Cavernous angiomas of the spinal cord

Five cases of histologically verified cavernous angiomas of the spinal cord are reported. Acute lower-extremity sensory disturbance was the initial symptom in four patients, and one presented with weakness of the hand. Progressive neurological deficit occurred in all patients, but the clinical course and outcome were extremely variable. Myelography revealed an intramedullary lesion in two cases but was completely normal in three; magnetic resonance imaging was diagnostic in these patients. Subtotal removal was accomplished in two cases, and myelotomy and biopsy were carried out in three. Four of the cavernous angiomas were located in the cervicothoracic region, whereas one was found in the thoracolumbar cord. All of the patients exhibited characteristic gross and microscopic features as well as hemosiderin-laden macrophages indicating remote hemorrhage. The diagnostic, therapeutic, and prognostic implications of this rare condition are discussed.     

Intraperitoneal infection with Salmonella abortusovis is partially controlled by a gene closely linked with the Ity gene.

The aim of the present study was to determine whether the Ity gene, which controls the resistance to S. typhimurium infection in mice, also governs the resistance to S. abortusovis, a serotype specific for goat and sheep. During either i.v. or i.p. infection, BALB/c mice (Itys) were not able to control the growth of S. abortusovis and eventually died from infection. In contrast CBA (Ityr) or (C.CB)F1 (Ityr/s) mice were able to control the growth of these bacteria. Using congenic C.D2 Ityr mice, we found that the gene controlling resistance to S. abortusovis was tightly linked to the Ity gene on chromosome 1. Furthermore, in the spleen and the liver of backcross BALB/c x (CBA x BALB/c) mice, the S. abortusovis resistance phenotype cosegregated with the two alleles of the Len-1 gene, a gene tightly linked to the Ity gene. By contrast, in these backcross mice, the level of infection of the peritoneal cavity, the site of inoculation, did not correlated with the Len-1 phenotype of the animal. These results provide evidence that after i.p. inoculation the control of S. abortusovis growth in the spleen and the liver is controlled by the Ity gene, but also suggest that additional gene(s) regulate the number of bacteria at the site of inoculation.     

Percutaneous transluminal coronary angioplasty in patients with spasm superimposed on atherosclerotic narrowing

Of 552 patients undergoing percutaneous transluminal coronary angioplasty 102 had coronary artery spasm superimposed on atherosclerotic narrowing. Coronary angioplasty was successful in 97 (95%). The patients were discharged on a regimen of nifedipine (40-60 mg/day). Seventy six patients were symptom free 6-8 months after the procedure. Restenosis was detected in 35% of patients. Coronary artery spasm was provoked in 38 (44%) of the 87 patients who underwent an ergometrine maleate test. Twenty seven of the 34 patients with restenosis had a provocation test and coronary artery spasm was superimposed on restenosis in 22 (81.5%). Coronary angioplasty is feasible in patients with coronary artery spasm superimposed on atherosclerotic narrowing but the rate of restenosis is high and coronary artery spasm could have a role in the pathogenesis of restenosis.     

Cytochromes of the P450 2C subfamily are the major enzymes involved in the O-demethylation of verapamil in humans

