The combination of mitogenic stimulation and DNA damage induces chondrocyte senescence.

OBJECTIVE: Cellular senescence is a phenotypic state characterized by stable cell-cycle arrest, enhanced lysosomal activity, and the secretion of inflammatory molecules and matrix degrading enzymes. Senescence has been implicated in osteoarthritis (OA) pathophysiology; however, the mechanisms that drive senescence induction in cartilage and other joint tissues are unknown. While numerous physiological signals are capable of initiating senescence, one emerging theme is that damaged cells convert to senescence in response to sustained mitogenic stimulation. The goal of this study was to develop an in vitro articular cartilage explant model to investigate the mechanisms of senescence induction. DESIGN: This study utilized healthy cartilage derived from cadaveric equine stifles and human ankles. Explants were irradiated to initiate DNA damage, and mitogenic stimulation was provided through serum-containing medium and treatment with transforming growth factor ß1 and basic fibroblastic growth factor. Readouts of senescence were a quantitative flow cytometry assay to detect senescence-associated ß galactosidase activity (SA-ß-gal), immunofluorescence for p16 and γH2AX, and qPCR for the expression of inflammatory genes. RESULTS: Human cartilage explants required both irradiation and mitogenic stimulation to induce senescence as compared to baseline control conditions (7.16% vs 2.34% SA-ß-gal high, p = 0.0007). These conditions also resulted in chondrocyte clusters within explants, a persistent DNA damage response, increased p16, and gene expression changes. CONCLUSIONS: Treatment of cartilage explants with mitogenic stimuli in the context of cellular damage reliably induces high levels of SA-ß-gal activity and other senescence markers, which provides a physiologically relevant model system to investigate the mechanisms of senescence induction.

Use of CHADS2 and CHA2DS2-VASc scores to predict prognosis after stroke.

INTRODUCTION: Stroke is one of the most devastating neurological disorders. Currently, we don't have an ideal score that predicts the prognosis of stroke patients. The CHADS2 and CHA2DS2-VASc scores are well-validated tools for the estimation of stroke risk in patients with atrial fibrillation. The purpose of this study was to investigate if these scores can predict the outcomes of all the patients who suffered an ischemic stroke regardless of atrial fibrillation. METHODS: Consecutive patients that were admitted with an acute ischemic stroke were classified into subgroups according to pre-stroke CHADS2 and CHA2DS2-VASc scores and after 2 years the functional outcome, stroke recurrence, major cardiovascular events and mortality were assessed. RESULTS: Among the 973 patients that were included in analysis, the mean age was 56.7 (SD 15.7) and 46.6% were female. There were 226 (23.2%), 365 (37.5%) and 382 (39.3%) patients with low, intermediate and high CHADS2 score, respectively. For CHADS2-VASc score there were 81 (8.3%), 268 (27.6%), and 624 (64.1%) patients with low, intermediate and high, respectively. Both high-risk scores were associated with middle-term poor functional outcome, stroke recurrence, major cardiovascular events and all-cause mortality. CHADS2 and CHA2DS2-VASc scores presented a high sensitivity and a high negative predictive value. CHA2DS2-VASc was more sensitive than CHADS2 score. CONCLUSION: CHADS2 and CHA2DS2-VASc scores were both associated with stroke outcomes regardless of atrial fibrillation. These scores can be useful tools for the prognosis stratification of a patient with an ischemic stroke.

Study of proteolysis in river buffalo mozzarella cheese using a proteomics approach.

The guarantee of the origin and quality of raw material is essential for the protection and valorization of Campana buffalo mozzarella cheese. The risk of utilization of semifinished products and stored milk in substitution for fresh milk is increasing, due to the continuous desire to reduce production costs. A proteomics approach and electrophoresis survey of retail mozzarella cheeses indicated different rates of proteolysis in the production of dairy industries. The use of fresh milk and correct cheesemaking protocol yielded only γ-caseins, which are derived from ß-casein by plasmin, and para-κ-casein, which is derived from κ-casein by chymosin. The detection of abnormal hydrolysis resulting in ß- and αS1-casein fragments, identified by mass spectrometry, indicates the use of stored milk or stored and pressed curd, or the reuse of unsold mozzarella cheese, to produce mozzarella. The formation of γ-caseins and other fragments during a long storage of raw materials at room or refrigeration temperature was ascribed to plasmin (endogenous milk enzyme), whereas formation of αS1-casein fragments, mainly αS1-I(6P)- and αS1-I(7P)-casein during the storage of curd was ascribed to the action of chymosin (exogenous enzyme) from rennet. Sodium dodecyl sulfate-PAGE and alkaline urea-PAGE permitted us to evaluate the freshness of the raw materials used in the manufacturing of buffalo mozzarella cheese and to reveal possible inappropriate preservation.

