Simvastatin protects against cholestasis-induced liver injury

Background:

Bile duct obstruction is associated with hepatic accumulation of leukocytes and liver injury. The aim of this study was to evaluate the effect of simvastatin on cholestasis-induced liver inflammation and tissue damage.

Experimental approach:

C57BL/6 mice were treated with simvastatin (0.02 and 0.2 mg·kg⁻¹) and vehicle before and after undergoing bile duct ligation (BDL) for 12 h. Leukocyte recruitment and microvascular perfusion in the liver were analysed using intravital fluorescence microscopy. CXC chemokines in the liver were determined by enzyme-linked immunosorbent assay. Liver damage was monitored by measuring serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Hepatic levels of myeloperoxidase (MPO) were also determined.

Key results:

Administration of 0.2 mg·kg⁻¹ simvastatin decreased ALT and AST by 87% and 83%, respectively, in BDL mice. This dose of simvastatin reduced hepatic formation of CXC chemokines by 37–82% and restored sinusoidal perfusion in cholestatic animals. Moreover, BDL-induced leukocyte adhesion in sinusoids and postsinusoidal venules, as well as MPO levels in the liver, was significantly reduced by simvastatin. Notably, administration of 0.2 mg·kg⁻¹ simvastatin 2 h after BDL induction also decreased cholestatic liver injury and inflammation.

Conclusions and implications:

These findings show that simvastatin protects against BDL-induced liver injury. The hepatoprotective effect of simvastatin is mediated, at least in part, by reduced formation of CXC chemokines and leukocyte recruitment. Thus, our novel data suggest that the use of statins may be an effective strategy to protect against the hepatic injury associated with obstructive jaundice.     

Fractionated stereotactic radiotherapy for optic nerve sheath meningioma: eight cases

Optic nerve sheath meningioma (ONSM) accounts for one-third of primary optic nerve tumors, and 2% of all meningiomas. ONSM must be distinguished from other meningiomas, in particular from cavernous meningiomas because of the different prognosis and treatment. The most frequent clinical sign is a progressive or sudden unilateral visual loss. Treatment of ONSM is still subject to discussion. This report covers a series of eight ONSM patients treated with fractionated stereotactic radiotherapy. MATERIAL AND METHODS: Between 2000 and 2006, we managed eight patients with ONSM. The average patient age was 47 years. There were five women and three men. The most frequent clinical signs were visual loss (100%), proptosis (35%), diplopia (25%). One patient was initially treated with surgery. All patient have been treated by fractionated stereotactic radiotherapy. 45 Gy in 25 fractions were delivered on the meningioma area at a rate of 5 fractions of 1.8 Gy per week. We used a Brainlab framework associated with a thermo-formed mask. A computed tomography then magnetic resonance imaging was obtained for each patient. The data was merged and planning took place on a Brainlab dosimetric console. The treatment was performed with a head-only Varion linear accelerator, with a Brainlab multi-blade collimator. RESULTS: The average follow-up was 27 months. Each patient had a complete radiological and ophthalmologic exam every 3 months during the first year, then every 6 months thereafter. Tumor control rate was 100%. Vision was re-established in five patients and three patients had improvement, including one patient during treatment. 100% of proptosis and diplopias regressed. No side effect was reported. CONCLUSION: This is still a preliminary study, but the results suggest that fractionated stereotactic radiotherapy may emerge as a primary treatment for ONSM, delaying surgery, which has proven functionally disappointing.     

An evaluation of cognitive disorders after anterior choroidal artery infarction

Anterior choroidal artery infarction (AChAI) can be the source of aphasia and spatial neglect, but we have no idea of the other possible cognitive disorders. Here, we investigated these disorders in a relatively large cohort of AChAI patients. Twenty patients with relatively recent infarction (left side: 13; mean delay = 47.4 days; 10 men; mean age = 59.6; mean education level, EL = 10.3) were included. We assessed nonspatial attention (alertness, Go Nogo, divided attention and visual vigilance from the computerized test TEA), spatial attention (bell test), language (BDAE) orientation (time, place), short-term memory (forward and backward digit spans, spatial span), executive functioning (WCST, TMT A and B, categorial evocation), delayed memory (Buschke verbal test, Rey figure test), and retrograde memory (questionnaire on famous events). The performance level was compared with that of 20 control subjects matched in age and EL. AChAI patients were impaired in several tests of attention (slowness, increase in omission and error rate), executive functioning (TMT B; categorical evocation) and delayed memory. Conversely, we found preservation of spatial attention, language, orientation, short-term memory, WCST, and retrograde memory. In conclusion, at the secondary phase post-stroke, these patients can present with moderate disorders of attention, memory and executive functioning, which are clearly less severe than what is usually observed following thalamic or cortical lesions.     

