Side effects of ergotamine

Ergotamine has been used for many years in the treatment of migraine, although there is little formal clinical evidence that it is significantly more efficacious than placebo. A number of side effects associated with ergotamine have been reported in the literature, including myocardial infarction, ischaemia of limb extremities, and fibrotic changes. Long-term use has led to reported cases of ergotamine-induced headache, vascular reactivity, and subclinical ergotism. When the safety profile of this drug is considered, coupled with its debatable efficacy from a clinical review previously published, the resulting poor risk: benefit ratio brings into question the continued use of ergotamine as a migraine treatment and calls for better controlled trials of its efficacy, or lack of, in the acute treatment of migraine.     

Visibility of gallstone fragments at US and fluoroscopy: implications for monitoring gallstone lithotripsy

To assess the value of ultrasound (US), fluoroscopy, and spot radiography in the detection, counting, and measurement of gallstone fragments during lithotripsy, in vitro visibility studies were conducted on fragments from 20 stones. Fluoroscopic visibility was evaluated during and after lithotripsy on 185 fragments placed in an anthropomorphic phantom. Three US experiments were performed on the fragments to study the visibility of fragments as a function of size, the accuracy of the count with large numbers of fragments, and the ability of observers to detect and count fragments larger than both 4 mm and 5 mm. With fluoroscopy, fragment detection rates ranged from 20% (fragments larger than 2.5 mm) to 80% (fragments larger than 4.5 mm). With US, all fragments larger than 1.5 mm were detected, and US was significantly better than fluoroscopy and spot radiography for detection of fragments 2.5 mm or smaller. US was also more accurate than fluoroscopy (11% vs 59% error) in the assessment of the number of fragments. When fragments larger than 4 mm or 5 mm were being counted with US, 92% of the fragments were visualized. The results suggest that US is more accurate for monitoring gallstone lithotripsy than fluoroscopy or spot radiography.     

Role of radiology in the treatment of malignant hilar biliary strictures 1: Review of the literature

Malignant strictures of the biliary tree are an uncommon cause of obstructive jaundice. There are a number of pathological subtypes, but tumours in this region tend to have similar clinical and diagnostic features and therapeutic and prognostic implications. We review the published literature on this topic discussing diagnostic modalities and treatment options with a focus on radiological intervention. Diagnosis currently is best achieved using a range of procedures. Direct cholangiography remains the gold standard in delineating anatomy, but the invasiveness of this procedure limits its use as a purely diagnostic tool. Magnetic resonance technology, in particular magnetic resonance cholangiopancreatography, has an increasing role as accessibility is improved. Treatment of these tumours is difficult. Surgical resection and palliative biliary enteric bypass are the most common methods used with endoscopic and percutaneous therapies reserved for palliating patients not fit for surgery. There is little firm evidence to suggest that any one palliative modality is superior. Interventional radiology is particularly suitable for palliative management of difficult and expansive lesions as the anatomy can preclude easy access by surgical or endoscopic techniques. Good palliative results with minimal mortality and morbidity can be achieved with percutaneous stenting .     

Anti-IgM induces transforming growth factor-beta sensitivity in a human B-lymphoma cell line: inhibition of growth is associated with a downregulation of mutant p53

We wished to examine the role of transforming growth factor-beta (TGF- beta) in the regulation of human lymphoma cell growth. The RL cell line is an immunoglobulin M (IgM)+, IgD+ B lymphoma cell line, which does not constitutively express receptors for TGF-beta, and thus has lost the ability to respond to the inhibitory effects of TGF-beta. We demonstrate here that anti-Ig antibodies can efficiently upregulate the expression of TGF-beta receptors and promote sensitivity to growth inhibition by TGF-beta. Furthermore, because TGF-beta has been shown to function in late G1 of the cell cycle, we examined the ability of TGF- beta to modulate two tumor suppressor proteins known to be critical regulators of the G1/S transition, Rb and p53. Rb is a 105- to 110-kD phosphoprotein, which has been shown to maintain its growth suppressive function when it is found in the hypophosphorylated state. Wild-type p53 is a 53-kD phosphoprotein that appears to be important in preventing cell-cycle progression and promoting apoptosis in cells with DNA damage, whereas mutant p53 can overcome those functions. We show here that TGF-beta treatment of phorbol myristate acetate (PMA) or anti- Ig-activated RL cells results in growth inhibition through a dual effect on Rb and mutant p53. After TGF-beta treatment, we observe a predominance of Rb in the hypophosphorylated, growth suppressive form. In addition, we show a decrease in levels of mRNA and protein for mutant p53. We also show that, although these changes are sufficient to halt progression through the cell cycle, the cells do not appear to undergo extensive programmed cell death following 72 hours of TGF-beta treatment. Thus, although these lymphoma cells maintain the capacity to be negatively growth regulated by TGF-beta, the ability of TGF-beta to induce apoptosis must be independently controlled.     

Future Directions for Intrathecal Pain Management: A Review and Update From the Interdisciplinary Polyanalgesic Consensus Conference 2007

Background. Expert panels of physicians and nonphysicians, all expert in intrathecal (IT) therapies, convened in the years 2000 and 2003 to make recommendations for the rational use of IT analgesics, based on the preclinical and clinical literature known up to those times, presentations of the expert panels, discussions on current practice and standards, and the result of surveys of physicians using IT agents. An expert panel of physicians and nonphysicians has convened in 2007 to update information known regarding IT therapies and to update information on new and novel opioid and nonopioid analgesic compounds that might show promise for IT use. Methods. A review of preclinical and clinical published relevant studies from 2000 to 2006 was undertaken and disseminated to a convened expert panel of physicians and nonphysicians to discuss new and novel analgesic agents for IT use. Results. The panelists identified several agents that were worthy of future studies for the clinical and rational use of IT agents that are presented in this article. Conclusions. A list of nonopioid IT analgesics, including gabapentin, adenosine, octreotide, the χ‐conopeptide, Xen2174, the conopeptide, neurotensis 1 agonist, CGX‐1160, the ω‐conotoxin, AM‐336, and physostigmine, were identified as worthy of future research by the panelists.     

Monitoring human tumor response to therapy by means of P-31 MR spectroscopy

Tumors in 23 patients were studied by means of in vivo phosphorus-31 magnetic resonance (MR) spectroscopy. In five patients, the response to chemotherapy and radiation therapy was monitored in a long-term follow-up study. In one patient, the P-31 MR spectra were recorded during the infusion of chemotherapeutic drugs. In comparison with healthy muscle tissue of patients, the tumors showed elevated inorganic phosphate, phosphomonoester, and phosphodiester peaks and reduced creatine phosphate peaks, whereas the nucleoside 5'-triphosphate levels remained nearly unchanged. Tumor treatment resulted in changes in the ratio of the signal intensity value of creatine phosphate to that of inorganic phosphate and in the sum of these values. In an osteosarcoma, an initial response followed by renewed tumor growth was clearly indicated by changes in these parameters. In the short-term follow-up examination, slight spectral changes were observed during the infusion of chemotherapeutic drugs. Changes in the concentrations of phosphorus metabolites during therapy can therefore be monitored in human tumors by means of P-31 MR spectroscopy.