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.     

Reduced temporal lobe blood flow in Alzheimer's disease.

We used single photon emission computed tomography with the blood flow tracer [123I]N-isopropyl-p-iodoamphetamine (IMP) to study regional cerebral blood flow (rCBF) in 50 mildly and moderately demented Alzheimer's disease (AD) patients to evaluate rCBF as a function of disease severity. Relative rCBF (normalized to occipital cortex) was significantly lower than controls in temporal cortex for both mildly and moderately demented patients. Similar numbers of patients in both groups demonstrated perfusion abnormalities in temporal neocortex. Parietal cortex was more variably involved with greater numbers of moderately than mildly demented patients showing perfusion abnormalities. Relative rCBF in dirsolateral frontal cortex was reduced only in the moderately demented patients. Disease severity, as measured by the Mini Mental Status Examination, was associated with relative rCBF only in dorsolateral frontal and parietal cortex. These results suggest that the temporal lobes are the first neocortical regions affected by AD and that other cortical areas become involved as the disease progresses.     

Positron emission tomography with [18F]fluorodeoxyglucose differentiates normal pressure hydrocephalus from Alzheimer-type dementia.

Because diagnostic criteria for normal pressure hydrocephalus have not been clearly determined, it is often difficult to differentiate patients with this potentially treatable condition from those with Alzheimer-type dementia. We have studied three patients with normal pressure hydrocephalus, 17 patients with Alzheimer-type dementia, and seven healthy elderly controls using positron emission tomography and [18F]Fluorodeoxyglucose (FDG). Both Alzheimer-type dementia and normal pressure hydrocephalus groups showed lower cortical rates of FDG utilisation than controls. However, the patterns of metabolic abnormality were distinctly different in the two dementia groups, with Alzheimer-type dementia subjects demonstrating bilateral temporoparietal hypometabolism while normal pressure hydrocephalus subjects showed globally diminished glucose use.