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Biomedical subjects

H C Roberts

Publications and source records attributed to H C Roberts.

27 records · Page 2Linked to original sources

[The algorithm of imaging diagnostics of pulmonary embolism: is it time for a new definition?].

Acute pulmonary embolism (PE) is an increasing and underdiagnosed cause of mortality and morbidity in hospitalised patients: pulmonary hypertension based on chronic pulmonary embolism is an uncommon, but severe and surgically curable complication. Since clinical signs might be silent or unspecific, both acute and chronic PE require imaging methods for diagnosis and treatment planning. Chest radiographic findings are usually non-specific. Scintigraphy provides a high sensitivity for PE, but lacks anatomic resolution and sufficient specificity. Pulmonary angiography, albeit accurate, is an invasive procedure associated with low but still not negligible morbidity and mortality. Hence, non-invasive methods offer advantages. Spiral CT, for example, is most reliable in the diagnosis of acute and chronic PE: Such fast CT techniques provide a non-invasive means to detect and differentiate acute emboli and organised thrombi, as well as perfusion abnormalities and other concomitant findings. MRI offers both morphological and functional information on lung perfusion and right heart function, but its image quality still needs improvement to be comparable with CT. Thus, while MRI must still be tested in clinical studies. CT is recommended as a screening method in acute and chronic pulmonary embolism.

Algorithms↗

Spiral CT of pulmonary hypertension and chronic thromboembolism.

Pulmonary hypertension caused by chronic pulmonary embolism (PE) represents an uncommon, but severe and surgically curable complication of recurrent acute embolism. Because clinical signs might be silent or nonspecific, chronic PE requires imaging methods for diagnosis and treatment planning. Chest radiographic findings are usually nonspecific. Scintigraphy provides a high sensitivity for PE, but lacks anatomic resolution and sufficient specificity. Pulmonary angiography, albeit accurate, is an invasive procedure associated with low but still considerable morbidity and mortality. Thus, noninvasive methods are required. Most reliably in the diagnosis of acute and chronic PE, fast computed tomography (CT) techniques like spiral CT provide noninvasive means to detect and differentiate organized mural thrombi, as well as perfusion abnormalities and concomitant findings. Magnetic resonance imaging offers morphologic as well as functional information on lung perfusion and right heart function, but image quality needs improvement to be comparable with spiral CT. Thus, although spiral CT is recommended as the screening method for acute and chronic PE, magnetic resonance imaging might be the method of the future.

Chronic Disease↗

The antiparasite effects of cyclosporin A: possible drug targets and clinical applications.

1. The immunosuppressive drug cyclosporin A, and some of its nonimmunosuppressive derivatives, are potent inhibitors of a range of parasites of humans. 2. Cyclosporin A and the structurally unrelated immunosuppressant FK506 are known to act on T-lymphocytes as complexes with their binding proteins, cyclophilins and FKBPs, respectively. 3. Cyclophilins and FKBPs have been structurally identified in a number of parasites and, in some instances, are believed to play roles in the antiparasitic actions of these drugs. 4. Nonimmunosuppressive cyclosporins and FK506 derivatives may have clinical potential in certain parasitic diseases, especially malaria and schistosomiasis, and identification of the targets of these drugs in parasites may lead to development of novel chemotherapeutic agents.

Amino Acid Isomerases↗

Hymenolepis diminuta and H. microstoma: uptake of cyclosporin A and drug binding to parasite cyclophilins.

Cyclosporin A (CsA) acts as a powerful immunosuppressant through its binding to the cytosolic isomerase, cyclophilin (CyP), forming a complex which inhibits the phosphatase activity of calcineurin. The drug is also selectively anti-parasitic but its mode of action remains unknown. The mouse tapeworm, Hymenolepis microstoma is sensitive to CsA, but the rat tapeworm, H. diminuta is not susceptible either in rats, mice or in vitro. Using these two tapeworm models, the uptake and binding of CsA were examined in relation to parasite cyclophilins. Uptake and compartmentalization of the drug were markedly different in the two species: H. microstoma takes up more drug than does H. diminuta and sequesters more drug into intracellular compartments. Characterization of cyclophilins using both CsA binding and isomerase activity assays reveals that H. microstoma possesses two cyclophilin isoforms (M(r) 17,700 and 21,400) with isomerase activity that is inhibited by CsA. using identical assays, we have been unable to demonstrate CsA-binding proteins or CsA-sensitive isomerase activity in H. diminuta. These data suggest that the anthelmintic action of CsA relates in some way to the presence and function of parasite cyclophilins.