The calcium channel blocker verapamil [2,8-bis-(3,4-dimethoxyphenyl)-6-methyl-2-isopropyl-6-azaoctanitrile] undergoes extensive biotransformation in man. We have previously demonstrated cytochrome P450 (CYP) 3A4 and 1A2 to be the enzymes responsible for verapamil N-dealkylation (formation of D-617 [2-(3,4-dimethoxyphenyl)-5-methylamino-2-isopropylvaleronitrile]), and verapamil N-demethylation (formation of norverapamil [2,8-bis(3,4-dimethoxyphenyl)-2-isopropyl-6-azaoctanitrile]), while there was no involvement of CYP3A4 and CYP1A2 in the third initial metabolic step of verapamil, which is verapamil O-demethylation. This pathway yields formation of D-703 [2-(4-hydroxy-3-methoxyphenyl)-8-(3,4-dimethoxyphenyl)-6-methyl-2-isopropyl-6-azaoctanitrile] and D-702 [2-(3,4-dimethoxyphenyl)-8-(4-hydroxy-3-methoxyphenyl)6-methyl-2-isopropyl-6-azaoctanitrile]. The enzymes catalyzing verapamil O-demethylation have not been characterized so far. We have therefore identified and characterized the enzymes involved in verapamil O-demethylation in humans by using the following in vitro approaches: (I) characterization of O-demethylation kinetics in the presence of the microsomal fraction of human liver, (II) inhibition of verapamil O-demethylation by specific antibodies and selective inhibitors and (111) investigation of metabolite formation in microsomes obtained from yeast strain Saccharomyces cerevisiae W(R), that was genetically engineered for stable expression of human CYP2C8, 2C9 and 2C18.In human liver microsomes (n=4), the intrinsic clearance (CL_int), as derived from the ratio of V _max/K_m, was significantly higher for O-demethylation to D-703 compared to formation of D-702 following incubation with racemic verapamil (13.9±1.0 vs 2.4±0.6 ml^*min^{-1 *}g^-1 mean±SD; p<0.05), S-Verapamil (16.8±3.3 vs 2.2±1.2 ml^* mini^*g^-1, p<0.05) and R-verapamil (12.1±2.9 vs 3.6 ±1.3 ml^*min^{-1 *} g^-1; p<0.05), thus indicating regioselectivity of verapamil O-demethylation process. The CL_int of D-703 formation in human liver microsomes showed a modest but significant degree of stereo selectivity (p<0.05) with a S/R-ratio of 1.41±0.17. Anti-LKM2 (anti-liver/kidney microsome) autoantibodies (which inhibit CYP2C9 and 2C19) and sulfaphenazole (a specific CYP2C9 inhibitor) reduced the maximum rate of formation of D-703 by 81.5±4.5% and 45%, that of D-702 by 52.7±7.5% and 72.5%, respectively. Both D-703 and D-702 were formed by stably expressed CYP2C9 and CYP2C18, whereas incubation with CYP2C8 selectively yielded D-703.In conclusion, our results show that enzymes of the CYP2C subfamily are mainly involved in verapamil O-demethylation. Verapamil therefore has the potential to interact with other drugs which inhibit or induce these enzymes.     

Early beneficial effect of streptokinase on left ventricular function in acute myocardial infarction

The effect of intravenous streptokinase therapy on the time course of functional recovery was investigated in a controlled study of 64 patients randomized within 3 hours after the onset of acute myocardial infarction (AMI). Contrast ventriculography was performed 1 to 4 days after AMI and repeated 5 weeks later. Wall motion was analyzed by the centerline method in the central infarct, peripheral infarct and noninfarct regions. In patients with ventriculographic data at the early catheterization, streptokinase-treated patients had less severe hypokinesia in the central infarct region than control patients (-2.9 +/- 0.9 [n = 29] vs -3.4 +/- 0.7 standard deviations below normal [n = 21], p less than 0.05). The benefit of streptokinase was more marked in the peripheral infarct region (-1.5 +/- 0.7 vs -2.1 +/- 0.6, p less than 0.001). As a result, the ejection fraction was slightly higher in treated versus control groups (46 +/- 10 vs 43 +/- 7%, respectively; difference not significant). At 5 weeks, function in the streptokinase and control groups had diverged further because of continued improvement in the streptokinase-treated patients. This study shows that streptokinase benefits left ventricular (LV) function by 1 to 4 days after AMI, earlier than previously reported. The benefit was not limited to the peripheral infarct region, where ischemia might have been less severe, but was also seen in the central infarct region. The implication is that thrombolytic therapy can improve LV function during the period of myocardial stunning, while myocardial function is still recovering.     

Assessment of olfactory and trigeminal function using chemosensory event-related potentials.

GOALS: To give an overview on the theoretical and practical applications of chemosensory event-related potentials. METHODS: Chemosensory event-related potentials (ERPs) may be elicited by brief and precisely defined odorous stimuli. Based on the principles of air-dilution olfactometry, a stimulator was developed in the late 1970s, which allows stimulation of the olfactory neuroepithelium and the nasal mucosa with no concomitant mechanical stimulation. Chemosensory ERPs were obtained after stimulation of the olfactory nerve (olfactory ERPs) or the trigeminal nerve (somatosensory or trigeminal ERPs). The characteristics of the stimulator for chemosensory research as well as the variables influencing the responses are discussed in this paper. RESULTS: Implementation and normative data from our department are reported with different clinical examples from otorhinolaryngologic clinic. The bulk of the evoked response consists of a large negative component (often referred to as N1), which occurs between 320 and 450 ms after stimulus onset. This component is followed by a large positive component, often referred to as P2, occurring between 530 and 800 ms after stimulus onset. Absence of olfactory ERPs and presence (even with subtle changes) of somatosensory ERPs is a strong indicator of the presence of an olfactory dysfunction. CONCLUSIONS: This review examines and discusses the methods of chemosensory stimulation as well as the electrophysiological correlates elicited by such stimuli. The clinical applications of chemosensory ERPs in neurology and otorhinolaryngology are outlined.     

