Efficacy of Temozolomide Therapy in Patients With Aggressive Pituitary Adenomas and Carcinomas-A German Survey.

CONTEXT: Despite growing evidence that temozolomide (TMZ) therapy is effective for the treatment of aggressive pituitary tumors (APTs) or carcinomas (PCs), individual therapy decisions remain challenging. OBJECTIVE: We therefore aimed to report on clinical characteristics leading to initiation of TMZ therapy and to add evidence on TMZ long-term effectiveness. DESIGN AND SUBJECTS: Retrospective survey on TMZ treatment in patients with APTs or PCs. TMZ therapy was initiated in 47 patients (22 females) with APTs (n = 34) or PCs (n = 13). Mean age at diagnosis was 45 ± 15 years. The immunohistochemical subtypes were corticotroph (n = 20), lactotroph (n = 18), and nonfunctioning (n = 9) tumors. TMZ therapy started 8 years after initial diagnosis using a standard regimen (median 6 cycles) for the majority of patients. RESULTS: Long-term radiological response to TMZ after a median follow-up of 32 months with 4 patients still on TMZ therapy was tumor regression for 9 (20%), stable disease for 8 (17%), and tumor progression for 29 patients (63%) (outcome data available for 46 patients). Progression occurred 16 months after initiation of TMZ. Median estimated progression-free survival was 23 months. Disease stabilization and median progression-free survival did not differ between patients with APTs or PCs. Predictors of tumor response were not identified. Overall, TMZ was well tolerated. CONCLUSION: We performed a nationwide survey on TMZ therapy in patients with APTs and PCs. While early response rates to TMZ are promising, long-term outcome is less favorable. Prolonged TMZ administration should be considered. We were not able to confirm previously reported predictors of tumor response to TMZ.

Different susceptibility of facilitatory and inhibitory spinal pathways to ischemia in the cat.

The sensitivity of different excitatory and inhibitory segmental reflex pathways to ischemia was investigated by monosynaptic reflex testing in the spinal cat. Spinal cord ischemia was established by aortal snare occlusion of 1-10 min duration. Excitatory and inhibitory spinal pathways showed statistically significant different susceptibility to ischemic impact. In the period of decreasing responses after the onset of ischemia the transmission through oligo- or polysynaptic, facilitatory or inhibitory pathways was found to be depressed earlier than that of monosynaptic pathways. The period from the end of ischemia until the beginning of recovery of reflex effects was significantly longer for inhibitory effects, compared to the monosynaptic reflexes alone.The results indicated that interneurones of excitatory segmental pathways may be less sensitive to ischemia than motoneurones, and motoneurones seem to be less sensitive to ischemia than interneurones of inhibitory pathways. In high spinal animals, with a relatively high level of extensor inhibition, the enhanced excitability of inhibitory interneurones to GS motoneurones may be responsible for their sensitivity to ischemia, due to an increased rate of O(2) consumption and exhaustion of high-energy phosphate resources.

Endothelin-converting enzyme activity in human cerebral circulation.

OBJECTIVE: An increased level of endothelin (ET)-1 seems to be involved in the development of augmented cerebrovascular resistance in different pathological conditions, most notably vasospasm after subarachnoid hemorrhage. Therefore, interfering with the ET synthesis or ET receptor blockade may be a promising approach in the treatment of cerebral vasospasm after subarachnoid hemorrhage. Although the receptors mediating the effects of ET-1 human cerebrovasculature are well characterized, data concerning the functionally relevant ET-converting enzyme (ECE) activity are scarce. METHODS: ECE activity was determined in organ bath studies by the use of intraoperatively harvested human pial arteries. The level of ECE activity was analyzed by comparing the shift in the concentration effect curves obtained for ET-1 and its precursor, big ET-1. In addition, the presence of ECE-1alpha immunoreactivity was studied in human cerebral tissue. RESULTS: ECE-1alpha immunoreactivity was found, although not consistently, in human cerebral arteries and was restricted to the endothelium. In isolated pial arterial segments, ET-1 and big ET-1 induced concentration-related contractions with mean pD(2) values of 9.25 +/- 0.34 and 7.13 +/- 0.17, respectively, yielding a 123-fold shift of big ET-1 versus mature ET-1. Preincubation with phosphoramidon (10(-4) mol/L) resulted in a small yet significant inhibition of the contraction induced by big ET-1. CONCLUSION: The results of our study indicate the presence of functional ECE activity and ECE-1alpha immunoreactivity in human cerebral arteries. Furthermore, the data suggest the presence of ECE-like activity that differs from that of ECE-1alpha.

First appearance and sense of the term "spinal column" in ancient Egypt. Historical vignette.

In contemporary anatomical nomenclature terms have often been derived from an ancient perspective of the human body. The term "spinal column" was used in ancient Egypt, symbolized by the "djet column." The authors discuss the first appearance of the term "spinal column," taking the ancient Egyptian interaction between religion and daily life into consideration, and they describe the different segments of the spinal column known to the ancient Egyptians. Inspection of medical papyri provides insight into the knowledge held by ancient Egyptian physicians and embalmers. It is assumed that hieroglyphs were used to depict the different vertebral regions of the spinal column (cervical, thoracic, and lumbar). The knowledge was gleaned, in fact, in pursuit of religious goals. The djet might be an example of how anatomical knowledge can improve understanding of a symbol that was previously thought to have a primarily religious meaning. The authors maintain that modern medical knowledge is useful for making a more precise and anatomically correct interpretation of the presumed sense intended by the ancient Egyptians.