Amino Acid Isomerases↗

Pain and its control in patients with fractures of the femoral neck while awaiting surgery.

A survey, by two methods, of the pain felt preoperatively by 100 elderly patients with an acute fracture of the femoral neck showed that most felt a great deal of pain and that a painless fracture was exceptional. No relationship was found between pain appreciation and the patient's fracture type or their age. One of the methods suggested that elderly patients with preserved mental function felt more pain, and the other that less pain was felt by those taking regular prefracture analgesia. The amount of analgesic drugs given to the patients in this survey seemed inadequate for their levels of perceived pain; accordingly regular measurement by nurses of the degree of pain felt preoperatively by patients with this condition is recommended, together with a greater medical review of the medication being prescribed.

Aged↗

Further studies on the action of 5-hydroxytryptamine in the dorsal lateral geniculate nucleus of the cat.

The possibility that 5-HT has a presynaptic inhibitory influence on the optic nerve input to the LGNd has been examined. We have compared the effect of iontophoretic application of 5-HT on the excitatory responses of LGNd neurons to visual stimulation and iontophoretic pulses of ACh and DLH. In contrast to previous studies the results suggest that 5-HT has only postsynaptic depressant effects and we found no evidence for a selective inhibition of the optic nerve input. It is proposed that the difference between the present result and those previously reported may reflect the method of stimulation of the optic nerve input. The weaker excitatory responses produced with electrical stimulation and diffuse light flashes of the earlier studies may be more susceptible to the postsynaptic depressant actions of 5-HT than the powerful visually evoked responses of the present study. Our data are only consistent with a postsynaptic depressant role for 5-HT in the LGNd.

Acetylcholine↗

Comparison of albumin-(Gd-DTPA)30 and Gd-DTPA-24-cascade-polymer for measurements of normal and abnormal microvascular permeability.

The purpose of this study was to compare a new MR macromolecular contrast medium (MMCM), gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)-24-cascade-polymer, to a well-studied prototype MMCM, for the potential of distinguishing tissues of varying endothelial permeability. Three tissue models of varying capillary permeability were studied in a total of 46 rats: normal myocardium (normal capillaries), subcutaneously implanted adenocarcinoma (mild capillary leak), and reperfused infarcted myocardium (high capillary leak). TI-weighted MRI was performed before and dynamically after injection of either albumin-(Gd-DTPA)30 or the cascade polymer (each .02 mmol gadolinium [Gd] per kg). Data analysis based on a two-compartment kinetic model yielded estimates of fractional blood volume (BV) (percentage) and fractional leak rate (FLR) (1 per hour). Permeability to the cascade polymer as reflected in FLR was considerable in normal myocardium (8.24 per hour), of similar value in tumors (8.55 per hour), but significantly greater in infarcted myocardium (39.17 per hour, P < .01) versus normal myocardium. The larger albumin-(Gd-DTPA)30 demonstrated minimal extravasation in normal myocardium (FLR .33 per hour); FLR in tumors was 100% higher (.66 per hour, P < .002) and FLR in reperfused capillaries was significantly greater (7.94 per hour, P < .001). Based on capillary permeability measurements, the cascade polymer may have limited utility for detection of mildly increased microvascular permeabilities. For severe tissue injury, the cascade polymer can resolve abnormal microvascular integrity.

Analysis of Variance↗

Multisection dynamic CT perfusion for acute cerebral ischemia: the "toggling-table" technique.

A new CT perfusion technique providing extended anatomic coverage was evaluated in 12 patients with suspected acute middle cerebral artery ischemia. With a multidetector CT scanner, scans were obtained in an alternating fashion at two distinct "toggling" table positions (two 1-cm sections each) during a 40-mL contrast agent bolus (approximately 5 seconds per image), and perfusion parameter maps were created. The CT perfusion results were compared with follow-up images. Nine patients showed focal perfusion abnormalities in at least one section, most commonly on mean transit time maps. Using a single table location would have underestimated or missed the involved tissue in most cases. In three of 12 patients, perfusion maps failed to delineate any abnormality. In two patients, perfusion and diffusion MR imaging confirmed the absence of perfusion abnormality and tissue injury, respectively. In one case, a small ischemic injury was revealed by diffusion MR imaging. By using the toggling-table approach, perfusion images can be obtained over an extended anatomic area and, thus, reveal the presence and the extent of presumed tissue injury.

Brain Ischemia↗