The burden of chronic kidney disease in long-term liver transplant recipients.

BACKGROUND: Chronic kidney disease (CKD) is an important risk factor for morbidity and mortality post-liver transplantation (OLT). This study focused on investigating the incidence and risk factors associated with the development CKD after OLT. METHODS: We performed a retrospective cohort study of recipients followed at least 5 years at our institution. CKD was diagnosed and classified according to National Kidney Foundation and the Kidney Disease Outcomes Quality Initiative guidelines. RESULTS: There were 231 patients, 64% men, 67% Caucasian, 16% African-American, and 17% others, with a mean age of 56 +/- 13 years. The mean glomerular filtration rate (GFR) of the population was 56 +/- 28 mL/min/1.73 m2. CKD was defined as GFR less than 60 mL/min; 144 patients (61%) were identified as having CKD. When these patients were compared to the non-CKD group, the former were significantly older (62 +/- 9 vs 52 +/- 12 years, P = .03), more likely to be hypertensive (59% vs 38%, P = .003), and required more antihypertensive medications (0.83 +/- 0.81 vs 0.52 +/- 0.77, P = .02); 26% of all patients had diabetes. However, the incidence of diabetes (43.3% vs 19.3%, P = .02) as well as the incidence of insulin dependency (21.6% vs 12.5%, P = .001) was significantly higher in the CKD population. Mean uric acid levels were higher in CKD patients compared to non-CKD patients (8.00 +/- 2.00 mg/dL vs 6.70 +/- 1.99 mg/dL respectively, P = .001); patients with uric acid more than 6.0 had a 1.7 risk of having CKD. CONCLUSIONS: CKD defined as GFR < 60 mL/min is highly prevalent in long-term OLT survivors. Older age, elevated systolic blood pressure, insulin-dependent diabetes mellitus, and elevated uric acid levels are independently associated with CKD.

An interesting case of a pituitary adenoma apoplexy mimicking an acute meningitis. Case report.

Apoplexy of a pituitary adenoma is a rare and under-diagnosed clinical occurrence. It results from either infarction or haemorrhage into an adenoma of the pituitary gland. Its clinical presentation more often includes rapid development of impaired consciousness, severe headache, visual disturbance and variable association of oculomotor nerve palsy. Meningeal irritation signs are considered very rare and usually not reported as presenting symptoms. A 33-year-old male suffered a pituitary macroadenoma apoplexy, clinically indistinguishable from an infectious meningitis at presentation. Three days after surgery, the patient developed a left ophthalmoplegia due to 3(rd) nerve palsy, which fully resolved within 2 months. A right pterional craniotomy was performed during which complete tumour removal was achieved. In conclusion the authors believe that, despite many reports in the literature, encouraging conservative management in pituitary apoplexy by administering intravenous steroids, surgery should be undertaken in order to avoid eventual visual field defects, relieve pituitary gland compression and prevent a possible recurrent apoplectic episode or tumor re-growth.

Anterior cervical corpectomy for cervical spondylotic myelopathy: experience and surgical results in a series of 70 consecutive patients.

