Nuclear magnetic resonance proton imaging of bone pathology

Thirty-two patients with diversified pathology were examined with a supraconductive NMR imager using spin echo with different TR and TE to obtain T1 and T2 weighted images. They included 20 tumors (12 primary, eight metastasis), six osteomyelitis, three fractures, two osteonecrosis, and one diffuse metabolic (Gaucher) disease. In all cases except for the stress fractures, the bone pathology was clearly visualized in spite of the normal lack of signal from the compact cortical bone. Nuclear magnetic resonance (NMR) imaging proved to be at least as sensitive as radionuclide scintigraphy but much more accurate than all other imaging procedures including computed tomography (CT) and angiography to assess the extension of the lesions, especially in tumors extended to soft tissue. This is due both to easy acquisition of sagittal and coronal sections and to different patterns of pathologic modifications of T1 and T2 which are beginning to be defined. It is hoped that more experience in clinical use of these patterns will help to discriminate between tumor extension and soft-tissue edema. We conclude that while radionuclide scintigraphy will probably remain the most sensitive and easy to perform screening test for bone pathology, NMR imaging, among noninvasive diagnostic procedures, appears to be at least as specific as CT. In addition, where the extension of the lesions is concerned, NMR imaging is much more informative than CT. In pathology of the spine, the easy visualization of the spinal cord should decrease the need for myelography.     

Crossed anomic aphasia: mild naming deficits following right brain damage in a dextral patient.

A detailed case study is reported of crossed aphasia (CA) in a dextral patient, bearing upon such controversial issues as intrahemispheric localisation of language function and hemispheric reversal of nonverbal function. DA, a man aged 37, developed a mild naming problem due to right temporal lobe haematoma. Apart from a mild acquired stutter, his continuous speech was fluent and had a normal proportion of open to closed class lexical items. His naming deficit appears to originate in the 'blocking' or 'disconnection' of the phonological lexicon: he could usually give a functional definition of un-named items and retrieve them with the help of a phonemic cue. Lexical retrieval appears his only language deficit, as he had no comprehension or phonological discrimination deficits. DA showed no visuo-spatial or auditory-nonverbal deficits, suggesting the complete reversal of hemispheric specialisation.     

Different impacts of intestinal lymphatic transport on the oral bioavailability of structurally similar synthetic lipophilic cannabinoids: Dexanabinol and PRS-211,220

The aim of this article was to investigate the role of intestinal lymphatic transport in the oral bioavailability of two structurally similar synthetic lipophilic cannabinoids: dexanabinol and PRS-211,220. For this purpose, the long chain triglyceride (LCT) solubility and affinity to chylomicrons ex vivo of both cannabinoids were evaluated. Their oral bioavailability was assessed in rats following administration in a lipid-free and a LCT-based formulation. The intestinal lymphatic transport of these two molecules was also directly measured in a freely moving rat model. LCT solubility of dexanabinol and PRS-211,220 was 7.9 ± 0.2 and 95.8 ± 5.3 mg/g, respectively. The uptake by chylomicrons was moderate (31.6 ± 5.2%) and high (66.1 ± 2.4%), respectively. The bioavailability of dexanabinol (37%) was not affected by LCT solution, whereas administration of PRS-211,220 in LCT improved the absolute oral bioavailability three-fold (from 13 to 35%) in comparison to the lipid-free formulation. The intestinal lymphatic transport of dexanabinol and PRS-211,220 was 7.5 ± 0.8 and 60.7 ± 6.8% of the absorbed dose, respectively. In conclusion, despite structural similarity and similar lipophilicity, dexanabinol and PRS-211,220 exhibited a very diverse pattern of oral absorption, and the lymphatic system played quite a different role in the oral bioavailability of these molecules. The low lymphatic transport of dexanabinol is likely driven by relatively lower affinity to chylomicrons and lower LCT solubility.     

Conversion of Ouabain-Induced Ventricular Tachycardia in Dogs with Epicardial Lidocaine: Pharmacodynamics and Functional Effects