Decompressive Surgery for Malignant Middle Cerebral Artery Infarcts: The Results of Randomized Trials Can Be Reproduced in Daily Practice

Background: In clinical randomized controlled trials (RCTs), decompressive surgery (DS) for malignant middle cerebral artery (MMCA) infarcts leads to a 50% absolute risk reduction in mortality, and improves the 1-year functional outcome. The reproducibility of these results in routine practice has never been evaluated. The purpose of this study was to test the hypothesis that the results of DS for MMCA in practice are similar to those observed in the surgical group of RCTs. Methods: We prospectively included the first 31 patients who underwent DS for MMCA. They were screened based on similar criteria as in the meta-analysis. The primary outcome was a modified Rankin Scale (mRS) score of ≤4, and secondary outcomes were mRS of ≤3 and death at 1 year. Results: Thirty-one patients underwent DS for MMCA. The 1-year mRS was ≤4 in 22 patients (71.0%) and ≤3 in 16 (51.6%). Seven patients died (22.6%). Conclusion: This observational study showed that DS for MMCA in a center without previous experience provides similar results as those obtained in the surgical arm of RCTs.     

Approche clinique du surentraînementClinical aspect of overtraining

Purpose. – Isolate the objective and subjective clinical symptoms usually obtained in routine medical practice which more clearly characterise the overtraining syndrom in order to improve its diagnosis. Compare objective parameters with subjective parameters obtained by using the SFMS questionnaire to assess its validity.Synthesis of facts. – The subjective parameters usually used in this questionnaire (sleep, appetite, muscular symptoms, anxiety, irritability, headache…) and objective parameters (biometry, nutritional status, cardio-respiratory and metabolic during rest and exercise) are retrospectively analysed in 17 athletes who suffered from overtraoning syndrome. Some objectives clinical parameters are frequently observed (alteration of the resting and submaximum exercise heart rate, lower differential resting blood pressure, higher submaximal exercise lactatemia, lower recovery index). The fat mass and maximal exercise lactatemia are correlated to the score of the overtraining questionnaire.Conclusion. – This retrospective study puts forward the valuability of the subjective symptoms assessed by the SFMS questionnaire in conjunction with simple objective clinical parameters obtained in routine laboratory to facilitate the diagnosis of overtraining syndrom.     

Neuropsychological changes related to unilateral lenticulostriate infarcts.

According to previous studies, focal capsulostriatal lesions may produce aphasia, hemineglect, gestural apraxia, frontal lobe dysfunction, and memory impairment. A few reports of capsulostriate infarcts secondary to involvement of lenticulostriate arteries have confirmed that aphasia and hemineglect may occur whereas gestural apraxia, anosognosia and frontal-lobe symptoms are rare. Most studies used CT scan assessment and did not exclude possible associated lesions. Neuropsychological changes in 11 patients with lenticulostriate infarcts diagnosed by CT scan were prospectively investigated. MRI in five of the 11 patients showed an associated cortical lesion not seen on CT scan. Patients with pure lenticulostriate infarcts on MRI may exhibit aphasia of mild severity whereas Broca's aphasia, hemineglect, gestural apraxia, and anosognosia were only seen in the subgroup with associated cortical lesions. Aphasia in patients with pure lenticulostriate infarcts was characterised by prominent expressive and lexicosemantic task impairments. The results strongly suggest that cortical involvement is critical to the extent and severity of neuropsychological changes in patients with lenticulostriate infarcts.     

Spinal metastases mimicking low back pain of mechanical origin: a case report

Spinal malignancies are an essential consideration when a patient presents to a chiropractic office with back pain. This single case report exemplifies the importance of patient presentation and physical examination findings. We must also consider the rationale for x-raying patients on an individual case basis. Textbook cases do not always exist and special diagnostic tests do not always provide a definitive diagnosis of underlying pathology. Even though history and examination findings suggest a routine diagnosis, continual re-evaluation and recognition of the need to change the diagnosis on occasion is extremely important. The patient should not only be thoroughly evaluated upon initial presentation, but also each time they present for treatment. The decision to x-ray a patient is considered important. X-ray examination can be used to confirm a diagnosis or to rule out potential pathologies, and not necessarily done as a routine screening procedure.A case report is presented in which the pathologic signs were not evident on plain film x-rays upon initial presentation.