Recently the debate over the management of cervical spondylotic myelopathy (CSM) has regained interest; more specifically whether treatment should be operative versus non-operative, raising the question about the real effectiveness of surgery in influencing the natural history of this pathology and about the choice of the most appropriate approach (anterior vs. posterior). The authors report a retrospective review of 70 consecutive patients who underwent elective anterior cervical corpectomy and fusion with iliac crest autograft or titanium mesh and placement of an anterior cervical plate for the treatment of CSM. The patients underwent pre-and postoperative evaluation, including history, and physical and neurological examination. Patients were also evaluated pre-and postoperatively using a modified version of the Japanese Orthopedics Association Scale (mJOA), which provides a fine semi-quantitative graded evaluation of overall function. Upon discharge home, patients were followed for an average of 42 months (range, 12-63 months). Following an anterior cervical decompression of the spinal cord, 94.2% of patients improved their functional status and 5.8% were unchanged; the mean preoperative mJOA score of all patients was 12.2, the postoperative was 15.4 and the amelioration was also documented by neurophysiological studies which showed an increase in amplitude and decrease in latency of somatosensory evoked potentials and motor evoked potential in 47 patients (67%). Older age and longer duration of preoperative symptoms both were not associated with a lower postoperative mJOA score (p < 0.47, p < 0.29, respectively). Single versus multiple level decompression was not predictive of a lower postoperative mJOA score (p < 0.18). Preoperative spinal cord low signal intensity changes on T1-weighted MRI were related to a lower postoperative mJOA score (p < 0.05), whereas spinal cord high-signal intensity changes on T2-weighted MRI were related to a higher postoperative mJOA score (p < 0.01); finally a lower preoperative mJOA score was highly predictive of a lower postoperative mJOA score (p < 0.0005). Anterior cervical corpectomy and fusion for CSM appears to be an effective procedure with a more favorable neurological improvement when compared to posterior decompressive laminectomy, minimally invasive procedures or non-surgical treatment. It is also a safe procedure even in the elderly population, with low morbidity and the potential for permanent spinal cord decompression and excellent bone stability.

Palm oil and cardiovascular disease: a randomized trial of the effects of hybrid palm oil supplementation on human plasma lipid patterns.

This study examines, for the first time, the effect of hybrid Elaeis oleifera × E. guineensis palm oil supplementation on human plasma lipids related to CVD risk factors. One hundred sixty eligible participants were randomized and assigned to one of the two treatments: 25 mL hybrid palm oil (HPO group) or 25 mL extra virgin olive oil (EVOO group) daily for 3 months. Fasting venous samples were obtained at baseline and after 1, 2 and 3 months for measurement of plasma lipids (TC, LDL-C, HDL-C and TAGs). Changes in body mass index and waist circumference were also assessed. Although there was an overall reduction in TC (7.4%, p < 0.001) and in LDL-C (15.6%, p < 0.001), no significant differences were found between the treatment groups in a repeated measures analysis of variance for TC (p = 0.0525), LDL-C (p = 0.2356), HDL-C (p = 0.8293) or TAGs (p = 0.3749). Furthermore, HPO consumption had similar effects on plasma lipids to EVOO, thus providing additional support for the concept that hybrid Elaeis oleifera × E. guineensis palm oil can be seen as a "tropical equivalent of olive oil".

Changes in the Fatty Acid Profile and Phospholipid Molecular Species Composition of Human Erythrocyte Membranes after Hybrid Palm and Extra Virgin Olive Oil Supplementation.

This work aims to evaluate and compare, for the first time, the effects of extra virgin olive oil (EVOO) and hybrid palm oil (HPO) supplementation on the fatty acid profile and phospholipid (PL) molecular species composition of human erythrocyte membranes. Results supported the effectiveness of both HPO and EVOO supplementation (3 months, 25 mL/day) in decreasing the lipophilic index of erythrocytes with no significant differences between HPO and EVOO groups at month 3. On the other hand, the novel and rapid ultraperformance liquid chromatography-tandem mass spectrometry method used for PL analysis reveals an increase in the levels of phosphatidylcholine and phosphatidylethanolamine species esterified with polyunsaturated fatty acids. This work demonstrates the ability of both EVOO and HPO to increase the degree of unsaturation of erythrocyte membrane lipids with an improvement in membrane fluidity that could be associated with a lower risk of developing cardiovascular diseases.

The use of virtual fluoroscopy in managing acute type II odontoid fracture with anterior single-screw fixation. A safe, effective, elegant and fast form of treatment.