Mechanobiology and force transduction in scars developed in darker skin types

BACKGROUND: Scarring is a complex process involving many cell types, cytokines and biological pathways including mechanobiology. Some subtle mechanical properties of skin can be assessed by measuring the speed of ultrasound shear wave propagation. The orientation of abnormal skin tension forces can be visualized, particularly in darker skin types, using dermoscopy showing distinct patterns of rete ridges' conformation. AIM: To assess some mechanobiological features of scars in darker skin types. PATIENTS AND METHODS: Large atrophic and hypertrophic surgical scars were examined on the trunk of 35 darker skin subjects. The surrounding skin was used as a comparator. Dermoscopic aspects were recorded. Resonance running time measurements (RRTM) were performed using a shear wave propagation device (Reviscometer). They were performed in four specific directions at given angles with regard to the long axis of the scar. The minimum, maximum and mean RRTM values were recorded at each site. RESULTS: Dermoscopy revealed patterns of melanin deposits in scars distinct from the normal honeycomb network seen in the surrounding skin. Hypertrophic scars showed a patchy pattern of large macular melanoderma dispersed in a lighter background. In these cases, low RRTM values were obtained with little variations according to the orientation of the measurements. By contrast, atrophic scars showed a streaky laddering melanotic pattern under dermoscopy. Higher RRTM values were often obtained, particularly in the transversal direction of the scars. Mechanical anisotropy was greater in the atrophic scars compared with the normal skin. DISCUSSION: Darker skin types represent a model for visualizing the main orientation of the epidermal rete ridges. A correlation was found between the pattern of melanized rete ridges of scars and the main orientation of the intrinsic forces in the skin.     

Use of stereotactic PET images in dosimetry planning of radiosurgery for brain tumors: clinical experience and proposed classification.

We developed a technique that allows the routine integration of PET in stereotactic neurosurgery, including radiosurgery. We report our clinical experience with the combined use of metabolic (i.e., PET) and anatomic (i.e., MRI and CT) images for the radiosurgical treatment of brain tumors. We propose a classification describing the relative role of the information provided by PET in this multimodality image-guided approach. METHODS: Between December 1999 and March 2003, 57 patients had stereotactic PET as part of their image acquisition for the planning of gamma knife radiosurgery. Together with stereotactic MRI and CT, stereotactic PET images were acquired on the same day using either (18)F-FDG or (11)C-methionine. PET images were imported in the planning software for the radiosurgery dosimetry, and the target volume was defined using the combined information of PET and MRI or CT. To analyze the specific contribution of the PET findings, we propose a classification that reflects the strategy used to define the target volume. RESULTS: The patients were offered radiosurgery with PET guidance when their tumor was ill-defined and we anticipated some limitation of target definition on MRI alone. This represents 10% of the radiosurgery procedures performed in our center during the same period of time. There were 40 primary brain lesions, 7 metastases, and 10 pituitary adenomas. Abnormal PET uptake was found in 62 of 72 targets (86%), and this information altered significantly the MRI-defined tumor in 43 targets (69%). CONCLUSION: The integration of PET in radiosurgery provides additional information that opens new perspectives for the optimization of the treatment of brain tumors.     

Does Preoperative Coronary Angioplasty Improve Perioperative Cardiac Outcome?

Background: Percutaneous coronary intervention (PCI) is performed in patients with coronary artery disease who are undergoing major noncardiac procedures to reduce perioperative cardiac morbidity and mortality. However, the impact of this approach on postoperative outcome remains controversial.

Methods: The authors analyzed a cohort of 1,152 patients after abdominal aortic surgery in which 78 patients underwent PCI. A propensity score analysis was performed. Also, using a logistic regression model, the authors determined variables associated with a severe postoperative coronary event or a death in patients without PCI. Then, in patients with PCI, they compared the expected and observed outcome.

Results: Five variables (age > 75 yr, blood transfusion > 3 units, repeated surgery, preoperative hemodialysis, and previous cardiac failure) independently predicted (with 94% correctly classified) a severe postoperative coronary event, and five variables (age > 75 yr, repeated surgery, previously abnormal ST segment/T waves, previous hypertension, and previous cardiac failure) independently predicted (with 97% correctly classified) postoperative death. In the PCI group, the observed percentages of patients with a severe postoperative coronary event (9.0% [95% confidence interval, 4.4-17.4]) or death (5.1% [95% confidence interval, 2.0-12.5]) were not significantly different from the expected percentages (8.2 and 6.9%, respectively). When all patients were pooled together, the odds ratios of PCI were not significant. The propensity score analysis provided a similar conclusion.