Acute ischemic stroke in tuberculous meningitis.

Background: The underlying mechanism for stroke in patients with tuberculous meningitis (TBM) remains unclear. This study aimed to investigate the predictors of acute ischemic stroke (AIS) in TBM and whether AIS mediates the relationship between inflammation markers and functional disability. Methods: TBM patients admitted to five hospitals between January 2011 and December 2021 were consecutively observed. Generalized linear mixed model and subgroup analyses were performed to investigate predictors of AIS in patients with and without vascular risk factors (VAFs). Mediation analyses were performed to explore the potential causal chain in which AIS may mediate the relationship between neuroimaging markers of inflammation and 90-day functional outcomes. Results: A total of 1,353 patients with TBM were included. The percentage rate of AIS within 30 days after admission was 20.4 (95% CI, 18.2-22.6). A multivariate analysis suggested that age ≥35 years (OR = 1.49; 95% CI, 1.06-2.09; P = 0.019), hypertension (OR = 3.56; 95% CI, 2.42-5.24; P < 0.001), diabetes (OR = 1.78; 95% CI, 1.11-2.86; P = 0.016), smoking (OR = 2.88; 95% CI, 1.68-4.95; P < 0.001), definite TBM (OR = 0.19; 95% CI, 0.06-0.42; P < 0.001), disease severity (OR = 2.11; 95% CI, 1.50-2.90; P = 0.056), meningeal enhancement (OR = 1.66; 95% CI, 1.19-2.31; P = 0.002), and hydrocephalus (OR = 2.98; 95% CI, 1.98-4.49; P < 0.001) were associated with AIS. Subgroup analyses indicated that disease severity (P for interaction = 0.003), tuberculoma (P for interaction = 0.008), and meningeal enhancement (P for interaction < 0.001) were significantly different in patients with and without VAFs. Mediation analyses revealed that the proportion of the association between neuroimaging markers of inflammation and functional disability mediated by AIS was 16.98% (95% CI, 7.82-35.12) for meningeal enhancement and 3.39% (95% CI, 1.22-6.91) for hydrocephalus. Conclusion: Neuroimaging markers of inflammation were predictors of AIS in TBM patients. AIS mediates < 20% of the association between inflammation and the functional outcome at 90 days. More attention should be paid to clinical therapies targeting inflammation and hydrocephalus to directly improve functional outcomes.

ALDH2*2 Allele is a Negative Risk Factor for Cerebral Infarction in Chinese Women.

Unlike its reported role in the cardiovascular diseases, little information is available for mitochondrial aldehyde dehydrogenase 2 (ALDH2) in the cerebrovascular function. We investigated the different effects of ALDH2 genotypes on the risk of cerebral infarction between the genders, because different genders had different smoking and/or dinking status which are also risk factors for cerebral infarction. 247 healthy Chinese Han people (controls, group 1), 287 Chinese Han male patients with cerebral infarction (group 2), and 82 Chinese Han female patients with cerebral infarction (group 3) were involved in this study. The frequencies of the ALDH2*2 allele in group 3 were significantly higher than those in other groups (with P = 0.001 and P = 0.002, respectively). The difference of ALDH2*2 allele frequency between group 1 and group 2 was not significant (P = 0.652). After adjustment for smoking and drinking status, the male patients without smoking or drinking status (group 4) had higher ALDH2*2 allele frequency than group 1, but the difference was still not significant (P = 0.139). Thus, we conclude that ALDH2*2 allele may be a significant negative risk factor for cerebral infarction in Chinese women [odds ratio (OR) = 2.207, 95% CI 1.416-3.439]. But for Chinese male patients, the negative effects of ALDH2*2 allele on cerebral infarction which might be concealed by other risk factors were not significant.

Individuals having variant genotypes of cytochrome P450 2C19 are at increased risk of developing primary liver cancer in Han populations, without infection with the hepatitis virus.

