotides across the human gastro-intestinal epithelium. In this initial study, we report on the cell-surface interactions of oligonucleotides with human intestinal cells. Methods. We have used the Caco-2 cell line as an in vitro model of the human intestinal epithelium to investigate the membrane binding interactions of 20-mer phosphodiester (PO) and phosphorothioate (PS) oligonucleotides. Results. The cellular association of both an internally [³H]-labelled and a 5end [³²P]-labelled PS oligonucleotide (3.0% at 0.4 µM extracellular concentration) was similar and was an order of magnitude greater than that of the 5end [³²P]-labelled PO oligonucleotide (0.2%) after 15 minutes incubation in these intestinal cells. The cellular association of PS was highly saturable with association being reduced to 0.9% at 5 µM whereas that of PO was less susceptible to competition (0.2% at 5 µM, 0.1% at 200 µM). Differential temperature-dependence was demonstrated; PS interactions were temperature-independent whereas the cellular association of PO decreased by 75% from 37°C to 17°C. Cell association of oligonucleotides was length and pH-dependent. A decrease in pH from 7.2 to 5.0 resulted in a 2- to 3-fold increase in cell-association for both backbone types. This enhanced association was not due to changes in lipophilicity as the octanol:aqueous buffer distribution coefficients remained constant over this pH range. The ability of NaCl washes to remove surface-bound PS oligonucleotides in a concentration-dependent manner suggests their binding may involve ionic interactions at the cell surface. Cell-surface washing with the proteolytic enzyme, Pronase^®, removed approximately 50% of the cell-associated oligonucleotide for both backbone types. Conclusions. Binding to surface proteins seems a major pathway for binding and internalization for both oligonucleotide chemistries and appear consistent with receptor (binding protein)-mediated endocytosis. Whether this binding protein-mediated entry of oligonucleotides can result in efficient transepithelial transport, however, requires further study.     

Chemometric Evaluation of Near Infrared,Fourier Transform Infrared,and Raman Spectroscopic Models for the Prediction of Nimodipine Polymorphs

The objective of this study was to assess the performance of the chemometric model to predict the proportion of the recrystallized polymorphs of nimodipine from the cosolvent formulations. Ranging from 100% to 0% (w/w) of polymorph I, the two polymorphs mixtures were prepared and characterized spectroscopically using Fourier transformed infrared spectroscopy (FTIR), near-infrared spectroscopy (NIR), and Raman spectroscopy. Instrumental responses were treated to construct multivariate calibration model using principal component regression (PCR) and partial least square regression approaches. Treated data showed better model fitting than without treatment, which demonstrated higher correlation coefficient (R²) and lower root mean square of standard error (RMSE) and standard error (SE). Multiple scattering correction and standard normal variate exhibited higher R² and lower RMSE and SE values than second derivative. Goodness of fit for FTIR and NIR (R² ~ 0.99) data was better than Raman (R² ~ 0.95). Furthermore, the models were applied on the recrystallized polymorphs obtained by storing nimodipine-cosolvent formulations at selected stability conditions. The relative composition of the polymorphs differed with storage conditions. NIR-chemical imaging on recrystallized sample of nimodipine at 15°C qualitatively corroborated the model-based prediction of the two polymorphs. Therefore, these studies strongly suggest the importance of the potential utility of the chemometric model in predicting nimodipine polymorphs.     

Choledocholithiasis in African American and Hispanic Patients: A Comparison Between Painless Presentation and Classical Biliary Pain with Regards to Clinical Manifestations and Outcomes

Choledocholithiasis (CDL) usually presents with biliary pain. Painless CDL is also known to occur, especially in the elderly. The purpose of this study is to determine whether the mode of presentation (painful vs. painless) influences the clinical course and outcomes of CDL in African American and Hispanic patients. Ten years of admission and discharge records (January 1998–December 2007) were reviewed retrospectively, yielding 527 community hospital patients, aged 23–97 years, with the final diagnosis of CDL. Patients with painless presentation had higher odds of having comorbidities compared to patients presenting with pain. However, patients who presented with biliary pain were predominantly younger (mean age 34 years), and 59 % were Hispanic females (p = 0.001). In our study painless CDL was associated with higher morbidity and mortality.