BACKGROUND: The management of odontoid fractures represents both a clinical and a technical challenge due to the singular anatomy and biomechanics of the region. At present there is still much controversy as far as any form of management (surgical vs. conservative) is concerned and in any case there is not sufficient evidence to support a standardized form of treatment. This study was designed to further evaluate safety and efficacy of anterior odontoid single-screw fixation and to better determine the usefulness of Image Guided Surgery Virtual Fluoroscopy in treating such cases assessing also its advantages over traditional fluoroscopy and CT-guided frameless stereotaxy in the upper cervical spine surgery. METHODS: This was a retrospective review of ten patients presented during a short period of 18 months with acute traumatic Type II odontoid fractures. Nine underwent fixation within a mean of 3 days after injury, whereas a patient had to be operated upon on the 22nd day due to poor alignment with conservative treatment and ongoing instability. All patients postoperatively were fitted in a collar and then followed-up with serial clinical and radiographic examinations. FINDINGS: Radiological signs of fusion were seen in 10 cases (100%) (mean follow-up: 16 months). No complications occurred during the surgical procedure, nor were any instrumentation failures recorded; all patients remained neurologically intact. CONCLUSIONS: We believe that anterior odontoid screw fixation using Image Guided Surgery virtual fluoroscopy is a safe, effective, less time consuming and low x-ray exposure technique and we recommend this as the preferred treatment method for acute Type II odontoid fractures. Moreover, the use of image guided technology affords more precision, confidence and safety enabling the surgeon to approach the upper cervical spine in an easier and faster way.

Antihypertensive and cardiovascular effects of nitrendipine: a controlled study vs. placebo.

The antihypertensive and cardiovascular effects of nitrendipine, a calcium entry blocker similar to nifedipine, have been evaluated in a double-blind, placebo-controlled study in 20 patients with hypertension. At baseline and at the end of the 8-week period (nitrendipine, 20 mg once a day, or placebo, 1 tablet once a day) the following parameters were measured: systolic and diastolic blood pressure (BP) and heart rate (HR) at rest by an automatic recorder; BP, HR, and cardiac workload (systolic BP X HR) during exercise testing on a bicycle; left ventricular mass (LVMe according to the method of Devereux) and cross-sectional area (CSA), and main parameters of systolic function (end diastolic volume, end systolic volume [ESV], and ejection fraction [EF]) by M mode echocardiography. There was a significant decrease in BP at rest (163/108 vs. 144/92 mm Hg; P less than 0.001) and during exercise in subjects receiving nitrendipine, while placebo did not modify these parameters. LVMe (from 195 to 188 gm; P less than 0.01) and CSA (from 20.2 to 19.8 cm2; P less than 0.05) were reduced by nitrendipine, which also improved cardiac performance (ESV fell from 44 to 38 ml [P less than 0.001] and EF fell from 62% to 66% [P less than 0.01]). No effect was observed in the placebo group. Our results indicate that nitrendipine is a powerful antihypertensive agent that also improves cardiac performance and slightly but significantly reduces left ventricular mass.

Antimetastatic action and toxicity on healthy tissues of Na[trans-RuCl4(DMSO)Im] in the mouse.

The ruthenium-dimethylsulfoxide complex Na(trans-RuCl4(DMSO)Im] was given i.v. to mice bearing MCa mammary carcinoma and its effects on tumor growth and on healthy host tissues were studied by macroscopic examination of primary tumor growth, by survival time, and by histological analysis using light microscopy and SEM. Either by means of vivo-vivo bioassays or by microscopic examination it appeared that the growth of lung tumors was markedly reduced, whereas the growth of the i.m. primary tumor was much less affected. These effects account for the prolongation of survival time and for the cure rate observed. The favourable effect on survival time was also influenced by the lack of significant cytotoxicity for normal tissues such as lung and kidney epithelia, muscle and liver cells, splenocytes and bone marrow. It thus appears that the selective interaction with tumor cells in the lungs cannot simply be attributed to a selectively higher localization of the compound at this site, nor to a modification of the histological structure of primary tumor. These results highlight the pharmacologic properties of this compound for the control of solid tumor metastases, an effect that was shown to be similarly exerted on advanced tumor metastases.

Efficacy and safety of oral ciprofloxacin in the treatment of respiratory tract infections associated with chronic hepatitis.

Twenty patients with lower respiratory tract infections presumably caused by ciprofloxacin-susceptible bacteria were admitted to a non-comparative, prospective clinical study. All patients were hospitalized for chronic hepatitis at various stages of the disease. Ciprofloxacin was given orally at a dose of 250 mg every 12 hours for five to 10 days. Patients had either acute bronchitis, chronic bronchitis in the acute phase, or acute tracheobronchitis. In 19 of 20 patients treated, there was a favorable outcome (15 cures and four improvements). In 17 patients, the presumably causative pathogen was eradicated. No side effect was observed except for oral candidiasis, which occurred in two patients. This study demonstrates the clinical and bacteriologic efficacy of ciprofloxacin in pulmonary infection in patients with severe impairment of liver function.