Recently, many researchers have reported that the genetic polymorphisms of CYP2C19 may account for the interpatient variability of the clinical course in cancers including primary liver cancer (PLC). Besides the genetic polymorphisms of CYP2C19, hepatitis viruses (HV, including HAV, HBV, HCV, HDV, HEV, especially HBV and/or HCV) also account for the interpatient variability of the clinical course in PLC. This research covered the above two factors and divided the patients with PLC into two groups (one group with HBV infection and another without any HV infection) to find out whether the genetic polymorphisms of CYP2C19 have different effects in the progressing of PLC in different groups of patients. Eight hundred sixty-four cancer-free Han people (controls, named group 1), 207 Han PLC patients with HBV infection (group 2), and 55 Han PLC patients without any HV infection (group 3) were involved in this study. A wild-type allele (CYP2C19*1) and two mutated alleles (CYP2C19*2 and CYP2C19*3) were identified. The frequencies of the mutant alleles and genotypes were then compared with each other. The frequencies of the homozygous and heterozygous variant genotypes (*2/*2, *2/*3, *3/*3) in group 3 (25.5 %) were significantly higher than those in other groups (11.9 % in group 1 and 13.5 % in group 2, P = 0.014, 95 % confidence interval (CI)). The differences were statistically significant between group 1 and group 3 (P = 0.004, 95 % CI), but they were not statistically significant between group 1 and group 2 (P = 0.527, 95 % CI). Thus, we conclude that people which were not infected with HV but with the homozygous or heterozygous variant genotypes (*2/*2, *2/*3, *3/*3) of CYP2C19 may have higher possibilities of getting PLC than people with other allelic genotypes (*1/*1, *1/*2, *1/*3) (odds ratio (OR) = 2.523, 95 % CI = 1.329 ~ 4.788). However, in patients with HBV infection, the genetic polymorphisms of CYP2C19 did not seem to be an important factor in the risk of developing PLC (OR = 1.156, 95 % CI = 0.738 ~ 1.810).

Determination of cefcapene acid by LC-MS and their application to a pharmacokinetic study in healthy Chinese volunteers.

Simple, rapid and specific liquid chromatography-mass spectrometry (LC-MS) methods have been developed and validated for the quantification of cefcapene acid in human plasma and urine. Plasma samples were simply pretreated with methanol for deproteinization. Urine samples were briefly diluted with methanol-water (50:50, v/v), and centrifuged to remove large particles. Chromatographic separation was performed on a Hedera ODS-2 column. For the plasma assay, the isocratic mobile phase consisted of 35% solvent A (Methanol) and 65% solvent B (10 mM ammonium acetate buffer solution containing 0.2% folic acid) with a flow rate of 0.3 mL/min. For the urine assay, the isocratic mobile phase consisted of 30% solvent A (Methanol) and 70% solvent B (10 mM ammonium acetate buffer solution containing 0.2% folic acid) with a flow rate of 0.3 mL/min. The assays were linear over the concentration ranges of 0.03-5 µg/mL in plasma and 0.1-400 µg/mL in urine, and were successfully applied to a pharmacokinetic study after single and multiple oral administrations of cefcapene pivoxil hydrochloride tablets in healthy Chinese volunteers.

[Clinical analysis of protionamide and para-aminosalicylic acid induced hepatotoxicity in 129 cases].

OBJECTIVE: To investigate drug-induced liver injury (DILI) in tuberculosis (TB) patients treated with protionamide (Pto) and (or) para-aminosalicylic acid (PAS), and therefore to provide data for using second-line anti-tuberculosis drugs and risk prediction of liver damage. METHODS: A retrospective analysis was performed for TB patients treated with regimens containing Pto and (or) PAS in Beijing Chest Hospital during Jan. 2008 to Jan. 2013. Cases with DILI were identified, and associated factors including patients' age and gender, time of onset, severity, clinical manifestations and prognosis of DILI were analyzed. The 2 groups were compared with χ(2) test. P < 0.05 was considered to be significant. RESULTS: A total of 1714 cases were admitted, among whom 226 experienced liver damage during treatment, of which 97 cases were excluded because of underlying alcoholic liver disease, viral hepatitis B and C. Finally, 129 cases were diagnosed as having DILI, resulting in an overall incidence of 7.5% (129/1714), being 9.2% (59/641) in females, and 6.5% (70/1073) in males (χ(2) = 4.143, P < 0.05). DILI in most patients occurred between 1 week to 2 months, with 30.2% (39/129) within 2-4 weeks. 47.3% (61/129) of the patients showed no obvious clinical symptoms of hepatotoxicity. Among different regimens, combination of Pto, PAS and PZA resulted in the highest rate of DILI (20.7%, 19/92), while the rate was 9.8% (8/82) for the combination of Pto and PZA, P < 0.05. CONCLUSIONS: DILI caused by Pto and PAS should be taken into account, especially in female patients and for multi-drug combination therapy. Liver function should be monitored even in patients without related clinical manifestations for early identification and treatment, and therefore avoiding severe liver damage.

