Effect of intracranial Cryptococcus neoformans infection on the function of efflux transporter breast cancer-resistance protein / 解放军医学杂志

Objective To explore the effect of intracranial Cryptococcus neoformans (Cr.neoformans) infection on the function of fluconazole transport by breast cancer-resistance protein (BCRP),a kind of efflux transporter on the blood-brain barrier (BBB).Methods Twenty-four male Sprague-Dawley rats were randomly divided into 4 groups (6 each):normal rats received 20mg/kg fluconazole by intravenous injection (Group A),normal rats received 20mg/kg fluconazole with co-administration of pantoprazole (a kind of BCRP inhibitor) by intravenous injection (Group B),rats with intracranial Cr.neoformans infection received 20mg/kg fluconazole (Group C),and infected rats received 20mg/kg fluconazole with co-administration of pantoprazole (Group D).Microdialysis probes were implanted into the rats' striatum to continuously collect brain extracellular fluid (ECF) after the intravenous infusion of fluconazole with or without BCRP inhibitor pantoprazole.High-performance liquid chromatography (HPLC) was applied to measure the fluconazole concentrations in blood and brain ECF.The area under the concentration-time curves of fluconazole and the penetration of fluconazole passing though BBB were then calculated.Results Meningoencephalitis rat model was successfully established by intracerebral inoculation of Cr.neoformans.The infection significantly increased the penetration of fluconazole passing through BBB (P＜0.05).Pantoprazole did not alter the distribution of fluconazole in normal rat's brain,but significantly increased the penetration of fluconazole passing through BBB of the infected rats (P＜0.05).Conclusion Cr.neoformans infection can reduce the BBB resistance to fluconazole,and induce the efflux transport of fluconazole from the brain ECF back into the blood by BCRP.

Long-term Effectiveness of Antiepileptic Drug Monotherapy in Partial Epileptic Patients: A 7-year Study in an Epilepsy Center in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It is important to choose an appropriate antiepileptic drug (AED) to manage partial epilepsy. Traditional AEDs, such as carbamazepine (CBZ) and valproate (VPA), have been proven to have good therapeutic effects. However, in recent years, a variety of new AEDs have increasingly been used as first-line treatments for partial epilepsy. As the studies regarding the effectiveness of new drugs and comparisons between new AEDs and traditional AEDs are few, it is determined that these are areas in need of further research. Accordingly, this study investigated the long-term effectiveness of six AEDs used as monotherapy in patients with partial epilepsy.</p><p><b>METHODS</b>This is a retrospective, long-term observational study. Patients with partial epilepsy who received monotherapy with one of six AEDs, namely, CBZ, VPA, topiramate (TPM), oxcarbazepine (OXC), lamotrigine (LTG), or levetiracetam (LEV), were identified and followed up from May 2007 to October 2014, and time to first seizure after treatment, 12-month remission rate, retention rate, reasons for treatment discontinuation, and adverse effects were evaluated.</p><p><b>RESULTS</b>A total of 789 patients were enrolled. The median time of follow-up was 56.95 months. CBZ exhibited the best time to first seizure, with a median time to first seizure of 36.06 months (95% confidential interval: 30.64-44.07). CBZ exhibited the highest 12-month remission rate (85.55%), which was significantly higher than those of TPM (69.38%, P = 0.006), LTG (70.79%, P = 0.001), LEV (72.54%, P = 0.005), and VPA (73.33%, P = 0.002). CBZ, OXC, and LEV had the best retention rate, followed by LTG, TPM, and VPA. Overall, adverse effects occurred in 45.87% of patients, and the most common adverse effects were memory problems (8.09%), rashes (7.76%), abnormal hepatic function (6.24%), and drowsiness (6.24%).</p><p><b>CONCLUSION</b>This study demonstrated that CBZ, OXC, and LEV are relatively effective in managing focal epilepsy as measured by time to first seizure, 12-month remission rate, and retention rate.</p>

Clinical analysis of 47 misdiagnosed cases of atypical tuberculous meningitis / 南方医科大学学报

<p><b>OBJECTIVE</b>To improve the differential diagnosis of tuberculous meningitis (TBM) and reduced potential misdiagnosis of TBM.</p><p><b>METHODS</b>The clinical data of 47 misdiagnosed cases of TBM between January, 1994 and June, 2009 were investigated retrospectively. The clinical presentations and causes for the misdiagnoses were analyzed.</p><p><b>RESULTS</b>The 47 patients with misdiagnosed TBM included 28 male and 19 female patients with a mean age of 36.84∓16.41 years. Eight patients had an acute onset, 10 had a subacute onset, and 29 had chronic disease. The initial symptoms, in the descending order of their frequencies, included fever and headache (87.2%), anergia and dyskinesia (27.7%), cerebral nerve damage (23.4%), decreased level of consciousness (14.9%), and urinary and fecal incontinence (2%). Meningeal irritation was present in 25 cases and positive Babinksi sign was found in 19 cases. Elevated intracranial pressure occurred in 51.1% of the cases, and 16 cases showed papilloedema. Non-purulent CSF with elevated protein was found in 86.7%, decreased glucose in 50%, and decreased chlorinate in 53.3% of the cases. Eight out of 23 cases showed a positive result of PPD test. MRI identified abnormitis with meningeal enhancement in 15 cases, hydrocephalus in 7 cases and infarction in 14 cases. Tuberculoma was found in 2 cases, and spinal cord lesions were found 4 cases. All the patients received anti-tuberculosis therapy, which resulted in symptomatic improvement in 39 cases, fluctuated condition in 2 cases; 5 patients discontinued the treatment and 1 died.</p><p><b>CONCLUSION</b>Early TBM often presents with atypical features and its differential diagnosis can be difficult. CSF monitoring and careful inspection of the radiographic data can be helpful in the diagnosis of suspected cases, for which early anti-TB treatment is an important means to reduce misdiagnosis.</p>

Value of tumor markers in the cerebrospinal fluid in the diagnosis of meningeal carcinomatosis / 南方医科大学学报

<p><b>OBJECTIVE</b>To assess the diagnostic value of tumor markers in the cerebrospinal fluid (CSF) for meningeal carcinomatosis (MC).</p><p><b>METHODS</b>Twenty-one MC patients (including 13 adenocarcinoma and 8 non-adenocarcinoma patients), 72 patients with tuberculous meningitis (TBM) and 23 with primary intracerebral tumors (PIT) were enrolled in this study. Blood and CSF tumor markers including CEA, CA125, CA15-3, CA19-9, CA72-4, CYFRA21-1, AFP and NSE were measured by Roche E170 electrochemiluminescence analyzer and sandwich assay.</p><p><b>RESULTS</b>CSF tumor markers CEA, CA125, CA199 and CYFRA21-1 and the serum tumor markers CEA, CA125, CA153, CA199 and AFP were significantly higher in MC group than in the other two groups. CSF CEA and CA15-3 were significantly higher in adenocarcinoma MC than in non-adenocarcinoma MC patients, but no significant differences were found in the serum tumor markers between the two groups (P>0.05). CSF tumor markers including CEA, CA125, CA15-3, CA72-4 and CYFRA21-1 were positively correlated to the serum tumor markers (P<0.05). CA199 was positively correlated to the disease course (P<0.05), and age was not correlated to any of the indexes (P>0.05).</p><p><b>CONCLUSION</b>Detection of the tumor markers in the CSF, especially CEA, CA125, CA19-9 and CYFRA21-1, may help in the early diagnosis of MC. CEA and CA15-3 can serve as indicators for differential diagnosis of adenocarcinoma and non-adenocarcinoma.</p>