Lysozyme induced recovery of the response to cona on mononuclear-cells harvested from mice bearing mca mammary-carcinoma.

The effects of lysozyme (hen egg-white lysozyme) on lymphocytes harvested from mice bearing MCa mammary carcinoma were tested at the daily dose of 100 mg/kg given orally for 10 consecutive days. With this experimental paradigm that consists of a significant reduction of lung metastasis formation, lysozyme was seen to be capable of stimulating the recovery of the response to ConA of mononuclear cells, reduced by tumor growth; this effect was particularly evident with splenocytes and GALT lymphocytes. The effects of lysozyme depended: (i) on the presence of plastic adherent cells, (ii) at least in in vitro experiments, on the amount of lysozyme used, being higher at the dose of 250 mug/ml of incubation mixture, and (iii) on the time of challenge with lysozyme. These effects were shown either by measuring the [H-3]-thymidine incorporation into DNA or by application of the sulphorhodamine test for protein synthesis. After in vivo treatment, lysozyme significantly modified the histological architecture of the mucosal immunity of the gut, by causing a significant reduction of the number of the lymphatic nodules placed immediately under the layer of epithelial cells of villi. At the same time no significant modification of Peyer's patches was noted. Together these data stress the role of lysozyme in the modulation of host immunity and, in particular, point out the relevance of the mucosal immunity of the gut as first target for lysozyme activity.

Stimulation of GALT and activation of mesenteric lymph node lymphocytes by a modified lysozyme in CBA mice with MCa mammary carcinoma.

Lysozyme (hen egg-white lysozyme) and its derivative mPEG-lyso (lysozyme coupled with polyoxyethyleneglycol) were tested in CBA mice bearing MCa mammary carcinoma for their effects on intestinal mucosal immunity (GALT) and mesenteric lymph node lymphocytes (MLNL), after oral administration. Following a cycle of administration of 100 mg/kg/day lysozyme or 350 mg/kg/day mPEG-lyso for 9 consecutive days, GALT was analyzed by using optical histology, and mesenteric lymph node lymphocytes were studied by cytofluorimetric analysis of CD3, CD4 and CD8 antigens, and of DNA and RNA content following in vitro culture with concanavalin A. Both lysozymes significantly increase the number of lymphatic nodules on gut epithelium as determined by histological analysis of sections of small bowel. mPEG-lyso, unlike native lysozyme, gives protection from the decline of the blastogenic activity of MLNL observed at early stages of tumor growth, as shown by the increased nucleic acid content of these cells. On the same cells, both lysozyme and mPEG-lyso also seem to prevent the decline of CD4+ cells observed during tumor growth in control animals. These data confirm the effects of lysozyme on GALT and show that the new lysozyme derivative mPEG-lyso has effects on host immunity greater than those of the native molecule.

Acute operation in cases of middle cerebral artery occlusion.

The authors describe their personal experience with middle cerebral artery embolectomy performed in four patients within 6 hours after the start of clinical symptoms. The work is of a preliminary nature. No conclusion can be drawn as to the ultimate value of this treatment, and further clinical trials seem justified.

In vitro down regulation of ICAM-1 and E-cadherin and in vivo reduction of lung metastases of TS/A adenocarcinoma by a lysozyme derivative.

The aim of the present investigation was to examine the effects of the lysozyme derivative mPEG-lyso (hen egg-white lysozyme coupled with polyoxyethylenglycol), on TS/A adenocarcinoma cell line in vivo and in vitro. mPEG-lyso reduces the number of ICAM-1+ and E-cadherin+ cells of TS/A adenocarcinoma cell line in vitro, and causes a marked decrease of spontaneous lung metastases in vivo. In both cases, mPEG-lyso reduces the number of tumour cells in sythesis and pre-mitotic phases. In connection with the reduction of cells expressing adhesion molecules, mPEG-lyso reduces the number of infiltrating leukocytes in the primary tumour in vivo and reduces the binding capacity of splenocytes to tumour cells in vitro. These data stress, for the first time, that the in vivo control of mPEG-lyso on lung metastasis formation of solid metastasising tumours may be due to a combination of effects on tumour cells in addition to those on host's immune system.