[Mycobacterium abscessus group lung disease: case reports and review of the literature].

OBJECTIVE: To analyze the clinical manifestations and efficacy of a combination antibiotic therapy including cefoxitin for Mycobacterium abscessus (M.abscessus) group lung disease. METHODS: We retrospectively analyzed the clinical manifestations of 16 patients with M.abscessus group lung disease, and the responses of 5 cases treated with whole-course clarithromycin and moxifloxacin, initially intensified with intravenous amikacin and cefoxitin therapy for the first 12 weeks. RESULTS: Radiological study showed that 14 patients with M.abscessus group pulmonary disease were classified as nodular bronchiectasis form, and 1 patient as upper lobe cavity form and 1 patient was unclassifiable. The radiological characteristics of M.abscessus group pulmonary disease included multiple micronodules (14/16), bronchiectasis (14/16), tree in bud sign (13/16), cavity (5/16), consolidation (5/16), nodules (5/16), and collapse of lung (3/16). Five cases were treated with a combination antibiotic therapy including cefoxitin. After 3 months treatment for the initial phase, 2 of them got improvement in symptoms, CT manifestations and sputum conversion. Two of them improved in symptoms and CT manifestations, but not in sputum conversion. One case showed no improvement in the initial phase, and continuation therapy also failed to improve symptoms, CT abnormalities or sputum conversion. CONCLUSIONS: Nodular bronchiectasis is the main manifestation of M.abscessus group lung disease. The main imaging characteristics included multiple micronodules, bronchiectasis and tree in bud sign. A therapeutic regimen including cefoxitin may be moderately effective in treating M.abscessus group lung disease.

[Comparison of clinical manifestations between Mycobacterium avium-intracellulare complex and Mycobacterium abscessus pulmonary diseases].

OBJECTIVE: To compare the clinical manifestations of nontuberculous mycobacterial (NTM) pulmonary diseases caused by Mycobacterium avium-intracellulare complex (MAC) and Mycobacterium abscessus. METHODS: The clinical manifestations of 18 patients with MAC and 9 patients with Mycobacterium abscessus pulmonary diseases diagnosed from 2010 to 2011 were reviewed. RESULTS: There were no significant differences in the gender, age, body mass index, predisposed diseases, symptoms and positive sputum acid-fast bacillus between MAC and Mycobacterium abscessus groups. Upper lobe cavities were more frequently observed in the MAC group (13/18), whereas nodular bronchiectatic changes were more frequent in the Mycobacterium abscessus group (3/9). Compared with MAC pulmonary diseases, several imaging characteristics were more common in the Mycobacterium abscessus group, including bilateral micro nodules (Mycobacterium abscessus group 8/9 vs MAC group 7/18), tree-in-bud sign (Mycobacterium abscessus group 7/9 vs MAC group 6/18) and multiple bronchiectasis (Mycobacterium abscessus group 8/9 vs MAC group 5/18). CONCLUSIONS: There was considerable overlap in clinical characteristics of MAC and Mycobacterium abscessus pulmonary diseases. However, bilateral micro nodules, tree-in-bud sign and multiple bronchiectasis were more frequently seen in Mycobacterium abscessus than in MAC pulmonary diseases, while upper lobe cavities were more frequently seen in MAC than in Mycobacterium abscessus pulmonary diseases.

[Susceptibility test of the Mycobacterium avium complex to sixteen anti-infective agents].

OBJECTIVE: To compare the in vitro activities of 13 anti-infective agents and 3 new quinolones (sitafloxacin, gatifloxacin and moxifloxacin) against Mycobacterium avium complex (MAC) isolates, and therefore to explore the possibility of using these quinolones to treat MAC diseases. METHODS: The minimal inhibitory concentration (MIC) of the above 16 anti-infective agents, including sitafloxacin, gatifloxacin and moxifloxacin against MAC isolates was determined by using agar dilution methods, and then the MIC90s of the different anti-infective agents were compared. RESULTS: The MICs of M. avium isolates showed a wider range and was less sensitive to most of the anti-infective agents as compared with M. intracellulare isolates. The MIC90s of clarithromycin against M. avium and M. intracellulare isolates were 32 mg/L and 16 mg/L, respectively, which were the lowest among 4 macrolide compounds. The MIC90 of rifalazil were 0.5 mg/L and 0.25 mg/L, respectively, which were the lowest among 4 rifamycin compounds. The MIC90 of sitafloxacin against M. avium and M. intracellulare isolates were both 4 mg/L, which were the lowest among 5 quinolones. For gatifloxacin and moxifloxacin, the MIC90 against M. avium and M. intracellulare isolates were both 8 mg/L. Two clarithromycin-sensitive strains (MIC=0.5 mg/L) showed a similar MIC of the lower limit for other compounds. Three clarithromycin-insensitive strains (MIC=64 mg/L) showed a similar MIC of the upper limit for other compounds except quinolones. CONCLUSION: Rifalazil, sitafloxacin, gatifloxacin and moxifloxacin showed acceptable in vitro activities against MAC isolates.