Epicardial antiarrhythmic drug administration was studied as a therapeutic approach for experimental ventricular tachycardia (VT) in an open-chest dog model. Lidocaine-polyurethane matrices (28%, w/w) were formulated as a model system. Matrices were placed on the left ventricular epicardium in each of 23 anesthetized open-chest dogs with ouabain-induced VT, to evaluate effectiveness in restoring sinus rhythm. Conversion occurred in all animals treated with matrices containing 300 mg or more of lidocaine after 1.5 to 7.0 min. The matrix lidocaine content correlated linearly with the time required for conversion to sinus rhythm (r = 0.75, P = 0.0002); irrespective of matrix size the myocardial/plasma lidocaine ratio was 20.1 ± 4.2 (mean ± SD) at the time of conversion. In a separate series of five dogs without ventricular tachycardia, systolic wall thickening measured with sonomicrometers after 5 min of controlled-release lidocaine administration (500- to 1000-mg matrix lidocaine content, 7.48 ± 3.49-mg/kg dose) was only minimally diminished (–14.1%) and this effect was observed only at the site of matrix placement on the anterior-apical epicardium. In contrast, intracoronary injection of 0.3 or 1.0 mg/kg of lidocaine-HCl resulted in complete elimination of wall thickening or replacement by systolic thinning. Thus epicardial administration of lidocaine from polyurethane matrices was an effective means of treating ouabain-induced ventricular tachycardia. Regional myocardial function in the vicinity of the matrices was modified to a very limited degree, supporting the view that the matrices can be used safely, without serious risk to ventricular contractile performance.     

Iatrogenic diaphragmatic hernia due to laparoscopic gastric banding

A patient developed a huge diaphragmatic hernia following laparoscopic gastric banding. Almost the entire stomach was incarcerated within the left chest. Segmental necrosis of the greater curvature of the stomach necessitated partial gastrectomy. The postoperative course was uneventful. The etiology, diagnosis and treatment of this previously undescribed complication of laparoscopic gastric banding are addressed in relation to the present case.     

Cognition in stroke

Introduction – Despite the current interest in criteria for vascular dementia, global, as opposed to focal, cognitive change after cerebral infarction has rarely been studied. Material and methods – We documented the neuropsychological changes one to three weeks and three months post infarct in 25 unselected patients with acute, first cerebral infarcts. Results – Improvements were seen in processes thought to have a large subcortical component and in those mediated in the right hemisphere. Memory was relatively lightly affected. Conclusion – The minimal deficits seen in memory and the predominance of subcortical changes are at variance with the currently suggested criteria for vascular dementia. Further data of this kind are needed before firm criteria can be proposed for the global pattern of cognitive changes expected in vascular dementia.     

The relationship between receptor-effector unit heterogeneity and the shape of the concentration-effect profile: Pharmacodynamic implications

The apparent concentration-effect relationship is the ensemble of many effector units (such as individual cells or channels) that do not always exhibit a uniform stimulus-effect relationship. This concept is substantiated by many observations of heterogeneity in receptor-effector populations including hormone secreting cells, response to hormonal stimuli, activity pattern of second messengers, stimulus-evoked synaptic currents, and single ion channels. The relationship between drug concentration and magnitude of pharmacologic response is commonly described by the sigmoidalE _max model which was derived from the Hill equation. The sigmoidicity factor (N) in this model is assumed to be a pure mathematical parameter without physiological connotations. This work demonstrates that the numerical value ofN (measured empirically) is the product of two factors: (i) the degree of heterogeneity of the effector subunits, i.e., the elemental component that upon drug stimulus contributes its pharmacological effect independently and does not interact with other subunits (it could range from a single receptor up to a whole tissue), and (ii) value ofN ^*—the shape factor of the subunits' concentration-effect relationship. A special case of this approach occurs whenN ^*>5, which is an on-off case. HereN is determined by the distribution (density equation) of the subunit values. In case of heterogeneity of the microparameters of the effector subunits the apparentN will always have a lower value thanN ^*. According to this theory it can be concluded that without knowledge of the distribution of the microparameters no mechanistic interpretation can be deduced from the apparentN value. If in the futureN ^* can be determined by theoretical or experimental methods, the distribution function relatingN ^* toN can be calculated. The relevance of this theory is increased in view of the progress being made in advanced research techniques which may enable us to determine the concentration-effect relationship at the level of the individual effector unit.     

Immediate root canal disinfection with ultraviolet light: an ex vivo feasibility study.

OBJECTIVE: The study was designed to test application of ultraviolet light to root canal walls, as a mean of complementary immediate disinfection after the use of sodium hypochlorite. STUDY DESIGN: Root canals were infected ex vivo with Enterococcus faecalis for 48 hours. Non-attached bacteria were washed away, and the remaining attached bacteria were subjected to disinfection, with 5% sodium hypochlorite alone or followed by exposure to ultraviolet light (254 nm, 300 mJ/cm(2)). Root canals were then tested for remaining viable bacteria. Canals were obturated and tested again after 14 days. RESULTS: Sodium hypochlorite alone achieved negative cultures in only 47% of the cases, but 96% was achieved with sodium hypochlorite followed by ultraviolet light (P < .001). This status was also maintained after 14 days. CONCLUSIONS: Illumination of root canals with ultraviolet light may be an effective supplementary means to achieve immediate disinfection of infected root canals.     

Colonic Drug Delivery: Enhanced Release of Indomethacin from Cross-Linked Chondroitin Matrix in Rat Cecal Content

Pharmaceutical Research -