Treatment of metastases of solid mouse tumours by NAMI-A: comparison with cisplatin, cyclophosphamide and dacarbazine.

The effects of NAMI-A, a novel ruthenium compound endowed with selective antimetastatic action, were tested on solid metastasising tumours of the mouse in comparison to cisplatin, cyclophosphamide and dacarbazine. Each compound was administered i.p. as freshly prepared solutions in isotonic saline in combination with surgical removal of primary tumour, and was used at the maximum tolerated dose. NAMI-A significantly reduced the growth of lung metastases either when given prior to surgery (early growing tumours) on TS/A adenocarcinoma or after surgical ablation of primary tumours (already established lung metasases) on Lewis lung carcinoma. The postsurgical treatment of mice bearing MCa mammary carcinoma caused a significant prolongation of the life-span of the treated animals. In the comparison experiments, dacarbazine was completely ineffective, cisplatin was as active as NAMI-A on MCa mammary carcinoma, slightly less active than NAMI-A on TS/A adenocarcinoma and inactive on Lewis lung carcinoma, and cyclophosphamide was always more active than any other treatment performed. These data stress that NAMI-A, independently of the lack of direct cell cytotoxicity, when compared to the reference drugs, has a potent therapeutic effect in mice bearing solid metastasising tumours.

Cytofluorimetric analysis of gut-intraepithelial and mesenteric lymph node lymphocytes of tumour bearing mice fed with egg-white lysozyme.

The effects of the oral administration of 100 mg/kg/day egg-white lysozyme (EWL) on the expression of CD3, CD4, CD8 and CD25 antigens of lymphocytes harvested from IEL and mesenteric lymph nodes (MLNL) were tested in mice bearing MCa mammary carcinoma. Lysozyme, after oral administration, retains its enzymatic activity along the entire small bowel and almost 10% of the administered dose is recovered 1 hr after treatment in the middle of the jejunum. Correspondingly, the number of cells expressing the test antigens in MLNL is greater than in controls after a few days of treatment and is maintained high up to the end of treatment but returns to control values after treatment withdrawal; CD4:CD8 ratio is decreased by EWL in favour of CD8 positive cells. Treatment with EWL does not modify the ratio between CD4+ and CD8+ cells vs controls in IEL nor does it change the % of CD3 positive cells or the expression of IL-2 receptor at this level. These data support the existence of the induction of an immunity communication by EWL along the axis GALT-mesenteric lymph nodes which is in agreement with the reported effects of the oral administration of EWL on tumour growth in experimental systems and on host immunity in humans.

Extra-intracranial arterial bypass in typical carotid reversible ischaemic deficits: long-term follow-up in 100 patients.

The long-term follow-up of 100 consecutive patients who suffered from a reversible ischaemic attack (RIA) in the carotid territory and were submitted to extra-intracranial arterial bypass (EIAB) surgery in seven Italian Neurosurgical Centres is reported. The preoperative angiographic and clinical features, and the surgical complications are reported. The follow-up ranged from two to seven years with a mean of thirty-five months. In this period in the territory served by the bypass only two completed strokes and six RIAs occurred. Four patients died, only one for cerebral ischaemic problems. The results of the present series have been compared with those of the literature: they appeared consistent with other surgical series and clearly better than those of medical treated patients. The EIAB can then be considered a good therapeutic choice for the treatment of RIAs in carotid territory.

Long-term follow-up in 257 ICA occlusion: comparison between EIAB-treated and untreated patients.

The purpose of this paper is to estimate the real value of the Extra-Intracranial Arterial Bypass (EIAB) in preventing or reducing further and more catastrophic ischaemic events in patients suffering from an Internal Carotid Artery (ICA) occlusion. 257 patients, suffering from ICA occlusion, are considered retrospectively: 122 of them submitted to EIAB and 135 medically treated or untreated. In both groups, homogeneous by sex, age, neurological grading distribution and length of follow-up, the following parameters were considered: the incidence of ischaemic recurrences during the follow-up period; the characters of the recurrences with particular reference to the fatal stroke; the rate of ischaemic events per year. The comparison between the outcome in surgically treated patients and in "untreated" ones indicates that the EIAB can be effective in preventing or reducing the ischaemic recurrences and the frequency of fatal stroke in TIA-, RIND, or stroke-patients suffering from ICA occlusion.