[Balloon dilation using fiberoptic bronchoscope in the management of bronchial stenosis due to tuberculosis].

OBJECTIVE: To investigate the safety and efficacy of balloon dilation using fiberoptic bronchoscope in the management of bronchial stenosis due to tuberculosis. METHODS: The clinical data and long term follow-up results of 25 patients with bronchial stenosis due to tuberculosis who had received balloon dilation using a fiberoptic bronchoscope were retrospectively analyzed. Before the procedure and immediately after the last operation, airway diameters were estimated in all patients. RESULTS: Two to seven operations were required to achieve satisfactory dilatation. After balloon dilatation, the average airway diameter increased from (2.8 +/- 1.1) mm to (6.7 +/- 2.3) mm (t = 5.471, P < 0.05). No complications occurred during inflation among all patients. After 2 to 36 months follow-up, no re-stenosis appeared. Sixteen patients were followed for more than 1 year, and the average airway diameter was (5.5 +/- 2.0) mm 1 year after the last balloon dilation. There was a significant difference compared with the average airway diameter before dilation (t = 2.834, P < 0.05). However, there was no significant difference as compared with the average airway diameter after the last balloon dilation. Of 11 patients with atelectasis, the atelectasis completely resolved after balloon dilation in 2 cases. CONCLUSION: Balloon dilation using fiberoptic bronchoscope is an effective, safe, and simple method for treatment of bronchial stenosis due to tuberculosis.

[A study on the association of 3'UTR polymorphisms of NRAMP1 gene with susceptibility to tuberculosis in Hans].

OBJECTIVE: To determine whether 3'UTR polymorphisms of the NRAMP1 gene are associated with tuberculosis in Hans. METHODS: 3'UTR polymorphisms of NRAMP1 gene were typed by PCR-RFLP among 147 patients with active tuberculosis and 145 healthy individuals. The relationship between 3'UTR polymorphisms and susceptibility to tuberculosis was studied, and cases were grouped according to genotypes. RESULTS: In the tuberculosis patients, genotype TGTG/TGTG, TGTG/TGTG deleted, and TGTG deleted/TGTG deleted were observed in 95, 50 and 2 cases respectively, while the genotypes of the healthy controls were TGTG/TGTG in 115, TGTG/TGTG deleted in 29 and TGTG deleted/TGTG deleted in 1 case. The frequency of the genotype TGTG/TGTG was found more often among controls than that in patients (chi(2) = 7.79, P < 0.01). The frequency of allele TGTG and the frequency of variant allele were 0.85 and 0.15 respectively. CONCLUSIONS: 3'UTR polymorphisms of NRAMP1 gene are associated with susceptibility to tuberculosis in Hans. The variant allele observed in Hans is more common than that in Caucasians. These observations might explain in part why Hans have greater susceptibility to tuberculosis than Caucasians.

[Nitric oxide production and expression of cytokines by macrophages infected by M. tuberculosis H(37)R(v)].

OBJECTIVE: To study nitric oxide (NO) production and cytokine expression by macrophages infected by M. tuberculosis H(37)R(v), and to compare the difference between dead and live M. tuberculosis in the induction of immune responses, and thus to show if dead bacteria could be a possible candidate for new vaccines. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) and ELISA were used to measure the production of NO and cytokines in macrophages infected by H(37)R(v). RESULTS: Macrophages infected by viable M. tuberculosis produced more NO, IL-1, IL-12, IL-18, TNF-alpha and inducible nitric oxide synthases (iNOS), as compared with macrophages infected by dead bacteria. The number of bacteria was also an important factor determining the production of NO and cytokines. CONCLUSIONS: Viable M. tuberculosis H(37)R(v) can induce the activation of macrophages and the production of more NO and cytokines which play important roles in the host immune response. Heat-killed M. tuberculosis H(37)R(v) failed to induce activation of macrophages and the production of NO and cytokines, which makes it unlikely to be a candidate for vaccine development.